Early initiation of post-sternotomy cardiac rehabilitation exercise training (SCAR): study protocol for a randomised controlled trial and economic evaluation

PubMed Central

Lobley, Grace; Worrall, Sandra; Powell, Richard; Kimani, Peter K; Banerjee, Prithwish; Barker, Thomas

2018-01-01

Introduction Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice is not based on empirical evidence, thus imposing potentially unnecessary activity restrictions. Delayed participation in CR exercise training promotes muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited data suggest no detrimental effect of beginning CR exercise training as early as 2 weeks post-surgery, but randomised controlled trials are yet to confirm this. The purpose of this trial is to compare CR exercise training commenced early (2 weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to informing future CR guidelines for patients recovering from sternotomy. Methods and analysis In this assessor-blind randomised controlled trial, 140 cardiac surgery patients, recovering from sternotomy, will be assigned to 8 weeks of twice-weekly supervised CR exercise training commencing at either 2 weeks (early CR) or 6 weeks (usual care CR) post-surgery. Usual care exercise training will adhere to current UK recommendations. Participants in the early CR group will undertake a highly individualised 2–3 week programme of functional mobility, strength and cardiovascular exercise before progressing to a usual care CR programme. Outcomes will be assessed at baseline (inpatient), pre-CR (2 or 6 weeks post-surgery), post-CR (10 or 14 weeks post-surgery) and 12 months. The primary outcome will be change in 6 min walk distance. Secondary outcomes will include measures of functional fitness, quality of life and cost-effectiveness. Ethics and dissemination Recruitment commenced on July 2017 and will complete by December 2019. Results will be disseminated via national governing bodies, scientific meetings and peer-reviewed journals. Trial registration number NCT03223558; Pre-results. PMID:29574443

Pre-operative nutrition support in patients undergoing gastrointestinal surgery.

PubMed

Burden, Sorrel; Todd, Chris; Hill, James; Lal, Simon

2012-11-14

Post-operative management in gastrointestinal (GI) surgery is becoming well established with 'Enhanced Recovery After Surgery' protocols starting 24 hours prior to surgery with carbohydrate loading and early oral or enteral feeding given to patients the first day following surgery. However, whether or not nutritional intervention should be initiated earlier in the preoperative period remains unclear. Poor pre-operative nutritional status has been linked consistently to an increase in post-operative complications and poorer surgical outcome. To review the literature on preoperative nutritional support in patients undergoing gastrointestinal surgery (GI). The searches were initially run in March 2011 and subsequently updated in February 2012. Databases including all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA and NHSEED) MEDLINE, EMBASE, AMED, British Nursing Index Archive using OvidSP were included and a search was run on each database separately after which duplicates were excluded. The inclusion criteria were randomised controlled trials that evaluated pre-operative nutritional support in GI surgical participants using a nutritional formula delivered by a parenteral, enteral or oral route. The primary outcomes included post-operative complications and length of hospital stay. Two observers screened the abstracts for inclusion in the review and performed data extraction. Bias was assessed for each of the included studies using the bias assessment tables in the Cochrane Software Review Manager (version 5.1, Cochrane Collaboration). The trials were analysed using risk ratios with Mantel-Haenszel in fixed effects methods displayed with heterogeneity. Meta-analyses were undertaken on trials evaluating immune enhancing (IE) nutrition, standard oral supplements, enteral and parenteral nutrition (PN) which were administered pre-operatively.Study characteristics were summarised in tables. Dichotomous and ratio data were entered into meta-analyses for the primary outcomes. These were then summarised in tables with assumed and corresponding risk with relative effect giving 95% confidence intervals. The searches identified 9900 titles and, after excluding duplicates, 6433 titles were initially screened. After the initial title screen, 6266 were excluded. Abstracts were screened for 167 studies and 33 articles were identified as meeting the inclusion criteria, of which 13 were included in the review after an assessment of the complete manuscripts.Seven trials evaluating IE nutrition were included in the review, of which 6 were combined in a meta-analysis. These studies showed a low to moderate level of heterogeneity and significantly reduced total post-operative complications (risk ratio (RR) 0.67 CI 0.53 to 0.84). Three trials evaluating PN were included in a meta-analysis and a significant reduction in post-operative complications was demonstrated (RR 0.64 95% CI 0.46 to 0.87) with low heterogeneity, in predominantly malnourished participants. Two trials evaluating enteral nutrition (RR 0.79, 95% CI 0.56 to 1.10) and 3 trials evaluating standard oral supplements (RR 1.01 95% CI 0.56 to 1.10) were included, neither of which showed any difference in the primary outcomes. There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions.

Low-intensity case management increases contact with primary care in recently released prisoners: a single-blinded, multisite, randomised controlled trial

PubMed Central

Alati, Rosa; Longo, Marie; Spittal, Matthew J; Boyle, Frances M; Williams, Gail M; Lennox, Nicholas G

2016-01-01

Background The world prison population is large and growing. Poor health outcomes after release from prison are common, but few programmes to improve health outcomes for ex-prisoners have been rigorously evaluated. The aim of this study was to evaluate the impact of individualised case management on contact with health services during the first 6 months post-release. Methods Single-blinded, randomised, controlled trial. Baseline assessment with N=1325 adult prisoners in Queensland, Australia, within 6 weeks of expected release; follow-up interviews 1, 3 and 6 months post-release. The intervention consisted of provision of a personalised booklet (‘Passport’) at the time of release, plus up to four brief telephone contacts in the first 4 weeks post-release. Results Of 1179 eligible participants, 1003 (85%) completed ≥1 follow-up interview. In intention-to-treat analyses, 53% of the intervention group and 41% of the control group reported contacting a general practitioner (GP) at 1 month post-release (difference=12%, 95% CI 5% to 19%). Similar effects were observed for GP contact at 3 months (difference=9%, 95% CI 2% to 16%) and 6 months (difference=8%, 95% CI 1% to 15%), and for mental health (MH) service contact at 6 months post release (difference=8%, 95% CI 3% to 14%). Conclusions Individualised case management in the month after release from prison increases usage of primary care and MH services in adult ex-prisoners for at least 6 months post-release. Given the poor health profile of ex-prisoners, there remains an urgent need to develop and rigorously evaluate interventions to increase health service contact in this profoundly marginalised population. Trial registration number ACTRN12608000232336. PMID:26787201

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

PubMed

Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2016-01-01

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Effects of Alpha-Lactalbumin or Whey Protein Isolate on Muscle Damage, Muscle Pain, and Mood States Following Prolonged Strenuous Endurance Exercise

PubMed Central

Qin, Lu; Wong, Stephen H. S.; Sun, Feng-Hua; Huang, Yu; Sheridan, Sinead; Sit, Cindy H. P.

2017-01-01

This study compared the effect of alpha-lactalbumin and whey protein on muscle damage, muscle pain, and mood states during short term recovery following strenuous prolonged exercise. In a two-stage crossover counterbalanced design, 12 endurance male runners were recruited (age: 30.4 ± 2.8 year, height: 172.7 ± 5.6 cm, body mass: 66.7 ± 6.5 kg, VO2max: 58.0 ± 6.9 ml/kg−/min), ran for 90 min at 70% VO2max, and followed by a 4-h recovery. Two treatments (carbohydrate+alpha-lactalbumin, CA; carbohydrate+whey protein isolate, CW) were applied during the main trials. During the first 2-h of recovery, CHO was served at the rate of 0.66 g/kg/h and PRO at 0.34 g/kg/h every 30 min. Creatine kinase (CK), interleukin-6 (IL-6), salivary cortisol, rating of muscle pain, pressure pain threshold (PPT), and mood states were evaluated before (Pre-ex), immediately (Post-ex0), 2 h (Post-ex2h) and 4 h (Post-ex4h) after exercise. 24 h after exercise (Post-ex24h), CK and IL-6, muscle pain, and PPT were evaluated. Compared with Pre-ex, Post-ex24h CK was higher in both trials of CA (398.16 ± 41.37 vs. 184.77 ± 22.68 IU/L, P = 0.039) and CW (418.17 ± 67.86 vs. 202.41 ± 22.26 IU/L, P = 0.037). IL-6 was also higher than Pre-ex at Post-ex0 and Post-ex2h in trials of CA (Post-ex0 vs. Pre-ex0: 7.87 ± 0.74 vs. 1.69 ± 0.23, P < 0.01; Post-ex2h vs. Pre-ex0: 5.39 ± 0.88 vs. 1.69 ± 0.23, P = 0.02) and CW (Post-ex0 vs. Pre-ex0: 8.63 ± 1.06 vs. 1.59 ± 0.19, P < 0.01; Post-ex2h vs. Pre-ex0: 5.75 ± 1.33 vs. 1.59 ± 0.19, P < 0.01). No difference was found in CK and IL-6 between two trials at all time points (all P > 0.05). Compared with Pre-ex0, salivary cortisol was elevated at Post-ex0 in both trials (CA: 0.96 ± 0.13 vs. 0.41 ± 0.05 ng/ml, P < 0.01; CW: 1.15 ± 0.18 vs. 0.43 ± 0.06 ng/ml, P < 0.01) and was lower at Post-ex24h than Pre-ex in CA trial (0.17 ± 0.02 vs. 0.41 ± 0.05 ng/ml, P < 0.01). Compared with CW, PPT was higher at Post-2h in CA trial (31.55 ± 3.09 vs. 26.99 ± 2.32 N/cm2, P < 0.01). Compared with Post-ex0, feeling of fatigue was lower at Post-ex2h (P = 0.014) and Post-ex4h (P < 0.01) in CA, while it was lower at Post-ex4h (P = 0.038) in CW. Compared with CW, feeling of fatigue was marginally lower in the CA trial at Post-ex2h (P = 0.056). In conclusion, compared with the co-ingestion of CHO and whey PRO isolate, co-ingestion of CHO and alpha-lactalbumin reduced sensitivity to the muscle pain, attenuated feeling of fatigue and was more beneficial to reduce the feeling of fatigue and cortisol responses during 4-h recovery following 90-min running at 70% VO2max. PMID:29033851

Evaluation of a training program of hypertension for accredited social health activists (ASHA) in rural India.

PubMed

Abdel-All, Marwa; Thrift, Amanda Gay; Riddell, Michaela; Thankappan, Kavumpurathu Raman Thankappan; Mini, Gomathyamma Krishnakurup; Chow, Clara K; Maulik, Pallab Kumar; Mahal, Ajay; Guggilla, Rama; Kalyanram, Kartik; Kartik, Kamakshi; Suresh, Oduru; Evans, Roger George; Oldenburg, Brian; Thomas, Nihal; Joshi, Rohina

2018-05-02

Hypertension is a major risk factor for cardiovascular disease, a leading cause of premature death and disability in India. Since access to health services is poor in rural India and Accredited Social Health Activists (ASHAs) are available throughout India for maternal and child health, a potential solution for improving hypertension control is by utilising this available workforce. We aimed to develop and implement a training package for ASHAs to identify and control hypertension in the community, and evaluate the effectiveness of the training program using the Kirkpatrick Evaluation Model. The training program was part of a cluster randomised feasibility trial of a 3-month intervention to improve hypertension outcomes in South India. Training materials incorporated details on managing hypertension, goal setting, facilitating group meetings, and how to measure blood pressure and weight. The 15 ASHAs attended a five-day training workshop that was delivered using interactive instructional strategies. ASHAs then led community-based education support groups for 3 months. Training was evaluated using Kirkpatrick's evaluation model for measuring reactions, learning, behaviour and results using tests on knowledge at baseline, post-training and post-intervention, observation of performance during meetings and post-intervention interviews. The ASHAs' knowledge of hypertension improved from a mean score of 64% at baseline to 76% post-training and 84% after the 3-month intervention. Research officers, who observed the community meetings, reported that ASHAs delivered the self-management content effectively without additional assistance. The ASHAs reported that the training materials were easy to understand and useful in educating community members. ASHAs can be trained to lead community-based group educational discussions and support individuals for the management of high blood pressure. The feasibility trial is registered with the Clinical Trials Registry - India (CTRI) CTRI/2016/02/006678 (25/02/2016).

Impact of Sustained Use of a Multifaceted Computerized Quality Improvement Intervention for Cardiovascular Disease Management in Australian Primary Health Care.

PubMed

Patel, Bindu; Peiris, David; Usherwood, Tim; Li, Qiang; Harris, Mark; Panaretto, Kathryn; Zwar, Nicholas; Patel, Anushka

2017-10-24

We evaluated a multifaceted, computerized quality improvement intervention for management of cardiovascular disease (CVD) risk in Australian primary health care. After completion of a cluster randomized controlled trial, the intervention was made available to both trial arms. Our objective was to assess intervention outcomes in the post-trial period and any heterogeneity based on original intervention allocation. Data from 41 health services were analyzed. Outcomes were (1) proportion of eligible population with guideline-recommended CVD risk factor measurements; and (2) the proportion at high CVD risk with current prescriptions for guideline-recommended medications. Patient-level analyses were conducted using generalized estimating equations to account for clustering and time effects and tests for heterogeneity were conducted to assess impact of original treatment allocation. Median follow-up for 22 809 patients (mean age, 64.2 years; 42.5% men, 26.5% high CVD risk) was 17.9 months post-trial and 35 months since trial inception. At the end of the post-trial period there was no change in CVD risk factor screening overall when compared with the end of the trial period (64.7% versus 63.5%, P =0.17). For patients at high CVD risk, there were significant improvements in recommended prescriptions at end of the post-trial period when compared with the end of the trial period (65.2% versus 56.0%, P <0.001). There was no heterogeneity of treatment effects on the outcomes based on original randomization allocation. CVD risk screening improvements were not observed in the post-trial period. Conversely, improvements in prescribing continued, suggesting that changes in provider and patient actions may take time when initiating medications. URL: http://www.anzctr.org.au. Unique identifier: 12611000478910. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Trial occlusion to assess the risk of persistent pulmonary arterial hypertension after closure of a large patent ductus arteriosus in adolescents and adults with elevated pulmonary artery pressure.

PubMed

Zhang, Duan-Zhen; Zhu, Xian-Yang; Lv, Bei; Cui, Chun-Sheng; Han, Xiu-Min; Sheng, Xiao-Tang; Wang, Qi-Guang; Zhang, Po

2014-08-01

No method is available to predict whether patients with patent ductus arteriosus (PDA) and severe pulmonary arterial hypertension (PAH) will show persistent postprocedural PAH (PP-PAH) after PDA closure. This study evaluated the usefulness of trial occlusion for predicting PP-PAH after transcatheter PDA closure in patients with severe PAH. Trial occlusion was performed in 137 patients (age ≥12 years) with PDA and severe PAH. All patients undergoing trial occlusion had a mean pulmonary artery pressure ≥45 mm Hg, pulmonary:systemic flow (Qp/Qs) ratio >1.5, and pulmonary:systemic resistance (Rp/Rs) ratio <0.7. A total of 135 patients (98%) showing stable hemodynamics during occlusion trial underwent successful device closure. Linear correlation analysis revealed weak or moderate relationships between the baseline and post-trial pulmonary artery pressures and pulmonary:systemic pressure (Pp/Ps) ratios. Patients were followed up for 1 to 10 years (median: 5 years). PP-PAH (systolic pulmonary artery pressure >50 mm Hg by Doppler echocardiography) was detected in 17 patients (13%), who displayed no significant differences in sex and age compared with patients without PP-PAH. According to discriminant analysis, the strongest discriminators between patients with and without PP-PAH were the baseline left ventricular end-diastolic volume and the baseline and post-trial systolic Pp/Ps ratios. In particular, a post-trial systolic Pp/Ps ratio >0.5 correctly classified 100% of the PP-PAH and non-PAH patients. Trial occlusion is a feasible method to predict PP-PAH in patients with PDA and severe PAH. A post-trial systolic Pp/Ps ratio >0.5 indicates a high risk of PP-PAH occurrence after device closure. © 2014 American Heart Association, Inc.

An randomized controlled trial of Post-it® notes did not increase postal response rates in older depressed participants.

PubMed

Lewis, Helen; Keding, Ada; Bosanquet, Katharine; Gilbody, Simon; Torgerson, David

2017-02-01

Our aim was to evaluate the effectiveness of a Post-it® note to increase response rates and shorten response times to a 4-month postal follow-up questionnaire sent to participants taking part in the Collaborative Care in Screen-Positive Elders (CASPER) trials. Our trial was a two-arm randomized controlled trial comparing response rates to questionnaires with a printed Post-it® note (intervention) and without (control), nested in multi centred randomized controlled trials of older people with varying levels of depressive symptoms; the CASPER + and CASPER Self Help for those At Risk of Depression (SHARD) trials. A total of 611 participants were eligible and randomized. The primary outcome was response rates, secondary outcomes were time to response and need for a reminder. Of 297 participants, 266 (89.6%) returned their 4-month questionnaire in the post-it note arm, compared with 282 of 314 participants (89.8%) in the control arm (OR = 0.97, 95% CI: 0.57, 1.65, P = 0.913). There were no statistically significant differences in time to respond or the need to be sent a reminder. Patients with a major depressive episode were more likely to return questionnaires with post-it notes (P of interaction = .019). There was no significant difference in response rates, time to response, or the need for a reminder between the intervention and control at 4-month follow up for older people with depressive symptoms. However, there was a significant interaction between the Post-it® note group and level of depression. © 2016 John Wiley & Sons, Ltd.

Lawyers and Legal Advocacy in Juvenile Courts: An Assessment.

ERIC Educational Resources Information Center

Puritz, Patricia; Burrell, Sue; Schwartz, Robert; Soler, Mark; Warboys, Loren

2000-01-01

Evaluates the juvenile justice system focusing on the barriers children encounter when seeking appropriate counsel and the quality of representation. Includes an assessment of the appointment of counsel, pretrial preparation and trial performance, post-trial maneuvers, and appeals. Finds that the most common obstacle is the overwhelming caseloads…

Cognitive-behaviour therapy for post-traumatic stress in schizophrenia. A randomized controlled trial.

PubMed

Steel, C; Hardy, A; Smith, B; Wykes, T; Rose, S; Enright, S; Hardcastle, M; Landau, S; Baksh, M F; Gottlieb, J D; Rose, D; Mueser, K T

2017-01-01

There is limited evidence for effective interventions in the treatment of post-traumatic stress symptoms within individuals diagnosed with schizophrenia. Clinicians have concerns about using exposure treatments with this patient group. The current trial was designed to evaluate a 16-session cognitive restructuring programme, without direct exposure, for the treatment of post-traumatic stress symptoms specifically within individuals diagnosed with schizophrenia. A multicentre randomized controlled single-blinded trial with assessments at 0 months, 6 months (post-treatment) and 12 months (follow-up) was conducted. A total of 61 participants diagnosed with schizophrenia and exhibiting post-traumatic stress symptoms were recruited. Those randomized to treatment were offered up to 16 sessions of cognitive-behaviour therapy (CBT, including psychoeducation, breathing training and cognitive restructuring) over a 6-month period, with the control group offered routine clinical services. The main outcome was blind rating of post-traumatic stress symptoms using the Clinician Administered PTSD Scale for Schizophrenia. Secondary outcomes were psychotic symptoms as measured by the Positive and Negative Symptom Scale and the Psychotic Symptom Rating Scale. Both the treatment and control groups experienced a significant decrease in post-traumatic stress symptoms over time but there was no effect of the addition of CBT on either the primary or secondary outcomes. The current trial did not demonstrate any effect in favour of CBT. Cognitive restructuring programmes may require further adaptation to promote emotional processing of traumatic memories within people diagnosed with a psychotic disorder.

Adverse event assessment and reporting in trials of newer treatments for post-operative pain.

PubMed

Hoffer, D; Smith, S M; Parlow, J; Allard, R; Gilron, I

2016-08-01

Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well-characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown. We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity. We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications. Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

Therapeutic chemical treatment of grape vines for root diseases

USDA-ARS?s Scientific Manuscript database

There is a need to develop post-plant treatment of soil pests for perennial vine and tree crops. Field trials were performed to evaluate post-plant treatment of established grape vines (Vitis vinifera var. Thompson Seedless) with known problems of soilborne plant-parasitic nematodes and pathogens us...

Technical success from endovascular aneurysm repair in the post-marketing era: a multicenter prospective trial.

PubMed

Naslund, Thomas C; Becker, Stacey Y

2003-01-01

Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was accomplished by review of a multicenter, prospective trial involving 46 centers and 163 patients. A second cohort of patients (n = 350) treated with the AEG under a controlled-use interval prior to the prospective trial was simultaneously evaluated. Technical success in both groups of patients (96.9% and 97.4%, respectively) was similar to what was reported in pre-market clinical trials. Operative implantation complications unique to the AEG included graft limb stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%, jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8 and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract jacket in 1.8 and 0.5% of patients involved in the multicenter trial and controlled-use interval, respectively. One of four patients undergoing conversion in the prospective trial had graft misdeployment as a mode of failure. Three were converted for access failure. The 30-day mortality rate in the prospective trial was 3.7%. Interventions to resolve implantation-related events included stenting, guide catheter manipulations, wire exchanges, and delivery catheter disassembly. These interventions were successful in virtually every case. Open surgical procedures were not needed to correct these operative problems. Results from this study demonstrate excellent technical success with the AEG in the post-market era. Interventions to resolve implantation complications, when utilized, are highly successful in facilitating AEG implantation and providing technical success.

Randomized Clinical Trial of Motivational Enhancement of Substance Use Treatment among Incarcerated Adolescents: Post-Release Condom Non-Use

ERIC Educational Resources Information Center

Rosengard, Cynthia; Stein, L. A. R.; Barnett, Nancy P.; Monti, Peter M.; Golembeske, Charles; Lebeau-Craven, Rebecca; Miranda, Robert

2007-01-01

Evaluated impact of motivational enhancement (ME) of substance abuse treatment compared to relaxation training (RT) on sex without condoms (overall and involving substance use) 3 months following release among incarcerated adolescents. This randomized clinical trial involved 114 incarcerated adolescents from the Northeast. Regression analyses…

[Discussion on development of four diagnostic information scale for clinical re-evaluation of postmarketing herbs].

