Promoting Recruitment using Information Management Efficiently (PRIME): study protocol for a stepped-wedge cluster randomised controlled trial within the REstart or STop Antithrombotics Randomised Trial (RESTART).

PubMed

Maxwell, Amy E; Dennis, Martin; Rudd, Anthony; Weir, Christopher J; Parker, Richard A; Al-Shahi Salman, Rustam

2017-03-01

Research into methods to boost recruitment has been identified as the highest priority for randomised controlled trial (RCT) methodological research in the United Kingdom. Slow recruitment delays the delivery of research and inflates costs. Using electronic patient records has been shown to boost recruitment to ongoing RCTs in primary care by identifying potentially eligible participants, but this approach remains relatively unexplored in secondary care, and for stroke in particular. The REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) is an ongoing RCT of secondary prevention after stroke due to intracerebral haemorrhage. Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped-wedge cluster randomised trial of a complex intervention to help RESTART sites increase their recruitment and attain their own target numbers of participants. Seventy-two hospital sites that were located in England, Wales or Scotland and were active in RESTART in June 2015 opted into PRIME. Sites were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location in Scotland vs. England/Wales) to one of 12 months in which the intervention would be delivered. All sites began in the control state. The intervention was delivered by a recruitment co-ordinator via a teleconference with each site. The intervention involved discussing recruitment strategies, providing software for each site to extract from their own stroke audit data lists of patients who were potentially eligible for RESTART, and a second teleconference to review progress 6 months later. The recruitment co-ordinator was blinded to the timing of the intervention until 2 months before it was due at a site. Staff at RESTART sites were blinded to the nature and timing of the intervention. The primary outcome is the total number of patients randomised into RESTART per month per site and will be analysed in a negative binomial generalised linear mixed model. PRIME began in September 2015. The last intervention was delivered in August 2016. Six-month follow-up will be complete in February 2017. The final results of PRIME will be analysed and disseminated in 2017. The PRIME study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial (SWAT) repository (SWAT22) on 23 December 2015.

The efficacy and safety of extended-release methylphenidate following traumatic brain injury: a randomised controlled pilot study.

PubMed

Dymowski, Alicia R; Ponsford, Jennie L; Owens, Jacqueline A; Olver, John H; Ponsford, Michael; Willmott, Catherine

2017-06-01

To investigate the feasibility, safety and efficacy of extended-release methylphenidate in enhancing processing speed, complex attentional functioning and everyday attentional behaviour after traumatic brain injury. Seven week randomised, placebo-controlled, double-blind, parallel pilot study. Inpatient and outpatient Acquired Brain Injury Rehabilitation Program. Eleven individuals with reduced processing speed and/or attention deficits following complicated mild to severe traumatic brain injury. Participants were allocated using a blocked randomisation schedule to receive daily extended-release methylphenidate (Ritalin ® LA at a dose of 0.6 mg/kg) or placebo (lactose) in identical capsules. Tests of processing speed and complex attention, and ratings of everyday attentional behaviour were completed at baseline, week 7 (on-drug), week 8 (off-drug) and 9 months follow-up. Vital signs and side effects were monitored from baseline to week 8. Three percent ( n = 11) of individuals screened participated (mean post-traumatic amnesia duration = 63.80 days, SD = 45.15). Results were analysed for six and four individuals on methylphenidate and placebo, respectively. Groups did not differ on attentional test performance or relative/therapist ratings of everyday attentional behaviour. One methylphenidate participant withdrew due to difficulty sleeping. Methylphenidate was associated with trends towards increased blood pressure and reported anxiety. Methylphenidate was not associated with enhanced processing speed, attentional functioning or everyday attentional behaviour after traumatic brain injury. Alternative treatments for attention deficits after traumatic brain injury should be explored given the limited feasibility of methylphenidate in this population.

The effect of blue-blocking intraocular lenses on circadian biological rhythm: protocol for a randomised controlled trial (CLOCK-IOL colour study).

PubMed

Nishi, Tomo; Saeki, Keigo; Obayashi, Kenji; Miyata, Kimie; Tone, Nobuhiro; Tsujinaka, Hiroki; Yamashita, Mariko; Masuda, Naonori; Mizusawa, Yutarou; Okamoto, Masahiro; Hasegawa, Taiji; Maruoka, Shinji; Ueda, Tetsuo; Kojima, Masashi; Matsuura, Toyoaki; Kurumatani, Norio; Ogata, Nahoko

2015-05-12

Blue light information plays an important role in synchronising internal biological rhythm within the external environment. Circadian misalignment is associated with the increased risk of sleep disturbance, obesity, diabetes mellitus, depression, ischaemic heart disease, stroke and cancer. Meanwhile, blue light causes photochemical damage to the retina, and may be associated with age-related macular degeneration (AMD). At present, clear intraocular lenses (IOLs) and blue-blocking IOLs are both widely used for cataract surgery; there is currently a lack of randomised controlled trials to determine whether clear or blue-blocking IOLs should be used. This randomised controlled trial will recruit 1000 cataract patients and randomly allocate them to receive clear IOLs or blue-blocking IOLs in a ratio of 1:1. The primary outcomes are mortality and the incidence of cardiovascular disease, cancer and AMD. Secondary outcomes are fasting plasma glucose, triglycerides, cholesterol, glycated haemoglobin, sleep quality, daytime sleepiness depressive symptoms, light sensitivity, the circadian rhythm of physical activity, wrist skin temperature and urinary melatonin metabolite. Primary outcomes will be followed until 20 years after surgery, and secondary outcomes will be assessed at baseline and 1 year after surgery. Ethical approval has been obtained from the Institutional Review Board of Nara Medical University (No. 13-032). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) home page. UMIN000014680. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Vitagliano, A; Saccone, G; Noventa, M; Borini, A; Coccia, M E; Nardelli, G B; Saccardi, C; Bifulco, G; Litta, P S; Andrisani, A

2018-06-03

Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. Pituitary block with GnRH antagonists does not improve the success of IUI cycles. © 2018 Royal College of Obstetricians and Gynaecologists.

A randomised trial of the analgesic efficacy of ultrasound-guided transversus abdominis plane block after caesarean delivery under general anaesthesia.

PubMed

Tan, Terry T; Teoh, Wendy H L; Woo, David C M; Ocampo, Cecilia E; Shah, Mukesh K; Sia, Alex T H

2012-02-01

Previous studies examining the efficacy of transversus abdominis plane block after caesarean section have mostly been in parturients under spinal anaesthesia. We postulated that the advantage of performing transversus abdominis plane block after caesarean section might be even more obvious after general anaesthesia, resulting in reduced 24-h consumption of morphine. DESIGN, SETTING, PATIENTS AND INTERVENTIONS: In this single centre, randomised double-blind controlled trial, 40 women who underwent caesarean delivery under general anaesthesia were allocated randomly to receive a transversus abdominis plane block or no block. In those who received the block, 20 ml of levobupivacaine 2.5 mg ml was deposited bilaterally into the transversus abdominis plane under ultrasound guidance using a Sonosite Titan (SonoSite, Bothell, Washington, USA) 7-13 MHz linear transducer at the end of surgery when the patient was still anaesthetised. We recorded patient-controlled intravenous morphine use for 24 h, pain scores at rest and activity, sedation, nausea and vomiting, use of antiemetic medication and overall maternal satisfaction. The primary outcome was 24-h morphine consumption. Patients who received the transversus abdominis plane block used significantly less morphine in 24 h than those in the control group [12.3 (2.6) vs. 31.4 mg (3.1), P<0.001) and had higher satisfaction scores [16 (80%) vs. 5 (25%), P = 0.012). There were no differences between groups in the visual analogue pain scores, sedation level, nausea and vomiting or the use of antiemetic medication. Ultrasound-guided transversus abdominis plane block reduced morphine consumption following caesarean section under general anaesthesia, with increased maternal satisfaction.

Analgesic effect of a single-dose of perineural dexamethasone on ultrasound-guided femoral nerve block after total knee replacement.

PubMed

Morales-Muñoz, C; Sánchez-Ramos, J L; Díaz-Lara, M D; González-González, J; Gallego-Alonso, I; Hernández-Del-Castillo, M S

2017-01-01

Total knee replacement is usually a very painful procedure. A single-dose of femoral nerve block has been shown to provide similar analgesia to an epidural, with fewer side effects, but limited in time. To compare the analgesia provided by dexamethasone used at perineural level in the femoral nerve block after total knee replacement with the one used at intravenous level, and with that of a control group. A prospective, randomised, double-blind controlled trial was conducted on 81 patients randomly assigned to one of three groups: 1)IV dexamethasone (8mg); 2)perineural dexamethasone (8mg), and 3)placebo. All patients received 20ml of ropivacaine 0.5% for femoral nerve block. The primary outcome was the duration of the sensory-analgesic block of the femoral nerve block. The secondary outcomes included pain intensity measurements, patient satisfaction, and incidence of complications. Randomisation was effective. Analgesia duration was significantly higher (P<.0001) in the perineural dexamethasone group (mean 1152.2min, 95% confidence interval [95% CI]: 756.9-1547.6) in comparison with the control group (mean 186min, 95%CI: 81.2-292) and dexamethasone IV group (mean 159.4min, 95%CI: 109.8-209). Postoperative pain, complications and side effects were also lower in this group. Dexamethasone prolongs sensory block of single dose of femoral nerve block using ropivacaine. It also provides better analgesia and patient satisfaction, with fewer side effects. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Practicalities of Using a Modified Version of the Cochrane Collaboration Risk of Bias Tool for Randomised and Non-Randomised Study Designs Applied in a Health Technology Assessment Setting

ERIC Educational Resources Information Center

Robertson, Clare; Ramsay, Craig; Gurung, Tara; Mowatt, Graham; Pickard, Robert; Sharma, Pawana

2014-01-01

We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. Objectives: (1) To assess time to complete RoB assessment; (2) To assess inter-rater agreement; and (3) To explore the association between RoB and treatment effect size. Methods: Cochrane risk of…

Adding a PECS II block for proximal arm arteriovenous access - a randomised study.

PubMed

Quek, K H; Low, E Y; Tan, Y R; Ong, A S C; Tang, T Y; Kam, J W; Kiew, A S C

2018-05-01

Brachial plexus block is often utilised for proximal arm arteriovenous access creation. However, the medial upper arm and axilla are often inadequately anaesthetised, requiring repeated, intraoperative local anaesthetic supplementation, or conversion into general anaesthesia. We hypothesised that the addition of a PECS II block would improve anaesthesia and analgesia for proximal arm arteriovenous access surgery. In this prospective, double-blinded, randomised proof-of-concept study, 36 consenting adults with end-stage renal disease aged between 21 and 90 years received either a combined supraclavicular and PECS II block (Group PECS, n = 18), or combined supraclavicular and sham block (Group SCB, n = 18) for proximal arm arteriovenous access surgery. Primary outcome was whether patients required intraoperative local anaesthetic supplementation by the surgeon. In Group PECS, 33.3% (6/18) needed local anaesthetic supplementation vs. 100% (18/18) in Group SCB. Group SCB had three times (RR 3.0, 95% CI 1.6-5.8; P < 0.001) the risk of requiring intraoperative local anaesthetic supplementation. Group PECS required lower volume of supplemental local anaesthetic compared to Group SCB (0.0 ml, IQR 0.0-6.3 ml vs. 15.0 ml, IQR 7.4-17.8 ml; P < 0.001). Group SCB had twice [RR 2.2, 95% CI 1.1-4.4; (P = 0.019)] the risk of needing additional sedation or analgesia. There were no significant differences between the groups with respect to postoperative visual analogue scale pain scores, time to first rescue analgesia or patient satisfaction. The results suggest that adding a PECS II block to a supraclavicular block improves regional anaesthesia for patients with end-stage renal disease undergoing proximal arm arteriovenous access surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Randomised Controlled Trials in Education Research: A Case Study of an Individually Randomised Pragmatic Trial

ERIC Educational Resources Information Center

Torgerson, Carole J.

2009-01-01

The randomised controlled trial (RCT) is an evaluative method used by social scientists in order to establish whether or not an intervention is effective. This contribution discusses the fundamental aspects of good RCT design. These are illustrated through the use of a recently completed RCT which evaluated an information and communication…

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

PubMed Central

Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

2011-01-01

Objective To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). Design An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline ‘trigger meals’ and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. Setting Outpatient internal medicine practice clinic. Patients 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised ‘food triggers’, no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11–30 years and 16% for more than 40 years. Interventions After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. Main outcome measures The primary analysis was number of patients who chose PEZ over placebo for the extended use. Results Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. Conclusions PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation. PMID:22095308

Novel needle guide reduces time to perform ultrasound-guided femoral nerve catheter placement: A randomised controlled trial.

PubMed

Turan, Alparslan; Babazade, Rovnat; Elsharkawy, Hesham; Esa, Wael Ali Sakr; Maheshwari, Kamal; Farag, Ehab; Zimmerman, Nicole M; Soliman, Loran Mounir; Sessler, Daniel I

2017-03-01

Ultrasound-guided nerve blocks have become the standard when performing regional nerve blocks in anaesthesia. Infiniti Plus (CIVCO Medical Solutions, Kalona, Iowa, USA) is a needle guide that has been recently developed to help clinicians in performing ultrasound-guided nerve blocks. We tested the hypothesis that femoral nerve catheter placement carried out with the Infiniti Plus needle guide will be quicker to perform than without the Infiniti Plus. Secondary aims were to assess whether the Infiniti Plus needle guide decreased the number of block attempts and also whether it improved needle visibility. A randomised, controlled trial. Cleveland Clinic, Cleveland, Ohio, USA. We enrolled adult patients having elective total knee arthroplasty with a femoral nerve block and femoral nerve catheter. Patients, who were pregnant or those who had preexisting neuropathy involving the surgical limb, coagulopathy, infection at the block site or allergy to local anaesthetics were excluded. Patients were randomised into two groups to receive the ultrasound-guided femoral nerve catheter placement with or without the Infiniti Plus needle guide. The time taken to place the femoral nerve catheter, the number of attempts, the success rate and needle visibility were recorded. We used an overall α of 0.05 for both the primary and secondary analyses; the secondary analyses were Bonferroni corrected to control for multiple comparisons. The median (interquartile range Q1 to Q3) time to perform the femoral nerve catheter placement was 118 (100 to 150) s with Infiniti Plus and 177 (130 to 236) s without Infiniti Plus. Infiniti Plus significantly reduced the time spent performing femoral nerve catheterisation, with estimated ratio of means [(95% confidence interval), P value] of 0.67 [(0.60 to 0.75), P < 0.001] with Infiniti Plus compared with no Infiniti Plus. However, Infiniti Plus had no effect on the odds of a successful femoral nerve catheter placement, number of attempts or percentage of perfect needle visibility. We found that the use of Infiniti Plus decreased the median time to successfully place a femoral nerve catheter by 33% compared with not using Infiniti Plus. This difference may be more apparent to clinicians undertaking this procedure less often or by those in training as our team was very experienced, had been trained in the technique and was working in a hospital with a large caseload. Clinicaltrials.gov identifier: NCT02080481.

A randomised controlled trial comparing three analgesia regimens following total knee joint replacement: continuous femoral nerve block, intrathecal morphine or both.

PubMed

Olive, D J; Barrington, M J; Simone, S A; Kluger, R

2015-07-01

This randomised controlled trial compared three analgesia regimens following primary unilateral total knee joint replacement: continuous femoral nerve block (CFNB), intrathecal morphine (ITM), and both. The primary outcome was pain ratings over the first 24 hours. Secondary outcomes included morphine consumption, nausea, pruritus and sedation ratings, oxygen saturation (SpO2) ratings, and ability to mobilise postoperatively. All patients received a spinal anaesthetic and a postoperative patient-controlled morphine pump. Patients were randomised to receive CFNB, ITM, or both. In patients with no CFNB, the use of ITM was blinded. Eighty-one patients were randomised and there were no withdrawals. At 24 hours, the ITM-only group had higher pain ratings than either of the other groups (P=0.04 versus CFNB, P=0.01 versus combination). In the 18 to 24 hour period, the ITM group used more morphine than either of the other groups. There were no statistically significant differences in pain ratings or morphine consumption at earlier time intervals. The ITM group were less likely to be able to sit out of bed on day one. Patients who received ITM were more likely to have pruritus. There were no statistically significant differences in nausea, SpO₂or sedation ratings. This study showed that a CFNB resulted in reduced pain and was also associated with less morphine consumption and improved mobilisation at 24 hours compared to ITM. This study did not show any statistically significant differences between CFNB alone and CFNB+ITM.

Is topical haloperidol a useful glaucoma treatment?

PubMed Central

Lavin, M. J.; Andrews, V.

1986-01-01

A randomised, double blind, single dose study of topical haloperidol, a dopamine receptor blocking drug, was performed on 20 healthy volunteers. After its administration a modest reduction in intraocular pressure was recorded over the six-hour study period, but the difference was not significant at the p less than 0.05 level. Although dopamine blocking agents are effective in reducing intraocular pressure in experimental animals, topical haloperidol appears unlikely to be clinically useful in the treatment of glaucoma. PMID:3718908

Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

PubMed

Hamada, T; Tsuchiya, M; Mizutani, K; Takahashi, R; Muguruma, K; Maeda, K; Ueda, W; Nishikawa, K

2016-04-01

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

Femoral nerve block in a representative sample of elderly people with hip fracture: A randomised controlled trial.

PubMed

Unneby, Anna; Svensson, Olle; Gustafson, Yngve; Olofsson, Birgitta

2017-07-01

The number of elderly people with hip fracture and dementia is increasing, and many of these patients suffer from pain. Opioids are difficult to adjust and side effects are common, especially with increased age and among patients with dementia. Preoperative femoral nerve block is an alternative pain treatment. To investigate whether preoperative femoral nerve block reduced acute pain and opioid use after hip fracture among elderly patients, including those with dementia. In this randomised controlled trial involving patients aged ≥70years with hip fracture (trochanteric and cervical), including those with dementia, we compared femoral nerve block with conventional pain management, with opioid use if required. The primary outcome was preoperative pain, measured at five timepoints using a visual analogue scale (VAS). Preoperative opioid consumption was also registered. The study sample comprised 266 patients admitted consecutively to the Orthopaedic Ward. The mean age was 84.1 (±6.9)years, 64% of participants were women, 44% lived in residential care facilities, and 120 (45.1%) had dementia diagnoses. Patients receiving femoral nerve block had significantly lower self-rated pain scores from baseline to 12h after admission than did controls. Self-rated and proxy VAS pain scores decreased significantly in these patients from baseline to 12h compared with controls (p<0.001 and p=0.003, respectively). Patients receiving femoral nerve block required less opioids than did controls, overall (2.3±4.0 vs. 5.7±5.2mg, p<0.001) and in the subgroup with dementia (2.1±3.3 vs. 5.8±5.0mg, p<0.001). Patients with hip fracture, including those with dementia, who received femoral nerve block had lower pain scores and required less opioids before surgery compared with those receiving conventional pain management. Femoral nerve block seems to be a feasible pain treatment for elderly people, including those with dementia. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of addition of dexamethasone to ropivacaine on post-operative analgesia in ultrasonography-guided transversus abdominis plane block for inguinal hernia repair: A prospective, double-blind, randomised controlled trial.

PubMed

Sharma, Uma Datt; Prateek; Tak, Himani

2018-05-01

Ultrasonography (USG)-guided transversus abdominis plane (TAP) block is an abdominal field block with high efficacy. This study was undertaken with the aim of determining the effect of the addition of dexamethasone to 0.5% ropivacaine on post-operative analgesia in USG-guided TAP block for inguinal hernia repair. A double-blind randomised control study was conducted on sixty patients posted for inguinal hernia repair with the American Society of Anesthesiologists physical Status I or II, who were allocated two groups of 30 each. Patients in Group RS received 0.5% ropivacaine (20 ml) and normal saline (2 ml) whereas patients in Group RD received 0.5% ropivacaine (20 ml) and dexamethasone (2 ml, i.e., 8 mg), in USG-guided TAP Block on the same side, after repair of inguinal hernia under spinal anaesthesia. Visual analogue scale (VAS) scores, time for request of first analgesia and total tramadol consumption in first 24 h were compared. Unpaired Student's t -test and Mann-Whitney U-test were performed using SPSS 23 Software. Patients in Group RD had significantly lower VAS scores as compared to Group RS from 4 th to 12 th h, postoperatively. Duration of analgesia was significantly more in Group RD (547.50 [530,530] min) when compared with Group RS (387.50 [370,400] min) ( P < 0.001). The demand for intravenous tramadol was significantly low in Group RD (223.33 ± 56.83 mg) as compared to Group RS (293.33 ± 25.71 mg) ( P < 0.001). Addition of dexamethasone to ropivacaine in USG-guided TAP block significantly reduces post-operative pain and prolongs the duration of post-operative analgesia, thereby reducing analgesic consumption.

Investigation into the visual perceptive ability of anaesthetists during ultrasound-guided interscalene and femoral blocks conducted on soft embalmed cadavers: a randomised single-blind study.

PubMed

Mustafa, A; Seeley, J; Munirama, S; Columb, M; McKendrick, M; Schwab, A; Corner, G; Eisma, R; Mcleod, G

2018-04-01

Errors may occur during regional anaesthesia whilst searching for nerves, needle tips, and test doses. Poor visual search impacts on decision making, clinical intervention, and patient safety. We conducted a randomised single-blind study in a single university hospital. Twenty trainees and two consultants examined the paired B-mode and fused B-mode and elastography video recordings of 24 interscalene and 24 femoral blocks conducted on two soft embalmed cadavers. Perineural injection was randomised equally to 0.25, 0.5, and 1.0 ml volumes. Tissue displacement perceived on both imaging modalities was defined as 'target' or 'distractor'. Our primary objective was to test the anaesthetists' perception of the number and proportion of targets and distractors on B-mode and fused elastography videos collected during femoral and sciatic nerve block on soft embalmed cadavers. Our secondary objectives were to determine the differences between novices and experts, and between test-dose volumes, and to measure the area and brightness of spread and strain patterns. All anaesthetists recognised perineural spread using 0.25 ml volumes. Distractor patterns were recognised in 133 (12%) of B-mode and in 403 (38%) of fused B-mode and elastography patterns; P<0.001. With elastography, novice recognition improved from 12 to 37% (P<0.001), and consultant recognition increased from 24 to 53%; P<0.001. Distractor recognition improved from 8 to 31% using 0.25 ml volumes (P<0.001), and from 15 to 45% using 1 ml volumes (P<0.001). Visual search improved with fusion elastography, increased volume, and consultants. A need exists to investigate image search strategies. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Improving the retention rate for residential treatment of substance abuse by sequential intervention for social anxiety.

PubMed

Staiger, Petra K; Kyrios, Michael; Williams, James S; Kambouropoulos, Nicolas; Howard, Alexandra; Gruenert, Stefan

2014-02-17

Residential drug rehabilitation is often seen as a treatment of last resort for people with severe substance abuse issues. These clients present with more severe symptoms, and frequent psychiatric comorbidities relative to outpatients. Given the complex nature of this client group, a high proportion of clients seeking treatment often do not enter treatment, and of those who do, many exit prematurely. Given the highly social nature of residential drug rehabilitation services, it has been argued that social anxieties might decrease the likelihood of an individual entering treatment, or increase the likelihood of them prematurely exiting treatment. The current paper reports on the protocol of a Randomised Control Trial which examined whether treatment of social anxiety prior to entry to treatment improves entry rates and retention in residential drug rehabilitation. A Randomised Control Trial comparing a social skills treatment with a treatment as usual control group was employed. The social skills training program was based on the principles of Cognitive Behaviour Therapy, and was adapted from Ron Rapee's social skills training program. A permutated block randomisation procedure was utilised. Participants are followed up at the completion of the program (or baseline plus six weeks for controls) and at three months following entry into residential rehabilitation (or six months post-baseline for participants who do not enter treatment). The current study could potentially have implications for addressing social anxiety within residential drug treatment services in order to improve entry and retention in treatment. The results might suggest that the use of additional screening tools in intake assessments, a focus on coping with social anxieties in support groups for clients waiting to enter treatment, and greater awareness of social anxiety issues is warranted. Australian New Zealand Clinical Trials Registry (ACTRN) registration number: ACTRN12611000579998.

Effects of a probiotic intervention in acute canine gastroenteritis--a controlled clinical trial.

PubMed

Herstad, H K; Nesheim, B B; L'Abée-Lund, T; Larsen, S; Skancke, E

2010-01-01

To evaluate the effect of a probiotic product in acute self-limiting gastroenteritis in dogs. Thirty-six dogs suffering from acute diarrhoea or acute diarrhoea and vomiting were included in the study. The trial was performed as a randomised, double blind and single centre study with stratified parallel group design. The animals were allocated to equal looking probiotic or placebo treatment by block randomisation with a fixed block size of six. The probiotic cocktail consisted of thermo-stabilised Lactobacillus acidophilus and live strains of Pediococcus acidilactici, Bacillus subtilis, Bacillus licheniformis and Lactobacillus farciminis. The time from initiation of treatment to the last abnormal stools was found to be significantly shorter (P = 0.04) in the probiotic group compared to placebo group, the mean time was 1.3 days and 2.2 days, respectively. The two groups were found nearly equal with regard to time from start of treatment to the last vomiting episode. The probiotic tested may reduce the convalescence time in acute self-limiting diarrhoea in dogs.

[Physical therapy of frozen shoulder: literature review].

PubMed

Alvado, A; Pélissier, J; Bénaim, C; Petiot, S; Hérisson, C

2001-03-01

To determine the efficacy of physical treatments in adhesive capsulitis of the shoulder by a systematic review of literature, attempting to perform a meta-analysis from randomised clinical trials. A systematic literature search was conducted to retrieve all randomised controlled trials of physical therapy such as physiotherapy and manipulation, but also arthrographic distension, mobilisation under general anaesthesia or nerve block, arthroscopic distension or arthrolysis, and intra-articular corticoid injections. The main outcome for meta-analysis was the restoration of range of movement between the sixth week and the third month. Only 16 articles could be selected, and only three about capsular distension were included in a meta-analysis because of the heterogeneity of the criteria assessing the functional results and of the poor methodological value of most of the articles. Some open studies stressed the value of daily manipulations and physiotherapy, intra-articular corticosteroid injections, but their quality was poor or limited. Nothing was written about antalgic drugs to facilitate joint mobilisation, and the use of a thoraco-brachial abduction device between exercises was only quoted. The most refractory cases might need more aggressive interventions: arthrographic distension with local anaesthesia and steroid injection; mobilisation under general or local anaesthesia, specially interscalene brachial plexus block; arthroscopic release. But there was no randomised controlled study comparing these three techniques and it seemed impossible to come to any conclusion about the superiority of one of them. The meta-analysis showed yet that capsular distension with intra-articular corticoid injections was better than corticoid injections alone. This demonstrated the need of a consensus about the criteria of assessment, the time of evaluation, before assessing by randomised clinical trials of good quality their therapeutic value.

A randomised controlled trial investigating the analgesic efficacy of transversus abdominis plane block for adult laparoscopic appendicectomy.

PubMed

Tupper-Carey, Darell Alexander; Fathil, Shahridan Mohd; Tan, Yin Kiat Glenn; Kan, Yuk Man; Cheong, Chern Yuen; Siddiqui, Fahad Javaid; Assam, Pryseley Nkouibert

2017-08-01

We conducted a single-centre, prospective randomised clinical trial to investigate the analgesic efficacy of transversus abdominis plane (TAP) block in adult patients undergoing laparoscopic appendicectomy. Patients undergoing urgent laparoscopic appendicectomy under general anaesthesia alone (control group) and general anaesthesia supplemented by TAP block (TAP intervention group) were compared. All patients received a multimodal analgesia regime, which included postoperative morphine via a patient-controlled analgesia device. The primary endpoints were morphine consumption at 12 hours and 24 hours postoperatively. Secondary endpoints included pain scores, incidence of nausea and vomiting, and time to hospital discharge. A total of 58 patients were recruited, with 29 patients in each group. Mean postoperative morphine consumption at 12 hours (control group: 11.45 ± 7.64 mg, TAP intervention group: 9.79 ± 8.09 mg; p = 0.4264) and 24 hours (control group: 13.38 ± 8.72 mg, TAP intervention group: 11.31 ± 8.66 mg; p = 0.3686) for the control and TAP intervention groups were not statistically different. Secondary outcomes were also not different between the two groups. Length of stay in the post-anaesthesia care unit was significantly shorter for the TAP intervention group, with a trend toward faster hospital discharge being observed. TAP block, a regional anaesthetic procedure performed immediately prior to skin incision for laparoscopic appendicectomy, did not significantly improve postoperative analgesia outcomes. Copyright: © Singapore Medical Association

An oral health intervention for people with serious mental illness (Three Shires Early Intervention Dental Trial): study protocol for a randomised controlled trial.

PubMed

Jones, Hannah F; Adams, Clive E; Clifton, Andrew; Simpson, Jayne; Tosh, Graeme; Liddle, Peter F; Callaghan, Patrick; Yang, Min; Guo, Boliang; Furtado, Vivek

2013-05-29

Oral health is an important part of general physical health and is essential for self-esteem, self-confidence and overall quality of life. There is a well-established link between mental illness and poor oral health. Oral health problems are not generally well recognized by mental health professionals and many patients experience barriers to treatment. This is the protocol for a pragmatic cluster randomised trial that has been designed to fit within standard care. Dental awareness training for care co-ordinators plus a dental checklist for service users in addition to standard care will be compared with standard care alone for people with mental illness. The checklist consists of questions about service users' current oral health routine and condition. Ten Early Intervention in Psychosis (EIP) teams in Nottinghamshire, Derbyshire and Lincolnshire will be cluster randomised (five to intervention and five to standard care) in blocks accounting for location and size of caseload. The oral health of the service users will be monitored for one year after randomisation. Current Controlled Trials ISRCTN63382258.

Does regional compared to local anaesthesia influence outcome after arteriovenous fistula creation?

PubMed

Macfarlane, Alan James Robert; Kearns, Rachel Joyce; Aitken, Emma; Kinsella, John; Clancy, Marc James

2013-08-19

An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis. Unfortunately, approximately one-third of fistulae fail at an early stage. Different anaesthetic techniques can influence factors associated with fistula success, such as intraoperative blood flow and venous diameter. A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone. This, however, has not yet been shown in a large trial to influence long-term fistula patency, the ultimate clinical measure of success.The aim of this study is to compare whether a regional anaesthetic block, compared to local anaesthetic infiltration, can improve long-term fistula patency. This study is an observer-blinded, randomised controlled trial. Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet, and consent will be obtained in keeping with the Declaration of Helsinki. Patients will be randomised to receive either: (i) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine, or (ii) local anaesthetic infiltration with lignocaine and levobupivicaine.A total of 126 patients will be recruited. The primary outcome is fistula primary patency at three months. Secondary outcomes include primary patency at 1 and 12 months, secondary patency and fistula flow at 1, 3 and 12 months, flow on first haemodialysis, procedural pain, patient satisfaction, change in cephalic vein diameter pre- and post-anaesthetic, change in radial or brachial artery flow pre- and post-anaesthetic, alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound, and fistula infection requiring antibiotics. No large randomised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae. If the performance of brachial plexus block increases fistulae patency, this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase, and the number of "redo" or revision procedures should be reduced. This study has been approved by the West of Scotland Research Ethics Committee 5 (reference no. 12/WS/0199) and is registered with the ClinicalTrials.gov database (reference no. NCT01706354).

Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

PubMed

O'Scanaill, P; Keane, S; Wall, V; Flood, G; Buggy, D J

2018-04-01

Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h -1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. AUC moving was mean (SD) 71 (34) mm h -1 vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. NCT 03024697. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial.

PubMed

de Bruin, Marijn; Oberjé, Edwin J M; Viechtbauer, Wolfgang; Nobel, Hans-Erik; Hiligsmann, Mickaël; van Nieuwkoop, Cees; Veenstra, Jan; Pijnappel, Frank J; Kroon, Frank P; van Zonneveld, Laura; Groeneveld, Paul H P; van Broekhuizen, Marjolein; Evers, Silvia M A A; Prins, Jan M

2017-06-01

No high-quality trials have provided evidence of effectiveness and cost-effectiveness of HIV treatment adherence intervention strategies. We therefore examined the effectiveness and cost-effectiveness of the Adherence Improving self-Management Strategy (AIMS) compared with treatment as usual. We did a pragmatic, multicentre, open-label, randomised controlled trial in seven HIV clinics at academic and non-academic hospitals in the Netherlands. Eligible participants were patients with HIV who were either treatment experienced (ie, with ≥9 months on combination antiretroviral therapy [ART] and at risk of viral rebound) or treatment-naive patients initiating their first combination ART regimen. We randomly assigned participants (1:1) to either AIMS or treatment as usual (ie, containing a range of common adherence intervention strategies) using a computer-generated randomisation table. Randomisation was stratified by treatment experience (experienced vs naive) and included block randomisation at nurse level with randomly ordered blocks of size four, six, and eight. 21 HIV nurses from the participating clinics received three training sessions of 6 h each (18 h in total) on AIMS and a 1·5 h booster training session at the clinic (two to three nurses per session) after each nurse had seen two to three patients. AIMS was delivered by nurses during routine clinic visits. We did mixed-effects, intent-to-treat analyses to examine treatment effects on the primary outcome of log 10 viral load collected at months 5, 10, and 15. The viral load results were exponentiated (with base 10) for easier interpretation. Using cohort data from 7347 Dutch patients with HIV to calculate the natural course of illness, we developed a lifetime Markov model to estimate the primary economic outcome of lifetime societal costs per quality-adjusted life-years (QALYs) gained. This trial is registered at ClinicalTrials.gov (number NCT01429142). We recruited participants between Sept 1, 2011, and April 2, 2013; the last patient completed the study on June 16, 2014. The intent-to-treat sample comprised 221 patients; 109 assigned to AIMS and 112 to treatment as usual. Across the three timepoints (months 5, 10, and 15), log viral load was 1·26 times higher (95% CI 1·04-1·52) in the treatment-as-usual group (estimated marginal mean 44·5 copies per mL [95% CI 35·5-55·9]) than in the AIMS group (estimated marginal mean 35·4 copies per mL [29·9-42·0]). Additionally, AIMS was cost-effective (ie, dominant: cheaper and more effective) since it reduced lifetime societal costs by €592 per patient and increased QALYs by 0·034 per patient. Findings from preparatory studies have shown that AIMS is acceptable, feasible to deliver in routine care, and has reproducible effects on medication adherence. In this study, AIMS reduced viral load, increased QALYs, and saved resources. Implementation of AIMS in routine clinical HIV care is therefore recommended. Netherlands Organisation for Health Research and Development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Post-deployment screening for mental disorders and tailored advice about help-seeking in the UK military: a cluster randomised controlled trial.

PubMed

Rona, Roberto J; Burdett, Howard; Khondoker, Mizanur; Chesnokov, Melanie; Green, Kevin; Pernet, David; Jones, Norman; Greenberg, Neil; Wessely, Simon; Fear, Nicola T

2017-04-08

The effectiveness of post-deployment screening for mental disorders has not been assessed in a randomised controlled trial. We aimed to assess whether post-deployment screening for post-traumatic stress disorder (PTSD), depression, anxiety, or alcohol misuse was effective. We defined screening as the presumptive identification of a previously unrecognised disorder using tests to distinguish those who probably had the disorder from those who probably did not so that those people with a probable disorder could be referred appropriately, and assessed effectiveness and consequences for help-seeking by the odds ratio at follow-up between those receiving tailored help-seeking advice and those who received general mental health advice. We did a cluster randomised controlled trial among Royal Marines and Army personnel in the UK military after deployment to Afghanistan. Platoons were randomly assigned (1:1 initially, then 2:1) by stratified block randomisation with randomly varying block sizes of two and four to the screening group, which received tailored help-seeking advice, or the control group, which received general mental health advice. Initial assessment took place 6-12 weeks after deployment; follow-up assessments were done 10-24 months later. Follow-up measures were the PTSD Checklist-Civilian Version, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 scale, Alcohol Use Disorder Identification Test (AUDIT), and self-reported help-seeking from clinical and welfare providers comparing those receiving tailored advice and those receiving only general advice. All participants and all investigators other than the person who analysed the data were masked to allocation. The primary outcomes were PTSD, depression or generalised anxiety disorder, and alcohol misuse at follow-up. A key secondary outcome was assessment of whether post-deployment screening followed by tailored advice would modify help-seeking behaviour. Comparisons were made between screening and control groups, with primary analyses by intention to treat. This trial is registered with the ISRCTN Registry, number ISRCTN19965528. Between Oct 24, 2011, and Oct 31, 2014, 434 platoons comprising 10 190 personnel were included: 274 (6350 personnel) in the screening group and 160 (3840 personnel) in the control group. 5577 (88%) of 6350 personnel received screening and 3996 (63%) completed follow-up, whereas 3149 (82%) of 3840 received the control questionnaire and 2369 (62%) completed follow-up. 1958 (35%) of 5577 personnel in the screening group declined to see the tailored advice, but those with PTSD (83%) or anxiety or depression (84%) were more likely than non-cases (64%) to view the advice (both p<0·0001). At follow-up, there were no significant differences in prevalence between groups for PTSD (adjusted odds ratio 0·92, 95% CI 0·75-1·14), depression or anxiety (0·91, 0·71-1·16), alcohol misuse (0·88, 0·73-1·06), or seeking support for mental disorders (0·92, 0·78-1·08). Post-deployment screening for mental disorders based on tailored advice was not effective at reducing prevalence of mental health disorders nor did it increase help-seeking. Countries that have implemented post-deployment screening programmes for mental disorders should consider monitoring the outcomes of their programmes. The US Army Medical Research and Materiel Command-Military Operational Medicine Research Program (USAMRMC-MOMRP). Copyright © 2017 Elsevier Ltd. All rights reserved.

A randomised controlled trial of three or one breathing technique training sessions for breathlessness in people with malignant lung disease.

PubMed

Johnson, Miriam J; Kanaan, Mona; Richardson, Gerry; Nabb, Samantha; Torgerson, David; English, Anne; Barton, Rachael; Booth, Sara

2015-09-07

About 90 % of patients with intra-thoracic malignancy experience breathlessness. Breathing training is helpful, but it is unknown whether repeated sessions are needed. The present study aims to test whether three sessions are better than one for breathlessness in this population. This is a multi-centre randomised controlled non-blinded parallel arm trial. Participants were allocated to three sessions or single (1:2 ratio) using central computer-generated block randomisation by an independent Trials Unit and stratified for centre. The setting was respiratory, oncology or palliative care clinics at eight UK centres. Inclusion criteria were people with intrathoracic cancer and refractory breathlessness, expected prognosis ≥3 months, and no prior experience of breathing training. The trial intervention was a complex breathlessness intervention (breathing training, anxiety management, relaxation, pacing, and prioritisation) delivered over three hour-long sessions at weekly intervals, or during a single hour-long session. The main primary outcome was worst breathlessness over the previous 24 hours ('worst'), by numerical rating scale (0 = none; 10 = worst imaginable). Our primary analysis was area under the curve (AUC) 'worst' from baseline to 4 weeks. All analyses were by intention to treat. Between April 2011 and October 2013, 156 consenting participants were randomised (52 three; 104 single). Overall, the 'worst' score reduced from 6.81 (SD, 1.89) to 5.84 (2.39). Primary analysis [n = 124 (79 %)], showed no between-arm difference in the AUC: three sessions 22.86 (7.12) vs single session 22.58 (7.10); P value = 0.83); mean difference 0.2, 95 % CIs (-2.31 to 2.97). Complete case analysis showed a non-significant reduction in QALYs with three sessions (mean difference -0.006, 95 % CIs -0.018 to 0.006). Sensitivity analyses found similar results. The probability of the single session being cost-effective (threshold value of £20,000 per QALY) was over 80 %. There was no evidence that three sessions conferred additional benefits, including cost-effectiveness, over one. A single session of breathing training seems appropriate and minimises patient burden. Registry: ISRCTN; ISRCTN49387307; http://www.isrctn.com/ISRCTN49387307 ; registration date: 25/01/2011.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.

PubMed

Holtzheimer, Paul E; Husain, Mustafa M; Lisanby, Sarah H; Taylor, Stephan F; Whitworth, Louis A; McClintock, Shawn; Slavin, Konstantin V; Berman, Joshua; McKhann, Guy M; Patil, Parag G; Rittberg, Barry R; Abosch, Aviva; Pandurangi, Ananda K; Holloway, Kathryn L; Lam, Raymond W; Honey, Christopher R; Neimat, Joseph S; Henderson, Jaimie M; DeBattista, Charles; Rothschild, Anthony J; Pilitsis, Julie G; Espinoza, Randall T; Petrides, Georgios; Mogilner, Alon Y; Matthews, Keith; Peichel, DeLea; Gross, Robert E; Hamani, Clement; Lozano, Andres M; Mayberg, Helen S

2017-11-01

Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Abbott (previously St Jude Medical). Copyright © 2017 Elsevier Ltd. All rights reserved.

Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.

PubMed

Watts, Gareth J; Clark, Katherine; Agar, Meera; Davidson, Patricia M; McDonald, Christine; Lam, Lawrence T; Sajkov, Dimitar; McCaffrey, Nicola; Doogue, Matthew; Abernethy, Amy P; Currow, David C

2016-11-29

Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. ACTRN12610000464066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Antenatal exercise in overweight and obese women and its effects on offspring and maternal health: design and rationale of the IMPROVE (Improving Maternal and Progeny Obesity Via Exercise) randomised controlled trial.

PubMed

Seneviratne, Sumudu N; Parry, Graham K; McCowan, Lesley Me; Ekeroma, Alec; Jiang, Yannan; Gusso, Silmara; Peres, Geovana; Rodrigues, Raquel O; Craigie, Susan; Cutfield, Wayne S; Hofman, Paul L

2014-04-26

Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life. The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of <20 weeks of gestation, from the Auckland region, are eligible for the trial. Exclusion criteria are ongoing smoking or medical contra-indications to antenatal exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition. The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their offspring. Australian New Zealand Clinical Trials Registry ACTRN12612000932864.

How completely are physiotherapy interventions described in reports of randomised trials?

PubMed

Yamato, Tiê P; Maher, Chris G; Saragiotto, Bruno T; Hoffmann, Tammy C; Moseley, Anne M

2016-06-01

Incomplete descriptions of interventions are a common problem in reports of randomised controlled trials. To date no study has evaluated the completeness of the descriptions of physiotherapy interventions. To evaluate the completeness of the descriptions of physiotherapy interventions in a random sample of reports of randomised controlled trials (RCTs). A random sample of 200 reports of RCTs from the PEDro database. We included full text papers, written in English, and reporting trials with two arms. We included trials evaluating any type of physiotherapy interventions and subdisciplines. The methodological quality was evaluated using the PEDro scale and completeness of intervention description using the Template for Intervention Description and Replication (TIDieR) checklist. The proportion and 95% confidence interval were calculated for intervention and control groups, and used to present the relationship between completeness and methodological quality, and subdisciplines. Completeness of intervention reporting in physiotherapy RCTs was poor. For intervention groups, 46 (23%) trials did not describe at least half of the items. Reporting was worse for control groups, 149 (75%) trials described less than half of the items. There was no clear difference in the completeness across subdisciplines or methodological quality. Our sample were restricted to trials published in English in 2013. Descriptions of interventions in physiotherapy RCTs are typically incomplete. Authors and journals should aim for more complete descriptions of interventions in physiotherapy trials. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

A pragmatic randomised controlled trial comparing the efficacy of a femoral nerve block and periarticular infiltration for early pain relief following total knee arthroplasty.

PubMed

Wall, P D H; Parsons, N R; Parsons, H; Achten, J; Balasubramanian, S; Thompson, P; Costa, M L

2017-07-01

The aim of this study was to compare the effectiveness of a femoral nerve block and a periarticular infiltration in the management of early post-operative pain after total knee arthroplasty (TKA). A pragmatic, single centre, two arm parallel group, patient blinded, randomised controlled trial was undertaken. All patients due for TKA were eligible. Exclusion criteria included contraindications to the medications involved in the study and patients with a neurological abnormality of the lower limb. Patients received either a femoral nerve block with 75 mg of 0.25% levobupivacaine hydrochloride around the nerve, or periarticular infiltration with 150 mg of 0.25% levobupivacaine hydrochloride, 10 mg morphine sulphate, 30 mg ketorolac trometamol and 0.25 mg of adrenaline all diluted with 0.9% saline to make a volume of 150 ml. A total of 264 patients were recruited and data from 230 (88%) were available for the primary analysis. Intention-to-treat analysis of the primary outcome measure of a visual analogue score for pain on the first post-operative day, prior to physiotherapy, was similar in both groups. The mean difference was -0.7 (95% confidence interval (CI) -5.9 to 4.5; p = 0.834). The periarticular group used less morphine in the first post-operative day compared with the femoral nerve block group (74%, 95% CI 55 to 99). The femoral nerve block group reported 39 adverse events, of which 27 were serious, in 31 patients and the periarticular group reported 51 adverse events, of which 38 were serious, in 42 patients up to six weeks post-operatively. None of the adverse events were directly attributed to either of the interventions under investigation. Periarticular infiltration is a viable and safe alternative to femoral nerve block for the early post-operative relief of pain following TKA. Cite this article: Bone Joint J 2017;99-B:904-11. ©2017 The British Editorial Society of Bone & Joint Surgery.

The effect of a conditional cash transfer on HIV incidence in young women in rural South Africa (HPTN 068): a phase 3, randomised controlled trial

PubMed Central

Pettifor, Audrey; MacPhail, Catherine; Hughes, James P; Selin, Amanda; Wang, Jing; Gómez-Olivé, F Xavier; Eshleman, Susan H; Wagner, Ryan G; Mabuza, Wonderful; Khoza, Nomhle; Suchindran, Chirayath; Mokoena, Immitrude; Twine, Rhian; Andrew, Philip; Townley, Ellen; Laeyendecker, Oliver; Agyei, Yaw; Tollman, Stephen; Kahn, Kathleen

2017-01-01

Summary Background Cash transfers have been proposed as an intervention to reduce HIV-infection risk for young women in sub-Saharan Africa. However, scarce evidence is available about their effect on reducing HIV acquisition. We aimed to assess the effect of a conditional cash transfer on HIV incidence among young women in rural South Africa. Methods We did a phase 3, randomised controlled trial (HPTN 068) in the rural Bushbuckridge subdistrict in Mpumalanga province, South Africa. We included girls aged 13–20 years if they were enrolled in school grades 8–11, not married or pregnant, able to read, they and their parent or guardian both had the necessary documentation necessary to open a bank account, and were residing in the study area and intending to remain until trial completion. Young women (and their parents or guardians) were randomly assigned (1:1), by use of numbered sealed envelopes containing a randomisation assignment card which were numerically ordered with block randomisation, to receive a monthly cash transfer conditional on school attendance (≥80% of school days per month) versus no cash transfer. Participants completed an Audio Computer-Assisted Self-Interview (ACASI), before test HIV counselling, HIV and herpes simplex virus (HSV)-2 testing, and post-test counselling at baseline, then at annual follow-up visits at 12, 24, and 36 months. Parents or guardians completed a Computer-Assisted Personal Interview at baseline and each follow-up visit. A stratified proportional hazards model was used in an intention-to-treat analysis of the primary outcome, HIV incidence, to compare the intervention and control groups. This study is registered at ClinicalTrials.gov (NCT01233531). Findings Between March 5, 2011, and Dec 17, 2012, we recruited 10 134 young women and enrolled 2537 and their parents or guardians to receive a cash transfer programme (n=1225) or not (control group; n=1223). At baseline, the median age of girls was 15 years (IQR 14–17) and 672 (27%) had reported to have ever had sex. 107 incident HIV infections were recorded during the study: 59 cases in 3048 person-years in the intervention group and 48 cases in 2830 person-years in the control group. HIV incidence was not significantly different between those who received a cash transfer (1.94% per person-years) and those who did not (1.70% per person-years; hazard ratio 1.17, 95% CI 0.80–1.72, p=0.42). Interpretation Cash transfers conditional on school attendance did not reduce HIV incidence in young women. School attendance significantly reduced risk of HIV acquisition, irrespective of study group. Keeping girls in school is important to reduce their HIV-infection risk. Funding National Institute of Allergy and Infectious Diseases, National Institute of Mental Health of the National Institutes of Health. PMID:27815148

Getting the balance right: a randomised controlled trial of physiotherapy and Exercise Interventions for ambulatory people with multiple sclerosis.

PubMed

Coote, Susan; Garrett, Maria; Hogan, Neasa; Larkin, Aidan; Saunders, Jean

2009-07-16

People with Multiple Sclerosis have a life long need for physiotherapy and exercise interventions due to the progressive nature of the disease and their greater risk of the complications of inactivity. The Multiple Sclerosis Society of Ireland run physiotherapy, yoga and exercise classes for their members, however there is little evidence to suggest which form of physical activity optimises outcome for people with the many and varied impairments associated with MS. This is a multi-centre, single blind, block randomised, controlled trial. Participants will be recruited via the ten regional offices of MS Ireland. Telephone screening will establish eligibility and stratification according to the mobility section of the Guys Neurological Disability Scale. Once a block of people of the same strand in the same geographical region have given consent, participants will be randomised. Strand A will concern individuals with MS who walk independently or use one stick to walk outside. Participants will be randomised to yoga, physiotherapy led exercise class, fitness instructor led exercise class or to a control group who don't change their exercise habits.Strand B will concern individuals with MS who walk with bilateral support or a rollator, they may use a wheelchair for longer distance outdoors. Participants will be randomised to 1:1 Physiotherapist led intervention, group intervention led by Physiotherapist, group yoga intervention or a control group who don't change their exercise habits. Participants will be assessed by physiotherapist who is blind to the group allocation at week 1, week 12 (following 10 weeks intervention or control), and at 12 week follow up. The primary outcome measure for both strands is the Multiple Sclerosis Impact Scale. Secondary outcomes are Modified Fatigue Impact Scale, 6 Minute Walk test, and muscle strength measured with hand held dynamometry. Strand B will also use Berg Balance Test and the Modified Ashworth Scale. Confounding variables such as sensation, coordination, proprioception, range of motion and other impairments will be recorded at initial assessment. Data analysis will analyse change in each group, and the differences between groups. Sub group analysis may be performed if sufficient numbers are recruited. ISRCTN77610415.

A randomised, controlled, double-blind trial of ultrasound-guided phrenic nerve block to prevent shoulder pain after thoracic surgery.

PubMed

Blichfeldt-Eckhardt, M R; Laursen, C B; Berg, H; Holm, J H; Hansen, L N; Ørding, H; Andersen, C; Licht, P B; Toft, P

2016-12-01

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel-group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer-generated list to receive an ultrasound-guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre-packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22-67%), relative risk reduction 65% (95% CI 41-80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound-guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

The benefit of tissue contact monitoring with an electrical coupling index during ablation of typical atrial flutter--a prospective randomised control trial.

PubMed

Jones, Michael A; Webster, David; Wong, Kelvin C K; Hayes, Christopher; Qureshi, Norman; Rajappan, Kim; Bashir, Yaver; Betts, Timothy R

2014-12-01

We sought to investigate the use of tissue contact monitoring by means of the electrical coupling index (ECI) in a prospective randomised control trial of patients undergoing cavotricuspid isthmus (CTI) ablation for atrial flutter. Patients with ECG-documented typical flutter undergoing their first CTI ablation were randomised to ECI™-guided or non-ECI™-guided ablation. An irrigated-tip ablation catheter was used in all cases. Consecutive 50-W, 60-s radiofrequency lesions were applied to the CTI, from the tricuspid valve to inferior vena cava, with no catheter movement permitted during radiofrequency (RF) delivery. The ablation endpoint was durable CTI block at 20 min post-ablation. Patients underwent routine clinic follow-up post-operatively. A total of 101 patients (79 male), mean age 66 (+/-11), 50 ECI-guided and 51 control cases were enrolled in the study. CTI block was achieved in all. There were no acute complications. All patients were alive at follow-up. CTI block was achieved in a single pass in 36 ECI-guided and 30 control cases (p = 0.16), and at 20 min post-ablation, re-conduction was seen in 5 and 12 cases, respectively (p = 0.07). There was no significant difference in total procedure time (62.7 ± 33 vs. 62.3 ± 33 min, p = 0.92), RF requirement (580 ± 312 vs. 574 ± 287 s, p = 0.11) or fluoroscopy time (718 ± 577 vs. 721 ± 583 s, p = 0.78). After 6 ± 4 months, recurrence of flutter had occurred in 1 (2 %) ECI vs. 8 (16 %) control cases (OR 0.13, 95 % CI 0.01-1.08, p = 0.06). ECI-guided CTI ablation demonstrated a non-statistically significant reduction in late recurrence of atrial flutter, at no cost to procedural time, radiation exposure or RF requirement.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

Study protocol of a multicentre randomised controlled trial of self-help cognitive behaviour therapy for working women with menopausal symptoms (MENOS@Work).

PubMed

Hunter, Myra S; Hardy, Claire; Norton, Sam; Griffiths, Amanda

2016-10-01

Hot flushes and night sweats (HFNS) - the main symptoms of the menopause transition - can reduce quality of life and are particularly difficult to manage at work. A cognitive behaviour therapy (CBT) intervention has been developed specifically for HFNS that is theoretically based and shown to reduce significantly the impact of HFNS in several randomised controlled trials (RCTs). Self-help CBT has been found to be as effective as group CBT for these symptoms, but these interventions are not widely available in the workplace. This paper describes the protocol of an RCT aiming to assess the efficacy of CBT for menopausal symptoms implemented in the workplace, with a nested qualitative study to examine acceptability and feasibility. One hundred menopausal working women, aged 45-60 years, experiencing bothersome HFNS for two months will be recruited from several (2-10) large organisations into a multicentre randomised controlled trial. Women will be randomly assigned to either treatment (a self-help CBT intervention lasting 4 weeks) or to a no treatment-wait control condition (NTWC), following a screening interview, consent, and completion of a baseline questionnaire. All participants will complete follow-up questionnaires at 6 weeks and 20 weeks post-randomisation. The primary outcome is the rating of HFNS; secondary measures include HFNS frequency, mood, quality of life, attitudes to menopause, HFNS beliefs and behaviours, work absence and presenteeism, job satisfaction, job stress, job performance, disclosure to managers and turnover intention. Adherence, acceptability and feasibility will be assessed at 20 weeks post-randomisation in questionnaires and qualitative interviews. Upon trial completion, the control group will also be offered the intervention. This is the first randomised controlled trial of a self-management intervention tailored for working women who have troublesome menopausal symptoms. Clin.Gov NCT02623374. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Using discrete choice experiments as a decision aid in total knee arthroplasty: study protocol for a randomised controlled trial.

PubMed

Dowsey, Michelle M; Scott, Anthony; Nelson, Elizabeth A; Li, Jinhu; Sundararajan, Vijaya; Nikpour, Mandana; Choong, Peter F M

2016-08-19

Osteoarthritis (OA) is a leading cause of disability in developed nations. Total knee arthroplasty (TKA) is a clinically effective treatment for people with end-stage knee OA, and represents one of the highest volume medical interventions globally. However, up to one in three patients remain dissatisfied following TKA. Research indicates that the strongest predictor of patient dissatisfaction following TKA is unmet expectations. This study will use a discrete choice experiment (DCE) provided to patients to improve knowledge of the expected outcomes of TKA. This increased knowledge is based on actual outcome data and is hypothesised to optimise patient expectations of TKA outcomes, thereby increasing their satisfaction and self-reported health outcomes. One hundred and thirty-two people with end-stage OA on the waiting list for TKA will be recruited and randomly allocated to one of two groups using computer-generated block randomisation. A randomised controlled trial (RCT) adhering to SPIRIT and CONSORT guidelines will evaluate the effect of administering a DCE prior to surgery on patient-reported pain and function and satisfaction following TKA. Patients in the intervention arm will complete a survey containing the DCE, compared to the control group who will complete a modified survey that does not contain the DCE activity. The DCE contains information on actual risks of postoperative complications, as well as health status after TKA. The DCE encourages patients to actively make trade-offs between risks and health outcomes to elicit their preferences. Participants in both groups will be required to complete the survey after consenting to have the procedure, but prior to surgery during their routine preadmission appointment at St. Vincent's Hospital, Melbourne, Australia (SVHM). Patients in both the intervention and control groups will also be required to complete a brief patient expectation survey 1 week prior to scheduled TKA. In addition, orthopaedic surgeons will complete a brief expectations survey for each patient consented for TKA to compare matched surgeon and patient expectations for recovery following TKA. Primary outcomes will be evaluated by a blinded examiner at 12 months post surgery using a validated self-reported pain and physical function scale, and a validated patient satisfaction scale. Secondary outcomes will include a range of validated measures of health and psychological wellbeing. All analyses will be conducted on an intention-to-treat basis using linear regression models. This study is the first of its kind to use a DCE to provide information to patients to optimise their expectations of the outcomes of surgery. Reducing the rate of patient dissatisfaction commonly seen in patients following TKA will help to reduce the burden associated with poor outcomes on the health system. Australian New Zealand Clinical Trials Registry ( ACTRN12615001226594p ). Version 1; registered on 9 November 2015.

Liposomal bupivacaine peripheral nerve block for the management of postoperative pain.

PubMed

Hamilton, Thomas W; Athanassoglou, Vassilis; Trivella, Marialena; Strickland, Louise H; Mellon, Stephen; Murray, David; Pandit, Hemant G

2016-08-25

Postoperative pain remains a significant issue with poor perioperative pain management associated with an increased risk of morbidity and mortality. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained release. To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration peripheral nerve block for the management of postoperative pain. We identified randomised trials of liposomal bupivacaine peripheral nerve block for the management of postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), Ovid MEDLINE (1946 to January Week 1 2016), Ovid MEDLINE In-Process (14 January 2016), EMBASE (1974 to 13 January 2016), ISI Web of Science (1945 to 14 January 2016), and reference lists of retrieved articles. We sought unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. The date of the most recent search was 15 January 2016. Randomised, double-blind, placebo- or active-controlled clinical trials of a single dose of liposomal bupivacaine administered as a peripheral nerve block in adults aged 18 years or over undergoing elective surgery at any surgical site. We included trials if they had at least two comparison groups for liposomal bupivacaine peripheral nerve block compared with placebo or other types of analgesia. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We performed analyses using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5. We planned to perform a meta-analysis, however there were insufficient data to ensure a clinically meaningful answer; as such we have produced a 'Summary of findings' table in a narrative format, and where possible we assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). We identified seven studies that met inclusion criteria for this review. Three were recorded as completed (or terminated) but no results were published. Of the remaining four studies (299 participants): two investigated liposomal bupivacaine transversus abdominis plane (TAP) block, one liposomal bupivacaine dorsal penile nerve block, and one ankle block. The study investigating liposomal bupivacaine ankle block was a Phase II dose-escalating/de-escalating trial presenting pooled data that we could not use in our analysis.The studies did not report our primary outcome, cumulative pain score between 0 and 72 hours, and secondary outcomes, mean pain score at 12, 24, 48, 72, or 96 hours. One study reported no difference in mean pain score during the first, second, and third postoperative 24-hour periods in participants receiving liposomal bupivacaine TAP block compared to no TAP block. Two studies, both in people undergoing laparoscopic surgery under TAP block, investigated cumulative postoperative opioid dose, reported opposing findings. One found a lower cumulative opioid consumption between 0 and 72 hours compared to bupivacaine hydrochloride TAP block and one found no difference during the first, second, and third postoperative 24-hour periods compared to no TAP block. No studies reported time to first postoperative opioid or percentage not requiring opioids over the initial 72 hours. No studies reported a health economic analysis or patient-reported outcome measures (outside of pain). The review authors sought data regarding adverse events but none were available, however there were no withdrawals reported to be due to adverse events.Using GRADE, we considered the quality of evidence to be very low with any estimate of effect very uncertain and further research very likely to have an important impact on our confidence in the estimate of effect. All studies were at high risk of bias due to their small sample size (fewer than 50 participants per arm) leading to uncertainty around effect estimates. Additionally, inconsistency of results and sparseness of data resulted in further downgrading of the quality of the data. A lack of evidence has prevented an assessment of the efficacy of liposomal bupivacaine administered as a peripheral nerve block. At present there is a lack of data to support or refute the use of liposomal bupivacaine administered as a peripheral nerve block for the management of postoperative pain. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial.

PubMed

Vietti Violi, Naïk; Duran, Rafael; Guiu, Boris; Cercueil, Jean-Pierre; Aubé, Christophe; Digklia, Antonia; Pache, Isabelle; Deltenre, Pierre; Knebel, Jean-François; Denys, Alban

2018-05-01

Radiofrequency ablation is the recommended treatment for patients with hepatocellular carcinoma who have lesions smaller than 3 cm and are therefore not candidates for surgery. Microwave ablation is a more recent technique with certain theoretical advantages that have not yet been confirmed clinically. We aimed to compare the efficacy of both techniques in the treatment of hepatocellular carcinoma lesions of 4 cm or smaller. We did a randomised controlled, single-blinded phase 2 trial at four tertiary university centres in France and Switzerland. Patients with chronic liver disease and hepatocellular carcinoma with up to three lesions of 4 cm or smaller who were not eligible for surgery were randomised to receive microwave ablation (experimental group) or radiofrequency ablation (control group). Randomisation was centralised and done by use of a fixed block method (block size 4). Patients were randomly assigned by a co-investigator by use of the sealed opaque envelope method and were masked to the treatment; physicians were not masked to treatment, since the devices used were different. The primary outcome was the proportion of lesions with local tumour progression at 2 years of follow-up. Local tumour progression was defined as the appearance of a new nodule with features typical of hepatocellular carcinoma in the edge of the ablation zone. All analyses were done in the per-protocol population. The study is completed, but patients will continue to be followed up for 5 years. This study is registered with ClinicalTrials.gov, number NCT02859753. Between Nov 15, 2011, and Feb 27, 2015, 152 patients were randomly assigned: 76 patients to receive microwave ablation and 76 patients to receive radiofrequency ablation. For the per-protocol analysis, five patients were excluded from the microwave ablation group as were three patients from the radiofrequency ablation group. Median follow-up was 26 months (IQR 18-29) in the microwave ablation group and 25 months (18-34) in the radiofrequency ablation group. At 2 years, six (6%) of 98 lesions had local tumour progression in the microwave ablation group as did 12 (12%) of 104 in the radiofrequency ablation group (risk ratio 1·62, 95% CI 0·66-3·94; p=0·27). Complications were infrequent, with only two grade 4 complications (two events of arterial bleeding requiring embolisation, both in the microwave ablation group) and three grade 3 complications (pneumothorax; lesion of the umbilical vein; and intrahepatic segmental necrosis, all in the radiofrequency ablation group). No treatment-related deaths were reported. Although we did not find that microwave ablation was more effective than radiofrequency ablation for treatment of hepatocellular carcinoma lesions of 4 cm or smaller, our results show that the proportion of lesions with local tumour progression at 2 years of follow-up was low with both tested percutaneous methods. Microsulis (AngioDynamics). Copyright © 2018 Elsevier Ltd. All rights reserved.

Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study

PubMed Central

van de Hei, Susanne; McKinstry, Steven; Bardsley, George; Weatherall, Mark; Beasley, Richard; Fingleton, James

2018-01-01

Objective To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. Design Open label, randomised, controlled feasibility study. Setting Single-centre research institute in New Zealand recruiting participants from the community. Participants 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. Interventions Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). Primary and secondary outcome measures The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. Results In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. Conclusions This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. Trial registration number ACTRN12616000470493; Results. PMID:29593018

Effect of two different house screening interventions on exposure to malaria vectors and on anaemia in children in The Gambia: a randomised controlled trial.

PubMed

Kirby, Matthew J; Ameh, David; Bottomley, Christian; Green, Clare; Jawara, Musa; Milligan, Paul J; Snell, Paul C; Conway, David J; Lindsay, Steve W

2009-09-19

House screening should protect people against malaria. We assessed whether two types of house screening--full screening of windows, doors, and closing eaves, or installation of screened ceilings--could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission. During 2006 and 2007, 500 occupied houses in and near Farafenni town in The Gambia, an area with low use of insecticide-treated bednets, were randomly assigned to receive full screening, screened ceilings, or no screening (control). Randomisation was done by computer-generated list, in permuted blocks of five houses in the ratio 2:2:1. Screening was not treated with insecticide. Exposure to mosquitoes indoors was assessed by fortnightly light trap collections during the transmission season. Primary endpoints included the number of female Anopheles gambiae sensu lato mosquitoes collected per trap per night. Secondary endpoints included frequency of anaemia (haemoglobin concentration <80 g/L) and parasitaemia at the end of the transmission season in children (aged 6 months to 10 years) who were living in the study houses. Analysis was by modified intention to treat (ITT), including all randomised houses for which there were some outcome data and all children from those houses who were sampled for haemoglobin and parasitaemia. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN51184253. 462 houses were included in the modified ITT analysis (full screening, n=188; screened ceilings, n=178; control, n=96). The mean number of A gambiae caught in houses without screening was 37.5 per trap per night (95% CI 31.6-43.3), compared with 15.2 (12.9-17.4) in houses with full screening (ratio of means 0.41, 95% CI 0.31-0.54; p<0.0001) and 19.1 (16.1-22.1) in houses with screened ceilings (ratio 0.53, 0.40-0.70; p<0.0001). 755 children completed the study, of whom 731 had complete clinical and covariate data and were used in the analysis of clinical outcomes. 30 (19%) of 158 children from control houses had anaemia, compared with 38 (12%) of 309 from houses with full screening (adjusted odds ratio [OR] 0.53, 95% CI 0.29-0.97; p=0.04), and 31 (12%) of 264 from houses with screened ceilings (OR 0.51, 0.27-0.96; p=0.04). Frequency of parasitaemia did not differ between intervention and control groups. House screening substantially reduced the number of mosquitoes inside houses and could contribute to prevention of anaemia in children. Medical Research Council.

Improving the retention rate for residential treatment of substance abuse by sequential intervention for social anxiety

PubMed Central

2014-01-01

Background Residential drug rehabilitation is often seen as a treatment of last resort for people with severe substance abuse issues. These clients present with more severe symptoms, and frequent psychiatric comorbidities relative to outpatients. Given the complex nature of this client group, a high proportion of clients seeking treatment often do not enter treatment, and of those who do, many exit prematurely. Given the highly social nature of residential drug rehabilitation services, it has been argued that social anxieties might decrease the likelihood of an individual entering treatment, or increase the likelihood of them prematurely exiting treatment. The current paper reports on the protocol of a Randomised Control Trial which examined whether treatment of social anxiety prior to entry to treatment improves entry rates and retention in residential drug rehabilitation. Method/design A Randomised Control Trial comparing a social skills treatment with a treatment as usual control group was employed. The social skills training program was based on the principles of Cognitive Behaviour Therapy, and was adapted from Ron Rapee’s social skills training program. A permutated block randomisation procedure was utilised. Participants are followed up at the completion of the program (or baseline plus six weeks for controls) and at three months following entry into residential rehabilitation (or six months post-baseline for participants who do not enter treatment). Discussion The current study could potentially have implications for addressing social anxiety within residential drug treatment services in order to improve entry and retention in treatment. The results might suggest that the use of additional screening tools in intake assessments, a focus on coping with social anxieties in support groups for clients waiting to enter treatment, and greater awareness of social anxiety issues is warranted. Australian New Zealand clinical trials registry Australian New Zealand Clinical Trials Registry (ACTRN) registration number: ACTRN12611000579998 PMID:24533512

Strategies to enhance self-efficacy and adherence to home-based pelvic floor muscle exercises did not improve adherence in women with urinary incontinence: a randomised trial.

PubMed

Sacomori, Cinara; Berghmans, Bary; Mesters, Ilse; de Bie, Rob; Cardoso, Fernando Luiz

2015-10-01

Do strategies to enhance self-efficacy and exercise mastery affect adherence to home-based pelvic floor muscle exercises in women with urinary incontinence? Two-arm, parallel, randomised, controlled trial with intention-to-treat analysis. Randomisation was performed using computer-generated random numbers in five blocks of 20 women. Eighty-six women with stress, urgency or mixed urinary incontinence. All participants underwent three individual physiotherapy clinic visits at Day 0, 15 and 30, and 2 further months of home-based pelvic floor muscle exercises. The experimental group also received self-efficacy enhancing interventions, including a structured discussion on accomplishments and goals, a 9-minute video with testimonials, and a reminder. The primary outcome - adherence to at least 20 fast and 20 slow contractions every day - was evaluated with a structured questionnaire at 15, 30 and 90 days after enrolment and completion of a daily diary. A validated questionnaire was used to assess urinary incontinence. Self-efficacy and pelvic floor muscle function were also measured. Seven women withdrew from each group before the Day-30 assessment. There was no difference in adherence to pelvic floor muscle exercises at 90 days between the groups (MD 0.5 points, 95% CI -1.1 to 2.1) on the questionnaire, which was scored from 2 to 21. At Day 90, 56% of the experimental group and 44% of the control group were performing the exercises every day. Adherence scores of both groups decreased during the 2-month follow-up period without any supervised physiotherapy session (p<0.05). The groups did not differ on the remaining secondary outcomes. Discussion of accomplishments and goals, a testimonial video and a reminder did not increase exercise adherence more than exercise mastery. Brazilian Registry of Clinical Trials UTN:U1111-1128-8684. Copyright © 2015 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.

PubMed

Krarup, A L; Ny, L; Astrand, M; Bajor, A; Hvid-Jensen, F; Hansen, M B; Simrén, M; Funch-Jensen, P; Drewes, A M

2011-05-01

Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment. To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Twenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. intention-to-treat. A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1-3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0-5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4±0.3 °C and 0.7±0.3 °C, respectively, P<0.05). AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD. © 2011 Blackwell Publishing Ltd.

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial.

PubMed

Clark, Lucy V; Pesola, Francesca; Thomas, Janice M; Vergara-Williamson, Mario; Beynon, Michelle; White, Peter D

2017-07-22

Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference -4·2 points, 95% CI -6·1 to -2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings. UK National Institute for Health Research Research for Patient Benefit Programme and the Sue Estermann Fund. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

High incidence of post-dural puncture headache in patients with spinal saddle block induced with Quincke needles for anorectal surgery: a randomised clinical trial.

PubMed

Schmittner, Marc D; Terboven, Tom; Dluzak, Michael; Janke, Andrea; Limmer, Marc E; Weiss, Christel; Bussen, Dieter G; Burmeister, Marc A; Beck, Grietje C

2010-06-01

Spinal saddle block represents nearly the ideal anaesthesia technique for anorectal surgery. Post-dural puncture headache (PDPH) is a dreaded complication but can be decreased by the use of non-cutting spinal needles to rates less than 1%. Though, cutting Quincke type needles are still widely used for economic reasons, leading to a higher rate of PDPH. We performed this study to demonstrate a reduction of PDPH by the use of very small 29-G compared with commonly used 25-G Quincke type spinal needles. Two hundred sixteen adult patients (male/female, 19-83 years, ASA status I-III) were randomised 1:1 to groups, in which either a 25-G or a 29-G Quincke type spinal needle was used for a spinal saddle block. The incidence of PDPH was assessed during 1 week after surgery. Thirty-nine of 216 patients developed PDPH but there was no difference between the two needle sizes (25-G, n = 18/106 vs. 29-G, n = 21/110, p = 0.6870). Women suffered significantly more from PDPH than men (23/86 vs. 16/130, p = 0.0069). Ambulatory patients had a later onset of PDPH than in-patients (24 h [0.5-72] vs. 2 h [0.2-96], p = 0.0002) and the headache was more severe in these patients (NRS 7 [2-10] vs. NRS 3 [1-8], p = 0.0009). The use of 29-G compared with 25-G Quincke needles led to no reduction of PDPH and is considerably higher compared with data from pencil-point needles. The use of non-cutting or pencil-point spinal needles should become the standard for performing spinal saddle block.

Recovery characteristics of patients receiving either sugammadex or neostigmine and glycopyrrolate for reversal of neuromuscular block: a randomised controlled trial.

PubMed

Paech, M J; Kaye, R; Baber, C; Nathan, E A

2018-03-01

Sugammadex more rapidly and reliably reverses rocuronium-induced neuromuscular block compared with neostigmine, but it is not known if subsequent patient outcomes, including nausea, vomiting and other aspects of recovery are modified. In this study, we compared the recovery characteristics of sugammadex and neostigmine/glycopyrrolate following reversal of neuromuscular block. This was a single-centre, randomised, blinded, parallel-group clinical trial in women undergoing elective day-surgical laparoscopic gynaecological surgery, with a standardised general anaesthesia regimen that included rocuronium. Neuromuscular block was reversed with either sugammadex 2 mg.kg -1 or neostigmine 40 μg.kg -1 and glycopyrrolate 400 μg. The primary outcome was the incidence of nausea and vomiting during the first six postoperative hours. Secondary outcomes included other measures of postoperative recovery such as patient symptoms and recovery scores. Three-hundred and four women were analysed by intention-to-treat (sugammadex n = 151, neostigmine n = 153), which included four major protocol violations. There was no significant difference between sugammadex and neostigmine groups in the incidence of early nausea and vomiting (49.0% vs. 51.0%, respectively; OR 0.92, 95%CI 0.59-1.45; p = 0.731). Double vision (11.5% vs. 20.0%; p = 0.044) and dry mouth (71.6% vs. 85.5%; p = 0.003) were less common after sugammadex. Sedation scores at 2 h were also lower after sugammadex (median (IQR [range]) 0 (0-3 [0-10]) vs. 2 (0-4.[0-10]); p = 0.021). Twenty-four-hour recovery scores were not significantly different between groups. Reversal with sugammadex in this patient population did not reduce postoperative nausea or vomiting compared with neostigmine/glycopyrrolate. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

A randomised controlled trial of the effect of a head-elevation pillow on intrathecal local anaesthetic spread in caesarean section.

PubMed

Elfil, H; Crowley, L; Segurado, R; Spring, A

2015-11-01

A head-elevation pillow places a patient in a ramped posture, which maximises the view of the larynx during laryngoscopy, particularly in obese parturients. In our institution an elevation pillow is used pre-emptively for neuraxial anaesthesia. We hypothesised that head-elevation may impair cephalad spread of local anaesthetic before caesarean section resulting in a lower block or longer time to achieve a T6 level. We aimed to investigate the effect of head-elevation on spread of intrathecal local anaesthetics during anaesthesia for caesarean section. One-hundred parturients presenting for caesarean section under combined spinal-epidural anaesthesia were randomised to either the standard supine position with lateral displacement or in the supine position with lateral displacement on an head-elevation pillow. Each patient received intrathecal hyperbaric bupivacaine 11 mg, morphine 100 μg and fentanyl 15 μg. Patients were assessed for adequacy of sensory block (T6 or higher) at 10 min. Sensory block to T6 was achieved within 10 min in 65.9% of parturients in the Elevation Pillow Group compared to 95.7% in the Control Group (P<0.05). Compared to the Control Group, patients in the Elevation Pillow Group had greater requirements for epidural supplementation (43.5% vs 2.1%, P<0.001) or conversion to general anaesthesia (9.3% vs 0%, P<0.04). Use of a ramped position with an head-elevation pillow following injection of the intrathecal component of a combined spinal-epidural anaesthetic for scheduled caesarean section was associated with a significantly lower block height at 10min. Copyright © 2015 Elsevier Ltd. All rights reserved.

Social Stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial.

PubMed

Marshall, David; Wright, Barry; Allgar, Victoria; Adamson, Joy; Williams, Christine; Ainsworth, Hannah; Cook, Liz; Varley, Danielle; Hackney, Lisa; Dempster, Paul; Ali, Shehzad; Trepel, Dominic; Collingridge Moore, Danielle; Littlewood, Elizabeth; McMillan, Dean

2016-08-11

To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. 37 primary schools in York, UK. 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. ISRCTN96286707; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Multiple imputation methods for bivariate outcomes in cluster randomised trials.

PubMed

DiazOrdaz, K; Kenward, M G; Gomes, M; Grieve, R

2016-09-10

Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

[Complete atrioventricular block in Duchenne muscular dystrophy].

PubMed

Kuru, Satoshi; Tanahashi, Tamotsu; Matsumoto, Shinjirou; Kitamura, Tetsuya; Konagaya, Masaaki

2012-01-01

We report a case of complete atrioventricular (AV) block in a 40-year-old patient with Duchenne muscular dystrophy (DMD). While he was bed-ridden and required mechanical ventilation, his cardiac involvement was mild. He had the deletion of exon 45-52 in the dystrophin gene. He underwent transient complete AV block and came to require pacemaker implantation due to recurrence of complete AV block ten days after the first attack. Electrophysiological study revealed mild prolonged AH and HV interval. Although DMD patients with AV block have been rarely reported so far, attention should be paid to AV block for patients who prolonged their lives.

Comparison of lidocaine spray and paracervical block application for pain relief during first-trimester surgical abortion: A randomised, double-blind, placebo-controlled trial.