PubMed

He, Wei; Xie, Yanming; Wang, Yongyan

2011-12-01

Post-marketing re-evaluation of Chinese herbs can well reflect Chinese medicine characteristics, which is the most easily overlooked the clinical re-evaluation content. Since little attention has been paid to this, study on the clinical trial design method was lost. It is difficult to improving the effectiveness and safety of traditional Chinese medicine. Therefore, more attention should be paid on re-evaluation of the clinical trial design method point about tcm syndrome such as the type of research program design, the study of Chinese medical information collection scale and statistical analysis methods, so as to improve the clinical trial design method study about tcm syndrome of Chinese herbs postmarketing re-evalutation status.

Boy Scout 5-a-day badge: Outcome results of a troop and internet intervention

USDA-ARS?s Scientific Manuscript database

The effects of a Boy Scout Five-A-Day Badge program on fruit-juice (FJ) and low fat vegetable (LV) consumption were evaluated using a two-condition (treatment, active-attention placebo-control) group randomized trial, with 3 data collection periods (baseline, immediate post, 6-month post). Forty-two...

The use of a non-benzodiazepine hypnotic sleep-aid (Zolpidem) in patients undergoing ACL reconstruction: a randomized controlled clinical trial.

PubMed

Tompkins, Marc; Plante, Matthew; Monchik, Keith; Fleming, Braden; Fadale, Paul

2011-05-01

Previous studies have addressed post-operative pain management after ACL reconstruction by examining the use of intra-articular analgesia and/or modification of anesthesia techniques. To our knowledge, however, no previous studies have evaluated the effect of zolpidem on post-operative narcotic requirements, pain, and fatigue in patients undergoing outpatient arthroscopic ACL reconstruction. The purpose of this prospective, blinded, randomized, controlled clinical study was to evaluate the effect of zolpidem on post-operative narcotic requirements, pain, and fatigue in patients undergoing outpatient arthroscopic ACL reconstruction. Twenty-nine patients undergoing arthroscopic ACL reconstruction were randomized to a treatment group or placebo group. Both groups received post-operative hydrocodone/acetaminophen bitartrate (Vicodin ES). Patients in the treatment group received a single dose of zolpidem for the first seven post-operative nights. Patients in the placebo group received a gelatin capsule similar in appearance to zolpidem. The amount of Vicodin used in each group, the amount of post-operative pain, and the amount of post-operative fatigue were analyzed. Following ACL reconstruction, a 28% reduction was seen in the total amount of narcotic consumed with zolpidem (P = 0.047) when compared to placebo. There were no significant differences in post-operative pain or fatigue levels between zolpidem and placebo. Adding zolpidem to the post-operative medication regimen after arthroscopic ACL reconstruction helps to lower the amount of narcotic pain medication required for adequate analgesia. Randomized controlled clinical trial, Level I.

Evaluation of a selected lactic acid bacteria-based probiotic on Salmonella enterica serovar Enteritidis colonization and intestinal permeability in broiler chickens.

PubMed

Prado-Rebolledo, Omar F; Delgado-Machuca, Jaime de Jesus; Macedo-Barragan, Rafael J; Garcia-Márquez, Luis J; Morales-Barrera, Jesus E; Latorre, Juan D; Hernandez-Velasco, Xochitl; Tellez, Guillermo

2017-02-01

Two experiments were conducted to evaluate the effect of a lactic acid bacteria-based probiotic (FloraMax-B11 ® ) against Salmonella enterica serovar Enteritidis intestinal colonization and intestinal permeability in broiler chickens. Experiment 1 consisted of two independent trials. In each trial, day-old broiler chicks were assigned to one of two groups: control + S. Enteritidis or probiotic + S. Enteritidis. At 72 h post-S. Enteritidis challenge, haematology and caecal content were evaluated for S. Enteritidis colonization. In Experiment 2, day-old broiler chicks were assigned to one of four groups: negative control; probiotic; control + S. Enteritidis; or probiotic + S. Enteritidis. At 72 h post-S. Enteritidis challenge, chickens in all groups were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). In both trials of Experiment 1, a significant reduction (P < 0.05) in colony-forming units/gram of S. Enteritidis in caecal content and a reduction in the incidence of S. Enteritidis enriched caecal samples were observed in probiotic + S. Enteritidis chickens. In addition, significant heterophilia and lymphopaenia were observed in control + S. Enteritidis chickens. In Experiment 2, a decrease in numbers of S. Enteritidis in caeca were observed in probiotic + S. Enteritidis chickens when compared to control + S. Enteritidis. Also, an increase in serum FITC-d concentration was detected in control + S. Enteritidis. These results suggest that early infection with S. Enteritidis can increase intestinal permeability, but the adverse effects can be prevented by the administration of the probiotic tested.

Human thermoregulatory function during exercise and immersion after 35 days of horizontal bed-rest and recovery.

PubMed

Mekjavic, Igor B; Golja, Petra; Tipton, Michael J; Eiken, Ola

2005-10-01

The present study evaluated the effect of 35 days of experimental horizontal bed-rest on exercise and immersion thermoregulatory function. Fifteen healthy male volunteers were assigned to either a Control (n = 5) or Bed-rest (n = 10) group. Thermoregulatory function was evaluated during a 30-min bout of submaximal exercise on a cycle ergometer, followed immediately by a 100-min immersion in 28 degrees C water. For the Bed-rest group, exercise and immersion thermoregulatory responses observed post-bed-rest were compared with those after a 5 week supervised active recovery period. In both trials, the absolute work load during the exercise portion of the test was identical. During the exercise and immersion, we recorded skin temperature, rectal temperature, the difference in temperature between the forearm and third digit of the right hand (DeltaT(forearm-fingertip))--an index of skin blood flow, sweating rate from the forehead, oxygen uptake and heart rate at minute intervals. Subjects provided ratings of temperature perception and thermal comfort at 5-min intervals. Exercise thermoregulatory responses after bed-rest and recovery were similar. Subjective ratings of temperature perception and thermal comfort during immersion indicated that subjects perceived similar combinations of Tsk and Tre to be warmer and thermally less uncomfortable after bed-rest. The average (SD) exercise-induced increase in Tre relative to resting values was not significantly different between the Post-bed-rest (0.4 (0.2) degrees C) and Recovery (0.5 (0.2) degrees C) trials. During the post-exercise immersion, the decrease in Tre, relative to resting values, was significantly (P < 0.05) greater in the Post-bed-rest trial (0.9 (0.5) degrees C) than after recovery (0.4 (0.3) degrees C). DeltaT(forearm-fingertip) was 5.2 (0.9) degrees C and 5.8 (1.0) degrees C at the end of the post-bed-rest and recovery immersions, respectively. The gain of the shivering response (increase in VO(2) relative to the decrease in Tre; VO(2)/Tre) was 1.19 l min(-1) degrees C(-1) in the Recovery trial, and was significantly attenuated to 0.51 l min(-1) degrees C(-1) in the Post-bed-rest trial. The greater cooling rate observed in the post-bed-rest trial is attributed to the greater heat loss and reduced heat production. The former is the result of attenuated cold-induced vasoconstriction and enhanced sweating rate, and the latter a result of a lower shivering VO(2) response.

Post-traumatic stress disorder in the context of terrorism and other civil conflict in Northern Ireland: randomised controlled trial

PubMed Central

Gillespie, Kate; Clark, David M

2007-01-01

Objective To evaluate the effectiveness of cognitive therapy for post-traumatic stress disorder related to terrorism and other civil conflict in Northern Ireland. Design Randomised controlled trial. Setting Community treatment centre, Northern Ireland. Participants 58 consecutive patients with chronic post-traumatic stress disorder (median 5.2 years, range 3 months to 32 years) mostly resulting from multiple traumas linked to terrorism and other civil conflict. Interventions Immediate cognitive therapy compared with a waiting list control condition for 12 weeks followed by treatment. Treatment comprised a mean of 5.9 sessions during 12 weeks and 2.0 sessions thereafter. Main outcome measures Primary outcome measures were patients' scores for post-traumatic stress disorder (post-traumatic stress diagnostic scale) and depression (Beck depression inventory). The secondary outcome measure was scores for occupational and social functioning (work related disability, social disability, and family related disability) on the Sheehan disability scale. Results At 12 weeks after randomisation, immediate cognitive therapy was associated with significantly greater improvement than the waiting list control group in the symptoms of post-traumatic stress disorder (mean difference 9.6, 95% confidence interval 3.6 to 15.6), depression (mean difference 10.1, 4.8 to 15.3), and self reported occupational and social functioning (mean difference 1.3, 0.3 to 2.5). Effect sizes from before to after treatment were large: post-traumatic stress disorder 1.25, depression 1.05, and occupational and social functioning 1.17. No change was observed in the control group. Conclusion Cognitive therapy is an effective treatment for post-traumatic stress disorder related to terrorism and other civil conflict. Trial registration Current Controlled Trials ISRCTN16228473. PMID:17495988

A Crossover Trial Evaluating an Educational-Behavioral Joint Protection Programme for People with Rheumatoid Arthritis.

ERIC Educational Resources Information Center

Hammond, A.; Lincoln, N.; Sutcliffe, L.

1999-01-01

Joint protection, a self-management technique taught to people with rheumatoid arthritis, was used in a group education program. A crossover trial (N=35) was conducted. No significant changes in measures of pain, functional disability, grip strength, self-efficacy or helplessness occurred post-education, although this may have been due to the…

Impact of School-Based HIV Prevention Program in Post-Conflict Liberia

ERIC Educational Resources Information Center

Atwood, Katharine A.; Kennedy, Stephen B.; Shamblen, Steve; Tegli, Jemee; Garber, Salome; Fahnbulleh, Pearl W.; Korvah, Prince M.; Kolubah, Moses; Mulbah-Kamara, Comfort; Fulton, Shannon

2012-01-01

This paper presents findings of a feasibility study to adapt and evaluate the impact of an evidence-based HIV prevention intervention on sexual risk behaviors of in-school 6th grade youth in post-conflict Liberia (n = 812). The study used an attention-matched, group randomized controlled trial. Four matched pairs of elementary/middle schools in…

Non-Speech Oro-Motor Exercises in Post-Stroke Dysarthria Intervention: A Randomized Feasibility Trial

ERIC Educational Resources Information Center

Mackenzie, C.; Muir, M.; Allen, C.; Jensen, A.

2014-01-01

Background: There has been little robust evaluation of the outcome of speech and language therapy (SLT) intervention for post-stroke dysarthria. Non-speech oro-motor exercises (NSOMExs) are a common component of dysarthria intervention. A feasibility study was designed and executed, with participants randomized into two groups, in one of which…

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PubMed

da Silva, Ricardo Eccard; Amato, Angélica Amorim; Sousa, Thiago do Rego; de Carvalho, Marta Rodrigues; Novaes, Maria Rita Carvalho Garbi

2018-05-12

Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

PubMed

Healy, Donagh; Clarke-Moloney, Mary; Gaughan, Brendan; O'Daly, Siobhan; Hausenloy, Derek; Sharif, Faisal; Newell, John; O'Donnell, Martin; Grace, Pierce; Forbes, John F; Cullen, Walter; Kavanagh, Eamon; Burke, Paul; Cross, Simon; Dowdall, Joseph; McMonagle, Morgan; Fulton, Greg; Manning, Brian J; Kheirelseid, Elrasheid A H; Leahy, Austin; Moneley, Daragh; Naughton, Peter; Boyle, Emily; McHugh, Seamus; Madhaven, Prakash; O'Neill, Sean; Martin, Zenia; Courtney, Donal; Tubassam, Muhammed; Sultan, Sherif; McCartan, Damian; Medani, Mekki; Walsh, Stewart

2015-04-23

Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial

PubMed Central

Fahlenkamp, Astrid V.; Stoppe, Christian; Cremer, Jan; Biener, Ingeborg A.; Peters, Dirk; Leuchter, Ricarda; Eisert, Albrecht; Apfel, Christian C.; Rossaint, Rolf; Coburn, Mark

2016-01-01

Objective Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV). We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis. Methods 220 subjects with elevated PONV risk (Apfel score ≥2) undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up. Results Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02–5.19, p = 0.044). Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138). After xenon, nausea occurred significantly earlier (p = 0.014), was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups. Conclusion In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea. Trial Registration EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663 PMID:27111335

Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.

PubMed

Grant, Aileen; Dreischulte, Tobias; Treweek, Shaun; Guthrie, Bruce

2012-08-28

Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.

Why caution is recommended with post-hoc individual patient matching for estimation of treatment effect in parallel-group randomized controlled trials: the case of acute stroke trials.

PubMed

Jafari, Nahid; Hearne, John; Churilov, Leonid

2013-11-10

A post-hoc individual patient matching procedure was recently proposed within the context of parallel group randomized clinical trials (RCTs) as a method for estimating treatment effect. In this paper, we consider a post-hoc individual patient matching problem within a parallel group RCT as a multi-objective decision-making problem focussing on the trade-off between the quality of individual matches and the overall percentage of matching. Using acute stroke trials as a context, we utilize exact optimization and simulation techniques to investigate a complex relationship between the overall percentage of individual post-hoc matching, the size of the respective RCT, and the quality of matching on variables highly prognostic for a good functional outcome after stroke, as well as the dispersion in these variables. It is empirically confirmed that a high percentage of individual post-hoc matching can only be achieved when the differences in prognostic baseline variables between individually matched subjects within the same pair are sufficiently large and that the unmatched subjects are qualitatively different to the matched ones. It is concluded that the post-hoc individual matching as a technique for treatment effect estimation in parallel-group RCTs should be exercised with caution because of its propensity to introduce significant bias and reduce validity. If used with appropriate caution and thorough evaluation, this approach can complement other viable alternative approaches for estimating the treatment effect. Copyright © 2013 John Wiley & Sons, Ltd.

A randomized controlled trial of manual therapy and pneumatic compression for recovery from prolonged running - an extended study.

PubMed

Heapy, Amanda M; Hoffman, Martin D; Verhagen, Heidie H; Thompson, Samuel W; Dhamija, Pavitra; Sandford, Fiona J; Cooper, Mary C

2018-03-07

Manual therapy (MT) and intermittent pneumatic compression (IPC) are recovery methods used by endurance athletes with little evidence supporting effectiveness. This randomized controlled trial evaluated effectiveness of four daily post-race treatments of a specific MT protocol and IPC compared with supine rest on recovery following an ultramarathon among 56 ultramarathoners. Groups were comparable across all characteristics examined, including post-race plasma creatine kinase concentration. Subject completed timed 400 m runs before the race and on days three, five, seven and 14 post- race, and also provided muscle pain and soreness ratings and fatigue scores immediately before and after treatments, and during the 14 days post- race. Daily subjective measures and 400 m run times were not improved by either treatment, but both treatments reduced (p < .05) muscular fatigue scores acutely after treatment following the race and on post-race day 1, and MT improved (p < .05) muscle pain and soreness acutely following the race.

Efficacy of the Lexicon Pirate Strategy Therapy for Improving Lexical Learning in School-Age Children: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Motsch, Hans-Joachim; Marks, Dana-Kristin

2015-01-01

Lexicon Pirate was originally developed as a strategy intervention programme to treat lexical disorders of pre-school children. To evaluate the therapy's effectiveness for school-age students, a randomized controlled trial (RCT, N = 157) was conducted. Based on a pre--post-test design, the programme's impacts were compared with a control group…

Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial.

PubMed

Tamura, Tomoyoshi; Hayashida, Kei; Sano, Motoaki; Onuki, Shuko; Suzuki, Masaru

2017-10-23

Hydrogen gas inhalation (HI) improved survival and neurological outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The feasibility and safety of HI for patients with PCAS was confirmed in a pilot study. The objective of this study is to evaluate the efficacy of HI for patients with PCAS. The efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II) trial is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8) patients who will be resuscitated following an out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized (1:1) to either the HI or control group. Patients in the HI group will inhale 2% hydrogen with 24% to 50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h after admission via mechanical ventilation. Multidisciplinary post-arrest care, including targeted temperature management (TTM) between 33 °C and 36 °C, will be provided in accordance with the latest guidelines. The primary outcome of interest is the 90-day neurological outcome, as evaluated using the Cerebral Performance Categories scale (CPC). The secondary outcomes of interest are the 90-day survival rate and other neurological outcomes. This study will provide 80% power to detect a 15% change in the proportion of patients with good neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall significance level of 0.05. The first multicenter randomized trial is underway to confirm the efficacy of HI on neurological outcomes in comatose out-of-hospital cardiac arrest survivors. Our study has the potential to address HI as an appealing and innovative therapeutic strategy for PCAS in combination with TTM. University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015.

Local anaesthetic infiltration for the rubber band ligation of early symptomatic haemorrhoids: a systematic review and meta-analysis.

PubMed

Sajid, M S; Bhatti, M I; Caswell, J; Sains, P; Baig, M K

2015-03-01

The objective of this article is to systematically analyse the randomized, controlled trials evaluating the effectiveness of local anaesthetic infiltration prior to the rubber band ligation of early symptomatic haemorrhoids. Published randomized, controlled trials comparing the use of local anaesthetic (LA) versus no-local anaesthetic (NLA) for the rubber band ligation of early symptomatic haemorrhoids were analysed using RevMan®, and the combined outcomes were expressed as odds ratios (OR) and standardized mean difference (SMD). Four randomized, controlled trials evaluating 387 patients were retrieved from the standard electronic databases. The risk of treatment failure (OR 0.44; 95% CI 0.07, 2.79; z = 0.87; p = 0.39) and post-procedure complications (OR 0.48; 95% CI 0.08, 2.76; z = 0.83; p = 0.41) was similar between two techniques. However, the post-procedure pain score (SMD -5.19; 95% CI -9.08, -1.30; z = 2.62; p < 0.009) was significantly lower in the group of patients undergoing rubber band ligation of haemorrhoids under local anaesthetic injection. The use of LA appears to have clinically measurable advantages over NLA in the rubber band ligation of early symptomatic haemorrhoids to lessen post-procedure pain.

Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

PubMed

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-12-01

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

[Sample size calculation in clinical post-marketing evaluation of traditional Chinese medicine].

PubMed

Fu, Yingkun; Xie, Yanming

2011-10-01

In recent years, as the Chinese government and people pay more attention on the post-marketing research of Chinese Medicine, part of traditional Chinese medicine breed has or is about to begin after the listing of post-marketing evaluation study. In the post-marketing evaluation design, sample size calculation plays a decisive role. It not only ensures the accuracy and reliability of post-marketing evaluation. but also assures that the intended trials will have a desired power for correctly detecting a clinically meaningful difference of different medicine under study if such a difference truly exists. Up to now, there is no systemic method of sample size calculation in view of the traditional Chinese medicine. In this paper, according to the basic method of sample size calculation and the characteristic of the traditional Chinese medicine clinical evaluation, the sample size calculation methods of the Chinese medicine efficacy and safety are discussed respectively. We hope the paper would be beneficial to medical researchers, and pharmaceutical scientists who are engaged in the areas of Chinese medicine research.

Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients (POPPI): protocol for a cluster-randomised clinical trial of a complex intervention

PubMed Central

Richards-Belle, Alvin; Mouncey, Paul R; Wade, Dorothy; Brewin, Chris R; Emerson, Lydia M; Grieve, Richard; Harrison, David A; Harvey, Sheila; Howell, David; Mythen, Monty; Sadique, Zia; Smyth, Deborah; Weinman, John; Welch, John; Rowan, Kathryn M

2018-01-01

Introduction Acute psychological stress, as well as unusual experiences including hallucinations and delusions, are common in critical care unit patients and have been linked to post-critical care psychological morbidity such as post-traumatic stress disorder (PTSD), depression and anxiety. Little high-quality research has been conducted to evaluate psychological interventions that could alleviate longer-term psychological morbidity in the critical care unit setting. Our research team developed and piloted a nurse-led psychological intervention, aimed at reducing patient-reported PTSD symptom severity and other adverse psychological outcomes at 6 months, for evaluation in the POPPI trial. Methods and analysis This is a multicentre, parallel group, cluster-randomised clinical trial with a staggered roll-out of the intervention. The trial is being carried out at 24 (12 intervention, 12 control) NHS adult, general, critical care units in the UK and is evaluating the clinical effectiveness and cost-effectiveness of a nurse-led preventative psychological intervention in reducing patient-reported PTSD symptom severity and other psychological morbidity at 6 months. All sites deliver usual care for 5 months (baseline period). Intervention group sites are then trained to carry out the POPPI intervention, and transition to delivering the intervention for the rest of the recruitment period. Control group sites deliver usual care for the duration of the recruitment period. The trial also includes a process evaluation conducted independently of the trial team. Ethics and dissemination This protocol was reviewed and approved by the National Research Ethics Service South Central - Oxford B Research Ethics Committee (reference: 15/SC/0287). The first patient was recruited in September 2015 and results will be disseminated in 2018. The results will be presented at national and international conferences and published in peer reviewed medical journals. Trial registration number ISRCTN53448131; Pre-results. PMID:29439083

"Healthy Habits, Healthy Girls—Brazil": an obesity prevention program with added focus on eating disorders

USDA-ARS?s Scientific Manuscript database

The purpose of the study was to evaluate the immediate post-intervention and 6-month post-intervention effects of a Brazilian school-based randomized controlled trial for girls targeting shared risk factors for obesity and disordered eating. A total of 253 girls, mean of 15.6 (0.05) years from 1st t...

Fish Oil and Post-Operative Atrial Fibrillation – Results of the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial

PubMed Central

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G.; Ferrazzi, Paolo; Gardner, Timothy J.; Latini, Roberto; Libby, Peter; Lombardi, Federico; O’Gara, Patrick T.; Page, Richard L.; Tavazzi, Luigi; Tognoni, Gianni

2013-01-01

Context Post-operative atrial fibrillation/flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and healthcare utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFA) reduce post-op AF, with mixed results. Objective To determine whether peri-operative n-3-PUFA supplementation reduces post-op AF. Design Randomized, double-blind, placebo-controlled, multinational, clinical trial. Patients A total of 1,516 patients scheduled for cardiac surgery across 28 centers in the US, Italy, and Argentina, enrolled between Aug 2010 and Jun 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Forty-eight percent of screened patients and 94% of eligible patients were enrolled. Intervention Patients were randomized to receive fish oil (1 g capsules containing ≥840 mg n-3-PUFA as ethyl esters) or placebo, with pre-operative loading of 10g over 3-5 days (or 8g over 2 days) followed post-operatively by 2g/d until hospital discharge or post-op day10, whichever first. Main Outcome Measures The primary endpoint was occurrence of post-op AF >30 sec. We also evaluated post-op AF lasting >1hr, resulting in symptoms, or treated with cardioversion; other secondary post-op AF endpoints; other tachyarrhythmias; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. All endpoints and analyses plans were prespecified. Results At enrollment, mean±SD age was 64±13 years, 72.2% were male, and 51.8% had planned valvular surgery. The primary endpoint occurred in 233 (30.7%) and 227 (30.0%) patients assigned to placebo and n-3-PUFA, respectively (OR=0.96, 95%CI=0.77-1.20; P=0.74). None of the secondary endpoints were significantly different, including post-op AF that was sustained, symptomatic, or treated (n=231 [30.5%] vs. n=224 [29.6%], P=0.70) or number of post-op AF episodes per patient (1 episode: n=220 [29.0%] vs. n=217 [28.6%]; 2 episodes: n=156 [20.6%] vs. n=157 [20.7%]; 3+ episodes: n=18 [2.4%] vs. n=21 [2.8%]; P=0.73). n-3-PUFA was generally well-tolerated, with no evidence for increased risk of bleeding or serious adverse events. Conclusions In this large multinational trial among patients undergoing cardiac surgery, peri-operative supplementation with n-3-PUFA, compared to placebo, did not reduce the risk of post-operative AF. PMID:23128104

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Constraint-induced aphasia therapy in post-stroke aphasia rehabilitation: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Bao, Yong; Xie, Qing; Xu, Yang; Zhang, Junmei

2017-01-01

Background Constraint-induced aphasia therapy (CIAT) has been widely used in post-stroke aphasia rehabilitation. An increasing number of clinical controlled trials have investigated the efficacy of the CIAT for the post-stroke aphasia. Purpose To systematically review the randomized controlled trials (RCTs) concerning the effect of the CIAT in post-stroke patients with aphasia, and to identify the useful components of CIAT in post-stroke aphasia rehabilitation. Methods A computerized database search was performed through five databases (Pubmed, EMbase, Medline, ScienceDirect and Cochrane library). Cochrane handbook domains were used to evaluate the methodological quality of the included RCTs. Results Eight RCTs qualified in the inclusion criteria. Inconsistent results were found in comparing the CIAT with conventional therapies without any component from the CIAT based on the results of three RCTs. Five RCTs showed that the CIAT performed equally well as other intensive aphasia therapies, in terms of improving language performance. One RCT showed that therapies embedded with social interaction were likely to enhance the efficacy of the CIAT. Conclusion CIAT may be useful for improving chronic post-stroke aphasia, however, limited evidence to support its superiority to other aphasia therapies. Massed practice is likely to be a useful component of CIAT, while the role of “constraint” is needed to be further explored. CIAT embedded with social interaction may gain more benefits. PMID:28846724

Constraint-induced aphasia therapy in post-stroke aphasia rehabilitation: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Zhang, Jiaqi; Yu, Jiadan; Bao, Yong; Xie, Qing; Xu, Yang; Zhang, Junmei; Wang, Pu

2017-01-01

Constraint-induced aphasia therapy (CIAT) has been widely used in post-stroke aphasia rehabilitation. An increasing number of clinical controlled trials have investigated the efficacy of the CIAT for the post-stroke aphasia. To systematically review the randomized controlled trials (RCTs) concerning the effect of the CIAT in post-stroke patients with aphasia, and to identify the useful components of CIAT in post-stroke aphasia rehabilitation. A computerized database search was performed through five databases (Pubmed, EMbase, Medline, ScienceDirect and Cochrane library). Cochrane handbook domains were used to evaluate the methodological quality of the included RCTs. Eight RCTs qualified in the inclusion criteria. Inconsistent results were found in comparing the CIAT with conventional therapies without any component from the CIAT based on the results of three RCTs. Five RCTs showed that the CIAT performed equally well as other intensive aphasia therapies, in terms of improving language performance. One RCT showed that therapies embedded with social interaction were likely to enhance the efficacy of the CIAT. CIAT may be useful for improving chronic post-stroke aphasia, however, limited evidence to support its superiority to other aphasia therapies. Massed practice is likely to be a useful component of CIAT, while the role of "constraint" is needed to be further explored. CIAT embedded with social interaction may gain more benefits.

Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

PubMed

Garland, Suzanne M; Paavonen, Jorma; Jaisamrarn, Unnop; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Castellsagué, Xavier; Teixeira, Júlio C; Skinner, S Rachel; Hedrick, James; Limson, Genara; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Del Rosario-Raymundo, M Rowena; Catteau, Grégory; Descamps, Dominique; Struyf, Frank; Lehtinen, Matti; Dubin, Gary

2016-12-15

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+. © 2016 UICC.

Onset of relief of symptoms of gastroesophageal reflux disease: post hoc analysis of two previously published studies comparing pantoprazole 20 mg once daily with nizatidine or ranitidine 150 mg twice daily.

PubMed

Haag, Sebastian; Holtmann, Gerald

2010-04-01

Systematic assessments of the onset of symptom relief in the treatment of gastroesophageal reflux disease (GERD) are lacking. This work evaluated the time interval until complete symptom relief from heartburn (including both daytime and nighttime heartburn) and acid regurgitation in patients with GERD or endoscopy-negative GERD (NERD) during the first 7 days of treatment with pantoprazole, nizatidine, or ranitidine. This was a post hoc reanalysis of data from 2 previously published, multicenter, randomized, double-blind, active-controlled, parallel-group studies. Male and female patients aged >or=18 years with endoscopically proven GERD or NERD (Hetzel-Dent grade >or= [trial 1] or Savary-Miller grade 0 or 1 [trial 2]) were enrolled. Patients were required to have had reflux symptoms for the previous >or=3 months, with >or=1 symptom (ie, daytime heartburn, nighttime heartburn, or acid regurgitation) for >or=4 of the past 7 days in trial 1 or >or=1 symptom (ie, heartburn, acid eructation, or painful swallowing) of at least moderate intensity for the past 3 days in trial 2. The treatments were pantoprazole 20 mg once daily in both trials, nizatidine 150 mg BID in trial 1, or ranitidine 150 mg BID in trial 2. Presence and severity of symptoms were recorded on daily diary cards using a 4-point Likert-type scale. In total, 114 patients from trial 1 and 307 patients from trial 2 were evaluable for heartburn, and 58 patients from trial l and 271 patients from trial 2 were evaluable for acid regurgitation. In both studies, there were no significant differences in baseline characteristics between pantoprazole recipients and nizatidine or ranitidine recipients, with the exception of more men than women in trial 1 compared with trial 2 (P < 0.001). On day 2 of trial 1, 23 (39.0%) and 8 (14.5%) of pantoprazole and nizatidine recipients, respectively, experienced complete relief from heartburn (P < 0.01). The differences between groups remained statistically significant through day 7, when 28 (47.5%) and 8 (14.5 %) of pantoprazole and nizatidine recipients had no heartburn (P < 0.001). There were no differences in control of acid regurgitation over 7 days with pantoprazole compared with nizatidine or ranitidine, except at days 2 and 4 of trial 1, when significantly more patients receiving pantoprazole experienced relief from acid regurgitation than those receiving nizatidine (day 2: 60.6% [n = 20] vs 20.0% [n = 5], P < 0.01; day 4: 48.5% [n =16] vs 24.0% [n = 6], P < 0.05). In this post hoc reanalysis of data from 2 previously published clinical trials, use of pantoprazole 20 mg once daily was associated with effective early relief from heartburn and acid regurgitation among these patients with GERD and NERD; relief occurred as fast as and, in some cases, even faster than that seen with nizatidine or ranitidine.

Therapeutic and prophylactic utility of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing electroconvulsive therapy: a randomized controlled trial.

PubMed

Prakash, Jyoti; Kotwal, Atul; Prabhu, Hra

2006-09-01

Substantial progress has been made in identifying how the treatment parameters used in electroconvulsive therapy (ECT) impact its cognitive side effects. However, there is limited information regarding the role of memory enhancers in post-ECT cognitive disturbances. We evaluated the therapeutic and prophylactic efficacy of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing ECT. A triple blind (the study subjects, clinician assessing the cognition, and the data analyst were unaware of subject allocation for trial assessment) randomized controlled trial was carried out in a General Hospital Psychiatry Unit. Subjects were randomized into 2 groups. One group received ECT with placebo, whereas the other group received ECT and donepezil (a memory-enhancing drug). Study participants were assessed in post-ECT period to analyze cognitive deficits and to compare the differences in 2 groups, as regards recovery of various aspects of cognition. The post-ECT recovery of various components of cognition was more rapid in patients using donepezil as compared to those not given donepezil (P < 0.05). This significant improvement in recovery time among patients receiving donepezil bears therapeutic implication in immediate post-ECT cognitive deficits.

Analysis of factors influencing the overall effect of racecadotril on childhood acute diarrhea. Results from a real-world and post-authorization surveillance study in Venezuela.

PubMed

Chacón, Jose

2010-07-21

Drug efficacy might differ from clinical trial results when performed in clinical daily conditions. Therefore, it is mandatory to conduct trials about effectiveness to improve external validity. This post-authorization, open-label, noncontrolled, prospective, multicenter, observational, and naturalistic trial was designed to search for factors influencing the racecadotril overall effect on childhood acute watery diarrhea in a real-world setting of Venezuela. There were 3,873 children with acute watery diarrhea treated with racecadotril, an enkephalin breakdown blocker plus oral rehydration therapy by 97 pediatricians. Evaluations were carried out daily until emission of two consecutive formed stools or absence of watery bowel movements for 24 hours. The primary end-point was time-to-relief, defined as the time from first racecadotril dose to the last watery bowel movement time. Age, gender, nursing type, nursing status during diarrhea, diarrhea severity, and co-medication were considered as factors in the statistical analysis. The primary end-point was evaluated by factors using UNIANOVA, and post-hoc tests were done. A multiple regression analysis was carried out to identify factors affecting drug performance, racecadotril effectiveness and tolerability overall assessment was searched by physicians and patients, and inter-observer agreement was evaluated by kappa statistics. The mean time-to-relief was 18.5 +/- 12.5 hours [95% confidence interval 17.9-19.0] and the diarrhea severity was the only variable with significant and independent weight on racecadotril effectiveness explaining 23% of time-to-relief variance, but even in severe diarrhea cases this time was less than 24 hours. High agreement about satisfactory perception on effectiveness and tolerability was reached among physicians and patients. In conclusion, the racecadotril overall effect, evaluated in a real-world setting of Venezuela, was in agreement with results of some earlier controlled trials. It was only influenced by severity of diarrhea episode, as well as being considered an effective and well tolerated treatment by physicians and patients.

Differences in Treatment Effect Size Between Overall Survival and Progression-Free Survival in Immunotherapy Trials: A Meta-Epidemiologic Study of Trials With Results Posted at ClinicalTrials.gov.

PubMed

Tan, Aidan; Porcher, Raphael; Crequit, Perrine; Ravaud, Philippe; Dechartres, Agnes

2017-05-20

Purpose We aimed to compare treatment effect sizes between overall survival (OS) and progression-free survival (PFS) in trials of US Food and Drug Administration-approved oncology immunotherapy drugs with results posted at ClinicalTrials.gov . Methods We searched ClinicalTrials.gov for phase II to IV cancer trials of Food and Drug Administration-approved immunotherapy drugs and selected those reporting results for both OS and PFS. For each trial, we extracted the hazard ratios (HRs) with 95% CIs for both outcomes and evaluated the differences by a ratio of HRs (rHRs): the HR for PFS to that for OS. We performed a random effects meta-analysis across trials to obtain a summary rHR. We also evaluated surrogacy of PFS for OS by the coefficient of determination and the surrogacy threshold effect, the minimal value of HR for PFS to predict a non-null effect on OS. Results We identified 51 trials assessing 14 drugs across 15 conditions. Treatment effect sizes were 17% greater, on average, with PFS than with OS (rHR, 0.83; 95% CI, 0.79 to 0.88; I 2 = 34.4%; P = .01; τ 2 = 0.0129). Nearly one half of the trials (n = 23, 45%) showed statistically significant benefits for PFS but not for OS. Differences were great for trials of obinutuzumab (rHR, 0.21; 95% CI, 0.08 to 0.54), bevacizumab (rHR, 0.75; 95% CI, 0.67 to 0.84), and rituximab (rHR, 0.79; 95% CI, 0.64 to 0.98). The coefficient of determination was 38% and the surrogacy threshold effect was 0.50. Conclusion Treatment effect sizes in trials of immunotherapy drugs were greater for PFS than for OS, with important differences for some drugs, which is consistent with surrogacy metrics. Caution must be taken when interpreting PFS in the absence of OS data.

Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials.

PubMed

Wang, L; Chang, Y; Kennedy, S A; Hong, P J; Chow, N; Couban, R J; McCabe, R E; Bieling, P J; Busse, J W

2018-06-01

Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]. Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. PROSPERO CRD42016047335. Copyright © 2017. Published by Elsevier Ltd.

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Conclusions Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors' Summary PMID:24311990

Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.

PubMed

Fahlenkamp, Astrid V; Stoppe, Christian; Cremer, Jan; Biener, Ingeborg A; Peters, Dirk; Leuchter, Ricarda; Eisert, Albrecht; Apfel, Christian C; Rossaint, Rolf; Coburn, Mark

2016-01-01

Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV). We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis. 220 subjects with elevated PONV risk (Apfel score ≥2) undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up. Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044). Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138). After xenon, nausea occurred significantly earlier (p = 0.014), was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups. In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea. EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.

Production and aerial application of wood shreds as a post-fire hillslope erosion mitigation treatment

Treesearch

Peter R. Robichaud; Louise E. Ashmun; Randy B. Foltz; Charles G. Showers; J. Scott Groenier; Jennifer Kesler; Claire DeLeo; Mary Moore

2013-01-01

Guidelines for the production and aerial application of wood shred mulch as a post-fire hillslope treatment were developed from laboratory and field studies, several field operations, and the evaluations of professionals involved in those operations. At two early trial sites, the wood shred mulch was produced off-site and transported to the area of use. At the 2010...

Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response Conflict are Altered in Pediatric Obsessive Compulsive Disorder

PubMed Central

Liu, Yanni; Gehring, William J.; Weissman, Daniel H.; Taylor, Stephan F.; Fitzgerald, Kate Dimond

2012-01-01

Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustments of cognitive control characterize young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness. PMID:22593744

Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles.

PubMed

Tang, Eve; Ravaud, Philippe; Riveros, Carolina; Perrodeau, Elodie; Dechartres, Agnes

2015-08-14

The reporting of serious adverse events (SAEs) in clinical trials is crucial to assess the balance between benefits and risks. For trials with serious adverse events posted at ClinicalTrials.gov, we assessed the consistency between SAEs posted at ClinicalTrials.gov and those published in corresponding journal articles. All records from ClinicalTrials.gov up to February 2014 were automatically exported in XML format. Among these, we identified all phase III or IV randomized controlled trials with at least one SAE posted. For a random sample of 300 of these trials, we searched for corresponding publications using MEDLINE via PubMed and extracted safety results from the articles. Among the sample of 300 trials with SAEs posted at ClinicalTrials.gov, 78 (26%) did not have a corresponding publication, and 20 (7%) had a publication that did not match the ClinicalTrials.gov record. For the 202 remaining trials, 26 published articles (13%) did not mention SAEs, 4 (2%) reported no SAEs, and 33 (16%) did not report the total number of SAEs per treatment group. Among the remaining 139 trials, for 44 (32%), the number of SAEs per group published did not match those posted at ClinicalTrials.gov. For 31 trials, the number of SAEs was greater at ClinicalTrials.gov than in the published article, with a difference ≥30 % for at least one group for 21. Only 33 trials (11%) had a publication reporting matching numbers of SAE and describing the type of SAE. Many trials with SAEs posted at ClinicalTrials.gov are not yet published, omit the reporting of these SAEs in corresponding publications, or report a discrepant number of SAEs as compared with ClinicalTrials.gov. These results underline the need to consult ClinicalTrials.gov for more information on serious harms.

A randomized, double-blind, placebo-controlled trial on the role of preemptive analgesia with acetaminophen [paracetamol] in reducing headache following electroconvulsive therapy [ECT].

PubMed

Isuru, Amila; Rodrigo, Asiri; Wijesinghe, Chamara; Ediriweera, Dileepa; Premadasa, Shan; Wijesekara, Carmel; Kuruppuarachchi, Lalith

2017-07-28

Electroconvulsive therapy (ECT) is a safe and efficient treatment for several severe psychiatric disorders, but its use is limited by side effects. Post-ECT headache is one of the commonest side effects. Preemptive analgesia is effective in post-surgical pain management. The most commonly used analgesic is acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for post-ECT headache has not been studied adequately. This study was conducted to compare the incidence and severity of post-ECT headache in patients who were administered acetaminophen pre-ECT with a placebo group. This study was a randomised, double-blind, placebo-controlled trial. Sixty-three patients received 1 g acetaminophen and 63 patients received a placebo identical to acetaminophen. The incidence and severity of headache 2 h before and after ECT were compared between placebo and acetaminophen groups. The severity was measured using a visual analog scale. Generalised linear models were used to evaluate variables associated with post ECT headache. Demographic and clinical variables of placebo and acetaminophen groups were comparable except for the energy level used to induce a seizure. Higher proportion of the placebo group (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P < 0.001). Model fitting showed that the administration of acetaminophen is associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P < 0.001). A significant reduction was seen in both the incidence and severity of post-ECT headache with preemptive analgesia with acetaminophen. Ethical approval was granted by an Ethic review committee, University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

Post-marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross-sectional study.

PubMed

Zeitoun, Jean-David; Baron, Gabriel; Vivot, Alexandre; Atal, Ignacio; Downing, Nicholas S; Ross, Joseph S; Ravaud, Philippe

2018-01-15

Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2,345 post-marketing trials; 1,362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials (range 8-530) and overall population to be enrolled per trial (1-8,381). Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3 to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low. © 2017 UICC.

A rehabilitation intervention to promote physical recovery following intensive care: a detailed description of construct development, rationale and content together with proposed taxonomy to capture processes in a randomised controlled trial.

PubMed

Ramsay, Pam; Salisbury, Lisa G; Merriweather, Judith L; Huby, Guro; Rattray, Janice E; Hull, Alastair M; Brett, Stephen J; Mackenzie, Simon J; Murray, Gordon D; Forbes, John F; Walsh, Timothy Simon

2014-01-29

Increasing numbers of patients are surviving critical illness, but survival may be associated with a constellation of physical and psychological sequelae that can cause ongoing disability and reduced health-related quality of life. Limited evidence currently exists to guide the optimum structure, timing, and content of rehabilitation programmes. There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period. This paper describes the construct development for a complex rehabilitation intervention intended to promote physical recovery following critical illness. The intervention is currently being evaluated in a randomised trial (ISRCTN09412438; funder Chief Scientists Office, Scotland). The intervention was developed using the Medical Research Council (MRC) framework for developing complex healthcare interventions. We ensured representation from a wide variety of stakeholders including content experts from multiple specialties, methodologists, and patient representation. The intervention construct was initially based on literature review, local observational and audit work, qualitative studies with ICU survivors, and brainstorming activities. Iterative refinement was aided by the publication of a National Institute for Health and Care Excellence guideline (No. 83), publicly available patient stories (Healthtalkonline), a stakeholder event in collaboration with the James Lind Alliance, and local piloting. Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant (GRA) role. Several rounds of external peer review during successive funding applications also contributed to development. The final construct for the complex intervention involved a dedicated GRA trained to pre-defined competencies across multiple rehabilitation domains (physiotherapy, dietetics, occupational therapy, and speech/language therapy), with specific training in post-critical illness issues. The intervention was from ICU discharge to 3 months post-discharge, including inpatient and post-hospital discharge elements. Clear strategies to provide information to patients/families were included. A detailed taxonomy was developed to define and describe the processes undertaken, and capture them during the trial. The detailed process measure description, together with a range of patient, health service, and economic outcomes were successfully mapped on to the modified CONSORT recommendations for reporting non-pharmacologic trial interventions. The MRC complex intervention framework was an effective guide to developing a novel post-ICU rehabilitation intervention. Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting. These data will be useful when interpreting the results of the randomised trial, will increase internal and external trial validity, and help others implement the intervention if the intervention proves clinically and cost effective.