PubMed

Aksoy, Huseyin; Aksoy, Ulku; Ozyurt, Sezin; Ozoglu, Nil; Acmaz, Gokhan; Aydın, Turgut; İdem Karadağ, Özge; Tayyar, Ahter Tanay

2016-07-01

Surgical abortion is one of the most frequently performed gynaecological procedures and its associated pain has always been a problem in gynaecology. Here we studied the analgesic efficacy of lidocaine spray and paracervical block (PCB) in patients undergoing first-trimester surgical abortion. A randomised double-blind placebo-controlled study was conducted on 108 women requesting pregnancy termination. The subjects were randomly assigned into four groups: Group 1 (PCB plus lidocaine spray) (n=27), Group 2 (PCB) (n=27), Group 3 (lidocaine spray) (n=27) and Group 4 (placebo) (n=27). Intra-procedural and post-procedural pain scores were measured with a standard visual analogue scale (VAS). The median VAS scores during procedure in placebo, lidocaine spray, PCB plus lidocaine spray and PCB groups were 8 (7-9), 5 (4-8), 4 (3-4) and 5 (3-5), respectively. The most effective method of pain relief during first-trimester abortion can be achieved through a combined use of PCB plus lidocaine spray. Therefore, lidocaine spray is a non-invasive complementary anaesthetic method versus traditional PCB for first-trimester surgical abortion.

Getting the Balance Right: A randomised controlled trial of physiotherapy and Exercise Interventions for ambulatory people with multiple sclerosis

PubMed Central

Coote, Susan; Garrett, Maria; Hogan, Neasa; Larkin, Aidan; Saunders, Jean

2009-01-01

Background People with Multiple Sclerosis have a life long need for physiotherapy and exercise interventions due to the progressive nature of the disease and their greater risk of the complications of inactivity. The Multiple Sclerosis Society of Ireland run physiotherapy, yoga and exercise classes for their members, however there is little evidence to suggest which form of physical activity optimises outcome for people with the many and varied impairments associated with MS. Methods and design This is a multi-centre, single blind, block randomised, controlled trial. Participants will be recruited via the ten regional offices of MS Ireland. Telephone screening will establish eligibility and stratification according to the mobility section of the Guys Neurological Disability Scale. Once a block of people of the same strand in the same geographical region have given consent, participants will be randomised. Strand A will concern individuals with MS who walk independently or use one stick to walk outside. Participants will be randomised to yoga, physiotherapy led exercise class, fitness instructor led exercise class or to a control group who don't change their exercise habits. Strand B will concern individuals with MS who walk with bilateral support or a rollator, they may use a wheelchair for longer distance outdoors. Participants will be randomised to 1:1 Physiotherapist led intervention, group intervention led by Physiotherapist, group yoga intervention or a control group who don't change their exercise habits. Participants will be assessed by physiotherapist who is blind to the group allocation at week 1, week 12 (following 10 weeks intervention or control), and at 12 week follow up. The primary outcome measure for both strands is the Multiple Sclerosis Impact Scale. Secondary outcomes are Modified Fatigue Impact Scale, 6 Minute Walk test, and muscle strength measured with hand held dynamometry. Strand B will also use Berg Balance Test and the Modified Ashworth Scale. Confounding variables such as sensation, coordination, proprioception, range of motion and other impairments will be recorded at initial assessment. Discussion Data analysis will analyse change in each group, and the differences between groups. Sub group analysis may be performed if sufficient numbers are recruited. Trial registration ISRCTN77610415 PMID:19607666

Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial.

PubMed

Behr, Jürgen; Bendstrup, Elisabeth; Crestani, Bruno; Günther, Andreas; Olschewski, Horst; Sköld, C Magnus; Wells, Athol; Wuyts, Wim; Koschel, Dirk; Kreuter, Michael; Wallaert, Benoît; Lin, Chin-Yu; Beck, Jürgen; Albera, Carlo

2016-06-01

Oral acetylcysteine (also known as N-acetylcysteine) is used with pirfenidone to treat idiopathic pulmonary fibrosis (IPF) in Europe. However, no randomised studies have investigated the safety and tolerability of this combination. The PANORAMA study assessed the safety and tolerability of acetylcysteine combined with pirfenidone in patients with IPF. Exploratory efficacy endpoints were also assessed. We did a double-blind randomised trial at 48 sites in eight countries. Patients with IPF aged 40-80 years and established on pirfenidone (at least 1602 mg/day for 8 weeks or longer) were randomly assigned in a 1:1 ratio by interactive voice response system to receive concomitant oral acetylcysteine (600 mg, three times daily) or placebo for 24 weeks. A stratified blocked randomisation scheme was used with a block size of 4. Randomisation was stratified by dose of pirfenidone (2403 mg/day [the maximum dose] or <2403 mg/day). Patients, physicians, study staff and the sponsor were masked to treatment group allocation. The primary endpoint was assessment of adverse events, which were collected at each visit and for 28 days after the last dose of study drug. Exploratory efficacy measurements included forced vital capacity (FVC), carbon monoxide diffusing capacity, and 6 min walk distance. Analyses were done in the modified intention-to-treat population, which included all patients who were randomised and received at least one dose of study medication. This study is registered with the European Clinical Trials Database (EudraCT number 2012-000564-14) and has been completed. 123 patients participated in the study between June 28, 2013, and Feb 24, 2015. 61 were assigned to the acetylcysteine group (60 received study medication and included in analysis) and 62 were assigned to the placebo group (all included in analysis). The occurrence of at least one adverse event (46 [77%] patients receiving acetylcysteine vs 50 [81%] receiving placebo), adverse events related to study treatment (17 [28%] vs 16 [26%]), and the number of patients experiencing severe adverse events (three [5%] vs two [3%]), life-threatening adverse events (one [2%] vs one [2%]), or death (one [2%] vs three [5%]) was similar between treatment groups. One case of diarrhoea in the acetylcysteine group was considered severe and related to study treatment. Nine serious adverse events were reported by seven patients: dyspnoea, headache, hypertension, intervertebral disc protrusion, and malignant lung neoplasm in the acetylcysteine group, and aortic aneurysm, contusion, forearm fracture, and worsening IPF in the placebo group. The most common adverse events were cough, nasopharyngitis, and diarrhoea. Photosensitivity occurred more frequently with acetylcysteine (eight [13%] patients) than placebo (one [2%] patient; difference 11·7%; 95% CI 2·6-20·9; p=0·016]), and was not attributable to differences in location, season, or concomitant medication. Four (7%) patients receiving acetylcysteine and three (5%) receiving placebo discontinued study treatment due to adverse events. In the exploratory analysis, change in FVC indicated that clinical benefit from addition of acetylcysteine to pirfenidone is unlikely, with the possibility of a harmful effect in patients with IPF (adjusted rate of decline 125·6 mL/6 months for acetylcysteine vs 34·3 mL/6 months for placebo; difference -91·3 mL; 95% CI -174·4 to -8·3; p=0·031). Findings from the PANORAMA study suggest that addition of acetylcysteine to pirfenidone does not substantially alter the tolerability profile of pirfenidone, and is unlikely to be beneficial in IPF. InterMune International AG (Roche). Copyright © 2016 Elsevier Ltd. All rights reserved.

Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials.

PubMed

Tattersall, Martin H N; Jefford, Michael; Martin, Andrew; Olver, Ian; Thompson, John F; Brown, Richard F; Butow, Phyllis N

2017-03-01

To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials. Tertiary cancer referral hospitals in three state capital cities in Australia. 88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial. We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial. Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. scores on the Quality of Informed Consent questionnaire (QuIC). 88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups. Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006. Results, ACTRN12606000214538. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pre-operative brachial plexus block compared with an identical block performed at the end of surgery: a prospective, double-blind, randomised clinical trial.

PubMed

Holmberg, A; Sauter, A R; Klaastad, Ø; Draegni, T; Raeder, J C

2017-08-01

We evaluated whether pre-emptive analgesia with a pre-operative ultrasound-guided infraclavicular brachial plexus block resulted in better postoperative analgesia than an identical block performed postoperatively. Fifty-two patients undergoing fixation of a fractured radius were included. All patients received general anaesthesia with remifentanil and propofol. Patients were randomly allocated into two groups: a pre-operative block or a postoperative block with 0.5 ml.kg -1 ropivacaine 0.75%. After surgery, all patients received regular paracetamol plus opioids for breakthrough pain. Mean (SD) time to first rescue analgesic after emergence from general anaesthesia was 544 (217) min in the pre-operative block group compared with 343 (316) min in the postoperative block group (p = 0.015). Postoperative pain scores were higher and more patients required rescue analgesia during the first 4 h after surgery in the postoperative block group. There were no significant differences in plasma stress mediators between the groups. Analgesic consumption was lower at day seven in the pre-operative block group. Pain was described as very strong at block resolution in 27 (63%) patients and 26 (76%) had episodes of mild pain after 6 months. We conclude that a pre-operative ultrasound-guided infraclavicular brachial plexus block provides longer and better analgesia in the acute postoperative period compared with an identical postoperative block in patients undergoing surgery for fractured radius. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial

PubMed Central

2011-01-01

Background Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes. The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes. Methods/Design Design: Multicentred randomised, controlled trial. Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies. Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice. Outcome assessors will be blinded to the allocated treatment group. Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age). Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed). Discussion This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN12607000161426 PMID:22026403

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial.

PubMed

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-08-01

The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient's outcome, and so the data are 'missing at random' . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (-0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (-0.054 to 0.198). We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download.

Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial.

PubMed

Rodger, Marc A; Hague, William M; Kingdom, John; Kahn, Susan R; Karovitch, Alan; Sermer, Mathew; Clement, Anne Marie; Coat, Suzette; Chan, Wee Shian; Said, Joanne; Rey, Evelyne; Robinson, Sue; Khurana, Rshmi; Demers, Christine; Kovacs, Michael J; Solymoss, Susan; Hinshaw, Kim; Dwyer, James; Smith, Graeme; McDonald, Sarah; Newstead-Angel, Jill; McLeod, Anne; Khandelwal, Meena; Silver, Robert M; Le Gal, Gregoire; Greer, Ian A; Keely, Erin; Rosene-Montella, Karen; Walker, Mark; Wells, Philip S

2014-11-08

Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4-24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8-26·3%]; risk difference -1·8% [95% CI -10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI -6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3-18·4; p=0·01). Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomised controlled trial

PubMed Central

Navani, Neal; Nankivell, Matthew; Lawrence, David R; Lock, Sara; Makker, Himender; Baldwin, David R; Stephens, Richard J; Parmar, Mahesh K; Spiro, Stephen G; Morris, Stephen; Janes, Sam M

2015-01-01

Summary Background The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis. We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer. Methods In this open-label, multicentre, pragmatic, randomised controlled trial, we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer, from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or conventional diagnosis and staging (CDS), for further investigation and staging. If a target node could not be accessed by EBUS-TBNA, then endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was allowed as an alternative procedure. Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre. We used a telephone randomisation method with permuted blocks of four generated by a computer. Because of the nature of the intervention, masking of participants and consenting investigators was not possible. The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose. This trial is registered with ClinicalTrials.gov, number NCT00652769. Findings Between June 10, 2008, and July 4, 2011, we randomly allocated 133 patients to treatment: 66 to EBUS-TBNA and 67 to CDS (one later withdrew consent). Two patients from the EBUS-TBNA group underwent EUS-FNA. The median time to treatment decision was shorter with EBUS-TBNA (14 days; 95% CI 14–15) than with CDS (29 days; 23–35) resulting in a hazard ratio of 1·98, (1·39–2·82, p<0·0001). One patient in each group had a pneumothorax from a CT-guided biopsy sample; the patient from the CDS group needed intercostal drainage and was admitted to hospital. Interpretation Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer, because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques. Funding UK Medical Research Council. PMID:25660225

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial.

PubMed

Raal, Frederick J; Santos, Raul D; Blom, Dirk J; Marais, A David; Charng, Min-Ji; Cromwell, William C; Lachmann, Robin H; Gaudet, Daniel; Tan, Ju L; Chasan-Taber, Scott; Tribble, Diane L; Flaim, Joann D; Crooke, Stanley T

2010-03-20

Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >/=50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins. ISIS Pharmaceuticals and Genzyme Corporation. Copyright 2010 Elsevier Ltd. All rights reserved.

A pragmatic randomised multi-centre trial of multifamily and single family therapy for adolescent anorexia nervosa.

PubMed

Eisler, Ivan; Simic, Mima; Hodsoll, John; Asen, Eia; Berelowitz, Mark; Connan, Frances; Ellis, Gladys; Hugo, Pippa; Schmidt, Ulrike; Treasure, Janet; Yi, Irene; Landau, Sabine

2016-11-24

Considerable progress has been made in recent years in developing effective treatments for child and adolescent anorexia nervosa, with a general consensus in the field that eating disorders focussed family therapy (often referred to as Maudsley Family Therapy or Family Based Treatment) currently offers the most promising outcomes. Nevertheless, a significant number do not respond well and additional treatment developments are needed to improve outcomes. Multifamily therapy is a promising treatment that has attracted considerable interest and we report the results of the first randomised controlled trial of multifamily therapy for adolescent anorexia nervosa. The study was a pragmatic multicentre randomised controlled superiority trial comparing two outpatient eating disorder focussed family interventions - multifamily therapy (MFT-AN) and single family therapy (FT-AN). A total of 169 adolescents with a DSM-IV diagnosis of anorexia nervosa or eating disorder not otherwise specified (restricting type) were randomised to the two treatments using computer generated blocks of random sizes to ensure balanced numbers in the trial arms. Independent assessors, blind to the allocation, completed evaluations at baseline, 3 months, 12 months (end of treatment) and 18 months. Both treatment groups showed clinically significant improvements with just under 60% achieving a good or intermediate outcome (on the Morgan-Russell scales) at the end of treatment in the FT-AN group and more than 75% in the MFT-AN group - a statistically significant benefit in favour of the multifamily intervention (OR = 2.55 95%; CI 1.17, 5.52; p = 0.019). At follow-up (18 months post baseline) there was relatively little change compared to end of treatment although the difference in primary outcome between the treatments was no longer statistically significant. Clinically significant gains in weight were accompanied by improvements in mood and eating disorder psychopathology. Approximately half the patients in FT-AN and nearly 60% of those in MFT-AN had started menstruating. This study confirms previous research findings demonstrating the effectiveness of eating disorder focused family therapy and highlights the additional benefits of bringing together groups of families that maximises the use of family resources and mutual support leading to improved outcomes. Current Controlled Trials ISRCTN11275465 ; Registered 29 January 2007 (retrospectively registered).

Intermittent energy restriction improves weight loss efficiency in obese men: the MATADOR study

PubMed Central

Byrne, N M; Sainsbury, A; King, N A; Hills, A P; Wood, R E

2018-01-01

Background/Objectives: The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER) improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER attenuated compensatory responses associated with ER. Subjects/Methods: Fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the intervention (CON: N=23, 39.4±6.8 years, 111.1±9.1 kg, 34.3±3.0 kg m−2; INT: N=24, 39.8±9.5 years, 110.2±13.8 kg, 34.1±4.0 kg m−2). During ER, energy intake was equivalent to 67% of weight maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) were measured throughout the study. Results: For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: −624±557 kJ d−1; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: −360±502 vs CON: −749±498 kJ d−1; P<0.05). Conclusions: Greater weight and fat loss was achieved with intermittent ER. Interrupting ER with energy balance ‘rest periods’ may reduce compensatory metabolic responses and, in turn, improve weight loss efficiency. PMID:28925405

Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial.

PubMed

Cortes, Jorge E; De Souza, Carmino Antonio; Ayala, Manuel; Lopez, Jose Luis; Bullorsky, Eduardo; Shah, Sandip; Huang, Xiaojun; Babu, K Govind; Abdulkadyrov, Kudrat; de Oliveira, José Salvador Rodrigues; Shen, Zhi-Xiang; Sacha, Tomasz; Bendit, Israel; Liang, Zhizhou; Owugah, Tina; Szczudlo, Tomasz; Khanna, Sadhvi; Fellague-Chebra, Rafik; le Coutre, Philipp D

2016-12-01

Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0-2. Before enrolment, all patients had received 3-18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months' follow-up. This study is registered with ClinicalTrials.gov (NCT00802841). Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95·18% CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 7·9% in favour of nilotinib; 95% CI -6·2 to 22·0, p=0·31). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0·058). Grade 3-4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related. While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included. Novartis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial.

PubMed

Chatterjee, Sudipto; Naik, Smita; John, Sujit; Dabholkar, Hamid; Balaji, Madhumitha; Koschorke, Mirja; Varghese, Mathew; Thara, Rangaswamy; Weiss, Helen A; Williams, Paul; McCrone, Paul; Patel, Vikram; Thornicroft, Graham

2014-04-19

Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers, when supervised by specialists, in low-income and middle-income countries. We did the COmmunity care for People with Schizophrenia in India (COPSI) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care. We did a multicentre, parallel-group, randomised controlled trial at three sites in India between Jan 1, 2009 and Dec 31, 2010. Patients aged 16-60 years with a primary diagnosis of schizophrenia according to the tenth edition of the International Classification of Diseases, Diagnostic Criteria for Research (ICD-10-DCR) were randomly assigned (2:1), via a computer-generated randomisation list with block sizes of three, six, or nine, to receive either collaborative community-based care plus facility-based care or facility-based care alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. The primary outcome was a change in symptoms and disabilities over 12 months, as measured by the positive and negative syndrome scale (PANSS) and the Indian disability evaluation and assessment scale (IDEAS). Analysis was by modified intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 56877013. 187 participants were randomised to the collaborative community-based care plus facility-based care group and 95 were randomised to the facility-based care alone group; 253 (90%) participants completed follow-up to month 12. At 12 months, total PANSS and IDEAS scores were lower in patients in the intervention group than in those in the control group (PANSS adjusted mean difference -3.75, 95% CI -7.92 to 0.42; p=0.08; IDEAS -0.95, -1.68 to -0.23; p=0.01). However, no difference was shown in the proportion of participants who had a reduction of more than 20% in overall symptoms (PANSS 85 [51%] in the intervention group vs 44 [51%] in the control group; p=0.89; IDEAS 75 [48%] vs 28 [35%]). We noted a significant reduction in symptom and disability outcomes at the rural Tamil Nadu site (-9.29, -15.41 to -3.17; p=0.003). Two patients (one in each group) died by suicide during the study, and two patients died because of complications of a road traffic accident and pre-existing cardiac disease. 18 (73%) patients (17 in the intervention group) were admitted to hospital during the course of the trial, of whom seven were admitted because of physical health problems, such as acute gastritis and vomiting, road accident, high fever, or cardiovascular disease. The collaborative community-based care plus facility-based care intervention is modestly more effective than facility-based care, especially for reducing disability and symptoms of psychosis. Our results show that the study intervention is best implemented as an initial service in settings where services are scarce, for example in rural areas. Wellcome Trust. Copyright © 2014 Chatterjee et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.

Making Nasopalatine Blocks Comfortable: A Randomised Prospective Clinical Comparison of Pain Associated with the Injection Using an Insulin Syringe and a Standard Disposable 3 mL Syringe.

PubMed

Prabhu, Sundararaman; Faizel, Syed; Pahlajani, Vedant; Prabhu, Shweta Jha

2013-12-01

This study was conducted to compare and evaluate the pain associated with administration of Nasopalatine blocks using a disposable insulin syringe and the conventional disposable 3 mL syringe. Forty patients requiring intraalveolar extractions of maxillary central incisors were randomly assigned to two groups of 20 patients each; one (Group A) received the nasopalatine block with a standard 3mL syringe and the other (Group B) received the block with an insulin syringe. Patients were asked to rate the pain associated with the injection on a visual analog scale (VAS) and the results were analysed using a Chi Square Test. The mean VAS score for Group A and B was 1.55 and 1 respectively. Chi Square value was calculated to be 8.603 (degree of freedom= 3, P value= 0.0351). There were no differences in the effectiveness of anesthesia between the groups. Pain associated with administration of the nasopalatine blocks may be significantly mitigated by using the Insulin syringe.

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

ERIC Educational Resources Information Center

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

Art participation for psychosocial wellbeing during stroke rehabilitation: a feasibility randomised controlled trial.

PubMed

Morris, Jacqui H; Kelly, Chris; Joice, Sara; Kroll, Thilo; Mead, Gillian; Donnan, Peter; Toma, Madalina; Williams, Brian

2017-08-30

To examine the feasibility of undertaking a pragmatic single-blind randomised controlled trial (RCT) of a visual arts participation programme to evaluate effects on survivor wellbeing within stroke rehabilitation. Stroke survivors receiving in-patient rehabilitation were randomised to receive eight art participation sessions (n = 41) or usual care (n = 40). Recruitment, retention, preference for art participation and change in selected outcomes were evaluated at end of intervention outcome assessment and three-month follow-up. Of 315 potentially eligible participants 81 (29%) were recruited. 88% (n = 71) completed outcome and 77% (n = 62) follow-up assessments. Of eight intervention group non-completers, six had no preference for art participation. Outcome completion varied between 97% and 77%. Running groups was difficult because of randomisation timing. Effectiveness cannot be determined from this feasibility study but effects sizes suggested art participation may benefit emotional wellbeing, measured on the positive and negative affect schedule, and self-efficacy for Art (d = 0.24-0.42). Undertaking a RCT of art participation within stroke rehabilitation was feasible. Art participation may enhance self-efficacy and positively influence emotional wellbeing. These should be outcomes in a future definitive trial. A cluster RCT would ensure art groups could be reliably convened. Fewer measures, and better retention strategies are required. Implications for Rehabilitation This feasibility randomised controlled trial (RCT) showed that recruiting and retaining stroke survivors in an RCT of a visual arts participation intervention within stroke rehabilitation was feasible. Preference to participate in art activities may influence recruitment and drop-out rates, and should be addressed and evaluated fully. Art participation as part of rehabilitation may improve some aspects of post-stroke wellbeing, including positive affect and self-efficacy for art. A future definitive cluster RCT would facilitate full evaluation of the value art participation can add to rehabilitation.

Complete atrioventricular block in acute coronary syndrome: prevalence, characterisation and implication on outcome.

PubMed

Aguiar Rosa, Silvia; Timóteo, Ana Teresa; Ferreira, Lurdes; Carvalho, Ramiro; Oliveira, Mario; Cunha, Pedro; Viveiros Monteiro, André; Portugal, Guilherme; Almeida Morais, Luis; Daniel, Pedro; Cruz Ferreira, Rui

2018-04-01

The aim was to characterise acute coronary syndrome patients with complete atrioventricular block and to assess the effect on outcome. Patients admitted with acute coronary syndrome were divided according to the presence of complete atrioventricular block: group 1, with complete atrioventricular block; group 2, without complete atrioventricular block. Clinical, electrocardiographic and echocardiographic characteristics and prognosis during one year follow-up were compared between the groups. Among 4799 acute coronary syndrome patients admitted during the study period, 91 (1.9%) presented with complete atrioventricular block. At presentation, group 1 patients presented with lower systolic blood pressure, higher Killip class and incidence of syncope. In group 1, 86.8% presented with ST-segment elevation myocardial infarction (STEMI), and inferior STEMI was verified in 79.1% of patients in group 1 compared with 21.9% in group 2 ( P<0.001). Right ventricular myocardial infarction was more frequent in group 1 (3.3% vs. 0.2%; P<0.001). Among patients who underwent fibrinolysis complete atrioventricular block was observed in 7.3% in contrast to 2.5% in patients submitted to primary percutaneous coronary intervention ( P<0.001). During hospitalisation group 1 had worse outcomes, with a higher incidence of cardiogenic shock (33.0% vs. 4.5%; P<0.001), ventricular arrhythmias (17.6% vs. 3.6%; P<0.001) and the need for invasive mechanical ventilation (25.3% vs. 5.1%; P<0.001). After a propensity score analysis, in a multivariate regression model, complete atrioventricular block was an independent predictor of hospital mortality (odds ratio 3.671; P=0.045). There was no significant difference in mortality at one-year follow-up between the study groups. Complete atrioventricular block conferred a worse outcome during hospitalisation, including a higher incidence of cardiogenic shock, ventricular arrhythmias and death.

Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial.

PubMed

Nakajima, Atsushi; Seki, Mitsunori; Taniguchi, Shinya; Ohta, Akira; Gillberg, Per-Göran; Mattsson, Jan P; Camilleri, Michael

2018-05-24

A subset of patients with constipation has reduced colonic bile acid concentrations, which are associated with slow colonic transit. In a previous study, elobixibat, a locally acting ileal bile acid transporter inhibitor, accelerated colonic transit in Japanese patients with functional constipation. In this study, we aimed to determine the efficacy of elobixibat for short-term treatment of chronic constipation, and safety, patient satisfaction, and quality of life with long-term treatment. We did two phase 3 studies of patients aged 20-80 years in Japan with at least 6 months of chronic constipation, who satisfied Rome III criteria for functional constipation, including fewer than three spontaneous bowel movements per week. The first trial, including patients enrolled at 16 clinics, was a 2-week, randomised, double-blind, placebo-controlled study in which (after a 2-week run-in period) patients were randomly assigned (1:1) to either elobixibat 10 mg/day for 2 weeks or placebo. Randomisation was done with permuted block method (block size six) without stratification. Masking to treatment allocation was achieved with identical appearances of elobixibat and placebo, which were supplied in sealed, opaque containers. Group assignment was concealed from patients, investigators, and analysts. The second trial, including patients enrolled at 34 clinics or hospitals, was an open-label, 1-year study in which all patients received elobixibat; participants could titrate the dose to 5 mg/day or 15 mg/day, or maintain the 10 mg/day dose. In both studies, participants took the study drug as an oral tablet once per day before breakfast. The primary outcome of the 2-week randomised trial was the change from baseline (ie, last week of the 2-week run-in) in the frequency of spontaneous bowel movements during week 1 of treatment. The primary outcome of the 52-week open-label trial was safety (type, severity, and incidence of adverse drug reactions) at all times from treatment initiation. All efficacy analyses were based on the modified intention-to-treat (ITT) population without imputation for any missing data. Safety analyses included all patients who received at least one dose of study drug. These trials are registered with the Japan Pharmaceutical Information Center (numbers JapicCTI-153061 and JapicCTI-153062) and have been completed. Between Nov 4, 2015, and June 11, 2016, we assigned 133 patients to treatment in the 2-week randomised trial: 70 to elobixibat (69 included in the modified ITT and safety populations) and 63 to placebo. The frequency of spontaneous bowel movements per week during week 1 of treatment was greater with elobixibat (least-squares mean 6·4, 95% CI 5·3-7·6) than with placebo (1·7, 1·2-2·2), p<0·0001). Between Oct 31, 2015, and March 15, 2017, we allocated 341 patients to 52 weeks of elobixibat (340 included in the modified ITT and safety populations). 163 (48%) patients in the 52-week trial had an adverse drug reaction, the most common of which were mild gastrointestinal disorders (in 135 [40%] patients). Inguinal hernia was reported in one patient with elobixibat in the 52-week study as a moderate adverse drug reaction. The most common adverse drug reactions in both trials were mild abdominal pain (13 [19%] patients with elobixibat and one [2%] with placebo in the 2-week randomised trial, and 82 [24%] patients in the 52-week trial) and diarrhoea (nine [13%] patients with elobixibat and none with placebo in the 2-week randomised trial and 50 [15%] in the 52-week trial). Elobixibat resolved constipation in the short-term, and was well tolerated with both short-term and long-term treatment. The evidence supports the use of this novel approach to increase intracolonic concentrations of endogenous bile acid for the treatment of chronic constipation. EA Pharma and Mochida Pharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impact of a web-based tool (WebCONSORT) to improve the reporting of randomised trials: results of a randomised controlled trial.

PubMed

Hopewell, Sally; Boutron, Isabelle; Altman, Douglas G; Barbour, Ginny; Moher, David; Montori, Victor; Schriger, David; Cook, Jonathan; Gerry, Stephen; Omar, Omar; Dutton, Peter; Roberts, Corran; Frangou, Eleni; Clifton, Lei; Chiocchia, Virginia; Rombach, Ines; Wartolowska, Karolina; Ravaud, Philippe

2016-11-28

The CONSORT Statement is an evidence-informed guideline for reporting randomised controlled trials. A number of extensions have been developed that specify additional information to report for more complex trials. The aim of this study was to evaluate the impact of using a simple web-based tool (WebCONSORT, which incorporates a number of different CONSORT extensions) on the completeness of reporting of randomised trials published in biomedical publications. We conducted a parallel group randomised trial. Journals which endorsed the CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not actively implement it (i.e. require authors to submit a completed CONSORT checklist) were invited to participate. Authors of randomised trials were requested by the editor to use the web-based tool at the manuscript revision stage. Authors registering to use the tool were randomised (centralised computer generated) to WebCONSORT or control. In the WebCONSORT group, they had access to a tool allowing them to combine the different CONSORT extensions relevant to their trial and generate a customised checklist and flow diagram that they must submit to the editor. In the control group, authors had only access to a CONSORT flow diagram generator. Authors, journal editors, and outcome assessors were blinded to the allocation. The primary outcome was the proportion of CONSORT items (main and extensions) reported in each article post revision. A total of 46 journals actively recruited authors into the trial (25 March 2013 to 22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166; control n = 158), of which 197 were reports of randomised trials (n = 94; n = 103). Over a third (39%; n = 127) of registered manuscripts were excluded from the analysis, mainly because the reported study was not a randomised trial. Of those included in the analysis, the most common CONSORT extensions selected were non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n = 10; n = 9). In a quarter of manuscripts, authors either wrongly selected an extension or failed to select the right extension when registering their manuscript on the WebCONSORT study site. Overall, there was no important difference in the overall mean score between WebCONSORT (mean score 0.51) and control (0.47) in the proportion of CONSORT and CONSORT extension items reported pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10). This study failed to show a beneficial effect of a customised web-based CONSORT checklist to help authors prepare more complete trial reports. However, the exclusion of a large number of inappropriately registered manuscripts meant we had less precision than anticipated to detect a difference. Better education is needed, earlier in the publication process, for both authors and journal editorial staff on when and how to implement CONSORT and, in particular, CONSORT-related extensions. ClinicalTrials.gov: NCT01891448 [registered 24 May 2013].

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

PubMed Central

2010-01-01

Background There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. Methods/Design Design: Multicentred randomised trial. Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible). Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power). Discussion This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation. Clinical Trial Registration Current Controlled Trials ISRCTN15761056 PMID:20973989

Feed intake and production parameters of lactating crossbred cows fed maize-based diets of stover, silage or quality protein silage.

PubMed

Gebrehawariat, Efrem; Tamir, Berhan; Tegegne, Azage

2010-12-01

Thirty-six Boran × Friesian dairy cows (392 ± 12 kg; mean ± SD) in early parity were used in a randomised complete block design. Cows were blocked by parity into three blocks of 12 animals and offered normal maize (NM) stover (T1), NM silage (T2) or quality protein maize (QPM) silage (T3) basal diets supplemented with a similar concentrate mix. Feed intake, body weight and condition changes and milk yield and composition were assessed. The daily intake of DM, OM, NDF and ADF for cows fed the NM stover-based diet was higher (P<0.05) than for the cows fed the NM silage and QPM silage-based diets. However, the daily intake of DOM (9.3 kg) and ME (140.8 MJ) for cows on QPM silage-based diet was higher (P<0.05) than for cows on NM stover-based diet (8.4 kg and 124.2 MJ) and NM silage-based diet (7.9 kg and 119.1 MJ). Body weight of cows was affected (P<0.05) by the diet, but diet had no effect (P>0.05) on body condition score, milk yield and milk composition. The digestible organic matter in the NM stover-based diet (724 g/kg DM) was lower (P<0.05) than that in the NM (770 g/kg DM) and QPM silage-based diet (762 g/kg DM). It was concluded that the performances of the cows on the NM silage and QPM silage diets were similar and were not superior to that of the NM stover-based diet.

Comparison of analgesic efficacy of four-quadrant transversus abdominis plane (TAP) block and continuous posterior TAP analgesia with epidural analgesia in patients undergoing laparoscopic colorectal surgery: an open-label, randomised, non-inferiority trial.

PubMed

Niraj, G; Kelkar, A; Hart, E; Horst, C; Malik, D; Yeow, C; Singh, B; Chaudhri, S

2014-04-01

Posterior transversus abdominis plane blocks have been reported to be an effective method of providing analgesia after lower abdominal surgery. We compared the efficacy of a novel technique of providing continuous transversus abdominis plane analgesia with epidural analgesia in patients on an enhanced recovery programme following laparoscopic colorectal surgery. A non-inferiority comparison was used. Adult patients undergoing elective laparoscopic colorectal surgery were randomly assigned to receive continuous transversus abdominis plane analgesia (n = 35) vs epidural analgesia (n = 35), in addition to a postoperative analgesic regimen comprising regular paracetamol, regular diclofenac and tramadol as required. Sixty-one patients completed the study. The transversus group received four-quadrant transversus abdominis plane blocks and bilateral posterior transversus abdominis plane catheters that were infused with levobupivacaine 0.25% for 48 h. The epidural group received an infusion of bupivacaine and fentanyl. The primary outcome measure was visual analogue scale pain score on coughing at 24 h after surgery. We found no significant difference in median (IQR [range]) visual analogue scores during coughing at 24 h between the transversus group 2.5 (1.0-3.0 [0-5.5]) and the epidural group 2.5 (1.0-5.0 [0-6.0]). The one-sided 97.5% CI was a 0.0 (∞-1.0) difference in means, establishing non-inferiority. There were no significant differences between the groups for tramadol consumption. Success rate was 28/30 (93%) in the transversus group vs 27/31 (87%) in the epidural group. Continuous transversus abdominis plane infusion was non-inferior to epidural infusion in providing analgesia after laparoscopic colorectal surgery. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Feed intake and production parameters of lactating crossbred cows fed maize-based diets of stover, silage or quality protein silage

PubMed Central

Gebrehawariat, Efrem; Tegegne, Azage

2010-01-01

Thirty-six Boran × Friesian dairy cows (392 ± 12 kg; mean ± SD) in early parity were used in a randomised complete block design. Cows were blocked by parity into three blocks of 12 animals and offered normal maize (NM) stover (T1), NM silage (T2) or quality protein maize (QPM) silage (T3) basal diets supplemented with a similar concentrate mix. Feed intake, body weight and condition changes and milk yield and composition were assessed. The daily intake of DM, OM, NDF and ADF for cows fed the NM stover-based diet was higher (P < 0.05) than for the cows fed the NM silage and QPM silage-based diets. However, the daily intake of DOM (9.3 kg) and ME (140.8 MJ) for cows on QPM silage-based diet was higher (P < 0.05) than for cows on NM stover-based diet (8.4 kg and 124.2 MJ) and NM silage-based diet (7.9 kg and 119.1 MJ). Body weight of cows was affected (P < 0.05) by the diet, but diet had no effect (P > 0.05) on body condition score, milk yield and milk composition. The digestible organic matter in the NM stover-based diet (724 g/kg DM) was lower (P < 0.05) than that in the NM (770 g/kg DM) and QPM silage-based diet (762 g/kg DM). It was concluded that the performances of the cows on the NM silage and QPM silage diets were similar and were not superior to that of the NM stover-based diet. PMID:20577806

Effectiveness and cost-effectiveness of embedded simulation in occupational therapy clinical practice education: study protocol for a randomised controlled trial.

PubMed

Imms, Christine; Chu, Eli Mang Yee; Guinea, Stephen; Sheppard, Loretta; Froude, Elspeth; Carter, Rob; Darzins, Susan; Ashby, Samantha; Gilbert-Hunt, Susan; Gribble, Nigel; Nicola-Richmond, Kelli; Penman, Merrolee; Gospodarevskaya, Elena; Mathieu, Erin; Symmons, Mark

2017-07-21

Clinical placements are a critical component of the training for health professionals such as occupational therapists. However, with growing student enrolments in professional education courses and workload pressures on practitioners, it is increasingly difficult to find sufficient, suitable placements that satisfy program accreditation requirements. The professional accrediting body for occupational therapy in Australia allows up to 200 of the mandatory 1000 clinical placement hours to be completed via simulation activities, but evidence of effectiveness and efficiency for student learning outcomes is lacking. Increasingly placement providers charge a fee to host students, leading educators to consider whether providing an internal program might be a feasible alternative for a portion of placement hours. Economic analysis of the incremental costs and benefits of providing a traditional versus simulated placement is required to inform decision-making. This study is a pragmatic, non-inferiority, single-blind, multicentre, two-group randomised controlled trial (RCT) with an embedded economic analysis. The RCT will compare a block of 40 hours of simulated placement (intervention) with a 40-hour block of traditional placement (comparator), with a focus on student learning outcomes and delivery costs. Six universities will instigate the educational intervention within their respective occupational therapy courses, randomly assigning their cohort of students (1:1 allocation) to the simulated or traditional clinical placements. The primary outcome is achievement of professional behaviours (e.g. communication, clinical reasoning) as assessed by a post-placement written examination. Secondary outcomes include proportions passing the placement assessed using the Student Practice Evaluation Form-Revised, changes in student confidence pre-/post-placement, student and educator evaluation of the placement experience and cost-effectiveness of simulated versus traditional clinical placements. Comprehensive cost data will be collected for both the simulated and traditional placement programs at each site for economic evaluation. Use of simulation in health-related fields like occupational therapy is common, but these activities usually relate to brief opportunities for isolated skill development. The simulated clinical placement evaluated in this trial is less common because it encapsulates a 5-day block of integrated activities, designed and delivered in a manner intended to emulate best-practice placement experiences. The planned study is rare due to inclusion of an economic analysis that aims to provide valuable information about the relationship between costs and outcomes across participating sites. Australian New Zealand Clinical Trials Registry, ACTRN12616001339448 . Registered 26 September 2016.

A comparison of the efficacy of intercostal nerve block and peritubal infiltration of ropivacaine for post-operative analgesia following percutaneous nephrolithotomy: A prospective randomised double-blind study.

PubMed

Jonnavithula, Nirmala; Chirra, Raveendra Reddy; Pasupuleti, Sai Lakshman; Devraj, Rahul; Sriramoju, Vidyasagar; Pisapati, Murthy Vln

2017-08-01

Intercostal nerve blockade (ICNB) and peritubal infiltration of the nephrostomy tract are well-established regional anaesthetic techniques for alleviating pain after percutaneous nephrolithotomy (PCNL). This prospective study compared the efficacy of ICNB and peritubal local anaesthetic infiltration of the nephrostomy tract in providing post-operative analgesia following PCNL. Sixty American Society of Anesthesiologist physical status 1 and II patients scheduled for PCNL requiring nephrostomy tube were randomised to receive either peritubal infiltration or ICNB. At the completion of the procedure, patients in Group P received peritubal infiltration and those in Group I received ICNB at 10, 11, 12 th spaces using fluoroscopy guidance. Postoperatively, patients were followed for 24 h for pain using Visual Analogue Scale (VAS) and Dynamic VAS. Rescue analgesia was inj. tramadol 1 mg/kg IV when pain score exceeded 4. Time to first rescue analgesia, number of doses and patient's satisfaction were noted in all patients. Pain scores were lower in the group I at all points of measurement than group P. The mean time to first demand for rescue analgesia was higher in Group I (13.22 ± 4.076 h vs 7.167 ± 3.92 h P - 0.001). The number of demands and the amount of analgesics consumed were less in Group I. ICNB provided superior analgesia as evidenced by longer time to first demand of analgesic, reduced number of demands and consumption of rescue analgesic. Peritubal infiltration, although less efficacious, may be a safe and simple alternative technique.

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

PubMed

Cuzick, Jack; Sestak, Ivana; Cawthorn, Simon; Hamed, Hisham; Holli, Kaija; Howell, Anthony; Forbes, John F

2015-01-01

Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8). These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention. Cancer Research UK (UK) and the National Health and Medical Research Council (Australia). Copyright © 2015 Cuzick et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

A feasibility randomised controlled trial of pre-operative occupational therapy to optimise recovery for patients undergoing primary total hip replacement for osteoarthritis (PROOF-THR).

PubMed

Jepson, Paul; Sands, Gina; Beswick, Andrew D; Davis, Edward T; Blom, Ashley W; Sackley, Catherine M

2016-02-01

To assess the feasibility of a pre-operative occupational therapy intervention for patients undergoing primary total hip replacement. Single blinded feasibility randomised controlled trial, with data collection prior to the intervention, and at 4, 12, and 26 weeks following surgery. Recruitment from two NHS orthopaedic outpatient centres in the West Midlands, UK. Patients awaiting primary total hip replacement due to osteoarthritis were recruited. Following pre-operative assessment, patients were individually randomised to intervention or control by a computer-generated block randomisation algorithm stratified by age and centre. The intervention group received a pre-surgery home visit by an occupational therapist who discussed expectations, assessed home safety, and provided appropriate adaptive equipment. The control group received treatment as usual. The study assessed the feasibility of recruitment procedures, delivery of the intervention, appropriateness of outcome measures and data collection methods. Health related quality of life and resource use were recorded at 4, 12 and 26 weeks. Forty-four participants were recruited, 21 were randomised to the occupational therapy intervention and 23 to usual care. Analysis of 26 week data included 18 participants in the intervention group and 21 in the control. The intervention was delivered successfully with no withdrawals or crossovers; 5/44 were lost to follow-up with further missing data for participation and resource use. The feasibility study provided the information required to conduct a definitive trial. Burden of assessment would need to be addressed. A total of 219 patients would be required in an efficacy trial. © The Author(s) 2015.

Masquerading bundle branch block as a presenting manifestation of complete atrioventricular block that caused syncope.

PubMed

Jiao, Zhenyu; Tian, Ying; Yang, Xinchun; Liu, Xingpeng

2017-10-01

A 59-year-old male patient was admitted with the main complaints of stuffiness and shortness of breath. An ECG from precordial leads on admission showed masquerading bundle branch block. Syncope frequently occurred after admission. During syncope episodes, ECG telemetry showed that the syncope was caused by intermittent complete atrioventricular block, with the longest RR interval lasting for 4.36 s. At the gap of syncope, ECG showed complete right bundle branch block accompanied by alternation of left anterior fascicular block and left posterior fascicular block. The patient was implanted with a dual-chamber permanent pacemaker. Follow-up of 9 months showed no reoccurrence of syncope.

Can we use lower volume of local anesthetic for infraclavicular brachial plexus nerve block under ultrasound guidance in children?

PubMed

Ince, Ilker; Aksoy, Mehmet; Dostbil, Aysenur; Tuncer, Kutsi

2017-09-01

To determine if the infraclavicular brachial plexus block can be applied with lower volume of local anesthetic. Randomised, double-blinded clinical trial. 60 patients aged 5-15years with ASA I-II who underwent emergent or elective arm, forearm or hand operations were included in the study. Patients were divided into two groups randomly; standard volume local anesthetic administered group (Group S, n=30) and low volume anesthetic administered group (Group L, n=30). Postoperative pain scores, sensory and motor block durations were noted. Pain scores (Wong-Baker Face Scale) were evaluated and the results were detected to be similar at all times (30min, 1, 2, 4, 8, 12, 24h). Durations of motor block were 168(±16) minutes and 268(±15) minutes in Group L and Group S respectively and the difference was statistically significant (p<0.001). Durations of sensory block were 385(±26) and 402(±39) in Group L and Group S respectively and no statistically significant difference was detected (p=0.064). Similar block success, postoperative sensory block durations and pain scores could be obtained during infraclavicular brachial plexus in pediatric patients with lower local anesthetic volumes. Copyright © 2016 Elsevier Inc. All rights reserved.

Two injection digital block versus single subcutaneous palmar injection block for finger lacerations.

PubMed

Okur, O M; Şener, A; Kavakli, H Ş; Çelik, G K; Doğan, N Ö; Içme, F; Günaydin, G P

2017-12-01

We aimed to compare two digital nerve block techniques in patients due to traumatic digital lacerations. This was a randomized-controlled study designed prospectively in the emergency department of a university-based training and research hospital. Randomization was achieved by sealed envelopes. Half of the patients were randomised to traditional (two-injection) digital nerve block technique while single-injection digital nerve block technique was applied to the other half. Score of pain due to anesthetic infiltration and suturing, onset time of total anesthesia, need for an additional rescue injection were the parameters evaluated with both groups. Epinephrin added lidocaine hydrochloride preparation was used for the anesthetic application. Visual analog scale was used for the evaluation of pain scores. Outcomes were compared by using Mann-Whitney U test and Student t-test. Fifty emergency department patients ≥18 years requiring digital nerve block were enrolled in the study. Mean age of the patients was 33 (min-max: 19-86) and 39 (78 %) were male. No statistically significant difference was found between the two groups in terms of our main parameters; anesthesia pain score, suturing pain score, onset time of total anesthesia and rescue injection need. Single injection volar digital nerve block technique is a suitable alternative for digital anesthesias in emergency departments.

Promoting Recruitment using Information Management Efficiently (PRIME): a stepped-wedge, cluster randomised trial of a complex recruitment intervention embedded within the REstart or Stop Antithrombotics Randomised Trial.

PubMed

Maxwell, Amy E; Parker, Richard A; Drever, Jonathan; Rudd, Anthony; Dennis, Martin S; Weir, Christopher J; Al-Shahi Salman, Rustam

2017-12-28

Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART. We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate. We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to have been randomised using the audit reports. Respondents frequently reported resource and time pressures as being key barriers to running the audit reports. The PRIME complex intervention did not significantly improve the recruitment rate to RESTART. Further research is needed to establish if PRIME might be beneficial at an earlier stage in a prevention trial or for prevention dilemmas that arise more often in clinical practice.

Return to work in sick-listed cancer survivors with job loss: design of a randomised controlled trial.

PubMed

van Egmond, Martine P; Duijts, Saskia F A; Vermeulen, Sylvia J; van der Beek, Allard J; Anema, Johannes R

2015-02-18

Despite long-term or permanent health problems, cancer survivors are often motivated to return to work. For cancer survivors who have lost their job, return to work can be more challenging compared to employed survivors, as they generally find themselves in a more vulnerable social and financial position. Cancer survivors with job loss may therefore be in need of tailored return to work support. However, there is a lack of return to work intervention programs specifically targeting these cancer survivors. The number of cancer survivors with job loss in developed countries is rising due to, amongst others, increases in the incidence and survivor rate of cancer, the retirement age and the proportion of flexible employment contracts. Hence, we consider it important to develop a tailored return to work intervention program for cancer survivors with job loss, and to evaluate its effectiveness compared to usual care. This study employs a two-armed randomised controlled trial with a follow-up period of 12 months. The study population (n = 164) will be recruited from a national sample of cancer survivors (18-60 years), who have been sick-listed for 12-36 months. Participants will be randomised by using computerized blocked randomisation (blocks of four). All participants will receive usual care as provided by the Dutch Social Security Agency. Additionally, participants in the intervention group will receive a tailored return to work intervention program, which includes vocational rehabilitation and supportive psychosocial components, as well as (therapeutic) placement at work. The primary outcome measure is duration until sustainable return to work; the secondary outcome measure is rate of return to work. Other parameters include, amongst others, fatigue, coping strategy and quality of life. We will perform Cox regression analyses to estimate hazard ratios for time to sustainable return to work. The hypothesis of this study is that a tailored approach for cancer survivors with job loss is more effective, regarding return to work, compared to usual care. The results of this study will provide insight into the ways in which return to work can be facilitated for cancer survivors with job loss. Netherlands Trial Register: NTR3562 .

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

PubMed

Muers, M F; Rudd, R M; O'Brien, M E R; Qian, W; Hodson, A; Parmar, M K B; Girling, D J

2004-02-01

The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. The planned phase III trial is feasible.

Complete radiotherapy response in rectal cancer: A review of the evidence.

PubMed

Couch, Daniel G; Hemingway, David M

2016-01-14

Complete response to chemoradiotherapy for rectal cancer is becoming a common clinical entity. Techniques to diagnose complete response and how to survey these patients without operative intervention are still unclear. We review the most recent evidence. Barriers to firm conclusions regarding this are heterogeneity of diagnostic definitions, differing surveillance protocols, and a lack of randomised studies.

Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial.

PubMed

Place, Andrew E; Stevenson, Kristen E; Vrooman, Lynda M; Harris, Marian H; Hunt, Sarah K; O'Brien, Jane E; Supko, Jeffrey G; Asselin, Barbara L; Athale, Uma H; Clavell, Luis A; Cole, Peter D; Kelly, Kara M; Laverdiere, Caroline; Leclerc, Jean-Marie; Michon, Bruno; Schorin, Marshall A; Welch, Jennifer J G; Lipshultz, Steven E; Kutok, Jeffery L; Blonquist, Traci M; Neuberg, Donna S; Sallan, Stephen E; Silverman, Lewis B

2015-12-01

l-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia, and is usually administered intramuscularly. Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than the native Escherichia coli (E coli) preparation, and can be more feasibly administered intravenously. The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05-001 (DFCI 05-001) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia. DFCI 05-001 enrolled patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia from 11 consortium sites in the USA and Canada. Patients were assigned to an initial risk group on the basis of their baseline characteristics and then underwent 32 days of induction therapy. Those who achieved complete remission after induction therapy were assigned to a final risk group and were eligible to participate in a randomised comparison of intravenous PEG-asparaginase (15 doses of 2500 IU/m(2) every 2 weeks) or intramuscular native E colil-asparaginase (30 doses of 25 000 IU/m(2) weekly), beginning at week 7 after study entry. Randomisation (1:1) was unmasked, and was done by a statistician-generated allocation sequence using a permuted blocks algorithm (block size of 4), stratified by final risk group. The primary endpoint of the randomised comparison was the overall frequency of asparaginase-related toxicities (defined as allergy, pancreatitis, and thrombotic or bleeding complications). Predefined secondary endpoints were disease-free survival, serum asparaginase activity, and quality of life during therapy as assessed by PedsQL surveys. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00400946. Between April 22, 2005, and Feb 12, 2010, 551 eligible patients were enrolled. 526 patients achieved complete remission after induction, of whom 463 were randomly assigned to receive intramuscular native E colil-asparaginase (n=231) or intravenous PEG-asparaginase (n=232). The two treatment groups did not differ significantly in the overall frequency of asparaginase-related toxicities (65 [28%] of 232 patients in the intravenous PEG-asparaginase group vs 59 [26%] of 231 patients in the intramuscular native E colil-asparaginase group, p=0·60), or in the individual frequency of allergy (p=0·36), pancreatitis (p=0·55), or thrombotic or bleeding complications (p=0·26). Median follow-up was 6·0 years (IQR 5·0-7·1). 5-year disease-free survival was 90% (95% CI 86-94) for patients assigned to intravenous PEG-asparaginase and 89% (85-93) for those assigned to intramuscular native E colil-asparaginase (p=0·58). The median nadir serum asparaginase activity was significantly higher in patients who received intravenous PEG-asparaginase than in those who received intramuscular native E colil-asparaginase. Significantly more anxiety was reported by both patients and parent-proxy in the intramuscular native E colil-asparaginase group than in the intravenous PEG-asparaginase group. Scores for other domains were similar between the groups. The most common grade 3 or worse adverse events were bacterial or fungal infections (47 [20%] of 232 in the intravenous PEG-asparaginase group vs 51 [22%] of 231 patients in the intramuscular E colil-asparaginase group) and asparaginase-related allergic reactions (14 [6%] vs 6 [3%]). Intravenous PEG-asparaginase was not more toxic than, was similarly efficacious to, and was associated with decreased anxiety compared with intramuscular native E colil-asparaginase, supporting its use as the front-line asparaginase preparation in children with newly diagnosed acute lymphoblastic leukaemia. National Cancer Institute and Enzon Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapid versus standard intravenous rehydration in paediatric gastroenteritis: pragmatic blinded randomised clinical trial

PubMed Central

Parkin, Patricia C; Willan, Andrew R; Schuh, Suzanne

2011-01-01

Objective To determine if rapid rather than standard intravenous rehydration results in improved hydration and clinical outcomes when administered to children with gastroenteritis. Design Single centre, two arm, parallel randomised pragmatic controlled trial. Blocked randomisation stratified by site. Participants, caregivers, outcome assessors, investigators, and statisticians were blinded to the treatment assignment. Setting Paediatric emergency department in a tertiary care centre in Toronto, Canada. Participants 226 children aged 3 months to 11 years; complete follow-up was obtained on 223 (99%). Eligible children were aged over 90 days, had a diagnosis of dehydration secondary to gastroenteritis, had not responded to oral rehydration, and had been prescribed intravenous rehydration. Children were excluded if they weighed less than 5 kg or more than 33 kg, required fluid restriction, had a suspected surgical condition, or had an insurmountable language barrier. Children were also excluded if they had a history of a chronic systemic disease, abdominal surgery, bilious or bloody vomit, hypotension, or hypoglycaemia or hyperglycaemia. Interventions Rapid (60 mL/kg) or standard (20 mL/kg) rehydration with 0.9% saline over an hour; subsequent fluids administered according to protocol. Main outcome measures Primary outcome: clinical rehydration, assessed with a validated scale, two hours after the start of treatment. Secondary outcomes: prolonged treatment, mean clinical dehydration scores over the four hour study period, time to discharge, repeat visits to emergency department, adequate oral intake, and physician’s comfort with discharge. Data from all randomised patients were included in an intention to treat analysis. Results 114 patients were randomised to rapid rehydration and 112 to standard. One child was withdrawn because of severe hyponatraemia at baseline. There was no evidence of a difference between the rapid and standard rehydration groups in the proportions of participants who were rehydrated at two hours (41/114 (36%) v 33/112 (30%); difference 6.5% (95% confidence interval −5.7% to 18.7%; P=0.32). The results did not change after adjustment for weight, baseline dehydration score, and baseline pH (odds ratio 1.8, 0.90 to 3.5; P=0.10). The rates of prolonged treatment were similar (52% rapid v 43% standard; difference 8.9%, 21% to −5%; P=0.19). Although dehydration scores were similar throughout the study period (P=0.96), the median time to discharge was longer in the rapid group (6.3 v 5.0 hours; P=0.03). Conclusions There are no relevant clinical benefits from the administration of rapid rather than standard intravenous rehydration to haemodynamically stable children deemed to require intravenous rehydration. Trail registration Clinical Trials NCT00392145. PMID:22094316

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial

PubMed Central

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-01-01

Background/aims: The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient’s outcome, and so the data are ‘missing at random’ . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. Methods: We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. Results: A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (−0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (−0.054 to 0.198). Conclusion: We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download. PMID:28675302

Evaluating the impact and use of Transparent Reporting of Evaluations with Non-randomised Designs (TREND) reporting guidelines

PubMed Central

Fuller, Thomas; Pearson, Mark; Peters, Jaime L; Anderson, Rob

2012-01-01

Introduction Accurate and full reporting of evaluation of interventions in health research is needed for evidence synthesis and informed decision-making. Evidence suggests that biases and incomplete reporting affect the assessment of study validity and the ability to include this data in secondary research. The Transparent Reporting of Evaluations with Non-randomised Designs (TREND) reporting guideline was developed to improve the transparency and accuracy of the reporting of behavioural and public health evaluations with non-randomised designs. Evaluations of reporting guidelines have shown that they can be effective in improving reporting completeness. Although TREND occupies a niche within reporting guidelines, and despite it being 8 years since publication, no study yet has assessed its impact on reporting completeness or investigated what factors affect its use by authors and journal editors. This protocol describes two studies that aim to redress this. Methods and analysis Study 1 will use an observational design to examine the uptake and use of TREND by authors, and by journals in their instructions to authors. A comparison of reporting completeness and study quality of papers that do and do not use TREND to inform reporting will be made. Study 2 will use a cross-sectional survey to investigate what factors inhibit or facilitate authors’ and journal editors’ use of TREND. Semistructured interviews will also be conducted with a subset of authors and editors to explore findings from study 1 and the surveys in greater depth. Ethics and dissemination These studies will generate evidence of how implementation and dissemination of the TREND guideline has affected reporting completeness in studies with experimental, non-randomised designs within behavioural and public health research. The project has received ethics approval from the Research Ethics Committee of the Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth. PMID:23257774

Reversible chronic acquired complete atrioventricular block.

PubMed

Rakovec, P; Milcinski, G; Voga, G; Korsic, L

1982-01-01

The return of atrioventricular conduction is reported in a case after nearly four years of complete acquired heart block. After recovery from atrioventricular block, right bundle branch block persisted, but P-R interval and H-V interval were normal. Three months later a relapse of second degree infranodal atrioventricular block was noted. A short review of similar cases from the literature is given.

Ultrasound-Guided Single-Injection Infraclavicular Block Versus Ultrasound-Guided Double-Injection Axillary Block: A Noninferiority Randomized Controlled Trial.

PubMed

Boivin, Ariane; Nadeau, Marie-Josée; Dion, Nicolas; Lévesque, Simon; Nicole, Pierre C; Turgeon, Alexis F

2016-01-01

Single-injection ultrasound-guided infraclavicular block is a simple, reliable, and effective technique. A simplified double-injection ultrasound-guided axillary block technique with a high success rate recently has been described. It has the advantage of being performed in a superficial and compressible location, with a potentially improved safety profile. However, its effectiveness in comparison with single-injection infraclavicular block has not been established. We hypothesized that the double-injection ultrasound-guided axillary block would show rates of complete sensory block at 30 minutes noninferior to the single-injection ultrasound-guided infraclavicular block. After approval by our research ethics committee and written informed consent, adults undergoing distal upper arm surgery were randomized to either group I, ultrasound-guided single-injection infraclavicular block, or group A, ultrasound-guided double-injection axillary block. In group I, 30 mL of 1.5% mepivacaine was injected posterior to the axillary artery. In group A, 25 mL of 1.5% mepivacaine was injected posteromedial to the axillary artery, after which 5 mL was injected around the musculocutaneous nerve. Primary outcome was the rate of complete sensory block at 30 minutes. Secondary outcomes were the onset of sensory and motor blocks, surgical success rates, performance times, and incidence of complications. All outcomes were assessed by a blinded investigator. The noninferiority of the double-injection ultrasound-guided axillary block was considered if the limits of the 90% confidence intervals (CIs) were within a 10% margin of the rate of complete sensory block of the infraclavicular block. At 30 minutes, the rate of complete sensory block was 79% in group A (90% CI, 71%-85%) compared with 91% in group I (90% CI, 85%-95%); the upper limit of CI of group A is thus included in the established noninferiority margin of 10%. The rate of complete sensory block was lower in group A (proportion difference of 12% [95% CI, 2-22]; P = 0.0091), as was surgical success rate (82% [95% CI, 74%-89%] vs 93% [95% CI, 86%-97%]; proportion difference of 11% [95% CI 1-20]; P = 0.0153). Sensory block onset also was slower in group A (log rank test P = 0.0020). Performance times were faster in group I (231 seconds [95% CI, 213-250]) than in group A (358 seconds [95% CI, 332-387]; P < 0.0001). No statistically significant difference was observed for vascular puncture, paresthesia during block performance, or procedure-related pain. No neurologic complication was noted at follow-up. We failed to demonstrate that the rate of complete sensory block of the double-injection axillary block is noninferior to the single-injection infraclavicular block. However, the rate of complete sensory block at 30 minutes is statistically significantly lower with the axillary block. The ultrasound-guided single-injection infraclavicular block thus seems to be the preferred technique over the axillary for upper arm anesthesia.

Effect of bilberry juice on indices of muscle damage and inflammation in runners completing a half-marathon: a randomised, placebo-controlled trial.

PubMed

Lynn, Anthony; Garner, Samantha; Nelson, Nichola; Simper, Trevor N; Hall, Anna C; Ranchordas, Mayur K

2018-01-01

Emerging evidence indicates that fruits rich in polyphenols may attenuate exercise-induced muscle damage and associated markers of inflammation and soreness. This study was conducted to determine whether bilberry juice (BJ), which is particularly rich in polyphenols, reduces markers of muscle damage in runners completing a half marathon. A total of 21 recreationally trained runners (age 30.9 ± 10.4 y; mass 71.6 ± 11.0 kg; M = 16; F = 5) were recruited to a single blind, randomised, placebo-controlled, parallel study. Participants were block randomised to consume 2 × 200 ml of BJ or energy-matched control drink (PLA) for 5 d before the Sheffield Half Marathon, on race day, and for 2 days post-race. Measurements of delayed onset muscle soreness (DOMS), muscle damage (creatine kinase; CK) and inflammation (c-reactive protein; CRP) were taken at baseline, pre-race, post-race, 24 h post-race and 48 h post-race. The effect of treatment on outcome measures was analysed using magnitude-based inferences based on data from 19 participants; 2 participants were excluded from the analyses because they did not provide samples for all time points. The half marathon caused elevations in DOMS, CRP and CK. BJ had a possibly harmful effect on DOMS from pre-race to immediately post-race (11.6%, 90% CI ± 14.7%), a likely harmful effect on CRP from pre-race to 24 h post-race (mean difference ES 0.56, 90% CI ± 0.72) and a possibly harmful effect on CRP from pre-race to 48 h post-race (ES 0.12, 90% CI ± 0.69). At other time points, the differences between the BJ and PLA groups in DOMS and CRP were unclear, possibly trivial or likely trivial . Differences in the changes in CK between BJ and PLA were unclear at every time point other than from baseline to pre-race, where BJ had a possibly harmful effect on reducing muscle damage (ES 0.23, 90% CI ± 0.57). Despite being a rich source of antioxidant and anti-inflammatory phytochemicals, BJ evoked small to moderate increases in exercise-induced DOMS and CRP. Further larger studies are required to confirm these unexpected preliminary results.

Ultrasound with neurostimulation compared with ultrasound guidance alone for lumbar plexus block: A randomised single blinded equivalence trial.

PubMed

Arnuntasupakul, Vanlapa; Chalachewa, Theerawat; Leurcharusmee, Prangmalee; Tiyaprasertkul, Worakamol; Finlayson, Roderick J; Tran, De Q

2018-03-01

Ultrasound-guided lumbar plexus blocks usually require confirmatory neurostimulation. A simpler alternative is to inject local anaesthetic inside the posteromedial quadrant of the psoas muscle under ultrasound guidance. We hypothesised that both techniques would result in similar total anaesthesia time, defined as the sum of performance and onset time. A randomised, observer-blinded, equivalence trial. Ramathibodi Hospital and Maharaj Nakorn Chiang Mai Hospital (Thailand) from 12 May 2016 to 10 January 2017. A total of 110 patients undergoing total hip or knee arthroplasty, who required lumbar plexus block for postoperative analgesia. In the combined ultrasonography-neurostimulation group, quadriceps-evoked motor response was sought at a current between 0.2 and 0.8 mA prior to local anaesthetic injection (30 ml of lidocaine 1% and levobupivacaine 0.25% with epinephrine 5 μg ml and 5 mg of dexamethasone). In the ultrasound guidance alone group, local anaesthetic was simply injected inside the posteromedial quadrant of the psoas muscle. We measured the total anaesthesia time, the success rate (at 30 min), the number of needle passes, block-related pain, cumulative opioid consumption (at 24 h) and adverse events (vascular puncture, paraesthesia, local anaesthetic spread to the epidural space). The equivalence margin was 7.4 min. Compared with ultrasound guidance alone, combined ultrasonography-neurostimulation resulted in decreased mean (±SD) total anaesthesia time [15.3 (±6.5) vs. 20.1 (±9.0) min; mean difference, -4.8; 95% confidence interval, -8.1 to -1.9; P = 0.005] and mean (±SD) onset time [10.2 (±5.6) vs. 15.5 (±9.0) min; P = 0.004). No inter-group differences were observed in terms of success rate, performance time, number of needle passes, block-related pain, opioid consumption or adverse events. Although the ultrasonography-neurostimulation technique results in a shorter total anaesthesia time compared with ultrasound guidance alone, this difference falls within our accepted equivalence margin (±7.4 min). www.clinicaltrials in the (Study ID: TCTR20160427003).

Poor description of non-pharmacological interventions: analysis of consecutive sample of randomised trials

PubMed Central

Erueti, Chrissy; Glasziou, Paul P

2013-01-01

Objectives To evaluate the completeness of descriptions of non-pharmacological interventions in randomised trials, identify which elements are most frequently missing, and assess whether authors can provide missing details. Design Analysis of consecutive sample of randomised trials of non-pharmacological interventions. Data sources and study selection All reports of randomised trials of non-pharmacological interventions published in 2009 in six leading general medical journals; 133 trial reports, with 137 interventions, met the inclusion criteria. Data collection Using an eight item checklist, two raters assessed the primary full trial report, plus any reference materials, appendices, or websites. Questions about missing details were emailed to corresponding authors, and relevant items were then reassessed. Results Of 137 interventions, only 53 (39%) were adequately described; this was increased to 81 (59%) by using 63 responses from 88 contacted authors. The most frequently missing item was the “intervention materials” (47% complete), but it also improved the most after author response (92% complete). Whereas some authors (27/70) provided materials or further information, other authors (21/70) could not; their reasons included copyright or intellectual property concerns, not having the materials or intervention details, or being unaware of their importance. Although 46 (34%) trial interventions had further information or materials readily available on a website, many were not mentioned in the report, were not freely accessible, or the URL was no longer functioning. Conclusions Missing essential information about interventions is a frequent, yet remediable, contributor to the worldwide waste in research funding. If trial reports do not have a sufficient description of interventions, other researchers cannot build on the findings, and clinicians and patients cannot reliably implement useful interventions. Improvement will require action by funders, researchers, and publishers, aided by long term repositories of materials linked to publications. PMID:24021722

ShopSmart 4 Health - protocol of a skills-based randomised controlled trial promoting fruit and vegetable consumption among socioeconomically disadvantaged women.

PubMed

Ball, Kylie; McNaughton, Sarah A; Le, Ha; Andrianopoulos, Nick; Inglis, Victoria; McNeilly, Briohny; Lichomets, Irene; Granados, Alba; Crawford, David

2013-05-14

There is a need for evidence on the most effective and cost-effective approaches for promoting healthy eating among groups that do not meet dietary recommendations for good health, such as those with low incomes or experiencing socioeconomic disadvantage. This paper describes the ShopSmart 4 Health study, a randomised controlled trial conducted by Deakin University, Coles Supermarkets and the Heart Foundation, to investigate the effectiveness and cost-effectiveness of a skill-building intervention for promoting increased purchasing and consumption of fruits and vegetables amongst women of low socioeconomic position (SEP). ShopSmart 4 Health employed a randomised controlled trial design. Women aged 18-60 years, holding a Coles store loyalty card, who shopped at Coles stores within socioeconomically disadvantaged neighbourhoods and met low-income eligibility criteria were invited to participate. Consenting women completed a baseline survey assessing food shopping and eating habits and food-related behaviours and attitudes. On receipt of their completed survey, women were randomised to either a skill-building intervention or a wait-list control condition. Intervention effects will be evaluated via self-completion surveys and using supermarket transaction sales data, collected at pre- and post-intervention and 6-month follow-up. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. Process evaluation will be undertaken to identify perceived value and effects of intervention components. This study will provide data to address the currently limited evidence base regarding the effectiveness and cost-effectiveness of skill-building intervention strategies aimed at increasing fruit and vegetable consumption among socioeconomically disadvantaged women, a target group at high risk of poor diets. Current Controlled Trials ISRCTN48771770.

A randomised controlled trial of complete denture impression materials.

PubMed

Hyde, T P; Craddock, H L; Gray, J C; Pavitt, S H; Hulme, C; Godfrey, M; Fernandez, C; Navarro-Coy, N; Dillon, S; Wright, J; Brown, S; Dukanovic, G; Brunton, P A

2014-08-01

There is continuing demand for non-implant prosthodontic treatment and yet there is a paucity of high quality Randomised Controlled Trial (RCT) evidence for best practice. The aim of this research was to provide evidence for best practice in prosthodontic impressions by comparing two impression materials in a double-blind, randomised, crossover, controlled, clinical trial. Eighty-five patients were recruited, using published eligibility criteria, to the trial at Leeds Dental Institute, UK. Each patient received two sets of dentures; made using either alginate or silicone impressions. Randomisations determined the order of assessment and order of impressions. The primary outcome was patient blinded preference for unadjusted dentures. Secondary outcomes were patient preference for the adjusted dentures, rating of comfort, stability and chewing efficiency, experience of each impression, and an OHIP-EDENT questionnaire. Seventy-eight (91.8%) patients completed the primary assessment. 53(67.9%) patients preferred dentures made from silicone impressions while 14(17.9%) preferred alginate impressions. 4(5.1%) patients found both dentures equally satisfactory and 7 (9.0%) found both equally unsatisfactory. There was a 50% difference in preference rates (in favour of silicone) (95%CI 32.7-67.3%, p<0.0001). There is significant evidence that dentures made from silicone impressions were preferred by patients. Given the strength of the clinical findings within this paper, dentists should consider choosing silicone rather than alginate as their material of choice for secondary impressions for complete dentures. ISRCTN 01528038. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A randomised trial of early palliative care for maternal stress in infants prenatally diagnosed with single-ventricle heart disease.

PubMed

Hancock, Hayley S; Pituch, Ken; Uzark, Karen; Bhat, Priya; Fifer, Carly; Silveira, Maria; Yu, Sunkyung; Welch, Suzanne; Donohue, Janet; Lowery, Ray; Aiyagari, Ranjit

2018-04-01

Children with single-ventricle disease experience high mortality and complex care. In other life-limiting childhood illnesses, paediatric palliative care may mitigate maternal stress. We hypothesised that early palliative care in the single-ventricle population may have the same benefit for mothers. In this pilot randomised trial of early palliative care, mothers of infants with prenatal single-ventricle diagnoses completed surveys measuring depression, anxiety, coping, and quality of life at a prenatal visit and neonatal discharge. Infants were randomised to receive early palliative care - structured evaluation, psychosocial/spiritual, and communication support before surgery - or standard care. Among 56 eligible mothers, 40 enrolled and completed baseline surveys; 38 neonates were randomised, 18 early palliative care and 20 standard care; and 34 postnatal surveys were completed. Baseline Beck Depression Inventory-II and State-Trait Anxiety Index scores exceeded normal pregnant sample scores (mean 13.76±8.46 versus 7.0±5.0 and 46.34±12.59 versus 29.8±6.35, respectively; p=0.0001); there were no significant differences between study groups. The early palliative care group had a decrease in prenatal to postnatal State-Trait Anxiety Index scores (-7.6 versus 0.3 in standard care, p=0.02), higher postnatal Brief Cope Inventory positive reframing scores (p=0.03), and a positive change in PedsQL Family Impact Module communication and family relationships scores (effect size 0.46 and 0.41, respectively). In conclusion, these data show that mothers of infants with single-ventricle disease experience significant depression and anxiety prenatally. Early palliative care resulted in decreased maternal anxiety, improved maternal positive reframing, and improved communication and family relationships.

Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial.

PubMed

Dodd, Jodie M; Grivell, Rosalie M; Deussen, Andrea R; Dekker, Gustaaf; Louise, Jennie; Hague, William

2016-11-21

Obesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m 2 . Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes. Further information evaluating alternative strategies is required. The aims of this randomised controlled trial are to assess whether the use of metformin as an adjunct therapy to dietary and lifestyle advice for overweight and obese women during pregnancy is effective in improving maternal, fetal and infant health outcomes. Design: Multicentre randomised, controlled trial. Women with a singleton, live gestation between 10 +0 -20 +0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m 2 ), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10 +0 and 20 +0 weeks gestation using an online computer randomisation system, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Metformin Group will receive a supply of 500 mg oral metformin tablets. Women randomised to the Placebo Group will receive a supply of identical appearing and tasting placebo tablets. Women will be instructed to commence taking one tablet daily for a period of one week, increasing to a maximum of two tablets twice daily over four weeks and then continuing until birth. Women, clinicians, researchers and outcome assessors will be blinded to the allocated treatment group. All women will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant), and three telephone calls over the course of their pregnancy, in which they will be provided with dietary and lifestyle advice, and encouraged to make change utilising a SMART goals approach. Primary Study Outcome: infant birth weight >4000 grams. 524 women to detect a difference from 15.5% to 7.35% reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two-tailed). This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. Australian and New Zealand Clinical Trials Registry ACTRN12612001277831 , prospectively registered 10 th of December, 2012.

45 CFR 96.49 - Due date for receipt of all information required for completion of tribal applications for the...

Code of Federal Regulations, 2010 CFR

2010-10-01

... for completion of tribal applications for the low-income home energy assistance block grants. 96.49 Section 96.49 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS... required for completion of tribal applications for the low-income home energy assistance block grants...

Role of ultrasound guided transversus abdominis plane block as a component of multimodal analgesic regimen for lower segment caesarean section: a randomized double blind clinical study.

PubMed

Jadon, Ashok; Jain, Priyanka; Chakraborty, Swastika; Motaka, Mayur; Parida, Sudhansu Sekhar; Sinha, Neelam; Agrawal, Amit; Pati, Asit Kumar

2018-05-14

While opioids are the mainstay for post-operative analgesia after lower segment caesarean section, they are associated with various untoward effects. Ultrasound guided transversus abdominis plane (TAP) block has been postulated to provide effective analgesia for caesarean section. We evaluated the analgesic efficacy of this block for post caesarean analgesia in a randomised controlled trial. One hundred thirty-nine mothers undergoing caesarean delivery were randomised to receive TAP block with either 20 ml 0.375% ropivacaine or 20 ml saline after obtaining informed consent. All the subjects received a standard spinal anaesthetic and diclofenac was administered for post-operative pain. Breakthrough pain was treated with tramadol. Post-operatively, all the subjects were assessed at 0, 2, 4, 6, 8, 10, 12, 18 & 24 h. The primary outcome was the time to first analgesic request. The secondary measures of outcome were pain, nausea, sedation, number of doses of tramadol administered and satisfaction with the pain management. The median (interquartile range) time to first analgesic request was prolonged in the TAP group compared to the control group (p < 0.0001); 11 h (8,12) and 4 h (2.5,6) respectively. The median (interquartile range) number of doses of tramadol consumed in the TAP group was 0 (0,1) compared to 2 (1,2) in the control group (p < 0.0001). At all points in the study, pain scores both at rest and on movement were lower in the study group (p < 0.0001). Maternal satisfaction with pain relief was also higher in the study group (p 0.0002). One subject in the TAP group had convulsions following injection of local anaesthetic solution. She was managed conservatively with supportive treatment following which she recovered. TAP block reduces pain, prolongs the duration of analgesia and decreases supplemental opioid consumption when used for multimodal analgesia for pain relief after caesarean section. However, the risk of local anaesthetic systemic toxicity remains unknown with this block. Hence larger safety trials and measures to limit this complication need to be ascertained. The trial was registered with the Clinical Trial Registry of India ( CTRI/2017/03/008194 ) on 23/03/2017 (trial registered retrospectively).

Complete radiotherapy response in rectal cancer: A review of the evidence

PubMed Central

Couch, Daniel G; Hemingway, David M

2016-01-01

Complete response to chemoradiotherapy for rectal cancer is becoming a common clinical entity. Techniques to diagnose complete response and how to survey these patients without operative intervention are still unclear. We review the most recent evidence. Barriers to firm conclusions regarding this are heterogeneity of diagnostic definitions, differing surveillance protocols, and a lack of randomised studies. PMID:26811600

Effect of sodium azide addition and aging storage on casein micelle size

NASA Astrophysics Data System (ADS)

Sinaga, H.; Deeth, H.; Bhandari, B.

2018-02-01

Casein micelles affected most of milk properties, therefore the use sodium azide as milk preservation is not expected to alter milk properties during storage, including the casein micelle size. The aim of this study was to analyse casein micelle size after the addition of sodium azide during storage. The experiment was performed as a complete block randomised design with three replications. The addition of 0.02-0.10% Na-azide do not lead to any noticeable differences in average casein size at the same day and show similar trend after 14 day-storage. At concentration of 0.02% sodium azide (Na-azide), the size of pasteurised milk did not change up to 12 days, while the size of raw skim milk slightly increased by ageing time at day 5. The treated concentration did not affect the size distribution, except for milk with 0.02% Na-azide which had narrower distribution compared to other treated and control milk. The finding from this study suggests that the role of Na-azide in this experiments during storage at 4°C is only for preventing the microbial growth.

Effect of microfluidization on casein micelle size of bovine milk

NASA Astrophysics Data System (ADS)

Sinaga, H.; Deeth, H.; Bhandari, B.

2018-02-01

The properties of milk are likely to be dependent on the casein micelle size, and various processing technologies produce particular change in the average size of casein micelles. The main objective of this study was to manipulate casein micelle size by subjecting milk to microfluidizer. The experiment was performed as a complete block randomised design with three replications. The sample was passed through the microfluidizer at the set pressure of 83, 97, 112 and 126 MPa for one, two, three, four, five and six cycles, except for the 112 MPa. The results showed that microfluidized milk has smaller size by 3% with pressure up to 126 MPa. However, at each pressure, no further reduction was observed after increasing the passed up to 6 cycles. Although the average casein micelle size was similar, elevating pressure resulted in narrower size distribution. In contrast, increasing the number of cycles had little effect on casein micelle distribution. The finding from this study can be applied for future work to characterize the fundamental and functional properties of the treated milk.

5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

PubMed

Bhattacharya, Sujit K; Sur, Dipika; Ali, Mohammad; Kanungo, Suman; You, Young Ae; Manna, Byomkesh; Sah, Binod; Niyogi, Swapan K; Park, Jin Kyung; Sarkar, Banwarilal; Puri, Mahesh K; Kim, Deok Ryun; Deen, Jacqueline L; Holmgren, Jan; Carbis, Rodney; Dhingra, Mandeep Singh; Donner, Allan; Nair, G Balakrish; Lopez, Anna Lena; Wierzba, Thomas F; Clemens, John D

2013-12-01

Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of contact on adolescents' mental health literacy and stigma: the SchoolSpace cluster randomised controlled trial.

PubMed

Chisholm, Katharine; Patterson, Paul; Torgerson, Carole; Turner, Erin; Jenkinson, David; Birchwood, Max

2016-02-19

To investigate whether intergroup contact in addition to education is more effective than education alone in reducing stigma of mental illness in adolescents. A pragmatic cluster randomised controlled trial compared education alone with education plus contact. Blocking was used to randomly stratify classes within schools to condition. Random allocation was concealed, generated by a computer algorithm, and undertaken after pretest. Data was collected at pretest and 2-week follow-up. Analyses use an intention-to-treat basis. Secondary schools in Birmingham, UK. The parents and guardians of all students in year 8 (age 12-13 years) were approached to take part. A 1-day educational programme in each school led by mental health professional staff. Students in the 'contact' condition received an interactive session with a young person with lived experience of mental illness. The primary outcome was students' attitudinal stigma of mental illness. Secondary outcomes included knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Participants were recruited between 1 May 2011 and 30 April 2012. 769 participants completed the pretest and were randomised to condition. 657 (85%) provided follow-up data. At 2-week follow-up, attitudinal stigma improved in both conditions with no significant effect of condition (95% CI -0.40 to 0.22, p=0.5, d=0.01). Significant improvements were found in the education-alone condition compared with the contact and education condition for the secondary outcomes of knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Contact was found to reduce the impact of the intervention for a number of outcomes. Caution is advised before employing intergroup contact with younger student age groups. The education intervention appeared to be successful in reducing stigma, promoting mental health knowledge, and increasing mental health literacy, as well as improving emotional well-being and resilience. A larger trial is needed to confirm these results. ISRCTN07406026; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Impact of contact on adolescents’ mental health literacy and stigma: the SchoolSpace cluster randomised controlled trial

PubMed Central

Chisholm, Katharine; Patterson, Paul; Torgerson, Carole; Turner, Erin; Jenkinson, David; Birchwood, Max

2016-01-01

Objectives To investigate whether intergroup contact in addition to education is more effective than education alone in reducing stigma of mental illness in adolescents. Design A pragmatic cluster randomised controlled trial compared education alone with education plus contact. Blocking was used to randomly stratify classes within schools to condition. Random allocation was concealed, generated by a computer algorithm, and undertaken after pretest. Data was collected at pretest and 2-week follow-up. Analyses use an intention-to-treat basis. Setting Secondary schools in Birmingham, UK. Participants The parents and guardians of all students in year 8 (age 12–13 years) were approached to take part. Interventions A 1-day educational programme in each school led by mental health professional staff. Students in the ‘contact’ condition received an interactive session with a young person with lived experience of mental illness. Outcomes The primary outcome was students’ attitudinal stigma of mental illness. Secondary outcomes included knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Results Participants were recruited between 1 May 2011 and 30 April 2012. 769 participants completed the pretest and were randomised to condition. 657 (85%) provided follow-up data. At 2-week follow-up, attitudinal stigma improved in both conditions with no significant effect of condition (95% CI −0.40 to 0.22, p=0.5, d=0.01). Significant improvements were found in the education-alone condition compared with the contact and education condition for the secondary outcomes of knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Conclusions Contact was found to reduce the impact of the intervention for a number of outcomes. Caution is advised before employing intergroup contact with younger student age groups. The education intervention appeared to be successful in reducing stigma, promoting mental health knowledge, and increasing mental health literacy, as well as improving emotional well-being and resilience. A larger trial is needed to confirm these results. Trial registration number ISRCTN07406026; Results. PMID:26895983

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children.

PubMed

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth; Mouncey, Paul; Peters, Mark J

2017-06-12

Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support. We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in 'planned' group B, and deferred in emergency situations (group A and 'rescue' group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study. Ethical approval was granted by the National Research Ethics Service Committee North East-Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences. NCT02612415; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children

PubMed Central

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth; Mouncey, Paul; Peters, Mark J

2017-01-01

Introduction Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support. Methods and analysis We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in ‘planned’ group B, and deferred in emergency situations (group A and ‘rescue’ group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study. Ethics and dissemination Ethical approval was granted by the National Research Ethics Service Committee North East—Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences. Trials registration number NCT02612415; pre-results. PMID:28606907

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

PubMed

Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

2009-09-19

Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. ZonMw.

Comparative evaluation of postoperative pain after using endodontic needle and EndoActivator during root canal irrigation: A randomised controlled trial.

PubMed

Ramamoorthi, Surendar; Nivedhitha, Malli Sureshbabu; Divyanand, Madras Jeyaprakash

2015-08-01

The purpose of this study was to evaluate and compare the postoperative level of pain after activation of irrigants using EndoActivator with conventional needle irrigation during root canal therapy. In this prospective randomised clinical trial, 72 symptomatic irreversible pulpitis patients were selected. Based on block randomisation after routine root canal preparation, patients were assigned to two groups. In group EN, procedures were performed with endodontic irrigating needle (n = 36) while group EA received activation using EndoActivator (n = 36) in the final irrigation protocol. All the participants were called through phone at 8, 24 and 48 h to analyse pain score using visual analogue scale. Those patients who developed pain were prescribed ibuprofen 200 mg. Pain score and frequency of tablet intake were recorded and statistically analysed. Results showed that group EA resulted in significantly less postoperative pain and analgesics intake than group EN. In conclusion, within the limitations of this study, the activation of irrigants using EndoActivator can be considered an effective method for reducing postoperative pain. © 2014 Australian Society of Endodontology.

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste

PubMed Central

Martins, Nelson; Morris, Peter

2009-01-01

Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Design Parallel group randomised controlled trial. Setting Three primary care clinics in Dili, Timor-Leste. Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis. Main outcome measures Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Results Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Trial registration Clinical Trials NCT0019256. PMID:19858174

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste.

PubMed

Martins, Nelson; Morris, Peter; Kelly, Paul M

2009-10-26

To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Parallel group randomised controlled trial. Three primary care clinics in Dili, Timor-Leste. 270 adults aged >or=18 with previously untreated newly diagnosed pulmonary tuberculosis. Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Clinical Trials NCT00192556.

Comparison of the Effects of Low Volume Prilocaine and Alkalinized Prilocaine for the Regional Intravenous Anesthesia Technique in Hand and Wrist Surgery

PubMed Central

Kapusuz, Ozlem; Argun, Guldeniz; Arikan, Murat; Toğral, Guray; Basarir, Aysun; Kadiogullari, Nihal

2014-01-01

Aim. Comparing the effectivity of prilocaine and prilocaine alkalinized with 8.4% NaHCO3 in terms of sensory and motor block onset and termination durations in RIVA technique considering patients' satisfaction and tolerance with application of tourniquet undergoing hand-wrist surgery. Materials and Methods. 64 patients were randomised into two groups. First group (Group P) was administered prilocaine and second group (Group PN) was administered prilocaine + %8.4 NaHCO3. Sensory and motor block onset and termination times and onset of tourniquet pain were recorded. Results. No significant difference was found between the two groups in terms of onset and termination of sensory block and the onset of motor block. The duration of the motor block was longer in Group PN than in Group P (P < 0.05). Tourniquet pain was more intense in Group P (P = 0.036). In Group PN, the use of additional drugs was recorded at a lower rate and patients' satisfaction was higher than Group P. Conclusion. In the present study, it was established that alkalinization of prilocaine had no effect on the duration of sensory block and it prolonged the duration of motor block, increased patients' satisfaction, and decreased tourniquet pain. It is our suggestion that future studies should be carried out on the issue by using different volumes. PMID:25133177

Reporting quality and risk of bias in randomised trials in health professions education.

PubMed

Horsley, Tanya; Galipeau, James; Petkovic, Jennifer; Zeiter, Jeanie; Hamstra, Stanley J; Cook, David A

2017-01-01

Complete reporting of research is essential to enable consumers to accurately appraise, interpret and apply findings. Quality appraisal checklists are giving way to tools that judge the risk for bias. We sought to determine the prevalence of these complementary aspects of research reports (completeness of reporting and perceived risk for bias) of randomised studies in health professions education. We searched bibliographic databases for randomised studies of health professions education. We appraised two cohorts representing different time periods (2008-2010 and 2014, respectively) and worked in duplicate to apply the CONSORT guidelines and Cochrane Risk of Bias tool. We explored differences between time periods using independent-samples t-tests or the chi-squared test, as appropriate. We systematically identified 180 randomised studies (2008-2010, n = 150; 2014, n = 30). Frequencies of reporting of CONSORT elements within full-text reports were highly variable and most elements were reported in fewer than 50% of studies. We found a statistically significant difference in the CONSORT reporting index (maximum score: 500) between the 2008-2010 (mean ± standard deviation [SD]: 242.7 ± 55.6) and 2014 (mean ± SD: 311.6 ± 53.2) cohorts (p < 0.001). High or unclear risk for bias was most common for allocation concealment (157, 87%) and blinding of participants (147, 82%), personnel (152, 84%) and outcome assessors (112, 62%). Most risk for bias elements were judged to be unclear (range: 51-84%). Risk for bias elements significantly improved over time for blinding of participants (p = 0.007), incomplete data (p < 0.001) and the presence of other sources of bias (p < 0.001). Reports of randomised studies in health professions education frequently omit elements recommended by the CONSORT statement. Most reports were assessed as having a high or unclear risk for bias. Greater attention to how studies are reported at study outset and in manuscript preparation could improve levels of complete transparent reporting. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Preoperative ropivacaine with or without tramadol for femoral nerve block in total knee arthroplasty.

PubMed

Tang, Q; Li, X; Yu, L; Hao, Y; Lu, G

2016-08-01

To compare the analgesic effect of preoperative ropivacaine with or without tramadol for femoral nerve block in total knee arthroplasty (TKA). 14 men and 46 women aged 59 to 80 years who were American Society of Anesthesiologists (ASA) grade I or II and were scheduled for TKA were randomised to receive preoperative femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 0 mg (n=15), 50 mg (n=15), or 100 mg (n=15), or no preoperative femoral nerve block (control) [n=15]. Femoral nerve block was performed by a single anaesthesiologist before the standardised combined spinal epidural anaesthesia. Postoperatively, patientcontrolled analgesia was given. The visual analogue score (VAS) for pain at rest and on movement was recorded at 8, 12, 24, 48, and 72 hours. Passive knee range of motion (ROM) was measured at 24, 48, and 72 hours. The 4 groups were comparable in terms of age, gender, weight, ASA grade, and operating time. Compared with patients who received no femoral nerve block or ropivacaine alone, those who received femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 50 mg or 100 mg recorded a lower VAS for pain at rest and on movement at 8 to 72 hours, longer sensory and motor block time, and lower demand, delivery, and total amount of patientcontrolled analgesia. The passive knee ROM at 24 to 72 hours was greater in patients with femoral nerve block than in those without. Preoperative femoral nerve block with 20 ml of 0.375% ropivacaine and 100 mg tramadol resulted in the best analgesic effect.

Magnesium sulphate: an adjuvant to tracheal intubation without muscle relaxation--a randomised study.

PubMed

Aissaoui, Younes; Qamous, Youssef; Serghini, Issam; Zoubir, Mohammed; Salim, Jaafar Lalaoui; Boughalem, Mohammed

2012-08-01

Tracheal intubation without administration of a neuromuscular blocking drug is used frequently in anaesthesia. Several techniques and adjuvants have been tried to improve intubating conditions. Magnesium sulphate is an agent with analgesic, anaesthetic and muscle relaxant effects. To assess the effect of magnesium sulphate on intubating conditions after induction of anaesthesia without a neuromuscular blocking drug. Double-blinded randomised study. Sixty patients with American Society of Anesthesiologists physical status 1/2 scheduled for elective surgery under general anaesthesia were included. Avicenna Military Hospital between June 2010 and March 2011. Before induction of general anaesthesia, patients were assigned to receive either a 10-min infusion of magnesium sulphate 45 mg kg(-1) in 100 ml of isotonic saline (magnesium group, n = 30) or the same volume of saline (control group, n = 30). Anaesthesia was induced with fentanyl 3 μg kg(-1) followed 3 min later by propofol 2.5 mg kg(-1). Intubating conditions were evaluated by a blinded anaesthesiologist using the criteria of the Copenhagen consensus conference: ease of laryngoscopy, vocal cord position and/or movement and response to intubation or cuff inflation (cough or diaphragmatic movement). Intubating conditions were considered as acceptable (excellent or good) or unacceptable (poor). Mean arterial pressure and heart rate were also recorded during the study period. The two groups were comparable in their demographic profiles. Clinically acceptable intubating conditions were observed more frequently in the magnesium group than in the control group: 25 (83%) vs. 18 patients (60%) (P = 0.042). There was no failed intubation. There were no differences between the groups with regard to haemodynamic variables. Addition of magnesium sulphate to propofol and fentanyl at induction of anaesthesia significantly improved intubating conditions without administration of a neuromuscular blocking drug.

Effect of a lifestyle intervention on weight change in south Asian individuals in the UK at high risk of type 2 diabetes: a family-cluster randomised controlled trial.

PubMed

Bhopal, Raj S; Douglas, Anne; Wallia, Sunita; Forbes, John F; Lean, Michael E J; Gill, Jason M R; McKnight, John A; Sattar, Naveed; Sheikh, Aziz; Wild, Sarah H; Tuomilehto, Jaakko; Sharma, Anu; Bhopal, Ruby; Smith, Joel B E; Butcher, Isabella; Murray, Gordon D

2014-03-01

The susceptibility to type 2 diabetes of people of south Asian descent is established, but there is little trial-based evidence for interventions to tackle this problem. We assessed a weight control and physical activity intervention in south Asian individuals in the UK. We did this non-blinded trial in two National Health Service (NHS) regions in Scotland (UK). Between July 1, 2007, and Oct 31, 2009, we recruited men and women of Indian and Pakistani origin, aged 35 years or older, with waist circumference 90 cm or greater in men or 80 cm or greater in women, and with impaired glucose tolerance or impaired fasting glucose determined by oral glucose tolerance test. Families were randomised (using a random number generator program, with permuted blocks of random size, stratified by location [Edinburgh or Glasgow], ethnic group [Indian or Pakistani], and number of participants in the family [one vs more than one]) to intervention or control. Participants in the same family were not randomised separately. The intervention group received 15 visits from a dietitian over 3 years and the control group received four visits in the same period. The primary outcome was weight change at 3 years. Analysis was by modified intention to treat, excluding participants who died or were lost to follow-up. We used linear regression models to provide mean differences in baseline-adjusted weight at 3 years. This trial is registered, number ISRCTN25729565. Of 1319 people who were screened with an oral glucose tolerance test, 196 (15%) had impaired glucose tolerance or impaired fasting glucose and 171 entered the trial. Participants were in 156 family clusters that were randomised (78 families with 85 participants were allocated to intervention; 78 families with 86 participants were allocated to control). 167 (98%) participants in 152 families completed the trial. Mean weight loss in the intervention group was 1.13 kg (SD 4.12), compared with a mean weight gain of 0.51 kg (3.65) in the control group, an adjusted mean difference of -1.64 kg (95% CI -2.83 to -0.44). Modest, medium-term changes in weight are achievable as a component of lifestyle-change strategies, which might control or prevent adiposity-related diseases. National Prevention Research Initiative, NHS Research and Development; NHS National Services Scotland; NHS Health Scotland. Copyright © 2014 Bhopal et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study.

PubMed

Kim, Jong S; Lee, Eun-Jae; Chang, Dae-Il; Park, Jong-Ho; Ahn, Seong Hwan; Cha, Jae-Kwan; Heo, Ji Hoe; Sohn, Sung-Il; Lee, Byung-Chul; Kim, Dong-Eog; Kim, Hahn Young; Kim, Seongheon; Kwon, Do-Young; Kim, Jei; Seo, Woo-Keun; Lee, Jun; Park, Sang-Won; Koh, Seong-Ho; Kim, Jin Young; Choi-Kwon, Smi

2017-01-01

Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke. This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498. Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 [13%] patients in the placebo group vs 27 [13%] in the escitalopram group; odds ratio [OR] 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 [14%] vs 35 [15%]; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 [6%] patients who received placebo vs 14 [6%] who received escitalopram), muscle pain (16 [7%] vs ten [4%]), and insomnia (12 [5%] vs 12 [5%]). Diarrhoea was more common in the escitalopram group (nine [4%] patients) than in the placebo group (two [1%] patients). Escitalopram did not significantly reduce moderate or severe depressive symptoms in patients with acute stroke. Dong-A Pharmaceutical and Ministry for Health, Welfare, and Family Affairs, South Korea. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial.

PubMed

Deterding, Katja; Grüner, Norbert; Buggisch, Peter; Wiegand, Johannes; Galle, Peter R; Spengler, Ulrich; Hinrichsen, Holger; Berg, Thomas; Potthoff, Andrej; Malek, Nisar; Großhennig, Anika; Koch, Armin; Diepolder, Helmut; Lüth, Stefan; Feyerabend, Sandra; Jung, Maria Christina; Rogalska-Taranta, Magdalena; Schlaphoff, Verena; Cornberg, Markus; Manns, Michael P; Wedemeyer, Heiner

2013-06-01

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment. In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946. Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI -4·6 to 32·0; p=0·071). 18 (72%) of 25 asymptomatic patients had a sustained virological response. 22 (42%) of 52 symptomatic patients allocated to receive delayed treatment did not complete follow-up compared with 20 (25%) of 80 symptomatic or asymptomatic patients assigned immediate treatment (p=0·037). 11 symptomatic patients (21%) assigned delayed treatment had spontaneous HCV clearance. 14 patients who received delayed pegylated interferon alfa-2b plus ribavirin treatment and completed follow-up achieved sustained virological response. Delayed treatment is effective although not of equal efficacy to immediate treatment; coupled with the rate of spontaneous clearance it can reduce unnecessary treatment in closely monitored populations. Immediate treatment seems preferable in populations where loss to follow-up is great. German Network of Competence on Viral Hepatitis (HepNet, funded by the German Federal Ministry of Education and Research, grants 01KI0102, 01KI0401, and 01KI0601), MSD, Schering-Plough. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

PubMed

McInnes, Rhona J; Hillan, Edith; Clark, Diana; Gilmour, Harper

2004-10-01

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. Randomised controlled trial. The South Glasgow University Hospitals NHS Trust. Primigravidae and multigravidae in labour at term (37-42 weeks). Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. Analgesia requirements during labour and women's satisfaction with the method of pain relief. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Sodium channel blockers for cystic fibrosis.

PubMed

Burrows, E; Southern, K W; Noone, P

2006-07-19

People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF. To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data. Most recent search of the Group's register: March 2006 Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. Two authors independently extracted data. Meta-analysis was limited due to differing study designs. Four RCTs, with a total of 205 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. For three studies, interventions for six months were completed and it was possible to calculate relative change in respiratory function (FVC). There was a significant difference found in relative change in FVC in favour of placebo (GIV analysis of weighted mean difference for FVC; 1.51% (95% confidence interval -2.77 to -0.25). There were no significant differences identified in other clinically relevant outcomes. We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

Adding a transversus abdominis plane block to parenteral opioid for postoperative analgesia following trans-abdominal hysterectomy in a low resource setting: a prospective, randomised, double blind, controlled study.

PubMed

Moyo, Nomaqhawe; Madzimbamuto, Farai D; Shumbairerwa, Samson

2016-01-28

The current gold standard treatment for acute postoperative pain after major abdominal surgery is multimodal analgesia using patient controlled analgesia delivery systems. Patient controlled analgesia systems are expensive and their routine use in very low income countries is not practical. The use of ultrasound in anaesthesia has made some regional anaesthesia blocks technically easy and safe to perform. This study aimed to determine whether adding an ultrasound guided transversus abdominis plane block as an adjunct to the current parenteral opioid based regimen would result in superior pain relief after a trans abdominal hysterectomy compared to using parenteral opioids alone. Thirty-two elective patients having trans abdominal hysterectomy were recruited into a prospective randomised double-blind, controlled study comparing a bilateral transversus abdominis plane block using 21 ml of 0.25% bupivacaine and 4.0 mg dexamethasone with a sham block containing 21 ml 0.9% saline. Sixteen patients were allocated to each group. Anaesthesia and postoperative analgesia was left to the attending anaesthetist's discretion. Primary outcome was visual analogue scale for pain at 2 h and 4 h. Secondary outcomes were time to first request for analgesia, visual analogue scale for comfort and bother. The data were analysed using the Statistical Package for Social Sciences (SPSS version 16). There was no statistically significant difference in the demographics of the two groups regarding weight, height, physical status and type of surgical incision. There was a statistically significant difference in visual analogue scale for pain at 4 h during movement with lower pain scales in the test group (p = 0.034). Women in the control group had an average pain free period of 56.8 min (median 56.5 min) before requesting a rescue analgesic compared to 116.5 min (median 103 min) in the study group. The between group difference in the average total analgesia duration was statistically significant at the 0.05 level (p = 0.005). The addition of a bupivacaine-dexamethasone transverse abdominis plane block to intramuscular opioid does produce superior acute post-operative pain relief following a hysterectomy. However a single-shot block has a limited duration of action, and we recommend a repeat block. Clinical trials registration was obtained PACTR201501000965252. http//www.pactr.org/ATMWeb/appmanager/atm/atmregistry?_nfpb=true&_windowLabel=BasicSearchUpdateController_1&BasicSearchUpdateController_1_actionOverride=%2Fpageflows%2Ftrial%2FbasicSearchUpdate%2FviewTrail&BasicSearchUpdateController_1id=965. The trial was registered on the 12th Dec 2014.

Sprint-based exercise and cognitive function in adolescents.

PubMed

Cooper, Simon B; Bandelow, Stephan; Nute, Maria L; Dring, Karah J; Stannard, Rebecca L; Morris, John G; Nevill, Mary E

2016-12-01

Moderate intensity exercise has been shown to enhance cognition in an adolescent population, yet the effect of high-intensity sprint-based exercise remains unknown and was therefore examined in the present study. Following ethical approval and familiarisation, 44 adolescents (12.6 ± 0.6 y) completed an exercise (E) and resting (R) trial in a counter-balanced, randomised crossover design. The exercise trial comprised of 10 × 10 s running sprints, interspersed by 50 s active recovery (walking). A battery of cognitive function tests (Stroop, Digit Symbol Substitution (DSST) and Corsi blocks tests) were completed 30 min pre-exercise, immediately post-exercise and 45 min post-exercise. Data were analysed using mixed effect models with repeated measures. Response times on the simple level of the Stroop test were significantly quicker 45 min following sprint-based exercise (R: 818 ± 33 ms, E: 772 ± 26 ms; p = 0.027) and response times on the complex level of the Stroop test were quicker immediately following the sprint-based exercise (R: 1095 ± 36 ms, E: 1043 ± 37 ms; p = 0.038), while accuracy was maintained. Sprint-based exercise had no immediate or delayed effects on the number of items recalled on the Corsi blocks test (p = 0.289) or substitutions made during the DSST (p = 0.689). The effect of high intensity sprint-based exercise on adolescents' cognitive function was dependant on the component of cognitive function examined. Executive function was enhanced following exercise, demonstrated by improved response times on the Stroop test, whilst visuo-spatial memory and general psycho-motor speed were unaffected. These data support the inclusion of high-intensity sprint-based exercise for adolescents during the school day to enhance cognition.

Effects of inclusion level on nutrient digestibility and energy content of wheat middlings and soya bean meal for growing pigs.

PubMed

Huang, Qiang; Piao, Xiangshu; Liu, Ling; Li, Defa

2013-01-01

Two experiments were conducted to determine the effects of inclusion level of wheat middlings and soya bean meal on apparent total tract digestibility (ATTD) of energy and chemical components of these ingredients in growing pigs. Furthermore, the effects of the inclusion level on their contents of digestible energy (DE) and metabolisable energy (ME) were also determined by the difference method. In Experiment 1, six diets were fed to 36 growing pigs according to a completely randomised design. The basal diet was a corn-soya bean meal diet while the other five diets contained 9.6%, 19.2%, 28.8%, 38.4% or 48.0% of wheat middlings added at the expense of corn and soya bean meal. The measured digestibility of energy and most nutrients of wheat middlings increased (p < 0.05) with increasing levels of that ingredient. Equations were obtained to predict digestibility by inclusion level. At an inclusion level of 9.6% wheat middlings, their DE contents were significantly lower (8.9 MJ/kg DM) than for the higher levels (10.7 to 11.9 MJ/kg DM, p < 0.01). In Experiment 2, three diets were fed to 18 growing pigs according to a completely randomised block design. The basal diet was a corn-based diet while the other two diets were based on corn and two levels of soya bean meal (22.2% and 33.6%). The content of DE in soya bean meal did not differ at 22.2% and 33.6% inclusion levels (16.2 and 16.3 MJ/kg DM, respectively), but the digestibility of dry matter (DM), organic matter and carbohydrates was increased at a higher inclusion level (p < 0.05). This study revealed that the estimated digestibility of nutrients from soya bean meal and wheat middlings was affected by their dietary inclusion levels. For soya bean meal, the estimated energy contents was independent of its inclusion level, but not for wheat middlings. Therefore, the inclusion level of wheat middlings has to be considered for estimating their energy value.

Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

PubMed

Sandborn, W J; Rutgeerts, P; Gasink, C; Jacobstein, D; Zou, B; Johanns, J; Sands, B E; Hanauer, S B; Targan, S; Ghosh, S; de Villiers, W J S; Colombel, J-F; Feagan, B G

2018-05-24

In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient-years) were similar among all placebo and ustekinumab patients (Week 0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed. Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355. © 2018 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Treatment of missing data in follow-up studies of randomised controlled trials: A systematic review of the literature.

PubMed

Sullivan, Thomas R; Yelland, Lisa N; Lee, Katherine J; Ryan, Philip; Salter, Amy B

2017-08-01

After completion of a randomised controlled trial, an extended follow-up period may be initiated to learn about longer term impacts of the intervention. Since extended follow-up studies often involve additional eligibility restrictions and consent processes for participation, and a longer duration of follow-up entails a greater risk of participant attrition, missing data can be a considerable threat in this setting. As a potential source of bias, it is critical that missing data are appropriately handled in the statistical analysis, yet little is known about the treatment of missing data in extended follow-up studies. The aims of this review were to summarise the extent of missing data in extended follow-up studies and the use of statistical approaches to address this potentially serious problem. We performed a systematic literature search in PubMed to identify extended follow-up studies published from January to June 2015. Studies were eligible for inclusion if the original randomised controlled trial results were also published and if the main objective of extended follow-up was to compare the original randomised groups. We recorded information on the extent of missing data and the approach used to treat missing data in the statistical analysis of the primary outcome of the extended follow-up study. Of the 81 studies included in the review, 36 (44%) reported additional eligibility restrictions and 24 (30%) consent processes for entry into extended follow-up. Data were collected at a median of 7 years after randomisation. Excluding 28 studies with a time to event primary outcome, 51/53 studies (96%) reported missing data on the primary outcome. The median percentage of randomised participants with complete data on the primary outcome was just 66% in these studies. The most common statistical approach to address missing data was complete case analysis (51% of studies), while likelihood-based analyses were also well represented (25%). Sensitivity analyses around the missing data mechanism were rarely performed (25% of studies), and when they were, they often involved unrealistic assumptions about the mechanism. Despite missing data being a serious problem in extended follow-up studies, statistical approaches to addressing missing data were often inadequate. We recommend researchers clearly specify all sources of missing data in follow-up studies and use statistical methods that are valid under a plausible assumption about the missing data mechanism. Sensitivity analyses should also be undertaken to assess the robustness of findings to assumptions about the missing data mechanism.

A randomised controlled trial of a cognitive behavioural intervention for women who have menopausal symptoms following breast cancer treatment (MENOS 1): Trial protocol

PubMed Central

2011-01-01

Background This trial aims to evaluate the effectiveness of a group cognitive behavioural intervention to alleviate menopausal symptoms (hot flushes and night sweats) in women who have had breast cancer treatment. Hot flushes and night sweats are highly prevalent but challenging to treat in this population. Cognitive behaviour therapy has been found to reduce these symptoms in well women and results of an exploratory trial suggest that it might be effective for breast cancer patients. Two hypotheses are tested: Compared to usual care, group cognitive behavioural therapy will: 1. Significantly reduce the problem rating and frequency of hot flushes and nights sweats after six weeks of treatment and at six months post-randomisation. 2. Improve mood and quality of life after six weeks of treatment and at six months post-randomisation. Methods/Design Ninety-six women who have completed their main treatment for breast cancer and who have been experiencing problematic hot flushes and night sweats for over two months are recruited into the trial from oncology and breast clinics in South East London. They are randomised to either six weekly group cognitive behavioural therapy (Group CBT) sessions or to usual care. Group CBT includes information and discussion about hot flushes and night sweats in the context of breast cancer, monitoring and modifying precipitants, relaxation and paced respiration, stress management, cognitive therapy for unhelpful thoughts and beliefs, managing sleep and night sweats and maintaining changes. Prior to randomisation women attend a clinical interview, undergo 24-hour sternal skin conductance monitoring, and complete questionnaire measures of hot flushes and night sweats, mood, quality of life, hot flush beliefs and behaviours, optimism and somatic amplification. Post-treatment measures (sternal skin conductance and questionnaires) are collected six to eight weeks later and follow-up measures (questionnaires and a use of medical services measure) at six months post-randomisation. Discussion MENOS 1 is the first randomised controlled trial of cognitive behavioural therapy for hot flushes and night sweats that measures both self-reported and physiologically indexed symptoms. The results will inform future clinical practice by developing an evidence-based, non-medical treatment, which can be delivered by trained health professionals. Trial Registration Current Controlled Trials ISRCTN13771934 PMID:21281461

The addition of a goal-based motivational interview to standardised treatment as usual to reduce dropouts in a service for patients with personality disorder: a feasibility study.

PubMed

McMurran, Mary; Cox, W Miles; Coupe, Stephen; Whitham, Diane; Hedges, Lucy

2010-10-14

Rates of non-completion of treatments for personality disorder are high and there are indications that those who do not complete treatment have worse outcomes than those who do. Improving both cost-efficiency and client welfare require attention to engaging people with personality disorder in treatment. A motivational interview, based on the Personal Concerns Inventory, may have the ability to enhance engagement and retention in therapy. Here, we report the protocol for a feasibility study for a randomised controlled trial (RCT). All referrals accepted to the psychological service of Nottinghamshire Healthcare NHS Trust's outpatient service for people with personality disorder are eligible for inclusion. Consenting participants are randomised to receive the Personal Concerns Inventory interview plus treatment as usual or treatment as usual only. We aim to recruit 100 participants over 11/2 years. A randomised controlled trial will be considered feasible if 1 the recruitment rate to the project is 54% of all referrals (95% CI 54-64), 2 80% of clients find the intervention acceptable in terms of its practicability and usefulness (95% CI 80-91), and 3 80% of therapists report finding the intervention helpful (95% CI 80-100). In a full-scale randomised controlled trial, the primary outcome measure will be completion of treatment i.e., entry into and completion of ≥ 75% of sessions offered. Therefore, information will be collected on recruitment rates, attendance at therapy sessions, and completion of treatment. The feasibility of examining the processes of engagement will be tested by assessing the value, coherence, and attainability of goals pre-treatment, and engagement in treatment. The costs associated with the intervention will be calculated, and the feasibility of calculating the cost-benefits of the intervention will be tested. The views of clients and therapists on the intervention, collected using semi-structured interviews, will be analysed using thematic analysis. The Personal Concerns Interview as a preparation for treatment of people with personality has the potential to maximise treatment uptake, reduce unfilled places in treatment programmes, and prevent group treatments faltering through non-attendance. Most importantly, it has the potential to improve patient outcomes, helping them to function better and reduce hospitalisation. ClinicalTrials.Gov.UK Identifier--NCT01132976.

Complete heart block in a 9 year old girl caused by borreliosis.

PubMed Central

Gildein, H P; Günther, S; Mocellin, R

1993-01-01

A complete atrioventricular block was seen in a nine year old girl in whom an infection with Borrelia burgdorferi was confirmed by serological testing. There were no other symptoms or cutaneous manifestations of the disease. Though a rash on the right ear was later recalled by her parents. The patient was treated with high dose penicillin and orciprenaline was given intermittently. The complete heart block disappeared within four days. PMID:8038006

Group sequential designs for stepped-wedge cluster randomised trials

PubMed Central

Grayling, Michael J; Wason, James MS; Mander, Adrian P

2017-01-01

Background/Aims: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Methods: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. Results: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial’s type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. Conclusion: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial. PMID:28653550

Group sequential designs for stepped-wedge cluster randomised trials.

PubMed

Grayling, Michael J; Wason, James Ms; Mander, Adrian P

2017-10-01

The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.

The DIAMIND study: postpartum SMS reminders to women who have had gestational diabetes mellitus to test for type 2 diabetes: a randomised controlled trial - study protocol.

PubMed

Heatley, Emer; Middleton, Philippa; Hague, William; Crowther, Caroline

2013-04-12

Postpartum follow up of women who have been found to have gestational diabetes during pregnancy is essential because of the strong association of gestational diabetes with subsequent type 2 diabetes. Postal reminders have been shown to increase significantly attendance for oral glucose tolerance testing postpartum. It is possible that a short message service (text) reminder system may also be effective. This trial aims to assess whether a text message reminder system for women who have experienced gestational diabetes in their index pregnancy will increase attendance for oral glucose tolerance testing within six months after birth. Single centre (Women's and Children's Hospital, South Australia), parallel group randomised controlled trial. Women diagnosed with gestational diabetes in their index pregnancy (oral glucose tolerance test with fasting glucose ≥ 5.5 mmol/L and/or two hour glucose ≥ 7.8 mmol/L), with access to a mobile phone, whose capillary blood glucose profile measurements prior to postnatal discharge are all normal (fasting glucose < 6.0 mmol/L, postprandial glucoses < 8.0 mmol/L). Pregestational diabetes mellitus, triplet/higher order multiple birth or stillbirth in the index pregnancy, requirement for interpreter.Trial entry and randomisation: Allocation to intervention will be undertaken using a telephone randomisation service (computer-generated random number sequence generation, with balanced variable blocks, and stratification by insulin requirement).Study groups: Women in the intervention group will receive a text reminder to attend for an oral glucose tolerance test at 6 weeks postpartum, with further reminders at 3 months and 6 months if they do not respond to indicate test completion. Women in the control group will receive a single text message reminder at 6 months postpartum.Blinding: Baseline data collection will be undertaken blinded. Blinding of participants and blinded collection of primary outcome data will not be possible for this study.Primary study outcome: Attendance for the oral glucose tolerance test within 6 months postpartum. 276 subjects will be required to show an 18% absolute increase in the rate of attendance (α=0.05 two tailed, β=80%, 5% loss to follow up) from 37% to 55% in the intervention group. Given the heightened risk of impaired glucose tolerance and type 2 diabetes in women who have had gestational diabetes, ensuring the highest possible rate of attendance for postpartum glucose tolerance testing, so that early diagnosis and intervention can occur, is important. A text message reminder system may prove to be an effective method for achieving improved attendance for such testing. This randomised controlled trial will assess whether such a system will increase rates of attendance for postpartum oral glucose tolerance testing in women who have experienced gestational diabetes. Australian New Zealand Clinical Trials Registry - ACTRN12612000621819.

A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.

PubMed

Jacob, S L; Brewer, C; Tang, T; Picton, H M; Barth, J H; Balen, A H

2016-12-01

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle? A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01). This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use. This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle. None. EudraCT number 2009-010952-81. 21 September 2009. 30 October 2009. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

15 CFR Supplement No. 1 to Part 752 - Instructions for Completing Form BIS-748P, Multipurpose Application for Requests for Special...

Code of Federal Regulations, 2010 CFR

2010-01-01

... instructions in Supplement No. 1 to part 748 of the EAR. Block 5: Type of Application. Enter an “x” in the... which forms are attached. Block 9: Special Purpose. This block should only be completed when requesting... to the instructions in Supplement No. 1 to part 748 of the EAR. Block 15: Other Party Authorized to...

15 CFR Supplement No. 1 to Part 752 - Instructions for Completing Form BIS-748P, Multipurpose Application for Requests for Special...

Code of Federal Regulations, 2012 CFR

2012-01-01

... instructions in Supplement No. 1 to part 748 of the EAR. Block 5: Type of Application. Enter an “x” in the... which forms are attached. Block 9: Special Purpose. This block should only be completed when requesting... to the instructions in Supplement No. 1 to part 748 of the EAR. Block 15: Other Party Authorized to...

Community-randomised controlled trial embedded in the Anishinaabek Cervical Cancer Screening Study: human papillomavirus self-sampling versus Papanicolaou cytology

PubMed Central

Zehbe, Ingeborg; Jackson, Robert; Wood, Brianne; Weaver, Bruce; Escott, Nicholas; Severini, Alberto; Krajden, Mel; Bishop, Lisa; Morrisseau, Kyla; Ogilvie, Gina; Burchell, Ann N; Little, Julian

2016-01-01

Objectives The incidence of cervical cancer is up to 20-fold higher among First Nations women in Canada than the general population, probably due to lower participation in screening. Offering human papillomavirus (HPV) self-sampling in place of Papanicolaou (Pap) testing may eventually increase screening participation and reduce cervical cancer rates in this population. Design A community-randomised controlled screening trial. Setting First Nations communities in Northwest Ontario, Canada. Participants Women aged between 25 and 69, living in Robinson Superior Treaty First Nations. The community was the unit of randomisation. Interventions Women were asked to complete a questionnaire and have screening by HPV self-sampling (arm A) or Pap testing (arm B). Primary outcome measures The number of women who participated in cervical screening. Randomisation Community clusters were randomised to include approximately equivalent numbers of women in each arm. Results 6 communities were randomised to arm A and 5 to arm B. One community withdrew, leaving 5 communities in each group (834 eligible women). Participation was <25%. Using clustered intention-to-treat (ITT) analysis, initial and cumulative averaged uptakes in arm A were 1.4-fold (20% vs 14.3%, p=0.628) and 1.3-fold (20.6% vs 16%, p=0.694) higher compared to arm B, respectively. Corresponding per protocol (PP) analysis indicates 2.2-fold (22.9% vs 10.6%, p=0.305) and 1.6-fold (22.9% vs 14.1%, p=0.448) higher uptakes in arm A compared to arm B. Screening uptake varied between communities (range 0–62.1%). Among women who completed a questionnaire (18.3% in arm A, 21.7% in arm B), the screening uptake was 1.8-fold (ITT; p=0.1132) or 3-fold (PP; p<0.01) higher in arm A versus arm B. Conclusions Pap and HPV self-sampling were compared in a marginalised, Canadian population. Results indicated a preference for self-sampling. More research on how to reach underscreened Indigenous women is necessary. Trial registration number ISRCTN84617261. PMID:27855089

Comparison of the post-operative analgesic effect of paravertebral block, pectoral nerve block and local infiltration in patients undergoing modified radical mastectomy: A randomised double-blind trial

PubMed Central

Syal, Kartik; Chandel, Ankita

2017-01-01

Background and Aims: Paravertebral block, pectoral nerve (Pecs) block and wound infiltration are three modalities for post-operative analgesia following breast surgery. This study compares the analgesic efficacy of these techniques for post-operative analgesia. Methods: Sixty-five patients with American Society of Anesthesiologists’ physical status 1 or 2 undergoing modified radical mastectomy with axillary dissection were recruited for the study. All patients received 21 mL 0.5% bupivacaine with adrenaline in the technique which was performed at the end of the surgery prior to extubation. Patients in Group 1 (local anaesthetic [LA], n = 22) received infiltration at the incision site after surgery, Group 2 patients (paravertebral block [PVB], n = 22) received ultrasound-guided ipsilateral paravertebral block while Group 3 patients [PECT] (n = 21) received ultrasound-guided ipsilateral Pecs blocks I and II. Patients were evaluated for pain scores at 0, 2, 4, 6, 12 and 24 h, duration of post-operative analgesia and rescue analgesic doses required. Non-normally distributed data were analysed using the Kruskal-Wallis test and Analysis of variance for normal distribution. Results: The post-operative visual analogue scale scores were lower in PVB group compared with others at 0, 2, 4, 12 and 24 h (P < 0.05). Mean duration of analgesia was significantly prolonged in PVB group (P < 0.001) with lesser rescue analgesic consumption up to 24 h. Conclusion: Ultrasound-guided paravertebral block reduces post-operative pain scores, prolongs the duration of analgesia and decreases demands for rescue analgesics in the first 24 h of post-operative period compared to ultrasound-guided Pecs block and local infiltration block. PMID:28890559

Comparison of the post-operative analgesic effect of paravertebral block, pectoral nerve block and local infiltration in patients undergoing modified radical mastectomy: A randomised double-blind trial.

PubMed

Syal, Kartik; Chandel, Ankita

2017-08-01

Paravertebral block, pectoral nerve (Pecs) block and wound infiltration are three modalities for post-operative analgesia following breast surgery. This study compares the analgesic efficacy of these techniques for post-operative analgesia. Sixty-five patients with American Society of Anesthesiologists' physical status 1 or 2 undergoing modified radical mastectomy with axillary dissection were recruited for the study. All patients received 21 mL 0.5% bupivacaine with adrenaline in the technique which was performed at the end of the surgery prior to extubation. Patients in Group 1 (local anaesthetic [LA], n = 22) received infiltration at the incision site after surgery, Group 2 patients (paravertebral block [PVB], n = 22) received ultrasound-guided ipsilateral paravertebral block while Group 3 patients [PECT] ( n = 21) received ultrasound-guided ipsilateral Pecs blocks I and II. Patients were evaluated for pain scores at 0, 2, 4, 6, 12 and 24 h, duration of post-operative analgesia and rescue analgesic doses required. Non-normally distributed data were analysed using the Kruskal-Wallis test and Analysis of variance for normal distribution. The post-operative visual analogue scale scores were lower in PVB group compared with others at 0, 2, 4, 12 and 24 h ( P < 0.05). Mean duration of analgesia was significantly prolonged in PVB group ( P < 0.001) with lesser rescue analgesic consumption up to 24 h. Ultrasound-guided paravertebral block reduces post-operative pain scores, prolongs the duration of analgesia and decreases demands for rescue analgesics in the first 24 h of post-operative period compared to ultrasound-guided Pecs block and local infiltration block.

Effectiveness of personalised risk information and taster sessions to increase the uptake of smoking cessation services (Start2quit): a randomised controlled trial.

PubMed

Gilbert, Hazel; Sutton, Stephen; Morris, Richard; Petersen, Irene; Galton, Simon; Wu, Qi; Parrott, Steve; Nazareth, Irwin

2017-02-25

National Health Service Stop Smoking Services (SSSs) offer help to smokers motivated to quit; however, attendance rates are low and recent figures show a downward trend. We aimed to assess the effectiveness of a two-component personalised intervention on attendance at SSSs. We did this randomised controlled trial in 18 SSSs in England. Current smokers (aged ≥16 years) were identified from medical records in 99 general practices and invited to participate by their general practitioner. Individuals who gave consent, were motivated to quit, and had not attended the SSS within the past 12 months, were randomly assigned (3:2), via computer-generated randomisation with permuted blocks (block size of five), to receive either an individually tailored risk letter and invitation to attend a no-commitment introductory session run by the local SSS (intervention group) or a standard generic letter advertising the local SSS (control group). Randomisation was stratified by sex. Masking of participants to receipt of a personal letter and invitation to a taster session was not possible. The personal letter was generated by a research assistant, but the remainder of the research team were masked to group allocation. General practitioners, practice staff, and SSS advisers were unaware of their patients' allocation. The primary outcome was attendance at the first session of an SSS course within 6 months from randomisation. We did analysis by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN 76561916. Recruitment, collection of baseline data, delivery of the intervention, and follow up of participants took place between Jan 31, 2011, and July 12, 2014. We randomly assigned 4384 smokers to the intervention group (n=2636) or the control group (n=1748); 4383 participants comprised the intention-to-treat population. Attendance at the first session of an SSS course was significantly higher in the intervention group than in the control group (458 [17·4%] vs 158 [9·0%] participants; unadjusted odds ratio 2·12 [95% CI 1·75-2·57]; p<0·0001). Delivery of personalised risk information alongside an invitation to an introductory session more than doubled the odds of attending the SSS compared with a standard generic invitation to contact the service. This result suggests that a more proactive approach, combined with an opportunity to experience local services, can reduce patient barriers to receiving treatment and has high potential to increase uptake. National Institutes of Health Research Health Technology Assessment. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

ShopSmart 4 Health – Protocol of a skills-based randomised controlled trial promoting fruit and vegetable consumption among socioeconomically disadvantaged women

PubMed Central

2013-01-01

Background There is a need for evidence on the most effective and cost-effective approaches for promoting healthy eating among groups that do not meet dietary recommendations for good health, such as those with low incomes or experiencing socioeconomic disadvantage. This paper describes the ShopSmart 4 Health study, a randomised controlled trial conducted by Deakin University, Coles Supermarkets and the Heart Foundation, to investigate the effectiveness and cost-effectiveness of a skill-building intervention for promoting increased purchasing and consumption of fruits and vegetables amongst women of low socioeconomic position (SEP). Methods/design ShopSmart 4 Health employed a randomised controlled trial design. Women aged 18–60 years, holding a Coles store loyalty card, who shopped at Coles stores within socioeconomically disadvantaged neighbourhoods and met low-income eligibility criteria were invited to participate. Consenting women completed a baseline survey assessing food shopping and eating habits and food-related behaviours and attitudes. On receipt of their completed survey, women were randomised to either a skill-building intervention or a wait-list control condition. Intervention effects will be evaluated via self-completion surveys and using supermarket transaction sales data, collected at pre- and post-intervention and 6-month follow-up. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. Process evaluation will be undertaken to identify perceived value and effects of intervention components. Discussion This study will provide data to address the currently limited evidence base regarding the effectiveness and cost-effectiveness of skill-building intervention strategies aimed at increasing fruit and vegetable consumption among socioeconomically disadvantaged women, a target group at high risk of poor diets. Trial registration Current Controlled Trials ISRCTN48771770 PMID:23668896

So you want to conduct a randomised trial? Learnings from a 'failed' feasibility study of a Crisis Resource Management prompt during simulated paediatric resuscitation.

PubMed

Teis, Rachel; Allen, Jyai; Lee, Nigel; Kildea, Sue

2017-02-01

No study has tested a Crisis Resource Management prompt on resuscitation performance. We conducted a feasibility, unblinded, parallel-group, randomised controlled trial at one Australian paediatric hospital (June-September 2014). Eligible participants were any doctor, nurse, or nurse manager who would normally be involved in a Medical Emergency Team simulation. The unit of block randomisation was one of six scenarios (3 control:3 intervention) with or without a verbal prompt. The primary outcomes tested the feasibility and utility of the intervention and data collection tools. The secondary outcomes measured resuscitation quality and team performance. Data were analysed from six resuscitation scenarios (n=49 participants); three control groups (n=25) and three intervention groups (n=24). The ability to measure all data items on the data collection tools was hindered by problems with the recording devices both in the mannequins and the video camera. For a pilot study, greater training for the prompt role and pre-briefing participants about assessment of their cardio-pulmonary resuscitation quality should be undertaken. Data could be analysed in real time with independent video analysis to validate findings. Two cameras would strengthen reliability of the methods. Copyright © 2016 College of Emergency Nursing Australasia. Published by Elsevier Ltd. All rights reserved.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

PubMed

Santarius, Thomas; Kirkpatrick, Peter J; Ganesan, Dharmendra; Chia, Hui Ling; Jalloh, Ibrahim; Smielewski, Peter; Richards, Hugh K; Marcus, Hani; Parker, Richard A; Price, Stephen J; Kirollos, Ramez W; Pickard, John D; Hutchinson, Peter J

2009-09-26

Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes. We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural haematoma for burr-hole drainage were assessed for eligibility. 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294). Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0.003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups. Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months. Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).

Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

PubMed

Aebi, Stefan; Gelber, Shari; Anderson, Stewart J; Láng, István; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P; Geyer, Charles E; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L

2014-02-01

Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG). Copyright © 2014 Elsevier Ltd. All rights reserved.

Rectal analgesia for the relief of perineal pain after childbirth: a randomised controlled trial of diclofenac suppositories.

PubMed

Dodd, Jodie M; Hedayati, Hedyeh; Pearce, Elizabeth; Hotham, Neil; Crowther, Caroline A

2004-10-01

To evaluate rectal diclofenac in the relief of perineal pain after trauma during childbirth. A randomised, double-blind trial. Delivery Suite, Women's and Children's Hospital, South Australia. Women with a second-degree (or greater) perineal tear or episiotomy. Women were randomly allocated to either diclofenac or placebo suppositories (Anusol), using a computer-generated randomisation schedule with stratification for parity and mode of birth. Treatment packs contained two x 100 mg diclofenac or two placebo suppositories, the first being inserted when suturing was complete, and the second 12-24 hours after birth. Women were asked to complete questionnaires at 24 and 48 hours after birth relating to their degree of perineal pain using the validated Short Form McGill Pain Questionnaire. Pain scores at 24 and 48 hours after birth. A total of 133 women were recruited, with 67 randomised to diclofenac suppositories and 66 to placebo. Women in the diclofenac group were significantly less likely to experience pain at 24 hours while walking (RR 0.8; 95% CI 0.6 to 1.0), sitting (RR 0.8; 95% CI 0.6 to 1.0), passing urine (RR 0.6; 95% CI 0.4 to 1.0) and on opening their bowels (RR 0.6; 95% CI 0.2 to 0.9) compared with those women who received placebo. These differences were not sustained 48 hours after birth. The use of rectal non-steroidal anti-inflammatory drug suppositories is a simple, effective and safe method of reducing the pain experienced by women following perineal trauma within the first 24 hours after childbirth.

Chocolate frogs do not increase completion of parent survey: randomised study.

PubMed

Price, Anna M H; Coates, Cathy; Symeonides, Christos; Hiscock, Harriet; Smith, Libby; York, Elissa; Hennel, Sabine

2014-11-01

Four months into a year-long, national survey assessing parents' experiences of a child's diagnosis of autism spectrum disorder, our response fraction was only 23%. We aimed to determine whether including a chocolate incentive in the postal survey would increase the response fraction. Families enrolled between 15 March and 25 May 2012 were randomised to receive a chocolate frog versus no chocolate frog. Both groups received a written reminder and replacement survey 2 weeks after the survey was posted and up to two telephone reminders thereafter. We analysed the effect of the incentive using χ(2) tests for the categorical response variable and t-tests for the continuous reminder and length of response variables at the end of (i) randomisation and (ii) the study (1 November 2012). A total of 137 families were randomised in the 6-week period. Parents who received an incentive were more likely to return a completed survey in the 6 weeks than those who did not (21% vs. 6%, P = 0.009). This effect faded by the end of the study (53% vs. 42%, P = 0.4). There were no differences between groups at either follow-up in the number of reminders that parents received or the number of days it took parents to return the survey. Including a chocolate-based incentive does not significantly increase response rate in a postal survey over and above standard reminder techniques like posting follow-up survey packs or phoning families. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

A pilot randomised trial of community-based care following discharge from hospital with a recent spinal cord injury in Bangladesh.

PubMed

Hossain, M S; Harvey, L A; Rahman, M A; Bowden, J L; Islam, M S; Taylor, V; Muldoon, S; Herbert, R D

2017-06-01

To explore the feasibility of conducting a full trial designed to determine the effectiveness of a model of community-based care for people with spinal cord injury in Bangladesh. A pilot randomised trial. Community, Bangladesh. Participants were 30 people with recent spinal cord injury who were wheelchair-dependent and soon to be discharged from hospital. Participants randomised to the intervention group received a package of care involving regular telephone contact and three home visits over two years. Participants randomised to the control group received usual care consisting of a telephone call and an optional home visit. Participants were assessed at baseline and two years after randomization. The primary outcome was mortality and secondary outcomes were measures of complications, depression, participation and quality of life. A total of 24 participants had a complete spinal cord injury and six participants had an incomplete spinal cord injury. Median (interquartile) age and time since injury at baseline were 31 years (24 to 36) and 7 months (4 to 13), respectively. Two participants, one in each group, died. Five participants had pressure ulcers at two years. There were no notable impediments to the conduct of the trial and no significant protocol violations. The phone calls and home visits were delivered according to the protocol 87% and 100% of the time, respectively. Follow-up data were 99% complete. This pilot trial demonstrates the feasibility of a full clinical trial of 410 participants, which has recently commenced. University of Sydney, Australia.

A rare coexistence of complete atrioventricular block and preexcitation in an elderly symptomatic patient.

PubMed

Erdogan, Okan

2008-07-01

The present case report describes an elderly patient with complete atrioventricular nodal block coexisting with intermittent preexcitation, which resulted in paroxysmal complete loss of atrioventricular conduction and symptoms. The patient ended up with pacemaker implantation without requiring ablation of accessory pathway.

Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005

PubMed Central

Davies, Mark; Hingorani, Aroon D; Hunter, Jackie

2018-01-01

Abstract Objective To investigate the distribution, design characteristics, and dissemination of clinical trials by funding organisation and medical specialty. Design Cross sectional descriptive analysis. Data sources Trial protocol information from clinicaltrials.gov, metadata of journal articles in which trial results were published (PubMed), and quality metrics of associated journals from SCImago Journal and Country Rank database. Selection criteria All 45 620 clinical trials evaluating small molecule therapeutics, biological drugs, adjuvants, and vaccines, completed after January 2006 and before July 2015, including randomised controlled trials and non-randomised studies across all clinical phases. Results Industry was more likely than non-profit funders to fund large international randomised controlled trials, although methodological differences have been decreasing with time. Among 27 835 completed efficacy trials (phase II-IV), 15 084 (54.2%) had disclosed their findings publicly. Industry was more likely than non-profit trial funders to disseminate trial results (59.3% (10 444/17 627) v 45.3% (4555/10 066)), and large drug companies had higher disclosure rates than small ones (66.7% (7681/11 508) v 45.2% (2763/6119)). Trials funded by the National Institutes of Health (NIH) were disseminated more often than those of other non-profit institutions (60.0% (1451/2417) v 40.6% (3104/7649)). Results of studies funded by large drug companies and NIH were more likely to appear on clinicaltrials.gov than were those from non-profit funders, which were published mainly as journal articles. Trials reporting the use of randomisation were more likely than non-randomised studies to be published in a journal article (6895/19 711 (34.9%) v 1408/7748 (18.2%)), and journal publication rates varied across disease areas, ranging from 42% for autoimmune diseases to 20% for oncology. Conclusions Trial design and dissemination of results vary substantially depending on the type and size of funding institution as well as the disease area under study. PMID:29875212

Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial

PubMed Central

Chang, Wei-Ju; Bennell, Kim L.; Hodges, Paul W.; Hinman, Rana S.; Young, Carolyn L.; Buscemi, Valentina; Liston, Matthew B.

2017-01-01

A randomised, assessor- and participant-blind, sham-controlled trial was conducted to assess the safety and feasibility of adding transcranial direct current stimulation (tDCS) to quadriceps strengthening exercise in knee osteoarthritis (OA), and provide data to inform a fully powered trial. Participants were randomised to receive active tDCS+exercise (AT+EX) or sham tDCS+exercise (ST+EX) twice weekly for 8 weeks whilst completing home exercises twice per week. Feasibility, safety, patient-perceived response, pain, function, pressure pain thresholds (PPTs) and conditioned pain modulation (CPM) were assessed before and after treatment. Fifty-seven people were screened for eligibility. Thirty (52%) entered randomisation and 25 (84%) completed the trial. One episode of headache in the AT+EX group was reported. Pain reduced in both groups following treatment (AT+EX: p<0.001, partial η2 = 0.55; ST+EX: p = 0.026, partial η2 = 0.18) but no between-group differences were observed (p = 0.18, partial η2 = 0.08). Function improved in the AT+EX (p = 0.01, partial η2 = 0.22), but not the ST+EX (p = 0.16, partial η2 = 0.08) group, between-group differences did not reach significance (p = 0.28, partial η2 = 0.052). AT+EX produced greater improvements in PPTs than ST+EX (p<0.05) (superolateral knee: partial η2 = 0.17; superior knee: partial η2 = 0.3; superomedial knee: partial η2 = 0.26). CPM only improved in the AT+EX group but no between-group difference was observed (p = 0.054, partial η2 = 0.158). This study provides the first feasibility and safety data for the addition of tDCS to quadriceps strengthening exercise in knee OA. Our data suggest AT+EX may improve pain, function and pain mechanisms beyond that of ST+EX, and provides support for progression to a fully powered randomised controlled trial. PMID:28665989

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

PubMed

Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

2016-05-01

Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Preventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention - IMPRINT study.

PubMed

Pascoe, Leona; Roberts, Gehan; Doyle, Lex W; Lee, Katherine J; Thompson, Deanne K; Seal, Marc L; Josev, Elisha K; Nosarti, Chiara; Gathercole, Susan; Anderson, Peter J

2013-09-16

Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm.In a cohort of extremely preterm (<28 weeks' gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years' post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks', 12 months' and 24 months' post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks' post-intervention. This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child's home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks', 12 months' and 24 months' post-intervention. To our knowledge, this study will be the first randomised controlled trial to (a) assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low birthweight children, while incorporating advanced imaging techniques to investigate neural changes associated with adaptive working memory training, and (b) employ long-term follow-up to assess the potential benefit of improved working memory on academic functioning. If effective, Cogmed would serve as a valuable, available intervention for improving developmental outcomes for this population. Australian New Zealand Clinical Trials Registry ACTRN12612000124831.

Comparison of efficacy and safety of lateral-to-medial continuous transversus abdominis plane block with thoracic epidural analgesia in patients undergoing abdominal surgery: A randomised, open-label feasibility study.

PubMed

Ganapathy, Sugantha; Sondekoppam, Rakesh V; Terlecki, Magdalena; Brookes, Jonathan; Das Adhikary, Sanjib; Subramanian, Lakshmimathy

2015-11-01

We recently described a lateral-to-medial approach for transversus abdominis plane (LM-TAP) block, which may permit preoperative initiation of the block. Our objective was to evaluate the feasibility of continuous LM-TAP blocks in clinical practice in comparison with thoracic epidural analgesia (TEA). A randomised, open-label study. University Hospital, London Health Sciences Centre, London, Ontario, Canada from July 2008 to August 2012. Fifty adult patients undergoing open abdominal surgery via laparotomy were allocated randomly to receive preoperative catheter-congruent TEA or ultrasound-guided continuous bilateral LM-TAP block for 72 h postoperatively. Reasons for noninclusion were American Society of Anesthesiologists' physical status more than 4, known allergy to study drugs, chronic pain/opioid dependence, spinal abnormalities or psychiatric illness. In the TEA group (n = 24), patient-controlled epidural analgesia was maintained using bupivacaine 0.1% with hydromorphone 10 μg ml⁻¹ after establishment of the initial block. In the LM-TAP group (n = 26), ultrasound-guided LM-TAP catheters were inserted on each side preoperatively after a bolus of 30 ml of ropivacaine 0.5% (20 ml subcostal and 10 ml subumbilical injections on both sides). Analgesia was maintained with an infusion of ropivacaine 0.35% at a rate of 2 to 2.5 ml h⁻¹ through each catheter, along with rescue intravenous patient-controlled analgesia. The primary outcome was pain score on coughing 24 h after the end of surgery. Secondary outcomes were pain scores from 24 to 72 h, intraoperative and postoperative opioid consumption, time to onset of bowel movement and side effect profiles. Mean [95% confidence interval (95% CI)] pain scores at rest ranged from 1. 7 (0.9 to 2.5) to 2.3 (1.1 to 3.4) in TEA vs. 1.5 (0.7 to 2.2) to 2.2 (1.3 to 3.0) in LM-TAP (P = 0.829). The dynamic pain scores ranged from 2.9 (1.5 to 4.4) to 3.8 (2.8 to 4.8) in TEA vs. 3.3 (2.4 to 4.3) to 3.8 (2.7 to 4.9) in LM-TAP (P = 0.551). The variability in pain scores was lower in the LM-TAP group than in the TEA group in the first 24 h postoperatively. Patient satisfaction and other secondary outcomes were similar. Continuous bilateral LM-TAP block can be initiated preoperatively and may provide comparable analgesia to TEA in patients undergoing laparotomy. not registered because registration was not mandatory at the time of starting the trial.

Duration of motor block with intrathecal ropivacaine versus bupivacaine for caesarean section: a meta-analysis.

PubMed

Malhotra, R; Johnstone, C; Halpern, S; Hunter, J; Banerjee, A

2016-08-01

Bupivacaine is a commonly used local anaesthetic for spinal anaesthesia for caesarean section, but may produce prolonged motor block, delaying discharge from the post-anaesthesia care unit. Ropivacaine may have a shorter time to recovery of motor function compared with bupivacaine. We performed a meta-analysis to assess the time difference in duration of motor block with intrathecal ropivacaine compared with bupivacaine for caesarean section. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases for randomised controlled trials comparing ropivacaine with bupivacaine in parturients undergoing elective caesarean section under spinal anaesthesia. The primary outcome was the duration of motor block. Secondary outcomes included the time to onset of sensory block, need for conversion to general anaesthesia and the incidence of hypotension. Thirteen trials comprising 743 spinal anaesthetics were included. Intrathecal ropivacaine resulted in a reduced duration of motor block, regressing 35.7min earlier compared with intrathecal bupivacaine (P<0.00001). There was no difference in the time to onset of sensory block (P=0.25) or the incidence of hypotension (P=0.10). Limited data suggested no difference in the rate of conversion to general anaesthesia, but an earlier request for postoperative analgesia with ropivacaine. Compared with bupivacaine, intrathecal ropivacaine is associated with more rapid recovery of motor block despite similar sensory properties and no increased rate of conversion to general anaesthesia. This may be useful in centres in which recovery of motor block is a criterion for discharge from the post-anaesthesia care unit. However, small numbers of trials and significant heterogeneity limit the interpretation of our results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing the height of block for caesarean section over the past three decades: trends from the literature.

PubMed

Hoyle, J; Yentis, S M

2015-04-01

There are multiple methods of assessing the height of block before caesarean section under regional anaesthesia, and surveys of practice suggest considerable variation in practice. So far, little emphasis has been placed on the guidance to be gained from published research literature or textbooks. We therefore set out to investigate the methods of block assessment documented in published articles and textbooks over the past 30 years. We performed two searches of PubMed for randomised clinical trials with caesarean section and either spinal anaesthesia or epidural anaesthesia as major Medical Subject Headings. A total of 284 papers, from 1984 to 2013, were analysed for methods of assessment of sensory and motor block, and the height of block deemed adequate for surgery. We also examined 45 editions of seven anaesthetic textbooks spanning 1950-2014 for recommended methods of assessment and height of block required for caesarean section. Analysis of published papers demonstrated a wide variation in techniques, though there has been a trend towards the increased use of touch, and an increased use of a block height of T5 over the study period. Only 115/284 (40.5%) papers described the method of assessing motor block, with most of those that did (102/115; 88.7%) describing it as the 'Bromage scale', although only five of these (4.9%) matched the original description by Bromage. The required height of block recommended by textbooks has risen over the last 30 years to T4, although only four textbooks made any recommendation about the preferred sensory modality. The variation in methods suggested by surveys of practice is reflected in variation in published trials, and there is little consensus or guidance in anaesthetic textbooks. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Palonosetron versus ondansetron for prevention of chemotherapy-induced nausea and vomiting in paediatric patients with cancer receiving moderately or highly emetogenic chemotherapy: a randomised, phase 3, double-blind, double-dummy, non-inferiority study.

PubMed

Kovács, Gábor; Wachtel, Antonio E; Basharova, Elena V; Spinelli, Tulla; Nicolas, Pierre; Kabickova, Edita

2016-03-01

Palonosetron has shown efficacy in the prevention of chemotherapy-induced nausea and vomiting in adults undergoing moderately or highly emetogenic chemotherapy. We assessed the efficacy and safety of palonosetron versus ondansetron in the prevention of chemotherapy-induced nausea and vomiting in paediatric patients. In this multicentre, multinational, double-blind, double-dummy, phase 3 study, paediatric patients aged between 0 and younger than 17 years, who were naive or non-naive to chemotherapy, and scheduled to undergo moderately or highly emetogenic chemotherapy for the treatment of malignant disease were randomised centrally (1:1:1) to receive up to four cycles of 10 μg/kg or 20 μg/kg palonosetron on day 1, or three 150 μg/kg doses of ondansetron on day 1, scheduled 4 h apart, according to a static central permuted block randomisation scheme by an interactive web response system. Randomisation was stratified according to age and emetogenicity. Treatment allocation was masked to project team members involved in data collection and analysis, and members of the investigator's team. The primary endpoint was complete response (no vomiting, retching, or use of rescue drugs) during the acute phase (0-24 h post-chemotherapy) of the first on-study chemotherapy cycle, as assessed in the population of randomly assigned patients who received moderately or highly emetogenic chemotherapy and an active study drug. The primary efficacy objective was to show the non-inferiority of palonosetron versus ondansetron during the acute phase (0-24 h post-chemotherapy) of the first on-study chemotherapy cycle through comparison of the difference in the proportions of patients who achieved a complete response with palonosetron (πT) minus ondansetron (πR) versus a preset non-inferiority margin (δ -15%). To be considered as non-inferior to ondansetron, for at least one of the doses of palonosetron, the lower limit of the 97·5% CI for the weighted sum of the differences in complete response rates had to be superior to -15%. Safety was assessed, according to treatment received. This study is registered with ClinicalTrials.gov, number NCT01442376, and has been completed. Between Sept 12, 2011, and Oct 26, 2012, we randomly assigned 502 patients; 169 were assigned to receive 10 μg/kg palonosetron, 169 to receive 20 μg/kg palonosetron, and 164 to receive 3 × 150 μg/kg ondansetron, of whom 166, 165, and 162, respectively, were included in the efficacy analysis. In the acute phase, complete responses were recorded in 90 (54%) patients in the 10 μg/kg palonosetron group, 98 (59%) in the 20 μg/kg palonosetron group, and 95 (59%) in the ondansetron group. Non-inferiority versus ondansetron was shown for 20 μg/kg palonosetron in the acute phase (weighted sum of the differences in complete response rates 0·36% [97·5% CI -11·7 to 12·4]; p=0·0022). Non-inferiority versus ondansetron was not shown for 10 μg/kg palonosetron in the acute phase (weighted sum of the differences in complete response rates -4·41% [97·5% CI -16·4 to 7·6]). In the first on-study treatment cycle, treatment-emergent adverse events were reported in 134 (80%) of 167 patients who received 10 μg/kg palonosetron, 113 (69%) of 163 who received 20 μg/kg palonosetron, and 134 (82%) of 164 who received ondansetron. The most common drug-related treatment-emergent adverse events were nervous system disorders, mainly headache, which occurred in three (2%) patients who received 10 μg/kg palonosetron, one (<1%) patient who received 20 μg/kg palonosetron, and two (1%) patients who received ondansetron. The incidence of serious adverse events in the first on-study treatment cycle was lower in the 20 μg/kg palonosetron group (43 [26%]) than in the 10 μg/kg palonosetron group (52 [31%]) and the ondansetron group (55 [34%]). Non-inferiority was shown for 20 μg/kg palonosetron during the acute phase of the first on-study chemotherapy cycle. 20 μg/kg palonosetron is now indicated by the European Medicines Agency and the US Food and Drug Administration for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients aged 1 month to younger than 17 years. Helsinn Healthcare. Copyright © 2016 Elsevier Ltd. All rights reserved.

Which Ultrasound-Guided Sciatic Nerve Block Strategy Works Faster? Prebifurcation or Separate Tibial-Peroneal Nerve Block? A Randomized Clinical Trial.

PubMed

Faiz, Seyed Hamid Reza; Imani, Farnad; Rahimzadeh, Poupak; Alebouyeh, Mahmoud Reza; Entezary, Saeed Reza; Shafeinia, Amineh

2017-08-01

Peripheral nerve block is an accepted method in lower limb surgeries regarding its convenience and good tolerance by the patients. Quick performance and fast sensory and motor block are highly demanded in this method. The aim of the present study was to compare 2 different methods of sciatic and tibial-peroneal nerve block in lower limb surgeries in terms of block onset. In this clinical trial, 52 candidates for elective lower limb surgery were randomly divided into 2 groups: sciatic nerve block before bifurcation (SG; n = 27) and separate tibial-peroneal nerve block (TPG; n = 25) under ultrasound plus nerve stimulator guidance. The mean duration of block performance, as well as complete sensory and motor block, was recorded and compared between the groups. The mean duration of complete sensory block in the SG and TPG groups was 35.4 ± 4.1 and 24.9 ± 4.2 minutes, respectively, which was significantly lower in the TPG group (P = 0.001). The mean duration of complete motor block in the SG and TPG groups was 63.3 ± 4.4 and 48.4 ± 4.6 minutes, respectively, which was significantly lower in the TPG group (P = 0.001). No nerve injuries, paresthesia, or other possible side effects were reported in patients. According to the present study, it seems that TPG shows a faster sensory and motor block than SG.

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

PubMed

Maxwell, Amy E; MacLeod, Mary Joan; Joyson, Anu; Johnson, Sharon; Ramadan, Hawraman; Bellfield, Ruth; Byrne, Anthony; McGhee, Caroline; Rudd, Anthony; Price, Fiona; Vasileiadis, Evangelos; Holden, Melinda; Hewitt, Jonathan; Carpenter, Michael; Needle, Ann; Valentine, Stacey; Patel, Farzana; Harrington, Frances; Mudd, Paul; Emsley, Hedley; Gregary, Bindu; Kane, Ingrid; Muir, Keith; Tiwari, Divya; Owusu-Agyei, Peter; Temple, Natalie; Sekaran, Lakshmanan; Ragab, Suzanne; England, Timothy; Hedstrom, Amanda; Jones, Phil; Jones, Sarah; Doherty, Mandy; McCarron, Mark O; Cohen, David L; Tysoe, Sharon; Al-Shahi Salman, Rustam

2017-04-05

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH. By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART. The trial coordinating centre invited all sites that kept screening logs to submit screening log data, followed by one reminder. We checked the integrity of data, focused on the completeness of data about potentially eligible patients and categorised the reasons they were not randomised. Of 108 active sites, 39 (36%) provided usable screening log data over a median of ten (interquartile range = 5-13) months of recruitment per site. During this time, sites screened 633 potentially eligible patients and randomised 53 (8%) of them. The main reasons why 580 patients were not randomised were: 43 (7%) patients started anticoagulation, 51 (9%) patients declined, 148 (26%) patients' stroke physicians were not uncertain about using antiplatelet drugs, 162 (28%) patients were too unwell and 176 (30%) patients were not randomised due to other reasons. RESTART recruited ~8% of eligible patients. If more physicians were uncertain about the therapeutic dilemma that RESTART is addressing, RESTART could have recruited up to four times as many participants. The trial coordinating centre continues to engage with physicians about their uncertainty. EU Clinical Trials, EudraCT 2012-003190-26 . Registered on 3 July 2012.

Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

PubMed

Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

2017-01-01

The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial.

PubMed

Dodd, Jodie M; Turnbull, Deborah; McPhee, Andrew J; Deussen, Andrea R; Grivell, Rosalie M; Yelland, Lisa N; Crowther, Caroline A; Wittert, Gary; Owens, Julie A; Robinson, Jeffrey S

2014-02-10

To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women. Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital. Three public maternity hospitals across South Australia. 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks' gestation, and BMI ≥ 25. 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information. Incidence of infants born large for gestational age (birth weight ≥ 90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles. 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups. For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes. Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

Chronic hand eczema--self-management and prognosis: a study protocol for a randomised clinical trial.

PubMed

Mollerup, Annette; Veien, Niels Kren; Johansen, Jeanne Duus

2012-06-12

Hand eczema has a one-year prevalence of approximately 10 % in the general Danish population. Often the disease becomes chronic with numerous implications for the individual's daily life, occupation and quality of life. However, no guidelines of self-management recommendations beyond the acute stage are given. Self-management of the disease is pivotal and involves self-monitoring of the condition, medication adherence, and preventive behaviour. Interventions best to support the individual in this ongoing process need to be developed. This paper describes the design of a randomised clinical trial to test a newly developed intervention of individual counselling versus conventional information. 300 patients consecutively referred to dermatologic treatment at two different settings are individually randomised to either the intervention programme, named 'The Healthy Skin Clinic' or to the control group. Block-wise randomisation according to setting and gender is carried out.The intervention offers a tool for self-monitoring; basic and specific individual counselling; the possibility of asynchronous communication with the intervention team; and an electronic patient dialogue forum. Primary outcome variable is objective assessment of the hand eczema severity performed at baseline prior to randomisation, and repeated at six months follow-up. Secondary outcome variables are dermatology related life quality and perceived global burden of disease. The trial aims at evaluating a newly developed guidance programme which is expected to support self-management of patients referred to dermatology treatment due to chronic hand eczema. The design of the protocol is pragmatic with blinding of neither participants nor the investigator. Thus, in the interpretation of the results, the investigator takes into account effects that may be attributed to actors of the interventions rather than the intervention per se as well of potential observer bias. Inclusion criterions are wide in order to increase transferability of the results. The trial is registered in ClinicalTrials.Gov with registration number NCT01482663.

The MATISSE study: a randomised trial of group art therapy for people with schizophrenia

PubMed Central

2010-01-01

Background Art Therapy has been promoted as a means of helping people who may find it difficult to express themselves verbally engage in psychological treatment. Group Art Therapy has been widely used as an adjunctive treatment for people with schizophrenia but there have been few attempts to examine its effects and cost effectiveness has not been examined. The MATISSE study aims to evaluate the clinical and cost effectiveness of group Art Therapy for people with schizophrenia. Method/Design The MATISSE study is a three-arm, parallel group, pragmatic, randomised, controlled trial of referral to group Art Therapy plus standard care, referral to an attention control 'activity' group plus standard care, or standard care alone. Study participants were recruited from inpatient and community-based mental health and social care services at four centres in England and Northern Ireland. Participants were aged over 18 years with a clinical diagnosis of schizophrenia, confirmed by an examination of case notes using operationalised criteria. Participants were then randomised via an independent and remote telephone randomisation service using permuted stacked blocks, stratified by site. Art Therapy and activity groups were made available to participants once a week for up to 12 months. Outcome measures were assessed by researchers masked to allocation status at 12 and 24 months after randomisation. Participants and care givers were aware which arm of the trial participants were allocated to. The primary outcomes for the study are global functioning (measured using the Global Assessment of Functioning scale) and mental health symptoms (measured using the Positive and Negative Syndrome Scale) assessed at 24 months. Secondary outcomes were assessed at 12 and 24 months and comprise levels of group attendance, social function, satisfaction with care, mental wellbeing, and costs. Discussion We believe that this is the first large scale pragmatic trial of Art Therapy for people with schizophrenia. Trial registration Current Controlled Trials ISRCTN46150447 PMID:20799930

Chronic hand eczema - self-management and prognosis: a study protocol for a randomised clinical trial

PubMed Central

2012-01-01

Background Hand eczema has a one-year prevalence of approximately 10 % in the general Danish population. Often the disease becomes chronic with numerous implications for the individual’s daily life, occupation and quality of life. However, no guidelines of self-management recommendations beyond the acute stage are given. Self-management of the disease is pivotal and involves self-monitoring of the condition, medication adherence, and preventive behaviour. Interventions best to support the individual in this ongoing process need to be developed. Methods/design This paper describes the design of a randomised clinical trial to test a newly developed intervention of individual counselling versus conventional information. 300 patients consecutively referred to dermatologic treatment at two different settings are individually randomised to either the intervention programme, named ‘The Healthy Skin Clinic’ or to the control group. Block-wise randomisation according to setting and gender is carried out. The intervention offers a tool for self-monitoring; basic and specific individual counselling; the possibility of asynchronous communication with the intervention team; and an electronic patient dialogue forum. Primary outcome variable is objective assessment of the hand eczema severity performed at baseline prior to randomisation, and repeated at six months follow-up. Secondary outcome variables are dermatology related life quality and perceived global burden of disease. Discussion The trial aims at evaluating a newly developed guidance programme which is expected to support self-management of patients referred to dermatology treatment due to chronic hand eczema. The design of the protocol is pragmatic with blinding of neither participants nor the investigator. Thus, in the interpretation of the results, the investigator takes into account effects that may be attributed to actors of the interventions rather than the intervention per se as well of potential observer bias. Inclusion criterions are wide in order to increase transferability of the results. Trial registration The trial is registered in ClinicalTrials.Gov with registration number NCT01482663. PMID:22691871

Congenital complete heart block in the newborn associated with maternal systemic lupus erythematosus and other connective tissue disorders.

PubMed Central

Hardy, J D; Solomon, S; Banwell, G S; Beach, R; Wright, V; Howard, F M

1979-01-01

Four babies with complete heart block associated with maternal systemic lupus erythematosus (SLE) are described, together with a 5th baby whose mother had serological abnormalities only. One baby had a rapidly fatal outcome, one has required digoxin for heart failure, and the remaining 3 are asymptomatic but remain in complete heart block. Additional manifestations were present in 2 of them. The spectrum of neonatal abnormalities that may occur in association with maternal SLE and related connective tissue disorders is discussed, together with the possible causes and the prognosis. We conclude that congenital heart block is more common than had previously been appreciated. Images Figure PMID:420526

Randomised controlled trial of expressive writing and quality of life in men and women treated for colon or rectal cancer.