A rehabilitation intervention to promote physical recovery following intensive care: a detailed description of construct development, rationale and content together with proposed taxonomy to capture processes in a randomised controlled trial

PubMed Central

2014-01-01

Background Increasing numbers of patients are surviving critical illness, but survival may be associated with a constellation of physical and psychological sequelae that can cause ongoing disability and reduced health-related quality of life. Limited evidence currently exists to guide the optimum structure, timing, and content of rehabilitation programmes. There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period. This paper describes the construct development for a complex rehabilitation intervention intended to promote physical recovery following critical illness. The intervention is currently being evaluated in a randomised trial (ISRCTN09412438; funder Chief Scientists Office, Scotland). Methods The intervention was developed using the Medical Research Council (MRC) framework for developing complex healthcare interventions. We ensured representation from a wide variety of stakeholders including content experts from multiple specialties, methodologists, and patient representation. The intervention construct was initially based on literature review, local observational and audit work, qualitative studies with ICU survivors, and brainstorming activities. Iterative refinement was aided by the publication of a National Institute for Health and Care Excellence guideline (No. 83), publicly available patient stories (Healthtalkonline), a stakeholder event in collaboration with the James Lind Alliance, and local piloting. Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant (GRA) role. Several rounds of external peer review during successive funding applications also contributed to development. Results The final construct for the complex intervention involved a dedicated GRA trained to pre-defined competencies across multiple rehabilitation domains (physiotherapy, dietetics, occupational therapy, and speech/language therapy), with specific training in post-critical illness issues. The intervention was from ICU discharge to 3 months post-discharge, including inpatient and post-hospital discharge elements. Clear strategies to provide information to patients/families were included. A detailed taxonomy was developed to define and describe the processes undertaken, and capture them during the trial. The detailed process measure description, together with a range of patient, health service, and economic outcomes were successfully mapped on to the modified CONSORT recommendations for reporting non-pharmacologic trial interventions. Conclusions The MRC complex intervention framework was an effective guide to developing a novel post-ICU rehabilitation intervention. Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting. These data will be useful when interpreting the results of the randomised trial, will increase internal and external trial validity, and help others implement the intervention if the intervention proves clinically and cost effective. PMID:24476530

77 FR 48611 - Rules of Practice for Trials Before the Patent Trial and Appeal Board and Judicial Review of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... consolidated set of rules relating to Board trial practice for inter partes review, post-grant review, the... rules relating to Board trial practice for inter partes review, post- grant review, the transitional...), to provide a consolidated set of rules relating to Board trial practice for inter partes review, post...

Immediate effects of acupuncture on biceps brachii muscle function in healthy and post-stroke subjects

PubMed Central

2012-01-01

Background The effects of acupuncture on muscle function in healthy subjects are contradictory and cannot be extrapolated to post-stroke patients. This study evaluated the immediate effects of manual acupuncture on myoelectric activity and isometric force in healthy and post-stroke patients. Methods A randomized clinical trial, with parallel groups, single-blinded study design, was conducted with 32 healthy subjects and 15 post-stroke patients with chronic hemiparesis. Surface electromyography from biceps brachii during maximal isometric voluntary tests was performed before and after 20-min intermittent, and manual stimulation of acupoints Quchi (LI11) or Tianquan (PC2). Pattern differentiation was performed by an automated method based on logistic regression equations. Results Healthy subjects showed a decrease in the root mean-squared (RMS) values after the stimulation of LI11 (pre: 1.392 ± 0.826 V; post: 0.612 ± 0.0.320 V; P = 0.002) and PC2 (pre: 1.494 ± 0.826 V; post: 0.623 ± 0.320 V; P = 0.001). Elbow flexion maximal isometric voluntary contraction (MIVC) was not significantly different after acupuncture stimulation of LI11 (pre: 22.2 ± 10.7 kg; post: 21.7 ± 9.5 kg; P = 0.288) or PC2 (pre: 18.8 ± 4.6 kg; post: 18.7 ± 6.0 kg; P = 0.468). Post-stroke patients did not exhibit any significant decrease in the RMS values after the stimulation of LI11 (pre: 0.627 ± 0.335 V; post: 0.530 ± 0.272 V; P = 0.187) and PC2 (pre: 0.601 ± 0.258 V; post: 0.591 ± 0.326 V; P = 0.398). Also, no significant decrease in the MIVC value was observed after the stimulation of LI11 (pre: 9.6 ± 3.9 kg; post: 9.6 ± 4.7 kg; P = 0.499) or PC2 (pre: 10.7 ± 5.6 kg; post: 10.2 ± 5.3 kg; P = 0.251). Different frequency of patterns was observed among healthy subjects and post-stroke patients groups (χ2 = 9.759; P = 0.021). Conclusion Manual acupuncture provides sufficient neuromuscular stimuli to promote immediate changes in motor unit gross recruitment without repercussion in maximal force output in healthy subjects. Post-stroke patients did not exhibit significant reduction on the myoelectric activity and maximal force output after manual acupuncture and needs further evaluation with a larger sample. Trial registration Brazilian Clinical Trials Registry RBR-5g7xqh. PMID:22417176

Preliminary Evaluation of Children's Psychosocial Rehabilitation for Youth with Serious Emotional Disturbance

ERIC Educational Resources Information Center

Williams, Nathaniel J.

2009-01-01

Objective: This article introduces and evaluates children's psychosocial rehabilitation, a home- and community-based treatment for children with serious emotional disturbance. Method: In an open-trial design, the author used repeated-measures analysis of variance and Wilcoxon signed-rank tests to assess pre-post outcome ratings for 218…

Biomarker Evaluation Does Not Confirm Efficacy of Computer-Tailored Nutrition Education

ERIC Educational Resources Information Center

Kroeze, Willemieke; Dagnelie, Pieter C.; Heymans, Martijn W.; Oenema, Anke; Brug, Johannes

2011-01-01

Objective: To evaluate the efficacy of computer-tailored nutrition education with objective outcome measures. Design: A 3-group randomized, controlled trial with posttests at 1 and 6 months post-intervention. Setting: Worksites and 2 neighborhoods in the urban area of Rotterdam. Participants: A convenience sample of healthy Dutch adults (n = 442).…

Evaluation of boric acid sugar baits against Aedes albopictus (Diptera: Culicidae) in tropical environments.

PubMed

Naranjo, Diana P; Qualls, Whitney A; Müller, Gunter C; Samson, Dayana M; Roque, Deborah; Alimi, Temitope; Arheart, Kristopher; Beier, John C; Xue, Rui-De

2013-04-01

Attractive toxic sugar bait (active ingredient, 1% boric acid) was evaluated against Aedes albopictus Skuse populations in the laboratory, semi-field trials, and field trials in residential communities in St. Augustine, Florida. Laboratory evaluations of boric acid sugar baits applied to the plant Pentas lanceolata (Rubiaceae) demonstrated 100 and 92% mortality of A. albopictus at day 7 and 14, respectively. A semi-field study evaluating the bait application to the upperside or topside of leaves resulted in no significant difference on mortality (P>0.05). Overall combined top and bottom boric acid sugar bait application mortality at day 7 was 95% based on leaf bioassays. Field application of the boric acid sugar baits significantly (P<0.05) decreased adult A. albopictus populations up to day 21 post-treatment compared to the pre-treatment population numbers. A significant reduction in oviposition was demonstrated both at day 7 and 14 post-application (P=0.001) as monitored by ovitraps. Attractive toxic sugar bait application in tropical environments demonstrated efficacy, persistence, and feasibility in controlling A. albopictus populations.

POWER for reproductive health: results from a social marketing campaign promoting female and male condoms.

PubMed

Bull, Sheana S; Posner, Samuel F; Ortiz, Charlene; Beaty, Brenda; Benton, Kathryn; Lin, Lillian; Pals, Sherri L; Evans, Tom

2008-07-01

To evaluate effects of a 6-month social marketing campaign on awareness of, attitudes toward and use of female as well as male condoms for 15-25 year-old-women. Using a time-space sampling methodology, we conducted a cross-sectional survey of 3407 women at pre-campaign in 12 western U.S. neighborhoods on female and male condom awareness, attitudes, and use. Six of the 12 study neighborhoods were randomly selected to receive the POWER social marketing campaign designed to impact condom knowledge, attitudes, and use. The campaign was followed with another cross-sectional survey of 3,003 women in all 12 study neighborhoods on condom knowledge, attitudes, use and awareness of POWER materials. We compared pre-and post-campaign surveys to determine the efficacy of POWER and conducted post hoc analyses on post-campaign data to determine if exposure to POWER was related to higher levels of positive condom attitudes and norms and condom use. We found no differences between neighborhoods with and without the POWER campaign with regard to our primary outcomes. To diagnose reasons for this null effect, we examined outcomes post hoc examining the influence of POWER exposure. Post hoc analyses show some evidence that exposure to POWER was associated with condom use. In the context of the nested trial, this raises concerns that post test only evaluations are limited. Establishing the efficacy of a social marketing campaign is challenging. This group randomized trial showed a null effect. Social marketing campaigns may need to have more media channels and saturation before they can show behavioral effects. Using a nested design with randomization at the community level and probability sampling introduces rigor not commonly seen in evaluations of social marketing campaigns.

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial

PubMed Central

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2017-01-01

Objective: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. Design: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Setting: Participants’ homes across Cambridgeshire, UK. Subjects: Eleven people with stroke and arm hemiparesis, 3–60 months post stroke, following discharge from community rehabilitation. Interventions: Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Main measures: Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. Results: A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. Conclusion: It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. Trial registration: ClinicalTrials.gov identifier NCT 02310438. PMID:28643570

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial.

PubMed

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2018-01-01

To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Participants' homes across Cambridgeshire, UK. Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation. Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. ClinicalTrials.gov identifier NCT 02310438.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial. PMID:21098066

Evidence-based intervention against bullying and cyberbullying: Evaluation of the NoTrap! program in two independent trials.

PubMed

Palladino, Benedetta E; Nocentini, Annalaura; Menesini, Ersilia

2016-01-01

The NoTrap! (Noncadiamointrappola!) program is a school-based intervention, which utilizes a peer-led approach to prevent and combat both traditional bullying and cyberbullying. The aim of the present study was to evaluate the efficacy of the third Edition of the program in accordance with the recent criteria for evidence-based interventions. Towards this aim, two quasi-experimental trials involving adolescents (age M = 14.91, SD = .98) attending their first year at different high schools were conducted. In Trial 1 (control group, n = 171; experimental group, n = 451), latent growth curve models for data from pre-, middle- and post-tests showed that intervention significantly predicted change over time in all the target variables (victimization, bullying, cybervictimization, and cyberbullying). Specifically, target variables were stable for the control group but decreased significantly over time for the experimental group. Long-term effects at the follow up 6 months later were also found. In Trial 2 (control group, n = 227; experimental group, n = 234), the moderating effect of gender was examined and there was a reported decrease in bullying and cyberbullying over time (pre- and post-test) in the experimental group but not the control group, and this decrease was similar for boys and girls. © 2016 Wiley Periodicals, Inc.

Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial.

PubMed

Boussi-Gross, Rahav; Golan, Haim; Fishlev, Gregori; Bechor, Yair; Volkov, Olga; Bergan, Jacob; Friedman, Mony; Hoofien, Dan; Shlamkovitch, Nathan; Ben-Jacob, Eshel; Efrati, Shai

2013-01-01

Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. "Mindstreams" was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. ClinicalTrials.gov NCT00715052.

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis.

PubMed

Thavaneswaran, Subotheni; Kok, Peey Sei; Price, Timothy

2017-10-01

Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC. We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included. Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation. There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed.

Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial

PubMed Central

Fishlev, Gregori; Bechor, Yair; Volkov, Olga; Bergan, Jacob; Friedman, Mony; Hoofien, Dan; Shlamkovitch, Nathan; Ben-Jacob, Eshel; Efrati, Shai

2013-01-01

Background Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. Methods and Findings The trial population included 56 mTBI patients 1–5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. “Mindstreams” was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. Conclusions HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. Trial Registration ClinicalTrials.gov NCT00715052 PMID:24260334

Effect of a facility-based multifaceted intervention on the quality of obstetrical care: a cluster randomized controlled trial in Mali and Senegal

PubMed Central

2013-01-01

Background Maternal mortality in referral hospitals in Mali and Senegal surpasses 1% of obstetrical admissions. Poor quality obstetrical care contributes to high maternal mortality; however, poor care is often linked to insufficient hospital resources. One promising method to improve obstetrical care is maternal death review. With a cluster randomized trial, we assessed whether an intervention, based on maternal death review, could improve obstetrical quality of care. Methods The trial began with a pre-intervention year (2007), followed by two years of intervention activities and a post-intervention year. We measured obstetrical quality of care in the post-intervention year using a criterion-based clinical audit (CBCA). We collected data from 32 of the 46 trial hospitals (16 in each trial arm) and included 658 patients admitted to the maternity unit with a trial of labour. The CBCA questionnaire measured 5 dimensions of care- patient history, clinical examination, laboratory examination, delivery care and postpartum monitoring. We used adjusted mixed models to evaluate differences in CBCA scores by trial arms and examined how levels of hospital human and material resources affect quality of care differences associated with the intervention. Results For all women, the mean percentage of care criteria met was 66.3 (SD 13.5). There were significantly greater mean CBCA scores in women treated at intervention hospitals (68.2) compared to control hospitals (64.5). After adjustment, women treated at intervention sites had 5 points’ greater scores than those at control sites. This difference was mostly attributable to greater clinical examination and post-partum monitoring scores. The association between the intervention and quality of care was the same, irrespective of the level of resources available to a hospital; however, as resources increased, so did quality of care scores in both arms of the trial. Trial registration The QUARITE trial is registered on the Current Controlled Trials website under ISRCTN46950658 PMID:23351269

The Efficacy of Massage in Reducing Nodule Formation After Poly-L-Lactic Acid Administration for Facial Volume Loss: A Randomized, Evaluator-Blinded Clinical Trial.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2016-11-01

The risk of nodule formation following poly-L-lactic acid (PLLA) injections for facial volume loss is well known. Traditionally, post-treatment massage according to the 5-5-5 rule (5 times per day for 5 minutes for 5 days) has been applied to mitigate this risk. However, such a regimen may be onerous for patient compliance. Using currently accepted injection technique and product dilution, the efficacy of massage for nodule prevention has never been formally evaluated. To evaluate the efficacy of massage in reducing the incidence of nodule formation post-PLLA injection. After obtaining informed consent, 20 subjects with facial lipoatrophy were enrolled in this randomized, evaluator-blinded clinical trial. Each subject was treated with 1 vial of PLLA each month for 3 months. Vials were diluted with 1 mL of 1% lidocaine and 7 ml of bacteriostatic water, shaken with a vortex and refrigerated for 24 to 48 hours before injection. Ten subjects were instructed to massage the treated areas according to the 5-5-5 rule and 10 subjects did not perform any massage post-treatment. Six-month follow-up data were collected for treatment efficacy and adverse events. No nodules were reported by subjects or detected by the blinded evaluator regardless of massage status. Significant improvements in facial lipoatrophy were detected 1, 3, and 6 months after the final treatment session and were not statistically different between the 2 groups. Using currently recommended guidelines for product preparation and injection, the application of massage post-PLLA facial treatment does not have a significant impact on nodule formation or treatment efficacy.

Post-fracture care: do we need to educate patients rather than doctors? The PREVOST randomized controlled trial.

PubMed

Merle, B; Chapurlat, R; Vignot, E; Thomas, T; Haesebaert, J; Schott, A-M

2017-05-01

We conducted a multicenter, randomized controlled trial to evaluate the impact of a population-based patient-centered post-fracture care program with a dedicated case manager, PREVention of OSTeoporosis (PREVOST), on appropriate post-fracture osteoporosis management. We showed that, compared to usual care, BMD investigation post-fracture was significantly improved (+20%) by our intervention program. Our study aims to evaluate the impact of a population-based patient-centered post-fracture care program, PREVOST, on appropriate post-fracture care. Multicenter, randomized controlled trial enrolling 436 women aged 50 to 85 years and attending a French hospital, for a low-energy fracture of the wrist or humerus. Randomization was stratified by age, hospital department, and site of fracture. The intervention was performed by a trained case manager who interacted only with the patients, with repeated oral and written information about fragility fractures and osteoporosis management, and prompting them to visit their primary care physicians. Control group received usual care. The primary outcome was the initiation of an appropriate post-fracture care defined by Bone Mineral Density (BMD) and/or anti-osteoporotic treatment prescription at 6 months. At 6 months, 53% of women in intervention group initiated a post-fracture care versus 33% for usual care (adjOR 2.35, 95%CI [1.58-3.50], p < 0.001). Post-fracture care was more frequent after wrist than humerus fracture (adjOR 1.93, 95%CI [1.14-3.30], p = 0.015) and decreased with age (adjOR for 10 years increase 0.76, 95%CI [0.61-0.96], p = 0.02). The intervention resulted in BMD prescription in 50% of patients (adjOR 2.10, 95%CI [1.41-3.11], p < 0.001) and in BMD performance in 41% of patients (adjOR 2.12, 95%CI [1.40-3.20], p < 0.001) versus 33 and 25% for usual care, respectively. Having performed a BMD increased treatment prescription; however, only 46% of women with a low BMD requiring a treatment according to the French guidelines received a prescription. A patient-centered care program with a dedicated case manager can significantly improve post-fracture BMD investigation.

Company observational post-marketing studies: drug risk assessment and drug research in special populations--a study-based analysis.

PubMed

Hasford, J; Lamprecht, T

1998-01-01

Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS compared with dramatic improvements of pre-approval trials - implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community.

An investigation of client mood in the initial and final sessions of cognitive-behavioral therapy and psychodynamic-interpersonal therapy.

PubMed

Mcclintock, Andrew S; Stiles, William B; Himawan, Lina; Anderson, Timothy; Barkham, Michael; Hardy, Gillian E

2016-01-01

Our aim was to examine client mood in the initial and final sessions of cognitive-behavioral therapy (CBT) and psychodynamic-interpersonal therapy (PIT) and to determine how client mood is related to therapy outcomes. Hierarchical linear modeling was applied to data from a clinical trial comparing CBT with PIT. In this trial, client mood was assessed before and after sessions with the Session Evaluation Questionnaire-Positivity Subscale (SEQ-P). In the initial sessions, CBT clients had higher pre-session and post-session SEQ-P ratings and greater pre-to-post session mood change than did clients in PIT. In the final sessions, these pre, post, and change scores were generally equivalent across CBT and PIT. CBT outcome was predicted by pre- and post-session SEQ-P ratings from both the initial sessions and the final sessions of CBT. However, PIT outcome was predicted by pre- and post-session SEQ-P ratings from the final sessions only. Pre-to-post session mood change was unrelated to outcome in both treatments. These results suggest different change processes are at work in CBT and PIT.

Oral isoflavone supplementation on endometrial thickness: a meta-analysis of randomized placebo-controlled trials

PubMed Central

Liu, Jie; Yuan, Feixiang; Gao, Jian; Shan, Boer; Ren, Yulan; Wang, Huaying; Gao, Ying

2016-01-01

Background Isoflavone from soy and other plants modulate hormonal effects in women, and the hormone disorder might result in different caners including endometrial cancer. However, it's effect on the risk of endometrial cancer is still inconclusive. We aimed to assess the effects of isoflavone on endometrial thickness, a risk factor of endometrial cancer in peri- and post-menopausal women. Methods A meta-analysis of randomized controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endometrial thickness in peri- and post-menopausal women. Electronic searches were performed on the PubMed, Embase, the Cochrane Library, web of science, CINAHL, and WHO ICTRP to August 1st, 2015. Reviews and reference lists of relevant articles were also searched to identify more studies. Summary estimates of standard mean differences (SMD's) and 95%CIs were obtained with random-effects models. Heterogeneity was evaluated with meta-regression and stratified analyses. Results A total of 23 trials were included in the current analysis. The overall results did not show significant change of endometrial thickness after oral isoflavone supplementation (23 studies, 2167subjects; SMD:-0.05; 95%CI:-0.23, 0.13; P=0.60). Stratified analysis suggested that a daily dose of more than 54mg could decrease the endometrial thickness for 0.26mm (10 trials, 984subjects; SMD:-0.26; 95%CI:-0.45, −0.07; P=0.007). Furthermore, isoflavone supplementation significantly decrease the endometrial thickness for 0.23mm in North American studies (7 trials, 726 subjects; SMD:-0.23; 95%CI:-0.44, −0.01; P=0.04), but it suggested an increase for 0.23mm in Asian studies (3 trials, 224 subjects; SMD: 0.23; 95%CI:-0.04, 0.50; P=0.10). Conclusion Oral isoflavone supplementation might have different effects in different populations and at different daily doses. Multiple-centre, larger, and long-term trials are deserved to further evaluate its effect. PMID:26967050

The effect of real-time CPR feedback and post event debriefing on patient and processes focused outcomes: A cohort study: trial protocol

PubMed Central

2011-01-01

Background Cardiac arrest affects 30-35, 000 hospitalised patients in the UK every year. For these patients to be given the best chance of survival, high quality cardiopulmonary resuscitation (CPR) must be delivered, however the quality of CPR in real-life is often suboptimal. CPR feedback devices have been shown to improve CPR quality in the pre-hospital setting and post-event debriefing can improve adherence to guidelines and CPR quality. However, the evidence for use of these improvement methods in hospital remains unclear. The CPR quality improvement initiative is a prospective cohort study of the Q-CPR real-time feedback device combined with post-event debriefing in hospitalised adult patients who sustain a cardiac arrest. Methods/design The primary objective of this trial is to assess whether a CPR quality improvement initiative will improve rate of return of sustained spontaneous circulation in in-hospital-cardiac-arrest patients. The study is set in one NHS trust operating three hospital sites. Secondary objectives will evaluate: any return of spontaneous circulation; survival to hospital discharge and patient cerebral performance category at discharge; quality of CPR variables and cardiac arrest team factors. Methods: All three sites will have an initial control phase before any improvements are implemented; site 1 will implement audiovisual feedback combined with post event debriefing, site 2 will implement audiovisual feedback only and site 3 will remain as a control site to measure any changes in outcome due to any other trust-wide changes in resuscitation practice. All adult patients sustaining a cardiac arrest and receiving resuscitation from the hospital cardiac arrest team will be included. Patients will be excluded if; they have a Do-not-attempt resuscitation order written and documented in their medical records, the cardiac arrest is not attended by a resuscitation team, the arrest occurs out-of-hospital or the patient has previously participated in this study. The trial will recruit a total of 912 patients from the three hospital sites. Conclusion This trial will evaluate patient and process focussed outcomes following the implementation of a CPR quality improvement initiative using real-time audiovisual feedback and post event debriefing. Trial registration ISRCTN56583860 PMID:22008636