PubMed

Lepore, Stephen J; Revenson, Tracey A; Roberts, Katherine J; Pranikoff, Julie R; Davey, Adam

2015-01-01

This randomised trial tested (i) whether a home-based expressive writing (EW) intervention improves quality of life in patients with colorectal cancer (CRC) and (ii) whether the intervention is more beneficial for men or for people who feel constrained in disclosing cancer-related concerns and feelings. Patients treated for CRC were randomised to an EW (n = 101) or control writing (CW; n = 92) group. Assessments were completed at 1 month pre- and post-intervention. Sex and perceived social constraints on disclosure were evaluated as moderators. Primary outcomes were depressive symptoms, sleep problems and quality of life indicators. Eighty-one per cent of participants completed all writing assignments. Consistent with hypotheses, relative to the CW group, participants in the EW group expressed more negative emotion in writing and rated their writings as more meaningful, personal and emotionally revealing. There were no significant main effects of EW or moderating effects of sex or social constraints on outcomes. Although EW is feasible to use with persons who have CRC, it was not effective as a stand-alone psychotherapeutic intervention. Neither was it more effective for men nor for people who felt they could not freely disclose cancer-related concerns and feelings.

For the Benefit of Others: Reasons Why Women with Breast Cancer Participate in RCTs.

PubMed

Jenkins, Valerie A; Fallowfield, Lesley J

2015-04-01

Appreciation of the barriers and drivers affecting enrolment in randomised clinical trials (RCTs) is important for future trial design, communication and information provision. As part of an intervention to facilitate UK multidisciplinary team communication about RCTs, women with breast cancer who discussed trials with doctors or research nurses completed questionnaires examining i) clarity of trial information and ii) reasons for their trial decision. 152 women completed the questionnaires; 113/152 (74%) consented to RCT enrolment. Patients' satisfaction with communication about the trial information was very good, irrespective of participation decisions. Acceptors' and decliners' responses to 9/16 statements concerning decisions about trial participation differed significantly. 'Wanting to help with doctor's research' influenced 100% acceptors compared to 57% of decliners (p < 0.001). Decliners were more likely to be 'worried about randomisation' (20 vs. 39%; p < 0.035) and to 'want doctor to choose treatment rather than be randomised' (31 vs. 53%; p < 0.031). Primary reason for trial acceptance was altruism; 'I feel that others with my illness will benefit from the results of the trial', 58/108 (54%). A majority of women accepted RCT entry citing altruistic motivations as the primary driver for participation. Trial design and setting (metastatic or adjuvant) had little impact on participation.

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade: a prospective, randomised pragmatic trial.

PubMed

Yadeau, J T; Goytizolo, E A; Padgett, D E; Liu, S S; Mayman, D J; Ranawat, A S; Rade, M C; Westrich, G H

2013-05-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR.

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade. A prospective, randomised pragmatic trial

PubMed Central

Goytizolo, Enrique A.; Padgett, Douglas E.; Liu, Spencer S.; Mayman, David J.; Ranawat, Amar S.; Rade, Matthew C.; Westrich, Geoffrey H.

2014-01-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine, and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR. PMID:23632672

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

PubMed

Garcia-del-Muro, X; Vadell, C; Pérez Manga, G; Bover, I; Rifá, J; Beltrán, M; Barros, M M; Germá, J R; Fabregat, X; Moreno, V; Salvador, A; Viladiu, P

1998-01-01

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Proposal for a new definition of congenital complete atrioventricular block.

PubMed

Brucato, A; Jonzon, A; Friedman, D; Allan, L D; Vignati, G; Gasparini, M; Stein, J I; Montella, S; Michaelsson, M; Buyon, J

2003-01-01

The classic old definition of congenital heart block by Yater (1929) is still generally accepted: 'Heart block established in a young patient. There must be some evidence of the existence of the slow pulse at a fairly early age and absence of a history of any infection which might cause the condition after birth: notably diphtheria, rheumatic fever, chorea and congenital syphilis'. However, other definitions are used. We systematically reviewed 1825 cases from 38 separate studies. We conclude that complete AV blocks detected in utero in the absence of structural abnormalities differ from blocks detected later in life with respect to pathogenesis (they are generally associated with maternal anti-Ro/SSA antibodies), poorer childhood prognosis, increased risk of developing late-onset dilated cardiomyopathy, different maternal clinical features and increased risk of recurrence in future pregnancies. For these reasons we propose a new modern definition of congenital complete AV block which might be acceptable to cardiologists, rheumatologists, pediatricians and obstetricians: 'an AV block is defined as congenital if it is diagnosed in utero, at birth or within the neonatal period (0-27 days after birth)'.

Migraine with prolonged aura: phenotype and treatment.

PubMed

Viana, Michele; Afridi, Shazia

2018-01-01

We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

Research designs for studies evaluating the effectiveness of change and improvement strategies.

PubMed

Eccles, M; Grimshaw, J; Campbell, M; Ramsay, C

2003-02-01

The methods of evaluating change and improvement strategies are not well described. The design and conduct of a range of experimental and non-experimental quantitative designs are considered. Such study designs should usually be used in a context where they build on appropriate theoretical, qualitative and modelling work, particularly in the development of appropriate interventions. A range of experimental designs are discussed including single and multiple arm randomised controlled trials and the use of more complex factorial and block designs. The impact of randomisation at both group and individual levels and three non-experimental designs (uncontrolled before and after, controlled before and after, and time series analysis) are also considered. The design chosen will reflect both the needs (and resources) in any particular circumstances and also the purpose of the evaluation. The general principle underlying the choice of evaluative design is, however, simple-those conducting such evaluations should use the most robust design possible to minimise bias and maximise generalisability.

Moderated online social therapy for carers of young people recovering from first-episode psychosis: study protocol for a randomised controlled trial.

PubMed

Gleeson, John; Lederman, Reeva; Herrman, Helen; Koval, Peter; Eleftheriadis, Dina; Bendall, Sarah; Cotton, Sue M; Alvarez-Jimenez, Mario

2017-01-17

First-episode psychosis most often has its onset during late adolescence. In caring for the young person, families endure high levels of stress and depression. Meanwhile, the social networks of families often erode. Our group has previously shown that family cognitive behaviour therapy (CBT) leads to significantly improved perceived stress compared with specialist first-episode treatment as usual; however, there are well-known barriers to the dissemination of effective family interventions. To address this, we have developed a novel online intervention entitled 'Altitudes' that fully integrates purpose-built online social networking, expert and peer moderation, and evidence-based psychoeducation within a single application. The primary aim of this trial is to evaluate the effectiveness of Altitudes in reducing stress in carers over a 6-month period. We describe here a single-blinded cluster randomised controlled trial (cRCT) with permutated blocks. The clusters comprise individual families. The two treatment conditions include Altitudes plus Specialist Treatment as Usual (STAU) and STAU alone. Altitudes involves participation in our novel online programme whereas STAU comprises specialist family work at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. We aim to recruit 160 family members of young, 15-27 year-old, patients registered for treatment for first-episode psychosis (FEP) at EPPIC. The design includes two assessment time points, namely, baseline and 6-month follow-up. The study is due for completion within 2 years including an 18-month recruitment period and a 6-month treatment phase. The primary outcome is carers' perceived stress at 6 months. Secondary outcome measures include a biomarker of stress, depressive symptoms, worry, substance use, loneliness, social support, satisfaction with life, and a range of measures that tap into coping resources. We seek to gain a dynamic picture of carer stress through our Smartphone Ecological Momentary Assessment (SEMA) tool. This is the first randomised controlled trial designed to evaluate an online intervention for carers of young people recovering from FEP. It has the potential to produce evidence in support of a highly novel, accessible, and cost-effective intervention to reduce stress in carers who are providing support to young people at a critical phase in their recovery from psychosis. Australian New Zealand Clinical Trial Registry, identifier: ACTRN12616000968471 . Retrospectively registered on 22 July 2016.

Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial.

PubMed

2017-04-29

Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes. In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks' gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152. Between Jan 6, 2010, and Aug 31, 2013, 47 062 women were randomly assigned (23 515 in the decision-support group and 23 547 in the no-decision-support group) and 46 042 were analysed (22 987 in the decision-support group and 23 055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups-172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82-1·25). At 2 years, no significant differences were noted in terms of developmental assessment. Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal monitoring in labour does not improve clinical outcomes for mothers or babies. National Institute for Health Research. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

On Your Feet to Earn Your Seat: pilot RCT of a theory-based sedentary behaviour reduction intervention for older adults.

PubMed

White, Isabelle; Smith, Lee; Aggio, Daniel; Shankar, Sahana; Begum, Saima; Matei, Raluca; Fox, Kenneth R; Hamer, Mark; Iliffe, Steve; Jefferis, Barbara J; Tyler, Nick; Gardner, Benjamin

2017-01-01

Of all age groups, older adults spend most of the time sitting and are least physically active. This sequential, mixed-methods feasibility study used a randomised controlled trial design to assess methods for trialling a habit-based intervention to displace older adults' sedentary behaviour with light activity and explore impact on behavioural outcomes. Eligibility criteria were age 60-74 years, retired, and ≥6 h/day leisure sitting. Data were collected across four sites in England. The intervention comprised a booklet outlining 15 'tips' for disrupting sedentary habits and integrating activity habits into normally inactive settings, and eight weekly self-monitoring sheets. The control was a non-habit-based factsheet promoting activity and sedentary reduction. A computer-generated 1:1 block-randomisation schedule was used, with participants blinded to allocation. Participants self-reported sedentary behaviour (two indices), sedentary habit, physical activity (walking, moderate, vigorous activity) and activity habit, at pre-treatment baseline, 8- and 12-week follow-ups and were interviewed at 12 weeks. Primary feasibility outcomes were attrition, adverse events and intervention adherence. The secondary outcome was behavioural change. Of 104 participants consented, 103 were randomised (intervention N  = 52, control N  = 51). Of 98 receiving allocated treatment, 91 (93%; intervention N  = 45; control N  = 46) completed the trial. One related adverse event was reported in the intervention group. Mean per-tip adherence across 7 weeks was ≥50% for 9/15 tips. Qualitative data suggested acceptability of procedures, and, particularly among intervention recipients, the allocated treatment. Both groups appeared to reduce sedentary behaviour and increase their physical activity, but there were no apparent differences between groups in the extent of change. Trial methods were acceptable and feasible, but the intervention conferred no apparent advantage over control, though it was not trialled among the most sedentary and inactive population for whom it was developed. Further development of the intervention may be necessary prior to a large-scale definitive trial. One possible refinement would combine elements of the intervention with an informational approach to enhance effectiveness. ISRCTN47901994 (registration date: 16th January 2014; trial end date 30th April 2015).

Training community healthcare workers on the use of information and communication technologies: a randomised controlled trial of traditional versus blended learning in Malawi, Africa.

PubMed

Mastellos, Nikolaos; Tran, Tammy; Dharmayat, Kanika; Cecil, Elizabeth; Lee, Hsin-Yi; Wong, Cybele C Peng; Mkandawire, Winnie; Ngalande, Emmanuel; Wu, Joseph Tsung-Shu; Hardy, Victoria; Chirambo, Baxter Griphin; O'Donoghue, John Martin

2018-04-02

Despite the increasing uptake of information and communication technologies (ICT) within healthcare services across developing countries, community healthcare workers (CHWs) have limited knowledge to fully utilise computerised clinical systems and mobile apps. The 'Introduction to Information and Communication Technology and eHealth' course was developed with the aim to provide CHWs in Malawi, Africa, with basic knowledge and computer skills to use digital solutions in healthcare delivery. The course was delivered using a traditional and a blended learning approach. Two questionnaires were developed and tested for face validity and reliability in a pilot course with 20 CHWs. Those were designed to measure CHWs' knowledge of and attitudes towards the use of ICT, before and after each course, as well as their satisfaction with each learning approach. Following validation, a randomised controlled trial was conducted to assess the effectiveness of the two learning approaches. A total of 40 CHWs were recruited, stratified by position, gender and computer experience, and allocated to the traditional or blended learning group using block randomisation. Participants completed the baseline and follow-up questionnaires before and after each course to assess the impact of each learning approach on their knowledge, attitudes, and satisfaction. Per-item, pre-post and between-group, mean differences for each approach were calculated using paired and unpaired t-tests, respectively. Per-item, between-group, satisfaction scores were compared using unpaired t-tests. Scores across all scales improved after attending the traditional and blended learning courses. Self-rated ICT knowledge was significantly improved in both groups with significant differences between groups in seven domains. However, actual ICT knowledge scores were similar across groups. There were no significant differences between groups in attitudinal gains. Satisfaction with the course was generally high in both groups. However, participants in the blended learning group found it more difficult to follow the content of the course. This study shows that there is no difference between blended and traditional learning in the acquisition of actual ICT knowledge among community healthcare workers in developing countries. Given the human resource constraints in remote resource-poor areas, the blended learning approach may present an advantageous alternative to traditional learning.

Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial.

PubMed

von Minckwitz, Gunter; Colleoni, Marco; Kolberg, Hans-Christian; Morales, Serafin; Santi, Patricia; Tomasevic, Zorica; Zhang, Nan; Hanes, Vladimir

2018-06-04

ABP 980 (Amgen Inc, Thousand Oaks, CA, USA) is a biosimilar of trastuzumab, with analytical, functional, and pharmacokinetic similarities. We compared the clinical safety and efficacy of ABP 980 with that of trastuzumab in women with HER2-positive early breast cancer. We did a randomised, multicentre, double-blind, active-controlled equivalence trial at 97 study centres in 20 countries, mainly in Europe and South America. Eligible women were aged 18 years or older, had histologically confirmed HER2-positive invasive early breast cancer, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and were planning to have surgical resection of the breast tumour with sentinel or axillary lymph node dissection and neoadjuvant chemotherapy. After four cycles of run-in anthracycline-based chemotherapy, patients were assigned 1:1 to receive ABP 980 or trastuzumab with a permuted block design (blocks of four) computer-generated randomisation schedule. Patients received neoadjuvant therapy with a loading dose (8 mg/kg) of ABP 980 or trastuzumab plus paclitaxel 175 mg/m 2 in a 90 min intravenous infusion, followed by three cycles of 6 mg/kg intravenous ABP 980 or trastuzumab plus paclitaxel 175 mg/m 2 every 3 weeks in 30 min intravenous infusions (or 80 mg/m 2 paclitaxel once per week for 12 cycles if that was the local standard of care). Randomisation was stratified by T stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographical region. Surgery was completed 3-7 weeks after the last dose of neoadjuvant treatment, after which adjuvant treatment with ABP 980 or trastuzumab was given every 3 weeks for up to 1 year after the first dose in the study. Patients had been randomly assigned at baseline to continue APB 980, continue trastuzumab, or switch from trastuzumab to APB 980 as their adjuvant treatment. The co-primary efficacy endpoints were risk difference and risk ratio (RR) of pathological complete response in breast tissue and axillary lymph nodes assessed at a local laboratory in all patients who were randomly assigned and received any amount of neoadjuvant investigational product and underwent surgery. We assessed safety in all patients who were randomly assigned and received any amount of investigational product. This trial is registered with ClinicalTrials.gov, number NCT01901146 and Eudra, number CT 2012-004319-29. Of 827 patients enrolled, 725 were randomly assigned to receive ABP 980 (n=364) or trastuzumab (n=361). The primary endpoint was assessable in 696 patients (358 who received ABP 980 and 338 who received trastuzumab). Pathological complete response was recorded in 172 (48%, 95% CI 43-53) of 358 patients in the ABP 980 group and 137 (41%, 35-46) of 338 in the trastuzumab group (risk difference 7·3%, 90% CI 1·2-13·4; RR 1·188, 90% CI 1·033-1·366), with the upper bounds of the CIs exceeding the predefined equivalence margins of 13% and 1·318, respectively. Pathological complete response in the central laboratory assessment was seen in 162 (48%) of 339 patients assigned to ABP 980 at baseline and 138 (42%) of 330 assigned to trastuzumab at baseline (risk difference 5·8%, 90% CI -0·5 to 12·0, and RR 1·142, 90% CI 0·993 to 1·312). Grade 3 or worse adverse events during the neoadjuvant phase occurred in 54 (15%) of 364 patients in the ABP 980 group and 51 (14%) of 361 patients in the trastuzumab group, of which the most frequent grade 3 or worse event of interest was neutropenia, occurring in 21 (6%) patients in both groups. In the adjuvant phase, grade 3 or worse adverse events occurred in 30 (9%) of 349 patients continuing ABP 980, 11 (6%) of 171 continuing trastuzumab, and 13 (8%) of 171 who switched from trastuzumab to ABP 980, the most frequent grade 3 or worse events of interest were infections and infestations (four [1%], two [1%], and two [1%]), neutropenia (three [1%], two [1%], and one [1%]), and infusion reactions (two [1%], two [1%], and three [2%]). Two patients died from adverse events judged to be unrelated to the investigational products: one died from pneumonia while receiving neoadjuvant ABP 980 and one died from septic shock while receiving adjuvant ABP 980 after trastuzumab. Although the lower bounds of the 90% CIs for RR and risk difference showed non-inferiority, the upper bounds exceeded the predefined equivalence margins when based on local laboratory review of tumour samples, meaning that non-superiority was non-conclusive. In our sensitivity analyses based on central laboratory evaluation of tumour samples, estimates for the two drugs were contained within the predefined equivalence margins, indicating similar efficacy. ABP 980 and trastuzumab had similar safety outcomes in both the neoadjuvant and adjuvant phases of the study. Amgen. Copyright © 2018 Elsevier Ltd. All rights reserved.

Plate fixation versus intramedullary nailing of completely displaced midshaft fractures of the clavicle: a prospective randomised controlled trial.

PubMed

Fuglesang, H F S; Flugsrud, G B; Randsborg, P H; Oord, P; Benth, J Š; Utvåg, S E

2017-08-01

This is a prospective randomised controlled trial comparing the functional outcomes of plate fixation and elastic stable intramedullary nailing (ESIN) of completely displaced mid-shaft fractures of the clavicle in the active adult population. We prospectively recruited 123 patients and randomised them to either plate fixation or ESIN. Patients completed the Quick Disabilities of the Arm, Shoulder and Hand (DASH) score at one to six weeks post-operatively. They were followed up at six weeks, three and six months and one year with radiographs, and their clinical outcome was assessed using both the DASH and the Constant Score. Plate fixation provided a faster functional recovery during the first six months compared with ESIN, but there was no difference after one year. The duration of surgery was shorter for ESIN (mean 53.4 minutes, 22 to 120) than for plate fixation (mean 69.7 minutes, 35 to 106, p < 0.001). The recovery after ESIN was slower with increasing fracture comminution and with open reduction (p < 0.05). Both methods return the patients to their pre-injury functional levels, but plate fixation has a faster recovery period in comminuted fractures than ESIN. ESIN has a shorter operative time and lower infection and implant rates of failure when using 2.5 mm nails or wider, suggesting that this is the preferred method in mid-shaft fractures with no comminution, whereas plate fixation is the superior method in comminuted fractures. Cite this article: Bone Joint J 2017;99-B:1095-1101. ©2017 The British Editorial Society of Bone & Joint Surgery.

Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

A systematic review of training programmes for recruiters to randomised controlled trials.

PubMed

Townsend, Daisy; Mills, Nicola; Savović, Jelena; Donovan, Jenny L

2015-09-28

Recruitment to randomised controlled trials (RCTs) is often difficult. Clinician related factors have been implicated as important reasons for low rates of recruitment. Clinicians (doctors and other health professionals) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants. Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking. The aim of our study was to systematically review the available evidence on training interventions for recruiters to randomised trials. Studies that evaluated training programmes for trial recruiters were included. Those that provided only general communication training not linked to RCT recruitment were excluded. Data extraction and quality assessment were completed by two reviewers independently, with a third author where necessary. Seventeen studies of 9615 potentially eligible titles and abstracts were included in the review: three randomised controlled studies, two non-randomised controlled studies, nine uncontrolled pre-test/post-test studies, two qualitative studies, and a post-training questionnaire survey. Most studies were of moderate or weak quality. Training programmes were mostly set within cancer trials, and usually consisted of workshops with a mix of health professionals over one or two consecutive days covering generic and trial specific issues. Recruiter training programmes were well received and some increased recruiters' self-confidence in communicating key RCT concepts to patients. There was, however, little evidence that this training increased actual recruitment rates or patient understanding, satisfaction, or levels of informed consent. There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in randomised trials.

Foot orthoses in the treatment of symptomatic midfoot osteoarthritis using clinical and biomechanical outcomes: a randomised feasibility study.

PubMed

Halstead, Jill; Chapman, Graham J; Gray, Janine C; Grainger, Andrew J; Brown, Sarah; Wilkins, Richard A; Roddy, Edward; Helliwell, Philip S; Keenan, Anne-Maree; Redmond, Anthony C

2016-04-01

This randomised feasibility study aimed to examine the clinical and biomechanical effects of functional foot orthoses (FFOs) in the treatment of midfoot osteoarthritis (OA) and the feasibility of conducting a full randomised controlled trial. Participants with painful, radiographically confirmed midfoot OA were recruited and randomised to receive either FFOs or a sham control orthosis. Feasibility measures included recruitment and attrition rates, practicality of blinding and adherence rates. Clinical outcome measures were: change from baseline to 12 weeks for severity of pain (numerical rating scale), foot function (Manchester Foot Pain and Disability Index) and patient global impression of change scale. To investigate the biomechanical effect of foot orthoses, in-shoe foot kinematics and plantar pressures were evaluated at 12 weeks. Of the 119 participants screened, 37 were randomised and 33 completed the study (FFO = 18, sham = 15). Compliance with foot orthoses and blinding of the intervention was achieved in three quarters of the group. Both groups reported improvements in pain, function and global impression of change; the FFO group reporting greater improvements compared to the sham group. The biomechanical outcomes indicated the FFO group inverted the hindfoot and increased midfoot maximum plantar force compared to the sham group. The present findings suggest FFOs worn over 12 weeks may provide detectable clinical and biomechanical benefits compared to sham orthoses. This feasibility study provides useful clinical, biomechanical and statistical information for the design and implementation of a definitive randomised controlled trial to evaluate the effectiveness of FFOs in treating painful midfoot OA.

Results of a pilot cluster randomised trial of the use of a Medication Review Tool for people taking antipsychotic medication.

PubMed

Moncrieff, Joanna; Azam, Kiran; Johnson, Sonia; Marston, Louise; Morant, Nicola; Darton, Katherine; Wood, Neil

2016-07-04

Government policy encourages increasing involvement of patients in their long-term care. This paper describes the development and pilot evaluation of a 'Medication Review Tool' designed to assist people to participate more effectively in discussions about antipsychotic drug treatment. The Medication Review Tool developed consisted of a form to help patients identify pros and cons of their current antipsychotic treatment and any desired changes. It was associated with a website containing information and links about antipsychotics. For the trial, participants diagnosed with psychotic disorders were recruited from community mental health services. Cluster randomisation was used to allocate health professionals (care co-ordinators) and their associated patients to use of the Medication Review Tool or usual care. All participants had a medical consultation scheduled, and those in the intervention group completed the Medication Review Tool, with the help of their health professional prior to this, and took the completed Form into the consultation. Two follow-up interviews were conducted up to three months after the consultation. The principal outcome was the Decision Self Efficacy Scale (DSES). Qualitative feedback was collected from patients in the intervention group. One hundred and thirty patients were screened, sixty patients were randomised, 51 completed the first follow-up assessment and 49 completed the second. Many patients were not randomised due to the timing of their consultation, and involvement of health professionals was inconsistent. There was no difference between the groups on the DSES (-4.16 95 % CI -9.81, 1.49), symptoms, side effects, antipsychotic doses or patient satisfaction. Scores on the Medication Adherence Questionnaire indicated an increase in participants' reported inclination to adherence in the intervention group (coefficient adjusted for baseline values -0.44; 95 % CI -0.76, -0.11), and there was a small increase in positive attitudes to antipsychotic medication (Drug Attitude Inventory, adjusted coefficient 1.65; 95 % CI -0.09, 3.40). Qualitative feedback indicated patients valued the Tool for identifying both positive and negative aspects of drug treatment. The trial demonstrated the design was feasible, although challenges included service re-configurations and maintaining health professional involvement. Results may indicate a more intensive and sustained intervention is required to facilitate participation in decision-making for this group of patients. Current controlled trials ISRCTN12055530 , Retrospectively registered 9/12/2013.

Conduction block of mammalian myelinated nerve by local cooling to 15–30°C after a brief heating

PubMed Central

Zhang, Zhaocun; Lyon, Timothy D.; Kadow, Brian T.; Shen, Bing; Wang, Jicheng; Lee, Andy; Kang, Audry; Roppolo, James R.; de Groat, William C.

2016-01-01

This study aimed at understanding thermal effects on nerve conduction and developing new methods to produce a reversible thermal block of axonal conduction in mammalian myelinated nerves. In 13 cats under α-chloralose anesthesia, conduction block of pudendal nerves (n = 20) by cooling (5–30°C) or heating (42–54°C) a small segment (9 mm) of the nerve was monitored by the urethral striated muscle contractions and increases in intraurethral pressure induced by intermittent (5 s on and 20 s off) electrical stimulation (50 Hz, 0.2 ms) of the nerve. Cold block was observed at 5–15°C while heat block occurred at 50–54°C. A complete cold block up to 10 min was fully reversible, but a complete heat block was only reversible when the heating duration was less than 1.3 ± 0.1 min. A brief (<1 min) reversible complete heat block at 50–54°C or 15 min of nonblock mild heating at 46–48°C significantly increased the cold block temperature to 15–30°C. The effect of heating on cold block fully reversed within ∼40 min. This study discovered a novel method to block mammalian myelinated nerves at 15–30°C, providing the possibility to develop an implantable device to block axonal conduction and treat many chronic disorders. The effect of heating on cold block is of considerable interest because it raises many basic scientific questions that may help reveal the mechanisms underlying cold or heat block of axonal conduction. PMID:26740534

Evaluating an extended rehabilitation service for stroke patients (EXTRAS): study protocol for a randomised controlled trial.

PubMed

Rodgers, Helen; Shaw, Lisa; Cant, Robin; Drummond, Avril; Ford, Gary A; Forster, Anne; Hills, Katie; Howel, Denise; Laverty, Anne-Marie; McKevitt, Christopher; McMeekin, Peter; Price, Christopher

2015-05-05

Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models. We describe the protocol for a multicentre randomised controlled trial which is evaluating an extended stroke rehabilitation service. The extended service commences when routine 'organised stroke care' (stroke unit and early supported discharge (ESD)) ends. This study is a multicentre randomised controlled trial with health economic and process evaluations. It is set within NHS stroke services which provide ESD. Participants are adults who have experienced a new stroke (and carer if appropriate), discharged from hospital under the care of an ESD team. The intervention group receives an extended stroke rehabilitation service provided for 18 months following completion of ESD. The extended rehabilitation service involves regular contact with a senior ESD team member who leads and coordinates further rehabilitation. Contact is usually by telephone. The control group receives usual stroke care post-ESD. Usual care may involve referral of patients to a range of rehabilitation services upon completion of ESD in accordance with local clinical practice. Randomisation is via a central independent web-based service. The primary outcome is extended activities of daily living (Nottingham Extended Activities of Daily Living Scale) at 24 months post-randomisation. Secondary outcomes (at 12 and 24 months post-randomisation) are health status, quality of life, mood and experience of services for patients, and quality of life, experience of services and carer stress for carers. Resource use and adverse events are also collected. Outcomes are undertaken by a blinded assessor. Implementation and delivery of the extended stroke rehabilitation service will also be described. Semi-structured interviews will be conducted with a subsample of participants and staff to gain insight into perceptions and experiences of rehabilitation services delivered or received. Allowing for 25% attrition, 510 participants are needed to provide 90% power to detect a difference in mean Nottingham Extended Activities of Daily Living Scale score of 6 with a 5% significance level. The provision of longer term support for stroke survivors is currently limited. The results from this trial will inform future stroke service planning and configuration. This trial was registered with ISRCTN (identifier: ISRCTN45203373 ) on 9 August 2012.

Computerised therapy for depression with clinician vs. assistant and brief vs. extended phone support: study protocol for a randomised controlled trial.

PubMed

Gega, Lina; Swift, Louise; Barton, Garry; Todd, Gillian; Reeve, Nesta; Bird, Kelly; Holland, Richard; Howe, Amanda; Wilson, Jon; Molle, Jo

2012-08-27

Computerised cognitive behaviour therapy (cCBT) involves standardised, automated, interactive self-help programmes delivered via a computer. Randomised controlled trials (RCTs) and observational studies have shown than cCBT reduces depressive symptoms as much as face-to-face therapy and more than waiting lists or treatment as usual. cCBT's efficacy and acceptability may be influenced by the "human" support offered as an adjunct to it, which can vary in duration and can be offered by people with different levels of training and expertise. This is a two-by-two factorial RCT investigating the effectiveness, cost-effectiveness and acceptability of cCBT supplemented with 12 weekly phone support sessions are either brief (5-10 min) or extended (20-30 min) and are offered by either an expert clinician or an assistant with no clinical training. Adults with non-suicidal depression in primary care can self-refer into the study by completing and posting to the research team a standardised questionnaire. Following an assessment interview, eligible referrals have access to an 8-session cCBT programme called Beating the Blues and are randomised to one of four types of support: brief-assistant, extended-assistant, brief-clinician or extended-clinician.A sample size of 35 per group (total 140) is sufficient to detect a moderate effect size with 90% power on our primary outcome measure (Work and Social Adjustment Scale); assuming a 30% attrition rate, 200 patients will be randomised. Secondary outcome measures include the Beck Depression and Anxiety Inventories and the PHQ-9 and GAD-7. Data on clinical outcomes, treatment usage and patient experiences are collected in three ways: by post via self-report questionnaires at week 0 (randomisation) and at weeks 12 and 24 post-randomisation; electronically by the cCBT system every time patients log-in; by phone during assessments, support sessions and exit interviews. The study's factorial design increases its efficiency by allowing the concurrent investigation of two types of adjunct support for cCBT with a single sample of participants. Difficulties in recruitment, uptake and retention of participants are anticipated because of the nature of the targeted clinical problem (depression impairs motivation) and of the studied interventions (lack of face-to-face contact because referrals, assessments, interventions and data collection are completed by phone, computer or post). Current Controlled Trials ISRCTN98677176.

The impact on health-related quality of life in the first 12 months: A randomised comparison of preoperative short-course radiation versus long-course chemoradiation for T3 rectal cancer (Trans-Tasman Radiation Oncology Group Trial 01.04).

PubMed

McLachlan, Sue-Anne; Fisher, Richard J; Zalcberg, John; Solomon, Michael; Burmeister, Bryan; Goldstein, David; Leong, Trevor; Ackland, Stephen P; McKendrick, Joseph; McClure, Bev; Mackay, John; Ngan, Samuel Y

2016-03-01

To assess health-related quality of life (HRQOL) in patients participating in a randomised trial of neoadjuvant short course radiation (SC) or long course chemoradiation (LC) for operable rectal cancer. Eligible patients with T3N0-2M0 rectal cancer completed the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) and the colorectal cancer specific module (QLQ C38) at randomisation and 1, 2, 3, 6, 9 and 12 months later. Of 326 patients randomised, 297 (SC 143, LC 154) were eligible for completion of HRQOL questionnaires. Baseline scores were comparable across the SC and LC groups. Patients reported low scores on sexual functioning and sexual enjoyment. Defaecation problems were the worst of the symptoms at baseline. Surgery had the most profoundly negative effect on HRQOL, seen in both the SC and LC treatment groups to the same extent. The most severely affected domains were physical function and role function and the most severely affected symptoms were fatigue, pain, appetite, weight loss and male sexual problems. Most domains and symptoms returned to baseline levels by 12 months apart from body image, sexual enjoyment and male sexual problems. Future perspective was better than prior to treatment. There is no overall difference in HRQOL between SC and LC neoadjuvant treatment strategies, in the first 12 months, after surgery. In the immediate postoperative period HRQOL was adversely affected in both groups but for the most part was temporary. Some residual sexual functioning concerns persisted at 12 months. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

PubMed

de Ruiter, Marieke Anna; Oosterlaan, Jaap; Schouten-van Meeteren, Antoinette Yvonne Narda; Maurice-Stam, Heleen; van Vuurden, Dannis Gilbert; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Caron, Huib N; Grootenhuis, Martha Alexandra

2016-09-01

Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Results of a feasibility randomised controlled study of the guidelines for exercise in multiple sclerosis project.

PubMed

Learmonth, Yvonne C; Adamson, Brynn C; Kinnett-Hopkins, Dominique; Bohri, Maria; Motl, Robert W

2017-03-01

There is increasing recognition that exercise is an efficacious strategy for managing many consequences of multiple sclerosis (MS), yet persons with MS are not engaging in sufficient exercise for accruing health benefits. Poor exercise uptake might be associated with the design of previous research. We conducted a randomised controlled trial (RCT) for examining the feasibility of a 4-month home-based, exercise-training program designed based on recent physical activity guidelines for MS and supplemented by behavioural strategies for compliance. Feasibility was assessed in the domains of process (e.g., recruitment), resource (e.g., monetary costs), management (e.g., personnel time requirements) and scientific outcomes (e.g., treatment effect). We recruited persons with mild-to-moderate MS who were randomised into an intervention or wait-list control condition. Intervention participants received a pedometer, elastic resistance bands, DVD, training manual, calendars, log-book, video coaching calls and newsletters. Participants in both conditions completed home-based assessments before and after the 4-month period. Ninety-nine persons with MS were assessed for eligibility, and 57 were randomised. Fifty-one persons completed the study (90%). Total costs of the study were US $5331.03. Personnel time to conduct the study totaled 263h. Participants in the intervention group complied fully with 71% of all exercise sessions. There was a moderate increase in self-reported exercise behaviour of the intervention participants as measured by the Godin Leisure-Time Exercise Questionnaire (d≥0.5). The results support the feasibility and acceptability of a home-based exercise intervention based on physical activity guidelines and supplemented with behavioural strategies for adults with mild-to-moderate MS. Copyright © 2016 Elsevier Inc. All rights reserved.

[Results of a randomised controlled trial on the acceptance and the outcomes of a counselling on medical inpatient rehabilitation in gainfully employed members of statutory health insurances with rheumatoid arthritis (clinicaltrials.gov identifier NCT00229541)].

PubMed

Schlademann, S; Hüppe, A; Raspe, H

2007-06-01

In a randomised controlled trial we examined the influence of a counselling (and implementation) of an inpatient rehabilitation programme on the somatic, mental and sociomedical course of rheumatoid arthritis (RA) in employees. Additionally, the recruitment of a study population via routine data of statutory health insurances was tested. Potential study participants were identified by health insurances via RA-specific data on work disability, hospital stays and medical prescriptions. These insurants entered a two-stage selection process (postal screening questionnaire, experts). Eligible participants completed a postal questionnaire on their subjective health status, the responders were randomised into intervention group (IG) and control group (CG), respectively. The IG was offered a counselling on medical rehabilitation, CG members received usual care. Pension funds and health insurances transferred data on sick leaves (cases, days), hospital treatment, disability pension and medical rehabilitation (primary outcomes). Twelve months after baseline, again a questionnaire on subjective health status was completed (secondary outcomes). Data were analysed on an intention to treat and as actual basis. Whilst the offered counselling was accepted very well (IG: 84.4%), the attendance in a medical inpatient rehabilitation was low (IG: 31.3%). Neither an intention to treat analysis (IG vs. CG) nor an as actual analysis (rehabilitation vs. no rehabilitation) perceived significant differences in the course of sick leave, hospital treatment or parameters of subjective health. The study showed the feasibility of a randomised controlled trial in rehabilitation-related Health Services Research. Recruitment via routine data of health insurances showed limitations. The low acceptance of a medical inpatient rehabilitation emphasises the need to establish alternative rehabilitative programs focussing on employed RA patients.

Psychosocial morbidity in women with abnormal cervical cytology managed by cytological surveillance or initial colposcopy: longitudinal analysis from the TOMBOLA randomised trial.

PubMed

Fielding, S; Rothnie, K; Gray, N M; Little, J; Cruickshank, M E; Neal, K; Walker, L G; Whynes, D; Cotton, S C; Sharp, L

2017-04-01

To compare psychosocial outcomes (follow-up related worries and satisfaction with follow-up related information and support) over 30 months of two alternative management policies for women with low-grade abnormal cervical cytology. Women aged 20-59 years with low-grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI -3.6 to -1.3) lower for follow-up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow-up related satisfaction with information and support (-2.4; -3.3 to -1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th- and 18th-month time points. These differences remained when the analysis was stratified by post-school education. Women with low-grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial.

PubMed

Wilkinson, Kate M; Krige, Anton; Brearley, Sarah G; Lane, Steven; Scott, Michael; Gordon, Anthony C; Carlson, Gordon L

2014-10-21

Thoracic epidural analgesia (TEA) is recommended for post-operative pain relief in patients undergoing major abdominal surgery via a midline incision. However, the effectiveness of TEA is variable with high failure rates reported post-operatively. Common side effects such as low blood pressure and motor block can reduce mobility and hinder recovery, and a number of rare but serious complications can also occur following their use.Rectus sheath catheters (RSC) may provide a novel alternative approach to somatic analgesia without the associated adverse effects of TEA. The aim of this study is to compare the efficacy of both techniques in terms of pain relief, patient experience, post-operative functional recovery, safety and cost-effectiveness. This is a single-centre randomised controlled non-blinded trial, which also includes a nested qualitative study. Over a two-year period, 132 patients undergoing major abdominal surgery via a midline incision will be randomised to receive either TEA or RSC for post-operative analgesia. The primary outcome measures pain scores on moving from a supine to a sitting position at 24 hours post wound closure, and the patient experience between groups evaluated through in-depth interviews. Secondary outcomes include pain scores at rest and on movement at other time points, opiate consumption, functional recovery, morbidity and cost-effectiveness. This will be the first randomised controlled trial comparing thoracic epidurals to ultrasound-guided rectus sheath catheters in adults undergoing elective midline laparotomy. The standardised care provided by an Enhanced Recovery Programme makes this a comparison between two complex pain packages and not simply two analgesic techniques, in order to ascertain if RSC is a viable alternative to TEA. Current Controlled Trials ISRCTN81223298 (16 January 2014).

Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial.

PubMed

Goette, Andreas; Merino, Jose L; Ezekowitz, Michael D; Zamoryakhin, Dmitry; Melino, Michael; Jin, James; Mercuri, Michele F; Grosso, Michael A; Fernandez, Victor; Al-Saady, Naab; Pelekh, Natalya; Merkely, Bela; Zenin, Sergey; Kushnir, Mykola; Spinar, Jindrich; Batushkin, Valeriy; de Groot, Joris R; Lip, Gregory Y H

2016-10-22

Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available. We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin-warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)-stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region-was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with ClinicalTrials.gov, number NCT02072434. Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin-warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA 2 DS 2 -VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin-warfarin group (odds ratio [OR] 0·46, 95% CI 0·12-1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin-warfarin (OR 1·48, 95% CI 0·64-3·55). The results were independent of the TEE-guided strategy and anticoagulation status. ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups. Daiichi Sankyo provided financial support for the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial.

PubMed

Poewe, Werner; Seppi, Klaus; Fitzer-Attas, Cheryl J; Wenning, Gregor K; Gilman, Sid; Low, Phillip A; Giladi, Nir; Barone, Paolo; Sampaio, Cristina; Eyal, Eli; Rascol, Olivier

2015-02-01

Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. Teva Pharmaceutical Industries and H Lundbeck A/S. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery.

PubMed

Charlton, Shona; Cyna, Allan M; Middleton, Philippa; Griffiths, James D

2010-12-08

The transversus abdominis plane (TAP) block is a peripheral nerve block which anaesthetises the abdominal wall. The increasing use of TAP block, as a form of pain relief after abdominal surgery warrants evaluation of its effectiveness as an adjunctive technique to routine care and, when compared with other analgesic techniques. To assess effects of TAP blocks (and variants) on postoperative analgesia requirements after abdominal surgery. We searched specialised registers of Cochrane Anaesthesia and Cochrane Pain, Palliative and Supportive Care Review Groups, CENTRAL, MEDLINE, EMBASE and CINAHL to June 2010. We included randomised controlled trials (RCTs) comparing TAP block or rectus sheath block with: no TAP or rectus sheath block; placebo; systemic, epidural or any other analgesia. At least two review authors assessed study eligibility and risk of bias, and extracted data. We included eight studies (358 participants), five assessing TAP blocks, three assessing rectus sheath blocks; with moderate risk of bias overall. All studies had a background of general anaesthesia in both arms in most cases.Compared with no TAP block or saline placebo, TAP block resulted in significantly less postoperative requirement for morphine at 24 hours (mean difference (MD) -21.95 mg, 95% confidence interval (CI) -37.91 to 5.96; five studies, 236 participants) and 48 hours (MD -28.50, 95% CI -38.92 to -18.08; one study of 50 participants) but not at two hours (all random-effects analyses). Pain at rest was significantly reduced in two studies, but not a third.Only one of three included studies of rectus sheath blocks found a reduction in postoperative analgesic requirements in participants receiving blocks. One study, assessing number of participants who were pain-free after their surgery, found more participants who received a rectus sheath block to be pain-free for up to 10 hours postoperatively. As with TAP blocks, rectus sheath blocks made no apparent impact on nausea and vomiting or sedation scores. No studies have compared TAP block with other analgesics such as epidural analgesia or local anaesthetic infiltration into the abdominal wound. There is only limited evidence to suggest use of perioperative TAP block reduces opioid consumption and pain scores after abdominal surgery when compared with no intervention or placebo. There is no apparent reduction in postoperative nausea and vomiting or sedation from the small numbers of studies to date. Many relevant studies are currently underway or awaiting publication.

Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial.

PubMed

Hakim, James G; Thompson, Jennifer; Kityo, Cissy; Hoppe, Anne; Kambugu, Andrew; van Oosterhout, Joep J; Lugemwa, Abbas; Siika, Abraham; Mwebaze, Raymond; Mweemba, Aggrey; Abongomera, George; Thomason, Margaret J; Easterbrook, Philippa; Mugyenyi, Peter; Walker, A Sarah; Paton, Nicholas I

2018-01-01

Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787. Between April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification. Protease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings. European and Developing Countries Clinical Trials Partnership (EDCTP), UK Medical Research Council, Instituto de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, Merck, ViiV Healthcare, WHO. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial.

PubMed

Rödel, Claus; Liersch, Torsten; Becker, Heinz; Fietkau, Rainer; Hohenberger, Werner; Hothorn, Torsten; Graeven, Ullrich; Arnold, Dirk; Lang-Welzenbach, Marga; Raab, Hans-Rudolf; Sülberg, Heiko; Wittekind, Christian; Potapov, Sergej; Staib, Ludger; Hess, Clemens; Weigang-Köhler, Karin; Grabenbauer, Gerhard G; Hoffmanns, Hans; Lindemann, Fritz; Schlenska-Lange, Anke; Folprecht, Gunnar; Sauer, Rolf

2012-07-01

Preoperative chemoradiotherapy, total mesorectal excision surgery, and adjuvant chemotherapy with fluorouracil is the standard combined modality treatment for rectal cancer. With the aim of improving disease-free survival (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard treatment. This was a multicentre, open-label, randomised, phase 3 study in patients with histologically proven carcinoma of the rectum with clinically staged T3-4 or any node-positive disease. Between July 25, 2006, and Feb 26, 2010, patients were randomly assigned to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (1000 mg/m(2) days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m(2) days 1-5 and 29; fluorouracil group); and an experimental group receiving preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (250 mg/m(2) days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) days 1, 8, 22, and 29), followed by surgery and eight cycles of adjuvant chemotherapy with oxaliplatin (100 mg/m(2) days 1 and 15), leucovorin (400 mg/m(2) days 1 and 15), and infusional fluorouracil (2400 mg/m(2) days 1-2 and 15-16; fluorouracil plus oxaliplatin group). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-4 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. DFS is the primary endpoint. Secondary endpoints, including toxicity, compliance, and histopathological response are reported here. Safety and compliance analyses included patients as treated, efficacy endpoints were analysed according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT00349076. Of the 1265 patients initially enrolled, 1236 were evaluable (613 in the fluorouracil plus oxaliplatin group and 623 in the fluorouracil group). Preoperative grade 3-4 toxic effects occurred in 140 (23%) of 606 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 127 (20%) of 624 patients who actually received fluorouracil chemoradiotherapy. Grade 3-4 diarrhoea was more common in those who received fluorouracil and oxaliplatin during chemoradiotherapy than in those who received fluorouracil during chemoradiotherapy (73 patients [12%] vs 52 patients [8%]), as was grade 3-4 nausea or vomiting (23 [4%] vs nine [1%]). 516 (85%) of the 606 patients who received fluorouracil and oxaliplatin-based chemoradiotherapy had the full dose of chemotherapy, and 571 (94%) had the full dose of radiotherapy; as did 495 (79%) and 601 (96%) of 624 patients who received fluorouracil-based chemoradiotherapy, respectively. A pathological complete response was achieved in 103 (17%) of 591 patients who underwent surgery in the fluorouracil and oxaliplatin group and in 81 (13%) of 606 patients who underwent surgery in the fluorouracil group (odds ratio 1·40, 95% CI 1·02-1·92; p=0·038). In the fluorouracil and oxaliplatin group, 352 (81%) of 435 patients who began adjuvant chemotherapy completed all cycles (with or without dose reduction), as did 386 (83%) of 463 patients in the fluorouracil group. Inclusion of oxaliplatin into modified fluorouracil-based combined modality treatment was feasible and led to more patients achieving a pathological complete response than did standard treatment. Longer follow-up is needed to assess DFS. German Cancer Aid (Deutsche Krebshilfe). Copyright © 2012 Elsevier Ltd. All rights reserved.

Visuospatial and Attentional Abilities Predict Driving Simulator Performance Among Older HIV-infected Adults

PubMed Central

Foley, J. M.; Gooding, A. L.; Thames, A. D.; Ettenhofer, M. L.; Kim, M. S.; Castellon, S. A.; Marcotte, T. D.; Sadek, J. R.; Heaton, R. K.; van Gorp, W. G.; Hinkin, C. H.

2013-01-01

Objectives To examine the effects of aging and neuropsychological (NP) impairment on driving simulator performance within a human immunodeficiency virus (HIV)-infected cohort. Methods Participants included 79 HIV-infected adults (n = 58 > age 50, n = 21 ≤ 40) who completed a NP battery and a personnel computer-based driving simulator task. Outcome variables included total completion time (time) and number of city blocks to complete the task (blocks). Results Compared to the younger group, the older group was less efficient in their route finding (blocks over optimum: 25.9 [20.1] vs 14.4 [16.9]; P = .02) and took longer to complete the task (time: 1297.6 [577.6] vs 804.4 [458.5] seconds; P = .001). Regression models within the older adult group indicated that visuospatial abilities (blocks: b = –0.40, P < .001; time: b = –0.40, P = .001) and attention (blocks: b = –0.49, P = .001; time: b = –0.42, P = .006) independently predicted simulator performance. The NP-impaired group performed more poorly on both time and blocks, compared to the NP normal group. Conclusions Older HIV-infected adults may be at risk of driving-related functional compromise secondary to HIV-associated neurocognitive decline. PMID:23314403

Comparison of Two Different Doses of Intrathecal Levobupivacaine for Transurethral Endoscopic Surgery

PubMed Central

Dizman, Secil; Turker, Gurkan; Gurbet, Alp; Mogol, Elif Basagan; Turkcan, Suat; Karakuzu, Ziyaatin

2011-01-01

Objective: To evaluate the effects of two different spinal isobaric levobupivacaine doses on spinal anesthesia characteristics and to find the minimum effective dose for surgery in patients undergoing transurethral resection (TUR) surgery. Materials and Methods: Fifty male patients undergoing TUR surgery were included in the study and were randomized into two equal groups: Group LB10 (n=25): 10 mg 0.5% isobaric levobupivacaine (2 ml) and Group LB15 (n=25): 15 mg 0.75% isobaric levobupivacaine (2 ml). Spinal anesthesia was administered via a 25G Quincke spinal needle through the L3–4 intervertebral space. Sensorial block levels were evaluated using the ‘pin-prick test’, and motor block levels were evaluated using the ‘Bromage scale’. The sensorial and motor block characteristics of patients during intraoperative and postoperative periods and recovery time from spinal anesthesia were evaluated. Results: In three cases in the Group LB10, sensorial block did not reach the T10 level. Complete motor block (Bromage=3) did not occur in eight cases in the Group LB10 and in five cases in the Group LB15. The highest sensorial dermatomal level detected was higher in Group LB15. In Group LB15, sensorial block initial time and the time of complete motor block occurrence were significantly shorter than Group LB10. Hypotension was observed in one case in Group LB15. No significant difference between groups was detected in two segments of regression times: the time to S2 regression and complete sensorial block regression time. Complete motor block regression time was significantly longer in Group LB15 than in Group LB10 (p<0.01). Conclusion: Our findings showed that the minimum effective spinal isobaric levobupivacaine dose was 10 mg for TUR surgery. PMID:25610173

Effects of an Isolated Complete Right Bundle Branch Block on Mechanical Ventricular Function.

PubMed

Zhang, Qin; Xue, Minghua; Li, Zhan; Wang, Haiyan; Zhu, Lei; Liu, Xinling; Meng, Haiyan; Hou, Yinglong

2015-12-01

The purpose of this study was to investigate the effects of an isolated complete right bundle branch block on mechanical ventricular function. Two groups of participants were enrolled in this study: a block group, consisting of 98 patients with isolated complete right bundle branch blocks without structural heart disease, and a control group, consisting of 92 healthy adults. The diameter, end-diastolic area, end-systolic area, and right ventricular (RV) fractional area change were obtained to evaluate morphologic and systolic function by 2-dimensional sonographic technology. Systolic and diastolic velocities and time interval parameters were measured to assess mechanical ventricular performance using pulsed wave tissue Doppler imaging. Although there was no significant difference in the RV fractional area change between the patients with blocks and controls, the diameter, end-diastolic area, and end-systolic area of the RV were significantly larger in the patients with blocks (P < .05). In the patients with blocks, the peak velocities during systole and early diastole and the ratio of the peak velocities during early and late diastole decreased. The block group had a prolonged pre-ejection period, electromechanical delay time, and isovolumic relaxation time, a decreased ejection time, and an increased pre-ejection period/ejection time ratio, and the myocardial performance index (Tei index) at the basal RV lateral wall was significantly increased. There were no significant differences in any echocardiographic parameters at different sites of the left ventricle. In patients with isolated complete right bundle branch blocks, systolic and diastolic functions are impaired in the RV, and follow-up is needed. © 2015 by the American Institute of Ultrasound in Medicine.

A cadaveric study to determine the minimum volume of methylene blue to completely color the nerves of brachial plexus in cats. An update in forelimb and shoulder surgeries.

PubMed

Mencalha, Rodrigo; Fernandes, Neide; Sousa, Carlos Augusto dos Santos; Abidu-Figueiredo, Marcelo

2014-06-01

To determine the minimum volume of methylene blue (MB) to completely color the brachial plexus (BP) nerves, simulating an effective anesthetic block in cats. Fifteen adult male cat cadavers were injected through subscapular approach with volumes of 2, 3, 4, 5 and 6 ml in both forelimbs, for a total of 30 brachial plexus blocks (BPB). After infusions, the specimens were carefully dissected preserving each nervous branch. The measurement of the effective area was indicated by the impregnation of MB. Nerves were divided into four segments from the origin at the spinal level until the insertion into the thoracic limb muscles. The blocks were considered effective only when all the nerves were strongly or totally colored. Volumes of 2, 3 and 4 ml were considered insufficient suggesting a failed block, however, volumes of 5 and 6 ml were associated with a successful block. The injection of methylene blue, in a volume of 6 ml, completely colored the brachial plexus. At volumes of 5 and 6 ml the brachial plexus blocks were considered a successful regional block, however, volumes of 2, 3 and 4 ml were considered a failed regional block.

Binocular treatment of amblyopia using videogames (BRAVO): study protocol for a randomised controlled trial.

PubMed

Guo, Cindy X; Babu, Raiju J; Black, Joanna M; Bobier, William R; Lam, Carly S Y; Dai, Shuan; Gao, Tina Y; Hess, Robert F; Jenkins, Michelle; Jiang, Yannan; Kowal, Lionel; Parag, Varsha; South, Jayshree; Staffieri, Sandra Elfride; Walker, Natalie; Wadham, Angela; Thompson, Benjamin

2016-10-18

Amblyopia is a common neurodevelopmental disorder of vision that is characterised by visual impairment in one eye and compromised binocular visual function. Existing evidence-based treatments for children include patching the nonamblyopic eye to encourage use of the amblyopic eye. Currently there are no widely accepted treatments available for adults with amblyopia. The aim of this trial is to assess the efficacy of a new binocular, videogame-based treatment for amblyopia in older children and adults. We hypothesise that binocular treatment will significantly improve amblyopic eye visual acuity relative to placebo treatment. The BRAVO study is a double-blind, randomised, placebo-controlled multicentre trial to assess the effectiveness of a novel videogame-based binocular treatment for amblyopia. One hundred and eight participants aged 7 years or older with anisometropic and/or strabismic amblyopia (defined as ≥0.2 LogMAR interocular visual acuity difference, ≥0.3 LogMAR amblyopic eye visual acuity and no ocular disease) will be recruited via ophthalmologists, optometrists, clinical record searches and public advertisements at five sites in New Zealand, Canada, Hong Kong and Australia. Eligible participants will be randomised by computer in a 1:1 ratio, with stratification by age group: 7-12, 13-17 and 18 years and older. Participants will be randomised to receive 6 weeks of active or placebo home-based binocular treatment. Treatment will be in the form of a modified interactive falling-blocks game, implemented on a 5th generation iPod touch device viewed through red/green anaglyphic glasses. Participants and those assessing outcomes will be blinded to group assignment. The primary outcome is the change in best-corrected distance visual acuity in the amblyopic eye from baseline to 6 weeks post randomisation. Secondary outcomes include distance and near visual acuity, stereopsis, interocular suppression, angle of strabismus (where applicable) measured at baseline, 3, 6, 12 and 24 weeks post randomisation. Treatment compliance and acceptability will also be assessed along with quality of life for adult participants. The BRAVO study is the first randomised controlled trial of a home-based videogame treatment for older children and adults with amblyopia. The results will indicate whether a binocular approach to amblyopia treatment conducted at home is effective for patients aged 7 years or older. This trial was registered in Australia and New Zealand Clinical Trials Registry ( ACTRN12613001004752 ) on 10 September 2013.

AnAnkle Trial study protocol: a randomised trial comparing pain profiles after peripheral nerve block or spinal anaesthesia for ankle fracture surgery.

PubMed

Sort, Rune; Brorson, Stig; Gögenur, Ismail; Møller, Ann Merete

2017-06-02

Ankle fracture surgery is a common procedure, but the influence of anaesthesia choice on postoperative pain and quality of recovery is poorly understood. Some authors suggest a benefit of peripheral nerve block (PNB) in elective procedures, but the different pain profile following acute fracture surgery and the rebound pain on cessation of the PNB both remain unexplored. We present an ongoing randomised study aiming to compare primary PNB anaesthesia with spinal anaesthesia for ankle fracture surgery regarding postoperative pain profiles and quality of recovery. AnAnkle Trial is a randomised, dual-centre, open-label, blinded analysis trial of 150 adult patients undergoing primary internal fixation of an ankle fracture. Main exclusion criteria are habitual opioid use, impaired pain sensation, other painful injuries or cognitive impairment. The intervention is ultrasound-guided popliteal sciatic (20 mL) and saphenal nerve (8 mL) PNB with ropivacaine 7.5 mg/mL, and controls receive spinal anaesthesia (2 mL) with hyperbaric bupivacaine 5 mg/mL. Postoperatively all receive paracetamol, ibuprofen and patient-controlled intravenous morphine on demand. Morphine consumption and pain scores are registered in the first 27 hours and reported as an integrated pain score as the primary endpoint. Pain score intervals are 3 hours and we will use the area under curve to get a longitudinal measure of pain. Secondary outcomes include rebound pain on cessation of anaesthesia, opioid side effects (Opioid-Related Symptom Distress Scale), quality of recovery (Danish Quality of Recovery-15 score) and pain scores and medication days 1-7 (diary). The study has been approved by the Regional Ethics Committees in the Capital Region of Denmark, the Danish Data Protection Agency and the Danish Health and Medical Authority. We will publish the results in international peer-reviewed medical journals. AnAnkle Trial is registered in the European Clinical Trials Database (EudraCT 2015-001108-76). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Block Transfer Handbook: Constructing and Negotiating Block Transfer Agreements.

ERIC Educational Resources Information Center

Finlay, Finola

The purpose of this handbook is to provide resources for institutions or articulation committees who are engaged in the task of investigating the feasibility of block transfer agreements. Block transfer is the process whereby a block of credits is granted to students who have successfully completed a certificate, diploma, or cluster of courses…

The adequate rocuronium dose required for complete block of the adductor muscles of the thigh.

PubMed

Fujimoto, M; Kawano, K; Yamamoto, T

2018-03-01

Rocuronium can prevent the obturator jerk during transurethral resection of bladder tumors. We investigated the adequate rocuronium dose required for complete block of the thigh adductor muscles, and its correlation with individual responses of the adductor pollicis muscle to rocuronium. Eleven patients scheduled for transurethral resection of bladder tumors under general anesthesia were investigated. After general anesthesia induction, neuromuscular monitoring of the adductor pollicis muscle and ultrasonography-guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg, was repeatedly administered intravenously. The adequate rocuronium dose required for complete block of the thigh muscles, defined as the cumulative dose of rocuronium administered until that time, and its correlation with the first twitch response of the adductor pollicis muscle on train-of-four stimulation after initial rocuronium administration was analyzed. The rocuronium dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in seven patients and 0.45 mg/kg in the remaining four patients, which did not correlate with the first twitch response. At the time of complete block of the thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle varied greatly, although the level was never more profound than a post-tetanic count of 1. Although the response of the adductor pollicis muscle to rocuronium cannot be used to determine the adequate rocuronium dose required for complete block of the thigh muscles, intense blockade, with maintenance of post-tetanic count at ≤ 1 in the adductor pollicis muscle is essential to prevent the obturator jerk. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A small unconditional non-financial incentive suggests an increase in survey response rates amongst older general practitioners (GPs): a randomised controlled trial study

PubMed Central

2013-01-01

Background Few studies have investigated the effect of small unconditional non-monetary incentives on survey response rates amongst GPs or medical practitioners. This study assessed the effectiveness of offering a small unconditional non-financial incentive to increase survey response rates amongst general practitioners within a randomised controlled trial (RCT). Methods An RCT was conducted within a general practice survey that investigated how to prolong working lives amongst ageing GPs in Australia. GPs (n = 125) were randomised to receive an attractive pen or no pen during their first invitation for participation in a survey. GPs could elect to complete the survey online or via mail. Two follow up reminders were sent without a pen to both groups. The main outcome measure was response rates. Results The response rate for GPs who received a pen was higher in the intervention group (61.9%) compared to the control group (46.8%). This study did not find a statistically significant effect of a small unconditional non-financial incentive (in the form of a pen) on survey response rates amongst GPs (Odds ratio, 95% confidence interval: 1.85 (0.91 to 3.77). No GPs completed the online version. Conclusion A small unconditional non-financial incentives, in the form of a pen, may improve response rates for GPs. PMID:23899116

Arabin cervical pessary for prevention of preterm birth in cases of twin-to-twin transfusion syndrome treated by fetoscopic LASER coagulation: the PECEP LASER randomised controlled trial.

PubMed

Rodó, Carlota; Arévalo, Sílvia; Lewi, Liesbeth; Couck, Isabel; Hollwitz, Bettina; Hecher, Kurt; Carreras, Elena

2017-08-01

Fetoscopic LASER coagulation of the placental anastomoses has changed the prognosis of twin-twin transfusion syndrome. However, the prematurity rate in this cohort remains very high. To date, strategies proposed to decrease the prematurity rate have shown inconclusive, if not unfavourable results. This is a randomised controlled trial to investigate whether a prophylactic cervical pessary will lower the incidence of preterm delivery in cases of twin-twin transfusion syndrome requiring fetoscopic LASER coagulation. Women eligible for the study will be randomised after surgery and allocated to either pessary or expectant management. The pessary will be left in place until 37 completed weeks or earlier if delivery occurs. The primary outcome is delivery before 32 completed weeks. Secondary outcomes are a composite of adverse neonatal outcome, fetal and neonatal death, maternal complications, preterm rupture of membranes and hospitalisation for threatened preterm labour. 352 women will be included in order to decrease the rate of preterm delivery before 32 weeks' gestation from 40% to 26% with an alpha-error of 0.05 and 80% power. The trial aims at clarifying whether the cervical pessary prolongs the pregnancy in cases of twin-twin transfusion syndrome regardless of cervical length at the time of fetoscopy. ClinicalTrials.gov Identifier: NCT01334489 . Registered 04 December 2011.

A small unconditional non-financial incentive suggests an increase in survey response rates amongst older general practitioners (GPs): a randomised controlled trial study.

PubMed

Pit, Sabrina Winona; Hansen, Vibeke; Ewald, Dan

2013-07-30

Few studies have investigated the effect of small unconditional non-monetary incentives on survey response rates amongst GPs or medical practitioners. This study assessed the effectiveness of offering a small unconditional non-financial incentive to increase survey response rates amongst general practitioners within a randomised controlled trial (RCT). An RCT was conducted within a general practice survey that investigated how to prolong working lives amongst ageing GPs in Australia. GPs (n = 125) were randomised to receive an attractive pen or no pen during their first invitation for participation in a survey. GPs could elect to complete the survey online or via mail. Two follow up reminders were sent without a pen to both groups. The main outcome measure was response rates. The response rate for GPs who received a pen was higher in the intervention group (61.9%) compared to the control group (46.8%). This study did not find a statistically significant effect of a small unconditional non-financial incentive (in the form of a pen) on survey response rates amongst GPs (Odds ratio, 95% confidence interval: 1.85 (0.91 to 3.77). No GPs completed the online version. A small unconditional non-financial incentives, in the form of a pen, may improve response rates for GPs.

The NAtional randomised controlled Trial of Tonsillectomy IN Adults (NATTINA): a clinical and cost-effectiveness study: study protocol for a randomised control trial.

PubMed

Rubie, Isabel; Haighton, Catherine; O'Hara, James; Rousseau, Nikki; Steen, Nick; Stocken, Deborah D; Sullivan, Frank; Vale, Luke; Wilkes, Scott; Wilson, Janet

2015-06-06

The role of tonsillectomy in the management of adult tonsillitis remains uncertain and UK regional variation in tonsillectomy rates persists. Patients, doctors and health policy makers wish to know the costs and benefits of tonsillectomy against conservative management and whether therapy can be better targeted to maximise benefits and minimise risks of surgery, hence maximising cost-effective use of resources. NATTINA incorporates the first attempt to map current NHS referral criteria against other metrics of tonsil disease severity. A UK multi-centre, randomised, controlled trial for adults with recurrent tonsillitis to compare the clinical and cost-effectiveness of tonsillectomy versus conservative management. An initial feasibility study comprises qualitative interviews to investigate the practicality of the protocol, including willingness to randomise and be randomised. Approximately 20 otolaryngology staff, 10 GPs and 15 ENT patients will be recruited over 5 months in all 9 proposed main trial participating sites. A 6-month internal pilot will then recruit 72 patients across 6 of the 9 sites. Participants will be adults with recurrent acute tonsillitis referred by a GP to secondary care. Randomisation between tonsillectomy and conservative management will be according to a blocked allocation method in a 1:1 ratio stratified by centre and baseline disease severity. If the pilot is successful, the main trial will recruit a further 528 patients over 18 months in all 9 participating sites. All participants will be followed up for a total of 24 months, throughout which both primary and secondary outcome data will be collected. The primary outcome is the number of sore throat days experienced over the 24-month follow-up. The pilot and main trials include an embedded qualitative process evaluation. NATTINA is designed to evaluate the relative effectiveness and efficiency of tonsillectomy versus conservative management in patients with recurrent sore throat who are eligible for surgery. Most adult tonsil disease and surgery has an impact on economically active age groups, with individual and societal costs through loss of earnings and productivity. Avoidance of unnecessary operations and prioritisation of those individuals likely to gain most from tonsillectomy would reduce costs to the NHS and society. ISRCTN55284102, Date of Registration: 4 August 2014.

Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multicentre, randomised, phase II trial (RT3VIN).

PubMed

Hurt, C N; Jones, Sef; Madden, T-A; Fiander, A; Nordin, A J; Naik, R; Powell, N; Carucci, M; Tristram, A

2018-01-16

To compare the recurrence rates after complete response to topical treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia (VIN) 3. A prospective, open, randomised multicentre trial. 32 general hospitals located in Wales and England. 180 patients were randomised consecutively between 21 October 2009 and 11 January 2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to imiquimod (of whom 42 completely responded to treatment). After 24 weeks of treatment, complete responders were followed up at 6-monthly intervals for 24 months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was assessed and any new lesions were biopsied for histology. Time to histologically confirmed disease recurrence (any grade of VIN). The median length of follow up was 18.4 months. At 18 months, more participants were VIN-free in the cidofovir arm: 94% (95% CI 78.2-98.5) versus 71.6% (95% CI 52.0-84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95-12.60, P = 0.059; multivariable HR 3.53, 95% CI 0.96-12.98, P = 0.057). The number of grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus cidofovir: 27/41 (66%), χ2 = 0.665, P = 0.415), with no grade 4+. Long-term data indicates a trend towards response being maintained for longer following treatment with cidofovir than with imiquimod, with similar low rates of adverse events for each drug. Adverse event rates indicated acceptable safety of both drugs TWEETABLE ABSTRACT: Long-term follow up in the RT3VIN trial suggests cidofovir may maintain response for longer than imiquimod. © 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

PubMed

Henao-Restrepo, Ana Maria; Camacho, Anton; Longini, Ira M; Watson, Conall H; Edmunds, W John; Egger, Matthias; Carroll, Miles W; Dean, Natalie E; Diatta, Ibrahima; Doumbia, Moussa; Draguez, Bertrand; Duraffour, Sophie; Enwere, Godwin; Grais, Rebecca; Gunther, Stephan; Gsell, Pierre-Stéphane; Hossmann, Stefanie; Watle, Sara Viksmoen; Kondé, Mandy Kader; Kéïta, Sakoba; Kone, Souleymane; Kuisma, Eewa; Levine, Myron M; Mandal, Sema; Mauget, Thomas; Norheim, Gunnstein; Riveros, Ximena; Soumah, Aboubacar; Trelle, Sven; Vicari, Andrea S; Røttingen, John-Arne; Kieny, Marie-Paule

2017-02-04

rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×10 7 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9-100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3-100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae. The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters. WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development). Copyright © 2017 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot).

PubMed

Sackley, Catherine M; Smith, Christina H; Rick, Caroline E; Brady, Marian C; Ives, Natalie; Patel, Smitaa; Woolley, Rebecca; Dowling, Francis; Patel, Ramilla; Roberts, Helen; Jowett, Sue; Wheatley, Keith; Kelly, Debbie; Sands, Gina; Clarke, Carl E

2018-01-01

Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.

Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005.

PubMed

Zwierzyna, Magdalena; Davies, Mark; Hingorani, Aroon D; Hunter, Jackie

2018-06-06

To investigate the distribution, design characteristics, and dissemination of clinical trials by funding organisation and medical specialty. Cross sectional descriptive analysis. Trial protocol information from clinicaltrials.gov, metadata of journal articles in which trial results were published (PubMed), and quality metrics of associated journals from SCImago Journal and Country Rank database. All 45 620 clinical trials evaluating small molecule therapeutics, biological drugs, adjuvants, and vaccines, completed after January 2006 and before July 2015, including randomised controlled trials and non-randomised studies across all clinical phases. Industry was more likely than non-profit funders to fund large international randomised controlled trials, although methodological differences have been decreasing with time. Among 27 835 completed efficacy trials (phase II-IV), 15 084 (54.2%) had disclosed their findings publicly. Industry was more likely than non-profit trial funders to disseminate trial results (59.3% (10 444/17 627) v 45.3% (4555/10 066)), and large drug companies had higher disclosure rates than small ones (66.7% (7681/11 508) v 45.2% (2763/6119)). Trials funded by the National Institutes of Health (NIH) were disseminated more often than those of other non-profit institutions (60.0% (1451/2417) v 40.6% (3104/7649)). Results of studies funded by large drug companies and NIH were more likely to appear on clinicaltrials.gov than were those from non-profit funders, which were published mainly as journal articles. Trials reporting the use of randomisation were more likely than non-randomised studies to be published in a journal article (6895/19 711 (34.9%) v 1408/7748 (18.2%)), and journal publication rates varied across disease areas, ranging from 42% for autoimmune diseases to 20% for oncology. Trial design and dissemination of results vary substantially depending on the type and size of funding institution as well as the disease area under study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A review of reporting of participant recruitment and retention in RCTs in six major journals

PubMed Central

Toerien, Merran; Brookes, Sara T; Metcalfe, Chris; de Salis, Isabel; Tomlin, Zelda; Peters, Tim J; Sterne, Jonathan; Donovan, Jenny L

2009-01-01

Background Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs. Methods We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July–December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes. Results 133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret. Conclusion The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart. PMID:19591685

A review of reporting of participant recruitment and retention in RCTs in six major journals.

PubMed

Toerien, Merran; Brookes, Sara T; Metcalfe, Chris; de Salis, Isabel; Tomlin, Zelda; Peters, Tim J; Sterne, Jonathan; Donovan, Jenny L

2009-07-10

Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs. We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July-December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes. 133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret. The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart.

Efficacy of progressive muscle relaxation training in reducing anxiety in patients with acute schizophrenia.

PubMed

Chen, Wen-Chun; Chu, Hsin; Lu, Ru-Band; Chou, Yuan-Hwa; Chen, Chung-Hua; Chang, Yue-Cune; O'Brien, Anthony Paul; Chou, Kuei-Ru

2009-08-01

The objective of this study was to examine the efficacy of progressive muscle relaxation training on anxiety in patients with acute schizophrenia. Many empirical studies have found progressive muscle relaxation training beneficial in reducing the psychological effects of anxiety. Progressive muscle relaxation training is also effective in reducing the distress symptoms associated with the symptomatology of schizophrenia. An experimental randomised controlled trial using repeated measures. The study was designed to examine the effects of progressive muscle relaxation training on patients diagnosed with schizophrenia. Study participants were acute psychiatric inpatients in Taiwan. Eighteen patients were block randomised and then assigned to an experimental or control group. The experimental group received progressive muscle relaxation training and the control group received a placebo intervention. Results from the Beck anxiety inventory were compared between groups as a pretest before intervention, on day 11 of intervention and one week post-test after the intervention was completed. Changes in finger temperature were measured throughout the experiment. The degree of anxiety improvement was significantly higher in the progressive muscle relaxation training group than in the control group after progressive muscle relaxation training intervention (p < 0.0001) and at follow-up (p = 0.0446; the mean BAI score fell from 16.4 pretest to -5.8 post-test. After adjusting for the change in patient finger temperature, the mean change in temperature was significantly different between the two patient groups. The average body temperature increased significantly after applying the progressive muscle relaxation training to patients with schizophrenia. This study demonstrated that progressive muscle relaxation training can effectively alleviate anxiety in patients with schizophrenia. Progressive muscle relaxation training is potentially an effective nursing intervention in the reduction of anxiety in patients diagnosed with schizophrenia, depending on the quality of their mental status at the time of intervention. Progressive muscle relaxation training is a useful intervention as it is proven to reduce anxiety levels across a spectrum of psychiatric disorders.

PMMA versus titanium cage after anterior cervical discectomy - a prospective randomized trial.

PubMed

Schröder, J; Grosse-Dresselhaus, F; Schul, C; Wassmann, H

2007-02-01

Nonautologous interbody fusion materials are utilised in increasing numbers after anterior cervical disc surgery to overcome the problem of donor site morbidity of autologous bone grafts. This study investigates the performance of two nonautologous materials, the bone cement Polymethylmethacrylate (PMMA) and titanium cages. This prospective randomised trial, with assessment of the results by an independent observer, evaluates whether a Polymethylmethacrylate (PMMA) spacer or a titanium cage provides a better fusion rate around the implant and a better clinical outcome. Between 2000 and 2002, 115 patients with monoradicular cervical nerve root compression syndrome caused by soft cervical disc herniation were eligible for this study. Myelopathy, excessive osteophyte formation, and adjacent level degeneration were exclusion criteria. A block-restricted randomisation was applied. The 2-year clinical outcome served as the primary endpoint of the study. Clinical outcome was assessed according to the Odom scale by an independent observer at the follow-up examination. Preoperative, postoperative, and follow-up radiographs were taken. The study was completed by 107 patients (53 with PMMA and 54 with titanium cage). No significant difference between the two groups could be established with respect to the clinical outcome. In each group, 26 patients scored excellent. Good results were found in 19 PMMA patients and 16 titanium cage patients; satisfactory results were found in 8 PMMA patients and 9 titanium cage patients; bad results were found in 3 titanium cage patients. In 47 titanium cage cases (87%), fusion occurred radiologically as bony bridging around the implant. The fusion rate was significantly lower (p=0.011) in the PMMA group, with 35 cases (66%) united at follow-up. The radiological result of the titanium cage is superior to that of PMMA with respect to the fusion rate. Although the titanium cage achieves a better fusion rate, there is no difference between titanium cages and PMMA with respect to the clinical outcome.

A prospective, randomised comparative study of weekly versus biweekly application of dehydrated human amnion/chorion membrane allograft in the management of diabetic foot ulcers

PubMed Central

Zelen, Charles M; Serena, Thomas E; Snyder, Robert J

2014-01-01

The aim of this study is to determine if weekly application of dehydrated human amnion/chorion membrane allograft reduce time to heal more effectively than biweekly application for treatment of diabetic foot ulcers. This was an institutional review board-approved, registered, prospective, randomised, comparative, non-blinded, single-centre clinical trial. Patients with non-infected ulcers of ≥ 4 weeks duration were included for the study. They were randomised to receive weekly or biweekly application of allograft in addition to a non-adherent, moist dressing with compressive wrapping. All wounds were offloaded. The primary study outcome was mean time to healing. Overall, during the 12-week study period, 92·5% (37/40) ulcers completely healed. Mean time to complete healing was 4·1 ± 2·9 versus 2·4 ± 1·8 weeks (P = 0·039) in the biweekly versus weekly groups, respectively. Complete healing occurred in 50% versus 90% by 4 weeks in the biweekly and weekly groups, respectively (P = 0·014). Number of grafts applied to healed wounds was similar at 2·4 ± 1·5 and 2·3 ± 1·8 for biweekly versus weekly groups, respectively (P = 0·841). These results validate previous studies showing that the allograft is an effective treatment for diabetic ulcers and show that wounds treated with weekly application heal more rapidly than with biweekly application. More rapid healing may decrease clinical operational costs and prevent long-term medical complications. PMID:24618401

Pre-procedure ultrasound-guided paramedian spinal anaesthesia at L5–S1: Is this better than landmark-guided midline approach? A randomised controlled trial

PubMed Central

Srinivasan, Karthikeyan Kallidaikurichi; Leo, Anne-Marie; Iohom, Gabriella; Loughnane, Frank; Lee, Peter J

2018-01-01

Background and Aims: Routine use of pre-procedural ultrasound guided midline approach has not shown to improve success rate in administering subarachnoid block. The study hypothesis was that the routine use of pre-procedural (not real time) ultrasound-guided paramedian spinals at L5-S1 interspace could reduce the number of passes (i.e., withdrawal and redirection of spinal needle without exiting the skin) required to enter the subarachnoid space when compared to the conventional landmark-guided midline approach. Methods: After local ethics approval, 120 consenting patients scheduled for elective total joint replacements (Hip and Knee) were randomised into either Group C where conventional midline approach with palpated landmarks was used or Group P where pre-procedural ultrasound was used to perform subarachnoid block by paramedian approach at L5-S1 interspace (real time ultrasound guidance was not used). Results: There was no difference in primary outcome (difference in number of passes) between the two groups. Similarly there was no difference in the number of attempts (i.e., the number of times the spinal needle was withdrawn from the skin and reinserted). The first pass success rates (1 attempt and 1 pass) was significantly greater in Group C compared to Group P [43% vs. 22%, P = 0.02]. Conclusion: Routine use of paramedian spinal anaesthesia at L5-S1 interspace, guided by pre-procedure ultrasound, in patients undergoing lower limb joint arthroplasties did not reduce the number of passes or attempts needed to achieve successful dural puncture. PMID:29416151

Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial

PubMed Central

Stark, Dan; Nankivell, Matthew; Pujade-Lauraine, Eric; Kristensen, Gunnar; Elit, Lorraine; Stockler, Martin; Hilpert, Felix; Cervantes, Andrés; Brown, Julia; Lanceley, Anne; Velikova, Galina; Sabate, Eduardo; Pfisterer, Jacobus; Carey, Mark S; Beale, Philip; Qian, Wendi; Swart, Ann Marie; Oza, Amit; Perren, Tim

2013-01-01

Summary Background In the Gynecologic Cancer Intergroup International Collaboration on Ovarian Neoplasms 7 (ICON7) trial, bevacizumab improved progression-free survival in patients with ovarian cancer when used in combination with first-line chemotherapy and as a single-drug continuation treatment for 18 cycles. In a preliminary analysis of a high-risk subset of patients, there was also an improvement in overall survival. This study aims to describe the health-related quality-of-life (QoL) outcomes from ICON7. Methods ICON7 is a randomised, multicentre, open-label phase 3 trial. Between Dec 18, 2006, and Feb 16, 2009, after a surgical procedure aiming to debulk the disease, women with International Federation of Gynecology and Obstetrics (FIGO) high-risk stage I–IV epithelial ovarian cancer were randomly allocated (1:1) by computer program and block randomisation to receive either six cycles of standard chemotherapy (total 18 weeks) with carboplatin (area under the curve 5 or 6) and paclitaxel (175 mg/m2) alone or with bevacizumab (7·5 mg/kg) given intravenously with chemotherapy and continued as a single drug thereafter (total 54 weeks). The primary QoL endpoint was global QoL from the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire–core 30 at week 54, analysed by ANOVA and adjusted for baseline score. Analyses were by intention to treat. The ICON7 trial has completed recruitment and remains in follow-up. This study is registered, number ISRCTN91273375. Findings 764 women were randomly assigned to the standard chemotherapy group and 764 to the bevacizumab group. At baseline, 684 (90%) of women in the standard chemotherapy group and 691 (90%) of those in the bevacizumab group had completed QoL questionnaires. At week 54, 502 (66%) women in the bevacizumab group and 388 (51%) women in the standard chemotherapy group provided QoL data. Overall, the mean global QoL score improved during chemotherapy by 7·2 points (SD 24·4) when analysed for all women with data at baseline and week 18. The mean global QoL score at 54 weeks was higher in the standard chemotherapy group than in the bevacizumab group (76·1 [SD 18·2] vs 69·7 [19·1] points; difference 6·4 points, 95% CI 3·7–9·0, p<0·0001). Interpretation Bevacizumab continuation treatment seems to be associated with a small but clinically significant decrement in QoL compared with standard treatment for women with ovarian cancer. The trade-off between the prolongation of progression-free survival and the quality of that period of time needs to be considered in clinical practice when making treatment decisions. Funding Roche and the National Institute for Health Research through the UK National Cancer Research Network. PMID:23333117

6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial.

PubMed

Samandari, Taraz; Agizew, Tefera B; Nyirenda, Samba; Tedla, Zegabriel; Sibanda, Thabisa; Shang, Nong; Mosimaneotsile, Barudi; Motsamai, Oaitse I; Bozeman, Lorna; Davis, Margarett K; Talbot, Elizabeth A; Moeti, Themba L; Moffat, Howard J; Kilmarx, Peter H; Castro, Kenneth G; Wells, Charles D

2011-05-07

In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33-0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09-0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38-1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0·50, 95% CI 0·26-0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups. In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. US Centers for Disease Control and Prevention and US Agency for International Development. Copyright © 2011 Elsevier Ltd. All rights reserved.

A protocol of a cross-sectional study evaluating an online tool for early career peer reviewers assessing reports of randomised controlled trials.

PubMed

Chauvin, Anthony; Moher, David; Altman, Doug; Schriger, David L; Alam, Sabina; Hopewell, Sally; Shanahan, Daniel R; Recchioni, Alessandro; Ravaud, Philippe; Boutron, Isabelle

2017-09-15

Systematic reviews evaluating the impact of interventions to improve the quality of peer review for biomedical publications highlighted that interventions were limited and have little impact. This study aims to compare the accuracy of early career peer reviewers who use an innovative online tool to the usual peer reviewer process in evaluating the completeness of reporting and switched primary outcomes in completed reports. This is a cross-sectional study of individual two-arm parallel-group randomised controlled trials (RCTs) published in the BioMed Central series medical journals, BMJ , BMJ Open and Annals of Emergency Medicine and indexed with the publication type 'Randomised Controlled Trial'. First, we will develop an online tool and training module based (a) on the Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist and the Explanation and Elaboration document that would be dedicated to junior peer reviewers for assessing the completeness of reporting of key items and (b) the Centre for Evidence-Based Medicine Outcome Monitoring Project process used to identify switched outcomes in completed reports of the primary results of RCTs when initially submitted. Then, we will compare the performance of early career peer reviewers who use the online tool to the usual peer review process in identifying inadequate reporting and switched outcomes in completed reports of RCTs at initial journal submission. The primary outcome will be the mean number of items accurately classified per manuscript. The secondary outcomes will be the mean number of items accurately classified per manuscript for the CONSORT items and the sensitivity, specificity and likelihood ratio to detect the item as adequately reported and to identify a switch in outcomes. We aim to include 120 RCTs and 120 early career peer reviewers. The research protocol was approved by the ethics committee of the INSERM Institutional Review Board (21 January 2016). The study is based on voluntary participation and informed written consent. NCT03119376. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Management of congenital complete heart block in a low-birth-weight infant.

PubMed

Nakanishi, Keisuke; Takahashi, Ken; Kawasaki, Shiori; Fukunaga, Hideo; Amano, Atsushi

2016-10-01

Pacemaker implantation in infants during the early postnatal period is difficult because of their small body size and susceptibility to infection. We describe the successful pacemaker implantation for complete heart block in an infant weighing 803 g. © 2016 Wiley Periodicals, Inc.

Audiovisual preconditioning enhances the efficacy of an anatomical dissection course: A randomised study.

PubMed

Collins, Anne M; Quinlan, Christine S; Dolan, Roisin T; O'Neill, Shane P; Tierney, Paul; Cronin, Kevin J; Ridgway, Paul F

2015-07-01

The benefits of incorporating audiovisual materials into learning are well recognised. The outcome of integrating such a modality in to anatomical education has not been reported previously. The aim of this randomised study was to determine whether audiovisual preconditioning is a useful adjunct to learning at an upper limb dissection course. Prior to instruction participants completed a standardised pre course multiple-choice questionnaire (MCQ). The intervention group was subsequently shown a video with a pre-recorded commentary. Following initial dissection, both groups completed a second MCQ. The final MCQ was completed at the conclusion of the course. Statistical analysis confirmed a significant improvement in the performance in both groups over the duration of the three MCQs. The intervention group significantly outperformed their control group counterparts immediately following audiovisual preconditioning and in the post course MCQ. Audiovisual preconditioning is a practical and effective tool that should be incorporated in to future course curricula to optimise learning. Level of evidence This study appraises an intervention in medical education. Kirkpatrick Level 2b (modification of knowledge). Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A randomised controlled study of mindfulness meditation versus relaxation therapy in the management of tinnitus.

PubMed

Arif, M; Sadlier, M; Rajenderkumar, D; James, J; Tahir, T

2017-06-01

Psychotherapeutic interventions have been adopted effectively in the management of tinnitus for a long time. This study compared mindfulness meditation and relaxation therapy for management of tinnitus. In this randomised controlled trial, patients were recruited for five sessions of mindfulness meditation or five sessions of relaxation therapy. Patients' responses were evaluated using the Tinnitus Reaction Questionnaire as a primary outcome measure, and the Hospital Anxiety and Depression Scale, visual analogue scale and a health status indicator as secondary outcome measures. A total of 86 patients were recruited. Thirty-four patients completed mindfulness meditation and 27 patients completed relaxation therapy. Statistically significant improvement was seen in all outcome measures except the health status indicator in both treatment groups. The change in treatment scores was greater in the mindfulness meditation group than in the relaxation therapy group. This study suggests that although both mindfulness meditation and relaxation therapy are effective in the management of tinnitus, mindfulness meditation is superior to relaxation therapy.

Effectiveness of educational poster on knowledge of emergency management of dental trauma--part 2: cluster randomised controlled trial for secondary school students.

PubMed

Young, Cecilia; Wong, Kin Yau; Cheung, Lim K

2014-01-01

To investigate the effectiveness of educational poster on improving secondary school students' knowledge of emergency management of dental trauma. A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnaire after 2 weeks. Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average. Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong. HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457.

The effects of 2 weeks of interval vs continuous walking training on glycaemic control and whole-body oxidative stress in individuals with type 2 diabetes: a controlled, randomised, crossover trial.

PubMed

Karstoft, Kristian; Clark, Margaret A; Jakobsen, Ida; Müller, Ida A; Pedersen, Bente K; Solomon, Thomas P J; Ried-Larsen, Mathias

2017-03-01

The aim of this study was to evaluate the effects of oxygen consumption-matched short-term interval walking training (IWT) vs continuous walking training (CWT) on glycaemic control, including glycaemic variability, in individuals with type 2 diabetes. We also assessed whether any training-induced improvements in glycaemic control were associated with systemic oxidative stress levels. Participants (n = 14) with type 2 diabetes completed a crossover trial using three interventions (control intervention [CON], CWT and IWT), each lasting 2 weeks. These were performed in a randomised order (computerised generated randomisation) and separated by washout periods of 4 or 8 weeks after CON or training interventions, respectively. Training included ten supervised treadmill sessions, lasting 60 min/session, and was performed at the research facility. CWT was performed at moderate walking speed (75.6% ± 2.5% of walking peak oxygen consumption [[Formula: see text

Cost-effective recruitment methods for a large randomised trial in people with diabetes: A Study of Cardiovascular Events iN Diabetes (ASCEND).

PubMed

Aung, Theingi; Haynes, Richard; Barton, Jill; Cox, Jolyon; Murawska, Aleksandra; Murphy, Kevin; Lay, Michael; Armitage, Jane; Bowman, Louise

2016-06-13

Clinical trials require cost-effective methods for identifying, randomising, and following large numbers of people in order to generate reliable evidence. ASCEND (A Study of Cardiovascular Events iN Diabetes) is a randomised '2 × 2 factorial design' study of aspirin and omega-3 fatty acid supplements for the primary prevention of cardiovascular events in people with diabetes; this study used central disease registers and a mail-based approach to identify, randomise, and follow 15,000 people. In collaboration with UK consultants and general practitioners (GPs), researchers identified potentially eligible people with diabetes from centrally held registers (e.g. for retinopathy screening) and GP-held disease registers. Permission was obtained under section 251 of the National Health Service Act 2006 (previously section 60 of the NHS act 2001) to allow invitation letters to be generated centrally in the name of the holder of the register. In addition, with the collaboration of the National Institutes for Health Research (NIHR) Diabetes and Primary Care Research Networks (DRN and PCRN), general practices sent pre-assembled invitation packs to people with a diagnosis of diabetes. Invitation packs included a cover letter, screening questionnaire (with consent form), information leaflet, and a Freepost envelope. Eligible patients entered a 2-month, pre-randomisation, run-in phase on placebo tablets and were only randomised if they completed a randomisation form and remained willing and eligible at the end of the run-in. Follow-up is ongoing, using mail-based approaches that are being supplemented by central registry data. Information on approximately 600,000 people listed on 58 centrally held diabetes registers was obtained, and 300,188 potentially eligible patients were invited to join the study. In addition, 785 GP practices mailed invitations to 120,875 patients. A further 2,340 potential study participants were identified via other routes. In total, 423,403 people with diabetes were invited to take part; 26,462 entered the 2-month, pre-randomisation, run-in phase; and 15,480 were randomised. If sufficient numbers of potentially eligible patients can be identified centrally and the trial treatments do not require participants to attend clinics, the recruitment and follow-up of patients by mail is feasible and cost-effective. Wider use of these methods could allow more, large, randomised trials to be undertaken successfully and cost-effectively. Current Controlled Trials, ISRCTN60635500 , registered on 14 July 2005.

Posture-related distribution of hyperbaric bupivacaine in cerebro-spinal fluid is influenced by spinal needle characteristics.

PubMed

Mardirosoff, C; Dumont, L; Deyaert, M; Leconte, M

2001-07-01

No studies have evaluated the relationship between duration of time sitting and spinal needle type on the maximal spread of local anaesthetics. The few trials available have studied the influence of time spent sitting on the spread of anaesthesia without standardising spinal needle types, and have not found any effect. In this randomised, blinded study, 60 patients scheduled for elective orthopaedic surgery of the lower limbs were divided into 4 groups. With the patient sitting erect, 15 mg hyperbaric bupivacaine were injected in a standard manner through a 24G Sprotte or a 27G Whitacre needle and patients were placed supine after 1 min (24G/1 group and 27G/1 group) or 4 min (24G/4 group and 27G/4 group). Time to achieve maximum block height after injection was similar in all groups. Block height levels were significantly lower at all time points for the 24G/4 group. Maximum block heights were Th4 in the 24G/1, 27G/1 and 27G/4 groups, and Th6 in the 24G/4 group (P<0.0001). In a standard spinal anaesthesia procedure, when different lengths of time spent sitting are compared, spinal needle characteristics influence the maximum spread of hyperbaric bupivacaine. However, within the limits of our study, a two-segment difference in block height is too small to consider using spinal needles as valuable tools to control block height during spinal anaesthesia in our daily practice.

Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.

PubMed

Wilcox, Joanne; Waite, Chantelle; Tomlinson, Lyndsey; Driscoll, Joanne; Karim, Asra; Day, Edward; Sharif, Adnan

2016-08-22

Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ).

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.

PubMed

Vilgrain, Valérie; Pereira, Helena; Assenat, Eric; Guiu, Boris; Ilonca, Alina Diana; Pageaux, Georges-Philippe; Sibert, Annie; Bouattour, Mohamed; Lebtahi, Rachida; Allaham, Wassim; Barraud, Hélène; Laurent, Valérie; Mathias, Elodie; Bronowicki, Jean-Pierre; Tasu, Jean-Pierre; Perdrisot, Rémy; Silvain, Christine; Gerolami, René; Mundler, Olivier; Seitz, Jean-Francois; Vidal, Vincent; Aubé, Christophe; Oberti, Frédéric; Couturier, Olivier; Brenot-Rossi, Isabelle; Raoul, Jean-Luc; Sarran, Anthony; Costentin, Charlotte; Itti, Emmanuel; Luciani, Alain; Adam, René; Lewin, Maïté; Samuel, Didier; Ronot, Maxime; Dinut, Aurelia; Castera, Laurent; Chatellier, Gilles

2017-12-01

Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 ( 90 Y) resin microspheres in patients with hepatocellular carcinoma. SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90 Y-loaded resin microspheres 2-5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9-33·6) in the SIRT group and 28·1 months (20·0-35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7-9·9) in the SIRT group versus 9·9 months (8·7-11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94-1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. Sirtex Medical Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Block randomization versus complete randomization of human perception stimuli: is there a difference?

NASA Astrophysics Data System (ADS)

Moyer, Steve; Uhl, Elizabeth R.

2015-05-01

For more than 50 years, the U.S. Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) has been studying and modeling the human visual discrimination process as it pertains to military imaging systems. In order to develop sensor performance models, human observers are trained to expert levels in the identification of military vehicles. From 1998 until 2006, the experimental stimuli were block randomized, meaning that stimuli with similar difficulty levels (for example, in terms of distance from target, blur, noise, etc.) were presented together in blocks of approximately 24 images but the order of images within the block was random. Starting in 2006, complete randomization came into vogue, meaning that difficulty could change image to image. It was thought that this would provide a more statistically robust result. In this study we investigated the impact of the two types of randomization on performance in two groups of observers matched for skill to create equivalent groups. It is hypothesized that Soldiers in the Complete Randomized condition will have to shift their decision criterion more frequently than Soldiers in the Block Randomization group and this shifting is expected to impede performance so that Soldiers in the Block Randomized group perform better.

CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial.

PubMed

Stebbing, Justin; Baranau, Yauheni; Baryash, Valeriy; Manikhas, Alexey; Moiseyenko, Vladimir; Dzagnidze, Giorgi; Zhavrid, Edvard; Boliukh, Dmytro; Stroyakovskii, Daniil; Pikiel, Joanna; Eniu, Alexandru; Komov, Dmitry; Morar-Bolba, Gabriela; Li, Rubi K; Rusyn, Andriy; Lee, Sang Joon; Lee, Sung Young; Esteva, Francisco J

2017-07-01

CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer. In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m 2 on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m 2 ], epirubicin [75 mg/m 2 ], and cyclophosphamide [500 mg/m 2 ]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting. Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%). CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer. Celltrion Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial.

PubMed

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-02-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant differences between sleep variables at baseline. Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings. The side effect profile was low and not significantly different between the two arms.

A randomised controlled trial of benefit finding in caregivers: The Building Resources in Caregivers Study Protocol

PubMed Central

Brand, Charles; O’Connell, Brenda H

2015-01-01

Caregivers may engage in benefit finding, that is, an increase in perceived positive growth, as a cognitive strategy for coping with stress. The Building Resources in Caregivers study will compare effects of a brief benefit finding writing intervention with a control intervention. Caregivers of people with mental and physical disabilities will be randomised into either a benefit-writing group or a neutral writing group. Caregivers will complete measures relating to themselves and care-recipients (e.g. sociodemographics and illness type) and psychometric measures of benefit finding, distress and quality of life at three time points. Additionally, qualitative commentary on participation experiences will be gathered. PMID:28070362

[Renal denervation as treatment option for hypertension].

PubMed

Blankestijn, P J; Bots, M L

2016-01-01

The rationale behind catheter-based renal denervation is that afferent and efferent renal nerves play a role in the pathogenesis and maintenance of high blood pressure, and that this can be prevented by blocking the function of the renal nerves. Since the introduction of catheter-based renal denervation, several observational and a small number of randomised controlled trials have been conducted. The available evidence does not allow for a definitive conclusion regarding its efficacy. There have been no serious side-effects reported. The development of this treatment concept has not been finalised; new trials have just commenced or will start in the near future.

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

PubMed Central

Gilbert, Cameron; Wald, Ron; Bell, Chaim; Perl, Jeff; Juurlink, David; Beyene, Joseph; Shah, Prakesh S

2012-01-01

Objective To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. Study selection Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes. Results 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89). Conclusion Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels. PMID:22232539

Selectivity of beta-adrenergic stimulating and blocking agents.

PubMed

Löfdahl, C G; Svedmyr, N

1984-01-01

Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

Electrophysiologic and histologic observations of chronic atrioventricular block induced by closed-chest catheter desiccation with radiofrequency energy.

PubMed

Huang, S K; Bharati, S; Lev, M; Marcus, F I

1987-07-01

Direct-current or laser energy has been used to induce atrioventricular (AV) block, but certain complications associated with this type of energy have been reported. We have previously documented that radiofrequency (RF) energy can effectively and safely induce acute AV block in closed-chest dogs during the 4-7 days of follow-up. This study was undertaken to determine if the ablation was permanent and to define the chronic pathology and site of AV block. Complete AV block was successfully achieved in four dogs immediately after ablation with a bipolar "standard" RF output (750 kHz) delivered between the tip electrode of a standard 7F USCI catheter and an external patch electrode on the left lateral chest wall. During 2 months of follow-up, three dogs had persistent complete AV block with a stable escape rhythm; the other had persistent 2:1 AV block. Repeat His bundle recordings were performed at 2 months prior to sacrifice of the dogs. Supra-His AV block was noted in two dogs; His bundle potential could not be recorded in another two. Histologically, the damaged area was well delineated. In all animals, the AV node and, in some dogs, part of the His bundle were completely replaced by granulation tissue and/or cartilage. There was fatty infiltration and also chronic inflammatory cells around the lesions. Neither perforation, hemorrhage nor vacuolation was seen in the adjacent area. Thrombus was not present. It is concluded that RF energy can effectively achieve chronic AV block and produce well-circumscribed pathological lesions.

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial

PubMed Central

Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

2015-01-01

Summary Background Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. Methods In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Findings Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1.0 [IQR 0.3–2.2]vs2.2 [1.3–3.1]; p=0.020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in the placebo group died of fat embolism, and another patient in the placebo group withdrew from the trial to address long-standing digestive issues. All other adverse events were mild: short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone, flushing occurred in one patient given placebo, and anxiety occurred in another patient given placebo. Interpretation In boys with Duchenne muscular dystrophy and preserved ejection fraction, addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function. Early use of available drugs warrants consideration in this population at high risk of cardiac death, but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy. Funding BallouSkies, Parent Project for Muscular Dystrophy, US National Center for Advancing Translational Sciences, and US National Institutes of Health. PMID:25554404

Student Scheduling Choices and Time to Completion of a Two-Year Credential

ERIC Educational Resources Information Center

Rzeznik, Mark A.

2017-01-01

All students need to decide how to schedule their classes to complete their credential. This study examined three types of student scheduling choices: full-block scheduling, partial-block scheduling, and traditional scheduling to address two research questions: How do the choices students make in scheduling classes-using three scheduling…

76 FR 36143 - Central Utah Project Completion Act: Availability of Draft Environmental Assessment; Block Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... DEPARTMENT OF THE INTERIOR Central Utah Project Completion Act: Availability of Draft Environmental Assessment; Block Notice 1A, Heber Sub-Area Irrigation to M&I Water Conversion, Wasatch County, UT AGENCY: Department of the Interior, Office of the Assistant Secretary-- Water and Science. ACTION: Notice...

Fermion-scalar conformal blocks

DOE PAGES

Iliesiu, Luca; Kos, Filip; Poland, David; ...

2016-04-13

In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

No Additional Benefits of Block- Over Evenly-Distributed High-Intensity Interval Training within a Polarized Microcycle

PubMed Central

McGawley, Kerry; Juudas, Elisabeth; Kazior, Zuzanna; Ström, Kristoffer; Blomstrand, Eva; Hansson, Ola; Holmberg, Hans-Christer

2017-01-01

Introduction: The current study aimed to investigate the responses to block- versus evenly-distributed high-intensity interval training (HIT) within a polarized microcycle. Methods: Twenty well-trained junior cross-country skiers (10 males, age 17.6 ± 1.5 and 10 females, age 17.3 ± 1.5) completed two, 3-week periods of training (EVEN and BLOCK) in a randomized, crossover-design study. In EVEN, 3 HIT sessions (5 × 4-min of diagonal-stride roller-skiing) were completed at a maximal sustainable intensity each week while low-intensity training (LIT) was distributed evenly around the HIT. In BLOCK, the same 9 HIT sessions were completed in the second week while only LIT was completed in the first and third weeks. Heart rate (HR), session ratings of perceived exertion (sRPE), and perceived recovery (pREC) were recorded for all HIT and LIT sessions, while distance covered was recorded for each HIT interval. The recovery-stress questionnaire for athletes (RESTQ-Sport) was completed weekly. Before and after EVEN and BLOCK, resting saliva and muscle samples were collected and an incremental test and 600-m time-trial (TT) were completed. Results: Pre- to post-testing revealed no significant differences between EVEN and BLOCK for changes in resting salivary cortisol, testosterone, or IgA, or for changes in muscle capillary density, fiber area, fiber composition, enzyme activity (CS, HAD, and PFK) or the protein content of VEGF or PGC-1α. Neither were any differences observed in the changes in skiing economy, V˙O2max or 600-m time-trial performance between interventions. These findings were coupled with no significant differences between EVEN and BLOCK for distance covered during HIT, summated HR zone scores, total sRPE training load, overall pREC or overall recovery-stress state. However, 600-m TT performance improved from pre- to post-training, irrespective of intervention (P = 0.003), and a number of hormonal and muscle biopsy markers were also significantly altered post-training (P < 0.05). Discussion: The current study shows that well-trained junior cross-country skiers are able to complete 9 HIT sessions within 1 week without compromising total work done and without experiencing greater stress or reduced recovery over a 3-week polarized microcycle. However, the findings do not support block-distributed HIT as a superior method to a more even distribution of HIT in terms of enhancing physiological or performance adaptions. PMID:28659826

No Additional Benefits of Block- Over Evenly-Distributed High-Intensity Interval Training within a Polarized Microcycle.

PubMed

McGawley, Kerry; Juudas, Elisabeth; Kazior, Zuzanna; Ström, Kristoffer; Blomstrand, Eva; Hansson, Ola; Holmberg, Hans-Christer

2017-01-01

Introduction: The current study aimed to investigate the responses to block- versus evenly-distributed high-intensity interval training (HIT) within a polarized microcycle. Methods: Twenty well-trained junior cross-country skiers (10 males, age 17.6 ± 1.5 and 10 females, age 17.3 ± 1.5) completed two, 3-week periods of training (EVEN and BLOCK) in a randomized, crossover-design study. In EVEN, 3 HIT sessions (5 × 4-min of diagonal-stride roller-skiing) were completed at a maximal sustainable intensity each week while low-intensity training (LIT) was distributed evenly around the HIT. In BLOCK, the same 9 HIT sessions were completed in the second week while only LIT was completed in the first and third weeks. Heart rate (HR), session ratings of perceived exertion (sRPE), and perceived recovery (pREC) were recorded for all HIT and LIT sessions, while distance covered was recorded for each HIT interval. The recovery-stress questionnaire for athletes (RESTQ-Sport) was completed weekly. Before and after EVEN and BLOCK, resting saliva and muscle samples were collected and an incremental test and 600-m time-trial (TT) were completed. Results: Pre- to post-testing revealed no significant differences between EVEN and BLOCK for changes in resting salivary cortisol, testosterone, or IgA, or for changes in muscle capillary density, fiber area, fiber composition, enzyme activity (CS, HAD, and PFK) or the protein content of VEGF or PGC-1α. Neither were any differences observed in the changes in skiing economy, [Formula: see text] or 600-m time-trial performance between interventions. These findings were coupled with no significant differences between EVEN and BLOCK for distance covered during HIT, summated HR zone scores, total sRPE training load, overall pREC or overall recovery-stress state. However, 600-m TT performance improved from pre- to post-training, irrespective of intervention ( P = 0.003), and a number of hormonal and muscle biopsy markers were also significantly altered post-training ( P < 0.05). Discussion: The current study shows that well-trained junior cross-country skiers are able to complete 9 HIT sessions within 1 week without compromising total work done and without experiencing greater stress or reduced recovery over a 3-week polarized microcycle. However, the findings do not support block-distributed HIT as a superior method to a more even distribution of HIT in terms of enhancing physiological or performance adaptions.

A randomised controlled trial of a web-based educational program in child mental health for schoolteachers.

PubMed

Pereira, Celina Andrade; Wen, Chao Lung; Miguel, Eurípedes Constantino; Polanczyk, Guilherme V

2015-08-01

Children affected by mental disorders are largely unrecognised and untreated across the world. Community resources, including the school system and teachers, are important elements in actions directed to promoting child mental health and preventing and treating mental disorders, especially in low- and middle-income countries. We developed a web-based program to educate primary school teachers on mental disorders in childhood and conducted a cluster-randomised controlled trial to test the effectiveness of the web-based program intervention in comparison with the same program based on text and video materials only and to a waiting-list control group. All nine schools of a single city in the state of São Paulo, Brazil, were randomised to the three groups, and teachers completed the educational programs during 3 weeks. Data were analysed according to complete cases and intention-to-treat approaches. In terms of gains of knowledge about mental disorders, the web-based program intervention was superior to the intervention with text and video materials, and to the waiting-list control group. In terms of beliefs and attitudes about mental disorders, the web-based program intervention group presented less stigmatised concepts than the text and video group and more non-stigmatised concepts than the waiting-list group. No differences were detected in terms of teachers' attitudes. This study demonstrated initial data on the effectiveness of a web-based program in educating schoolteachers on child mental disorders. Future studies are necessary to replicate and extend the findings.

Brief psychological intervention after self-harm: randomised controlled trial from Pakistan.

PubMed

Husain, Nusrat; Afsar, Salahuddin; Ara, Jamal; Fayyaz, Hina; Rahman, Raza Ur; Tomenson, Barbara; Hamirani, Munir; Chaudhry, Nasim; Fatima, Batool; Husain, Meher; Naeem, Farooq; Chaudhry, Imran B

2014-06-01

Self-harm is a major risk factor for completed suicide. To determine the efficacy of a brief psychological intervention - culturally adapted manual-assisted problem-solving training (C-MAP) - delivered following an episode of self-harm compared with treatment as usual (TAU). The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation. A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU. The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention. Royal College of Psychiatrists.

Efficacy of Intravenous Haloperidol on the duration of Delirium and Coma in Critically Ill Patients (Hope-ICU): a Randomised, Placebo-Controlled Trial

PubMed Central

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2016-01-01

Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p= 0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs. six in the placebo) and QTc prolongation (seven in haloperidol group and six in the placebo group). No patient had a serious adverse event related to study drug. Interpretation These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for the short-term management of acute agitation. Funding National Institute for Health Research PMID:24461612

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

PubMed

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2013-09-01

Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0.53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. National Institute for Health Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Social network targeting to maximise population behaviour change: a cluster randomised controlled trial.

PubMed

Kim, David A; Hwong, Alison R; Stafford, Derek; Hughes, D Alex; O'Malley, A James; Fowler, James H; Christakis, Nicholas A

2015-07-11

Information and behaviour can spread through interpersonal ties. By targeting influential individuals, health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not. Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population-level behaviour change. In this cluster randomised trial, participants were recruited from villages of the Department of Lempira, Honduras. We blocked villages on the basis of network size, socioeconomic status, and baseline rates of water purification, for delivery of two public health interventions: chlorine for water purification and multivitamins for micronutrient deficiencies. We then randomised villages, separately for each intervention, to one of three targeting methods, introducing the interventions to 5% samples composed of either: randomly selected villagers (n=9 villages for each intervention); villagers with the most social ties (n=9); or nominated friends of random villagers (n=9; the last strategy exploiting the so-called friendship paradox of social networks). Participants and data collectors were not aware of the targeting methods. Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method. This trial is registered with ClinicalTrials.gov, number NCT01672580. Between Aug 4, and Aug 14, 2012, 32 villages in rural Honduras (25-541 participants each; total study population of 5773) received public health interventions. For each intervention, nine villages (each with 1-20 initial target individuals) were randomised, using a blocked design, to each of the three targeting methods. In nomination-targeted villages, 951 (74·3%) of 1280 available multivitamin tickets were redeemed compared with 940 (66·2%) of 1420 in randomly targeted villages and 744 (61·0%) of 1220 in indegree-targeted villages. All pairwise differences in redemption rates were significant (p<0·01) after correction for multiple comparisons. Targeting nominated friends increased adoption of the nutritional intervention by 12·2% compared with random targeting (95% CI 6·9-17·9). Targeting the most highly connected individuals, by contrast, produced no greater adoption of either intervention, compared with random targeting. Introduction of a health intervention to the nominated friends of random individuals can enhance that intervention's diffusion by exploiting intrinsic properties of human social networks. This method has the additional advantage of scalability because it can be implemented without mapping the network. Deployment of certain types of health interventions via network targeting, without increasing the number of individuals targeted or the resources used, could enhance the adoption and efficiency of those interventions, thereby improving population health. National Institutes of Health, The Bill & Melinda Gates Foundation, Star Family Foundation, and the Canadian Institutes of Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial.

PubMed

Diener, Markus K; Knebel, Phillip; Kieser, Meinhard; Schüler, Philipp; Schiergens, Tobias S; Atanassov, Vladimir; Neudecker, Jens; Stein, Erwin; Thielemann, Henryk; Kunz, Reiner; von Frankenberg, Moritz; Schernikau, Utz; Bunse, Jörg; Jansen-Winkeln, Boris; Partecke, Lars I; Prechtl, Gerald; Pochhammer, Julius; Bouchard, Ralf; Hodina, René; Beckurts, K Tobias E; Leißner, Lothar; Lemmens, Hans-Peter; Kallinowski, Friedrich; Thomusch, Oliver; Seehofer, Daniel; Simon, Thomas; Hyhlik-Dürr, Alexander; Seiler, Christoph M; Hackert, Thilo; Reissfelder, Christoph; Hennig, René; Doerr-Harim, Colette; Klose, Christina; Ulrich, Alexis; Büchler, Markus W

2014-07-12

Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 [14·8%] of 587) and the PDS II group (96 [16·1%] of 598; OR 0·91, 95% CI 0·66-1·25; p=0·64). Serious adverse events also did not differ between the groups-146 of 583 (25·0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22·9%) patients treated with PDS II; p=0·39). Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. Johnson & Johnson Medical Limited. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical and cost-effectiveness of compression hosiery versus compression bandages in treatment of venous leg ulcers (Venous leg Ulcer Study IV, VenUS IV): a randomised controlled trial.

PubMed

Ashby, Rebecca L; Gabe, Rhian; Ali, Shehzad; Adderley, Una; Bland, J Martin; Cullum, Nicky A; Dumville, Jo C; Iglesias, Cynthia P; Kang'ombe, Arthur R; Soares, Marta O; Stubbs, Nikki C; Torgerson, David J

2014-03-08

Drawbacks exist with the standard treatment (four-layer compression bandages) for venous leg ulcers. We have therefore compared the clinical effectiveness and cost-effectiveness of two-layer compression hosiery with the four-layer bandage for the treatment of such ulcers. We undertook this pragmatic, open, randomised controlled trial with two parallel groups in 34 centres in England and Northern Ireland. The centres were community nurse teams or services, family doctor practices, leg ulcer clinics, tissue viability clinics or services, and wound clinics. Participants were aged 18 years or older with a venous leg ulcer and an ankle brachial pressure index of at least 0·8, and were tolerant of high compression. We randomly allocated participants (1:1) to receive two-layer compression hosiery or a four-layer bandage, using a remote randomisation service and prevalidated computer randomisation program. Participants were stratified by ulcer duration and ulcer area with permuted blocks (block sizes four and six). The primary endpoint was time to ulcer healing, with a maximum follow-up of 12 months. Although participants and health-care providers were not masked to treatment allocation, the primary endpoint was measured by masked assessment of photographs. Primary analysis was intention to treat with Cox regression, with adjustment for ulcer area, ulcer duration, physical mobility, and centre. This trial is registered with the ISRCTN register, number ISRCTN49373072. We randomly allocated 457 participants to the two treatment groups: 230 to two-layer hosiery and 227 to the four-layer bandage, of whom 453 (230 hosiery and 223 bandage) contributed data for analysis. Median time to ulcer healing was 99 days (95% CI 84-126) in the hosiery group and 98 days (85-112) in the bandage group, and the proportion of ulcers healing was much the same in the two groups (70·9% hosiery and 70·4% bandage). More hosiery participants changed their allocated treatment (38·3% hosiery vs 27·0% bandage; p=0·02). 300 participants had 895 adverse events, of which 85 (9·5%) were classed as serious but unrelated to trial treatment. Two-layer compression hosiery is a viable alternative to the four-layer bandage-it is equally as effective at healing venous leg ulcers. However, a higher rate of treatment changes in participants in the hosiery group than in the bandage group suggests that hosiery might not be suitable for all patients. NIHR Health Technology Assessment programme (07/60/26). Copyright © 2014 Elsevier Ltd. All rights reserved.

The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature.

PubMed

van den Berg, Joyce; Gordon, Bernardus B M; Snijders, Marcus P M L; Vandenbussche, Frank P H A; Coppus, Sjors F P J

2015-12-01

Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation rates between 53% and 87%. Some reports suggest that sequential treatment with mifepristone and misoprostol leads to higher success rates than misoprostol alone. To evaluate the added value of mifepristone to current non-surgical treatment regimens in women with EPF we performed a systematic literature search. Electronic databases were searched: PubMed, Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. Clinical studies, both randomised and non-randomised trials, reporting on the added value of mifepristone to current non-surgical treatment regimens in women with EPF were included. Data of sixteen studies were extracted using a data extraction sheet (based on the Cochrane Consumers and Communication Review Group's data extraction template). The methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. In five randomised and eleven non-randomised trials, success rates of sequential treatment with mifepristone and misoprostol in case of EPF varied between 52% and 95%. Large heterogeneity existed in treatment regimens and comparators between studies. The existing evidence is insufficient to draw firm conclusions about the added value of mifepristone to misoprostol alone. A sufficiently powered randomised, double blinded placebo-controlled trial is urgently required to test whether, in EPF, the sequential combination of mifepristone with misoprostol is superior to misoprostol only. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial.

PubMed

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst; Brodersen, John

2012-01-01

To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales 'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and 'introvert', with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants-both the participants in the screen group and the control group. This negative impact was greatest for the control group.

Psychosocial consequences in the Danish randomised controlled lung cancer screening trial (DLCST).

PubMed

Rasmussen, Jakob F; Siersma, V; Pedersen, J H; Brodersen, J

2015-01-01

To measure the psychosocial consequences in the Danish lung cancer screening trial (DLCST) and compare those between the computed tomography (CT) group and the control group. This study was a single centre randomised controlled trial with five annual screening rounds. Healthy current or former heavy smokers aged 50-70 years (men and women) were randomised 1:1 to a CT group and a control group. Heavy smokers were defined by having smoked ≥20 pack years and former smokers by being abstinent ≤10 years. Both groups were invited annually to the screening clinic to complete the validated lung-cancer-specific questionnaire consequences of screening lung cancer (COS-LC). The CT group was also offered a low dose CT scan of the lungs. The COS-LC measures nine scales with psychosocial properties: Anxiety, Behaviour, Dejection, Negative impact on sleep, Self-blame, Focus on Airway Symptoms, Stigmatisation, Introvert, and Harm of Smoking. 4104 participants were randomised to the DLCST and the COS-LC completion rates for the CT group and the control group were 95.5% and 73.6%, respectively. There was a significant increase in negative psychosocial consequences from baseline through rounds 2-5 for both the CT group and the control group (mean increase >0, p<.0001 for 3 of 4 possible scales). During rounds 2-5 the control group experienced significantly more negative psychosocial consequences in seven of nine scales compared with the CT group (mean Δ score >0 and p<.033). Lung cancer CT-screening trials induced more negative psychosocial reactions in both the CT group and the control group compared with the baseline psychosocial profile. The CT group experienced less negative psychosocial consequences compared with the control group, which might be explained by reassurance among those with normal screening results. ClinicalTrials.gov: NCT00496977. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation and treatment of low and anxious mood in Chinese-speaking international students studying in Scotland: study protocol of a pilot randomised controlled trial.

PubMed

Zheng, Mengyi; McClay, Carrie-Anne; Wilson, Sarah; Williams, Christopher

2015-01-01

Low mood is a common mental health problem affecting up to 121 million people worldwide and is common in students, particularly international students. Cognitive behavioural therapy (CBT) is known to be effective as a treatment for low mood and anxiety when delivered one to one by an expert practitioner, however this can be expensive and many services have waiting lists and delayed access. A range of additional ways of increasing access to services includes the offer of online courses such as computerised CBT as a possible additional pathway for care. This project aims to test the feasibility of a pilot randomised controlled trial of an online CBT-based life skills course with Chinese-speaking international students experiencing low mood and anxiety. Chinese-speaking international students with symptoms of low mood and/or anxiety will be recruited from the University of Glasgow, Scotland. Participants will be remotely randomised to receive either immediate access (IA) or delayed access (DA) to a guided/supported online CBT-based life skills package, the "Living Life" package (Chinese version). Participants will be randomly assigned to IA or DA to the intervention. The primary end point will be at 3 months when the delayed group will be offered the intervention. Levels of depression, anxiety, social functioning and satisfaction will be assessed. This pilot study will test the trial design, ability to recruit, gather completed questionnaires, test drop-out rates and investigate completion and acceptability of the package. The study aims to reduce uncertainties about the delivery of a future substantive study and will also inform a sample size calculation for that subsequent substantive randomised controlled trial (RCT) which will be carried out to determine the effectiveness of the online package in improving low mood and anxiety in the Chinese-speaking student population. Current Controlled Trials ISRCTN30816908.

A multicentre prospective randomised study of single-incision mini-sling (Ajust®) versus tension-free vaginal tape-obturator (TVT-O™) in the management of female stress urinary incontinence: pain profile and short-term outcomes.

PubMed

Mostafa, Alyaa; Agur, Wael; Abdel-All, Mohamed; Guerrero, Karen; Lim, Chi; Allam, Mohamed; Yousef, Mohamed; N'Dow, James; Abdel-fattah, Mohamed

2012-11-01

To compare the postoperative pain profile, peri-operative details, and short-term patient-reported and objective success rates of single-incision mini-slings (SIMS) versus standard mid-urethral slings (SMUS). In a multicentre prospective randomised trial in six UK centres in the period between October 2009 and October 2010, 137 women were randomised to either adjustable SIMS (Ajust®, C. R. Bard Inc., NJ, USA), performed under local anaesthesia as an opt-out policy (n=69), or SMUS (TVT-O™, Ethicon Inc., Somerville, USA) performed under general anaesthesia (n=68). Randomisation was done through number-allocation software and using telephone randomisation. Postoperative pain profile (primary outcome) was assessed on a ten-point visual analogue scale at fixed time-points. Pre- and post operatively (4-6 months) women completed symptom severity, urgency perception scale (UPS), quality of life and sexual function questionnaires. In addition, women completed a Patient Global Impression of Improvement Questionnaire and underwent a cough stress test at 4-6 months follow up. Sample size calculation was performed and data were analysed using SPSS 18. Descriptive analyses are given and between-group comparisons were performed using chi-square, Fischer exact test and Mann-Whitney test as appropriate. Significance level was set at 5%. Women in the SIMS Ajust® group had a significantly lower postoperative pain profile up to 4 weeks (p=<0.001, 95% CI 1.151, 2.480). There was no significant difference in peri-operative complications between groups. All 137 women completed the 4-6 months follow-up. Patient-reported and objective cure rates were not significantly different: 85.5% versus 91.2% (p=0.443) and 90% versus 97% (p=0.165) between the SIMS Ajust® and TVT-O™ groups respectively. There was a trend towards higher rates of de novo urgency or worsening of pre-existing urgency in the SIMS Ajust® group (21.7% versus 8.8%) but this did not reach statistical significance (p=0.063). Women in the SIMS Ajust® group had shorter hospital stay (median (IQR) 3.65 (2.49, 4.96)) compared to (4.42 (3.16, 5.56)) the TVT-O™ group 95% CI (-0.026, 1.326), with significantly earlier return to normal activities (p=0.025) and to work (p=0.006). The adjustable single-incision mini-sling (Ajust®) is associated with a significantly improved postoperative pain profile and earlier return to work when compared to standard mid-urethral slings (TVT-O™), with encouraging results in patient-reported and objective success rates at short-term follow-up. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.

PubMed

Mathers, John C; Movahedi, Mohammad; Macrae, Finlay; Mecklin, Jukka-Pekka; Moeslein, Gabriela; Olschwang, Sylviane; Eccles, Diana; Evans, Gareth; Maher, Eamonn R; Bertario, Lucio; Bisgaard, Marie-Luise; Dunlop, Malcolm; Ho, Judy W C; Hodgson, Shirley; Lindblom, Annika; Lubinski, Jan; Morrison, Patrick J; Murday, Victoria; Ramesar, Raj; Side, Lucy; Scott, Rodney J; Thomas, Huw J W; Vasen, Hans; Gerdes, Anne-Marie; Barker, Gail; Crawford, Gillian; Elliott, Faye; Pylvanainen, Kirsi; Wijnen, Juul; Fodde, Riccardo; Lynch, Henry; Bishop, D Timothy; Burn, John

2012-12-01

Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer. In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was done with a block size of 16. Post-intervention, patients entered into double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint for this analysis was development of colorectal cancer in participants randomly assigned to resistant starch or resistant-starch placebo with both intention-to-treat and per-protocol analyses. This study is registered, ISRCTN 59521990. 463 patients were randomly assigned to receive resistant starch and 455 to receive resistant-starch placebo. At a median follow-up 52·7 months (IQR 28·9-78·4), 53 participants developed 61 primary colorectal cancers (27 of 463 participants randomly assigned to resistant starch, 26 of 455 participants assigned to resistant-starch placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 1·40 (95% CI 0·78-2·56; p=0·26) and Poisson regression accounting for multiple primary events gave an incidence rate ratio (IRR) of 1·15 (95% CI 0·66-2·00; p=0·61). For those completing 2 years of intervention, per-protocol analysis yielded a HR of 1·09 (0·55-2·19, p=0·80) and an IRR of 0·98 (0·51-1·88, p=0·95). No information on adverse events was gathered during post-intervention follow-up. Resistant starch had no detectable effect on cancer development in carriers of hereditary colorectal cancer. Dietary supplementation with resistant starch does not emulate the apparently protective effect of diets rich in dietary fibre against colorectal cancer. European Union, Cancer Research UK, Bayer Corporation, National Starch and Chemical Co, UK Medical Research Council, Newcastle Hospitals Trustees, Cancer Council of Victoria Australia, THRIPP South Africa, The Finnish Cancer Foundation, SIAK Switzerland, and Bayer Pharma. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study

PubMed Central

Ravandi, Farhad; Ritchie, Ellen K.; Sayar, Hamid; Lancet, Jeffrey E.; Craig, Michael D.; Vey, Norbert; Strickland, Stephen A.; Schiller, Gary J.; Jabbour, Elias; Erba, Harry P.; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M.; Cortes, Jorge; Roboz, Gail J.; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L.; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R.; Fox, Judith A.; Ward, Renee; Smith, Jennifer A.; Acton, Gary; Mehta, Cyrus; Stuart, Robert K.; Kantarjian, Hagop M.

2016-01-01

Summary Background Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML. Methods VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m2 IV days 1,4) plus cytarabine (1 g/m2 IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801). Findings Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6·1 months with pla/cyt (hazard ratio 0·87; unstratified log-rank p=0·061; stratified p=0·0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6·7 and 5·3 months; p=0·0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30·1% vs 16·3%, p<0·0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7·9% vs 6·6%; 60-day, 19·7% vs 19·4%). Treatment-related deaths occurred at any time in 18 patients (5·1%) with vos/cyt and 8 (2·3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Interpretation Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML, increasing CR rates with equivalent early mortality. These results support vos/cyt as an option for salvage therapy in AML patients. Funding Sunesis Pharmaceuticals PMID:26234174

The effect of motivational interviewing on glycaemic control and perceived competence of diabetes self-management in patients with type 1 and type 2 diabetes mellitus after attending a group education programme: a randomised controlled trial.

PubMed

Rosenbek Minet, L K; Wagner, L; Lønvig, E M; Hjelmborg, J; Henriksen, J E

2011-07-01

The aim of this study was to measure the efficacy of motivational interviewing (MI) compared with usual care on changes in glycaemic control and competence of diabetes self-management in patients with diabetes mellitus. Patients were eligible if they had type 1 or 2 diabetes mellitus, were over 18 years of age and had participated in a 4 day group education programme offered at a diabetes clinic at a university hospital in Denmark. Exclusion criteria included pregnancy, severe debilitating disease and cognitive deficit. Out of 469 patients who attended the group education programme, 349 patients were randomised to either a usual care control group or an intervention group, which received up to five individual counselling sessions in 1 year based on MI, in addition to usual care. A randomised parallel design was used and open-label allocation was done by random permuted blocks, with allocation concealment by sequentially numbered, sealed, opaque envelopes. The primary outcome was glycated haemoglobin (HbA(1c)). Analysis regarding measurements of glycated haemoglobin (HbA(1c)) and competence of self-management (using the Problem Areas in Diabetes Scale [PAID] and Perceived Competence for Diabetes Scale [PCDS]) was based on 298 participants followed for a 24 month period. Data were collected at the Department of Endocrinology at Odense University Hospital. Our hypotheses were that MI could: (1) reduce HbA(1c) levels; (2) increase self-efficacy; and (3) increase diabetes self-care, compared with usual care. Out of the 176 included in the control group and 173 in the intervention group, 153 and 145 were analysed in the groups, respectively. When using the baseline value as covariate there were no significant differences in change score between the two study groups with regard to mean level of HbA(1c) (0.131, p = 0.221), PAID scores (-1.793, p = 0.191) or PCDS scores (0.017, p = 0.903) at the 24 month follow-up, using a mixed effects regression model. The patients in the intervention group showed significantly higher levels of perceived competence in dealing with diabetes compared with the control group (mean change score = -0.387, p = 0.002) following 1 year of intervention. We were unable to demonstrate any benefit, over or above usual care, of MI in patients with diabetes who have just completed a diabetes education programme, and who have well-regulated diabetes. Clinical Trials NCT00555854.

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

PubMed

Lungenhausen, Margitta; Lange, Stefan; Maier, Christoph; Schaub, Claudia; Trampisch, Hans J; Endres, Heinz G

2007-11-22

The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews. A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes. Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points). Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires.

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

PubMed Central

Lungenhausen, Margitta; Lange, Stefan; Maier, Christoph; Schaub, Claudia; Trampisch, Hans J; Endres, Heinz G

2007-01-01

Background The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews. Methods A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes. Results Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points). Conclusion Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires. PMID:18034900

Online parent-targeted cognitive-behavioural therapy intervention to improve quality of life in families of young cancer survivors: study protocol for a randomised controlled trial.

PubMed

Wakefield, Claire E; Sansom-Daly, Ursula M; McGill, Brittany C; McCarthy, Maria; Girgis, Afaf; Grootenhuis, Martha; Barton, Belinda; Patterson, Pandora; Osborn, Michael; Lowe, Cherie; Anazodo, Antoinette; Miles, Gordon; Cohn, Richard J

2015-04-11

Due to advances in multimodal therapies, most children survive cancer. In addition to the stresses of diagnosis and treatment, many families are now navigating the challenges of survivorship. Without sufficient support, the ongoing distress that parents experience after their child's cancer treatment can negatively impact the quality of life and psychological wellbeing of all family members. The 'Cascade' (Cope, Adapt, Survive: Life after C AncEr) study is a three-arm randomised controlled trial to evaluate the feasibility and efficacy of a new intervention to improve the quality of life of parents of young cancer survivors. Cascade will be compared to a peer-support group control and a 6-month waitlist control. Parents (n = 120) whose child (under 16 years of age) has completed cancer treatment in the past 1 to 12 months will be recruited from hospitals across Australia. Those randomised to receive Cascade will participate in four, weekly, 90-minute online group sessions led live by a psychologist. Cascade involves peer discussion on cognitive-behavioural coping skills, including behavioural activation, thought challenging, mindfulness and acceptance, communication and assertiveness skills training, problem-solving and goal-setting. Participants randomised to peer support will receive four, weekly, 90-minute, live, sessions of non-directive peer support. Participants will complete measures at baseline, directly post-intervention, one month post-intervention, and 6 months post-intervention. The primary outcome will be parents' quality of life. Secondary outcomes include parent depression, anxiety, parenting self-agency, and the quality of life of children in the family. The child cancer survivor and all siblings aged 7 to 15 years will be invited to complete self-report quality of life measures covering physical, emotional, social and school-related domains. This article reviews the empirical rationale for group-based, online cognitive-behavioural therapy in parents of children who have recently finished cancer treatment. The potential challenges of delivering skills-based programs online are highlighted. Cascade's videoconferencing technology has the potential to address the geographic and psychological isolation of families after cancer treatment. Teaching parents coping skills as they resume their normal lives after their child's cancer may see long-term benefits for the quality of life of the family as a whole. ACTRN12613000270718 (registered 6 March 2013).

Conquer fear: protocol of a randomised controlled trial of a psychological intervention to reduce fear of cancer recurrence.

PubMed

Butow, Phyllis N; Bell, Melanie L; Smith, Allan B; Fardell, Joanna E; Thewes, Belinda; Turner, Jane; Gilchrist, Jemma; Beith, Jane; Girgis, Afaf; Sharpe, Louise; Shih, Sophy; Mihalopoulos, Cathrine

2013-04-23

Up to 70% of cancer survivors report clinically significant levels of fear of cancer recurrence (FCR). Despite the known negative impact of FCR on psychological wellbeing and quality of life, little research has investigated interventions for high FCR. Our team has developed and piloted a novel intervention (Conquer Fear) based on the Self-Regulatory Executive Function Model and Relational Frame Theory and is evaluating Conquer Fear in a randomised controlled trial (RCT). We aim to compare the efficacy and cost-efficacy of the Conquer Fear Intervention and relaxation training in reducing the impact of FCR. This study is a multi-centre RCT with 260 participants randomised either to the Conquer Fear Intervention or relaxation training. Both interventions will be delivered in five sessions over 10 weeks by trained psychologists, psychiatrists and social workers with five or more years experience in oncology. Conquer Fear sessions use attentional training, detached mindfulness, meta-cognitive therapy, values clarification and psycho-education to help patients change the way they regulate and respond to thoughts about cancer recurrence. Relaxation training includes training in progressive and passive muscle relaxation, meditative relaxation, visualisation and "quick relaxation" techniques. Relaxation was chosen to control for therapist time and attention and has good face-validity as an intervention. The primary outcome is fear of cancer recurrence. Secondary outcomes include distress, quality of life, unmet needs, and health care utilisation. Participants complete questionnaires prior to starting the intervention, immediately after completing the intervention, 3 and 6 months later. Eligible participants are early-stage breast or colorectal cancer survivors who have completed hospital-based treatment between 2 months and 5 years prior to study entry and report a score in the clinical range on the Fear of Cancer Recurrence Inventory. The biostatistician is blinded to group allocation and participants are blinded to which intervention is being evaluated. Randomisation is computer generated, stratified by therapist, and uses sequentially numbered sealed envelopes. If successful, the study will provide an evidence-based intervention to reduce psychological morbidity in cancer survivors, and reduce overall health care costs due to more appropriate use of follow-up care and other health services in this very large population. ACTRN12612000404820.

Conquer fear: protocol of a randomised controlled trial of a psychological intervention to reduce fear of cancer recurrence

PubMed Central

2013-01-01

Background Up to 70% of cancer survivors report clinically significant levels of fear of cancer recurrence (FCR). Despite the known negative impact of FCR on psychological wellbeing and quality of life, little research has investigated interventions for high FCR. Our team has developed and piloted a novel intervention (Conquer Fear) based on the Self-Regulatory Executive Function Model and Relational Frame Theory and is evaluating Conquer Fear in a randomised controlled trial (RCT). We aim to compare the efficacy and cost-efficacy of the Conquer Fear Intervention and relaxation training in reducing the impact of FCR. Methods/design This study is a multi-centre RCT with 260 participants randomised either to the Conquer Fear Intervention or relaxation training. Both interventions will be delivered in five sessions over 10 weeks by trained psychologists, psychiatrists and social workers with five or more years experience in oncology. Conquer Fear sessions use attentional training, detached mindfulness, meta-cognitive therapy, values clarification and psycho-education to help patients change the way they regulate and respond to thoughts about cancer recurrence. Relaxation training includes training in progressive and passive muscle relaxation, meditative relaxation, visualisation and “quick relaxation” techniques. Relaxation was chosen to control for therapist time and attention and has good face-validity as an intervention. The primary outcome is fear of cancer recurrence. Secondary outcomes include distress, quality of life, unmet needs, and health care utilisation. Participants complete questionnaires prior to starting the intervention, immediately after completing the intervention, 3 and 6 months later. Eligible participants are early-stage breast or colorectal cancer survivors who have completed hospital-based treatment between 2 months and 5 years prior to study entry and report a score in the clinical range on the Fear of Cancer Recurrence Inventory. The biostatistician is blinded to group allocation and participants are blinded to which intervention is being evaluated. Randomisation is computer generated, stratified by therapist, and uses sequentially numbered sealed envelopes. Discussion If successful, the study will provide an evidence-based intervention to reduce psychological morbidity in cancer survivors, and reduce overall health care costs due to more appropriate use of follow-up care and other health services in this very large population. Trial registration Trial registration: ACTRN12612000404820 PMID:23617696

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Kim, Dong Yeon; Cho, Sooyoung

2015-09-01

Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. A randomised, double-blind controlled trial. Single university tertiary care centre. One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

Successful emergency cardiac pacing and permanent pacemaker insertion in a preterm 29-week gestation hydropic baby with congenital complete heart block.

PubMed

Beake, Matthew Jonathan; Bhole, Vinay; Johnston, Tracey; Rasiah, Shree Vishna

2015-02-01

A preterm 29-week gestation baby was delivered because of gross foetal hydrops secondary to congenital complete heart block. Despite a poor prognosis, she survived stabilisation and received emergency epicardial pacing followed by permanent pacemaker insertion on day 13, weighing 1.2 kg.

Modifying Alcohol Consumption to Reduce Obesity (MACRO): development and feasibility trial of a complex community-based intervention for men.

PubMed

Crombie, Iain K; Cunningham, Kathryn B; Irvine, Linda; Williams, Brian; Sniehotta, Falko F; Norrie, John; Melson, Ambrose; Jones, Claire; Briggs, Andrew; Rice, Peter M; Achison, Marcus; McKenzie, Andrew; Dimova, Elena; Slane, Peter W

2017-04-01

Obese men who consume alcohol are at a greatly increased risk of liver disease; those who drink > 14 units of alcohol per week have a 19-fold increased risk of dying from liver disease. To develop an intervention to reduce alcohol consumption in obese men and to assess the feasibility of a randomised controlled trial (RCT) to investigate its effectiveness. The intervention was developed using formative research, public involvement and behaviour change theory. It was organised in two phases, comprising a face-to-face session with trained laypeople (study co-ordinators) followed by a series of text messages. Participants explored how alcohol consumption contributed to weight gain, both through direct calorie consumption and through its effect on increasing food consumption, particularly of high-calorie foodstuffs. Men were encouraged to set goals to reduce their alcohol consumption and to make specific plans to do so. The comparator group received an active control in the form of a conventional alcohol brief intervention. Randomisation was carried out using the secure remote web-based system provided by the Tayside Clinical Trials Unit. Randomisation was stratified by the recruitment method and restricted using block sizes of randomly varying lengths. Members of the public were involved in the development of all study methods. Men were recruited from the community, from primary care registers and by time-space sampling (TSS). The intervention was delivered in community settings such as the participant's home, community centres and libraries. Men aged 35-64 years who had a body mass index (BMI) of > 30 kg/m 2 and who drank > 21 units of alcohol per week. The screening methods successfully identified participants meeting the entry criteria. Trial recruitment was successful, with 69 men (36 from 419 approached in primary care, and 33 from 470 approached via TSS) recruited and randomised in 3 months. Of the 69 men randomised, 35 were allocated to the intervention group and 34 to the control group. The analysis was conducted on 31 participants from the intervention group and 30 from the control group. The participants covered a wide range of ages and socioeconomic statuses. The average alcohol consumption of the men recruited was 47.2 units per week, more than twice that of the entry criterion (> 21 units per week). Most (78%) engaged in binge drinking (> 8 units in a session) at least weekly. Almost all (95%) exceeded the threshold for a 19-fold increase in the risk of dying from liver disease (BMI of > 30 kg/m 2 and > 14 units of alcohol per week). Despite this, they believed that they were at low risk of harm from alcohol, possibly because they seldom suffered acute harms (e.g. hangovers) and made few visits to a general practitioner or hospital. The intervention was delivered with high fidelity. A high follow-up rate was achieved (98%) and the outcomes for the full RCT were measured. A process evaluation showed that participants engaged with the main components of the intervention. The acceptability of the study methods was high. This feasibility study developed a novel intervention and evaluated all of the stages of a RCT that would test the effectiveness of the intervention. The main stages of a trial were completed successfully: recruitment, randomisation, intervention delivery, follow-up and measurement of study outcomes. Most of the men recruited drank very heavily and were also obese. This places them at a very high risk of liver disease, making them a priority for intervention. A RCT to test the effectiveness and cost-effectiveness of the intervention. Current Controlled Trials ISRCTN55309164. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 19. See the NIHR Journals Library website for further project information.

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial.

PubMed

Schrijver, Edmée J M; de Vries, Oscar J; van de Ven, Peter M; Bet, Pierre M; Kamper, Ad M; Diepeveen, Sabine H A; van Marum, Rob J; van Strien, Astrid M; Anten, Sander; Lagaay, Anne M; Boelaarts, Leo; Bloemers, Frank W; Kramer, Mark H H; Nanayakkara, Prabath W B

2018-01-01

because the few randomised placebo-controlled trials investigating the potential role for prophylactic haloperidol in delirium prevention have focused on specific surgical populations, we investigated its efficacy and safety in acutely hospitalised older patients. this multi-centre, double-blind, stratified, block randomised, placebo-controlled trial was conducted at six Dutch hospitals. Patients age ≥70 years, acutely admitted through the emergency department for general medicine or surgical specialties and at risk for delirium were randomised (n = 245) to haloperidol or placebo 1 mg orally twice-daily (maximum of 14 doses) on top of standard nonpharmacological prevention strategies. The primary outcome was delirium incidence. Other endpoints included delirium severity and duration, drug safety and clinical outcomes. intention-to-treat analysis included 242 participants (calculated sample size n = 390, statistical power of current sample 59%) allocated to haloperidol (n = 118) or placebo (n = 124). In the haloperidol and placebo group, delirium incidence was 19.5 versus 14.5% (OR 1.43, 95% CI 0.72 to 2.78); median (IQR) delirium duration 4 (2, 5) versus 3 (1, 6) days (P = 0.366); maximum DRS-R-98 score 16 (9.8, 19.5) versus 10 (5.5, 22.5) (P = 0.549; 53.7% missing data); hospital LOS 7 (4, 10.3) versus 7 (5, 11.8) days (P = 0.343); 3-month mortality 9.9 versus 12.5% (OR 0.77, 95% CI 0.34 to 1.75), respectively. No treatment-limiting side effects were noted. prophylactic low-dose oral haloperidol did not reduce delirium incidence in acutely hospitalised older patients. Therefore, prophylactic use of haloperidol in this population is not recommended. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

PIMS (Positioning In Macular hole Surgery) trial - a multicentre interventional comparative randomised controlled clinical trial comparing face-down positioning, with an inactive face-forward position on the outcome of surgery for large macular holes: study protocol for a randomised controlled trial.

PubMed

Pasu, Saruban; Bunce, Catey; Hooper, Richard; Thomson, Ann; Bainbridge, James

2015-11-17

Idiopathic macular holes are an important cause of blindness. They have an annual incidence of 8 per 100,000 individuals, and prevalence of 0.2 to 3.3 per 1000 individuals with visual impairment. The condition occurs more frequently in adults aged 75 years or older. Macular holes can be repaired by surgery in which the causative tractional forces in the eye are released and a temporary bubble of gas is injected. To promote successful hole closure individuals may be advised to maintain a face-down position for up to 10 days following surgery. The aim of this study is to determine whether advice to position face-down improves the surgical success rate of closure of large (>400 μm) macular holes, and thereby reduces the need for further surgery. This will be a multicentre interventional, comparative randomised controlled clinical trial comparing face-down positioning with face-forward positioning. At the conclusion of standardised surgery across all sites, participants still eligible for inclusion will be allocated randomly 1:1 to 1 of the 2 treatment arms stratified by site, using random permuted blocks of size 4 or 6 in equal proportions. We will recruit 192 participants having surgery for large macular holes (>400 μm); 96 in each of the 2 arms of the study. The primary objective is to determine the impact of face-down positioning on the likelihood of closure of large (≥400 μm) full-thickness macular holes following surgery. This will be the first multicentre randomised control trial to investigate the value of face-down positioning following macular hole standardised surgery. UK CRN: 17966 (date of registration 26 November 2014).

Wordless intervention for people with epilepsy and learning disabilities (WIELD): a randomised controlled feasibility trial

PubMed Central

Mengoni, Silvana E; Gates, Bob; Parkes, Georgina; Wellsted, David; Barton, Garry; Ring, Howard; Khoo, Mary Ellen; Monji-Patel, Deela; Friedli, Karin; Zia, Asif; Irvine, Lisa; Durand, Marie-Anne

2016-01-01

Objective To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. Trial design A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Setting Epilepsy clinics in 1 English National Health Service (NHS) Trust. Participants Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Intervention Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. Outcome measures 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. Outcome The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. Conclusions All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. Trial registration number ISRCTN80067039. PMID:28186943

Wordless intervention for people with epilepsy and learning disabilities (WIELD): a randomised controlled feasibility trial.

PubMed

Mengoni, Silvana E; Gates, Bob; Parkes, Georgina; Wellsted, David; Barton, Garry; Ring, Howard; Khoo, Mary Ellen; Monji-Patel, Deela; Friedli, Karin; Zia, Asif; Irvine, Lisa; Durand, Marie-Anne

2016-11-10

To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Epilepsy clinics in 1 English National Health Service (NHS) Trust. Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. ISRCTN80067039. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

PC6 acupoint stimulation for the prevention of postcardiac surgery nausea and vomiting: a protocol for a two-group, parallel, superiority randomised clinical trial

PubMed Central

Cooke, Marie; Rickard, Claire; Rapchuk, Ivan; Shekar, Kiran; Marshall, Andrea P; Comans, Tracy; Doi, Suhail; McDonald, John; Spooner, Amy

2014-01-01

Introduction Postoperative nausea and vomiting (PONV) are frequent but unwanted complications for patients following anaesthesia and cardiac surgery, affecting at least a third of patients, despite pharmacological treatment. The primary aim of the proposed research is to test the efficacy of PC6 acupoint stimulation versus placebo for reducing PONV in cardiac surgery patients. In conjunction with this we aim to develop an understanding of intervention fidelity and factors that support, or impede, the use of PC6 acupoint stimulation, a knowledge translation approach. Methods and analysis 712 postcardiac surgery participants will be recruited to take part in a two-group, parallel, superiority, randomised controlled trial. Participants will be randomised to receive a wrist band on each wrist providing acupressure to PC six using acupoint stimulation or a placebo. Randomisation will be computer generated, use randomly varied block sizes, and be concealed prior to the enrolment of each patient. The wristbands will remain in place for 36 h. PONV will be evaluated by the assessment of both nausea and vomiting, use of rescue antiemetics, quality of recovery and cost. Patient satisfaction with PONV care will be measured and clinical staff interviewed about the clinical use, feasibility, acceptability and challenges of using acupressure wristbands for PONV. Ethics and dissemination Ethics approval will be sought from appropriate Human Research Ethics Committee/s before start of the study. A systematic review of the use of wrist acupressure for PC6 acupoint stimulation reported minor side effects only. Study progress will be reviewed by a Data Safety Monitoring Committee (DSMC) for nausea and vomiting outcomes at n=350. Dissemination of results will include conference presentations at national and international scientific meetings and publications in peer-reviewed journals. Study participants will receive a one-page lay-summary of results. Trial registration number Australian New Zealand Clinical Trials Registry—ACTRN12614000589684. PMID:25394818

Interventions for promoting smoke alarm ownership and function.

PubMed

DiGuiseppi, C; Higgins, J P

2001-01-01

Residential fires caused at least 67 deaths and 2,500 non-fatal injuries to children aged 0-16 in the United Kingdom in 1998. Smoke alarm ownership is associated with a reduced risk of residential fire death. We evaluated interventions to promote residential smoke alarms, to assess their effect on smoke alarm ownership, smoke alarm function, fires and burns and other fire-related injuries. We searched the Cochrane Controlled Trials Register, Cochrane Injuries Group database, MEDLINE, EMBASE, PsycLIT, CINAHL, ERIC, Dissertation Abstracts, International Bibliography of Social Sciences, ISTP, FIREDOC and LRC. Conference proceedings, published case studies, and bibliographies were systematically searched, and investigators and relevant organisations were contacted, to identify trials. Randomised, quasi-randomised or nonrandomised controlled trials completed or published after 1969 evaluating an intervention to promote residential smoke alarms. Two reviewers independently extracted data and assessed trial quality. We identified 26 trials, of which 13 were randomised. Overall, counselling and educational interventions had only a modest effect on the likelihood of owning an alarm (OR=1.26; 95% CI: 0.87 to 1.82) or having a functional alarm (OR=1.19; 0.85 to 1.66). Counselling as part of primary care child health surveillance had greater effects on ownership (OR=1.96; 1.03 to 3.72) and function (OR=1.72; 0.78 to 3.80). Results were sensitive to trial quality, however, and effects on fire-related injuries were not reported. In two non randomised trials, direct provision of free alarms significantly increased functioning alarms and reduced fire-related injuries. Media and community education showed little benefit in non randomised trials. Counselling as part of child health surveillance may increase smoke alarm ownership and function, but its effects on injuries are unevaluated. Community smoke alarm give-away programmes apparently reduce fire-related injuries, but these trials were not randomised and results must be interpreted cautiously. Further efforts to promote smoke alarms in primary care or through give-away programmes should be evaluated by adequately designed randomised controlled trials measuring injury outcomes.

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

PubMed

Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

2005-04-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.

Evaluation of the effects of an offer of a monetary incentive on the rate of questionnaire return during follow-up of a clinical trial: a randomised study within a trial.

PubMed

Hardy, Pollyanna; Bell, Jennifer L; Brocklehurst, Peter

2016-07-15

A systematic review on the use of incentives to promote questionnaire return in clinical trials suggest they are effective, but not all studies have sufficient funds to use them. Promising an incentive once data are returned can reduce the cost-burden of this approach, with possible further cost-savings if the offer were restricted to reminder letters only. This study aimed to evaluate the effect of promising a monetary incentive at first mailout versus a promise on reminder letters only. This was a randomised Study Within A Trial (SWAT) nested within BUMPES, a multicentre randomised controlled trial of maternal position in the late stage of labour in women with an epidural. The follow-up questionnaire asked for information on the women's health, wellbeing and health service use one year following the birth of their baby. Women who consented to be contacted were randomised to a promise of a monetary incentive at first mailout or a promise on reminder letters only. Women were given an option of completing the questionnaire on paper or on online. The incentive was posted out on receipt of a completed questionnaire. The primary outcome was the overall return rate, and secondary outcomes were the return rate without any chasing from the study office, and the total cost of the vouchers. A total of 1,029 women were randomised, 508 to the first mailout group and 518 to the reminder group. There was no evidence to suggest a difference between groups in the overall return rate (adjusted RR 1.03 (95 % CI 0.96 to 1.11), however the proportion returned without chasing was higher in the first mailout group (adjusted RR 1.22, 95 % CI 1.07 to 1.39). The total cost of the vouchers per participant was higher in the first mailout group (mean difference £4.56, 95 % CI £4.02 to £5.11). Offering a monetary incentive when a reminder is required could be cost-effective depending on the sample size of the study and the resources available to administer the reminder letters. The BUMPES Trial is registered with Current Controlled Trials: ISRCTN35706297 , 26(th) August 2009.

Clinical effectiveness of a patient decision aid to improve decision quality and glycaemic control in people with diabetes making treatment choices: a cluster randomised controlled trial (PANDAs) in general practice

PubMed Central

Mathers, Nigel; Ng, Chirk Jenn; Campbell, Michael Joseph; Colwell, Brigitte; Brown, Ian; Bradley, Alastair

2012-01-01

Objective To determine the effectiveness of a patient decision aid (PDA) to improve decision quality and glycaemic control in people with diabetes making treatment choices using a cluster randomised controlled trial (RCT). Design A cluster RCT. Setting 49 general practices in UK randomised into intervention (n=25) and control (n=24). Participants General practices Inclusion criteria: >4 medical partners; list size >7000; and a diabetes register with >1% of practice population. 191 practices assessed for eligibility, and 49 practices randomised and completed the study. Patients People with type 2 diabetes mellitus (T2DM) taking at least two oral glucose-lowering drugs with maximum tolerated dose with a glycosolated haemoglobin (HbA1c) greater than 7.4% (IFCC HbA1c >57 mmol/mol) or advised in the preceeding 6 months to add or consider changing to insulin therapy. Exclusion criteria: currently using insulin therapy; difficulty reading or understanding English; difficulty in understanding the purpose of the study; visual or cognitive impairment or mentally ill. A total of 182 assessed for eligibility, 175 randomised to 95 intervention and 80 controls, and 167 completion and analysis. Intervention Brief training of clinicians and use of PDA with patients in single consultation. Primary outcomes Decision quality (Decisional Conflict Scores, knowledge, realistic expectations and autonomy) and glycaemic control (glycosolated haemoglobin, HbA1c). Secondary outcomes Knowledge and realistic expectations of the risks and benefits of insulin therapy and diabetic complications. Results Intervention group: lower total Decisional Conflict Scores (17.4 vs 25.2, p<0.001); better knowledge (51.6% vs 28.8%, p<0.001); realistic expectations (risk of ‘hypo’, ‘weight gain’, ‘complications’; 81.0% vs 5.2%, 70.5% vs 5.3%, 26.3% vs 5.0% respectively, p<0.001); and were more autonomous in decision-making (64.1% vs 42.9%, p=0.012). No significant difference in the glycaemic control between the two groups. Conclusions Use of the PANDAs decision aid reduces decisional conflict, improves knowledge, promotes realistic expectations and autonomy in people with diabetes making treatment choices in general practice. ISRCTN Trials Register Number 14842077. PMID:23129571

Evaluation of community-level interventions to increase early initiation of antenatal care in pregnancy: protocol for the Community REACH study, a cluster randomised controlled trial with integrated process and economic evaluations.

PubMed

Sawtell, Mary; Sweeney, Lorna; Wiggins, Meg; Salisbury, Cathryn; Eldridge, Sandra; Greenberg, Lauren; Hunter, Rachael; Kaur, Inderjeet; McCourt, Christine; Hatherall, Bethan; Findlay, Gail; Morris, Joanne; Reading, Sandra; Renton, Adrian; Adekoya, Ruth; Green, Belinda; Harvey, Belinda; Latham, Sarah; Patel, Kanta; Vanlessen, Logan; Harden, Angela

2018-03-05

The provision of high-quality maternity services is a priority for reducing inequalities in health outcomes for mothers and infants. Best practice includes women having their initial antenatal appointment within the first trimester of pregnancy in order to provide screening and support for healthy lifestyles, well-being and self-care in pregnancy. Previous research has identified inequalities in access to antenatal care, yet there is little evidence on interventions to improve early initiation of antenatal care. The Community REACH trial will assess the effectiveness and cost-effectiveness of engaging communities in the co-production and delivery of an intervention that addresses this issue. The study design is a matched cluster randomised controlled trial with integrated process and economic evaluations. The unit of randomisation is electoral ward. The intervention will be delivered in 10 wards; 10 comparator wards will have normal practice. The primary outcome is the proportion of pregnant women attending their antenatal booking appointment by the 12th completed week of pregnancy. This and a number of secondary outcomes will be assessed for cohorts of women (n = approximately 1450 per arm) who give birth 2-7 and 8-13 months after intervention delivery completion in the included wards, using routinely collected maternity data. Eight hospitals commissioned to provide maternity services in six NHS trusts in north and east London and Essex have been recruited to the study. These trusts will provide anonymised routine data for randomisation and outcomes analysis. The process evaluation will examine intervention implementation, acceptability, reach and possible causal pathways. The economic evaluation will use a cost-consequences analysis and decision model to evaluate the intervention. Targeted community engagement in the research process was a priority. Community REACH aims to increase early initiation of antenatal care using an intervention that is co-produced and delivered by local communities. This pragmatic cluster randomised controlled trial, with integrated process and economic evaluation, aims to rigorously assess the effectiveness of this public health intervention, which is particularly complex due to the required combination of standardisation with local flexibility. It will also answer questions about scalability and generalisability. ISRCTN registry: registration number 63066975 . Registered on 18 August 2015.

Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study).

PubMed

Wylie, Gavin; Menz, Hylton B; McFarlane, Sarah; Ogston, Simon; Sullivan, Frank; Williams, Brian; Young, Zoe; Morris, Jacqui

2017-07-12

Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses 'all or most of the time'. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

Complete atrioventricular block as initial manifestation of systemic lupus erythematosus.

PubMed

Arce-Salinas, C A; Carmona-Escamilla, M A; Rodríguez-García, F

2009-01-01

Only a few cases of complete atrioventricular block (AVB) in adult lupus patients have been previously described, but only one as the initial manifestation. A 19-year-old woman who presented with seizures and loss of consciousness, was diagnosed with complete ABV and underwent pacemaker placement. Over the next weeks she developed serositis, joint, cutaneous, and renal involvement; positive antinuclear antibodies and high anti-SSA/Ro titers. This is the second case with AVB as a feature of SLE at onset. A review of previous complete AVB cases of adult SLE patients is presented.

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

Specificity and effector mechanisms of autoantibodies in congenital heart block.

PubMed

Wahren-Herlenius, Marie; Sonesson, Sven-Erik

2006-12-01

Complete congenital atrio-ventricular (AV) heart block develops in 2-5% of fetuses of Ro/SSA and La/SSB autoantibody-positive pregnant women. During pregnancy, the Ro/SSA and La/SSB antibodies are transported across the placenta and affect the fetus. Emerging data suggest that this happens by a two-stage process. In the first step, maternal autoantibodies bind fetal cardiomyocytes, dysregulate calcium homestasis and induce apoptosis in affected cells. This step might clinically correspond to a first-degree heart block, and be reversible. La/SSB antibodies can bind apoptotic cardiomyocytes and thus increase Ig deposition in the heart. The tissue damage could, as a second step, lead to spread of inflammation in genetically pre-disposed fetuses, progressing to fibrosis and calcification of the AV-node and subsequent complete congenital heart block. Early intrauterine treatment of an incomplete AV-block with fluorinated steroids has been shown to prevent progression of the heart block, making it clinically important to find specific markers to identify the high-risk pregnancies.

Effectiveness of Educational Poster on Knowledge of Emergency Management of Dental Trauma - Part 2: Cluster Randomised Controlled Trial for Secondary School Students

PubMed Central

Young, Cecilia; Wong, Kin Yau; Cheung, Lim K.

2014-01-01

Objective To investigate the effectiveness of educational poster on improving secondary school students' knowledge of emergency management of dental trauma. Methods A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnarie after 2 weeks. Results Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average. Conclusion Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong. Trial Registration HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457 PMID:25093728

Evaluating the effect of metronidazole plus amoxicillin-clavulanate versus amoxicillin-clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice.