Ethical Challenges of Randomized Violence Intervention Trials: Examining the SHARE intervention in Rakai, Uganda

PubMed Central

Wagman, Jennifer A.; Paul, Amy; Namatovu, Fredinah; Ssekubugu, Robert; Nalugoda, Fred

2016-01-01

Objective We identify complexities encountered, including unanticipated crossover between trial arms and inadequate ‘standard of care’ violence services, during a cluster randomized trial (CRT) of a community-level intimate partner violence (IPV) and HIV prevention intervention in Uganda. Methods Concepts in public health ethics - beneficence, social value of research, fairness, standard of care, and researcher responsibilities for post-trial benefits - are used to critically reflect on lessons learned and guide discussion on practical and ethical challenges of violence intervention CRTs. Results Existing ethical guidelines provide incomplete guidance for responding to unexpected crossover in CRTs providing IPV services. We struggled to balance duty of care with upholding trial integrity, and identifying and providing appropriate standard of care. While we ultimately offered short-term IPV services to controls, we faced additional challenges related to sustaining services beyond the ‘short-term’ and post-trial. Conclusion Studies evaluating community-level violence interventions, including those combined with HIV reduction strategies, are limited yet critical for developing evidence-based approaches for effectively preventing IPV. Although CRTs are a promising design, further guidance is needed to implement trials that avoid introducing tensions between validity of findings, researchers’ responsibilities to protect participants, and equitable distribution of CRT benefits. PMID:27453794

Hydrotherapy as a recovery strategy after exercise: a pragmatic controlled trial

PubMed Central

2013-01-01

Background Our aim was to evaluate the recovery effects of hydrotherapy after aerobic exercise in cardiovascular, performance and perceived fatigue. Methods A pragmatic controlled repeated measures; single-blind trial was conducted. Thirty-four recreational sportspeople visited a Sport-Centre and were assigned to a Hydrotherapy group (experimental) or rest in a bed (control) after completing a spinning session. Main outcomes measures including blood pressure, heart rate, handgrip strength, vertical jump, self-perceived fatigue, and body temperature were assessed at baseline, immediately post-exercise and post-recovery. The hypothesis of interest was the session*time interaction. Results The analysis revealed significant session*time interactions for diastolic blood pressure (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy resulted in recovered heart rate and diastolic blood pressure similar to baseline values after the spinning session. Further, hydrotherapy resulted in decreased self-perceived fatigue after the spinning session. Conclusions Our results support that hydrotherapy is an adequate strategy to facilitate cardiovascular recovers and perceived fatigue, but not strength, after spinning exercise. Trial registration ClinicalTrials.gov Identifier: NCT01765387 PMID:23866725

The utility of e-Learning to support training for a multicentre bladder online adaptive radiotherapy trial (TROG 10.01-BOLART).

PubMed

Foroudi, Farshad; Pham, Daniel; Bressel, Mathias; Tongs, David; Rolfo, Aldo; Styles, Colin; Gill, Suki; Kron, Tomas

2013-10-01

An e-Learning programme appeared useful for providing training and information regarding a multi-centre image guided radiotherapy trial. The aim of this study is to demonstrate the utility of this e-Learning programme. Modules were created on relevant pelvic anatomy, Cone Beam CT soft tissue recognition and trial details. Radiation therapist participants' knowledge and confidence were evaluated before, at the end of, and after at least 6 weeks of e-Learning (long term). One hundred and eighty-five participants were recruited from 12 centres, with 118 in the first, and 67 in the second cohort. One hundred and forty-six participants had two tests (pre and post e-Learning) and 39 of these had three tests (pre, post, and long term). There was an increase confidence after completion of modules (p<0.001). The first cohort pre scores increased from 67 ± 11 to 79 ± 8 (p<0.001) post. The long term same question score was 73 ± 14 (p=0.025, comparing to pre-test), and different questions' score was 77 ± 13 (p=0.014). In the second cohort, pre-test scores were 64 ± 10, post-test same question score 78 ± 9 (p<0.001) and different questions' score 81 ± 11 (p<0.001). e-Learning for a multi-centre clinical trial was feasible and improved confidence and knowledge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Pilot Evaluation of an Internet Educational Module for Agricultural Safety

ERIC Educational Resources Information Center

Schwab, Charles V.; Freeman, Steven A.

2011-01-01

An important component of the safe operation of agricultural equipment is the ability to read and understand universal symbols. The Internet educational module is designed to help participants recognize these symbols. The impact of using it was evaluated using a field trial study. Assessment consisted of pre- and post-tests. Youth who had access…

Reducing depressive or anxiety symptoms in post-stroke patients: Pilot trial of a constructive integrative psychosocial intervention

PubMed Central

Fang, Yihong; Mpofu, Elias; Athanasou, James

2017-01-01

Background: About 30% of stroke survivors clinically have depressive symptoms at some point following stroke and anxiety prevalence is around 20-25%. Objective: The purpose of this brief report is to evaluate a pilot trial of a constructive integrative psychosocial intervention (CIPI) over standard care in post-stroke depression or anxiety. Methods: Patients were randomly assigned to either CIPI (n = 23) or standard care (n = 19). Patients were assessed using the Hospital Anxiety and Depression Scale at the 1st, 3rd, and 6th months to monitor changes of mood. Results: A Wilcoxon signed-rank test indicated that compared to admission baseline, patients with the intervention had significantly normal post-stroke depression symptom levels at the 1st, 3rd, and 6th months (P < 0.005). Conclusion: CIPI appears to be of incremental value in treating depression as well as anxiety in subacute care. PMID:29085269

The Sustained Influence of an Error on Future Decision-Making.

PubMed

Schiffler, Björn C; Bengtsson, Sara L; Lundqvist, Daniel

2017-01-01

Post-error slowing (PES) is consistently observed in decision-making tasks after negative feedback. Yet, findings are inconclusive as to whether PES supports performance accuracy. We addressed the role of PES by employing drift diffusion modeling which enabled us to investigate latent processes of reaction times and accuracy on a large-scale dataset (>5,800 participants) of a visual search experiment with emotional face stimuli. In our experiment, post-error trials were characterized by both adaptive and non-adaptive decision processes. An adaptive increase in participants' response threshold was sustained over several trials post-error. Contrarily, an initial decrease in evidence accumulation rate, followed by an increase on the subsequent trials, indicates a momentary distraction of task-relevant attention and resulted in an initial accuracy drop. Higher values of decision threshold and evidence accumulation on the post-error trial were associated with higher accuracy on subsequent trials which further gives credence to these parameters' role in post-error adaptation. Finally, the evidence accumulation rate post-error decreased when the error trial presented angry faces, a finding suggesting that the post-error decision can be influenced by the error context. In conclusion, we demonstrate that error-related response adaptations are multi-component processes that change dynamically over several trials post-error.

Patient and carer experience of hospital-based rehabilitation from intensive care to hospital discharge: mixed methods process evaluation of the RECOVER randomised clinical trial

PubMed Central

Ramsay, Pam; Huby, Guro; Merriweather, Judith; Salisbury, Lisa; Rattray, Janice; Griffith, David; Walsh, Timothy

2016-01-01

Objectives To explore and compare patient/carer experiences of rehabilitation in the intervention and usual care arms of the RECOVER trial (ISRCTN09412438); a randomised controlled trial of a complex intervention of post-intensive care unit (ICU) acute hospital-based rehabilitation following critical illness. Design Mixed methods process evaluation including comparison of patients' and carers' experience of usual care versus the complex intervention. We integrated and compared quantitative data from a patient experience questionnaire (PEQ) with qualitative data from focus groups with patients and carers. Setting Two university-affiliated hospitals in Scotland. Participants 240 patients discharged from ICU who required ≥48 hours of mechanical ventilation were randomised into the trial (120 per trial arm). Exclusion criteria comprised: primary neurologic diagnosis, palliative care, current/planned home ventilation and age <18 years. 182 patients completed the PEQ at 3 months postrandomisation. 22 participants (14 patients and 8 carers) took part in focus groups (2 per trial group) at >3 months postrandomisation. Interventions A complex intervention of post-ICU acute hospital rehabilitation, comprising enhanced physiotherapy, nutritional care and information provision, case-managed by dedicated rehabilitation assistants (RAs) working within existing ward-based clinical teams, delivered between ICU discharge and hospital discharge. Comparator was usual care. Outcome measures A novel PEQ capturing patient-reported aspects of quality care. Results The PEQ revealed statistically significant between-group differences across 4 key intervention components: physiotherapy (p=0.039), nutritional care (p=0.038), case management (p=0.045) and information provision (p<0.001), suggesting greater patient satisfaction in the intervention group. Focus group data strongly supported and helped explain these findings. Specifically, case management by dedicated RAs facilitated greater access to physiotherapy, nutritional care and information that cut across disciplinary boundaries and staffing constraints. Patients highly valued its individualisation according to their needs, abilities and preferences. Conclusions Case management by dedicated RAs improves patients' experiences of post-ICU hospital-based rehabilitation and increases perceived quality of care. Trial registration number ISRCTN09412438. PMID:27481624

The effect of real-time CPR feedback and post event debriefing on patient and processes focused outcomes: a cohort study: trial protocol.

PubMed

Perkins, Gavin D; Davies, Robin P; Quinton, Sarah; Woolley, Sarah; Gao, Fang; Abella, Ben; Stallard, Nigel; Cooke, Matthew W

2011-10-18

Cardiac arrest affects 30-35, 000 hospitalised patients in the UK every year. For these patients to be given the best chance of survival, high quality cardiopulmonary resuscitation (CPR) must be delivered, however the quality of CPR in real-life is often suboptimal. CPR feedback devices have been shown to improve CPR quality in the pre-hospital setting and post-event debriefing can improve adherence to guidelines and CPR quality. However, the evidence for use of these improvement methods in hospital remains unclear. The CPR quality improvement initiative is a prospective cohort study of the Q-CPR real-time feedback device combined with post-event debriefing in hospitalised adult patients who sustain a cardiac arrest. The primary objective of this trial is to assess whether a CPR quality improvement initiative will improve rate of return of sustained spontaneous circulation in in-hospital-cardiac-arrest patients. The study is set in one NHS trust operating three hospital sites. Secondary objectives will evaluate: any return of spontaneous circulation; survival to hospital discharge and patient cerebral performance category at discharge; quality of CPR variables and cardiac arrest team factors. All three sites will have an initial control phase before any improvements are implemented; site 1 will implement audiovisual feedback combined with post event debriefing, site 2 will implement audiovisual feedback only and site 3 will remain as a control site to measure any changes in outcome due to any other trust-wide changes in resuscitation practice. All adult patients sustaining a cardiac arrest and receiving resuscitation from the hospital cardiac arrest team will be included. Patients will be excluded if; they have a Do-not-attempt resuscitation order written and documented in their medical records, the cardiac arrest is not attended by a resuscitation team, the arrest occurs out-of-hospital or the patient has previously participated in this study. The trial will recruit a total of 912 patients from the three hospital sites. This trial will evaluate patient and process focussed outcomes following the implementation of a CPR quality improvement initiative using real-time audiovisual feedback and post event debriefing. ISRCTN56583860.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Improving Diabetes care through Examining, Advising, and prescribing (IDEA): protocol for a theory-based cluster randomised controlled trial of a multiple behaviour change intervention aimed at primary healthcare professionals

PubMed Central

2014-01-01

Background New clinical research findings may require clinicians to change their behaviour to provide high-quality care to people with type 2 diabetes, likely requiring them to change multiple different clinical behaviours. The present study builds on findings from a UK-wide study of theory-based behavioural and organisational factors associated with prescribing, advising, and examining consistent with high-quality diabetes care. Aim To develop and evaluate the effectiveness and cost of an intervention to improve multiple behaviours in clinicians involved in delivering high-quality care for type 2 diabetes. Design/methods We will conduct a two-armed cluster randomised controlled trial in 44 general practices in the North East of England to evaluate a theory-based behaviour change intervention. We will target improvement in six underperformed clinical behaviours highlighted in quality standards for type 2 diabetes: prescribing for hypertension; prescribing for glycaemic control; providing physical activity advice; providing nutrition advice; providing on-going education; and ensuring that feet have been examined. The primary outcome will be the proportion of patients appropriately prescribed and examined (using anonymised computer records), and advised (using anonymous patient surveys) at 12 months. We will use behaviour change techniques targeting motivational, volitional, and impulsive factors that we have previously demonstrated to be predictive of multiple health professional behaviours involved in high-quality type 2 diabetes care. We will also investigate whether the intervention was delivered as designed (fidelity) by coding audiotaped workshops and interventionist delivery reports, and operated as hypothesised (process evaluation) by analysing responses to theory-based postal questionnaires. In addition, we will conduct post-trial qualitative interviews with practice teams to further inform the process evaluation, and a post-trial economic analysis to estimate the costs of the intervention and cost of service use. Discussion Consistent with UK Medical Research Council guidance and building on previous development research, this pragmatic cluster randomised trial will evaluate the effectiveness of a theory-based complex intervention focusing on changing multiple clinical behaviours to improve quality of diabetes care. Trial registration ISRCTN66498413. PMID:24886606

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial.

PubMed

Glazener, Cathryn; Constable, Lynda; Hemming, Christine; Breeman, Suzanne; Elders, Andrew; Cooper, Kevin; Freeman, Robert; Smith, Anthony R B; Hagen, Suzanne; McDonald, Alison; McPherson, Gladys; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; Goulao, Beatriz; Norrie, John

2016-09-08

One in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events. VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation. Demonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally. Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013.

Post-trial apomorphine at an autoreceptor dose level can eliminate apomorphine conditioning and sensitization: support for the critical role of dopamine in re-consolidation.

PubMed

Carrera, Marinete Pinheiro; Carey, Robert J; Cruz Dias, Flávia Regina; dos Santos Sampaio, Maria de Fátima; de Matos, Liana Wermelinger

2013-01-01

Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.05 mg/kg) and a high (2.0mg/kg) dose were used to inhibit or to enhance dopamine activity, respectively. Initially, groups received 5 daily apomorphine (2.0mg/kg)/vehicle treatments either paired or unpaired to open-field placement. The paired treatments generated a progressive locomotor response. Subsequently, all groups received a 5 min non-drug test for conditioning and a conditioned locomotor response was observed in the paired group. The groups received another apomorphine (2.0mg/kg)/vehicle treatment as a re-induction treatment. At this stage the post-trial protocol was initiated. One set of paired, unpaired and vehicle groups were given a low dose of apomorphine (0.05 mg/kg) post-trial; another set received a high dose of apomorphine (2.0mg/kg) post-trial. The remaining group set received vehicle post-trial. The low dose post-trial treatment eliminated the conditioned and sensitized locomotor response and the high dose post-trial treatment enhanced the conditioned and sensitized locomotor response. The efficacy of the post-trial apomorphine treatments to modify the conditioned and the sensitized response after a brief non-drug exposure to test cues supports the proposition that exteroceptive cues control conditioning and sensitization and that the interoceptive drug cues make little or no associational contribution to apomorphine conditioning and sensitization. In addition, the findings point to the importance of dopamine activation in both the acquisition and re-consolidation of conditioning processes. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluating a community-partnered cancer clinical trials pilot intervention with African American communities.

PubMed

Green, Melissa A; Michaels, Margo; Blakeney, Natasha; Odulana, Adebowale A; Isler, Malika Roman; Richmond, Alan; Long, Debra G; Robinson, William S; Taylor, Yhenneko J; Corbie-Smith, Giselle

2015-03-01

Cancer clinical trial (CCT) accrual and retention rates remain disproportionately low among African Americans. Awarenesss and access to trials are crucial facilitators of trial participation. Strategies developed within a community-based participatory framework (CBPR) are potential solutions to increase awareness and access to CCTs. In this study, we describe the pilot phase of three innovative community-centered modules to improve basic CCT knowledge, awareness of locations to access CCT information, and opportunities to participate in CCTs. Four community organizations completed Community Bridges to CCT training-of-the-trainer and recruited adult African American volunteers to participate in one of three CCT education modules: a workshop about CCTs, a role play describing one person's experience with CCTs, or a call and response session reviewing myths and facts about CCTs. Pre- and post-test surveys were collected and analyzed using McNemar agreement statistic to evaluate changes in knowledge and attitudes regarding trials. Trainers enrolled 125 participants in the call and response (n = 22), role play (n = 60), and workshop (n = 43) modules. Module participants were mostly African American, female, and with a mean age of 53 years. Comparison of pre- and post-test responses demonstrates favorable changes in awareness of CCTs and where to access CCTs across the sample. Analysis by module type indicates significant increases for participants in the call and response (p < 0.01) and role play modules (p < 0.001), but not the workshop module. Despite measures taken to increase the participation and retention rate of African Americans in clinical trials, little advancement has been made. Developing tailored community education modules on CCTs within the CBPR framework is a promising innovation to increase knowledge about CCTs and favorable attitudes about participation that are known precursors to trial enrollment.

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

PubMed

Yang, Shanli; Ye, Haicheng; Huang, Jia; Tao, Jing; Jiang, Cai; Lin, Zhicheng; Zheng, Guohua; Chen, Lidian

2014-08-07

Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.

Effectiveness of proactive telephone counselling for smoking cessation in parents: Study protocol of a randomized controlled trial

PubMed Central

2011-01-01

Background Smoking is the world's fourth most common risk factor for disease, the leading preventable cause of death, and it is associated with tremendous social costs. In the Netherlands, the smoking prevalence rate is high. A total of 27.7% of the population over age 15 years smokes. In addition to the direct advantages of smoking cessation for the smoker, parents who quit smoking may also decrease their children's risk of smoking initiation. Methods/Design A randomized controlled trial will be conducted to evaluate the effectiveness of proactive telephone counselling to increase smoking cessation rates among smoking parents. A total of 512 smoking parents will be proactively recruited through their children's primary schools and randomly assigned to either proactive telephone counselling or a control condition. Proactive telephone counselling will consist of up to seven counsellor-initiated telephone calls (based on cognitive-behavioural skill building and Motivational Interviewing), distributed over a period of three months. Three supplementary brochures will also be provided. In the control condition, parents will receive a standard brochure to aid smoking cessation. Assessments will take place at baseline, three months after start of the intervention (post-measurement), and twelve months after start of the intervention (follow-up measurement). Primary outcome measures will include sustained abstinence between post-measurement and follow-up measurement and 7-day point prevalence abstinence and 24-hours point prevalence abstinence at both post- and follow-up measurement. Several secondary outcome measures will also be included (e.g., smoking intensity, smoking policies at home). In addition, we will evaluate smoking-related cognitions (e.g., attitudes towards smoking, social norms, self-efficacy, intention to smoke) in 9-12 year old children of smoking parents. Discussion This study protocol describes the design of a randomized controlled trial to evaluate the effectiveness of proactive telephone counselling in smoking cessation. It is expected that, in the telephone counseling condition, parental smoking cessation rates will be higher and children's cognitions will be less favorable about smoking compared to the control condition. Trial registration The protocol for this study is registered with the Netherlands Trial Register NTR2707. PMID:21943207

Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis.

PubMed

Leber, Werner; Beresford, Lee; Nightingale, Claire; Barbosa, Estela Capelas; Morris, Stephen; El-Shogri, Farah; McMullen, Heather; Boomla, Kambiz; Delpech, Valerie; Brown, Alison; Hutchinson, Jane; Apea, Vanessa; Symonds, Merle; Gilliham, Samantha; Creighton, Sarah; Shahmanesh, Maryam; Fulop, Naomi; Estcourt, Claudia; Anderson, Jane; Figueroa, Jose; Griffiths, Chris

2017-12-14

HIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets). Service evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses. The chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners. © 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.

A Single-Blind randomized controlled trial to evaluate the effect of extended counseling on uptake of pre-antiretroviral care in eastern uganda

PubMed Central

2011-01-01

Background Many newly screened people living with HIV (PLHIV) in Sub-Saharan Africa do not understand the importance of regular pre-antiretroviral (ARV) care because most of them have been counseled by staff who lack basic counseling skills. This results in low uptake of pre-ARV care and late treatment initiation in resource-poor settings. The effect of providing post-test counseling by staff equipped with basic counseling skills, combined with home visits by community support agents on uptake of pre-ARV care for newly diagnosed PLHIV was evaluated through a randomized intervention trial in Uganda. Methods An intervention trial was performed consisting of post-test counseling by trained counselors, combined with monthly home visits by community support agents for continued counseling to newly screened PLHIV in Iganga district, Uganda between July 2009 and June 2010, Participants (N = 400) from three public recruitment centres were randomized to receive either the intervention, or the standard care (the existing post-test counseling by ARV clinic staff who lack basic training in counseling skills), the control arm. The outcome measure was the proportion of newly screened and counseled PLHIV in either arm who had been to their nearest health center for clinical check-up in the subsequent three months +2 months. Treatment was randomly assigned using computer-generated random numbers. The statistical significance of differences between the two study arms was assessed using chi-square and t-tests for categorical and quantitative data respectively. Risk ratios and 95% confidence intervals were used to assess the effect of the intervention. Results Participants in the intervention arm were 80% more likely to accept (take up) pre-ARV care compared to those in the control arm (RR 1.8, 95% CI 1.4-2.1). No adverse events were reported. Conclusions Provision of post-test counseling by staff trained in basic counseling skills, combined with home visits by community support agents had a significant effect on uptake of pre-ARV care and appears to be a cost-effective way to increase the prerequisites for timely ARV initiation. Trial registration The trial was registered by Current Controlled Trials Ltd C/OBioMed Central Ltd as ISRCTN94133652 and received financial support from Sida and logistical support from the European Commission. PMID:21794162

Using digital multimedia to improve parents' and children's understanding of clinical trials.