PubMed

Ortiz, V; Klein, L; Channell, S; Simpson, B; Wright, B; Edwards, C; Gilbert, R; Day, R; Caddy, S L

2018-06-07

To investigate the benefit of supplementing amoxicillin-clavulanic acid therapy with metronidazole in dogs presenting to a primary care veterinary practice with severe haemorrhagic diarrhoea. Prospective randomised blinded trial on dogs presenting with haemorrhagic diarrhoea of less than 3 days duration to a primary care veterinary hospital and also requiring intravenous fluid therapy. Cases were randomised to receive either metronidazole or saline, in addition to standard supportive therapy consisting of amoxicillin-clavulanic acid, intravenous fluid therapy, buprenorphine and omeprazole. Treatment efficacy was measured by duration of hospitalisation and daily scoring of disease severity. Thirty-four cases successfully completed the trial. There was no significant difference in hospitalisation time between treatment groups (mean for dogs receiving metronidazole was 29.6 hours and for controls was 26.3 hours) nor in daily clinical scores. This study strongly suggests that addition of metronidazole is not an essential addition to amoxicillin-clavulanic acid therapy for treatment of severe cases of haemorrhagic diarrhoea in dogs. © 2018 British Small Animal Veterinary Association.

Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial.

PubMed

Zhu, Feng-Cai; Wurie, Alie H; Hou, Li-Hua; Liang, Qi; Li, Yu-Hua; Russell, James B W; Wu, Shi-Po; Li, Jing-Xin; Hu, Yue-Mei; Guo, Qiang; Xu, Wen-Bo; Wurie, Abdul R; Wang, Wen-Juan; Zhang, Zhe; Yin, Wen-Jiao; Ghazzawi, Manal; Zhang, Xu; Duan, Lei; Wang, Jun-Zhi; Chen, Wei

2017-02-11

A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose. We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone-China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18-50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 10 11 viral particles), low-dose vaccine (8·0 × 10 10 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed. During Oct 10-28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 [26%] in high-dose group and 31 [25%] in low-dose group) than in those receiving placebo (17 [14%]; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 [95% CI 976·6-1602·5] in low-dose group and 1728·4 [1459·4-2047·0] in high-dose group) and peaked at day 28 (1471·8 [1151·0-1881·8] and 2043·1 [1762·4-2368·4]), but declined quickly in the following months (223·3 [148·2-336·4] and 254·2 [185·0-349·5] at day 168). Geometric mean titres in the placebo group remained around 6·0-6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine. The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 10 10 viral particles was the optimal dose. Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study protocol: a stepped wedge cluster randomised controlled trial of a healthy lifestyle intervention for people attending residential substance abuse treatment.

PubMed

Kelly, Peter J; Baker, Amanda L; Deane, Frank P; Callister, Robin; Collins, Clare E; Oldmeadow, Christopher; Attia, John R; Townsend, Camilla J; Ingram, Isabella; Byrne, Gerard; Keane, Carol A

2015-05-03

Cardiovascular disease and cancer are leading causes of mortality for people with a history of alcohol or other substance use disorders. These chronic diseases share the same four primary behavioural risk factors i.e. excessive alcohol use, smoking, low intake of fruit and vegetables and physical inactivity. In addition to addressing problematic alcohol use, there is the potential for substance abuse treatment services to also address these other behaviours. Healthy Recovery is an 8-session group-based intervention that targets these multiple behavioural health risk factors and was developed specifically for people attending substance abuse treatment. This protocol describes a Cancer Institute NSW funded study that assesses the effectiveness of delivering Healthy Recovery for people who are attending residential alcohol and other substance abuse treatment. The study uses a stepped wedge randomised controlled design, where randomisation occurs at the service level. Participants will be recruited from residential rehabilitation programs provided by The Australian Salvation Army. All participants who (1) currently smoke tobacco and (2) are expected to be in the residential program for the duration of the 5-week intervention will be asked to participate in the study. Those participants residing at the facilities assigned to the treatment condition will complete Healthy Recovery. The intervention is manual guided and will be delivered over a 5-week period, with participants attending 8 group sessions. All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based, modified therapeutic community. Participants in the control condition will complete treatment as usual. Research staff blind to treatment allocation will complete the primary and secondary outcome assessments at baseline and then at weeks 8, 20 and 32 weeks post intervention. This study will provide comprehensive data on the effect of delivering a healthy lifestyle intervention (i.e. Healthy Recovery) within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. Australian and New Zealand Clinical Trials Register (ANZCTR): ACTRN12615000165583. Registered 19(th) February 2015.

A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials.gov: findings from a review of randomised controlled trials of rheumatoid arthritis.

PubMed

Kirkham, Jamie J; Clarke, Mike; Williamson, Paula R

2017-05-17

Objective  To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries. Design  Review of randomised trials. Setting  ClinicalTrials.gov. Subjects  273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science. Main outcome measure  The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications. Results  The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189). Conclusions  The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cognitive bias modification for social anxiety in adults who stutter: a feasibility study of a randomised controlled trial

PubMed Central

Gascoine, Sally; Carroll, Amy; Humby, Kate; Kingston, Mary; Shepstone, Lee; Risebro, Helen; Mackintosh, Bundy; Thompson, Tammy Davidson; Hodgekins, Jo

2017-01-01

Objective To determine the feasibility and acceptability of a computerised treatment for social anxiety disorder for adults who stutter including identification of recruitment, retention and completion rates, large cost drivers and selection of most appropriate outcome measure(s) to inform the design of a future definitive trial. Design Two-group parallel design (treatment vs placebo), double-blinded feasibility study. Participants: 31 adults who stutter. Intervention Attention training via an online probe detection task in which the stimuli were images of faces displaying neutral and disgusted expressions. Main outcome measures Psychological measures: Structured Clinical Interview Global Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic evaluation: resource use questionnaire; EuroQol three-dimension questionnaire. Acceptability: Likert Scale questionnaire of experience of trial, acceptability of the intervention and randomisation procedure. Results Feasibility of recruitment strategy was demonstrated. Participant feedback indicated that the intervention and definitive trial, including randomisation, would be acceptable to adults who stutter. Of the 31 participants who were randomised, 25 provided data at all three data collection points. Conclusions The feasibility study informed components of the intervention. Modifications to the design are needed before a definitive trial can be undertaken. Trial registration number I SRCTN55065978; Post-results. PMID:29061602

Transport for abciximab facilitated primary angioplasty versus on-site thrombolysis with a liberal rescue policy: the randomised Holland Infarction Study (HIS).

PubMed

Dieker, Hendrik-Jan; van Horssen, Elvira V; Hersbach, Ferry M R J; Brouwer, Marc A; van Boven, Ad J; van 't Hof, Arnoud W J; Aengevaeren, Wim R M; Verheugt, Freek W A; Bär, Frits W H M

2006-08-01

As of to date, the only large transportation trial comparing on-site fibrin-specific thrombolysis with transfer for primary angioplasty in patients presenting in a referral centre is the DANAMI-2 trial, with only 3% rescue angioplasty. The Holland Infarction Study (HIS) compared abciximab facilitated primary angioplasty (FP) with on-site fibrin-specific thrombolytic therapy (TT) with a liberal protocol-driven rescue angioplasty (transport to intervention centre in case < 50% ST resolution at 60 min). Patients in a referral centre without shock and < 4.5 h of chest pain presenting with ST-elevation having > or = 12 mm ST-segment shift were randomised to either strategy. Of the originally planned 900 patients only 48 were included due to suspension of financial funding. Death, recurrent MI and stroke at one year was 8% for the FP-group and 22% for the TT-group (p = 0.2). Two hours after randomisation the rates of complete ST-segment resolution (> or =70%) were 52% and 35%, respectively (p = 0.2). This prematurely discontinued randomised transportation trial shows favorable trends with respect to long-term clinical outcome and early ST-resolution for abciximab facilitated primary angioplasty. In view of the real world delays associated with interhospital transport for primary angioplasty, treatment strategies focusing on early fibrin-specific lysis with a liberal selective rescue policy are warranted.

Feasibility and potential effectiveness of a non-pharmacological multidisciplinary care programme for persons with generalised osteoarthritis: a randomised, multiple-baseline single-case study

PubMed Central

Kwakkenbos, Linda; Rietveld, Leonie; den Broeder, Alfons A; de Bie, Rob A; van den Ende, Cornelia H M

2012-01-01

Objectives To evaluate the feasibility and potential effectiveness of a 12-week, non-pharmacological multidisciplinary intervention in patients with generalised osteoarthritis (GOA). Design A randomised, concurrent, multiple-baseline single-case design. During the baseline period, the intervention period and the postintervention period, all participants completed several health outcomes twice a week on Visual Analogue Scales. Setting Rheumatology outpatient department of a specialised hospital in the Netherlands. Participants 1 man and four women (aged 51–76 years) diagnosed with GOA. Primary outcome measures To assess feasibility, the authors assessed the number of dropouts and adverse events, adherence rates and patients' satisfaction. Secondary outcome measures To assess the potential effectiveness, the authors assessed pain and self-efficacy using visual data inspection and randomisation tests. Results The intervention was feasible in terms of adverse events (none) and adherence rate but not in terms of participants' satisfaction with the intervention. Visual inspection of the data and randomisation testing demonstrated no effects on pain (p=0.93) or self-efficacy (p=0.85). Conclusions The results of the present study indicate that the proposed intervention for patients with GOA was insufficiently feasible and effective. The data obtained through this multiple-baseline study have highlighted several areas in which the therapy programme can be optimised. PMID:22815466

Streambank Protection Guidelines,

DTIC Science & Technology

1983-10-01

the types of rubble suitable for dumping on an eroding bank include broken pavement, bricks, building blocks , slag , and quarry waste. Large flat slabs...not provide any long-termn protection. blocks , and house brick. I rfbiae omrilgbo akt Completed gabion revetment made from prefabricated baskets...prevent pressure buildup that could cause revetment failure. BLOCKS . Precast cellular blocks can be ypi i .,, p no- , ,,, ,hag ,.,.,,,,t

Publication status of contemporary oncology randomised controlled trials worldwide.

PubMed

Chen, Yu-Pei; Liu, Xu; Lv, Jia-Wei; Li, Wen-Fei; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2016-10-01

Little is known about the extent of selective publication in contemporary oncology randomised controlled trials (RCTs) worldwide. This study aimed to evaluate the rates of publication and timely publication (within 24 months) for contemporary oncology RCTs from all over the world. We also investigated the trial characteristics associated with publication and timely publication. We identified all phase III oncology RCTs registered on ClinicalTrials.gov with a primary completion date between January 2008 and December 2012. We searched PubMed and EMBASE to identify publications. The final search date was 31 December 2015. Our primary outcome measure was the time to publication from the primary completion date to the date of primary publication in a peer-reviewed journal. We identified 598 completed oncology RCTs; overall, 398 (66.6%) had been published. For published trials, the median time to publication was 25 months (interquartile range, 16-37 months). Only 192 trials (32.1%) were published within 24 months. Timely publication was independently associated with trials completed late in 2012. Trials conducted in Asia and other regions were less likely to have timely publication, but trials conducted in different locations were all equally likely to be published. Industry- and NIH-funded trials were equally likely to be published timely or at any time after trial completion. Among 391 published trials with clear primary outcomes, there was a trend for timely publication of positive trials compared with negative trials. Despite the ethical obligations and societal expectations of disclosing findings promptly, oncology RCTs performed poorly. Copyright © 2016 Elsevier Ltd. All rights reserved.

A protocol for a randomised active-controlled trial to evaluate the effects of an online mindfulness intervention on executive control, critical thinking and key thinking dispositions in a university student sample.

PubMed

Noone, Chris; Hogan, Michael J

2016-04-12

While most modern research focuses on the clinical benefits of mindfulness, an emerging body of work suggests that mindfulness can facilitate self-regulation of everyday thinking in typically developing individuals. This behaviour is best captured using critical thinking assessments. The aim of this paper is to describe a rigorous, pre-registered study which will investigate the effect of an online mindfulness intervention on Executive Functioning, critical thinking skills and associated thinking dispositions. The design employed is a randomised-controlled 2 (condition) X 2 (time) parallel-group design which is explanatory in nature. A sample of at least 60 participants will be recruited from the pool of students at NUI Galway, with those between the ages of 18 and 65 with an adequate level of English included. Participants will be randomly assigned following screening, using block randomisation with a fixed block of 6 and a 1:1 ratio, to either the mindfulness meditation group or a sham meditation group. Both groups will be given access to the Headspace app. This is an app which provides guided meditations to users. Participants in each group will receive unique codes granting access to either the experimental or active-control intervention materials. Group allocation will be double-blinded. The primary outcome measures will assess mindfulness, executive functioning, critical thinking, actively open-minded thinking and need for cognition. Secondary outcome measures will assess eudaimonic and hedonic wellbeing, positive and negative affect, and real-world outcomes. These will be measured at baseline and at the end of the intervention. Manipulation checks will assess adherence to the intervention, meditation quality and task difficulty and enjoyment. If this intervention proves effective, it will show the potential of mindfulness practice to facilitate everyday critical thinking and should stimulate more interest in this line of research. If ineffective, claims regarding mindfulness and thinking skills should be tempered. This research was funded by a Galway Doctoral Research Scholarship awarded to the first author and was facilitated by Headspace Inc. who provided the intervention materials. The trial is registered in the ISRCTN registry and any protocol amendments will be recorded there (RCT ID: ISRCTN16588423. Registered 7th January 2016).

Biventricular non-compaction hypertrophic cardiomyopathy in association with congenital complete heart block and type I mitochondrial complex deficiency.

PubMed

Dhar, Ranjana; Reardon, William; McMahon, Colin J

2015-06-01

We report a baby girl with an antenatal diagnosis of biventricular non-compaction and complete heart block detected at 22 weeks' gestation. Postnatal echocardiography confirmed severe biventricular non-compaction hypertrophic cardiomyopathy, multiple muscular ventricular septal defects, and mild-moderate pulmonary valve stenosis. Skeletal muscle biopsy confirmed complex 1 mitochondrial respiratory chain deficiency. An epicardial VVI pacemaker was implanted on day 3 of life and revised at 7 years of age. She remains stable at 8 years of age following pacing and medical treatment with carvedilol, aspirin, co-enzyme Q10, and carnitine. This represents the first report of biventricular non-compaction hypertrophic phenotype in association with congenital complete heart block and complex 1 mitochondrial respiratory chain deficiency in a child.

High-dose versus low-dose local anaesthetic for transversus abdominis plane block post-Caesarean delivery analgesia: a meta-analysis.

PubMed

Ng, S C; Habib, A S; Sodha, S; Carvalho, B; Sultan, P

2018-02-01

The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I 2 =93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I 2 =98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Effects of Peer-Facilitated, Video-Based and Combined Peer-and-Video Education on Anxiety Among Patients Undergoing Coronary Angiography: Randomised controlled trial.

PubMed

Habibzadeh, Hosein; Milan, Zahra D; Radfar, Moloud; Alilu, Leyla; Cund, Audrey

2018-02-01

Coronary angiography can be stressful for patients and anxiety-caused physiological responses during the procedure increase the risk of dysrhythmia, coronary artery spasms and rupture. This study therefore aimed to investigate the effects of peer, video and combined peer-and-video training on anxiety among patients undergoing coronary angiography. This single-blinded randomised controlled clinical trial was conducted at two large educational hospitals in Iran between April and July 2016. A total of 120 adult patients undergoing coronary angiography were recruited. Using a block randomisation method, participants were assigned to one of four groups, with those in the control group receiving no training and those in the three intervention groups receiving either peer-facilitated training, video-based training or a combination of both. A Persian-language validated version of the State-Trait Anxiety Inventory was used to measure pre- and post-intervention anxiety. There were no statistically significant differences in mean pre-intervention anxiety scores between the four groups (F = 0.31; P = 0.81). In contrast, there was a significant reduction in post-intervention anxiety among all three intervention groups compared to the control group (F = 27.71; P <0.01); however, there was no significant difference in anxiety level in terms of the type of intervention used. Peer, video and combined peer-and-video education were equally effective in reducing angiography-related patient anxiety. Such techniques are recommended to reduce anxiety amongst patients undergoing coronary angiography in hospitals in Iran.

A prospective randomised trial of four-layer versus short stretch compression bandages for the treatment of venous leg ulcers.

PubMed Central

Scriven, J. M.; Taylor, L. E.; Wood, A. J.; Bell, P. R.; Naylor, A. R.; London, N. J.

1998-01-01

This trial was undertaken to examine the safety and efficacy of four-layer compared with short stretch compression bandages for the treatment of venous leg ulcers within the confines of a prospective, randomised, ethically approved trial. Fifty-three patients were recruited from a dedicated venous ulcer assessment clinic and their individual ulcerated limbs were randomised to receive either a four-layer bandage (FLB)(n = 32) or a short stretch bandage (SSB)(n = 32). The endpoint was a completely healed ulcer. However, if after 12 weeks of compression therapy no healing had been achieved, that limb was withdrawn from the study and deemed to have failed to heal with the prescribed bandage. Leg volume was measured using the multiple disc model at the first bandaging visit, 4 weeks later, and on ulcer healing. Complications arising during the study were recorded. Data from all limbs were analysed on an intention to treat basis; thus the three limbs not completing the protocol were included in the analysis. Of the 53 patients, 50 completed the protocol. At 1 year the healing rate was FLB 55% and SSB 57% (chi 2 = 0.0, df = 1, P = 1.0). Limbs in the FLB arm of the study sustained one minor complication, whereas SSB limbs sustained four significant complications. Leg volumes reduced significantly after 4 weeks of compression, but subsequent volume changes were insignificant. Ulcer healing rates were not influenced by the presence of deep venous reflux, post-thrombotic deep vein changes nor by ulcer duration. Although larger ulcers took longer to heal, the overall healing rates for large (> 10 cm2) and small (10 cm2 or less) ulcers were comparable. Four-layer and short stretch bandages were equally efficacious in healing venous ulcers independent of pattern of venous reflux, ulcer area or duration. FLB limbs sustained fewer complications than SSB. PMID:9682649

Evaluating the effectiveness of home exercise programmes using an online exercise prescription tool in children with cerebral palsy: protocol for a randomised controlled trial

PubMed Central

Williams, Sian A; Gucciardi, Daniel F; Bear, Natasha; Gibson, Noula

2018-01-01

Introduction Children with cerebral palsy (CP) and other neurodevelopmental disabilities often receive a home programme of exercises to assist in reaching their therapy goals. Adherence to exercise programmes is necessary to attain the level of practice required to achieve goals; however, adherence can be difficult to accomplish. In this paper, we describe the protocol for a randomised controlled trial to evaluate the effectiveness of delivering a home exercise programme to school-age children with disabilities using Physitrack, an online exercise prescription tool with a website or app interface. Methods and analysis Participants aged 6–17 years, with CP or other neurodevelopmental disabilities, receiving community physiotherapy services in Western Australia, will be recruited. Participants will be stratified by age and functional mobility and randomised to either the intervention group, who will complete an 8-week home exercise programme using Physitrack, or the control group, who will complete an 8-week exercise programme without Physitrack. Researcher blinding to group allocation, and participant blinding to outcome, will be maintained. The primary outcome measures are adherence to the home exercise programme with weekly collection of home exercise logs; achievement of individualised goals by phone interview before and after intervention; and correctness of exercise performance by collection and analysis of videos of participants performing home exercises. Secondary outcome measures include enjoyment of physical activity, confidence to complete exercise programme, preferred method of delivery of programme and usability of Physitrack. A sample size of 58 participants will be necessary to see an effect on home programme adherence. Data will be analysed using the intention-to-treat principle. Ethics and dissemination Ethical approval was obtained from Curtin University Human Research Ethics Committee in July 2016 (10391). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. Trial registration number ACTRN12616000743460; Pre-results. PMID:29362255

Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer

PubMed Central

Emery, Jon; Doorey, Juanita; Jefford, Michael; King, Madeleine; Pirotta, Marie; Hayne, Dickon; Martin, Andrew; Trevena, Lyndal; Lim, Tee; Constable, Roger; Hawks, Cynthia; Hyatt, Amelia; Hamid, Akhlil; Violet, John; Gill, Suki; Frydenberg, Mark; Schofield, Penelope

2014-01-01

Introduction Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer. Methods and analysis The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial. Ethics and dissemination Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria. Results of this phase II trial will be reported in peer-reviewed publications and in conference presentations. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12610000938000 PMID:24604487

Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy

PubMed Central

Brophy, Sinead; Burrows, Claire L; Brooks, Caroline; Gravenor, Michael B; Siebert, Stefan; Allen, Stephen J

2008-01-01

Background The clinical effectiveness of complementary and alternative medicines (CAMs) is widely debated because of a lack of clinical trials. The internet may provide an effective and economical approach for undertaking randomised controlled trials (RCTs) of low-risk interventions. We investigated whether the internet could be used to perform an internet-based RCT of a CAM fulfilling the revised CONSORT (Consolidated Standards of Reporting Trials) statement quality checklist for reporting of RCTs. A secondary aim was to examine the effect of probiotics compared to placebo in terms of well-being over 12 weeks. Methods People aged ≥18 years with confirmed spondyloarthropathy living in the United Kingdom with internet access were invited to participate in an internet-based RCT of probiotic compared to placebo for improving well-being and bowel symptoms. The intervention was a probiotic containing 4 strains of live bacteria or identical placebo taken by mouth daily for 3 months. The primary outcome measure was the performance of the trial according to the revised CONSORT statement. Results 147 people were randomised into the trial. The internet-based trial of the CAM fulfilled the revised CONSORT statement such as efficient blinding, allocation concealment, intention to treat analysis and flow of participants through the trial. Recruitment of the required number of participants was completed in 19 months. Sixty-five percent (96/147) completed the entire 3 months of the trial. The trial was low cost and demonstrated that in an intention to treat analysis, probiotics did not improve well-being or bowel symptoms. Conclusion The internet-based RCT proved to be a successful and economical method for examining this CAM intervention. Recruitment, adherence and completion rate were all similar to those reported with conventional RCTs but at a fraction of the cost. Internet-based RCTs can fulfil all the criteria of the revised CONSORT statement and are an appropriate method for studying low-risk interventions. Trial registration ISRCTN36133252 PMID:18190710

Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial.

PubMed

van Vilsteren, Frederike G I; Pouw, Roos E; Seewald, Stefan; Alvarez Herrero, Lorenza; Sondermeijer, Carine M T; Visser, Mike; Ten Kate, Fiebo J W; Yu Kim Teng, Karl C; Soehendra, Nib; Rösch, Thomas; Weusten, Bas L A M; Bergman, Jacques J G H M

2011-06-01

After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤ 5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. In patients with BO ≤ 5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.

Comparison of brief versus extended personalised feedback in an online intervention for cannabis users: Short-term findings of a randomised trial.

PubMed

Copeland, Jan; Rooke, Sally; Rodriquez, Dan; Norberg, Melissa M; Gibson, Lisa

2017-05-01

Previous studies have shown brief online self-help interventions to be a useful method of treating cannabis use and related problems; however, no studies have compared the effects of brief versus extended feedback for online brief intervention programs. The current study was a two arm randomised trial aimed at testing the short term effectiveness of a brief and extended feedback version of Grassessment, a brief online intervention for cannabis users that provides individualised feedback regarding use, motives, and harms. Participants (n=287) reporting at least one symptom of DSM IV cannabis abuse or dependence were recruited using online and offline advertising methods. Participants were randomised to receive either a brief or extended feedback version of the Grassessment program and were required to complete a one month follow up questionnaire. One hundred and ninety four participants completed the one month follow up. Wilcoxon analyses showed a significant decrease in past month quantity and frequency of cannabis use (ps<0.001; r=-0.41 and -0.40 respectively) and lower severity of dependence scores (p=0.002; r=-0.31) among those in the brief feedback condition. Participants in the extended feedback group also demonstrated significant decreases in patterns of use (ps<0.002; r=-0.39 and -0.33) but not severity of dependence (p=0.09; r=0.18). A Generalized Estimating Equation (GEE) analysis showed no significant interaction between length of feedback received and past month cannabis use frequency (p=0.78), quantity (p=0.73), or severity of dependence (p=0.47). This study adds support for the use of brief online self-complete interventions to reduce cannabis use and related problems in the short term. The findings suggest that in the case of the brief online screening and feedback program Grassessment, extended feedback does not lead to superior outcomes over brief feedback. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Pagliaro, Umberto; Raffaelli, Eugenia; Nieri, Michele

2015-01-01

The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure β-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were detected for chair-time (P = 0.3524), for VAS pain immediately after surgery (P = 0.5644), VAS pain after 1 week (P = 0.5074) and VAS pain after 2 weeks (P = 0.6950). A slight difference (0.24 mm, 95%CI from 0.0004 to 0.47, P = 0.0464) was detected in radiographic peri-implant bone loss favouring the CJ group. No significant differences, except for radiographic bone loss, were observed in this randomised controlled trial comparing anorganic bovine bone with collagen porcine membranes versus synthetic resorbable bone made of pure β-tricalcium phosphate with pericardium collagen membranes for horizontal augmentation.

Evaluation of a smartphone nutrition and physical activity application to provide lifestyle advice to pregnant women: The SNAPP randomised trial.

PubMed

Dodd, Jodie M; Louise, Jennie; Cramp, Courtney; Grivell, Rosalie M; Moran, Lisa J; Deussen, Andrea R

2018-01-01

Our objective was to evaluate the impact of a smartphone application as an adjunct to face-to-face consultations in facilitating dietary and physical activity change among pregnant women. This multicentre, nested randomised trial involved pregnant women with a body mass index ≥18.5 kg/m 2 , with a singleton pregnancy between 10 and 20 weeks' gestation, and participating in 2 pregnancy nutrition-based randomised trials across metropolitan Adelaide, South Australia. All women participating in the SNAPP trial received a comprehensive dietary, physical activity, and behavioural intervention, as part of the GRoW or OPTIMISE randomised trials. Women were subsequently randomised to either the "Lifestyle Advice Only Group," where women received the above intervention, or the "Lifestyle Advice plus Smartphone Application Group," where women were additionally provided access to the smartphone application. The primary outcome was healthy eating index (HEI) assessed by maternal food frequency questionnaire completed at trial entry, and 28 and 36 weeks' gestation. Analyses were performed using intention-to-treat principles, with statistical significance at p = .05. One hundred sixty-two women participated: 77 allocated to the Lifestyle Advice plus Smartphone Application Group and 85 to the Lifestyle Advice Only Group. Mean difference in HEI score at 28 weeks of pregnancy was 0.01 (CI [-2.29, 2.62]) and at 36 weeks of pregnancy -1.16 (CI [-4.60, 2.28]). There was no significant additional benefit from the provision of the smartphone application in improving HEI score (p = .452). Although all women improved dietary quality across pregnancy, use of the smartphone application was poor. Our findings do not support addition of the smartphone application. © 2017 John Wiley & Sons Ltd.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial

PubMed Central

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst

2012-01-01

Objective To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. Method The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. Results There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales ‘anxiety’, ‘behaviour’, ‘dejection’, ‘self-blame’, ‘focus on airway symptoms’ and ‘introvert’, with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Conclusions Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants—both the participants in the screen group and the control group. This negative impact was greatest for the control group. PMID:22382119

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

PubMed Central

Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

2016-01-01

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.

PubMed

Schäfer, Rebekka; Strnad, Vratislav; Polgár, Csaba; Uter, Wolfgang; Hildebrandt, Guido; Ott, Oliver J; Kauer-Dorner, Daniela; Knauerhase, Hellen; Major, Tibor; Lyczek, Jaroslaw; Guinot, Jose Luis; Dunst, Jürgen; Miguelez, Cristina Gutierrez; Slampa, Pavel; Allgäuer, Michael; Lössl, Kristina; Kovács, György; Fischedick, Arnt-René; Fietkau, Rainer; Resch, Alexandra; Kulik, Anna; Arribas, Leo; Niehoff, Peter; Guedea, Ferran; Schlamann, Annika; Gall, Christine; Polat, Bülent

2018-04-20

Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. German Cancer Aid. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multiphase complete exchange on a circuit switched hypercube

NASA Technical Reports Server (NTRS)

Bokhari, Shahid H.

1991-01-01

On a distributed memory parallel computer, the complete exchange (all-to-all personalized) communication pattern requires each of n processors to send a different block of data to each of the remaining n - 1 processors. This pattern is at the heart of many important algorithms, most notably the matrix transpose. For a circuit switched hypercube of dimension d(n = 2(sup d)), two algorithms for achieving complete exchange are known. These are (1) the Standard Exchange approach that employs d transmissions of size 2(sup d-1) blocks each and is useful for small block sizes, and (2) the Optimal Circuit Switched algorithm that employs 2(sup d) - 1 transmissions of 1 block each and is best for large block sizes. A unified multiphase algorithm is described that includes these two algorithms as special cases. The complete exchange on a hypercube of dimension d and block size m is achieved by carrying out k partial exchange on subcubes of dimension d(sub i) Sigma(sup k)(sub i=1) d(sub i) = d and effective block size m(sub i) = m2(sup d-di). When k = d and all d(sub i) = 1, this corresponds to algorithm (1) above. For the case of k = 1 and d(sub i) = d, this becomes the circuit switched algorithm (2). Changing the subcube dimensions d, varies the effective block size and permits a compromise between the data permutation and block transmission overhead of (1) and the startup overhead of (2). For a hypercube of dimension d, the number of possible combinations of subcubes is p(d), the number of partitions of the integer d. This is an exponential but very slowly growing function and it is feasible over these partitions to discover the best combination for a given message size. The approach was analyzed for, and implemented on, the Intel iPSC-860 circuit switched hypercube. Measurements show good agreement with predictions and demonstrate that the multiphase approach can substantially improve performance for block sizes in the 0 to 160 byte range. This range, which corresponds to 0 to 40 floating point numbers per processor, is commonly encountered in practical numeric applications. The multiphase technique is applicable to all circuit-switched hypercubes that use the common e-cube routing strategy.

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

2016-03-01

Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70 invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive disease-free survival rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [<1%] vs grade 3, n=23 [2%] in the placebo group), vomiting (grade 3, n=47 [3%] vs n=5 [<1%]), and nausea (grade 3, n=26 [2%] vs n=2 [<1%]). QT prolongation occurred in 49 (3%) patients given neratinib and 93 (7%) patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 (1%) and 15 (1%) patients, respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 (6%) patients in the placebo group. Seven (<1%) deaths (four patients in the neratinib group and three patients in the placebo group) unrelated to disease progression occurred after study drug discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were attributed to study treatment in either group. Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer. Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained. Wyeth, Pfizer, Puma Biotechnology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Complete atrioventricular block following mediastinal irradiation: A report of six cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slama, M.S.; Le Guludec, D.; Sebag, C.

1991-07-01

Complete atrioventricular block (AVB) following radiotherapy has been reported rarely, usually after high dose mediastinal irradiation for Hodgkin's disease or lung or breast carcinoma. The authors report six new cases of episodic complete infranodal AVB, requiring permanent pacemaker implantation. The mean age was 48-years old (ranging from 25-60) at the first Adams Stokes attack, mean delay was 12 years after irradiation (10-18), and mean radiation dose was 5,200 rads (4,000-6,500). All patients had abnormal interval electrocardiograms (right bundle branch block in two, left bundle branch block in three, alternating left and right bundle branch block in one). Electrocardiograms during themore » episode of AVB or Holter recordings were consistent with infranodal block in all patients; electrophysiological study performed in five patients confirmed infranodal AVB in four, and one was normal. Pericardial disease was constant, which included pericardial constriction in four patients. Two patients died after failure of pericardiectomy to improve congestive heart failure, due to epicardial, myocardial, and endocardial involvement. Noncardiac mediastinal lesions were present in four cases. Since this delayed complication may occur in patients of such age that the relation between the AVB and the chest irradiation is questionable, they propose the following etiologic criteria; high radiation dose (over 4,000 rads); delay of 10 years or more; abnormal interval tracings; pericardial involvement; and associated cardiac or mediastinal radiation-induced lesions.« less

Young Children's Block Play and Mathematical Learning

ERIC Educational Resources Information Center

Park, Boyoung; Chae, Jeong-Lim; Boyd, Barbara Foulks

2008-01-01

This qualitative study investigated young children's mathematical engagement in play with wooden unit blocks. Two boys, ages 6 and 7, were independently observed completing the task of filling outlined regions with the various sets of blocks. Three major mathematical actions were observed: categorizing geometric shapes, composing a larger shape…

Impact of online education on intern behaviour around joint commission national patient safety goals: a randomised trial.

PubMed

Shaw, Tim J; Pernar, Luise I; Peyre, Sarah E; Helfrick, John F; Vogelgesang, Kaitlin R; Graydon-Baker, Erin; Chretien, Yves; Brown, Elizabeth J; Nicholson, James C; Heit, Jeremy J; Co, John Patrick T; Gandhi, Tejal

2012-10-01

To compare the effectiveness of two types of online learning methodologies for improving the patient-safety behaviours mandated in the Joint Commission National Patient Safety Goals (NPSG). This randomised controlled trial was conducted in 2010 at Massachusetts General Hospital and Brigham and Women's Hospital (BWH) in Boston USA. Incoming interns were randomised to either receive an online Spaced Education (SE) programme consisting of cases and questions that reinforce over time, or a programme consisting of an online slide show followed by a quiz (SQ). The outcome measures included NPSG-knowledge improvement, NPSG-compliant behaviours in a simulation scenario, self-reported confidence in safety and quality, programme acceptability and programme relevance. Both online learning programmes improved knowledge retention. On four out of seven survey items measuring satisfaction and self-reported confidence, the proportion of SE interns responding positively was significantly higher (p<0.05) than the fraction of SQ interns. SE interns demonstrated a mean 4.79 (36.6%) NPSG-compliant behaviours (out of 13 total), while SQ interns completed a mean 4.17 (32.0%) (p=0.09). Among those in surgical fields, SE interns demonstrated a mean 5.67 (43.6%) NPSG-compliant behaviours, while SQ interns completed a mean 2.33 (17.9%) (p=0.015). Focus group data indicates that SE was more contextually relevant than SQ, and significantly more engaging. While both online methodologies improved knowledge surrounding the NPSG, SE was more contextually relevant to trainees and was engaging. SE impacted more significantly on both self-reported confidence and the behaviour of surgical residents in a simulated scenario.

A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.

PubMed

Semb, Gunvor; Enemark, Hans; Friede, Hans; Paulin, Gunnar; Lilja, Jan; Rautio, Jorma; Andersen, Mikael; Åbyholm, Frank; Lohmander, Anette; Shaw, William; Mølsted, Kirsten; Heliövaara, Arja; Bolund, Stig; Hukki, Jyri; Vindenes, Hallvard; Davenport, Peter; Arctander, Kjartan; Larson, Ola; Berggren, Anders; Whitby, David; Leonard, Alan; Neovius, Erik; Elander, Anna; Willadsen, Elisabeth; Bannister, R Patricia; Bradbury, Eileen; Henningsson, Gunilla; Persson, Christina; Eyres, Philip; Emborg, Berit; Kisling-Møller, Mia; Küseler, Annelise; Granhof Black, Birthe; Schöps, Antje; Bau, Anja; Boers, Maria; Andersen, Helene Søgaard; Jeppesen, Karin; Marxen, Dorte; Paaso, Marjukka; Hölttä, Elina; Alaluusua, Suvi; Turunen, Leena; Humerinta, Kirsti; Elfving-Little, Ulla; Tørdal, Inger Beate; Kjøll, Lillian; Aukner, Ragnhild; Hide, Øydis; Feragen, Kristin Billaud; Rønning, Elisabeth; Skaare, Pål; Brinck, Eli; Semmingsen, Ann-Magritt; Lindberg, Nina; Bowden, Melanie; Davies, Julie; Mooney, Jeanette; Bellardie, Haydn; Schofield, Nina; Nyberg, Jill; Lundberg, Maria; Karsten, Agneta Linder-Aronson; Larson, Margareta; Holmefjord, Anders; Reisæter, Sigvor; Pedersen, Nina-Helen; Rasmussen, Therese; Tindlund, Rolf; Sæle, Paul; Blomhoff, Reidunn; Jacobsen, Gry; Havstam, Christina; Rizell, Sara; Enocson, Lars; Hagberg, Catharina; Najar Chalien, Midia; Paganini, Anna; Lundeborg, Inger; Marcusson, Agneta; Mjönes, Anna-Britta; Gustavsson, Annica; Hayden, Christine; McAleer, Eilish; Slevan, Emma; Gregg, Terry; Worthington, Helen

2017-02-01

Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project. Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes. Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years. The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series. ISRCTN29932826.

The impact of a point-of-care testing device on CVD risk assessment completion in New Zealand primary-care practice: A cluster randomised controlled trial and qualitative investigation.

PubMed

Wells, Sue; Rafter, Natasha; Kenealy, Timothy; Herd, Geoff; Eggleton, Kyle; Lightfoot, Rose; Arcus, Kim; Wadham, Angela; Jiang, Yannan; Bullen, Chris

2017-01-01

To assess the effect of a point of care (POC) device for testing lipids and HbA1c in addition to testing by community laboratory facilities (usual practice) on the completion of cardiovascular disease (CVD) risk assessments in general practice. We conducted a pragmatic, cluster randomised controlled trial in 20 New Zealand general practices stratified by size and rurality and randomised to POC device plus usual practice or usual practice alone (controls). Patients aged 35-79 years were eligible if they met national guideline criteria for CVD risk assessment. Data on CVD risk assessments were aggregated using a web-based decision support programme common to each practice. Data entered into the on-line CVD risk assessment form could be saved pending blood test results. The primary outcome was the proportion of completed CVD risk assessments. Qualitative data on practice processes for CVD risk assessment and feasibility of POC testing were collected at the end of the study by interviews and questionnaire. The POC testing was supported by a comprehensive quality assurance programme. A CVD risk assessment entry was recorded for 7421 patients in 10 POC practices and 6217 patients in 10 control practices; 99.5% of CVD risk assessments had complete data in both groups (adjusted odds ratio 1.02 [95%CI 0.61-1.69]). There were major external influences that affected the trial: including a national performance target for CVD risk assessment and changes to CVD guidelines. All practices had invested in systems and dedicated staff time to identify and follow up patients to completion. However, the POC device was viewed by most as an additional tool rather than as an opportunity to review practice work flow and leverage the immediate test results for patient education and CVD risk management discussions. Shortly after commencement, the trial was halted due to a change in the HbA1c test assay performance. The trial restarted after the manufacturing issue was rectified but this affected the end use of the device. Performance incentives and external influences were more powerful modifiers of practice behaviours than the POC device in relation to CVD risk assessment completion. The promise of combining risk assessment, communication and management within one consultation was not realised. With shifts in policy focus, the utility of POC devices for patient engagement in CVD preventive care may be demonstrated if fully integrated into the clinical setting. Australian New Zealand Clinical Trials Registry ACTRN12613000607774.

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

PubMed

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis). Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Trial registration Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14. PMID:22540770

Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

PubMed

Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

2009-05-16

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272). This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy. Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

Action to Support Practices Implement Research Evidence (ASPIRE): protocol for a cluster-randomised evaluation of adaptable implementation packages targeting 'high impact' clinical practice recommendations in general practice.

PubMed

Willis, Thomas A; Hartley, Suzanne; Glidewell, Liz; Farrin, Amanda J; Lawton, Rebecca; McEachan, Rosemary R C; Ingleson, Emma; Heudtlass, Peter; Collinson, Michelle; Clamp, Susan; Hunter, Cheryl; Ward, Vicky; Hulme, Claire; Meads, David; Bregantini, Daniele; Carder, Paul; Foy, Robbie

2016-02-29

There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice. The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences. ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability. ISRCTN91989345.

Characteristics of cholinoreceptors on identified TAN neurons of the ground snail Achatina fulica.

PubMed

Stepanov, I I; Losev, N A

2000-01-01

The characteristics of cholinoreceptors located on neurons TAN1, TAN2, and TAN3 of the ground snail Achatina fulica were studied by incubation of the central ganglia in a bath with cholinotropic preparations during intracellular recording of background neuron spike activity. Acetylcholine, nicotine, the selective n-cholinoreceptor agonist suberyldicholine, and the selective n-cholinoreceptor agonist 5-methylfurmethide concentration-dependently inhibited background spike activity to the level of complete blockade at concentrations of 500 microM. The m-cholinoblocker metamizil (500 microM) completely prevented the inhibitory activity of concentrations of 5-methylfurmethide of up to 500 microM. The central n-cholinoblocker etherophen (500 microM) completely blocked the inhibitory activity of 500 microM suberyldicholine. However, metamizil and etherophen added separately only partially decreased the inhibitory effects of acetylcholine but could not completely block the effect of acetylcholine. At the same time, mixtures of metamizil and etherophen (500 microM each) completely blocked the inhibition of background spike activity induced by acetylcholine. These results show that both classes of cholinoreceptors act on TAN neurons in the same direction.

Supraclavicular block versus interscalene brachial plexus block for shoulder surgery: A meta-analysis of clinical control trials.

PubMed

Guo, C W; Ma, J X; Ma, X L; Lu, B; Wang, Y; Tian, A X; Sun, L; Wang, Y; Dong, B C; Teng, Y B

2017-09-01

The ultrasound-guided interscalene block (ISB) has been considered a standard technique in managing pain after shoulder surgery. However, this method was associated with the incidence of hemi-diaphragmatic paresis. In contrast to ISB, supraclavicular block (SCB) was suggested to provide effective anaesthesia for shoulder surgery with a low rate of side-effects. Thus, we performed a meta-analysis of randomised controlled trials (RCTs) to compare SCB with ISB for evaluating the efficacy and safety. The literature was searched from PubMed, Wiley Online Library, EMBASE, and the Cochrane Library by two reviewers up to April 2017. All available RCTs written in English that met the criteria were included. Two authors pulled data from relevant articles and assessed the quality with the Cochrane Handbook. Review Manager 5.3 software was used to analyse the data. Five RCTs and one prospective clinical study met the eligibility criteria and were included in the meta-analysis. We considered that there were no statistically significant differences between supraclavicular and interscalene groups in procedural time (P = 0.81), rescue analgesia (P = 0.53), and dyspnoea (P = 0.6). The incidence of hoarseness and Horner syndrome was statistically lower in the SCB group than in the ISB group (P = 0.0002 and P < 0.00001, respectively). The meta-analysis showed that ultrasound-guided SCB could become a feasible alternative technique to the ISB in shoulder surgery. Copyright © 2017. Published by Elsevier Ltd.

Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs.

PubMed

Choquette, Amélie; Troncy, Eric; Guillot, Martin; Varin, France; Del Castillo, Jérôme R E

2017-01-01

Adrenaline is known to prolong the duration of local anesthesia but its effects on the pharmacokinetic processes of local anesthetic drugs are not fully understood. Our objective was to develop a compartmental model for quantification of adrenaline's impact on the pharmacokinetics of perineurally-injected lidocaine in the dog. Dogs were subjected to paravertebral brachial plexus block using lidocaine alone or adrenalinated lidocaine. Data was collected through a prospective, randomised, blinded crossover protocol performed over three periods. Blood samples were collected during 180 minutes following block execution. Compartmental pharmacokinetic models were developed and their goodness-of-fit were compared. The lowering effects of adrenaline on the absorption of lidocaine were statistically determined with one-sided tests. A one-compartment disposition model with two successive zero-order absorption processes best fitted our experimental data. Adrenaline decreased the peak plasma lidocaine concentration by approximately 60% (P < 0.001), decreased this local anesthetic's fast and slow zero-order absorption rates respectively by 50% and 90% (P = 0.046, and P < 0.001), which respective durations were prolonged by 90% and 1300% (P < 0.020 and P < 0.001). Lidocaine demonstrated a previously unreported atypical absorption profile following its paravertebral injection in dogs. Adrenaline decreased the absorption rate of lidocaine and prolonged the duration of its absorption.

Predicting Outcome of Face-to-Face and Telephone Counselling for Occupational Stress

ERIC Educational Resources Information Center

Karatzias, Thanos; Chouliara, Zoe; Power, Kevin; Kilfedder, Catherine

2011-01-01

The aim of the present study was to investigate predictors of outcome of counselling, using mean change scores of three outcome measures, at treatment completion and at 4-months follow-up, in a randomised trial of face-to-face (n = 30) versus telephone counselling (n = 30) for occupational stress. Factors associated with treatment outcome were…

Streambank Protection Guidelines for Landowners and Local Governments,

DTIC Science & Technology

1983-10-01

building blocks , slag , and quarry waste. UNCHE SON / / Large flat slabs should be broken up into /smaller pieces. Garbage, vegetation, scrap lumber...concrete blocks , and house brick. but will not provide any long-term protection. Preabrfirated commercial gabion basket. Completed gabion revetment made...prevent pressure buildup that could cause revetment failure. BLOCKS . Precast cellular blocks can be *,-’e : Typi.tal sa.d- e, .t bag r ’etment

A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604).

PubMed

Huddart, Robert A; Gabe, Rhian; Cafferty, Fay H; Pollock, Philip; White, Jeff D; Shamash, Jonathan; Cullen, Michael H; Stenning, Sally P

2015-03-01

Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial. We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres. BEP (bleomycin 30,000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15,000 IU). Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates. A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS. The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial. In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration. ISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Lay public's understanding of equipoise and randomisation in randomised controlled trials.

PubMed

Robinson, E J; Kerr, C E P; Stevens, A J; Lilford, R J; Braunholtz, D A; Edwards, S J; Beck, S R; Rowley, M G

2005-03-01

To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. Healthy adults with a wide range of educational backgrounds and ages. Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.

Prevalence, economic analysis and chemotherapeutic control of small ruminant fasciolosis in the Sargodha district of Punjab, Pakistan.

PubMed

Ahmad, Mansoor; Khan, Muhammad Nisar; Sajid, Muhammad Sohail; Muhammad, Ghulam; Qudoos, Abdul; Rizwan, Hafiz Muhammad

2017-03-31

This study describes the epidemiology, the economic significance of small ruminant fasciolosis in animals slaughtered in the abattoirs of the Sargodha district, Punjab, Pakistan between January and June 2012. In vivo fasciolicidal efficacy of commercially available compounds was examined using a randomised complete block design. Microscopically screened faecal samples revealed 40.51% positive animals for fasciolosis. The prevalent species included Fasciola hepatica (35.64%) and Fasciola gigantica (8.21%). Mixed infections were noted in 3.33% subjects. Prevalence rates were significantly higher in females (42.25%) than in males (39.52%), and in adults (51.20%) compared to younger animals (33.98%). The disease was recorded more often in emaciated animals (63.63%) followed in order by average (43.45%), thin (43.22%), and fat (32.12%) animals. Between January and June 2012, fasciolosis in Sargodha district, Punjab, Pakistan, was estimated to incur US$0.036 million and US$0.177 million direct (liver condemnation) and indirect (carcass depreciation) economic losses, respectively. In vivo fasciolicidal efficacy of oxyclozanide proved to be the most effective method of control, compared to triclabendazole, and levamisole. Results provide useful information on the frequency distribution of fasciolosis and its economic significance. Finally, data on in vivo fasciolicidal trials show that oxyclozanide is the most efficacious compound for the treatment of the disease in the district Sargodha, Punjab, Pakistan.

A Mixed Methods Small Pilot Study to Describe the Effects of Upper Limb Training Using a Virtual Reality Gaming System in People with Chronic Stroke

PubMed Central

O'Connor, Deborah A.; Smith, Phil; Moss, Sylvia; Allsop, Lizzie; Edge, Wendy

2017-01-01

Introduction. This small pilot study aimed to examine the feasibility of an upper limb rehabilitation system (the YouGrabber) in a community rehabilitation centre, qualitatively explore participant experiences, and describe changes after using it. Methods and Material. Chronic stroke participants attending a community rehabilitation centre in the UK were randomised to either a YouGrabber or a gym group and completed 18 training sessions over 12 weeks. The motor activity log, box and block, and fatigue severity score were administered by a blinded assessor before and after the intervention. Semistructured interviews were used to ascertain participants' views about using the YouGrabber. Results. Twelve participants (6 females) with chronic stroke were recruited. All adhered to the intervention. There were no adverse events, dropouts, or withdrawal. There were no significant differences between the YouGrabber and gym groups although there were significant within group improvements on the motor activity log (median change: 0.59, range: 0.2–1.25; p < 0.05) within the YouGrabber group. Participants reported that the YouGrabber was motivational but they expressed frustration with technical challenges. Conclusions. The YouGrabber appeared practical and may improve upper limb activities in people several months after stroke. Future work could examine cognition, cost effectiveness, and different training intensities. PMID:28197341

A Mixed Methods Small Pilot Study to Describe the Effects of Upper Limb Training Using a Virtual Reality Gaming System in People with Chronic Stroke.

PubMed

Stockley, Rachel C; O'Connor, Deborah A; Smith, Phil; Moss, Sylvia; Allsop, Lizzie; Edge, Wendy

2017-01-01

Introduction . This small pilot study aimed to examine the feasibility of an upper limb rehabilitation system (the YouGrabber) in a community rehabilitation centre, qualitatively explore participant experiences, and describe changes after using it. Methods and Material . Chronic stroke participants attending a community rehabilitation centre in the UK were randomised to either a YouGrabber or a gym group and completed 18 training sessions over 12 weeks. The motor activity log, box and block, and fatigue severity score were administered by a blinded assessor before and after the intervention. Semistructured interviews were used to ascertain participants' views about using the YouGrabber. Results . Twelve participants (6 females) with chronic stroke were recruited. All adhered to the intervention. There were no adverse events, dropouts, or withdrawal. There were no significant differences between the YouGrabber and gym groups although there were significant within group improvements on the motor activity log (median change: 0.59, range: 0.2-1.25; p < 0.05) within the YouGrabber group. Participants reported that the YouGrabber was motivational but they expressed frustration with technical challenges. Conclusions . The YouGrabber appeared practical and may improve upper limb activities in people several months after stroke. Future work could examine cognition, cost effectiveness, and different training intensities.

Role of grapevine vegetative expression on Aspergillus spp. incidence and OTA accumulation in wines produced in a temperate humid climate.

PubMed

Ferrari, Virginia; Dellacassa, Eduardo; Coniberti, Andrés; Disegna, Edgardo

2017-02-01

Aspergillus spp. and Penicillium spp. are the main producers of ochratoxin A (OTA), a mycotoxin responsible for fatal human diseases. Some authorities have established a maximum of 2 μg/L of OTA in wine. Although the incidence and occurrence of OTA in grapes and wine is highly related to climate conditions, as has been extensively documented, there is no conclusive information on the effects of cultivation systems on the presence of OTA. This study focuses on determining the effect of the trellis system, planting density and cordon height on plant microclimate and thus on Aspergillus spp. contamination and OTA production in Tannat wines in Southern Uruguay. Two experiments were conducted during the 2010-2011 growing season: (1) a strip split plot design with five replicates and two cordon heights (CH) (0.5 m and 1.0 m above the soil) were compared in two planting densities (PD) (0.8 and 1.5 m between plants); (2) a randomised complete block design, vertical shoot positioning (VSP) versus Lyra trellis systems were evaluated. The results suggest that, even the macro- and micro-climate growing conditions play an important part in Aspergillus developing on grapes. Agronomical practices also have an undoubted impact on the risk and control of OTA accumulation in wine.

A hydrostatic weighing method using total lung capacity and a small tank.

PubMed Central

Warner, J G; Yeater, R; Sherwood, L; Weber, K

1986-01-01

The purpose of this study was to establish the validity and reliability of a hydrostatic weighing method using total lung capacity (measuring vital capacity with a respirometer at the time of weighing) the prone position, and a small oblong tank. The validity of the method was established by comparing the TLC prone (tank) method against three hydrostatic weighing methods administered in a pool. The three methods included residual volume seated, TLC seated and TLC prone. Eighty male and female subjects were underwater weighed using each of the four methods. Validity coefficients for per cent body fat between the TLC prone (tank) method and the RV seated (pool), TLC seated (pool) and TLC prone (pool) methods were .98, .99 and .99, respectively. A randomised complete block ANOVA found significant differences between the RV seated (pool) method and each of the three TLC methods with respect to both body density and per cent body fat. The differences were negligible with respect to HW error. Reliability of the TLC prone (tank) method was established by weighing twenty subjects three different times with ten-minute time intervals between testing. Multiple correlations yielded reliability coefficients for body density and per cent body fat values of .99 and .99, respectively. It was concluded that the TLC prone (tank) method is valid, reliable and a favourable method of hydrostatic weighing. PMID:3697596

A hydrostatic weighing method using total lung capacity and a small tank.

PubMed

Warner, J G; Yeater, R; Sherwood, L; Weber, K

1986-03-01

The purpose of this study was to establish the validity and reliability of a hydrostatic weighing method using total lung capacity (measuring vital capacity with a respirometer at the time of weighing) the prone position, and a small oblong tank. The validity of the method was established by comparing the TLC prone (tank) method against three hydrostatic weighing methods administered in a pool. The three methods included residual volume seated, TLC seated and TLC prone. Eighty male and female subjects were underwater weighed using each of the four methods. Validity coefficients for per cent body fat between the TLC prone (tank) method and the RV seated (pool), TLC seated (pool) and TLC prone (pool) methods were .98, .99 and .99, respectively. A randomised complete block ANOVA found significant differences between the RV seated (pool) method and each of the three TLC methods with respect to both body density and per cent body fat. The differences were negligible with respect to HW error. Reliability of the TLC prone (tank) method was established by weighing twenty subjects three different times with ten-minute time intervals between testing. Multiple correlations yielded reliability coefficients for body density and per cent body fat values of .99 and .99, respectively. It was concluded that the TLC prone (tank) method is valid, reliable and a favourable method of hydrostatic weighing.

Apparent metabolisable energy and digestibility of shea (Vitellaria paradoxa) fat, cocoa (Theobroma cacao) fat and soybean oil in broiler chicks.

PubMed

Dei, H K; Rose, S P; Mackenzie, A M

2006-10-01

1. The objective of this experiment was to determine and compare the apparent lipid digestibility coefficient and apparent metabolisable energy (AME) value of shea nut (Vitellaria paradoxa, Gaertn.) fat in broiler chickens with that of soybean oil and cocoa fat. 2. One hundred and sixty 13-d-old male broiler chicks were used in a randomised complete block design. The fats were added at 30, 60 and 90 g/kg to a basal diet. A tenth dietary treatment was the basal feed with no added fats or oils. The birds were fed on the diets for 8 d and all droppings were collected for the final 4 d. 3. The mean coefficient of apparent lipid digestibility for shea fat (0.58) was similar to that of cocoa fat (0.54) but lower than that of soybean oil (0.95). There was evidence of a lipid x concentration interaction with the 90 g/kg shea fat diet having low lipid digestibility (0.43). 4. There was an interaction between the effects of dietary lipid concentration and test lipid on AME but, at dietary levels of 60 g/kg and below, the AME of shea fat (22.0 MJ/kg DM) and cocoa fat (26.4 MJ/kg DM) was significantly lower than that of soybean oil (39.8 MJ/kg DM).

Newborn infant with maternal anti-SSA antibody-induced complete heart block accompanying cardiomyopathy.

PubMed

Iida, Midori; Inamura, Noboru; Takeuchi, Makoto

2006-01-01

Newborn case of maternal anti-SSA antibody-induced congenital complete heart block (CCHB) accompanying cardiomyopathy is presented. Unexpectedly, she died of ventricular tachycardia, not bradycardia, 6 days after birth. Autopsy revealed left ventricular cardiomyopathy with endocardial fibroelastosis. Thus, when evaluating fetal cardiac performance in cases of maternal anti-SSA antibody-induced CCHB, it is necessary to pay attention to myocardial attributes such as endocardial hyperplasia.

A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia.

PubMed

Yağan, Özgür; Taş, Nilay; Küçük, Ahmet; Hancı, Volkan

2016-01-01

The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mg mL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia].

PubMed

Yağan, Özgür; Taş, Nilay; Küçük, Ahmet; Hancı, Volkan

2016-01-01

The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mgmL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

The surgical rectus sheath block for post-operative analgesia: a modern approach to an established technique.

PubMed

Crosbie, Emma J; Massiah, Nadine S; Achiampong, Josephine Y; Dolling, Stuart; Slade, Richard J

2012-02-01

To describe the surgical rectus sheath block for post-operative pain relief following major gynaecological surgery. Local anaesthetic (20 ml 0.25% bupivacaine bilaterally) is administered under direct vision to the rectus sheath space at the time of closure of the anterior abdominal wall. We conducted a retrospective case note review of 98 consecutive patients undergoing major gynaecological surgery for benign or malignant disease who received either standard subcutaneous infiltration of the wound with local anaesthetic (LA, n=51) or the surgical rectus sheath block (n=47) for post-operative pain relief. (1) Pain scores on waking, (2) duration of morphine-based patient controlled analgesia (PCA), (3) quantity of morphine used during the first 48 post-operative hours and (4) length of post-operative stay. The groups were similar in age, the range of procedures performed and the type of pathology observed. Patients who received the surgical rectus sheath block had lower pain scores on waking [0 (0-1) vs. 2 (1-3), p<0.001], required less morphine post-operatively [12 mg (9-26) vs. 36 mg (30-48), p<0.001], had their PCAs discontinued earlier [24h (18-34) vs. 37 h (28-48), p<0.001] and went home earlier [4 days (3-4) vs. 5 days post-op (4-8), p<0.001] [median (interquartile range)] than patients receiving standard subcutaneous local anaesthetic into the wound. The surgical rectus sheath block appears to provide effective post-operative analgesia for patients undergoing major gynaecological surgery. A randomised controlled clinical trial is required to assess its efficacy further. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Blay, Jean-Yves; Pápai, Zsuzsanna; Tolcher, Anthony W; Italiano, Antoine; Cupissol, Didier; López-Pousa, Antonio; Chawla, Sant P; Bompas, Emmanuelle; Babovic, Nada; Penel, Nicolas; Isambert, Nicolas; Staddon, Arthur P; Saâda-Bouzid, Esma; Santoro, Armando; Franke, Fabio A; Cohen, Patrick; Le-Guennec, Solenn; Demetri, George D

2015-05-01

Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0-2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27·9 (IQR 20·9-33·2) in the placebo group and 30·5 months (20·7-37·6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1·54 months [95% CI 1·45-2·69] vs 1·41 [1·38-1·58] months; hazard ratio 0·76 [95% CI 0·59-0·98]; p=0·0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. Sanofi. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL).

PubMed

Barrera, Carlos M; Mykietiuk, Analia; Metev, Hristo; Nitu, Mimi Floarea; Karimjee, Najumuddin; Doreski, Pablo Alexis; Mitha, Ismail; Tanaseanu, Cristina Mihaela; Molina, Joseph McDermott; Antonovsky, Yuri; Van Rensburg, Dirkie Johanna; Rowe, Brian H; Flores-Figueroa, Jose; Rewerska, Barbara; Clark, Kay; Keedy, Kara; Sheets, Amanda; Scott, Drusilla; Horwith, Gary; Das, Anita F; Jamieson, Brian; Fernandes, Prabhavathi; Oldach, David

2016-04-01

Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP. We did this global, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged ≥18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2-5, placebo on days 6-7) or oral moxifloxacin (400 mg on days 1-7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non-inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339. Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28-35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78·2%) patients had an early clinical response in the solithromycin group versus 338 (77·9%) patients in the moxifloxacin group (difference 0·29, 95% CI -5·5 to 6·1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients). Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication. Cempra. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial.

PubMed

Wijting, Ingeborg; Rokx, Casper; Boucher, Charles; van Kampen, Jeroen; Pas, Suzan; de Vries-Sluijs, Theodora; Schurink, Carolina; Bax, Hannelore; Derksen, Maarten; Andrinopoulou, Eleni-Rosalina; van der Ende, Marchina; van Gorp, Eric; Nouwen, Jan; Verbon, Annelies; Bierman, Wouter; Rijnders, Bart

2017-12-01

The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands. Eligible patients (aged ≥18 years) were on combination ART, had been virologically suppressed (HIV RNA <50 copies per mL) for at least 6 months, and had CD4 nadirs of 200 cells per μL or higher, HIV RNA zeniths of 100 000 copies per mL or less, and no history of virological failure. Patients were randomly assigned (1:1), via a web-based block randomisation method (variable block sizes of 4 and 6), to switch to dolutegravir monotherapy (50 mg once a day) either immediately or after a delay of 24 weeks of continued combination ART. Randomisation was stratified by HIV RNA zenith (<50 000 copies per mL vs 50 000-99 999 copies per mL). Investigators and patients were not masked to group allocation. The primary endpoint was the proportion of patients with plasma HIV RNA viral loads of less than 200 copies per mL at week 24, with a non-inferiority margin of 12%. We did analyses in the on-treatment and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, NCT02401828. Between March 10, 2015, and Feb 4, 2016, we randomly assigned 51 patients to the immediate switch group and 53 patients to the delayed switch group. One patient who received immediate monotherapy discontinued treatment at week 12 because of disturbed sleep. At week 24, dolutegravir monotherapy was non-inferior to combination ART, with plasma HIV RNA loads of 200 copies per mL or higher observed in 2% (1/50) of patients in the immediate switch group and in no patients in the delayed switch group (difference 2%, 95% CI -5 to 12). Of patients assigned to the delayed switch group, 47 (89%) switched to dolutegravir monotherapy at week 24, two (4%) of whom subsequently discontinued monotherapy because of headache (n=1) and disturbed sleep (n=1). Eight (8%) of the 95 patients who remained on dolutegravir monotherapy had virological failure; all had therapeutic plasma concentrations of dolutegravir. In three (38%) of the eight patients, mutations associated with resistance were detected in the integrase gene. According to a predefined stopping rule, detection of these mutations led to premature study discontinuation. Dolutegravir monotherapy was non-inferior to combination ART at 24 weeks. However, virological failure continued to occur thereafter and led to dolutegravir resistance. Dolutegravir should not be used as maintenance monotherapy. Erasmus Trustfonds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study.

PubMed

Shilyansky, Carrie; Williams, Leanne M; Gyurak, Anett; Harris, Anthony; Usherwood, Timothy; Etkin, Amit

2016-05-01

Antidepressant treatment failure is a common problem worldwide. In this study, we assess whether or not an important aspect of depression, cognitive impairment, is untreated by antidepressants by studying the effect of acute antidepressant treatment on a range of cognitive domains. In this randomised longitudinal study, which is part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, we assessed the effects of acute antidepressant treatment in a large patient population, across clinical remission outcomes, on a range of cognitive domains: attention, response inhibition, executive function during visuospatial navigation, cognitive flexibility, verbal memory, working memory, decision speed, information processing speed, and psychomotor response speed. We enrolled patients from primary or specialty care clinics in a multicentre, international, open-label, randomised, prospective trial. Eligible patients (aged 18-65 years) were previously untreated or were willing to undergo a 1-week medication washout before the study start, and could not have had inadequate response to study medications in the past. We enrolled a large population of medication-free (ie, untreated) outpatients in a depressive episode and assessed them for cognitive function at enrolment (pre-treatment), and again after 8 weeks of treatment with one of three antidepressant drugs (escitalopram, sertraline, or venlafaxine extended-release). Patients were randomly assigned (1:1:1) to one of the three antidepressants using a blocked randomisation procedure (block size of 12). As a comparison group, we also simultaneously enrolled matched healthy participants. Healthy participants received no medication or intervention, but were assessed for change in cognitive and clinical measures during the same interval and testing protocol. Therefore, this group acts as a test-retest control for the primary outcome measure examined in this study, change in cognitive measures over 8 weeks of treatment in depressed patients. This study is registered with ClinicalTrials.gov, number NCT00693849. Between Dec 8, 2008, and Sept 30, 2011, we enrolled 1008 eligible people into the study. Impairment in five domains-attention, response inhibition, verbal memory, decision speed, and information processing-showed no relative improvement with acute treatment (controlling for time or repeated testing), irrespective of antidepressant treatment group, even in patients whose depression remitted acutely according to clinical measures. Broader cognitive impairment was associated with greater illness chronicity (earlier illness onset) but not with symptom severity or previous antidepressant failures. Depression is associated with impairments in higher-order cognitive functions and information processing, which persist independently of clinical symptom change with treatment. We recorded no difference between the three antidepressants tested, with none showing efficacy for these impairments. Although the 8-week treatment period limits interpretation to acute treatment effects, it does highlight cognitive impairment as an untargeted contributor to incomplete treatment success. Brain Resource Company Operations Pty Ltd and NIH. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

PubMed Central

McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N

2016-01-01

Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences. PMID:26364263

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.

PubMed

McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N

2016-01-02

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences. Copyright © 2016 McCormack et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Patient ratings of chewing ability from a randomised crossover trial: lingualised vs. first premolar/canine-guided occlusion for complete dentures.

PubMed

Heydecke, Guido; Akkad, Ahmed Shadi; Wolkewitz, Martin; Vogeler, Michael; Türp, Jens C; Strub, Joerg R

2007-06-01

Complex procedures involving a facebow transfer and the use of lingualised teeth are deemed to have a positive influence on the chewing ability with complete dentures. To determine if patients' ratings of their ability to chew depend on the method of complete denture fabrication. Edentulous patients (n = 20) participated in a within-subject crossover trial. Each patient received two sets of new complete dentures. One pair was manufactured based on intraoral tracing of centric relation and facebow transfer; semi-anatomical teeth with lingualised occlusion denture (LOD) were chosen. The second pair was made using a simplified procedure without facebow transfer; jaw relations were recorded with wax occlusion rims, and anatomical teeth with a first premolar/canine-guidance (CGD) were selected. The dentures were delivered in randomised order, and each was worn for 3 months. Three months after delivery, patients' ratings of each new prosthesis were recorded on visual analogue scales for their ability to chew seven index foods. Repeated measurements analysis of variance was performed to investigate possible carry-over effects accounting for confounding by treatment period. When comparing the two treatments, participants rated their ability to chew in general, to masticate carrots, hard sausage, steak and raw apple in particular, was significantly better with the CGD (anatomical teeth) than with the LOD (p < 0.05). Comprehensive methods for the fabrication of complete dentures including semi-anatomical lingualised teeth and a full registration do not seem to influence the perceived chewing ability, when compared with more simple procedures. Chewing ability for tough foods appears to benefit from the use of anatomical teeth.

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

PubMed

Bøtker, Hans Erik; Kharbanda, Rajesh; Schmidt, Michael R; Bøttcher, Morten; Kaltoft, Anne K; Terkelsen, Christian J; Munk, Kim; Andersen, Niels H; Hansen, Troels M; Trautner, Sven; Lassen, Jens Flensted; Christiansen, Evald Høj; Krusell, Lars R; Kristensen, Steen D; Thuesen, Leif; Nielsen, Søren S; Rehling, Michael; Sørensen, Henrik Toft; Redington, Andrew N; Nielsen, Torsten T

2010-02-27

Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes. Fondation Leducq. Copyright 2010 Elsevier Ltd. All rights reserved.

A mixed methods study to evaluate the clinical and cost-effectiveness of a self-managed exercise programme versus usual physiotherapy for chronic rotator cuff disorders: protocol for the SELF study.

PubMed

Littlewood, Chris; Ashton, Jon; Mawson, Sue; May, Stephen; Walters, Stephen

2012-04-30

Shoulder pain is the third most common reason for consultation with a physiotherapist and up to 26% of the general population might be expected to experience an episode at any one time. Disorders of the shoulder muscles and tendons (rotator cuff) are thought to be the commonest cause of this pain. The long-term outcome is frequently poor despite treatment. This means that many patients are exposed to more invasive treatment, e.g. surgery, and/or long-term pain and disability.Patients with this disorder typically receive a course of physiotherapy which might include a range of treatments. Specifically the value of exercise against gravity or resistance (loaded exercise) in the treatment of tendon disorders is promising but appears to be under-used. Loaded exercise in other areas of the body has been favourably evaluated but further investigation is needed to evaluate the impact of these exercises in the shoulder and particularly the role of home based or supervised exercise versus usual treatment requiring clinic attendance. A single-centre pragmatic unblinded parallel group randomised controlled trial will evaluate the effectiveness of a self-managed loaded exercise programme versus usual clinic based physiotherapy. A total of 210 study participants with a primary complaint of shoulder pain suggestive of a rotator cuff disorder will be recruited from NHS physiotherapy waiting lists and allocated to receive a programme of self-managed exercise or usual physiotherapy using a process of block randomisation with sealed opaque envelopes. Baseline assessment for shoulder pain, function and quality of life will be undertaken with the Shoulder Pain & Disability Index, the Patient Specific Functional Scale and the SF-36. Follow-up evaluations will be completed at 3, 6 and 12 months by postal questionnaire. Both interventions will be delivered by NHS Physiotherapist's.An economic analysis will be conducted from an NHS and Personal Social Services perspective to evaluate cost-effectiveness and a qualitative investigation will be undertaken to develop greater understanding of the experience of undertaking or prescribing exercise as a self-managed therapy. ISRCTN84709751.

Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial.

PubMed

Khan, Habib Rehman; Kralj-Hans, Ines; Haldar, Shouvik; Bahrami, Toufan; Clague, Jonathan; De Souza, Anthony; Francis, Darrel; Hussain, Wajid; Jarman, Julian; Jones, David Gareth; Mediratta, Neeraj; Mohiaddin, Raad; Salukhe, Tushar; Jones, Simon; Lord, Joanne; Murphy, Caroline; Kelly, Joanna; Markides, Vias; Gupta, Dhiraj; Wong, Tom

2018-02-20

Atrial fibrillation is the commonest arrhythmia which raises the risk of heart failure, thromboembolic stroke, morbidity and death. Pharmacological treatments of this condition are focused on heart rate control, rhythm control and reduction in risk of stroke. Selective ablation of cardiac tissues resulting in isolation of areas causing atrial fibrillation is another treatment strategy which can be delivered by two minimally invasive interventions: percutaneous catheter ablation and thoracoscopic surgical ablation. The main purpose of this trial is to compare the effectiveness and safety of these two interventions. Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre, randomised controlled trial within three NHS tertiary cardiovascular centres specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with symptomatic, long-standing, persistent atrial fibrillation will be randomly allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio. Pre-determined lesion sets will be delivered in each treatment arm with confirmation of appropriate conduction block. All patients will have an implantable loop recorder (ILR) inserted subcutaneously immediately following ablation to enable continuous heart rhythm monitoring for at least 12 months. The devices will be programmed to detect episodes of atrial fibrillation and atrial tachycardia ≥ 30 s in duration. The patients will be followed for 12 months, completing appropriate clinical assessments and questionnaires every 3 months. The ILR data will be wirelessly transmitted daily and evaluated every month for the duration of the follow-up. The primary endpoint in the study is freedom from atrial fibrillation and atrial tachycardia at the end of the follow-up period. The CASA-AF Trial is a National Institute for Health Research-funded study that will provide first-class evidence on the comparative efficacy, safety and cost-effectiveness of thoracoscopic surgical ablation and conventional percutaneous catheter ablation for long-standing persistent atrial fibrillation. In addition, the results of the trial will provide information on the effects on patients' quality of life. ISRCTN Registry, ISRCTN18250790 . Registered on 24 April 2015.

Randomised controlled trial of school-based humanistic counselling for emotional distress in young people: Feasibility study and preliminary indications of efficacy

PubMed Central

2010-01-01

Aims The purpose of this study was to test the feasibility of a randomised controlled trial comparing six weeks of humanistic school-based counselling versus waiting list in the reduction of emotional distress in young people, and to obtain initial indications of efficacy. Methods Following a screening procedure, young people (13 - 15 years old) who experienced emotional distress were randomised to either humanistic counselling or waiting list in this multi-site study. Outcomes were assessed using a range of self-report mental health measures, with the emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) acting as the primary outcome indicator. Results Recruitment procedures were successful, with 32 young people consenting to participate in the trial and 27 completing endpoint measures. Trial procedures were acceptable to all involved in the research. No significant differences were found between the counselling and waiting list groups in reductions in levels of emotional symptoms (Hedges' g = 0.03), but clients allocated to counselling showed significantly greater improvement in prosocial behaviour (g = 0.89) with an average effect size (g) across the nine outcome measures of 0.25. Participants with higher levels of depressive symptoms showed significantly greater change. Conclusion This study suggested that a randomised controlled trial of counselling in schools is acceptable and feasible, although initial indications of efficacy are mixed. Trial registration Current Controlled Trials ISRCTN68290510. PMID:20412578

Bimatoprost 0.03%/timolol 0.5% preservative-free ophthalmic solution versus bimatoprost 0.03%/timolol 0.5% ophthalmic solution (Ganfort) for glaucoma or ocular hypertension: a 12-week randomised controlled trial

PubMed Central

Goldberg, Ivan; Gil Pina, Rafael; Lanzagorta-Aresti, Aitor; Schiffman, Rhett M; Liu, Charlie; Bejanian, Marina

2014-01-01

Aim To compare the efficacy and safety of single-dose bimatoprost 0.03%/timolol 0.5% preservative-free (PF) ophthalmic solution with bimatoprost 0.03%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. Methods In this multicentre, randomised, parallel-group study, patients were randomised to bimatoprost/timolol PF or bimatoprost/timolol once daily in the morning for 12 weeks. Primary efficacy endpoints, reflecting differing regional regulatory requirements, included change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12, and the average eye IOP at weeks 2, 6 and 12 in the intent-to-treat population. Results 561 patients were randomised (278 to bimatoprost/timolol PF; 283 to bimatoprost/timolol); 96.3% completed the study. Both treatment groups showed statistically and clinically significant mean decreases from baseline in worse eye IOP and in average eye IOP at all follow-up time points (p<0.001). Bimatoprost/timolol PF met all pre-established criteria for non-inferiority and equivalence to bimatoprost/timolol. Ocular adverse events were similar between treatment groups, with conjunctival hyperaemia being the most frequent. Most were mild or moderate in severity. Conclusions Bimatoprost/timolol PF demonstrated non-inferiority and equivalence in IOP lowering compared with bimatoprost/timolol, with no significant differences in safety and tolerability. Trial registration number NCT01177098. PMID:24667994

Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis.

PubMed

Wildt, Signe; Krag, Aleksander; Gluud, Liselotte

2011-01-01

Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. Methods Randomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results 105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. Conclusion The quality of registration of randomised controlled trials still needs improvement.

A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.

PubMed

McPherson, Stuart; Wilkinson, Nina; Tiniakos, Dina; Wilkinson, Jennifer; Burt, Alastair D; McColl, Elaine; Stocken, Deborah D; Steen, Nick; Barnes, Jane; Goudie, Nicola; Stewart, Stephen; Bury, Yvonne; Mann, Derek; Anstee, Quentin M; Day, Christopher P

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. Experimental and small clinical trials have demonstrated that angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this randomised controlled trial was to assess whether treatment with Losartan for 96 weeks slowed, halted or reversed the progression of fibrosis in patients with non-alcoholic steatohepatitis (NASH). Double-blind randomised-controlled trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with histological evidence of NASH. The primary outcome for the study was change in histological fibrosis stage from pre-treatment to end-of-treatment. The study planned to recruit 214 patients. However, recruitment was slower than expected, and after 45 patients were randomised (median age 55; 56% male; 60% diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients (15 losartan and 17 placebo) completed follow up period: one patient (6.7%) treated with losartan and 4 patients (23.5%) in the placebo group were "responders" (lower fibrosis stage at follow up compared with baseline). The major reason for slow recruitment was that 39% of potentially eligible patients were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and 15% were taking other prohibited medications. Due to the widespread use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient patients to determine whether losartan has anti-fibrotic effects in the liver. ISRCTN 57849521.

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

PubMed

Bath, Philip M; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A; Robinson, Thompson G; Saver, Jeffrey L; Sprigg, Nikola; Wardlaw, Joanna M; In Acute Stroke Collaboration Basc, Blood Pressure

2016-01-01

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

Directed self-assembly of block copolymers for nanolithography: fabrication of isolated features and essential integrated circuit geometries.

PubMed

Stoykovich, Mark P; Kang, Huiman; Daoulas, Kostas Ch; Liu, Guoliang; Liu, Chi-Chun; de Pablo, Juan J; Müller, Marcus; Nealey, Paul F

2007-10-01

Self-assembling block copolymers are of interest for nanomanufacturing due to the ability to realize sub-100 nm dimensions, thermodynamic control over the size and uniformity and density of features, and inexpensive processing. The insertion point of these materials in the production of integrated circuits, however, is often conceptualized in the short term for niche applications using the dense periodic arrays of spots or lines that characterize bulk block copolymer morphologies, or in the long term for device layouts completely redesigned into periodic arrays. Here we show that the domain structure of block copolymers in thin films can be directed to assemble into nearly the complete set of essential dense and isolated patterns as currently defined by the semiconductor industry. These results suggest that block copolymer materials, with their intrinsically advantageous self-assembling properties, may be amenable for broad application in advanced lithography, including device layouts used in existing nanomanufacturing processes.

How Much Volume of Local Anesthesia and How Long Should You Wait After Injection for an Effective Wrist Median Nerve Block?

PubMed

Lovely, Lyndsay M; Chishti, Yasmin Z; Woodland, Jennifer L; Lalonde, Donald H

2018-05-01

Many surgeons and emergentologists use non-ultrasound-guided wrist nerve blocks. There is little evidence to guide the ideal volume of local anesthesia or how long we should wait after injection before performing pain-free procedures. This pilot study examined time to maximal anesthesia to painful needle stick in 14 volunteer participants receiving bilateral wrist blocks of 6 versus 11 mL of local. One surgeon performed all 14 bilateral wrist median nerve blocks in participants who remained blinded until after bandages were applied to their wrist. No one could see which wrist received the larger 11-mL volume injection versus the 6-mL block. Blinded sensory assessors then measured perceived maximal numbness time and numbness to needle stick pain in the fingertips of the median nerve distribution. Failure to get a complete median nerve block occurred in seven of fourteen 6-mL wrist blocks versus failure in only one of fourteen 11-mL blocks. Perceived maximal numbness occurred at roughly 40 minutes after injection, but actual numbness to painful needle stick took around 100 minutes. Incomplete median nerve numbness occurred with both 6- and 11-mL non-ultrasound-guided blocks at the wrist. In those with complete blocks, it took a surprisingly long time of 100 minutes for maximal anesthesia to occur to painful needle stick stimuli to the fingertips of the median nerve distribution. Non-ultrasound-guided median nerve blocks at the wrist as described in this article lack reliability and take too long to work.

'Seizure First Aid Training' for people with epilepsy who attend emergency departments, and their family and friends: study protocol for intervention development and a pilot randomised controlled trial.

PubMed

Noble, A J; Marson, A G; Tudur-Smith, C; Morgan, M; Hughes, D A; Goodacre, S; Ridsdale, L

2015-07-24

People with chronic epilepsy (PWE) often make costly but clinically unnecessary emergency department (ED) visits. Offering them and their carers a self-management intervention that improves confidence and ability to manage seizures may lead to fewer visits. As no such intervention currently exists, we describe a project to develop and pilot one. To develop the intervention, an existing group-based seizure management course that has been offered by the Epilepsy Society within the voluntary sector to a broader audience will be adapted. Feedback from PWE, carers and representatives from the main groups caring for PWE will help refine the course so that it addresses the needs of ED attendees. Its behaviour change potential will also be optimised. A pilot randomised controlled trial will then be completed. 80 PWE aged ≥16 who have visited the ED in the prior 12 months on ≥2 occasions, along with one of their family members or friends, will be recruited from three NHS EDs. Dyads will be randomised to receive the intervention or treatment as usual alone. The proposed primary outcome is ED use in the 12 months following randomisation. For the pilot, this will be measured using routine hospital data. Secondary outcomes will be measured by patients and carers completing questionnaires 3, 6 and 12 months postrandomisation. Rates of recruitment, retention and unblinding will be calculated, along with the ED event rate in the control group and an estimate of the intervention's effect on the outcome measures. Ethical approval: NRES Committee North West-Liverpool East (Reference number 15/NW/0225). The project's findings will provide robust evidence on the acceptability of seizure management training and on the optimal design of a future definitive trial. The findings will be published in peer-reviewed journals and presented at conferences. ISRCTN13 871 327. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study.

PubMed

Tulloh, R M R; Garratt, V; Tagney, J; Turner-Cobb, J; Marques, E; Greenwood, R; Howard, L; Gin-Sing, W; Barton, A; Ewings, P; Craggs, P; Hollingworth, W

2018-01-01

Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to £120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness-based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between £2234 (Cardiff) and £4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial. Achieving better MBSR intervention attendance or use of an Internet-based programme might maximise the benefit of MBSR.

Health on the Web: Randomised Controlled Trial of Online Screening and Brief Alcohol Intervention Delivered in a Workplace Setting

PubMed Central

Khadjesari, Zarnie; Freemantle, Nick; Linke, Stuart; Hunter, Rachael; Murray, Elizabeth

2014-01-01

Background Alcohol misuse in England costs around £7.3 billion (US$12.2 billion) annually from lost productivity and absenteeism. Delivering brief alcohol interventions to employees as part of a health check may be acceptable, particularly with online delivery which can provide privacy for this stigmatised behaviour. Research to support this approach is limited and methodologically weak. The aim was to determine the effectiveness of online screening and personalised feedback on alcohol consumption, delivered in a workplace as part of a health check. Methods and Findings This two-group online individually randomised controlled trial recruited employees from a UK-based private sector organisation (approx. 100,000 employees). 3,375 employees completed the online health check in the three week recruitment period. Of these, 1,330 (39%) scored five or more on the AUDIT-C (indicating alcohol misuse) and were randomised to receive personalised feedback on their alcohol intake, alongside feedback on other health behaviours (n = 659), or to receive feedback on all health behaviours except alcohol intake (n = 671). Participants were mostly male (75%), with a median age of 48 years and half were in managerial positions (55%). Median Body Mass Index was 26, 12% were smokers, median time undertaking moderate/vigorous physical activity a week was 173 minutes and median fruit and vegetable consumption was three portions a day. Eighty percent (n = 1,066) of participants completed follow-up questionnaires at three months. An intention to treat analysis found no difference between experimental groups for past week drinking (primary outcome) (5.6% increase associated with the intervention (95% CI −4.7% to 16.9%; p = .30)), AUDIT (measure of alcohol-related harm) and health utility (EQ-5D). Conclusions There was no evidence to support the use of personalised feedback within an online health check for reducing alcohol consumption among employees in this organisation. Further research is needed on how to engage a larger proportion of employees in screening. Trial Registration International Standard Randomised Controlled Trial Number Register ISRCTN50658915 PMID:25409454

A Televised, Web-Based Randomised Trial of an Herbal Remedy (Valerian) for Insomnia

PubMed Central

Oxman, Andrew D.; Flottorp, Signe; Håvelsrud, Kari; Fretheim, Atle; Odgaard-Jensen, Jan; Austvoll-Dahlgren, Astrid; Carling, Cheryl; Pallesen, Ståle; Bjorvatn, Bjørn

2007-01-01

Background This trial was conducted as part of a project that aims to enhance public understanding and use of research in decisions about healthcare by enabling viewers to participate in research and to follow the process, through television reports and on the web. Valerian is an herbal over-the-counter drug that is widely used for insomnia. Systematic reviews have found inconsistent and inconclusive results about its effects. Methods Participants were recruited through a weekly nationally televised health program in Norway. Enrolment and data collection were over the Internet. 405 participants who were 18 to 75 years old and had insomnia completed a two week diary-keeping run-in period without treatment and were randomised and mailed valerian or placebo tablets for two weeks. All participants and investigators were blind to treatment until after the analysis was completed. Findings For the primary outcome of a minimally important improvement in self-reported sleep quality (≥0.5 units on a 7 point scale), the difference between the valerian group (29%) and the placebo group (21%) was not statistically significant (difference 7.5%; 95% CI-0.9 to 15.9; p = 0.08). On the global self-assessment question at the end of the treatment period 5.5% (95% CI 0.2 to 10.8) more participants in the valerian group perceived their sleep as better or much better (p = 0.04). There were similar trends favouring the valerian group for night awakenings (difference = 6.0%, 95% CI-0.5 to 12.5) and sleep duration (difference = 7.5%, 95% CI-1.0 to 16.1). There were no serious adverse events and no important or statistically significant differences in minor adverse events. Interpretation Based on this and previous studies, valerian appears to be safe, but with modest beneficial effects at most on insomnia compared to placebo. The combined use of television and the Internet in randomised trials offers opportunities to answer questions about the effects of health care interventions and to improve public understanding and use of randomised trials. Trial Registration Controlled-Trials.com ISRCTN72748991 PMID:17940604

A pilot cluster randomised controlled trial of a support and training intervention to improve the mental health of secondary school teachers and students - the WISE (Wellbeing in Secondary Education) study.

PubMed

Kidger, Judi; Stone, Tracey; Tilling, Kate; Brockman, Rowan; Campbell, Rona; Ford, Tamsin; Hollingworth, William; King, Michael; Araya, Ricardo; Gunnell, David

2016-10-06

Secondary school teachers are at heightened risk of psychological distress, which can lead to poor work performance, poor quality teacher-student relationships and mental illness. A pilot cluster randomised controlled trial (RCT) - the WISE study - evaluated the feasibility of a full-scale RCT of an intervention to support school staff's own mental health, and train them in supporting student mental health. Six schools were randomised to an intervention or control group. In the intervention schools i) 8-9 staff received Mental Health First Aid (MHFA) training and became staff peer supporters, and ii) youth MHFA training was offered to the wider staff body. Control schools continued with usual practice. We used thematic qualitative data analysis and regression modelling to ascertain the feasibility, acceptability and potential usefulness of the intervention. Thirteen training observations, 14 staff focus groups and 6 staff interviews were completed, and 438 staff (43.5 %) and 1,862 (56.3 %) students (years 8 and 9) completed questionnaires at baseline and one year later. MHFA training was considered relevant for schools, and trainees gained in knowledge, confidence in helping others, and awareness regarding their own mental health. Suggestions for reducing the length of the training and focusing on helping strategies were made. A peer support service was established in all intervention schools and was perceived to be helpful in supporting individuals in difficulty - for example through listening, and signposting to other services - and raising the profile of mental health at a whole school level. Barriers to use included lack of knowledge about the service, concerns about confidentiality and a preference for accessing support from pre-existing networks. The WISE intervention is feasible and acceptable to schools. Results support the development of a full-scale cluster RCT, if steps are taken to improve response rates and implement the suggested improvements to the intervention. International Standard Randomised Controlled Trial Number: ISRCTN13255300 retrospectively registered 28/09/16.

Complete-block scheduling for advanced pharmacy practice experiences.

PubMed

Hatton, Randy C; Weitzel, Kristin W

2013-12-01

An innovative approach to meeting increased student demand for advanced pharmacy practice experiences (APPEs) is described, including lessons learned during a two-year pilot project. To achieve more efficient allocation of preceptor resources, the University of Florida College of Pharmacy (UFCOP) adopted a new APPE rotation model in which 20 pharmacy students per year complete all required and elective APPEs at one practice site, an affiliated academic medical center. Relative to the prevailing model of experiential training for Pharm.D. students, the "complete-block scheduling" model offers a number of potential benefits to students, preceptors, and the pharmacy school. In addition to potentially reduced student housing expenses and associated conveniences, complete-block scheduling may enable (1) more efficient use of teaching resources, (2) increased collaboration among preceptors, (3) greater continuity and standardization of educational experiences, and (4) enhanced opportunities for students to engage in longer and more complex research projects. The single-site APPE rotation model also can provide value to the training site by enabling the extension of clinical pharmacy services; for example, UFCOP students perform anticoagulation monitoring and discharge medication counseling at the host institution. Despite logistical and other challenges encountered during pilot testing of the new scheduling model, the program has been well received by students and preceptors alike. Complete-block APPE scheduling is a viable model for some health systems to consider as a means of streamlining experiential education practices and helping to ensure high-quality clinical rotations for Pharm.D. students.

Herbst appliance with skeletal anchorage versus dental anchorage in adolescents with Class II malocclusion: study protocol for a randomised controlled trial.

PubMed

Batista, Klaus Barretto Dos Santos Lopes; Lima, Tatiana; Palomares, Nathália; Carvalho, Felipe de Assis; Quintão, Cátia; Miguel, José Augusto Mendes; Lin, Yin-Ling; Su, Ting-Li; O'Brien, Kevin

2017-11-25

The Herbst appliance is an orthodontic appliance that is used for the correction of class II malocclusion with skeletal discrepancies. Research has shown that this is effective. However, a potential harm is excessive protrusion of the lower front teeth. This is associated with gingival recession, loss of tooth support, and root resorption. This trial evaluates a method of reducing this problem. The study is a single-center, randomised, assessor-blinded, superiority clinical trial with parallel 1:1 allocation. Male and female young people (10-14 years old) with prominent front teeth (class II, division 1) will be treated in one orthodontic clinic. Group 1 will be treated with the conventional Herbst appliance with dental anchorage and group 2 with the Herbst appliance with indirect skeletal anchorage for 12 months. The primary objective will be to compare the proclination of the lower incisors between the Herbst appliance with dental anchorage and skeletal anchorage. Secondary objectives will be to evaluate the changes occurring between the groups in the mandible, maxilla, lower and upper molars, and in gingival recession and root resorption at the end of the treatment. Additionally, the young patient's experience using the appliances will be assessed. The primary outcome measure will be the amount of lower incisor proclination at the end of treatment. This will be assessed by cone-beam computed tomography (CBCT) superimposition. Secondary outcome measures will be the changes in the mandible, maxilla, lower and upper molars at the end of treatment assessed by tomography superimposition and the young patient's experience using the appliances assessed by self-reported questionnaires and semi-structured interviews. The randomisation method will be blocked randomisation, using software to generate a randomised list. The allocation concealment will be done in opaque envelopes numbered from 1 to 40 containing the treatment modality. The randomisation will be implemented by the secretary of the Department of Orthodontics of Rio de Janeiro State University before the beginning of the study. The patients and the orthodontists who will treat the patients cannot be blinded, as they will know the type of appliance used. The technician who will take the CBCT image and the data analyst will be blinded to patients' group allocation. If this new intervention is effective, the findings can change orthodontic practice and may also be relevant to other forms of treatment in which appliances are fixed to the bones of the jaws. However, if the bone anchoring is not effective, the trial will provide much needed information on the use of this comparatively new development. ClinicalTrials.gov, protocol ID: NCT0241812 . Registered on 26 March 2015.

A randomised controlled trial using mobile advertising to promote safer sex and sun safety to young people.

PubMed

Gold, J; Aitken, C K; Dixon, H G; Lim, M S C; Gouillou, M; Spelman, T; Wakefield, M; Hellard, M E

2011-10-01

Mobile phone text messages (SMS) are a promising method of health promotion, but a simple and low cost way to obtain phone numbers is required to reach a wide population. We conducted a randomised controlled trial with simultaneous brief interventions to (i) evaluate effectiveness of messages related to safer sex and sun safety and (ii) pilot the use of mobile advertising for health promotion. Mobile advertising subscribers aged 16-29 years residing in Victoria, Australia (n = 7606) were randomised to the 'sex' or 'sun' group and received eight messages during the 2008-2009 summer period. Changes in sex- and sun-related knowledge and behaviour were measured by questionnaires completed on mobile phones. At follow-up, the sex group had significantly higher sexual health knowledge and fewer sexual partners than the sun group. The sun group had no change in hat-wearing frequency compared with a significant decline in hat-wearing frequency in the sex group. This is the first study of mobile advertising for health promotion, which can successfully reach most young people. Challenges experienced with project implementation and evaluation should be considered as new technological approaches to health promotion continue to be expanded.

Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.

PubMed

Vibholm, Helle Annette; Pedersen, Jesper; Faltinsen, Erlend; Marcussen, Michael H; Gluud, Christian; Storebø, Ole Jakob

2018-06-08

This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

Does peer-assisted learning improve academic performance? A scoping review.

PubMed

Williams, Brett; Reddy, Priya

2016-07-01

Due to the diverse and ever-changing nature of the healthcare industry, teaching pedagogies such as peer-assisted learning (PAL) are being implemented to align with external competency standards. A scoping review was conducted in order to map the breadth of literature available on PAL and its impact on student performance. This review used Arksey and O'Malley's six stage scoping methodology. The databases searched included: Cinahl, Ovid Medline, Proquest and Embase as well as grey literature sites and dissertations. 22 articles were included in this review, 10 of which were mixed methods randomised controlled trials, one retrospective study, four controlled trials, two randomised cross over controlled trial, three prospective randomised controlled trials, one thesis and one comparative research design. Analysis of the included articles identified three major themes outlining student performance. Student teachers themselves showed the most significant improvement in objective outcomes. The predominant healthcare field addressed were medical students with very few studies being completed on other professions. The search indicated an overall positive response to PAL with the measurable outcome of student tutors being of most significance. Further research is required to determine the relevance for the wider healthcare community. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relative Reliability and Validity of the Block Kids Questionnaire among Youth Aged 10 to 17 Years

USDA-ARS?s Scientific Manuscript database

This cross-sectional study tested the reliability and validity of the Block Kids Questionnaire to assess diet during the past 7 days. Within a 7-day period, 10- to 17-year-old children and adolescents completed two 24-hour dietary recalls by telephone, followed by the Block Kids Questionnaire at the...

15 CFR Supplement No. 2 to Part 752 - Instructions for Completing Form BIS-748P-A, “Item Annex”

Code of Federal Regulations, 2014 CFR

2014-01-01

... within the lines for each block or box. Block 1: Application Control No. Enter the application control... or reexport a computer or equipment that contains a computer. Instructions on calculating the APP are... processing of your application. Block 24: Continuation of Additional Information. Enter any identifying...

15 CFR Supplement No. 2 to Part 752 - Instructions for Completing Form BIS-748P-B, “Item Annex”

Code of Federal Regulations, 2012 CFR

2012-01-01

... within the lines for each block or box. Block 1: Application Control No. Enter the application control... or reexport a computer or equipment that contains a computer. Instructions on calculating the APP are... processing of your application. Block 24: Continuation of Additional Information. Enter any identifying...

15 CFR Supplement No. 2 to Part 752 - Instructions for Completing Form BIS-748P-B, “Item Annex”

Code of Federal Regulations, 2013 CFR

2013-01-01

... within the lines for each block or box. Block 1: Application Control No. Enter the application control... or reexport a computer or equipment that contains a computer. Instructions on calculating the APP are... processing of your application. Block 24: Continuation of Additional Information. Enter any identifying...

15 CFR Supplement No. 2 to Part 752 - Instructions for Completing Form BIS-748P-B, “Item Annex”

Code of Federal Regulations, 2011 CFR

2011-01-01

... within the lines for each block or box. Block 1: Application Control No. Enter the application control... or reexport a computer or equipment that contains a computer. Instructions on calculating the APP are... processing of your application. Block 24: Continuation of Additional Information. Enter any identifying...

The experimental design of the Missouri Ozark Forest Ecosystem Project

Treesearch

Steven L. Sheriff; Shuoqiong He

1997-01-01

The Missouri Ozark Forest Ecosystem Project (MOFEP) is an experiment that examines the effects of three forest management practices on the forest community. MOFEP is designed as a randomized complete block design using nine sites divided into three blocks. Treatments of uneven-aged, even-aged, and no-harvest management were randomly assigned to sites within each block...

Epidural therapy for the treatment of severe pre-eclampsia in non labouring women.

PubMed

Ray, Amita; Ray, Sujoy

2017-11-28

Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required. To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review. The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction. We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomesThe included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups. Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.

Complete A-V block: incidental or a part of cor triatriatum dexter.

PubMed

Guler, Y; Akgun, T; Toprak, C; Guler, A; Esen, A M

2014-05-01

Cor triatriatum dexter (CTD) is an extremely rare cardiac anomaly in which the right atrium is divided into two distinct chambers by a membrane. The persistence of the right valve of sinus venosus results in a complete septation of the right atrium. This anomaly is frequently associated with other right-sided cardiac abnormalities. Its clinical manifestation and the need for intervention are determined by the number and the size of the fenestrations on the membrane, associated cardiac anomalies and arrhythmias. We describe a case of CTD in a patient with complete atrioventricular (A-V) block.

Naloxone Antagonizes Soman-induced Central Respiratory Depression in Rats.

PubMed

Škrbić, Ranko; Stojiljković, Miloš P; Ćetković, Slavko S; Dobrić, Silva; Jeremić, Dejan; Vulović, Maja

2017-06-01

The influence of naloxone on respiration impaired by the highly toxic organophosphate nerve agent soman in anaesthetized rats was investigated. Soman, administered in a dose that was ineffective in blocking the electrically induced contractions of the phrenic nerve-diaphragm preparation in situ, induced a complete block of the spontaneous respiratory movements of the diaphragm, indicating the domination of central over the peripheral effects. Naloxone dose-dependently antagonized the soman-induced respiratory blockade. Atropine, at a dose that was per se ineffective in counteracting soman-induced respiratory depression, potentiated the protective effects of naloxone and completely restored respiration. Naloxone remained completely ineffective in antagonizing respiratory depression induced by the muscarinic receptor agonist the oxotremorine. It is assumed that naloxone antagonizes soman-induced respiratory inhibition by blocking endogenous opioidergic respiratory control pathways that are independent of the stimulation of muscarinic receptors. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Acceptability of the aquatic environment for exercise training by people with chronic obstructive pulmonary disease with physical comorbidities: Additional results from a randomised controlled trial.

PubMed

McNamara, Renae J; McKeough, Zoe J; McKenzie, David K; Alison, Jennifer A

2015-06-01

Water-based exercise training is a relatively new concept in the management of people with COPD. This study aimed to examine the acceptability of the aquatic environment as a medium for exercise training in people with COPD with physical comorbidities. Following a supervised eight week, three times a week, water-based exercise training programme conducted in a hospital hydrotherapy pool as part of a randomised controlled trial, participants completed a questionnaire about their experience with exercise training in the pool including adverse events, barriers and factors enabling exercise programme completion, satisfaction with the aquatic environment and their preference for an exercise training environment. All 18 participants (mean (SD) age 72 (10) years; FEV1% predicted 60 (10) %) who commenced the water-based exercise training programme completed the questionnaire. Three participants withdrew from training. High acceptability of the water and air temperature, shower and change-room facilities, staff assistance and modes of pool entry was reported (94% to 100%). Six factors were highly rated as enabling exercise programme adherence and completion: staff support (chosen by 93% of participants), enjoyment (80%), sense of achievement (80%), noticeable improvements (73%), personal motivation (73%) and participant support (53%). Eighty-nine percent of the participants indicated they would continue with water-based exercise. This study provides the first insight into the acceptability of the aquatic environment for exercise training in people with COPD and indicates water-based exercise and the aquatic environment is well accepted. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial

PubMed Central

2013-01-01

Background Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the ‘holistic’ approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. Methods/design A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. Discussion This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612000889853 The trial is now in progress with 12 villages already have been randomised. PMID:23675705

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing

PubMed Central

2011-01-01

Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. Trial registration number Current Controlled Trials ISRCTN71327395 assigned 7th June 2010. PMID:21733166

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial.

PubMed

Merom, Dafna; Cumming, Robert; Mathieu, Erin; Anstey, Kaarin J; Rissel, Chris; Simpson, Judy M; Morton, Rachael L; Cerin, Ester; Sherrington, Catherine; Lord, Stephen R

2013-05-15

Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the 'holistic' approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Australian New Zealand Clinical Trials Registry ACTRN12612000889853The trial is now in progress with 12 villages already have been randomised.

Pharmacist-led management of chronic pain in primary care: results from a randomised controlled exploratory trial

PubMed Central

Bruhn, Hanne; Bond, Christine M; Elliott, Alison M; Hannaford, Philip C; Lee, Amanda J; McNamee, Paul; Smith, Blair H; Watson, Margaret C; Holland, Richard; Wright, David

2013-01-01

Objectives To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain. Design An exploratory randomised controlled trial. Setting Six general practices with prescribing pharmacists in Grampian (3) and East Anglia (3). Participants Patients on repeat prescribed pain medication (4815) were screened by general practitioners (GPs), and mailed invitations (1397). 196 were randomised and 180 (92%) completed. Exclusion criteria included: severe mental illness, terminally ill, cancer related pain, history of addiction. Randomisation and intervention Patients were randomised using a remote telephone service to: (1) pharmacist medication review with face-to-face pharmacist prescribing; (2) pharmacist medication review with feedback to GP and no planned patient contact or (3) treatment as usual (TAU). Blinding was not possible. Outcome measures Outcomes were the SF-12v2, the Chronic Pain Grade (CPG), the Health Utilities Index 3 and the Hospital Anxiety and Depression Scale (HADS). Outcomes were collected at 0, 3 and 6 months. Results In the prescribing arm (n=70) two patients were excluded/nine withdrew. In the review arm (n=63) one was excluded/three withdrew. In the TAU arm (n=63) four withdrew. Compared with baseline, patients had an improved CPG in the prescribing arm, 47.7% (21/44; p=0.003) and in the review arm, 38.6% (17/44; p=0.001), but not the TAU group, 31.3% (15/48; ns). The SF-12 Physical Component Score showed no effect in the prescribing or review arms but improvement in TAU (p=0.02). The SF-12 Mental Component Score showed no effect for the prescribing or review arms and deterioration in the TAU arm (p=0.002). HADS scores improved within the prescribing arm for depression (p=0.022) and anxiety (p=0.007), between groups (p=0.022 and p=0.045, respectively). Conclusions This is the first randomised controlled trial of pharmacist prescribing in the UK, and suggests that there may be a benefit for patients with chronic pain. A larger trial is required. Trial registration: www.isrctn.org/ISRCTN06131530. Medical Research Council funding. PMID:23562814

Association of cardiac implantable electronic devices with survival in bifascicular block and prolonged PR interval on electrocardiogram.

PubMed

Moulki, Naeem; Kealhofer, Jessica V; Benditt, David G; Gravely, Amy; Vakil, Kairav; Garcia, Santiago; Adabag, Selcuk

2018-06-16

Bifascicular block and prolonged PR interval on the electrocardiogram (ECG) have been associated with complete heart block and sudden cardiac death. We sought to determine if cardiac implantable electronic devices (CIED) improve survival in these patients. We assessed survival in relation to CIED status among 636 consecutive patients with bifascicular block and prolonged PR interval on the ECG. In survival analyses, CIED was considered as a time-varying covariate. Average age was 76 ± 9 years, and 99% of the patients were men. A total of 167 (26%) underwent CIED (127 pacemaker only) implantation at baseline (n = 23) or during follow-up (n = 144). During 5.4 ± 3.8 years of follow-up, 83 (13%) patients developed complete or high-degree atrioventricular block and 375 (59%) died. Patients with a CIED had a longer survival compared to those without a CIED in the traditional, static analysis (log-rank p < 0.0001) but not when CIED was considered as a time-varying covariate (log-rank p = 0.76). In the multivariable model, patients with a CIED had a 34% lower risk of death (hazard ratio 0.66, 95% confidence interval 0.52-0.83; p = 0.001) than those without CIED in the traditional analysis but not in the time-varying covariate analysis (hazard ratio 1.05, 95% confidence interval 0.79-1.38; p = 0.76). Results did not change in the subgroup with a pacemaker only. Bifascicular block and prolonged PR interval on ECG are associated with a high incidence of complete atrioventricular block and mortality. However, CIED implantation does not have a significant influence on survival when time-varying nature of CIED implantation is considered.

Evaluating OpenSHMEM Explicit Remote Memory Access Operations and Merged Requests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boehm, Swen; Pophale, Swaroop S; Gorentla Venkata, Manjunath

The OpenSHMEM Library Specification has evolved consid- erably since version 1.0. Recently, non-blocking implicit Remote Memory Access (RMA) operations were introduced in OpenSHMEM 1.3. These provide a way to achieve better overlap between communication and computation. However, the implicit non-blocking operations do not pro- vide a separate handle to track and complete the individual RMA opera- tions. They are guaranteed to be completed after either a shmem quiet(), shmem barrier() or a shmem barrier all() is called. These are global com- pletion and synchronization operations. Though this semantic is expected to achieve a higher message rate for the applications, themore » drawback is that it does not allow fine-grained control over the completion of RMA operations. In this paper, first, we introduce non-blocking RMA operations with requests, where each operation has an explicit request to track and com- plete the operation. Second, we introduce interfaces to merge multiple requests into a single request handle. The merged request tracks multiple user-selected RMA operations, which provides the flexibility of tracking related communication operations with one request handle. Lastly, we explore the implications in terms of performance, productivity, usability and the possibility of defining different patterns of communication via merging of requests. Our experimental results show that a well designed and implemented OpenSHMEM stack can hide the overhead of allocating and managing the requests. The latency of RMA operations with requests is similar to blocking and implicit non-blocking RMA operations. We test our implementation with the Scalable Synthetic Compact Applications (SSCA #1) benchmark and observe that using RMA operations with requests and merging of these requests outperform the implementation using blocking RMA operations and implicit non-blocking operations by 49% and 74% respectively.« less

Fluconazole use and safety in the nursery.

PubMed

Castagnola, E; Jacqz-Aigrain, E; Kaguelidou, F; Maragliano, R; Stronati, M; Rizzollo, S; Farina, D; Manzoni, P

2012-05-01

Fluconazole is a triazole antifungal agent that is widely used in the nursery. It is available in both intravenous and oral formulation, and is active against most of the fungal pathogens that require treatment when retrieved from culture samples in neonatal intensive care units. Although clinical use has been wide for over 15 years, there have been small safety and efficacy studies completed in young infants. Randomised clinical trials assessing effectiveness of this agent in prevention of systemic fungal infections in neonates have been published in the last decade, and one large additional randomised study has been recently completed. Nevertheless, a certain degree of uncertainty still exists regarding the kinetics and appropriate dosing of this agent in premature and term infants, as well as regarding safety. Areas of poignant debate include the feasibility of loading dose strategies, appropriate dosages in the early days of life in the different subgroups of preterm infants, and long-term safety of fluconazole administered in prophylaxis during the first weeks of life in extremely premature infants. This paper reviews the most recent evidence on fluconazole and its role in the NICU settings. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Does an on-road motorcycle coaching program reduce crashes in novice riders? A randomised control trial.

PubMed

Ivers, Rebecca Q; Sakashita, Chika; Senserrick, Teresa; Elkington, Jane; Lo, Serigne; Boufous, Soufiane; de Rome, Liz

2016-01-01

Motorcycle riding is increasing globally and confers a high risk of crash-related injury and death. There is community demand for investment in rider training programs but no high-quality evidence about its effectiveness in preventing crashes. This randomised trial of an on-road rider coaching program aimed to determine its effectiveness in reducing crashes in novice motorcycle riders. Between May 2010 and October 2012, 2399 newly-licensed provisional riders were recruited in Victoria, Australia and completed a telephone interview before randomisation to intervention or control groups. Riders in the intervention group were offered an on-road motorcycle rider coaching program which involved pre-program activities, 4h riding and facilitated discussion in small groups with a riding coach. Outcome measures were collected for all participants via telephone interviews at 3 and 12 months after program delivery (or equivalent for controls), and via linkage to police-recorded crash and offence data. The primary outcome was a composite measure of police-recorded and self-reported crashes; secondary outcomes included traffic offences, near crashes, riding exposure, and riding behaviours and motivations. Follow-up was 89% at 3 months and 88% at 12 months; 60% of the intervention group completed the program. Intention-to-treat analyses conducted in 2014 indicated no effect on crash risk at 3 months (adjusted OR 0.90, 95% CI: 0.65-1.27) or 12 months (adjusted OR 1.00, 95% CI: 0.78-1.29). Riders in the intervention group reported increased riding exposure, speeding behaviours and rider confidence. There was no evidence that this on-road motorcycle rider coaching program reduced the risk of crash, and we found an increase in crash-related risk factors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A randomised controlled trial of a web-based multi-modal therapy program to improve executive functioning in children and adolescents with acquired brain injury.

PubMed

Piovesana, Adina; Ross, Stephanie; Lloyd, Owen; Whittingham, Koa; Ziviani, Jenny; Ware, Robert S; McKinlay, Lynne; Boyd, Roslyn N

2017-10-01

To examine the efficacy of a multi-modal web-based therapy program, Move it to improve it (Mitii™) delivered at home to improve Executive Functioning (EF) in children with an acquired brain injury (ABI). Randomised Waitlist controlled trial. Home environment. Sixty children with an ABI were matched in pairs by age and intelligence quotient then randomised to either 20-weeks of Mitii™ training or 20 weeks of Care As Usual (waitlist control; n=30; 17 males; mean age=11y, 11m (±2y, 6m); Full Scale IQ=76.24±17.84). Fifty-eight children completed baseline assessments (32 males; mean age=11.87±2.47; Full Scale IQ=75.21±16.76). Executive functioning was assessed on four domains: attentional control, cognitive flexibility, goal setting, and information processing using subtests from the Wechsler Intelligence Scale for Children (WISC-IV), Delis-Kaplan Executive Functioning System (D-KEFS), Comprehensive Trail Making Test (CTMT), Tower of London (TOL), and Test of Everyday Attention for Children (Tea-Ch). Executive functioning performance in everyday life was assessed via parent questionnaire (Behaviour Rating Inventory of Executive Functioning; BRIEF). No differences were observed at baseline measures. Groups were compared at 20-weeks using linear regression with no significant differences found between groups on all measures of EF. Out of a potential total dose of 60 hours, children in the Mitii™ group completed a mean of 17 hours of Mitii™ intervention. Results indicate no additional benefit to receiving Mitii™ compared to standard care. Mitii™, in its current form, was not shown to improve EF in children with ABI.

A pilot study to assess the utility of a freely downloadable mobile application simulator for undergraduate clinical skills training: a single-blinded, randomised controlled trial.

PubMed

Bartlett, Richard D; Radenkovic, Dina; Mitrasinovic, Stefan; Cole, Andrew; Pavkovic, Iva; Denn, Peyton Cheong Phey; Hussain, Mahrukh; Kogler, Magdalena; Koutsopodioti, Natalia; Uddin, Wasima; Beckley, Ivan; Abubakar, Hana; Gill, Deborah; Smith, Daron

2017-12-11

Medical simulators offer an invaluable educational resource for medical trainees. However, owing to cost and portability restrictions, they have traditionally been limited to simulation centres. With the advent of sophisticated mobile technology, simulators have become cheaper and more accessible. Touch Surgery is one such freely downloadable mobile application simulator (MAS) used by over one million healthcare professionals worldwide. Nevertheless, to date, it has never been formally validated as an adjunct in undergraduate medical education. Medical students in the final 3 years of their programme were recruited and randomised to one of three revision interventions: 1) no formal revision resources, 2) traditional revision resources, or 3) MAS. Students completed pre-test questionnaires and were then assessed on their ability to complete an undisclosed male urinary catheterisation scenario. Following a one-hour quarantined revision period, all students repeated the scenario. Both attempts were scored by allocation-blinded examiners against an objective 46-point mark scheme. A total of 27 medical students were randomised (n = 9 per group). Mean scores improved between baseline and post-revision attempts by 8.7% (p = 0.003), 19.8% (p = 0.0001), and 15.9% (p = 0.001) for no resources, traditional resources, and MAS, respectively. However, when comparing mean score improvements between groups there were no significant differences. Mobile simulators offer an unconventional, yet potentially useful adjunct to enhance undergraduate clinical skills education. Our results indicate that MAS's perform comparably to current gold-standard revision resources; however, they may confer significant advantages in terms of cost-effectiveness and practice flexibility. Not applicable.

Effectiveness of an audience response system on orthodontic knowledge retention of undergraduate dental students--a randomised control trial.

PubMed

Robson, Nicholas; Popat, Hashmat; Richmond, Stephen; Farnell, Damian J J

2015-01-01

To determine the effect of an audience response system (ARS) on knowledge retention of dental students and to gauge student perceptions of using the ARS. Randomised control study. School of Dentistry, Cardiff University. Seventy four second-year dental students were stratified by gender and randomised anonymously to one of two groups. One group received a lecture on orthodontic terminology and diagnosis in a traditional didactic format and the other received the same lecture integrated with ARS slides. Students completed an assessment of multiple-choice questions (MCQs) scored out of 20, before and immediately after the lecture. Students were also asked to complete a self-reported questionnaire on their perceptions of ARS. Both groups had statistically significant increases in MCQ scores post-lecture (ARS mean increase 3.6 SD2.0, 95% CI 2.2-3.5 and Didactic mean increase 2.9 SD2.3, 95% CI 2.8-4.3). A mixed-design analysis of variance showed that ARS led to an improved MCQ score (by 0.8 or 25%) compared to the didactic group, although this effect was not significant (P = 0.15). The effect of gender at baseline (P = 0.49), post-lecture (P = 0.73) and increase in MCQ score split by group (P = 0.46) was also not significant. Students reported that the ARS was easy to use, helped them engage with the lecture and encouraged them to work harder. The ARS did not lead to a significant increase in short-term orthodontic knowledge recall of students compared with didactic teaching. However, the use of ARS within orthodontic teaching could make lectures more interactive and engaging.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.

PubMed

Dean, Olivia M; Gray, Kylie M; Villagonzalo, Kristi-Ann; Dodd, Seetal; Mohebbi, Mohammadreza; Vick, Tanya; Tonge, Bruce J; Berk, Michael

2017-03-01

Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

A cluster randomised controlled trial evaluating the effectiveness of eHealth-supported patient recruitment in primary care research: the TRANSFoRm study protocol.

PubMed

Mastellos, Nikolaos; Andreasson, Anna; Huckvale, Kit; Larsen, Mark; Curcin, Vasa; Car, Josip; Agreus, Lars; Delaney, Brendan

2015-02-03

Opportunistic recruitment is a highly laborious and time-consuming process that is currently performed manually, increasing the workload of already busy practitioners and resulting in many studies failing to achieve their recruitment targets. The Translational Medicine and Patient Safety in Europe (TRANSFoRm) platform enables automated recruitment, data collection and follow-up of patients, potentially improving the efficiency, time and costs of clinical research. This study aims to assess the effectiveness of TRANSFoRm in improving patient recruitment and follow-up in primary care trials. This multi-centre, parallel-arm cluster randomised controlled trial will compare TRANSFoRm-supported with standard opportunistic recruitment. Participants will be general practitioners and patients with gastro-oesophageal reflux disease from 40 primary care centres in five European countries. Randomisation will take place at the care centre level. The intervention arm will use the TRANSFoRm tools for recruitment, baseline data collection and follow-up. The control arm will use web-based case report forms and paper self-completed questionnaires. The primary outcome will be the proportion of eligible patients successfully recruited at the end of the 16-week recruitment period. Secondary outcomes will include the proportion of recruited patients with complete baseline and follow-up data and the proportion of participants withdrawn or lost to follow-up. The study will also include an economic evaluation and measures of technology acceptance and user experience. The study should shed light on the use of eHealth to improve the effectiveness of recruitment and follow-up in primary care research and provide an evidence base for future eHealth-supported recruitment initiatives. Reporting of results is expected in October 2015. EudraCT: 2014-001314-25.

Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.

PubMed

Nishimura, Junichi; Satoh, Taroh; Fukunaga, Mutsumi; Takemoto, Hiroyoshi; Nakata, Ken; Ide, Yoshihito; Fukuzaki, Takayuki; Kudo, Toshihiro; Miyake, Yasuhiro; Yasui, Masayoshi; Morita, Shunji; Sakai, Daisuke; Uemura, Mamoru; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ohno, Yuko; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Nezu, Riichiro; Doki, Yuichiro; Mori, Masaki

2015-07-01

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of self-hypnosis on hay fever symptoms - a randomised controlled intervention study.

PubMed

Langewitz, Wolf; Izakovic, Jan; Wyler, Jane; Schindler, Christian; Kiss, Alexander; Bircher, Andreas J

2005-01-01

Many people suffer from hay fever symptoms. Hypnosis has proved to be a useful adjunct in the treatment of conditions where allergic phenomena have an important role. Randomised parallel group study over an observation period of two consecutive pollen seasons. Outcome data include nasal flow under hypnosis, pollinosis symptoms from diaries and retrospective assessments, restrictions in well-being and use of anti-allergic medication. We investigated 79 patients with a mean age of 34 years (range 19-54 years; 41 males), with moderate to severe allergic rhinitis to grass or birch pollen of at least 2 years duration and mild allergic asthma. The intervention consisted of teaching self-hypnosis during a mean of 2.4 sessions (SD 1.7; range 2-5 sessions) and continuation of standard anti-allergic pharmacological treatment. Of 79 randomised patients, 66 completed one, and 52 completed two seasons. Retrospective VAS scores yielded significant improvements in year 1 in patients who had learned self-hypnosis: pollinosis symptoms -29.2 (VAS score, range 0-100; SD 25.4; p < 0.001), restriction of well-being -26.2 (VAS score, range 0-100; SD 28.7; p < 0.001. In year 2, the control group improved significantly having learned self-hypnosis as well: pollinosis symptoms -24.8 (SD 29.1; p < 0.001), restriction of well-being -23.7 (SD 30.0; p < 0.001). Daily self-reports of subjects who learnt self-hypnosis do not show a significant improvement. The hazard ratio of reaching a critical flow of 70% in nasal provocation tests was 0.333 (95% CI 0.157-0.741) after having learnt and applied self-hypnosis.

Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease.

PubMed

Scorletti, Eleonora; Afolabi, Paul R; Miles, Elizabeth A; Smith, Debbie E; Almehmadi, Amal; Alshathry, Albandri; Moyses, Helen E; Clough, Geraldine F; Wright, Mark; Patel, Janisha; Bindels, Laure; Delzenne, Nathalie M; Calder, Philip C; Byrne, Christopher D

2018-05-19

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. In a randomised double-blind placebo controlled trial, 104 participants were randomised to 10-14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640. Copyright © 2017. Published by Elsevier Inc.

Randomised trial of two nicotine patch protocols distributed through a state quitline.

PubMed

Burns, Emily K; Hood, Nancy E; Goforth, Emma; Levinson, Arnold H

2016-03-01

Most telephone quitlines provide free nicotine replacement therapy (NRT). An 8-week course is recommended, but few users complete it. Information is needed to help quitlines distribute NRT cost-effectively. Randomised two-group trial. Colorado QuitLine callers who smoked 16-20 cigarettes per day at enrolment and who were eligible for and agreed to receive free NRT. Provision of 4-week versus 8-week NRT supply; the 8-week supply was shipped in halves and required participants to request the second half (split-shipment protocol). Enrolment occurred during March 2010-February 2011, follow-up concluded in November 2011, and analysis was performed in 2012. Point abstinence (7 and 30 day) and prolonged abstinence (6 month) from tobacco use. Overall, 1495 study participants were enrolled and 57.7% completed follow-up. Abstinence rates did not differ significantly between study conditions: 13.8% versus 12.4% in 4-week versus 8-week arms, respectively, (30-day point abstinence, non-respondents treated as smokers). NRT duration was similar in both groups, due in part to purchase of additional patches in the 4-week group. About one-third of the 8-week group requested the full 8-week supply and had higher abstinence rates. Cost per quit was lower in the 4-week (compared to 8-week) group. A randomised trial did not find worse cessation outcomes among quitline users who received half the minimum recommended course of NRT, but offering the full recommended course using a split-shipment protocol may be reasonably cost-effective and supportive of NRT adherers. NCT01889771. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

PubMed

Cockayne, E Sarah

2010-02-08

Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. Current Controlled Trials ISRCTN18994246.

Randomised controlled crossover trial of the effect on PtCO2 of oxygen-driven versus air-driven nebulisers in severe chronic obstructive pulmonary disease.

PubMed

Edwards, Llifon; Perrin, Kyle; Williams, Mathew; Weatherall, Mark; Beasley, Richard

2012-11-01

The comparative safety of oxygen versus air-driven nebulised bronchodilators in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain. A randomised controlled trial was performed to assess the effect on the arterial partial pressure of carbon dioxide of nebulised bronchodilator driven with oxygen versus air in stable severe COPD. In an open label randomised study, 18 subjects with stable severe COPD attended on 2 days to receive nebulised bronchodilator therapy driven by air or oxygen. Subjects received 5 mg salbutamol and 0.5 mg ipratropium bromide by nebulisation over 15 min, then, after 5 min, 5 mg salbutamol nebulised over 15 min, followed by 15 min of observation. Transcutaneous carbon dioxide tension (PtCO(2)) and oxygen saturations were recorded at 5 min intervals during the study. The primary outcome was the PtCO(2) after the completion of the second bronchodilator treatment. PtCO(2) was higher with nebulised bronchodilator therapy delivered by oxygen, but decreased back to the level associated with air nebulisation 15 min after completion of the second nebulised dose. One subject experienced an increase in PtCO(2) of 11 mm Hg after the first bronchodilator nebulisation driven by oxygen. The mean PtCO(2) difference between the oxygen and air groups after the second nebulisation was 3.1 mm Hg (95% CI 1.6 to 4.5, p<0.001). Nebulisers driven with oxygen result in significantly higher levels of PtCO(2) than those driven with air in patients with severe COPD. The study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12610000080022).

The long-term effect of minimalist shoes on running performance and injury: design of a randomised controlled trial

PubMed Central

Fuller, Joel T; Thewlis, Dominic; Tsiros, Margarita D; Brown, Nicholas A T; Buckley, Jonathan D

2015-01-01

Introduction The outcome of the effects of transitioning to minimalist running shoes is a topic of interest for runners and scientists. However, few studies have investigated the longer term effects of running in minimalist shoes. The purpose of this randomised controlled trial (RCT) is to investigate the effects of a 26 week transition to minimalist shoes on running performance and injury risk in trained runners unaccustomed to minimalist footwear. Methods and analysis A randomised parallel intervention design will be used. Seventy-six trained male runners will be recruited. To be eligible, runners must be aged 18–40 years, run with a habitual rearfoot footfall pattern, train with conventional shoes and have no prior experience with minimalist shoes. Runners will complete a standardised transition to either minimalist or control shoes and undergo assessments at baseline, 6 and 26 weeks. 5 km time-trial performance (5TT), running economy, running biomechanics, triceps surae muscle strength and lower limb bone mineral density will be assessed at each time point. Pain and injury will be recorded weekly. Training will be standardised during the first 6 weeks. Primary statistical analysis will compare 5TT between shoe groups at the 6-week time point and injury incidence across the entire 26-week study period. Ethics and dissemination This RCT has been approved by the Human Research Ethics Committee of the University of South Australia. Participants will be required to provide their written informed consent prior to participation in the study. Study findings will be disseminated in the form of journal publications and conference presentations after completion of planned data analysis. Trial registration number This RCT has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000642785). PMID:26297368

Effectiveness of an audience response system on orthodontic knowledge retention of undergraduate dental students – a randomised control trial

PubMed Central

Robson, Nicholas; Popat, Hashmat; Richmond, Stephen; Farnell, Damian J. J.

2015-01-01

Objective:: To determine the effect of an audience response system (ARS) on knowledge retention of dental students and to gauge student perceptions of using the ARS. Design:: Randomised control study. Setting:: School of Dentistry, Cardiff University. Participants:: Seventy four second-year dental students were stratified by gender and randomised anonymously to one of two groups. Methods:: One group received a lecture on orthodontic terminology and diagnosis in a traditional didactic format and the other received the same lecture integrated with ARS slides. Students completed an assessment of multiple-choice questions (MCQs) scored out of 20, before and immediately after the lecture. Students were also asked to complete a self-reported questionnaire on their perceptions of ARS. Results:: Both groups had statistically significant increases in MCQ scores post-lecture (ARS mean increase 3.6 SD2.0, 95% CI 2.2–3.5 and Didactic mean increase 2.9 SD2.3, 95% CI 2.8–4.3). A mixed-design analysis of variance showed that ARS led to an improved MCQ score (by 0.8 or 25%) compared to the didactic group, although this effect was not significant (P = 0.15). The effect of gender at baseline (P = 0.49), post-lecture (P = 0.73) and increase in MCQ score split by group (P = 0.46) was also not significant. Students reported that the ARS was easy to use, helped them engage with the lecture and encouraged them to work harder. Conclusion:: The ARS did not lead to a significant increase in short-term orthodontic knowledge recall of students compared with didactic teaching. However, the use of ARS within orthodontic teaching could make lectures more interactive and engaging. PMID:26282015

Online testable concept maps: benefits for learning about the pathogenesis of disease.

PubMed

Ho, Veronica; Kumar, Rakesh K; Velan, Gary

2014-07-01

Concept maps have been used to promote meaningful learning and critical thinking. Although these are crucially important in all disciplines, evidence for the benefits of concept mapping for learning in medicine is limited. We performed a randomised crossover study to assess the benefits of online testable concept maps for learning in pathology by volunteer junior medical students. Participants (n = 65) were randomly allocated to either of two groups with equivalent mean prior academic performance, in which they were given access to either online maps or existing online resources for a 2-week block on renal disease. Groups then crossed over for a 2-week block on hepatic disease. Outcomes were assessed using timed online quizzes, which included questions unrelated to topics in the pathogenesis maps as an internal control. Questionnaires were administered to evaluate students' acceptance of the maps. In both blocks, the group with access to pathogenesis maps achieved significantly higher average scores than the control group on quiz questions related to topics covered by the maps (Block 1: p < 0.001, Cohen's d = 0.9; Block 2: p = 0.008, Cohen's d = 0.7). However, mean scores on unrelated questions did not differ significantly between the groups. In a third block on pancreatic disease, both groups received pathogenesis maps and collectively performed significantly better on quiz topics related to the maps than on unrelated topics (p < 0.01, Cohen's d = 0.5). Regression analysis revealed that access to pathogenesis maps was the dominant contributor to variance in performance on map-related quiz questions. Responses to questionnaire items on pathogenesis maps were overwhelmingly positive in both groups. These results indicate that online testable pathogenesis maps are well accepted and can improve learning of concepts in pathology by medical students. © 2014 John Wiley & Sons Ltd.

Blood pressure response to combined general anaesthesia/interscalene brachial plexus block for outpatient shoulder arthroscopy.

PubMed

Janssen, Hauke; Stosch, Roland von; Pöschl, Rupert; Büttner, Benedikt; Bauer, Martin; Hinz, José Maria; Bergmann, Ingo

2014-01-01

Shoulder surgery is often performed in the beach-chair position, a position associated with arterial hypotension and subsequent risk of cerebral ischaemia. It can be performed under general anaesthesia or with an interscalene brachial plexus block, each of which has specific advantages but also specific negative effects on blood pressure control. It would be worthwhile to combine the advantages of the two, but the effects of the combination on the circulation are not well investigated. We studied blood pressure, heart rate, and incidence of adverse circulatory events in patients undergoing shoulder surgery in general anaesthesia with or without an interscalene block. Prospective, randomised, blinded study in outpatients (age 18 to 80 years) undergoing shoulder arthroscopy. General anaesthesia was with propofol/opioid, interscalene block with 40 ml 1% mepivacaine. Hypotension requiring treatment was defined as a mean arterial pressure <60 mmHg or a systolic pressure <80% of baseline; relevant bradycardia was a heart rate <50 bpm with a decrease in blood pressure. Forty-two patients had general anaesthesia alone, 41 had general anaesthesia plus interscalene block. The average systolic blood pressure under anaesthesia in the beach-chair position was 114 ± 7.3 vs. 116 ± 8.3 mmHg (p = 0.09; all comparisons General vs. General-Regional). The incidence of a mean arterial pressure under 60 mmHg or a decrease in systolic pressure of more than 20% from baseline was 64% vs. 76% (p = 0.45). The number of patients with a heart rate lower than 50 and a concomitant blood pressure decrease was 8 vs. 5 (p = 0.30). One can safely combine interscalene block with general anaesthesia for surgery in the beach-chair position in ASA I and II patients. DRKS00005295.

Treatment of retained placenta with misoprostol: a randomised controlled trial in a low-resource setting (Tanzania).

PubMed

van Beekhuizen, Heleen J; Pembe, Andrea B; Fauteck, Heiner; Lotgering, Fred K

2009-10-23

Retained placenta is one of the common causes of maternal mortality in developing countries where access to appropriate obstetrical care is limited. Current treatment of retained placenta is manual removal of the placenta under anaesthesia, which can only take place in larger health care facilities. Medical treatment of retained placenta with prostaglandins E1 (misoprostol) could be cost-effective and easy-to-use and could be a life-saving option in many low-resource settings. The aim of this study is to assess the efficacy and safety of sublingually administered misoprostol in women with retained placenta in a low resource setting. Multicentered randomised, double-blind, placebo-controlled trial, to be conducted in 5 hospitals in Tanzania, Africa. Women with retained placenta, at a gestational age of 28 weeks or more and blood loss less than 750 ml, 30 minutes after delivery of the newborn despite active management of third stage of labour. Trial Entry & Randomisation & Study Medication: After obtaining informed consent, eligible women will be allocated randomly to the treatment groups using numbered envelopes that will be randomized in variable blocks containing identical capsules with either 800 microgram of misoprostol or placebo. The drugs will be given sublingually. The women, maternal care providers and researchers will be blinded to treatment allocation. 117 women, to show a 40% reduction in manual removals of the placenta (p = 0.05, 80% power). The randomization will be misoprostol: placebo = 2:1. PRIMARY STUDY OUTCOME: Expulsion of the placenta without manual removal. Secondary outcome is the number of blood transfusions. This is a protocol for a randomized trial in a low resource setting to assess if medical treatment of women with retained placenta with misoprostol reduces the incidence of manual removal of the placenta. Current Controlled Trials ISRCTN16104753.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

PubMed

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-07-17

Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effectiveness of osteopathic manipulative treatment in neonatal intensive care units: protocol for a multicentre randomised clinical trial

PubMed Central

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; D'Incecco, Carmine; Fusilli, Paola; Perri, Paolo Francesco; Tubaldi, Lucia; Barlafante, Gina

2013-01-01

Introduction Neonatal care has been considered as one of the first priorities for improving quality of life in children. In 2010, 10% of babies were born prematurely influencing national healthcare policies, economic action plans and political decisions. The use of complementary medicine has been applied to the care of newborns. One previous study documented the positive effect of osteopathic manipulative treatment (OMT) in reducing newborns’ length of stay (LOS). Aim of this multicentre randomised controlled trial is to examine the association between OMT and LOS across three neonatal intensive care units (NICUs). Methods and analysis 690 preterm infants will be recruited from three secondary and tertiary NICUs from north and central Italy and allocated into two groups, using permuted-block randomisation. The two groups will receive standard medical care and OMT will be applied, twice a week, to the experimental group only. Outcome assessors will be blinded of study design and group allocation. The primary outcome is the mean difference in days between discharge and entry. Secondary outcomes are difference in daily weight gain, number of episodes of vomit, regurgitation, stooling, use of enema, time to full enteral feeding and NICU costs. Statistical analyses will take into account the intention-to-treat method. Missing data will be handled using last observation carried forward (LOCF) imputation technique. Ethics and dissemination Written informed consent will be obtained from parents or legal guardians at study enrolment. The trial has been approved by the ethical committee of Macerata hospital (n°22/int./CEI/27239) and it is under review by the other regional ethics committees. Results Dissemination of results from this trial will be through scientific medical journals and conferences. Trial registration This trial has been registered at http://www.clinicaltrials.org (identifier NCT01645137). PMID:23430598

Effect of the patient education - Learning and Coping strategies - in cardiac rehabilitation on return to work at one year: a randomised controlled trial show (LC-REHAB).

PubMed

Bitsch, Birgitte Laier; Nielsen, Claus Vinther; Stapelfeldt, Christina Malmose; Lynggaard, Vibeke

2018-05-21

Personal resources are identified as important for the ability to return to work (RTW) for patients with ischaemic heart disease (IHD) or heart failure (HF) undergoing cardiac rehabilitation (CR). The patient education 'Learning and Coping' (LC) addresses personal resources through a pedagogical approach. This trial aimed to assess effect of adding LC strategies in CR compared to standard CR measured on RTW status at one-year follow-up after CR. In an open parallel randomised controlled trial, patients with IHD or HF were block-randomised in a 1:1 ratio to the LC arm (LC plus CR) or the control arm (CR alone) across three Danish hospital units. Eligible patients were aged 18 to ≤60 and had not left the labour market. The intervention was developed from an inductive pedagogical approach consisting of individual interviews and group based teaching by health professionals with experienced patients as co-educators. The control arm consisted of deductive teaching (standard CR). RTW status was derived from the Danish Register for Evaluation of Marginalisation (DREAM). Blinding was not possible. The effect was evaluated by logistic regression analysis and reported as crude and adjusted odds ratios (OR) with 95% confidence interval (CI). The population for the present analysis was N = 244 (LC arm: n = 119 versus control arm: n = 125). No difference in RTW status was found at one year across arms (LC arm: 64.7% versus control arm: 68.8%, adjusted odds ratio OR: 0.76, 95% CI: 0.43-1.31). Addition of LC strategies in CR showed no improvement in RTW at one year follow-up. www.clinicaltrials.gov identifier NCT01668394. First Posted: August 20, 2012.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

PubMed Central

Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-01-01

Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0–10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results. PMID:28716797

Shoulder function and work disability after decompression surgery for subacromial impingement syndrome: a randomised controlled trial of physiotherapy exercises and occupational medical assistance.

PubMed

Svendsen, Susanne W; Christiansen, David H; Haahr, Jens Peder; Andrea, Linda C; Frost, Poul

2014-06-21

Surgery for subacromial impingement syndrome is often performed in working age and postoperative physiotherapy exercises are widely used to help restore function. A recent Danish study showed that 10% of a nationwide cohort of patients retired prematurely within two years after surgery. Few studies have compared effects of different postoperative exercise programmes on shoulder function, and no studies have evaluated workplace-oriented interventions to reduce postoperative work disability. This study aims to evaluate the effectiveness of physiotherapy exercises and occupational medical assistance compared with usual care in improving shoulder function and reducing postoperative work disability after arthroscopic subacromial decompression. The study is a mainly pragmatic multicentre randomised controlled trial. The trial is embedded in a cohort study of shoulder patients referred to public departments of orthopaedic surgery in Central Denmark Region. Patients aged ≥18-≤63 years, who still have shoulder symptoms 8-12 weeks after surgery, constitute the study population. Around 130 participants are allocated to: 1) physiotherapy exercises, 2) occupational medical assistance, 3) physiotherapy exercises and occupational medical assistance, and 4) usual care. Intervention manuals allow individual tailoring. Primary outcome measures include Oxford Shoulder Score and sickness absence due to symptoms from the operated shoulder. Randomisation is computerised with allocation concealment by randomly permuted block sizes. Statistical analyses will primarily be performed according to the intention-to-treat principle. The paper presents the rationale, design, methods, and operational aspects of the Shoulder Intervention Project (SIP). SIP evaluates a new rehabilitation approach, where physiotherapy and occupational interventions are provided in continuity of surgical episodes of care. If successful, the project may serve as a model for rehabilitation of surgical shoulder patients. Current Controlled Trials ISRCTN55768749.

Music therapy in Huntington's disease: a protocol for a multi-center randomized controlled trial.

PubMed

van Bruggen-Rufi, Monique; Vink, Annemieke; Achterberg, Wilco; Roos, Raymund

2016-07-26

Huntington's disease is a progressive, neurodegenerative disease with autosomal dominant inheritance, characterized by motor disturbances, cognitive decline and behavioral and psychological symptoms. Since there is no cure, all treatment is aimed at improving quality of life. Music therapy is a non-pharmacological intervention, aiming to improve the quality of life, but its use and efficacy in patients with Huntington's disease has hardly been studied. In this article, a protocol is described to study the effects of music therapy in comparison with a control intervention to improve quality of life through stimulating expressive and communicative skills. By targeting these skills we assume that the social-cognitive functioning will improve, leading to a reduction in behavioral problems, resulting in an overall improvement of the quality of life in patients with Huntington's disease. The study is designed as a multi-center single-blind randomised controlled intervention trial. Sixty patients will be randomised using centre-stratified block-permuted randomisation. Patients will be recruited from four long-term care facilities specialized in Huntington's disease-care in The Netherlands. The outcome measure to assess changes in expressive and communication skills is the Behaviour Observation Scale Huntington and changes in behavior will be assessed by the Problem Behaviour Assesment-short version and by the BOSH. Measurements take place at baseline, then 8, 16 (end of intervention) and 12 weeks after the last intervention (follow-up). This randomized controlled study will provide greater insight into the effectiveness of music therapy on activities of daily living, social-cognitive functioning and behavior problems by improving expressive and communication skills, thus leading to a better quality of life for patients with Huntington's disease. Netherlands Trial Register: NTR4904 , registration date Nov. 15, 2014.

Atrioventricular Block Induced by Mad-Honey Intoxication

PubMed Central

Cagli, Kumral Ergun; Tufekcioglu, Omac; Sen, Nihat; Aras, Dursun; Topaloglu, Serkan; Basar, Nur; Pehlivan, Sevil

2009-01-01

An unusual type of food poisoning, mad-honey intoxication, can be observed in the Black Sea region of Turkey and various other parts of the world. It can occur after ingestion of grayanotoxin-contaminated honey produced from the nectar of Rhododendron ponticum and other plant species, chiefly of the Ericaceae and Sapindaceae families. Mad-honey intoxication can result in severe cardiac complications, such as complete atrioventricular block. The diagnosis is generally reached on the basis of the patient's history of honey intake. In this report, we describe the case of a patient who had mad-honey–related complete atrioventricular block; in this instance, the diagnosis was confirmed by a pollen analysis of the suspect honey. PMID:19693312

Complications with the MICRA TPS Pacemaker System: Persistent Complete Heart Block and Late Capture Failure.

PubMed

Holm, Niels; Müller, Andreas; Zbinden, Rainer

2017-04-01

A Medtronic MICRA transcatheter pacing system (Medtronic, Minneapolis, MN, USA) was implanted in an 86-year-old patient with sick sinus syndrome and left bundle branch block after transfemoral aortic valve implantation. During implantation she developed a persistent complete heart block due to manipulation with the large-bore delivery catheter. Two weeks later, acute pacemaker dysfunction occurred due to massive increase of pacing threshold and impedance without obvious pacemaker dislocation or myocardial perforation. Recurrent capture failure was seen with pacing output set at 5 V/1.0 ms. Hence, microdislocation or fixation of the tines in the right ventricular trabeculae has to be assumed. © 2016 Wiley Periodicals, Inc.

Potent malaria transmission-blocking antibody responses elicited by Plasmodium falciparum Pfs25 expressed in Escherichia coli after successful protein refolding.

PubMed

Kumar, Rajesh; Angov, Evelina; Kumar, Nirbhay

2014-04-01

Production of Pfs25, a Plasmodium falciparum transmission-blocking vaccine target antigen, in functional conformation with the potential to elicit effective immunogenicity still remains a major challenge. In the current study, codon-harmonized recombinant Pfs25 (CHrPfs25) was expressed in Escherichia coli, and purified protein after simple oxidative refolding steps retained reduction-sensitive conformational epitopes of transmission-blocking monoclonal antibodies. CHrPfs25 formulated in several adjuvants elicited strong immunogenicity in preclinical studies in mice. Antibodies elicited after immunization recognized native Pfs25 on the surface of live gametes of P. falciparum and demonstrated complete malaria transmission-blocking activity. The transmission-blocking efficacy was 100% even after a 1:128 dilution of sera from immunized mice in the complete Freund's adjuvant and Montanide ISA51 groups and after a 1:16 dilution of sera from mice in the alum group. The blocking was mediated by antibodies; purified IgG at concentrations as low as 31.25 μg/ml exhibited 100% transmission blocking in membrane feeding assays employing two different species of mosquitoes, Anopheles gambiae and Anopheles stephensi. This study provides the first evidence for successful expression of biologically functional rPfs25 in E. coli. The extremely potent malaria transmission-blocking activity of antibodies elicited by immunization with purified protein provides strong support for further evaluation of E. coli-derived CHrPfs25 as a malaria transmission-blocking vaccine in human clinical trials.

Real-time evaluation of diffusion of the local anesthetic solution during peribulbar block using ultrasound imaging and clinical correlates of diffusion.

PubMed

Luyet, Cédric; Eng, Kenneth T; Kertes, Peter J; Avila, Arsenio; Muni, Rajeev H; McHardy, Paul

2012-01-01

The aims of this prospective observational study were to assess the incidence of intraconal spread during peribulbar (extraconal) anesthesia by real-time ultrasound imaging of the retro-orbital compartment and to determine whether a complete sensory and motor block (with akinesia) of the eye is directly related to the intraconal spread. Ultrasound imaging was performed in 100 patients who underwent a surgical procedure on the posterior segment of the eye. All patients received a peribulbar block using the inferolateral approach. Once the needle was in place, a linear ultrasound transducer was placed over the eyelid and the spread of local anesthetics was assessed during the injection (real time). Akinesia was assessed by a blinded observer 10 minutes after block placement. The incidence of intraconal spread and its correlation with a complete akinesia was measured. The overall block failure rate was 28% in terms of akinesia, and the rate of rescue blocks was 20%. Clear intraconal spread during injection of the local anesthetic mixture could be detected with ultrasound imaging in 61 of 100 patients. The positive predictive value for successful block when intraconal spread was detected was 98% (95% confidence interval, 91%-100%). The association between clear and no evidence of intraconal spread and effective block was statistically significant (χ test, P < 0.001). Ultrasound imaging provides information of local anesthetic spread within the retro-orbital space, which might assist in the prediction of block success.

Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial

PubMed Central

Baselga, José; Bradbury, Ian; Eidtmann, Holger; Di Cosimo, Serena; de Azambuja, Evandro; Aura, Claudia; Gómez, Henry; Dinh, Phuong; Fauria, Karine; Van Dooren, Veerle; Aktan, Gursel; Goldhirsch, Aron; Chang, Tsai-Wang; Horváth, Zsolt; Coccia-Portugal, Maria; Domont, Julien; Tseng, Ling-Min; Kunz, Georg; Sohn, Joo Hyuk; Semiglazov, Vladimir; Lerzo, Guillermo; Palacova, Marketa; Probachai, Volodymyr; Pusztai, Lajos; Untch, Michael; Gelber, Richard D; Piccart-Gebhart, Martine

2017-01-01

Summary Background The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. Methods In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/kg, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m2) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00553358. Findings 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1–59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4–37·5]; difference 21·1%, 9·1–34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1–32·3]) and the trastuzumab (difference −4·8%, −17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%]). Interpretation Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting. Funding GlaxoSmithKline. PMID:22257673

Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.

PubMed

Wilke, Hansjochen; Muro, Kei; Van Cutsem, Eric; Oh, Sang-Cheul; Bodoky, György; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Lipatov, Oleg; Kim, Tae-You; Cunningham, David; Rougier, Philippe; Komatsu, Yoshito; Ajani, Jaffer; Emig, Michael; Carlesi, Roberto; Ferry, David; Chandrawansa, Kumari; Schwartz, Jonathan D; Ohtsu, Atsushi

2014-10-01

VEGFR-2 has a role in gastric cancer pathogenesis and progression. We assessed whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel. This randomised, placebo-controlled, double-blind, phase 3 trial was done at 170 centres in 27 countries in North and South America, Europe, Asia, and Australia. Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy (platinum plus fluoropyrimidine with or without an anthracycline) were randomly assigned with a centralised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15, plus paclitaxel 80 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle. A permuted block randomisation, stratified by geographic region, time to progression on first-line therapy, and disease measurability, was used. The primary endpoint was overall survival. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one treatment with study drug. This trial is registered with ClinicalTrials.gov, number NCT01170663, and has been completed; patients who are still receiving treatment are in the extension phase. Between Dec 23, 2010, and Sept 23, 2012, 665 patients were randomly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel. Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group (median 9·6 months [95% CI 8·5-10·8] vs 7·4 months [95% CI 6·3-8·4], hazard ratio 0·807 [95% CI 0·678-0·962]; p=0·017). Grade 3 or higher adverse events that occurred in more than 5% of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia (133 [41%] of 327 vs 62 [19%] of 329), leucopenia (57 [17%] vs 22 [7%]), hypertension (46 [14%] vs eight [2%]), fatigue (39 [12%] vs 18 [5%]), anaemia (30 [9%] vs 34 [10%]), and abdominal pain (20 [6%] vs 11 [3%]). The incidence of grade 3 or higher febrile neutropenia was low in both groups (ten [3%] vs eight [2%]). The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel, and could be regarded as a new standard second-line treatment for patients with advanced gastric cancer. Eli Lilly and Company. Copyright © 2014 Elsevier Ltd. All rights reserved.

WELLFOCUS PPT – modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial

PubMed Central

2014-01-01

Background The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. Methods/Design This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18–65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. Discussion This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. Trial registration Current Controlled Trials ISRCTN04199273 – WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013. PMID:24888479

The HubBLe trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for haemorrhoids.

PubMed

Tiernan, Jim; Hind, Daniel; Watson, Angus; Wailoo, Allan J; Bradburn, Michael; Shephard, Neil; Biggs, Katie; Brown, Steven

2012-10-25

Haemorrhoids (piles) are a very common condition seen in surgical clinics. After exclusion of more sinister causes of haemorrhoidal symptoms (rectal bleeding, perianal irritation and prolapse), the best option for treatment depends upon persistence and severity of the symptoms. Minor symptoms often respond to conservative treatment such as dietary fibre and reassurance. For more severe symptoms treatment such as rubber band ligation may be therapeutic and is a very commonly performed procedure in the surgical outpatient setting. Surgery is usually reserved for those who have more severe symptoms, as well as those who do not respond to non-operative therapy; surgical techniques include haemorrhoidectomy and haemorrhoidopexy. More recently, haemorrhoidal artery ligation has been introduced as a minimally invasive, non destructive surgical option.There are substantial data in the literature concerning efficacy and safety of 'rubber band ligation including multiple comparisons with other interventions, though there are no studies comparing it to haemorrhoidal artery ligation. A recent overview has been carried out by the National Institute for Health and Clinical Excellence which concludes that current evidence shows haemorrhoidal artery ligation to be a safe alternative to haemorrhoidectomy and haemorrhoidopexy though it also highlights the lack of good quality data as evidence for the advantages of the technique. The aim of this study is to establish the clinical effectiveness and cost effectiveness of haemorrhoidal artery ligation compared with conventional rubber band ligation in the treatment of people with symptomatic second or third degree (Grade II or Grade III) haemorrhoids. A multi-centre, parallel group randomised controlled trial. The primary outcome is patient-reported symptom recurrence twelve months following the intervention. Secondary outcome measures relate to symptoms, complications, health resource use, health related quality of life and cost effectiveness following the intervention. 350 patients with grade II or grade III haemorrhoids will be recruited in surgical departments in up to 14 NHS hospitals. A multi-centre, parallel group randomised controlled trial. Block randomisation by centre will be used, with 175 participants randomised to each group. The results of the research will help inform future practice for the treatment of grade II and III haemorrhoids. ISRCTN41394716.

Impact on caesarean section rates following injections of sterile water (ICARIS): a multicentre randomised controlled trial.

PubMed

Lee, Nigel; Mårtensson, Lena B; Homer, Caroline; Webster, Joan; Gibbons, Kristen; Stapleton, Helen; Dos Santos, Natalie; Beckmann, Michael; Gao, Yu; Kildea, Sue

2013-05-03

Sterile water injections have been used as an effective intervention for the management of back pain during labour. The objective of the current research is to determine if sterile water injections, as an intervention for back pain in labour, will reduce the intrapartum caesarean section rate. A double blind randomised placebo controlled trialSetting: Maternity hospitals in AustraliaParticipants: 1866 women in labour, ≥18 years of age who have a singleton pregnancy with a fetus in a cephalic presentation at term (between 37 + 0 and 41 + 6 weeks gestation), who assess their back pain as equal to or greater than seven on a visual analogue scale when requesting analgesia and able to provide informed consent. Participants will be randomised to receive either 0.1 to 0.3 millilitres of sterile water or a normal saline placebo via four intradermal injections into four anatomical points surrounding the Michaelis' rhomboid over the sacral area. Two injections will be administered over the posterior superior iliac spine (PSIS) and the remaining two at two centimetres posterior, and one centimetre medial to the PSIS respectively. Proportion of women who have a caesarean section in labour.Randomisation: Permuted blocks stratified by research site.Blinding (masking):Double-blind trial in which participants, clinicians and research staff blinded to group assignment. Funded by the National Health and Medical Research CouncilTrial registration:Australian New Zealand Clinical Trials Registry (No ACTRN12611000221954). Sterile water injections, which may have a positive effect on reducing the CS rate, have been shown to be a safe and simple analgesic suitable for most maternity settings. A procedure that could reduce intervention rates without adversely affecting safety for mother and baby would benefit Australian families and taxpayers and would reduce requirements for maternal operating theatre time. Results will have external validity, as the technique may be easily applied to maternity populations outside Australia. In summary, the results of this trial will contribute High level evidence on the impact of SWI on intrapartum CS rates and provide evidence of the analgesic effect of SWI on back pain.

Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial.

PubMed

Camenzind, Edoardo; Wijns, William; Mauri, Laura; Kurowski, Volkhard; Parikh, Keyur; Gao, Runlin; Bode, Christoph; Greenwood, John P; Boersma, Eric; Vranckx, Pascal; McFadden, Eugene; Serruys, Patrick W; O'Neil, William W; Jorissen, Brenda; Van Leeuwen, Frank; Steg, Ph Gabriel

2012-10-20

We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Medtronic, Inc. Copyright © 2012 Elsevier Ltd. All rights reserved.

WELLFOCUS PPT - modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial.

PubMed

Schrank, Beate; Riches, Simon; Coggins, Tony; Rashid, Tayyab; Tylee, Andre; Slade, Mike

2014-06-03

The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18-65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. Current Controlled Trials ISRCTN04199273 - WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013.

Protocol, and practical challenges, for a randomised controlled trial comparing the impact of high intensity interval training against standard care before major abdominal surgery: study protocol for a randomised controlled trial.

PubMed

Woodfield, John; Zacharias, Matthew; Wilson, Genevieve; Munro, Fran; Thomas, Kate; Gray, Andrew; Baldi, James

2018-06-25

Risk factors, such as the number of pre-existing co-morbidities, the extent of the underlying pathology and the magnitude of the required operation, cannot be changed before surgery. It may, however, be possible to improve the cardiopulmonary fitness of the patient with an individualised exercise program. We are performing a randomised controlled trial (RCT) assessing the impact of High Intensity Interval Training (HIIT) on preoperative cardiopulmonary fitness and postoperative outcomes in patients undergoing major abdominal surgery. Consecutive eligible patients undergoing elective abdominal surgery are being randomised to HIIT or standard care in a 1:1 ratio. Participants allocated to HIIT will perform 14 exercise sessions on a stationary cycle ergometer, over a period of 4-6 weeks before surgery. The sessions, which are individualised, aim to start with ten repeated 1-min blocks of intense exercise with a target of reaching a heart rate exceeding 90% of the age predicted maximum, followed by 1 min of lower intensity cycling. As endurance improves, the duration of exercise is increased to achieve five 2-min intervals of high intensity exercise followed by 2 min of lower intensity cycling. Each training session lasts approximately 30 min. The primary endpoint, change in peak oxygen consumption (Peak VO 2 ) measured during cardiopulmonary exercise testing, is assessed at baseline and before surgery. Secondary endpoints include postoperative complications, length of hospital stay and three clinically validated scores: the surgical recovery scale; the postoperative morbidity survey; and the SF-36 quality of life score. The standard deviation for changes in Peak VO 2 will be assessed after the first 30 patients and will be used to calculate the required sample size. We want to assess if 14 sessions of HIIT is sufficient to improve Peak VO 2 by 2 mL/kg/min in patients undergoing major abdominal surgery and to explore the best clinical endpoint for a subsequent RCT designed to assess if improving Peak VO 2 will translate into improving clinical outcomes after surgery. Australian New Zealand Clinical Trials Registry, ACTRN12617000587303 . Registered on 26 April 2017.

Multicentre randomised study of the effect and experience of an early inhome programme (PreHomeCare) for preterm infants using video consultation and smartphone applications compared with inhospital consultations: protocol of the PreHomeCare study

PubMed Central

Hägi-Pedersen, Mai-Britt

2017-01-01

Introduction Although premature infants and their parents are discharged earlier to inhomecare programmes, how to optimally support parents during this transition remains unknown. The aim of this study is to compare the effects of early inhomecare (PreHomeCare) including video consultations and mobile applications with those of inhospital consultations regarding breast feeding, parental confidence and parent–infant interactions. Methods and analysis A randomised controlled intervention study will be conducted in four neonatal departments offering PreHomeCare (ie, premature infant inhomecare) in Denmark. Parents of hospitalised premature infants who fulfil the inclusion criteria for PreHomeCare will be randomised during hospitalisation to either the intervention (n=80) or control group (n=80) using 1:1 block randomisation. During PreHomeCare, the intervention group will receive a smartphone application with a video system and an infant scale, and the control group will receive usual care (ie, hospital consultations). Additionally, both groups will have planned nurse consultations two to three times a week: the intervention group through video consultations and the control group through inhospital consultations. Data collection will occur at inclusion/baseline, at the end of PreHomeCare and 1 month after discharge using questionnaires and hospital records. The primary outcome is the proportion of exclusively breastfed infants 1 month after discharge/end of PreHomeCare, the secondary outcomes are parent–infant interactions measured by the Mother and baby interaction scale and family confidence in caring for infants measured by the Karitane Parenting Confidence Scale. The process evaluation will consist of two qualitative studies: a field study and an interview study. Data collection will initially involve field observations of three scheduled video consultations with six families from the intervention group. These families will also be interviewed 1 month after PreHomeCare has ended. Ethics and dissemination The project has been approved by the Regional Ethics Committee and the Danish Data Protection Agency. Trial registration number NCT02581800. PMID:28279994

A pilot study to evaluate the efficacy of adding a structured home visiting intervention to improve outcomes for high-risk families attending the Incredible Years Parent Programme: study protocol for a randomised controlled trial.