PubMed

Tait, Alan R; Voepel-Lewis, Terri; Levine, Robert

2015-06-01

Data show that many research subjects have difficulty understanding study information using traditional paper consent documents. This study, therefore, was designed to evaluate the effect of an interactive multimedia program on improving parents' and children's understanding of clinical trial concepts and participation. Parents (n=148) and children (n=135) were each randomised to receive information regarding clinical trials using either a traditional paper format (TF) or an interactive iPad program (IP) with inline exercises. Participants' understanding of the information was assessed using semistructured interviews prior to (pretest) and after (post-test) receiving the information. Participants also completed a short survey to assess their perceptions of information delivery and satisfaction with the process. Regardless of the mode of information delivery, all participants demonstrated improved pretest to post-test understanding. While there were no statistical differences in parents' post-test understanding between the TF and IP groups, children in the IP group had significantly greater post-test understanding compared with children in the TF group (11.65 (4.1) vs 8.85 (4.1) (2.8, 1.4, 4.2) 0-18 scale where 18=complete understanding). Furthermore, the IP was found to be significantly 'easier to follow' and 'more effective' in presenting information compared with the TF. Results demonstrated the importance of providing information regarding clinical trial concepts to parents and children. Importantly, the ability of interactive multimedia to improve understanding of clinical trial concepts and satisfaction with information delivery, particularly among children, supports this approach as a novel and effective vehicle for enhancing the informed consent process. 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.

Brain-computer interfaces for post-stroke motor rehabilitation: a meta-analysis.

PubMed

Cervera, María A; Soekadar, Surjo R; Ushiba, Junichi; Millán, José Del R; Liu, Meigen; Birbaumer, Niels; Garipelli, Gangadhar

2018-05-01

Brain-computer interfaces (BCIs) can provide sensory feedback of ongoing brain oscillations, enabling stroke survivors to modulate their sensorimotor rhythms purposefully. A number of recent clinical studies indicate that repeated use of such BCIs might trigger neurological recovery and hence improvement in motor function. Here, we provide a first meta-analysis evaluating the clinical effectiveness of BCI-based post-stroke motor rehabilitation. Trials were identified using MEDLINE, CENTRAL, PEDro and by inspection of references in several review articles. We selected randomized controlled trials that used BCIs for post-stroke motor rehabilitation and provided motor impairment scores before and after the intervention. A random-effects inverse variance method was used to calculate the summary effect size. We initially identified 524 articles and, after removing duplicates, we screened titles and abstracts of 473 articles. We found 26 articles corresponding to BCI clinical trials, of these, there were nine studies that involved a total of 235 post-stroke survivors that fulfilled the inclusion criterion (randomized controlled trials that examined motor performance as an outcome measure) for the meta-analysis. Motor improvements, mostly quantified by the upper limb Fugl-Meyer Assessment (FMA-UE), exceeded the minimal clinically important difference (MCID=5.25) in six BCI studies, while such improvement was reached only in three control groups. Overall, the BCI training was associated with a standardized mean difference of 0.79 (95% CI: 0.37 to 1.20) in FMA-UE compared to control conditions, which is in the range of medium to large summary effect size. In addition, several studies indicated BCI-induced functional and structural neuroplasticity at a subclinical level. This suggests that BCI technology could be an effective intervention for post-stroke upper limb rehabilitation. However, more studies with larger sample size are required to increase the reliability of these results.

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).

Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine.

PubMed

Honig, Adriaan; Kuyper, Astrid M G; Schene, Aart H; van Melle, Joost P; de Jonge, Peter; Tulner, Dorien M; Schins, Annique; Crijns, Harry J G M; Kuijpers, Petra M J C; Vossen, Helen; Lousberg, Richel; Ormel, Johan

2007-01-01

To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited. In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale. Using the "last observation carried forward" (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant. This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression.

Post-acute crisis text messaging outreach for suicide prevention: a pilot study.

PubMed

Berrouiguet, Sofian; Gravey, Michel; Le Galudec, Mickaël; Alavi, Zarrin; Walter, Michel

2014-07-30

Several post-suicide prevention strategies such as sending postcards or making phone calls have been used to keep in contact with suicide attempters. The continuity of care has been beneficial to the prevention of post-acute suicidal behaviors. The aim of the study was to evaluate the technical feasibility and acceptability of text messaging outreach in post-acute suicide attempters. Eighteen post-suicidal patients were included in a prospective, monocentric, open-label, 2 months pilot study. The text messages were sent from the intranet program that we specially developed for the study. Technical feasibility of this text message intervention was evaluated by the analysis of text message reports. Acceptability of such intervention was evaluated by a standardized phone interview. Our study showed that receiving text messages sent from an intranet program after a suicide attempt is technically possible. This post-crisis outreach program was accepted by the patients who found it to have a positive preventive impact. Text messaging outreach offers several advantages such as lower cost, and easier utilization compared to current post-acute care strategies. We suggest further randomized controlled trials in a large sample of suicidal patients to assess the efficacy of this novel outreach tool for prevention of post-acute suicide. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.

PubMed

Isaacson, R S; Haynes, N; Seifan, A; Larsen, D; Christiansen, S; Berger, J C; Safdieh, J E; Lunde, A M; Luo, A; Kramps, M; McInnis, M; Ochner, C N

2014-01-01

Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). Observational. Online. Men/Women, aged 25+, recruited via facebook.com. Alzheimer's Universe (www.AlzU.org) education research platform. Pre/post-test performance, self-reported Likert-scale ratings, completion rates. Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.

PACE-UP (Pedometer and consultation evaluation--UP)--a pedometer-based walking intervention with and without practice nurse support in primary care patients aged 45-75 years: study protocol for a randomised controlled trial.

PubMed

Harris, Tess; Kerry, Sally M; Victor, Christina R; Shah, Sunil M; Iliffe, Steve; Ussher, Michael; Ekelund, Ulf; Fox-Rushby, Julia; Whincup, Peter; David, Lee; Brewin, Debbie; Ibison, Judith; DeWilde, Stephen; Limb, Elizabeth; Anokye, Nana; Furness, Cheryl; Howard, Emma; Dale, Rebecca; Cook, Derek G

2013-12-05

Most adults do not achieve the 150 minutes weekly of at least moderate intensity activity recommended for health. Adults' most common physical activity (PA) is walking, light intensity if strolling, moderate if brisker. Pedometers can increase walking; however, most trials have been short-term, have combined pedometer and support effects, and have not reported PA intensity. This trial will investigate whether pedometers, with or without nurse support, can help less active 45-75 year olds to increase their PA over 12 months. Primary care-based 3-arm randomized controlled trial with 12-month follow-up and health economic and qualitative evaluations. Less active 45-75 year olds (n = 993) will be recruited by post from six South West London general practices, maximum of two per household and households randomised into three groups. Step-count and time spent at different PA intensities will be assessed for 7 days at baseline, 3 and 12 months by accelerometer. Questionnaires and anthropometric assessments will be completed. The pedometer-alone group will be posted a pedometer (Yamax Digi-Walker SW-200), handbook and diary detailing a 12-week pedometer-based walking programme, using targets from their baseline assessment. The pedometer-plus-support group will additionally receive three practice nurse PA consultations. The handbook, diary and consultations include behaviour change techniques (e.g., self-monitoring, goal-setting, relapse prevention planning). The control group will receive usual care. Changes in average daily step-count (primary outcome), time spent sedentary and in at least moderate intensity PA weekly at 12 months, measured by accelerometry. Other outcomes include change in body mass index, body fat, self-reported PA, quality of life, mood and adverse events. Cost-effectiveness will be assessed by the incremental cost of the intervention to the National Health Service and incremental cost per change in step-count and per quality adjusted life year. Qualitative evaluations will explore reasons for trial non-participation and the interventions' acceptability. The PACE-UP trial will determine the effectiveness and cost-effectiveness of a pedometer-based walking intervention delivered by post or practice nurse to less active primary care patients aged 45-75 years old. Approaches to minimise bias and challenges anticipated in delivery will be discussed. ISRCTN98538934.

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

PubMed

Rodgers, Helen; Shaw, Lisa; Bosomworth, Helen; Aird, Lydia; Alvarado, Natasha; Andole, Sreeman; Cohen, David L; Dawson, Jesse; Eyre, Janet; Finch, Tracy; Ford, Gary A; Hislop, Jennifer; Hogg, Steven; Howel, Denise; Hughes, Niall; Krebs, Hermano Igo; Price, Christopher; Rochester, Lynn; Stamp, Elaine; Ternent, Laura; Turner, Duncan; Vale, Luke; Warburton, Elizabeth; van Wijck, Frederike; Wilkes, Scott

2017-07-20

Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. NHS stroke services. adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Suicide risk in patients with anxiety disorders: a meta-analysis of the FDA database.

PubMed

Khan, Arif; Leventhal, Robyn M; Khan, Shirin; Brown, Walter A

2002-04-01

Previous reports of suicide risk in patients with anxiety disorders have been inconsistent. Using the FDA database, we assessed suicide and suicide attempt risk among patients, participating in recent clinical trials evaluating new anti-anxiety medications, with diagnosis of panic disorder (PD), social anxiety disorder or social phobia (SP), generalized anxiety disorder (GAD), post traumatic stress disorder (PTSD), and obsessive compulsive disorder (OCD). Overall, among 20076 participating anxious patients, 12 committed suicide and 28 attempted suicide. The annual suicide risk rate was 193/100000 patients and annual suicide attempt risk was 1350/100000 patients. Clinical trial data have limited applicability to clinical practice. Participants in clinical trials are a highly selected, nonrepresentative sample of the clinical population. A number of patients never complete clinical trials and thus data are based on a limited sub-sample. These trials were not primarily designed to assess suicide risk. Suicide risk in patients with anxiety disorders is higher than previously thought. Patients with anxiety disorders warrant explicit evaluation for suicide risk.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

PubMed

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-11-01

Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Spot drip application of dimethyl disulfide as a post-plant treatment for the control of plant parasitic nematodes and soilborne pathogens in grape production.

PubMed

Cabrera, J Alfonso; Wang, Dong; Gerik, James S; Gan, Jay

2014-07-01

Plant parasitic nematodes and soilborne pathogens can reduce the overall productivity in grape production. Not all grape growers apply soil fumigants before planting, and there is no single rootstock resistant to all nematode species. The aim of this investigation was to evaluate the effect of dimethyl disulfide (DMDS) applied at 112, 224, 448 and 897 kg ha(-1) as a post-plant treatment against soilborne plant parasitic nematodes and pathogens on the grape yield in established grapevines. In microplot and field trials, post-plant fumigation with DMDS controlled citrus (Tylenchulus semipenetrans), root-knot (Meloidogyne spp.), pin (Paratylenchus spp.) and ring (Mesocriconema xenoplax) nematodes in established Thomson Seedless grapevines. However, DMDS did not control the soilborne pathogens Pythium ultimum and Fusarium oxysporum. No indications of phytotoxicity were detected after post-plant fumigation with DMDS. In the field trial, grape yield was significantly higher with the lowest DMDS rate, but no difference among other rates was observed in comparison with the untreated control. Post-plant fumigation with DMDS controlled plant parasitic nematodes in established grapevines but was less efficacious against soilborne pathogens. Low rates of DMDS were sufficient for nematode control and increased the grape yield, probably without affecting beneficial soil organisms. Further research on evaluating the potential effect of DMDS against beneficial soil organisms is needed. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury

PubMed Central

Estrella, Michelle M.; Coresh, Josef; Brower, Roy G.; Liu, Kathleen D.

2011-01-01

Summary Background and objectives Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients. Design, setting, participants, & measurements Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria. Results 306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P = 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased. Conclusions A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance. PMID:21393482

The Effect of Massage on Acute Postoperative Pain in Critically and Acutely Ill Adults Post-thoracic Surgery: Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Boitor, Madalina; Gélinas, Céline; Richard-Lalonde, Melissa; Thombs, Brett D

Critical care practice guidelines identify a lack of clear evidence on the effectiveness of massage for pain control. To assess the effect of massage on acute pain in critically and acutely ill adults post-thoracic surgery. Medline, Embase, CINAHL, PsychInfo, Web of Science, Scopus and Cochrane Library databases were searched. Eligible studies were randomized controlled trials (RCTs) evaluating the effect of massage compared to attention control/sham massage or standard care alone on acute pain intensity post-thoracic surgery. Twelve RCTs were included. Of these, nine evaluated massage in addition to standard analgesia, including 2 that compared massage to attention control/sham massage in the intensive care unit (ICU), 6 that compared massage to standard analgesia alone early post-ICU discharge, and 1 that compared massage to both attention control and standard care in the ICU. Patients receiving massage with analgesia reported less pain (0-10 scale) compared to attention control/sham massage (3 RCTs; N = 462; mean difference -0.80, 95% confidence interval [CI] -1.25 to -0.35; p < 0.001; I 2  = 13%) and standard care (7 RCTs; N = 1087; mean difference -0.85, 95% CI -1.28 to -0.42; p < 0.001; I 2  = 70%). Massage, in addition to pharmacological analgesia, reduces acute post-cardiac surgery pain intensity. Copyright © 2017 Elsevier Inc. All rights reserved.

Perioperative Ketamine Administration for Thoracotomy Pain.

PubMed

Moyse, Daniel W; Kaye, Alan D; Diaz, James H; Qadri, Muhammad Y; Lindsay, David; Pyati, Srinivas

2017-03-01

Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative morbidity. Multiple pain generators contribute to the severity of post-thoracotomy pain, and therefore a multimodal analgesic therapy is considered to be a necessary strategy. Along with opioids, thoracic epidural analgesia, and paravertebral blocks, N-Methyl-D-Aspartate (NMDA) receptor antagonists such as ketamine have been used as adjuvants to improve analgesia. We reviewed the evidence for the efficacy of intravenous and epidural administration of ketamine in acute post-thoracotomy pain management, and its effectiveness in reducing chronic post-thoracotomy pain. Systematic literature review and an analytic study of a data subset were performed. We searched PubMed, Embase, and Cochrane reviews using the key terms "ketamine," "neuropathic pain," "postoperative," and "post-thoracotomy pain syndrome." The search was limited to human trials and included all studies published before January 2015. Data from animal studies, abstracts, and letters were excluded. All studies not available in the English language were excluded. The manuscript bibliographies were reviewed for additional related articles. We included randomized controlled trials and retrospective studies, while excluding individual case reports. This systematic literature search yielded 15 randomized control trials evaluating the efficacy of ketamine in the treatment of acute post-thoracotomy pain; fewer studies assessed its effect on attenuating chronic post-thoracotomy pain. The majority of reviewed studies demonstrated that ketamine has efficacy in reduction of acute pain, but the evidence is limited on the long-term benefits of ketamine to prevent post-thoracotomy pain syndrome, regardless of the route of administration. A nested analytical study found there is a statistically significant reduction in acute post-thoracotomy pain with IV or epidural ketamine. However currently, the evidence for a role of ketamine as a preventative agent for chronic post-thoracotomy pain is insufficient due to the heterogeneity of the studies reviewed with regard to the route of administration, dosage, and outcome measures. The evidence for a role of ketamine as a preventative agent for chronic post-thoracotomy pain is insufficient due to the heterogeneity of the studies reviewed. The majority of randomized controlled trials reviewed show no role for ketamine in attenuating or preventing post-thoracotomy pain syndrome at variable follow-up lengths. Therefore, additional research is warranted with consideration of risk factors and long-term follow-up for chronic post-thoracotomy pain though the evidence for benefit appears clear for acute post-thoracotomy pain.Key words: Ketamine, postoperative, thoracotomy pain, post thoracotomy pain syndrome, neuropathic pain.

Successful peripheral nerve field stimulation for thoracic radiculitis following Brown-Sequard syndrome.

PubMed

Desai, Mehul J; Desai, Mehul; Jacob, Lisa; Leiphart, James

2011-01-01

  The objective of this study is to present a novel approach to the treatment of thoracic radiculitis following Brown-Sequard syndrome with peripheral nerve field stimulation (PNFS). Furthermore, we endeavor to discuss the role of PNFS in the management of refractory neuropathic pain conditions including post-traumatic and post-surgical neuropathy particularly with regards to the post-surgical spine.   Presented is a 57-year-old man with history of thoracic microdiscectomy resulting in Brown-Sequard syndrome presented with chronic post-operative thoracic radicular pain radiating to the abdomen, refractory to conservative management. The patient underwent three intercostal nerve blocks from T7 to T9 with transient symptomatic relief. The patient's options were limited to chemomodulation, neuromodulation, or selective intercostal nerve surgical neurectomy. He subsequently underwent a PNFS trial and reported >75% pain reduction. Permanent percutaneous PNFS electrodes were implanted subcutaneously over the right T7 and T9 intercostal nerves and replicated the trial results.   Neuromodulation produced pain relief with >90% improvement in pain compared with baseline both during the trial and following permanent implantation of the PNFS system.   Chronic radicular pain may be difficult to manage in the post-surgical patient and often requires the use of multiple therapeutic modalities. In this case, we successfully utilized PNFS as it demonstrated greater technical feasibility when compared with dorsal column stimulation and repeat surgery; therefore, it may be considered for the management of post-surgical neuropathy. Further controlled studies are needed to evaluate the efficacy of PNFS as a treatment option. © 2011 International Neuromodulation Society.

Analysis of factors influencing the overall effect of racecadotril on childhood acute diarrhea. Results from a real-world and post-authorization surveillance study in Venezuela

PubMed Central

Chacón, Jose

2010-01-01

Drug efficacy might differ from clinical trial results when performed in clinical daily conditions. Therefore, it is mandatory to conduct trials about effectiveness to improve external validity. This post-authorization, open-label, noncontrolled, prospective, multicenter, observational, and naturalistic trial was designed to search for factors influencing the racecadotril overall effect on childhood acute watery diarrhea in a real-world setting of Venezuela. There were 3,873 children with acute watery diarrhea treated with racecadotril, an enkephalin breakdown blocker plus oral rehydration therapy by 97 pediatricians. Evaluations were carried out daily until emission of two consecutive formed stools or absence of watery bowel movements for 24 hours. The primary end-point was time-to-relief, defined as the time from first racecadotril dose to the last watery bowel movement time. Age, gender, nursing type, nursing status during diarrhea, diarrhea severity, and co-medication were considered as factors in the statistical analysis. The primary end-point was evaluated by factors using UNIANOVA, and post-hoc tests were done. A multiple regression analysis was carried out to identify factors affecting drug performance, racecadotril effectiveness and tolerability overall assessment was searched by physicians and patients, and inter-observer agreement was evaluated by kappa statistics. The mean time-to-relief was 18.5 ± 12.5 hours [95% confidence interval 17.9–19.0] and the diarrhea severity was the only variable with significant and independent weight on racecadotril effectiveness explaining 23% of time-to-relief variance, but even in severe diarrhea cases this time was less than 24 hours. High agreement about satisfactory perception on effectiveness and tolerability was reached among physicians and patients. In conclusion, the racecadotril overall effect, evaluated in a real-world setting of Venezuela, was in agreement with results of some earlier controlled trials. It was only influenced by severity of diarrhea episode, as well as being considered an effective and well tolerated treatment by physicians and patients. PMID:20668711

Influence of clinical baseline findings on the survival of 2 post systems: a randomized clinical trial.

PubMed

Schmitter, Marc; Rammelsberg, Peter; Gabbert, Olaf; Ohlmann, Brigitte

2007-01-01

The aim of this prospective randomized controlled trial was to evaluate the influence of clinical baseline characteristics on the survival of 2 post systems. One hundred patients needing a post were included. Half the patients received a glass fiber-reinforced post (FRP), and the other half received metal screw posts (MSP). The posts were assigned randomly. In addition to demographic data, the following parameters were recorded: type of tooth (incisor/canine versus molar/premolar), length of the post in relation to root length (percentage), extent of coronal tooth destruction (percentage), ferrule height (in millimeters), type of restoration (fixed or removable partial denture), and presence of antagonistic contacts (yes/no). After at least 1 year (mean: 13.84 months), the patients were recalled. Statistical analysis was performed using the log-rank test and Cox regression analysis. The survival rate of FRPs was 93.5%. In the MSP group, the survival rate was significantly lower (75.6%; log-rank test, P = .049). Additionally, the metal posts were associated with more unfavorable complications, for example, root fracture. The type of the tooth and the degree of coronal tooth destruction influenced the survival of MSPs, whereas no influence of these variables could be seen for FRPs. FRPs are superior to MSPs with respect to short-term clinical performance. Especially for MSPs, clinical survival depends on several variables.

Aripiprazole for Post-traumatic Stress Disorder: A Systematic Review.

PubMed

Britnell, Sara R; Jackson, Anna D; Brown, Jamie N; Capehart, Bruce P

The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD). A search of both MEDLINE (1956 to May 2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole" and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD." Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole as monotherapy or adjunct therapy were analyzed for relevance. Those that met the objective of this study were included for evaluation: 1 placebo-controlled trial; 4 open-label trials; and 1 retrospective chart review. In patients with a history of PTSD, aripiprazole resulted in significant improvements in the primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD Checklist-Military scores, in all but 1 study analyzed. Study durations ranged from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily that could be titrated up or down in the range of 2 to 30 mg daily based on efficacy and tolerability. Overall, aripiprazole was well tolerated with the most common treatment-related study discontinuations attributed to the adverse events of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence. Based on the reviewed literature, aripiprazole is a reasonable therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger randomized controlled trials are needed to better understand the role of this atypical antipsychotic in patients with PTSD.