PubMed

Lees, Dianne G; Fergusson, David M; Frampton, Christopher M; Merry, Sally N

2014-02-25

Antisocial behaviour and adult criminality often have their origins in childhood and are best addressed early in the child's life using evidence-based treatments such as the 'Incredible Years Parent Programme'. However, families with additional risk factors who are at highest risk for poor outcomes do not always make sufficient change while attending such programmes. Additional support to address barriers and improve implementation of positive parenting strategies while these families attend the Incredible Years Programme may improve overall outcomes.The study aims to evaluate the efficacy of adding a structured home visiting intervention (Home Parent Support) to improve outcomes in families most at risk of poor treatment response from the Incredible Years intervention. This study will inform the design of a larger prospective randomised controlled trial. A pilot single-blind, parallel, superiority, randomised controlled trial. Randomisation will be undertaken using a computer-generated sequence in a 1:1 ratio to the two treatments arranged in permuted blocks with stratification by age, sex, and ethnicity. One hundred and twenty six participants enrolled in the Incredible Years Parent Programme who meet the high-risk criteria will be randomly allocated to receive either Incredible Years Parent Programme and Home Parent Support, or the Incredible Years Parent Programme alone. The Home Parent Support is a 10-session structured home visiting intervention provided by a trained therapist, alongside the usual Incredible Years Parent Programme, to enhance the adoption of key parenting skills. The primary outcome is the change in child behaviour from baseline to post-intervention in parent reported Eyberg Child Behavior Inventory Problem Scale. This is the first formal evaluation of adding Home Parent Support alongside Incredible Years Parent Programme for families with risk factors who typically have poorer treatment outcomes. We anticipate that the intervention will help vulnerable families stay engaged, strengthen the adoption of effective parenting strategies, and improve outcomes for both the children and families. Australian New Zealand Clinical Trials Registry ACTRN12612000878875.

Efficacy of a dual-ring wound protector for prevention of incisional surgical site infection after Whipple's procedure (pancreaticoduodenectomy) with preoperatively-placed intrabiliary stents: protocol for a randomised controlled trial.

PubMed

Bressan, Alexsander K; Roberts, Derek J; Edwards, Janet P; Bhatti, Sana U; Dixon, Elijah; Sutherland, Francis R; Bathe, Oliver; Ball, Chad G

2014-08-21

Among surgical oncology patients, incisional surgical site infection is associated with substantially increased morbidity, mortality and healthcare costs. Moreover, while adults undergoing pancreaticoduodenectomy with preoperative placement of an intrabiliary stent have a high risk of this type of infection, and wound protectors may significantly reduce its risk, no relevant studies of wound protectors yet exist involving this patient population. This study will evaluate the efficacy of a dual-ring wound protector for prevention of incisional surgical site infection among adults undergoing pancreaticoduodenectomy with preoperatively-placed intrabiliary stents. This study will be a parallel, dual-arm, randomised controlled trial that will utilise a more explanatory than pragmatic attitude. All adults (≥18 years) undergoing a pancreaticoduodenectomy at the Foothills Medical Centre in Calgary, Alberta, Canada with preoperative placement of an intrabiliary stent will be considered eligible. Exclusion criteria will include patient age <18 years and those receiving long-term glucocorticoids. The trial will employ block randomisation to allocate patients to a commercial dual-ring wound protector (the Alexis Wound Protector) or no wound protector and the current standard of care. The main outcome measure will be the rate of surgical site infection as defined by the Centers for Disease Control and Prevention criteria within 30 days of the index operation date as determined by a research assistant blinded to treatment allocation. Outcomes will be analysed by a statistician blinded to allocation status by calculating risk ratios and 95% CIs and compared using Fisher's exact test. This will be the first randomised trial to evaluate the efficacy of a dual-ring wound protector for prevention of incisional surgical site infection among patients undergoing pancreaticoduodenectomy. Results of this study are expected to be available in 2016/2017 and will be disseminated using an integrated and end-of-grant knowledge translation strategy. ClinicalTrials.gov identifier NCT01836237. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PC6 acupoint stimulation for the prevention of postcardiac surgery nausea and vomiting: a protocol for a two-group, parallel, superiority randomised clinical trial.

PubMed

Cooke, Marie; Rickard, Claire; Rapchuk, Ivan; Shekar, Kiran; Marshall, Andrea P; Comans, Tracy; Doi, Suhail; McDonald, John; Spooner, Amy

2014-11-13

Postoperative nausea and vomiting (PONV) are frequent but unwanted complications for patients following anaesthesia and cardiac surgery, affecting at least a third of patients, despite pharmacological treatment. The primary aim of the proposed research is to test the efficacy of PC6 acupoint stimulation versus placebo for reducing PONV in cardiac surgery patients. In conjunction with this we aim to develop an understanding of intervention fidelity and factors that support, or impede, the use of PC6 acupoint stimulation, a knowledge translation approach. 712 postcardiac surgery participants will be recruited to take part in a two-group, parallel, superiority, randomised controlled trial. Participants will be randomised to receive a wrist band on each wrist providing acupressure to PC six using acupoint stimulation or a placebo. Randomisation will be computer generated, use randomly varied block sizes, and be concealed prior to the enrolment of each patient. The wristbands will remain in place for 36 h. PONV will be evaluated by the assessment of both nausea and vomiting, use of rescue antiemetics, quality of recovery and cost. Patient satisfaction with PONV care will be measured and clinical staff interviewed about the clinical use, feasibility, acceptability and challenges of using acupressure wristbands for PONV. Ethics approval will be sought from appropriate Human Research Ethics Committee/s before start of the study. A systematic review of the use of wrist acupressure for PC6 acupoint stimulation reported minor side effects only. Study progress will be reviewed by a Data Safety Monitoring Committee (DSMC) for nausea and vomiting outcomes at n=350. Dissemination of results will include conference presentations at national and international scientific meetings and publications in peer-reviewed journals. Study participants will receive a one-page lay-summary of results. Australian New Zealand Clinical Trials Registry--ACTRN12614000589684. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Cognitive Remediation in Bipolar (CRiB) pilot study: study protocol for a randomised controlled trial.

PubMed

Strawbridge, Rebecca; Fish, Jessica; Halari, Rozmin; Hodsoll, John; Reeder, Clare; Macritchie, Karine; McCrone, Paul; Wykes, Til; Young, Allan H

2016-07-29

People with bipolar disorder often show difficulties with cognitive functioning, and though these difficulties are identified as important targets for intervention, few treatment options are available. Preliminary evidence suggests that cognitive remediation therapy (a psychological treatment proven beneficial for people diagnosed as having schizophrenia) is helpful for people with bipolar disorders. We are conducting a pilot trial to determine whether individual, computerised, cognitive remediation therapy (CRT) for people with bipolar disorder 1) increases cognitive function; 2) improves global functioning, goal attainment and mood symptoms; 3) is acceptable and feasible for participants; and 4) can be addressed in a comprehensive, larger, randomised, controlled trial. The study is designed as a two-arm, randomised, controlled trial comparing cognitive remediation therapy with treatment-as-usual (TAU) for euthymic bipolar patients. Participants are eligible to take part if aged between 18 and 65 with a diagnosis of bipolar disorder (type I) and currently in euthymic state, and no neurological, substance or personality disorder diagnoses. Sixty participants will be recruited (mainly through secondary and tertiary care) and will be block-randomised to receive either treatment-as-usual alone or in addition to a 12-week course of cognitive remediation therapy totalling 20-40 therapy hours. The intervention will comprise regular sessions with a therapist and computer-based training. Research assessments will take place before and after the intervention period and at a 12-week follow-up, and will include evaluation of neuropsychological, symptom-related, demographic and social factors, as well as collecting qualitative data regarding CRT expectations and satisfaction. Intention-to-treat analyses will examine the efficacy of cognitive remediation therapy primarily on cognition and additionally on functioning, quality of life and mood symptoms. Furthermore, we will examine the acceptability of CRT and undertake a preliminary health economics analysis to ascertain the cost of delivering the intervention. The results of this trial will provide valuable information about whether cognitive remediation therapy may be beneficial for people diagnosed with bipolar disorder in a euthymic state. ISRCTN registry, ISRCTN32290525 . Registered on 2 March 2016.

Neurodevelopmental outcome at two years of age after general and awake-regional anaesthesia in infancy: a randomised controlled trial

PubMed Central

Davidson, Andrew J.; Disma, Nicola; de Graaff, Jurgen C.; Withington, Davinia E.; Dorris, Liam; Bell, Graham; Stargatt, Robyn; Bellinger, David C.; Schuster, Tibor; Arnup, Sarah J.; Hardy, Pollyanna; Hunt, Rodney W.; Takagi, Michael J.; Giribaldi, Gaia; Hartmann, Penelope L.; Salvo, Ida; Morton, Neil S.; von Ungern Sternberg, Britta S; Locatelli, Bruno Guido; Wilton, Niall; Lynn, Anne; Thomas, Joss J.; Polaner, David; Bagshaw, Oliver; Szmuk, Peter; Absalom, Anthony R.; Frawley, Geoff; Berde, Charles; Ormond, Gillian D; Marmor, Jacki; Ellen, Mary

2016-01-01

Summary Background There is pre-clinical evidence that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia may have an increased risk of poorer neurodevelopmental outcome. This trial aims to determine if GA in infancy has any impact on neurodevelopmental outcome. The primary outcome for the trial is neurodevelopmental outcome at 5 years of age. The secondary outcome is neurodevelopmental outcome at two years of age and is reported here. Methods We performed an international assessor-masked randomised controlled equivalence trial in infants less than 60 weeks post-menstrual age, born at greater than 26 weeks gestational age having inguinal herniorrhaphy. Infants were excluded if they had existing risk factors for neurologic injury. Infants were randomly assigned to awake-regional (RA) or sevoflurane-based general anaesthesia (GA). Web-based randomisation was performed in blocks of two or four and stratified by site and gestational age at birth. The outcome for analysis was the composite cognitive score of the Bayley Scales of Infant and Toddler Development, Third Edition. The analysis was as-per-protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. The trial was registered at ANZCTR, ACTRN12606000441516 and ClinicalTrials.gov, NCT00756600. Findings Between February 2007, and January 2013, 363 infants were randomised to RA and 359 to GA. Outcome data were available for 238 in the RA and 294 in the GA arms. The median duration of anaesthesia in the GA arm was 54 minutes. For the cognitive composite score there was equivalence in means between arms (RA-GA: +0·169, 95% CI −2·30 to +2·64). Interpretation For this secondary outcome we found no evidence that just under an hour of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at two years of age compared to RA. PMID:26507180

Protocol investigating the clinical utility of an objective measure of attention, impulsivity and activity (QbTest) for optimising medication management in children and young people with ADHD 'QbTest Utility for Optimising Treatment in ADHD' (QUOTA): a feasibility randomised controlled trial.

PubMed

Hall, Charlotte L; James, Marilyn; Brown, Sue; Martin, Jennifer L; Brown, Nikki; Selby, Kim; Clarke, Julie; Vijayan, Hena; Guo, Boliang; Sayal, Kapil; Hollis, Chris; Groom, Madeleine J

2018-02-15

Attention-deficit hyperactivity disorder (ADHD) is characterised by symptoms of inattention, hyperactivity and impulsivity. To improve outcomes, the National Institute for Health and Care Excellence ADHD guidelines recommend regular monitoring of symptoms when children commence medication. However, research suggests that routine monitoring rarely happens, and clinicians often rely on subjective information such as reports from parents and teachers to ascertain improvement. These sources can be unreliable and difficult to obtain. The addition of an objective test of attention and activity (QbTest) may improve the objectivity, reliability and speed of clinical decision-making and so reduce the time to identify the optimal medication dose. This study aims to assess the feasibility and acceptability of a QbTest medication management protocol delivered in routine healthcare services for children with ADHD. This multisite feasibility randomised controlled trial (RCT) will recruit 60 young people (aged 6-17 years old), diagnosed with ADHD, and starting stimulant medication who are seen by Child and Adolescent Mental Health Services or Community Paediatric services. Participants will be randomised into one of two arms. In the experimental arm (QbTest protocol), the participant will complete a QbTest at baseline (prior to medication initiation), and two follow-up QbTests on medication (2-4 weeks and 8-10 weeks later). In the control arm, participants will receive treatment as usual, with at least two follow-up consultations. Measures of parent-, teacher- and clinician-rated symptoms and global functioning will be completed at each time point. Health economic measures will be completed. Clinicians will record treatment decision-making. Acceptability and feasibility of the protocol will be assessed alongside outcome measure completion rates. Qualitative interviews will be conducted. The findings will be used to inform the development of a fully powered RCT. The results will be submitted for publication in peer-reviewed journals. The study has ethical approval. NCT03368573; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Basic Radio Circuits and Vacuum Tube AM Troubleshooting; Radio and Television Service, Intermediate: 9785.03.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

The 135-hour quinmester course covers study of basic radio circuits as applied to vacuum tube radios in six blocks of instruction: orientation; AM receivers with tubes; no signal, audio failure; distortion; weak, noisy signals; and a post-test. Each block is subdivided into several units, and block objectives are outlined. Completion of AC…

Disaster management curricula: strategy to create doctors with disaster resilience in Aceh, Indonesia

NASA Astrophysics Data System (ADS)

Wahyuniati, N.; Maulana, R.; Ichsan, I.

2017-02-01

Faculty of Medicine of Syiah Kuala University has one special block called Disaster Management block (the last block on the curricula) on Competency-Based Curriculum of Medical Sciences with the Problem-Based Learning method. This block has four credits, allocated seven weeks learning period including one week for evaluation. The placement of disaster management block in the 7th semester (last semester) aims to allow students to implement more easily the complete basic and clinical medical knowledge and then have it integrated with the management capabilities during adisaster. This article evaluates two components: 1) Disaster management module, by comparing the content of modules used in three different academic years, the academic year 2013/2014, 2014/2015 and 2015/2016, 2) The final grade, by comparing the final grade of disaster management block in 4 years (comparing students class of 2008, 2009, 2010 and 2011). The results revealed that on every academic year there were additions and strengthening of the material to ensure that students achieve a complete learning experience, and there was a slight increase in student’s grades where the number of students who receive grades A has increased while the number of students who receive grades E decreased.

Creating a Quality Improvement Course for Undergraduate Medical Education: Practice What You Teach.

PubMed

Bradham, Tamala S; Sponsler, Kelly C; Watkins, Scott C; Ehrenfeld, Jesse M

2018-05-02

More than half of U.S. medical schools have implemented curricula addressing quality improvement (QI); however, the evidence on which pedagogical methods are most effective is limited. As of January 2015, students at Vanderbilt University School of Medicine are required to take a QI course consisting of three 1-month-long (4 hours per week) blocks during their third or fourth year, in which student-identified faculty sponsors are paired with highly trained QI professionals from Vanderbilt University Medical Center. The three blocks of the QI course include didactic instruction using Institute for Healthcare Improvement Open School modules, readings, weekly assignments, and experiential learning activities (i.e., students develop and implement a QI project with two Plan-Do-Study-Act cycles using a systematic approach that employs the principles of improvement science, which they present as a poster on the last day of the third block). From January 2015 to January 2017, 132 students completed all three blocks, resulting in 110 completed QI projects. On evaluations (distributed after each completed block), a majority of students rated the clinical relevance of the blocks highly (191/273, 70%), agreed the blocks contributed to their development as a physician (192/273, 70%), and reported the blocks motivated them to continue to learn more about QI (168/273, 62%). The authors have applied QI tools and methods to improve the QI course and will aim to measure and assess the sustainability of the course by tracking clinical outcomes related to the projects and students' ongoing involvement in QI after graduation.Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

[Premature outflow tract ventricular contraction combined with complete bundle branch block: the characteristic electrocardiographic and ablation target potential features].

PubMed

Di, C Y; Wan, Z; Li, K; Ding, Y S; Lin, W H

2017-12-01

Objective: To explore the characteristics of electrocardiogram(ECG) and target potential features of premature ventricular contraction (PVC) in patients with complete left/right bundle branch block (CL/RBBB) and compare with those without CL/RBBB. Methods: A retrospective analysis was done in 8 outflow tract PVC patients with CL/RBBB, who successfully underwent radiofrequency ablation from August 2009 to June 2017. According to the bundle branch block chamber, patients were divided into the complete right bundle branch block (CRBBB) group ( n= 4) and the complete left bundle branch block (CLBBB) group ( n= 4). The control group were those who successfully underwent ablation at the same position as the above two groups but without CL/RBBB. The characteristics of ECG and target potential features were compared among groups. Results: One case in the CRBBB group was successfully ablated in the great cardiac vein with precordial R/S>1 transition at V(1) and one case in the CLBBB group was successfully ablated in the right coronary cusp with precordial R/S>1 transition at V(2), while other 6 cases were all with precordial R/S>1 transition at lead V(4). Precordial R/S>1 transition was not later than sinus rhythm (SR) in the CLBBB group. No statistical difference was found in the QRS complex duration between SR and PVC in the CL/RBBB patients [(134.38±23.80)ms vs (156.75±25.93)ms, P> 0.05], while statistical difference was shown in the control group [(92.63±5.76)ms vs (140.25±15.97)ms, P< 0.05]. Conclusion: Bundle branch block can lead to misjudgment of PVC origin with CL/RBBB during sinus rhythm, thus the origin chamber of the PVC should be determined according to the mapping and ablation result.

Tunable PhoXonic Band Gap Materials from Self-Assembly of Block Copolymers and Colloidal Nanocrystals (NBIT Phase II)

DTIC Science & Technology

2013-12-12

their application in sensors and as displays. We found that the thermochromic behavior of a lamellar block copolymer poly(styrene-b-2-vinylpyridine...the solution pH. The findings of this work provide the basis for understanding and controlling the properties of thermochromic block copolymers...by the glassy PS layers . The glassy layers completely constrain the lateral expansion of the P2VP gel block and the dislocation defect network that

An inhibitor of polyamine synthesis arrests cells at an earlier stage of G1 than does calcium deprivation.

PubMed Central

Cheetham, B F

1983-01-01

Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation. Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells blocked by calcium deprivation. PMID:6843551

A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis

PubMed Central

Eversden, Lis; Maggs, Fiona; Nightingale, Peter; Jobanputra, Paresh

2007-01-01

Background Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. Methods One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change – a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. Results Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. Conclusion Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores. PMID:17331241

A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis.

PubMed

Eversden, Lis; Maggs, Fiona; Nightingale, Peter; Jobanputra, Paresh

2007-03-01

Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change--a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores.

A prospective, randomized comparison between single- and multiple-injection techniques for ultrasound-guided subgluteal sciatic nerve block.

PubMed

Yamamoto, Hiroto; Sakura, Shinichi; Wada, Minori; Shido, Akemi

2014-12-01

It is believed that local anesthetic injected to obtain circumferential spread around nerves produces a more rapid onset and successful blockade after some ultrasound-guided peripheral nerve blocks. However, evidence demonstrating this point is limited only to the popliteal sciatic nerve block, which is relatively easy to perform by via a high-frequency linear transducer. In the present study, we tested the hypothesis that multiple injections of local anesthetic to make circumferential spread would improve the rate of sensory and motor blocks compared with a single-injection technique for ultrasound-guided subgluteal sciatic nerve block, which is considered a relatively difficult block conducted with a low-frequency, curved-array transducer. Ninety patients undergoing knee surgery were divided randomly into 2 groups to receive the ultrasound-guided subgluteal approach to sciatic nerve block with 20 mL of 1.5% mepivacaine with epinephrine. For group M (the multiple-injection technique), the local anesthetic was injected to create circumferential spread around the sciatic nerve without limitation on the number of needle passes. For group S (the single-injection technique), the number of needle passes was limited to 1, and the local anesthetic was injected to create spread along the dorsal surface of the sciatic nerve, during which no adjustment of the needle tip was made. Sensory and motor blockade were assessed in double-blind fashion for 30 minutes after completion of the block. The primary outcome was sensory blockade of all sciatic components tested, including tibial, superficial peroneal, and sural nerves at 30 minutes after injection. Data from 86 patients (43 in each group) were analyzed. Block execution took more time for group M than group S. The proportion of patients with complete sensory blockade of all sciatic components at 30 minutes after injection was significantly larger for group M than group S (41.9% vs 16.3%, P = 0.018). Complete motor blockade of foot and toes extension also was observed more frequently in group M than in group S (67.4% vs 34.9%, P = 0.005 and 51.2% vs 25.6%, P = 0.027, respectively). When ultrasound-guided subgluteal sciatic nerve block is conducted, multiple injections of local anesthetic to make a circumferential spread around the sciatic nerve improve the rate of sensory and motor blocks compared with a single injection.

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

PubMed

Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E; Atik, Ruth Bender; Bloemenkamp, Kitty Wm; Brady, Rebecca; Briley, Annette; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin; Eapen, Abey; Essex, Holly; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Parrott, Steve; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Trépel, Dominic; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark David; Khalaf, Yacoub; Goddijn, Mariëtte; Regan, Lesley; Rai, Rajendra

2016-05-01

Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341. There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM. This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle. Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM. Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial.

PubMed

García-Donas, Jesus; Font, Albert; Pérez-Valderrama, Begoña; Virizuela, José Antonio; Climent, Miquel Ángel; Hernando-Polo, Susana; Arranz, José Ángel; Del Mar Llorente, Maria; Lainez, Nuria; Villa-Guzmán, José Carlos; Mellado, Begoña; Del Alba, Aránzazu González; Castellano, Daniel; Gallardo, Enrique; Anido, Urbano; Del Muro, Xavier García; Domènech, Montserrat; Puente, Javier; Morales-Barrera, Rafael; Pérez-Gracia, Jose Luis; Bellmunt, Joaquim

2017-05-01

Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m 2 or at 280 mg/m 2 in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One patient from the vinflunine group was lost to follow-up immediately after randomisation and was excluded from the analyses. One patient in the best supportive care group became ineligible for the study and did not receive treatment due to a delay in enrolment, but was included in the intention-to-treat efficacy analysis. After a median follow-up of 15·6 months (IQR 8·5-26·0), 29 (66%) of 44 patients in the vinflunine group had disease progression and 24 (55%) had died, compared with 36 (84%) of 43 patients with disease progression and 32 (74%) deaths in the best supportive care group. Median progression-free survival was 6·5 months (95% CI 2·0-11·1) in the vinflunine group and 4·2 months (2·1-6·3) in the best supportive care group (hazard ratio 0·59, 95% CI 0·37-0·96, p=0·031). The most common grade 3 or 4 adverse events were neutropenia (eight [18%] of 44 in the vinflunine group vs none of 42 in the best supportive care group), asthenia or fatigue (seven [16%] vs one [2%]), and constipation (six [14%] vs none). 18 serious adverse events were reported in the vinflunine group and 14 in the best supportive care group. One patient in the vinflunine group died from pneumonia that was deemed to be treatment related. In patients with disease control after first-line chemotherapy, progression-free survival exceeded the acceptable threshold with vinflunine maintenance therapy. Moreover, progression-free survival was longer with vinflunine maintenance therapy than with best supportive care. Vinflunine maintenance had an acceptable safety profile. Further studies of the role of vinflunine are warranted. Pierre-Fabre Médicament. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial.

PubMed

Garnett, Claire; Crane, David; Michie, Susan; West, Robert; Brown, Jamie

2016-07-08

Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (2(5)) experimental conditions after downloading the 'Drink Less' app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between-subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and evaluated against a minimal control in a definitive randomised control trial with long-term outcomes. ISRCTN40104069 Date of registration: 10/2/2016.

Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial

PubMed Central

Stewart, Ian; Beevers, Andrea; Fraser, John F; Platts, David

2017-01-01

Objective To examine whether providing thermal clothing improved the health of patients with heart failure during winter. Design Parallel group randomised controlled trial. Setting Large public hospital in Brisbane during winter 2016. Participants 91 patients with systolic or diastolic heart failure who were over 50 years old. Intervention 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients’ data were available for the primary outcome which was collected blind to randomised group. Main outcome measures The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the ‘clo’. Monitors inside the participants’ homes recorded indoor temperatures throughout winter. Results The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference –1.2 days, 95% CI –4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18°C during midwinter. Conclusions There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. Trial registration number ACTRN12615001023549; Results. PMID:28993390

Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial.

PubMed

Barnett, Adrian Gerard; Stewart, Ian; Beevers, Andrea; Fraser, John F; Platts, David

2017-10-08

To examine whether providing thermal clothing improved the health of patients with heart failure during winter. Parallel group randomised controlled trial. Large public hospital in Brisbane during winter 2016. 91 patients with systolic or diastolic heart failure who were over 50 years old. 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients' data were available for the primary outcome which was collected blind to randomised group. The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the 'clo'. Monitors inside the participants' homes recorded indoor temperatures throughout winter. The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference -1.2 days, 95% CI -4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18°C during midwinter. There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. ACTRN12615001023549; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effectiveness of Stepping Stones Triple P: the design of a randomised controlled trial on a parenting programme regarding children with mild intellectual disability and psychosocial problems versus care as usual.

PubMed

Kleefman, Marijke; Jansen, Daniëlle E M C; Reijneveld, Sijmen A

2011-08-30

Children with an intellectual disability are at increased risk of psychosocial problems. This leads to serious restrictions in the daily functioning of the children and to parental stress. Stepping Stones Triple P aims to prevent severe behavioural, emotional and developmental problems in children with a (intellectual) disability by enhancing parenting knowledge and skills, and the self-confidence of parents. This paper aims to describe the design of a study of the effectiveness of parenting counselling using Stepping Stones Triple P compared to Care as Usual. The effects of Stepping Stones Triple P will be studied in a Randomised Controlled Trial. Parents of children aged 5-12 years with an IQ of 50-85 will be recruited from schools. Prior to randomisation, parents complete a screening questionnaire about their child's psychosocial problems and their parenting skills. Subsequently, parents of children with increased levels of psychosocial problems (score on Strengths and Difficulties Questionnaire ≥ 14) will be invited to participate in the intervention study. After obtaining consent, parents will be randomised either to the experimental group (Stepping Stones Triple P) or to Care as Usual. The primary outcome is a change in the child's psychosocial problems according to parents and teachers. The secondary outcome is a change in parenting skills. Data will be collected before the start of the intervention, immediately after the intervention, and six months after. This paper presents an outline of the background and design of a randomised controlled trial to investigate the effectiveness of Stepping Stones Triple P, which aims to decrease psychosocial problems in children with a mild intellectual disability. Stepping Stones Triple P seems promising, but evidence on its effectiveness for this population is still lacking. This study provides evidence about the effects of this intervention in a community-based population of children with a mild intellectual disability. Netherlands Trial Register (NTR): NTR2624.

Physical therapy for Bell s palsy (idiopathic facial paralysis).

PubMed

Teixeira, Lázaro Juliano; Soares, Bernardo Garcia de Oliveira; Vieira, Vanessa Pedrosa; Prado, Gilmar F

2008-07-16

Bell's palsy (idiopathic facial paralysis) is commonly treated by physical therapy services with various therapeutic strategies and devices. There are many questions about their efficacy and effectiveness. To evaluate the efficacy of physical therapies on the outcome of Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Trials Register (February 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2007), MEDLINE (January 1966 to February 2008), EMBASE (January 1980 to February 2008), LILACS (January 1982 to February 2008), PEDro (from 1929 to February 2008), and CINAHL (January 1982 to February 2008). We selected randomised or quasi-randomised controlled trials involving any physical therapy. We included participants of any age with a diagnosis of Bell's palsy and all degrees of severity. The outcome measures were: incomplete recovery six months after randomisation, motor synkinesis, crocodile tears or facial spasm six months after onset, incomplete recovery after one year and adverse effects attributable to the intervention. Titles and abstracts identified from the register were scrutinized. The assessment of methodological quality took into account secure method of randomisation, allocation concealment, observer blinding, patient blinding, differences at baseline of the experimental groups, and completeness of follow-up. Data were extracted using a specially constructed data extraction form. Separate subgroup analyses of participants with more and less severe disability were undertaken. The search identified 45 potentially relevant articles. Six studies met the inclusion criteria. Three trials studied the efficacy of electrostimulation (294 participants) and three exercises (253 participants). Neither treatment produced significantly more improvement than the control treatment or no treatment. There was limited evidence that improvement began earlier in the exercise group. There is no evidence of significant benefit or harm from any physical therapy for idiopathic facial paralysis. The possibility that facial exercise reduces time to recover and sequelae needs confirming with good quality randomised controlled trials.

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

PubMed Central

Brown, Simon G A; Ball, Emma L; Perrin, Kyle; Read, Catherine A; Asha, Stephen E; Beasley, Richard; Egerton-Warburton, Diana; Jones, Peter G; Keijzers, Gerben; Kinnear, Frances B; Kwan, Ben C H; Lee, Y C Gary; Smith, Julian A; Summers, Quentin A; Simpson, Graham

2016-01-01

Introduction Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. Methods and analysis This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. Ethics and dissemination Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high-impact international journal and presentation at major international Emergency Medicine and Respiratory meetings. Trial registration number ACTRN12611000184976; Pre-results. PMID:27625060

Home-based Reach-to-Grasp training for people after stroke is feasible: a pilot randomised controlled trial.

PubMed

Turton, A J; Cunningham, P; van Wijck, F; Smartt, Hjm; Rogers, C A; Sackley, C M; Jowett, S; Wolf, S L; Wheatley, K; van Vliet, P

2017-07-01

To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. single-blind parallel group RCT. Residual arm deficit less than 12 months post-stroke. Reach-to-Grasp training in 14 one-hour therapist's visits over 6 weeks, plus one hour self-practice per day (total 56 hours). Usual care. Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial.

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

PubMed

Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Continuity of care by a primary midwife (caseload midwifery) increases women's satisfaction with antenatal, intrapartum and postpartum care: results from the COSMOS randomised controlled trial.

PubMed

Forster, Della A; McLachlan, Helen L; Davey, Mary-Ann; Biro, Mary Anne; Farrell, Tanya; Gold, Lisa; Flood, Maggie; Shafiei, Touran; Waldenström, Ulla

2016-02-03

Continuity of care by a primary midwife during the antenatal, intrapartum and postpartum periods has been recommended in Australia and many hospitals have introduced a caseload midwifery model of care. The aim of this paper is to evaluate the effect of caseload midwifery on women's satisfaction with care across the maternity continuum. Pregnant women at low risk of complications, booking for care at a tertiary hospital in Melbourne, Australia, were recruited to a randomised controlled trial between September 2007 and June 2010. Women were randomised to caseload midwifery or standard care. The caseload model included antenatal, intrapartum and postpartum care from a primary midwife with back-up provided by another known midwife when necessary. Women allocated to standard care received midwife-led care with varying levels of continuity, junior obstetric care, or community-based general practitioner care. Data for this paper were collected by background questionnaire prior to randomisation and a follow-up questionnaire sent at two months postpartum. The primary analysis was by intention to treat. A secondary analysis explored the effect of intrapartum continuity of carer on overall satisfaction rating. Two thousand, three hundred fourteen women were randomised: 1,156 to caseload care and 1,158 to standard care. The response rate to the two month survey was 88% in the caseload group and 74% in the standard care group. Compared with standard care, caseload care was associated with higher overall ratings of satisfaction with antenatal care (OR 3.35; 95% CI 2.79, 4.03), intrapartum care (OR 2.14; 95% CI 1.78, 2.57), hospital postpartum care (OR 1.56, 95% CI 1.32, 1.85) and home-based postpartum care (OR 3.19; 95% CI 2.64, 3.85). For women at low risk of medical complications, caseload midwifery increases women's satisfaction with antenatal, intrapartum and postpartum care. Australian New Zealand Clinical Trials Registry ACTRN012607000073404 (registration complete 23rd January 2007).

Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

PubMed

Ishigaki, Sayaka; Ogura, Takahiro; Kanaya, Ayana; Miyake, Yu; Masui, Kenichi; Kazama, Tomiei

2017-01-01

The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. Randomised, single-blinded study. A secondary hospital from October 2013 to July 2014. In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. Arterial plasma rocuronium concentrations. Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 μg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. Umin identifier: UMIN000011981.

Intrathecal dexmedetomidine as adjuvant for spinal anaesthesia for perianal ambulatory surgeries: A randomised double-blind controlled study.

PubMed

Nethra, S S; Sathesha, M; Dixit, Aanchal; Dongare, Pradeep A; Harsoor, S S; Devikarani, D

2015-03-01

The newer trend in regional anaesthesia for ambulatory anorectal surgeries advocate use of lower dose of local anaesthetic, providing segmental block with adjuvants such as opioids and α2 agonists to prolong analgesia. The current study investigated effects of addition of 5 μg of dexmedetomidine to 6 mg of hyperbaric bupivacaine on duration of analgesia, sensory and motor block characteristics for perianal ambulatory surgeries. This study is a prospective randomised controlled double blind study. Forty adult patients between 18 and 55 years of age were divided into 2 groups. Group D received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml) with injection dexmedetomidine 5 μg in 0.5 ml of normal saline and Group N received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml) with 0.5 ml of normal saline. The parameters assessed were time to regression of sensory blockade, motor blockade, ambulation, time to void, first administration of analgesic. Statistical analysis was done using appropriate tests. Time for regression of sensory level and time for first administration of analgesic were prolonged in Group D (430.05 ± 89.13 min, 459.8 ± 100.9 min, respectively) in comparison to Group N (301.10 ± 94.86 min, 321.85 ± 95.08 min, respectively). However, the duration of motor blockade, time to ambulation, and time to void were also significantly prolonged in Group D (323.05 ± 54.58 min, 329.55 ± 54.06 min, 422.30 ± 87.59 min) than in Group N (220.10 ± 63.61 min, 221.60 ± 63.84 min, 328.45 ± 113.38 min). Intrathecal dexmedetomidine 5 μg added to intrathecal bupivacaine 6 mg as adjuvant may not be suitable for ambulatory perianal surgeries due to prolongation of motor blockade.

Effects of human trampling on a rocky shore fauna on the Sao Paulo coast, southeastern Brazil.

PubMed

Ferreira, M N; Rosso, S

2009-11-01

Increased tourist activity in coastal regions demands management strategies to reduce impacts on rocky shores. The highly populated coastal areas in southeastern Brazil are an example of degradation caused by development of industry and tourism. Among different shore impacts, trampling has been intensively studied, and may represent a significant source of stress for intertidal fauna. A randomised blocks design was applied to experimentally study the effects of two different trampling intensities on richness, diversity, density and biomass of the rocky shore fauna of Obuseiro beach, Guarujá, southeastern Brazil. Blocks were distributed in two portions of the intertidal zone, dominated respectively by Chthamalus bisinuatus (Cirripedia) and Isognomon bicolor (Bivalvia). Blocks were trampled over three months, simulating the vacation period in Brazil and were monitored for the following nine months. Results indicate that Chthamalus bisinuatus is vulnerable to trampling impacts. Richness, diversity and turn-over index tended to be higher in trampled plots four months after trampling ceased. In general, results agree with previous trampling studies, suggesting that even low intensities of trampling may cause some impact on intertidal communities. Management strategies should include isolation of sensitive areas, construction of boardwalks, visitor education and monitoring programmes. In Brazil, additional data obtained from experimental studies are necessary in order to achieve a better understanding of trampling impacts on rocky shore communities.

Spinal manipulative therapy versus Graston Technique in the treatment of non-specific thoracic spine pain: Design of a randomised controlled trial

PubMed Central

Crothers, Amy; Walker, Bruce; French, Simon D

2008-01-01

Background The one year prevalence of thoracic back pain has been estimated as 17% compared to 64% for neck pain and 67% for low back pain. At present only one randomised controlled trial has been performed assessing the efficacy of spinal manipulative therapy (SMT) for thoracic spine pain. In addition no high quality trials have been performed to test the efficacy and effectiveness of Graston Technique® (GT), a soft tissue massage therapy using hand-held stainless steel instruments. The objective of this trial is to determine the efficacy of SMT and GT compared to a placebo for the treatment of non specific thoracic spine pain. Methods Eighty four eligible people with non specific thoracic pain mid back pain of six weeks or more will be randomised to one of three groups, either SMT, GT, or a placebo (de-tuned ultrasound). Each group will receive up to 10 supervised treatment sessions at the Murdoch University Chiropractic student clinic over a 4-week period. Treatment outcomes will be measured at baseline, one week after their first treatment, upon completion of the 4-week intervention period and at three, six and twelve months post randomisation. Outcome measures will include the Oswestry Back Pain Disability Index and the Visual Analogue Scale (VAS). Intention to treat analysis will be utilised in the statistical analysis of any group treatment effects. Trial Registration This trial was registered with the Australia and New Zealand Clinical Trials Registry on the 7th February 2008. Trial number: ACTRN12608000070336 PMID:18959807

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Thomson, Claire; Doré, Caroline J; Cro, Suzie; Round, Jeff; Molloy, Andrew; Davies, Mark; Karski, Michael; Kim, Louise; Cooke, Paul

2016-01-01

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555. PMID:27601503

Evaluation of a complex intervention to improve activities of daily living of disabled cancer patients: protocol for a randomised controlled study and feasibility of recruitment and intervention

PubMed Central

2014-01-01

Background Many cancer patients have problems performing activities of daily living (ADL). A randomised controlled trial was designed to examine the effects of an ADL intervention in addition to standard treatment and care in a hospital setting. The objective of this article was to present the study and to analyse the feasibility of the recruitment process and the intervention. Methods Adult disabled cancer patients at Næstved Hospital in Denmark were enrolled between 1 March 2010 and 30 June 2011 and randomised into an ADL intervention or to a control group. The intervention was performed by occupational therapists. The feasibility of the recruitment was analysed with regard to success in achieving the estimated number of participants and identification of barriers, and feasibility of the intervention was based on calculations of patient attendance and patient acceptability. The primary outcome of the randomised controlled trial was patients’ health-related quality of life 2 and 8 weeks after baseline. Results A total of 118 disabled cancer patients were enrolled in the study over a time span of 16 months. Very few meetings between occupational therapist and patient were cancelled. Time spent on the intervention varied considerably, but for the majority of patients, time consumption was between 1–3 hours. Conclusions Despite difficulties with recruitment, participation was considered feasible and the intervention was accepted among patients. Missing data in the follow-up period were mostly due to death among participants. Very few participants declined to complete questionnaires during follow-up. PMID:24779438

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

PubMed Central

2012-01-01

Abstract Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid. Trial registration Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151. PMID:22369511

A low cost virtual reality system for home based rehabilitation of the arm following stroke: a randomised controlled feasibility trial

PubMed Central

Standen, PJ; Threapleton, K; Richardson, A; Connell, L; Brown, DJ; Battersby, S; Platts, F; Burton, A

2016-01-01

Objective: To assess the feasibility of conducting a randomised controlled trial of a home-based virtual reality system for rehabilitation of the arm following stroke. Design: Two group feasibility randomised controlled trial of intervention versus usual care. Setting: Patients’ homes. Participants: Patients aged 18 or over, with residual arm dysfunction following stroke and no longer receiving any other intensive rehabilitation. Interventions: Eight weeks’ use of a low cost home-based virtual reality system employing infra-red capture to translate the position of the hand into game play or usual care. Main measures: The primary objective was to collect information on the feasibility of a trial, including recruitment, collection of outcome measures and staff support required. Patients were assessed at three time points using the Wolf Motor Function Test, Nine-Hole Peg Test, Motor Activity Log and Nottingham Extended Activities of Daily Living. Results: Over 15 months only 47 people were referred to the team. Twenty seven were randomised and 18 (67%) of those completed final outcome measures. Sample size calculation based on data from the Wolf Motor Function Test indicated a requirement for 38 per group. There was a significantly greater change from baseline in the intervention group on midpoint Wolf Grip strength and two subscales of the final Motor Activity Log. Training in the use of the equipment took a median of 230 minutes per patient. Conclusions: To achieve the required sample size, a definitive home-based trial would require additional strategies to boost recruitment rates and adequate resources for patient support. PMID:27029939

A low cost virtual reality system for home based rehabilitation of the arm following stroke: a randomised controlled feasibility trial.

PubMed

Standen, P J; Threapleton, K; Richardson, A; Connell, L; Brown, D J; Battersby, S; Platts, F; Burton, A

2017-03-01

To assess the feasibility of conducting a randomised controlled trial of a home-based virtual reality system for rehabilitation of the arm following stroke. Two group feasibility randomised controlled trial of intervention versus usual care. Patients' homes. Patients aged 18 or over, with residual arm dysfunction following stroke and no longer receiving any other intensive rehabilitation. Eight weeks' use of a low cost home-based virtual reality system employing infra-red capture to translate the position of the hand into game play or usual care. The primary objective was to collect information on the feasibility of a trial, including recruitment, collection of outcome measures and staff support required. Patients were assessed at three time points using the Wolf Motor Function Test, Nine-Hole Peg Test, Motor Activity Log and Nottingham Extended Activities of Daily Living. Over 15 months only 47 people were referred to the team. Twenty seven were randomised and 18 (67%) of those completed final outcome measures. Sample size calculation based on data from the Wolf Motor Function Test indicated a requirement for 38 per group. There was a significantly greater change from baseline in the intervention group on midpoint Wolf Grip strength and two subscales of the final Motor Activity Log. Training in the use of the equipment took a median of 230 minutes per patient. To achieve the required sample size, a definitive home-based trial would require additional strategies to boost recruitment rates and adequate resources for patient support.

What Role Does Sleep Play in Weight Gain in the First Semester of University?

PubMed Central

Roane, BM; Seifer, R; Sharkey, KM; Van Reen, E; Bond, TLY; Raffray, T; Carskadon, MA

2016-01-01

Objectives We hypothesized that shorter sleep durations and greater variability in sleep patterns are associated with weight gain in the first semester of university. Methods Students (N=132) completed daily sleep diaries for 9-weeks, completed the MEQ (chronotype) and CES-D (depressed mood) at week9, and self-reported weight/height (weeks 1&9). Mean and variability scores were calculated for sleep duration (TST,TSTv), bedtime (BT,BTv), and wake time (WT,WTv). Results An initial hierarchical regression evaluated (block1) sex, ethnicity; (block2) depressed mood, chronotype; (block3) TST; (block4) BT, WT; and (block5; R2change=0.09, p=0.005) TSTv, BTv, WTv with weight change. A sex-by-TSTv interaction was found. A final model showed that ethnicity, TST, TSTv, and BTv accounted for 31% of the variance in weight change for males; TSTv was the most significant contributor (R2 change=0.21, p<0.001). Conclusions Daily variability in sleep duration contributes to males’ weight gain. Further investigation needs to examine sex-specific outcomes for sleep and weight. PMID:25115969

Intermittent bradyarrhythmia in a Hispaniolan Amazon parrot (Amazona ventralis).

PubMed

Rembert, Melanie S; Smith, Julie A; Strickland, Keith N; Tully, Thomas N

2008-03-01

A clinically normal 2-year-old Hispaniolan Amazon parrot (Amazona ventralis) was found to have periodic second-degree atrioventricular (AV) block with variable nodal conductions while anesthetized with isoflurane during a thermal-support research project. Arrhythmias were observed on 5 successive weekly electrocardiograms. A complete cardiac evaluation, including a diagnostic electrocardiogram, revealed intermittent bradyarrhythmias ranging from a 2:1 to a 7:1 second-degree AV block, with concurrent hypotensive episodes during the nodal blocks. Results of a complete blood cell count, plasma biochemical profile, blood gas analysis, and atropine-response test, as well as radiography and auscultation, revealed no obvious cause for the arrhythmias. Echocardiography demonstrated cardiac wall thickness, chamber size, and systolic function similar to other psittacine birds. On return to the colony, the parrot continued to be outwardly asymptomatic despite the dramatic conduction disturbances. Although cardiac arrhythmias, including second-degree AV block, have been widely reported in birds, the wide variation of nodal conductions, the intermittent nature, and an arrhythmia with a 7:1 second-degree AV block that spontaneously reverts to normal as seen in this case have not been well documented in parrots.

Impact of a cognitive rehabilitation intervention on neuropsychiatric symptoms in mild to moderate Alzheimer's disease.

PubMed

Brunelle-Hamann, Laurence; Thivierge, Stéphanie; Simard, Martine

2015-01-01

The main goal of this study was to evaluate the impact of a cognitive rehabilitation programme on 12 behavioural and psychological symptoms of dementia (BPSD) in patients with mild to moderate Alzheimer's disease (AD). This six-month single-blind block-randomised cross-over controlled study was conducted with 15 mild to moderate AD participants and their caregivers. All participants received a four-week home-based cognitive rehabilitation programme to learn/re-learn an instrumental activity of daily living. They were assessed up until three months following the end of the intervention. The Neuropsychiatric Inventory (NPI-12) was employed to evaluate patients' BPSD at seven assessment points during the course of the study. A general linear mixed model analysis performed on the NPI data revealed that aberrant motor behaviours (AMB) increased significantly more in the treatment condition than in the control condition. In addition, both groups registered a significant reduction of delusional symptoms during the second half of the study. Employing a multi-symptom approach to assess participants' BPSD, this cross-over randomised controlled study showed that an individualised cognitive rehabilitation intervention was generally well-tolerated by mild to moderate AD patients. Future cognitive rehabilitation studies conducted with this population should pay attention to AMB symptom changes.

The safety of peri-articular local anaesthetic injection for patients undergoing total knee replacement with autologous blood transfusion: a randomised trial.

PubMed

Wallace, D F; Emmett, S R; Kang, K K; Chahal, G S; Hiskens, R; Balasubramanian, S; McGuinness, K; Parsons, H; Achten, J; Costa, M L

2012-12-01

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient's surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 μg/ml (sd 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion. The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery.

Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.

PubMed

Powell, Colin; Kolamunnage-Dona, Ruwanthi; Lowe, John; Boland, Angela; Petrou, Stavros; Doull, Iolo; Hood, Kerenza; Williamson, Paula

2013-06-01

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO(4)) in acute asthma in children. We assessed the effect of MgSO(4) treatment in children with severe acute asthma. In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2-16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO(4) (250 mmol/L; 151 mg per dose; MgSO(4) group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894. Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO(4) and 256 to placebo. Mean ASS at 60 min was lower in the MgSO(4) group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference -0·25, 95% CI -0·48 to -0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups. Overall, nebulised isotonic MgSO(4), given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO(2)<92%) at presentation and those with preceding symptoms lasting less than 6 h. National Institute for Health Research Health Technology Assessment Programme. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

PubMed

Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

2016-02-20

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. Janssen Research & Development, LLC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Understanding influences on teachers' uptake and use of behaviour management strategies within the STARS trial: process evaluation protocol for a randomised controlled trial.

PubMed

Hansford, Lorraine; Sharkey, Siobhan; Edwards, Vanessa; Ukoumunne, Obioha; Byford, Sarah; Norwich, Brahm; Logan, Stuart; Ford, Tamsin

2015-02-10

The 'Supporting Teachers And childRen in Schools' (STARS) study is a cluster randomised controlled trial evaluating the Incredible Years Teacher Classroom Management (TCM) programme as a public health intervention. TCM is a 6 day training course delivered to groups of 8-12 teachers. The STARS trial will investigate whether TCM can improve children's behaviour, attainment and wellbeing, reduce teachers' stress and improve their self-efficacy. This protocol describes the methodology of the process evaluation embedded within the main trial, which aims to examine the uptake and implementation of TCM strategies within the classroom plus the wider school environment and improve the understanding of outcomes. The STARS trial will work with eighty teachers of children aged 4-9 years from eighty schools. Teachers will be randomised to attend the TCM course (intervention arm) or to "teach as normal" (control arm) and attend the course a year later. The process evaluation will use quantitative and qualitative approaches to assess fidelity to model, as well as explore headteachers' and teachers' experiences of TCM and investigate school factors that influence the translation of skills learnt to practice. Four of the eight groups of teachers (n = 40) will be invited to participate in focus groups within one month of completing the TCM course, and again a year later, while 45 of the 80 headteachers will be invited to take part in telephone interviews. Standardised checklists will be completed by group leaders and each training session will be videotaped to assess fidelity to model. Teachers will also complete standardised session evaluations. This study will provide important information about whether the Teacher Classroom Management course influences child and teacher mental health and well-being in both the short and long term. The process evaluation will provide valuable insights into factors that may facilitate or impede any impact. The trial has been registered with ISCTRN (Controlled Trials Ltd) and assigned an ISRCTN number ISRCTN84130388 . Date assigned: 15 May 2012.

Protocol for a multicentre randomised feasibility STUdy evaluating the impact of a prognostic model for Management of BLunt chest wall trauma patients: STUMBL trial.

PubMed

Battle, Ceri; Abbott, Zoe; Hutchings, Hayley A; O'Neill, Claire; Groves, Sam; Watkins, Alan; Lecky, Fiona E; Jones, Sally; Gagg, James; Body, Richard; Evans, Philip A

2017-07-10

A new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the emergency department (ED). A definitive randomised controlled trial (impact trial) is required to assess the clinical and cost effectiveness of the new model before it can be accepted in clinical practice. The purpose of this trial is to assess the feasibility and acceptability of such a definitive trial and inform its design. This feasibility trial is designed to test the methods of a multicentre, cluster-randomised (stepped- wedge) trial, with a substantial qualitative component. Four EDs in England and Wales will collect data for all blunt chest wall trauma patients over a 5-month period; in the initial period acting as the controls (normal care), and in the second period acting as the interventions (in which the new model will be used). Baseline measurements including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient outcome data will then be collected for any subsequent hospitalisations. Data collection will conclude with a 6-week follow-up completion of two surveys (SF-12v2 and Client Services Receipt Inventory). Analysis of outcomes will focus on feasibility, acceptability and trial processes and will include recruitment and retention rates, attendance at clinician training rates and use of model in the ED. Qualitative feedback will be obtained through clinician interviews and a research nurse focus group. An evaluation of the feasibility of health economics outcomes data will be completed. Wales Research Ethics Committee 6 granted approval for the trial in September 2016. Patient recruitment will commence in February 2017. Planned dissemination is through publication in a peer-reviewed Emergency Medicine Journal , presentation at appropriate conferences and to stakeholders at professional meetings. ISRCTN95571506; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

12 A multi-centre randomised feasibility study evaluating the impact of a prognostic model for management of blunt chest wall trauma patients: stumbl trial.

PubMed

Battle, Ceri; Hutchings, Hayley; Abbott, Zoe; O'neill, Claire; Groves, Sam; Watkins, Alan; Lecky, Fiona; Jones, Sally; Gagg, James; Body, Rick; Evans, Phillip

2017-12-01

A new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the Emergency Department (ED). A definitive randomised controlled trial (impact trial), is required to assess the clinical and cost effectiveness of the new model, before it can be accepted in clinical practice. The purpose of this trial is to assess the feasibility and acceptability of such a definitive trial and inform its design. This feasibility trial is designed to test the methods of a multi-centre, cluster-randomised (stepped wedge) trial, with a substantial qualitative component. Four EDs in England and Wales will collect data for all blunt chest wall trauma patients over a five month period; in the initial period acting as the controls (normal care) and the second period, acting as the interventions (in which the new model will be used). Baseline measurements including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient outcome data will then be collected for any subsequent hospitalisations. Data collection will conclude with a six week follow-up completion of two surveys (SF-12v2 and Client Services Receipt Inventory).Analysis of outcomes will focus on feasibility, acceptability and trial processes and will include recruitment and retention rates, attendance at clinician training rates and use of model in the ED. Qualitative feedback will be obtained through clinician interviews and a research nurse focus group. An evaluation of the feasibility of health economics outcomes data will be completed. Wales Research Ethics Committee 6 granted approval for the trial in September 2016. Health Care Research Wales Research Permissions and the HRA have granted approval for the study. Patient recruitment commenced in February 2017. Planned dissemination is through publication in a peer-reviewed Emergency Medicine Journal, presentation at appropriate conferences and to stakeholders at Professional Meetings. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Computerised cognitive-behavioural therapy for depression in adolescents: feasibility results and 4-month outcomes of a UK randomised controlled trial.

PubMed

Wright, Barry; Tindall, Lucy; Littlewood, Elizabeth; Allgar, Victoria; Abeles, Paul; Trépel, Dominic; Ali, Shehzad

2017-01-27

Computer-administered cognitive-behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. Single centre RCT feasibility study. The trial was run within community and clinical settings in York, UK. Adolescents (aged 12-18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. ISRCTN31219579. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Computerised cognitive–behavioural therapy for depression in adolescents: feasibility results and 4-month outcomes of a UK randomised controlled trial

PubMed Central

Wright, Barry; Tindall, Lucy; Littlewood, Elizabeth; Allgar, Victoria; Abeles, Paul; Trépel, Dominic; Ali, Shehzad

2017-01-01

Objectives Computer-administered cognitive–behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. Design Single centre RCT feasibility study. Setting The trial was run within community and clinical settings in York, UK. Participants Adolescents (aged 12–18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. Interventions An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). Primary and secondary outcome measures Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. Results From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. Conclusions With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. Trial registration number ISRCTN31219579. PMID:28132000

Evaluation of Talking Parents, Healthy Teens, a new worksite based parenting programme to promote parent-adolescent communication about sexual health: randomised controlled trial

PubMed Central

Corona, Rosalie; Elliott, Marc N; Kanouse, David E; Eastman, Karen L; Zhou, Annie J; Klein, David J

2008-01-01

Objective To evaluate a worksite based parenting programme—Talking Parents, Healthy Teens—designed to help parents learn to address sexual health with their adolescent children. Design Randomised controlled trial (April 2002-December 2005). Setting 13 worksites in southern California. Participants 569 parents completed baseline surveys at work, gave permission for confidential surveys to be posted to their adolescent children, and were randomised to intervention or control groups. Parents and adolescents completed follow-up surveys at one week, three months, and nine months after the programme. Intervention Talking Parents, Healthy Teens consists of eight weekly one hour sessions at worksites for parents of adolescent children in 6th-10th grade (about ages 11-16 years). Main outcome measures Parent-adolescent communication about a list of sexual topics; whether parent taught adolescent how to use a condom; ability to communicate with parent/adolescent about sex; openness of parent-adolescent communication about sex. Results Differences between intervention and control groups were significant for the mean number of new sexual topics that parents and adolescents reported discussing between baseline and each follow-up (P<0.001 for each); intervention parents were less likely than controls to discuss no new topics (8% v 29%, 95% confidence interval for difference 16% to 24%) and more likely to discuss seven or more new topics (38% v 8%, 19% to 41%) at nine months. Some differences increased after completion of the programme: at one week after the programme, 18% of adolescents in the intervention group and 3% in the control group (6% to 30%) said that their parents had reviewed how to use a condom since baseline (P<0.001); this grew to 29% v 5% (13% to 36%) at nine months (P<0.001). Compared with controls at nine months, parents and adolescents in the intervention group reported greater ability to communicate with each other about sex (P<0.001) and more openness in communication about sex (P<0.001). Conclusions A worksite based programme can have substantial effects on communication between parents and adolescents about sexual health. Trial registration Clinical Trials NCT00465010. PMID:18617492

F 35 JOINT STRIKE FIGHTER DOD Needs to Complete Developmental Testing Before Making Significant New Investments

DTIC Science & Technology

2017-04-01

from contractors . Until Block 3F testing is complete, DOD will not have the knowledge it needs to present a sound business case for Block 4. Second...January 2017 the details of this plan were unclear because DOD’s 2018 budget was not final and negotiations with the contractors were ongoing...management reports and historical test data; discussed key aspects of F-35 development with program management and contractor officials; and compared

Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial.

PubMed

Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Fox, Christopher P; Schorb, Elisabeth; La Rosée, Paul; Binder, Mascha; Fabbri, Alberto; Torri, Valter; Minacapelli, Eleonora; Falautano, Monica; Ilariucci, Fiorella; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Johnson, Peter; Linton, Kim M; Pukrop, Tobias; Sønderskov Gørløv, Jette; Balzarotti, Monica; Hess, Georg; Keller, Ulrich; Stilgenbauer, Stephan; Panse, Jens; Tucci, Alessandra; Orsucci, Lorella; Pisani, Francesco; Levis, Alessandro; Krause, Stefan W; Schmoll, Hans J; Hertenstein, Bernd; Rummel, Mathias; Smith, Jeffery; Pfreundschuh, Michael; Cabras, Giuseppina; Angrilli, Francesco; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Finke, Jürgen; Reni, Michele; Cavalli, Franco; Zucca, Emanuele; Illerhaus, Gerald

2017-11-01

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of methotrexate 3·5 g/m 2 on day 1 plus cytarabine 2 g/m 2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m 2 on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m 2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4-10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m 2 on day -6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70-90) in group D and 69% (59-79) in group E (hazard ratio 1·50, 95% CI 0·83-2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. Agenzia Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

15 CFR Supplement No. 1 to Part 752 - Instructions for Completing Form BIS-748P, Multipurpose Application for Requests for Special...

Code of Federal Regulations, 2014 CFR

2014-01-01

... within the lines for each Block or box, except where a signature is required. Where there is a choice of... Special Comprehensive License box. Block 6: Documents Submitted with Application. Enter an “x” in the appropriate boxes to indicate which forms are attached. Block 7: Documents on File with Applicant. Leave blank...

15 CFR Supplement No. 1 to Part 752 - Instructions for Completing Form BIS-748P, Multipurpose Application for Requests for Special...

Code of Federal Regulations, 2011 CFR

2011-01-01

... within the lines for each Block or box, except where a signature is required. Where there is a choice of... Special Comprehensive License box. Block 6: Documents Submitted with Application. Enter an “x” in the appropriate boxes to indicate which forms are attached. Block 7: Documents on File with Applicant. Leave blank...

15 CFR Supplement No. 1 to Part 752 - Instructions for Completing Form BIS-748P, Multipurpose Application for Requests for Special...

Code of Federal Regulations, 2013 CFR

2013-01-01

... within the lines for each Block or box, except where a signature is required. Where there is a choice of... Special Comprehensive License box. Block 6: Documents Submitted with Application. Enter an “x” in the appropriate boxes to indicate which forms are attached. Block 7: Documents on File with Applicant. Leave blank...

Modifying Alcohol Consumption to Reduce Obesity (MACRO): development and feasibility trial of a complex community-based intervention for men.

PubMed Central

Crombie, Iain K; Cunningham, Kathryn B; Irvine, Linda; Williams, Brian; Sniehotta, Falko F; Norrie, John; Melson, Ambrose; Jones, Claire; Briggs, Andrew; Rice, Peter M; Achison, Marcus; McKenzie, Andrew; Dimova, Elena; Slane, Peter W

2017-01-01

BACKGROUND Obese men who consume alcohol are at a greatly increased risk of liver disease; those who drink > 14 units of alcohol per week have a 19-fold increased risk of dying from liver disease. OBJECTIVES To develop an intervention to reduce alcohol consumption in obese men and to assess the feasibility of a randomised controlled trial (RCT) to investigate its effectiveness. DESIGN OF THE INTERVENTION The intervention was developed using formative research, public involvement and behaviour change theory. It was organised in two phases, comprising a face-to-face session with trained laypeople (study co-ordinators) followed by a series of text messages. Participants explored how alcohol consumption contributed to weight gain, both through direct calorie consumption and through its effect on increasing food consumption, particularly of high-calorie foodstuffs. Men were encouraged to set goals to reduce their alcohol consumption and to make specific plans to do so. The comparator group received an active control in the form of a conventional alcohol brief intervention. Randomisation was carried out using the secure remote web-based system provided by the Tayside Clinical Trials Unit. Randomisation was stratified by the recruitment method and restricted using block sizes of randomly varying lengths. Members of the public were involved in the development of all study methods. SETTING Men were recruited from the community, from primary care registers and by time-space sampling (TSS). The intervention was delivered in community settings such as the participant's home, community centres and libraries. PARTICIPANTS Men aged 35-64 years who had a body mass index (BMI) of > 30 kg/m(2) and who drank > 21 units of alcohol per week. RESULTS The screening methods successfully identified participants meeting the entry criteria. Trial recruitment was successful, with 69 men (36 from 419 approached in primary care, and 33 from 470 approached via TSS) recruited and randomised in 3 months. Of the 69 men randomised, 35 were allocated to the intervention group and 34 to the control group. The analysis was conducted on 31 participants from the intervention group and 30 from the control group. The participants covered a wide range of ages and socioeconomic statuses. The average alcohol consumption of the men recruited was 47.2 units per week, more than twice that of the entry criterion (> 21 units per week). Most (78%) engaged in binge drinking (> 8 units in a session) at least weekly. Almost all (95%) exceeded the threshold for a 19-fold increase in the risk of dying from liver disease (BMI of > 30 kg/m(2) and > 14 units of alcohol per week). Despite this, they believed that they were at low risk of harm from alcohol, possibly because they seldom suffered acute harms (e.g. hangovers) and made few visits to a general practitioner or hospital. INTERVENTION The intervention was delivered with high fidelity. A high follow-up rate was achieved (98%) and the outcomes for the full RCT were measured. A process evaluation showed that participants engaged with the main components of the intervention. The acceptability of the study methods was high. CONCLUSIONS This feasibility study developed a novel intervention and evaluated all of the stages of a RCT that would test the effectiveness of the intervention. The main stages of a trial were completed successfully: recruitment, randomisation, intervention delivery, follow-up and measurement of study outcomes. Most of the men recruited drank very heavily and were also obese. This places them at a very high risk of liver disease, making them a priority for intervention. FUTURE WORK A RCT to test the effectiveness and cost-effectiveness of the intervention. TRIAL REGISTRATION Current Controlled Trials ISRCTN55309164. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 19. See the NIHR Journals Library website for further project information. PMID:28414020

Dietary supplements for preventing postnatal depression.

PubMed

Miller, Brendan J; Murray, Linda; Beckmann, Michael M; Kent, Terrence; Macfarlane, Bonnie

2013-10-24

Postnatal depression is a medical condition that affects many women and the development of their infants. There is a lack of evidence for treatment and prevention strategies that are safe for mothers and infants. Certain dietary deficiencies in a pregnant or postnatal woman's diet may cause postnatal depression. By correcting these deficiencies postnatal depression could be prevented in some women. Specific examples of dietary supplements aimed at preventing postnatal depression include: omega-3 fatty acids, iron, folate, s-adenosyl-L-methionine, cobalamin, pyridoxine, riboflavin, vitamin D and calcium. To assess the benefits of dietary supplements for preventing postnatal depression either in the antenatal period, postnatal period, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). Randomised controlled trials, involving women who were pregnant or who had given birth in the previous six weeks, who were not depressed or taking antidepressants at the commencement of the trials. The trials could use as intervention any dietary supplementation alone or in combination with another treatment compared with any other preventive treatment, or placebo, or standard clinical care. Two review authors independently assessed trials for inclusion and assessed the risk of bias for the two included studies. Two review authors extracted data and the data were checked for accuracy. We included two randomised controlled trials.One trial compared oral 100 microgram (µg) selenium yeast tablets with placebo, taken from the first trimester until birth. The trial randomised 179 women but outcome data were only provided for 85 women. Eighty-three women were randomised to each arm of the trial. Sixty-one women completed the selenium arm, 44 of whom completed an Edinburgh Postnatal Depression Scale (EPDS). In the placebo arm, 64 women completed the trial, 41 of whom completed an EPDS. This included study (n = 85) found selenium had an effect on EPDS scores but did not reach statistical significance (P = 0.07). There was a mean difference (MD) of -1.90 (95% confidence interval (CI) -3.92 to 0.12) of the self-reported EPDS completed by participants within eight weeks of delivery. There was a high risk of attrition bias due to a large proportion of women withdrawing from the study or not completing an EPDS. This included study did not report on any of the secondary outcomes of this review.The other trial compared docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) with placebo. The trial randomised 126 women at risk of postpartum depression to three arms: 42 were allocated to EPA, 42 to DHA, and 42 to placebo. Three women in the EPA arm, four in the DHA arm, and one woman in the placebo arm were lost to follow-up. Women who were found to have major depressive disorder, bipolar disorder, current substance abuse or dependence, suicidal ideation or schizophrenia at recruitment were excluded from the study. The women who discontinued the intervention (five in the EPA arm, four in the DHA arm and seven in the placebo arm) were included in the intention-to-treat analysis, while those who were lost to follow-up were not. Women received supplements or placebo from recruitment at a gestational age of 12 to 20 weeks until their final review visit six to eight weeks postpartum. The primary outcome measure was the Beck Depression Inventory (BDI) score at the fifth visit (six to eight weeks postpartum). No benefit was found for EPA-rich fish oil (MD 0.70, 95% CI -1.78 to 3.18) or DHA-rich fish oil supplementation (MD 0.90, 95% CI -1.33 to 3.13) in preventing postpartum depression. No difference was found in the effect on postnatal depression comparing EPA with DHA (MD -0.20, 95% CI -2.61 to 2.21). No benefit or significant effect was found in terms of the secondary outcomes of the presence of major depressive disorder at six to eight weeks postpartum, the number of women who commenced antidepressants, maternal estimated blood loss at delivery or admission of neonates to the neonatal intensive care unit. There is insufficient evidence to conclude that selenium, DHA or EPA prevent postnatal depression. There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression.

Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials.

PubMed

Gane, Edward J; Pianko, Stephen; Roberts, Stuart K; Thompson, Alexander J; Zeuzem, Stefan; Zuckerman, Eli; Ben-Ari, Ziv; Foster, Graham R; Agarwal, Kosh; Laursen, Alex L; Gerstoft, Jan; Gao, Wei; Huang, Hsueh-Cheng; Fitzgerald, Brian; Fernsler, Doreen; Li, Jerry J; Grandhi, Anjana; Liu, Hong; Su, Feng-Hsiu; Wan, Shuyan; Zeng, Zhen; Chen, Huei-Ling; Dutko, Frank J; Nguyen, Bach-Yen T; Wahl, Janice; Robertson, Michael N; Barr, Eliav; Yeh, Wendy W; Plank, Rebeca M; Butterton, Joan R; Esteban, Rafael

2017-11-01

New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibitor, either elbasvir (50 mg once daily) or ruzasvir (MK-8408; 60 mg once daily), and to evaluate the safety and tolerability of these combination regimens in individuals infected with genotypes 1, 2, or 3. Part A of these phase 2, randomised, multicentre, open-label, clinical trials enrolled participants from 11 countries, aged 18 years or older, chronically infected with HCV genotypes 1, 2, or 3, with HCV RNA of at least 10 000 IU/mL, without evidence of cirrhosis, who had not received previous treatment for HCV infection. Within each HCV genotype, participants were randomly assigned (1:1:1:1) with a block size of 4, to open-label treatment to one of four treatment groups: grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (300 mg/day); grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (450 mg/day); grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (300 mg/day); or grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (450 mg/day), according to a computer-generated allocation schedule. Randomisation was centrally implemented using an interactive voice response system and integrated web response system. The primary endpoint was the proportion of participants achieving sustained virological response at 12 weeks (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the end of all study therapy) in the per-protocol analysis set, which included all participants who were randomised and received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT02332707 and NCT02332720. 241 participants were randomised between Feb 18, 2015, and March 16, 2015. 240 participants completed 8 weeks of treatment and reached follow-up 12 weeks after the end of treatment. Of the four regimens, grazoprevir plus ruzasvir plus uprifosbuvir 450 mg had the most consistently high SVR12 (>90%) for participants infected with genotype 1 (21 [91%] of 23), genotype 2 (15 [94%] of 16), and genotype 3 (20 [91%] of 22). In particular, among those with genotype 2 infection, the grazoprevir plus ruzasvir plus uprifosbuvir 450 mg regimen had a higher SVR12 (15 [94%] of 16) than the grazoprevir plus ruzasvir plus uprifosbuvir 300 mg regimen (ten [71%] of 14), grazoprevir plus elbasvir plus uprifosbuvir 300 mg regimen (11 [69%] of 16), or grazoprevir plus elbasvir plus uprifosbuvir 450 mg regimen (nine [60%] of 15). Overall, the most common adverse events were headache (55 [23%] of 240), fatigue (47 [20%] of 240), and nausea (32 [13%] of 240). Two (<1%) of 240 participants had serious adverse events (pharyngeal abscess and keratitis), which were not considered drug related by the respective investigators. These results support further evaluation of the three-drug direct-acting antiviral agent regimen of grazoprevir 100 mg plus ruzasvir 60 mg plus uprifosbuvir 450 mg among a more diverse HCV-infected population, including those with compensated cirrhosis, previous treatment with an interferon-containing regimen, and HCV-HIV co-infection. Merck & Co, Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial.

PubMed

Torrico, Faustino; Gascon, Joaquim; Ortiz, Lourdes; Alonso-Vega, Cristina; Pinazo, María-Jesús; Schijman, Alejandro; Almeida, Igor C; Alves, Fabiana; Strub-Wourgaft, Nathalie; Ribeiro, Isabela

2018-04-01

Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia. Patients were randomised with a computer-generated randomisation list, which was stratified by centre and used a block size of ten. Patients were randomly assigned (1:1:1:1:1) to five oral treatment groups: high-dose E1224 (duration 8 weeks, total dose 4000 mg), low-dose E1224 (8 weeks, 2000 mg), short-dose E1224 (4 weeks + 4 weeks placebo, 2400 mg), benznidazole (60 days, 5 mg/kg per day), or placebo (8 weeks, E1224-matched tablets). Double-blinding was limited to the E1224 and placebo arms, and assessors were masked to all treatment allocations. The primary efficacy endpoint was parasitological response to E1224 at the end of treatment, assessed by PCR. The secondary efficacy endpoints were parasitological response to benznidazole at end of treatment, assessed by PCR; sustainability of parasitological response until 12 months; parasite clearance and changes in parasite load; incidence of conversion to negative response in conventional and non-conventional (antigen trypomastigote chemiluminescent ELISA [AT CL-ELISA]) serological response; changes in levels of biomarkers; and complete response. The primary analysis population consisted of all randomised patients by their assigned treatment arms. This trial is registered with ClinicalTrials.gov, number NCT01489228. Between July 19, 2011, and July 26, 2012, we screened 560 participants with confirmed Chagas disease, of whom 231 were enrolled and assigned to high-dose E1224 (n=45), low-dose E1224 (n=48), short-dose E1224 (n=46), benznidazole (n=45), or placebo (n=47). Parasite clearance was observed with E1224 during the treatment phase, but no sustained response was seen with low-dose and short-dose regimens, whereas 13 patients (29%, 95% CI 16·4-44·3) had sustained response with the high-dose regimen compared with four (9%, 2·4-20·4) in the placebo group (p<0·0001). Benznidazole had a rapid and sustained effect on parasite clearance, with 37 patients (82%, 67·9-92·0) with sustained response at 12-month follow-up. After 1 week of treatment, mean quantitative PCR repeated measurements showed a significant reduction in parasite load in all treatment arms versus placebo. Parasite levels in the low-dose and short-dose E1224 groups gradually returned to placebo levels. Both treatments were well tolerated. Reversible, dose-dependent liver enzyme increases were seen with E1224 and benznidazole. 187 (81%) participants developed treatment-emergent adverse events and six (3%) developed treatment-emergent serious adverse events. Treatment-emergent adverse events were headaches, nausea, pruritus, peripheral neuropathy, and hypersensitivity. E1224 is the first new chemical entity developed for Chagas disease in decades. E1224 displayed a transient, suppressive effect on parasite clearance, whereas benznidazole showed early and sustained efficacy until 12 months of follow-up. Despite PCR limitations, our results support increased diagnosis and access to benznidazole standard regimen, and provide a development roadmap for novel benznidazole regimens in monotherapy and in combinations with E1224. Drugs for Neglected Diseases initiative. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.

PubMed

Butts, Charles; Socinski, Mark A; Mitchell, Paul L; Thatcher, Nick; Havel, Libor; Krzakowski, Maciej; Nawrocki, Sergiusz; Ciuleanu, Tudor-Eliade; Bosquée, Lionel; Trigo, José Manuel; Spira, Alexander; Tremblay, Lise; Nyman, Jan; Ramlau, Rodryg; Wickart-Johansson, Gun; Ellis, Peter; Gladkov, Oleg; Pereira, José Rodrigues; Eberhardt, Wilfried Ernst Erich; Helwig, Christoph; Schröder, Andreas; Shepherd, Frances A

2014-01-01

Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation. The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188. From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25.6 months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8) compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0], respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups. We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted. Merck KGaA (Darmstadt, Germany). Copyright © 2014 Elsevier Ltd. All rights reserved.

Extradural cold block for selective neurostimulation of the bladder: development of a new technique.

PubMed

Schumacher, S; Bross, S; Scheepe, J R; Seif, C; Jünemann, K P; Alken, P

1999-03-01

Cryotechnique for selective block of the urethral sphincter and simultaneous activation of the bladder was developed to achieve physiological micturition during sacral anterior root stimulation (SARS). In ten foxhounds SARS of S2 was carried out while extradurally both spinal nerves S2 were cooled down from positive 25C in a stepwise fashion until a sphincter block was observed. Subsequently, SARS of S2 was performed while the pudendal nerves were cooled down from + 15C. The effects of spinal and pudendal nerve cold block on the urethral sphincter and bladder during SARS and the recovery time were monitored by urodynamic investigation. A complete cold block of the urethral sphincter during spinal nerve cooling was achieved in all cases. During pudendal nerve cooling, the sphincter was completely blocked in two, and incompletely blocked in four dogs. Cold block temperature of the spinal nerves averaged +11.7C and of the pudendal nerves +6.2C. During SARS and spinal nerve cooling, an increase in intravesical pressure up to 13 cm. water was recognized, and recovery time was on average 6.6 minutes. Intravesical pressure remained unchanged during pudendal nerve cooling, with recovery time being less than 1 minute. The cold block was always reversible. Cryotechnique is an excellent method for selective and reversible block of the urethral sphincter during SARS to avoid detrusor-sphincter-dyssynergia. The application of cryotechnique in functional electrical stimulation leads to an improvement of quality of life in para- or tetraplegic patients because of selective nerve stimulation with optimization of micturition, standing, walking and grasping and does so without the necessity of surgical dorsal root rhizotomy.

Ultrasound-Guided Selective Versus Conventional Block of the Medial Brachial Cutaneous and the Intercostobrachial Nerves: A Randomized Clinical Trial.

PubMed

Magazzeni, Philippe; Jochum, Denis; Iohom, Gabriella; Mekler, Gérard; Albuisson, Eliane; Bouaziz, Hervé

2018-06-13

For superficial surgery of anteromedial and posteromedial surfaces of the upper arm, the medial brachial cutaneous nerve (MBCN) and the intercostobrachial nerve (ICBN) must be selectively blocked, in addition to an axillary brachial plexus block. We compared efficacy of ultrasound-guided (USG) versus conventional block of the MBCN and the ICBN. Eighty-four patients, undergoing upper limb surgery, were randomized to receive either USG (n = 42) or conventional (n = 42) block of the MBCN and the ICBN with 1% mepivacaine. Sensory block was evaluated using light-touch on the upper and lower half of the anteromedial and posteromedial surfaces of the upper arm at 5, 10, 15, 20 minutes after nerve blocks. The primary outcome was the proportion of patients who had no sensation in all 4 regions innervated by the MBCN and the ICBN at 20 minutes. Secondary outcomes were onset time of complete anesthesia, volume of local anesthetic, tourniquet tolerance, and quality of ultrasound images. In the USG group, 37 patients (88%) had no sensation at 20 minutes in any of the 4 areas tested versus 8 patients (19%) in the conventional group (P < 0.001). When complete anesthesia was obtained, it occurred within 10 minutes in more than 90% of patients, in both groups. Mean total volumes of local anesthetic used for blocking the MBCN and the ICBN were similar in the 2 groups. Ultrasound images were of good quality in only 20 (47.6%) of 42 patients. Forty-one patients (97.6%) who received USG block were comfortable with the tourniquet versus 16 patients (38.1%) in the conventional group (P < 0.001). Ultrasound guidance improved the efficacy of the MBCN and ICBN blocks. This study was registered at ClinicalTrials.gov, identifier NCT02940847.

Creatine for women in pregnancy for neuroprotection of the fetus.

PubMed

Dickinson, Hayley; Bain, Emily; Wilkinson, Dominic; Middleton, Philippa; Crowther, Caroline A; Walker, David W

2014-12-19

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury. To assess the effects of creatine when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014). We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of creatine. We identified no completed or ongoing randomised controlled trials. We found no randomised controlled trials for inclusion in this review. As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

A preliminary RCT of a mind body skills based intervention addressing mood and coping strategies in patients with acute orthopaedic trauma.

PubMed

Vranceanu, Ana-Maria; Hageman, Michiel; Strooker, Joost; ter Meulen, Dirk; Vrahas, Mark; Ring, David

2015-04-01

To test the acceptability and feasibility of a mind body skills-based intervention (RRCB) and estimate its preliminary effect in reducing disability and pain intensity as compared to standard care (SC) in patients with acute musculoskeletal trauma. Randomised controlled trial. Level I trauma centre. Adult patients with acute fractures at risk for chronic pain and disability based on scores on two coping with pain measures who presented to an orthopedic trauma center and met inclusion and exclusion criteria. Participants were randomied to either RRCB with SC or SC alone. Disability (short musculoskeletal functional assessment, SMFA) and pain (Numerical Analogue Scale). coping strategies (Pain Catastrophizing Scale, PCS and Pain Anxiety Scale, PAS) and mood (CESD Depression and PTSD checklist). Among the 50 patients consented, two did not complete the initial assessment. Of these, the first four received the intervention as part of an open pilot and the next 44 were randomised (24 RRCBT and 20 UC) and completed initial assessment. We combined the patients who received RRCB into one group, N=28. Of the entire sample, 34 completed time two assessments (24 RRCBT and 10 SC). The RRCB proved to be feasible and accepted (86% retention, 28 out of 24 completers). Analyses of covariance ANCOVA showed a significant (p<05) improvement and large effect sizes for all time two main study variables (.2-.5) except pain with activity where the effect size was medium (.08). Improvement for pain at rest was not significantly higher in the RRCB as compared to the control, for a small effect size (.03). The RRCB is feasible, acceptable and potentially efficacious. Level 1 prognostic. Copyright © 2014 Elsevier Ltd. All rights reserved.