Prediction of black box warning by mining patterns of Convergent Focus Shift in clinical trial study populations using linked public data.

PubMed

Ma, Handong; Weng, Chunhua

2016-04-01

To link public data resources for predicting post-marketing drug safety label changes by analyzing the Convergent Focus Shift patterns among drug testing trials. We identified 256 top-selling prescription drugs between 2003 and 2013 and divided them into 83 BBW drugs (drugs with at least one black box warning label) and 173 ROBUST drugs (drugs without any black box warning label) based on their FDA black box warning (BBW) records. We retrieved 7499 clinical trials that each had at least one of these drugs for intervention from the ClinicalTrials.gov. We stratified all the trials by pre-marketing or post-marketing status, study phase, and study start date. For each trial, we retrieved drug and disease concepts from clinical trial summaries to model its study population using medParser and SNOMED-CT. Convergent Focus Shift (CFS) pattern was calculated and used to assess the temporal changes in study populations from pre-marketing to post-marketing trials for each drug. Then we selected 68 candidate drugs, 18 with BBW warning and 50 without, that each had at least nine pre-marketing trials and nine post-marketing trials for predictive modeling. A random forest predictive model was developed to predict BBW acquisition incidents based on CFS patterns among these drugs. Pre- and post-marketing trials of BBW and ROBUST drugs were compared to look for their differences in CFS patterns. Among the 18 BBW drugs, we consistently observed that the post-marketing trials focused more on recruiting patients with medical conditions previously unconsidered in the pre-marketing trials. In contrast, among the 50 ROBUST drugs, the post-marketing trials involved a variety of medications for testing their associations with target intervention(s). We found it feasible to predict BBW acquisitions using different CFS patterns between the two groups of drugs. Our random forest predictor achieved an AUC of 0.77. We also demonstrated the feasibility of the predictor for identifying long-term BBW acquisition events without compromising prediction accuracy. This study contributes a method for post-marketing pharmacovigilance using Convergent Focus Shift (CFS) patterns in clinical trial study populations mined from linked public data resources. These signals are otherwise unavailable from individual data resources. We demonstrated the added value of linked public data and the feasibility of integrating ClinicalTrials.gov summaries and drug safety labels for post-marketing surveillance. Future research is needed to ensure better accessibility and linkage of heterogeneous drug safety data for efficient pharmacovigilance. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of virtual reality for stroke individuals based on the International Classification of Functioning and Health: a systematic review.

PubMed

Palma, Gisele Carla Dos Santos; Freitas, Tatiana Beline; Bonuzzi, Giordano Márcio Gatinho; Soares, Marcos Antonio Arlindo; Leite, Paulo Henrique Wong; Mazzini, Natália Araújo; Almeida, Murilo Ruas Groschitz; Pompeu, José Eduardo; Torriani-Pasin, Camila

2017-05-01

This review determines the effects of virtual reality interventions for stroke subjects based on the International Classification of Functioning, Disability,and Health (ICF) framework. Virtual reality is a promising tool for therapy for stroke rehabilitation, but the effects of virtual reality interventions on post-stroke patients based on the specific ICF domains (Body Structures, Body Functions, Activity, and Participation) have not been investigated. A systematic review was conducted, including trials with adults with a clinical diagnosis of a chronic, subacute, or acute stroke. Eligible trials had to include studies with an intervention protocol and follow-up, with a focus on upper limbs and/or lower limbs and/or balance. The Physiotherapy Evidence Database (PEDro) was used to assess the methodological quality of randomized controlled trials. Each trial was separated according to methodological quality into a high-quality trial (PEDro ≥ 6) and a low-quality trial (PEDro ≤ 6). Only high-quality trials were analyzed specifically based on the outcome of these trials. In total, 54 trials involving 1811 participants were included. Of the papers included and considered high quality, 14 trials evaluated areas of the Body Structures component, 20 trials of the Body Functions domain, 17 trials of the Activity component, and 8 trials of the Participation domain. In relation to ICF Part 2, four trials evaluated areas of the Personal Factors component and one trial evaluated domains of the Environmental Factors component. The effects of virtual reality on stroke rehabilitation based on the ICF framework are positive in Body Function and Body Structure. However, the results in the domains Activity and Participation are inconclusive. More high-quality clinical trials are needed to confirm the effectiveness of virtual reality in the domains of Activity and Participation.

Calorie and protein-enriched formula versus standard term formula for improving growth and development in preterm or low birth weight infants following hospital discharge.

PubMed

Henderson, G; Fahey, T; McGuire, W

2005-04-18

Preterm and low birth weight infants are often growth-restricted at hospital discharge. Feeding infants post-hospital discharge with calorie and protein-enriched formula milk might facilitate "catch-up" growth and improve development. To review the evidence from randomised controlled trials that feeding following hospital discharge with calorie and protein-enriched formula compared with standard term formula improves growth and development for preterm or low birth weight infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004), MEDLINE (1966 - December 2004), EMBASE (1980 - December 2004), CINAHL (1982 - December 2004), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared the effect of feeding preterm or low birth weight infants post-hospital discharge with calorie and protein-enriched formula compared with standard term formula. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis of data using weighted mean difference and a fixed effects model for meta-analysis. We found six trials that were eligible for inclusion. These recruited a total of 424 infants and were generally of good methodological quality. These trials found little evidence that feeding with calorie and protein-enriched formula milk affected growth and development. Because of differences in the way individual trials measured and presented outcomes, data synthesis was limited. Meta-analysis of data from two trials found a statistically significant effect on crown-heel length at 18 months post-term (weighted mean difference 9.7 millimetres (95% confidence interval 3.2 to 16.2)), but not on weight or head circumference. Meta-analysis of data from the two trials that assessed neurodevelopment at 18 months post-term did not reveal a statistically significant difference in either Bayley Mental Development Index (weighted mean difference 0.23 (95% confidence interval -2.99 to 3.45)) or Psychomotor Development Index (weighted mean difference 0.56 (95% confidence interval -1.95 to 3.07)). There are not yet any data on growth or development through later childhood. The limited available data do not provide strong evidence that feeding preterm or low birth weight infants following hospital discharge with calorie and protein-enriched formula compared with standard term formula affects growth rates or development up to 18 months post-term.

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination

PubMed Central

Williams, Rebecca J.; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A.

2015-01-01

Background Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study. PMID:26011295

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination.

PubMed

Williams, Rebecca J; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A

2015-01-01

Clinical trials that end prematurely (or "terminate") raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Trial registration Current Controlled Trials ISRCTN19506752 PMID:21672213

Telephone Problem Solving for Service Members with Mild Traumatic Brain Injury: A Randomized, Clinical Trial.

PubMed

Bell, Kathleen R; Fann, Jesse R; Brockway, Jo Ann; Cole, Wesley R; Bush, Nigel E; Dikmen, Sureyya; Hart, Tessa; Lang, Ariel J; Grant, Gerald; Gahm, Gregory; Reger, Mark A; St De Lore, Jef; Machamer, Joan; Ernstrom, Karin; Raman, Rema; Jain, Sonia; Stein, Murray B; Temkin, Nancy

2017-01-15

Mild traumatic brain injury (mTBI) is a common injury for service members in recent military conflicts. There is insufficient evidence of how best to treat the consequences of mTBI. In a randomized, clinical trial, we evaluated the efficacy of telephone-delivered problem-solving treatment (PST) on psychological and physical symptoms in 356 post-deployment active duty service members from Joint Base Lewis McChord, Washington, and Fort Bragg, North Carolina. Members with medically confirmed mTBI sustained during deployment to Iraq and Afghanistan within the previous 24 months received PST or education-only (EO) interventions. The PST group received up to 12 biweekly telephone calls from a counselor for subject-selected problems. Both groups received 12 educational brochures describing common mTBI and post-deployment problems, with follow-up for all at 6 months (end of PST), and at 12 months. At 6 months, the PST group significantly improved on a measure of psychological distress (Brief Symptom Inventory; BSI-18) compared to the EO group (p = 0.005), but not on post-concussion symptoms (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]; p = 0.19), the two primary endpoints. However, these effects did not persist at 12-month follow-up (BSI, p = 0.54; RPQ, p = 0.45). The PST group also had significant short-term improvement on secondary endpoints, including sleep (p = 0.01), depression (p = 0.03), post-traumatic stress disorder (p = 0.04), and physical functioning (p = 0.03). Participants preferred PST over EO (p < 0.001). Telephone-delivered PST appears to be a well-accepted treatment that offers promise for reducing psychological distress after combat-related mTBI and could be a useful adjunct treatment post-mTBI. Further studies are required to determine how to sustain its effects. (Trial registration: ClinicalTrials.gov Identifier: NCT01387490 https://clinicaltrials.gov ).

Effect of 1% sodium alendronate in the non-surgical treatment of periodontal intraosseous defects: a 6-month clinical trial

PubMed Central

DUTRA, Bernardo Carvalho; OLIVEIRA, Alcione Maria Soares Dutra; OLIVEIRA, Peterson Antônio Dutra; MANZI, Flavio Ricardo; CORTELLI, Sheila Cavalca; COTA, Luís Otávio de Miranda; COSTA, Fernando Oliveira

2017-01-01

Abstract Background and objectives Few studies have evaluated the effect of the topical application of sodium alendronate (ALN) on the treatment of intrabuccal bone defects, especially those caused by periodontitis. This 6-month randomized placebo controlled clinical trial aimed at evaluating the effect of non-surgical periodontal treatment associated with the use of 1% ALN, through clinical evaluations and cone-beam computed tomography (CBCT). Material and Methods Twenty individuals with chronic periodontitis underwent periodontal examination at the baseline as well as 3 and 6 months after periodontal treatment, registering clinical attachment level (CAL), periodontal probing depth (PPD), and bleeding on probing (BOP) as the clinical outcomes. After manual scaling and root planing, 40 bilateral sites with interproximal vertical bone defects were randomly treated with either 1% ALN gel or a placebo. Bone defects were evaluated through CBCT at the baseline and 6 months post-treatment. The clinical and CBCT parameters were compared using the Wilcoxon and Friedman tests (p<0.05). Results Although ALN produced a greater CAL gain when compared to the placebo at 6 months post-treatment (p=0.021), both treatments produced similar effects on the PPD, BOP, and bone height. Significant differences in bone fill were observed only in patients of the ALN group (4.5 to 3.8 mm; p=0.003) at 6 months post-treatment. Conclusions Topical application of 1% ALN might be a beneficial adjuvant to non-surgical periodontal therapy. PMID:28678950

Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation of a Randomized Controlled Trial

PubMed Central

Voorn, Eric L.; Koopman, Fieke S.; Brehm, Merel A.; Beelen, Anita; de Haan, Arnold; Gerrits, Karin H. L.; Nollet, Frans

2016-01-01

Objective To explore reasons for the lack of efficacy of a high intensity aerobic exercise program in post-polio syndrome (PPS) on cardiorespiratory fitness by evaluating adherence to the training program and effects on muscle function. Design A process evaluation using data from an RCT. Patients Forty-four severely fatigued individuals with PPS were randomized to exercise therapy (n = 22) or usual care (n = 22). Methods Participants in the exercise group were instructed to exercise 3 times weekly for 4 months on a bicycle ergometer (60–70% heart rate reserve). Results The attendance rate was high (median 89%). None of the participants trained within the target heart rate range during >75% of the designated time. Instead, participants exercised at lower intensities, though still around the anaerobic threshold (AT) most of the time. Muscle function did not improve in the exercise group. Conclusion Our results suggest that severely fatigued individuals with PPS cannot adhere to a high intensity aerobic exercise program on a cycle ergometer. Despite exercise intensities around the AT, lower extremity muscle function nor cardiorespiratory fitness improved. Improving the aerobic capacity in PPS is difficult through exercise primarily focusing on the lower extremities, and may require a more individualized approach, including the use of other large muscle groups instead. Trial Registration Netherlands National Trial Register NTR1371 PMID:27419388

Programs for the Prevention of Youth Depression: Evaluation of Efficacy, Effectiveness, and Readiness for Dissemination

PubMed Central

Brunwasser, Steven M.; Garber, Judy

2015-01-01

Objective To evaluate the current state of evidence of the effectiveness of depression prevention programs for youth, assess the degree to which current evidence supports broad implementation, and outline additional steps needed to close the gap between effectiveness and dissemination. Method We used the Society for Prevention Research’s Standards of Evidence (Flay et al., 2005) to evaluate the degree to which existing depression prevention programs have established intervention efficacy, effectiveness, and readiness for dissemination. We reviewed all depression prevention programs for youth that have been evaluated in at least two published, randomized controlled trials in which the intervention was compared to a no-intervention control group. A total of 37 studies evaluating 11 different programs were reviewed with regard to depressive symptoms and diagnoses post intervention and at follow-up (at least 6 months). Results Eight programs demonstrated significant main effects on depressive symptoms relative to controls in multiple RCTs; five programs had at least one trial with significant main effects present at least one year post-intervention. Two programs demonstrated efficacy for both depressive symptoms and depressive episodes across multiple independent trials. Regarding effectiveness, six programs had at least one study showing significant effects when delivered by endogenous service providers; four programs had significant effects in studies conducted independently of the program developers. Conclusions Several programs have demonstrated promise in terms of efficacy, but no depression prevention program for children or adolescents as yet has garnered sufficient evidence of effectiveness under real-world conditions to warrant widespread dissemination at this time. PMID:25933173

Physiological Markers of Arousal Change with Psychological Treatment for Insomnia: A Preliminary Investigation

PubMed Central

Miller, Christopher B.; Kyle, Simon D.; Gordon, Christopher J.; Espie, Colin A.; Grunstein, Ronald R.; Mullins, Anna E.; Postnova, Svetlana; Bartlett, Delwyn J.

2015-01-01

Objectives The aim of this preliminary study was to evaluate if Sleep Restriction Therapy for insomnia is associated with modifications to physiological arousal, indexed through overnight measures of plasma cortisol concentrations and core body temperature. Methods In a pre-to-post open label study design, eleven patients with chronic and severe Psychophysiological Insomnia underwent 5 weeks of Sleep Restriction Therapy. Results Eight (73%) patients out of 11 consented completed therapy and showed a decrease in insomnia severity pre-to-post treatment (mean (SD): 18.1 (2.8) versus 8.4 (4.8); p = .001). Six patients were analyzed with pre-to-post overnight measures of temperature and cortisol. Contrary to our hypothesis, significantly higher levels of plasma cortisol concentrations were found during the early morning at post-treatment compared to baseline (p < .01), while no change was observed in the pre-sleep phase or early part of the night. Core body temperature during sleep was however reduced significantly (overall mean [95% CI]: 36.54 (°C) [36.3, 36.8] versus 36.45 [36.2, 36.7]; p < .05). Conclusions Sleep Restriction Therapy therefore was associated with increased early morning cortisol concentrations and decreased core body temperature, supporting the premise of physiological changes in functioning after effective therapy. Future work should evaluate change in physiological variables associated with clinical treatment response. Trial Registration Australian New Zealand Clinical Trials Registry ANZCTR 12612000049875 PMID:26683607

PACE-UP (Pedometer and consultation evaluation - UP) – a pedometer-based walking intervention with and without practice nurse support in primary care patients aged 45–75 years: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Most adults do not achieve the 150 minutes weekly of at least moderate intensity activity recommended for health. Adults’ most common physical activity (PA) is walking, light intensity if strolling, moderate if brisker. Pedometers can increase walking; however, most trials have been short-term, have combined pedometer and support effects, and have not reported PA intensity. This trial will investigate whether pedometers, with or without nurse support, can help less active 45–75 year olds to increase their PA over 12 months. Methods/design Design: Primary care-based 3-arm randomized controlled trial with 12-month follow-up and health economic and qualitative evaluations. Participants: Less active 45–75 year olds (n = 993) will be recruited by post from six South West London general practices, maximum of two per household and households randomised into three groups. Step-count and time spent at different PA intensities will be assessed for 7 days at baseline, 3 and 12 months by accelerometer. Questionnaires and anthropometric assessments will be completed. Intervention: The pedometer-alone group will be posted a pedometer (Yamax Digi-Walker SW-200), handbook and diary detailing a 12-week pedometer-based walking programme, using targets from their baseline assessment. The pedometer-plus-support group will additionally receive three practice nurse PA consultations. The handbook, diary and consultations include behaviour change techniques (e.g., self-monitoring, goal-setting, relapse prevention planning). The control group will receive usual care. Outcomes: Changes in average daily step-count (primary outcome), time spent sedentary and in at least moderate intensity PA weekly at 12 months, measured by accelerometry. Other outcomes include change in body mass index, body fat, self-reported PA, quality of life, mood and adverse events. Cost-effectiveness will be assessed by the incremental cost of the intervention to the National Health Service and incremental cost per change in step-count and per quality adjusted life year. Qualitative evaluations will explore reasons for trial non-participation and the interventions’ acceptability. Discussion The PACE-UP trial will determine the effectiveness and cost-effectiveness of a pedometer-based walking intervention delivered by post or practice nurse to less active primary care patients aged 45–75 years old. Approaches to minimise bias and challenges anticipated in delivery will be discussed. Trial registration ISRCTN98538934 PMID:24304838

Treatment of traumatized refugees with Sertraline versus Venlafaxine in combination with psychotherapy – study protocol for a randomized clinical trial

PubMed Central

2013-01-01

Background Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially Sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. Design This study will include approximately 150 patients, randomized into two different groups treated with either Sertraline or Venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. Discussion This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. Trial registration ClinicalTrials.gov NCT01569685 PMID:23663588

"Ferrule Comes First. Post Is Second!" Fake News and Alternative Facts? A Systematic Review.

PubMed

Naumann, Michael; Schmitter, Marc; Frankenberger, Roland; Krastl, Gabriel

2018-02-01

Both the role of an endodontic post and the ferrule effect have been discussed for decades. The clinical impact of endodontic posts compared with post-free restoration with or without ferrule support was not systematically reviewed so far. It was assumed that the effect of an endodontic post compared with a post-free restoration can be evaluated only when at the same time a ferrule or no-ferrule situation was clinically compared. The specific PICO question was as follows: Patient: adults with sufficient endodontic treatment needing a core or post; Intervention: post-endodontic treatment using posts with or without ferrule; Comparison: post-endodontic treatment without posts with or without ferrule; Outcomes: failure rates of post/core complexes with or without ferrule support. A Medline search was performed via PubMed in June 2017 using relevant electronic databases. Additionally, hand search was performed. Only prospective clinical studies in humans comparing the success/survival of teeth restored with or without posts over a minimum time of observation of 5 years were included. In total, 7 randomized controlled trials and 1 prospective clinical trial met inclusion criteria. Cochrane rating showed high risk of bias in 5 studies. Two of 3 studies support the ferrule-effect concept. Seven of 8 show no post effect. Clinical evidence regarding the influence of tooth location on its survival is scarce. Ferrule effect and maintaining cavity walls are the predominant factors with regard to tooth and restoration survival of endodontically treated teeth. Most studies do not confirm a positive effect of post placement. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery.

PubMed

Gong, J; Xie, Z; Zhang, T; Gu, L; Yao, W; Guo, Z; Li, Y; Lu, N; Zhu, W; Li, N; Li, J

2016-04-01

Previous studies have shown that recovery of colonic transit is a major determinant of post-operative ileus and clinical recovery after gastrointestinal surgery. Prucalopride is a highly selective 5-hydroxytryptamine receptor-4 agonist with colonic pro-motility effects. To evaluate the effect and safety of prucalopride on post-operative ileus and surgical outcomes after elective gastrointestinal surgery. In this phase II randomised clinical trial, 110 patients undergoing elective gastrointestinal surgery were randomised to either oral prucalopride (2 mg/day) (n = 55) or placebo (n = 55). Intervention was started 24 h after surgery and stopped after defecation or maximally at 7 days. The primary outcome was time to defecation. Secondary outcomes included time to first passage of flatus, tolerance of solid food, nasogastric tube reinsertion, post-operative length of stay, hospital readmission, overall cost, time to walk independently, surgical complications and inflammatory parameters. Patients who received prucalopride had a shorter time to defecation (65.0 vs. 94.5 h, P = 0.001), passage of flatus (53.0 vs. 73.0 h, P < 0.001), and post-operative length of stay (7.0 vs. 8.0 days, P = 0.001) than controls. The number of patients with prolonged ileus (>5 days) (16.4% vs. 34.5%, P = 0.026) and the C-reactive protein level on post-operative day 5 (35.67 vs. 59.07 mg/L, P = 0.040) were lower in the prucalopride group. There was no significant difference in post-operative Clavien-Dindo grade III and IV complications (P = 0.606) between the groups. Prucalopride is a safe and effective treatment to reduce post-operative ileus and systemic inflammation without affecting post-operative complications in patients undergoing elective gastrointestinal surgery. ClinicalTrials.gov: NCT02004652. © 2016 John Wiley & Sons Ltd.

Clinical efficacy of Daikenchuto for gastrointestinal dysfunction following colon surgery: a randomized, double-blind, multicenter, placebo-controlled study (JFMC39-0902)

PubMed Central

Katsuno, Hidetoshi; Maeda, Koutarou; Kaiho, Takashi; Kunieda, Katsuyuki; Funahashi, Kimihiko; Sakamoto, Junichi; Kono, Toru; Hasegawa, Hirotoshi; Furukawa, Yoshiyuki; Imazu, Yoshihiro; Morita, Satoshi; Watanabe, Masahiko

2015-01-01

Objective This exploratory trial was performed to determine whether Daikenchuto accelerates recovery of gastrointestinal function in patients undergoing open colectomy for colon cancer. Methods A total of 386 patients undergoing colectomy at 1 of the 51 clinical trial sites in Japan from January 2009 to June 2011 were registered for the study (JFMC39-0902). Patients received either placebo or Daikenchuto (15.0 g/day, t.i.d) between post-operative day 2 and post-operative day 8. Primary end-points included time to first bowel movement, frequency of bowel movement and stool form. The incidence of intestinal obstruction was evaluated post-operatively. The safety profile of Daikenchuto until post-operative day 8 was also evaluated. Results The results for 336 patients (Daikenchuto, n = 174; placebo, n = 162) were available for statistical analysis. The time to first bowel movement did not differ significantly between the two groups. All patients reported having diarrhea or soft stools immediately after surgery, and the time until stool normalization (50th percentile) in the Daikenchuto and placebo groups was 6 days and 7 days, respectively. The placebo group had a significantly greater number of hard stools at post-operative day 8 (P = 0.016), and bowel movement frequency continued to increase until post-operative day 8 as well. In contrast, bowel movement frequency in the Daikenchuto group increased until post-operative day 6, however decreased from post-operative day 7 and was significantly lower at post-operative day 8 compared with the placebo group (P = 0.024). Conclusion The moderate effects of Daikenchuto were observed ∼1 week after the operation. Although Daikenchuto had an effect on gastrointestinal function after open surgery in patients with colon cancer, this study did not show its clinical benefits adequately. PMID:25972515

Low and high-frequency TENS in post-episiotomy pain relief: a randomized, double-blind clinical trial.

PubMed

Pitangui, Ana C R; Araújo, Rodrigo C; Bezerra, Michelle J S; Ribeiro, Camila O; Nakano, Ana M S

2014-01-01

To evaluate the effectiveness of low-frequency TENS (LFT) and high-frequency TENS (HFT) in post-episiotomy pain relief. A randomized, controlled, double-blind clinical trial with placebo composed of 33 puerperae with post-episiotomy pain. TENS was applied for 30 minutes to groups: HFT(100 Hz; 100 µs), LFT (5 Hz; 100 µs), and placebo (PT). Four electrodes were placed in parallel near the episiotomy and four pain evaluations were performed with the numeric rating scale. The first and the second evaluation took place before TENS application and immediately after its removal and were done in the resting position and in the activities of sitting and ambulating. The third and fourth evaluation took place 30 and 60 minutes after TENS removal, only in the resting position. Intragroup differences were verified using the Friedman and Wilcoxon tests, and the intergroup analysis employed the Kruskal-Wallis test. In the intragroup analysis, there was no significant difference in the PT during rest, sitting, and ambulation (P>0.05). In the HFT and LFT, a significant difference was observed in all activities (P<0.001). In the intergroup analysis, there was a significant difference in the resting position in the HFT and LFT (P<0.001). In the sitting activity, a significant difference was verified in the second evaluation in the HFT and LFT (P<0.008). No significant difference was verified among the groups in ambulation (P<0.20). LFT and HFT are an effective resource that may be included in the routine of maternity wards.

Baduanjin Exercise Prevents post-Myocardial Infarction Left Ventricular Remodeling (BE-PREMIER trial): Design and Rationale of a Pragmatic Randomized Controlled Trial.

PubMed

Mao, Shuai; Zhang, Xiaoxuan; Shao, Biying; Hu, Xiyan; Hu, Yanan; Li, Winny; Guo, Liheng; Zhang, Minzhou

2016-06-01

Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. Clinical Trials.gov: NCT02693795.

How long-lasting is the post-conflict slowing after incongruent trials? Evidence from the Stroop, Simon, and flanker tasks.

PubMed

Rey-Mermet, Alodie; Meier, Beat

2017-10-01

The purpose of the present study was to determine how long-lasting the post-conflict slowing following incongruent stimuli is. In previous research, incongruent stimuli have been used to induce a conflict because they have relevant features for two different response alternatives. So far, the post-conflict slowing following incongruent stimuli has mainly been assessed up to one trial. In the first two experiments, we assessed the persistence of the post-conflict slowing across several trials. To this end, we presented a few incongruent stimuli among non-conflict stimuli. The results showed a consistent slowing for the first few trials immediately following the incongruent trials. In addition, a sporadic slowing was still found on later trials. In two subsequent experiments, we investigated to what extent the infrequency of incongruent trials - rather than their conflict - induced this slowing. To determine this, we used the same design as in the first two experiments, but we presented non-conflict stimuli as infrequent stimuli. The results showed a slowing on one subsequent trial, ruling out the possibility that the post-conflict slowing following incongruent trials was only caused by infrequency. Together, the findings of the present study indicate that the conflict induced by incongruent trials can have a longer lasting impact on subsequent trials than previously thought.

Does self-management for return to work increase the effectiveness of vocational rehabilitation for chronic compensated musculoskeletal disorders? - Protocol for a randomised controlled trial

PubMed Central

2010-01-01

Background Musculoskeletal disorders are common and costly disorders to workers compensation and motor accident insurance systems and are a leading contributor to the burden of ill-health. In Australia, vocational rehabilitation is provided to workers to assist them to stay in, or return to work. Self-management training may be an innovative addition to improve health and employment outcomes from vocational rehabilitation. Methods/Design The research plan contains mixed methodology consisting of a single blind randomised controlled trial, an economic evaluation and qualitative research. Participants (n = 366) are volunteers with compensated musculoskeletal disorders of 3 months to 3 years in duration who were working at the time of the injury/onset of the chronic disorder. The trial tests the effectiveness of usual vocational rehabilitation plus the Chronic Disease Self-Management Program (CDSMP) to which two additional and newly-developed modules have been added, against vocational rehabilitation alone (control) The modules added to the CDSMP focus on how to navigate through compensation systems and manage the return to work process, and aim to be relevant to those in a vocational rehabilitation setting. The primary outcome of this study is readiness for return to work which will be evaluated using the Readiness for Return-to-Work scale. Secondary outcomes include return to work status, health efficacy (heiQ™ questionnaire) and general health status (SF-12v2® Health Survey). Measures will be taken at baseline, immediately post-intervention and at 6- and 12- months post-intervention by an independent assessor. An economic evaluation will compare the costs and outcomes between the intervention and control groups in terms of cost-effectiveness and a partial cost-benefit or cost analysis. The impact of the intervention will also be evaluated qualitatively, in terms of its acceptability to stakeholders. Discussion This article describes the protocol for a single blind randomised controlled trial with a one year follow-up. The results will provide evidence for the addition or not of self-management training within vocational rehabilitation for chronic compensated musculoskeletal disorders. Trial Registration Australia and New Zealand Clinical Trials Registry ACTRN12609000843257 PMID:20534168

Homeopathic Arnica montana for post-tonsillectomy analgesia: a randomised placebo control trial.

PubMed

Robertson, A; Suryanarayanan, R; Banerjee, A

2007-01-01

To evaluate the efficacy of Homeopathic Arnica in reducing the morbidity following tonsillectomy. Randomised double blind, placebo controlled trial at a tertiary referral centre. 190 patients over the age of 18 undergoing tonsillectomy were randomised into intervention and control groups receiving either Arnica 30c or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work. 111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p < 0.05. The two groups did not differ significantly on analgesic consumption or any of the other secondary outcome measures (number of post-operative visits to GP, use of antibiotics and secondary haemorrhage readmissions). The results of this trial suggest that Arnica montana given after tonsillectomy provides a small, but statistically significant, decrease in pain scores compared to placebo.

A Systems Biology Approach Investigating the Effect of Probiotics on the Vaginal Microbiome and Host Responses in a Double Blind, Placebo-Controlled Clinical Trial of Post-Menopausal Women

PubMed Central

Bisanz, Jordan E.; Seney, Shannon; McMillan, Amy; Vongsa, Rebecca; Koenig, David; Wong, LungFai; Dvoracek, Barbara; Gloor, Gregory B.; Sumarah, Mark; Ford, Brenda; Herman, Dorli; Burton, Jeremy P.; Reid, Gregor

2014-01-01

A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains. Trial Registration ClinicalTrials.gov NCT02139839 PMID:25127240

Cognitive-behavioural therapy does not meaningfully reduce depression in most people with epilepsy: a systematic review of clinically reliable improvement.

PubMed

Noble, Adam J; Reilly, James; Temple, James; Fisher, Peter L

2018-05-07

Psychological treatment is recommended for depression and anxiety in those with epilepsy. This review used standardised criteria to evaluate, for the first time, the clinical relevance of any symptom change these treatments afford patients. Databases were searched until March 2017 for relevant trials in adults. Trial quality was assessed and trial authors asked for individual participants' pre-treatment and post-treatment distress data. Jacobson's methodology determined the proportion in the different trial arms demonstrating reliable symptom change on primary and secondary outcome measures and its direction. Search yielded 580 unique articles; only eight eligible trials were identified. Individual participant data for five trials-which included 398 (85%) of the 470 participants randomised by the trials-were received. The treatments evaluated lasted ~7 hours and all incorporated cognitive-behavioural therapy (CBT). Depression was the primary outcome in all; anxiety a secondary outcome in one. On average, post-treatment assessments occurred 12 weeks following randomisation; 2 weeks after treatment had finished. There were some limitations in how trials were conducted, but overall trial quality was 'good'. Pooled risk difference indicated likelihood of reliable improvement in depression symptoms was significantly higher for those randomised to CBT. The extent of gain was though low-the depressive symptoms of most participants (66.9%) receiving CBT were 'unchanged' and 2.7% 'reliably deteriorated'. Only 30.4% made a 'reliable improvement. This compares with 10.2% of participants in the control arms who 'reliably improved' without intervention. The effect of the treatments on secondary outcome measures, including anxiety, was also low. Existing CBT treatments appear to have limited benefit for depression symptoms in epilepsy. Almost 70% of people with epilepsy do not reliably improve following CBT. Only a limited number of trials have though been conducted in this area and there remains a need for large, well-conducted trials. © 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.

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

The impact of an employee wellness programme in clothing/textile manufacturing companies: a randomised controlled trial.

PubMed

Edries, Naila; Jelsma, Jennifer; Maart, Soraya

2013-01-11

The prevalence of health risk behaviours is growing amongst South African employees. Health risk behaviours have been identified as a major contributor to reduced health related quality of life (HRQoL) and the increased prevalence of non-communicable diseases. Worksite wellness programmes promise to promote behaviour changes amongst employees and to improve their HRQoL. The aim of this study was to evaluate the short-term effects of an employee wellness programme on HRQoL, health behaviour change, body mass index (BMI) and absenteeism amongst clothing and textile manufacturing employees. The study used a randomised control trial design. The sample consisted of 80 subjects from three clothing manufacturing companies in Cape Town, South Africa. The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks. The control group received a once-off health promotion talk and various educational pamphlets, with no further intervention. Measurements were recorded at baseline and at six weeks post-intervention. Outcome measures included the EQ-5D, Stanford Exercise Behaviours Scale, body mass index and absenteeism.Data was analysed with the Statistica-8 software program. Non-parametric tests were used to evaluate the differences in the medians between the two groups and to determine the level of significance. The Sign test was used to determine the within group changes. The Mann-Whitney U test was used to determine the difference between the two groups. At six weeks post intervention the experimental group (39 subjects) demonstrated improvement in almost every parameter. In contrast, apart from an overall decrease in time off work and a reduction in BMI for all study participants, there was no significant change noted in the behaviour of the control group (41 subjects). Seventy percent of the experimental group had improved HRQoL EQ-5D VAS scores post intervention, indicating improved perceived HRQoL. In comparison, only 58% of the control group had improved HRQoL EQ-5D VAS scores post intervention. There was no significant difference between the two groups at baseline or at six weeks post intervention. An employee wellness programme based on the principles of CBT combined with weekly aerobic exercise class was beneficial in improving the perceived HRQoL and changing health-related behaviours of clothing manufacturing employees. However, it cannot be concluded that the EWP was more effective than the once off health promotion talk as no significant changes were noted between the two groups at 6-weeks post intervention.This trial has been registered with ClinicalTrials.gov (trial registration number NCT01625039).

The impact of an employee wellness programme in clothing/textile manufacturing companies: a randomised controlled trial

PubMed Central

2013-01-01

Background The prevalence of health risk behaviours is growing amongst South African employees. Health risk behaviours have been identified as a major contributor to reduced health related quality of life (HRQoL) and the increased prevalence of non-communicable diseases. Worksite wellness programmes promise to promote behaviour changes amongst employees and to improve their HRQoL. The aim of this study was to evaluate the short-term effects of an employee wellness programme on HRQoL, health behaviour change, body mass index (BMI) and absenteeism amongst clothing and textile manufacturing employees. Methods The study used a randomised control trial design. The sample consisted of 80 subjects from three clothing manufacturing companies in Cape Town, South Africa. The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks. The control group received a once-off health promotion talk and various educational pamphlets, with no further intervention. Measurements were recorded at baseline and at six weeks post-intervention. Outcome measures included the EQ-5D, Stanford Exercise Behaviours Scale, body mass index and absenteeism. Data was analysed with the Statistica-8 software program. Non-parametric tests were used to evaluate the differences in the medians between the two groups and to determine the level of significance. The Sign test was used to determine the within group changes. The Mann–Whitney U test was used to determine the difference between the two groups. Results At six weeks post intervention the experimental group (39 subjects) demonstrated improvement in almost every parameter. In contrast, apart from an overall decrease in time off work and a reduction in BMI for all study participants, there was no significant change noted in the behaviour of the control group (41 subjects). Seventy percent of the experimental group had improved HRQoL EQ-5D VAS scores post intervention, indicating improved perceived HRQoL. In comparison, only 58% of the control group had improved HRQoL EQ-5D VAS scores post intervention. There was no significant difference between the two groups at baseline or at six weeks post intervention. Conclusion An employee wellness programme based on the principles of CBT combined with weekly aerobic exercise class was beneficial in improving the perceived HRQoL and changing health-related behaviours of clothing manufacturing employees. However, it cannot be concluded that the EWP was more effective than the once off health promotion talk as no significant changes were noted between the two groups at 6-weeks post intervention.This trial has been registered with ClinicalTrials.gov (trial registration number NCT01625039). PMID:23311458

Adaptation of adhesive post and cores to dentin after in vitro occlusal loading: evaluation of post material influence.

PubMed

Dietschi, Dider; Ardu, Stefano; Rossier-Gerber, Anne; Krejci, Ivo

2006-12-01

Fatigue resistance of post and cores is critical to the long term behavior of restored nonvital teeth. The purpose of this in vitro trial was to evaluate the influence of the post material's physical properties on the adaptation of adhesive post and core restorations after cyclic mechanical loading. Composite post and cores were made on endodontically treated deciduous bovine teeth using 3 anisotropic posts (made of carbon, quartz, or quartz-and-carbon fibers) and 3 isotropic posts (zirconium, stainless steel, titanium). Specimens were submitted to 3 successive loading phases--250,000 cycles at 50 N, 250,000 at 75 N, and 500,000 at 100 N--at a rate of 1.5 Hz. Restoration adaptation was evaluated under SEM, before and during loading (margins) and after test completion (margins and internal interfaces). Six additional samples were fabricated for the characterization of interface micromorphology using confocal microscopy. Mechanical loading increased the proportion of marginal gaps in all groups; carbon fiber posts presented the lowest final gap proportion (7.11%) compared to other stiffer metal-ceramic or softer fiber posts (11.0% to 19.1%). For internal adaptation, proportions of debonding between dentin and core or cement varied from 21.69% (carbon post) to 47.37% (stainless steel post). Debonding at the post-cement interface occurred only with isotropic materials. Confocal microscopy observation revealed that gaps were generally associated with an incomplete hybrid layer and reduced resin tags. Regardless of their rigidity, metal and ceramic isotropic posts proved less effective than fiber posts at stabilizing the post and core structure in the absence of the ferrule effect, due to the development of more interfacial defects with either composite or dentin.

Mind the gap: An empirical study of post-trial access in HIV biomedical prevention trials.

PubMed

Haire, Bridget; Jordens, Christopher

2015-08-01

The principle of providing post-trial access for research participants to successful products of that research is widely accepted and has been enshrined in various declarations and guidelines. While recent ethical guidelines recognise that the responsibility to provide post-trial access extends to sponsors, regulators and government bodies as well as to researchers, it is the researchers who have the direct duty of care to participants. Researchers may thus need to act as advocates for trial participants, especially where government bodies, sponsors, and regulatory bodies have complex interests vested in decisions about whether or not new interventions are made available, how, and to whom. This paper provides an empirical account of post-trial access in the context of HIV prevention research. It describes both access to the successful products of research and the provision antiretroviral drugs for trial participants who acquire HIV. First, we provide evidence that, in the current system, there is considerable variation in the duration and timeliness of access. We then argue that by analysing the difficulties faced by researchers to this point, and their efforts to meet this obligation, much can be learned about how to secure post-trial access in HIV biomedical preventions trials. While researchers alone have a limited obligation, their advocacy on behalf of trial participants may be necessary to call the other parties to account. © 2013 John Wiley & Sons Ltd.

Soil intake of lactating dairy cows in intensive strip grazing systems.

PubMed

Jurjanz, S; Feidt, C; Pérez-Prieto, L A; Ribeiro Filho, H M N; Rychen, G; Delagarde, R

2012-08-01

Involuntary soil intake by cows on pasture can be a potential route of entry for pollutants into the food chain. Therefore, it appears necessary to know and quantify factors affecting soil intake in order to ensure the food safety in outside rearing systems. Thus, soil intake was determined in two Latin square trials with 24 and 12 lactating dairy cows. In Trial 1, the effect of pasture allowance (20 v. 35 kg dry matter (DM) above ground level/cow daily) was studied for two sward types (pure perennial ryegrass v. mixed perennial ryegrass-white clover) in spring. In Trial 2, the effect of pasture allowance (40 v. 65 kg DM above ground level/cow daily) was studied at two supplementation levels (0 or 8 kg DM of a maize silage-based supplement) in autumn. Soil intake was determined by the method based on acid-insoluble ash used as an internal marker. The daily dry soil intake ranged, between treatments, from 0.17 to 0.83 kg per cow in Trial 1 and from 0.15 to 0.85 kg per cow in Trial 2, reaching up to 1.3 kg during some periods. In both trials, soil intake increased with decreasing pasture allowance, by 0.46 and 0.15 kg in Trials 1 and 2, respectively. In Trial 1, this pasture allowance effect was greater on mixed swards than on pure ryegrass swards (0.66 v. 0.26 kg reduction of daily soil intake between medium and low pasture allowance, respectively). In Trial 2, the pasture allowance effect was similar at both supplementation levels. In Trial 2, supplemented cows ate much less soil than unsupplemented cows (0.20 v. 0.75 kg/day, respectively). Differences in soil intake between trials and treatments can be related to grazing conditions, particularly pre-grazing and post-grazing sward height, determining at least in part the time spent grazing close to the ground. A post-grazing sward height lower than 50 mm can be considered as a critical threshold. Finally, a dietary supplement and a low grazing pressure, that is, high pasture allowance increasing post-grazing sward height, would efficiently limit the risk for high level of soil intake, especially when grazing conditions are difficult. Pre-grazing and post-grazing sward heights, as well as faecal crude ash concentration appear to be simple and practical tools for evaluating the risk for critical soil intake in grazing dairy cows.

Pharmacist leadership in ICU quality improvement: coordinating spontaneous awakening and breathing trials.

PubMed

Stollings, Joanna L; Foss, Julie J; Ely, E Wesley; Ambrose, Anna M; Rice, Todd W; Girard, Timothy D; Wheeler, Arthur P

2015-08-01

Coordinating efforts across disciplines in the intensive care unit is a key component of quality improvement (QI) efforts. Spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) are considered key components of guidelines, yet unfortunately are often not done or coordinated properly. To determine if a pharmacist-driven awakening and breathing coordination (ABC) QI program would improve compliance (ie, process measures) as compared with the previous protocol, which did not involve pharmacists. The QI program included pharmacist-led education, daily discussion on rounds, and weekly performance reports to staff. Using a pre-QI versus during-QI versus post-QI intervention design, we compared data from 500 control ventilator-days (pre-QI period) versus 580 prospective ventilator-days (during-QI period). We then evaluated the sustainability of the QI program in 216 ventilator-days in the post-QI period. SAT safety screens were performed on only 20% pre-QI patient-days versus 97% of during-QI patient-days (P < 0.001) and 100% of post-QI patient-days (P = 0.25). The rates of passing the SAT safety screen in pre-QI and during-QI periods were 63% versus 78% (P = 0.03) and 81% in the post-QI period (P = 0.86). The rates of SATs among eligible patients on continuous infusions were only 53% in the pre-QI versus 85% in the during-QI (P = 0.0001) and 87% in the post-QI (P = 1) periods. In this QI initiative, a pharmacist-driven, interdisciplinary ABC protocol significantly improved process measures compliance, comparing the pre-QI versus during-QI rates of screening, performing, and coordinating SAT and SBTs, and these results were sustained in the 8-month follow-up period post-QI program. © The Author(s) 2015.

Gabexate in the prophylaxis of post-ERCP pancreatitis: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Minghua; Chen, Yongping; Yang, Xinjun; Li, Ji; Zhang, Youcai; Zeng, Qiqiang

2007-02-12

Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography and the benefit of its pharmacological treatment is unclear. Although prophylactic use of gabexate for the reduction of pancreatic injury after ERCP has been evaluated, the discrepancy about gabexate's beneficial effect on pancreatic injury still exists. This study aimed to evaluate the effectiveness and safety of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We employed the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials (RCTs) of gabexate in the prevention of post-ERCP pancreatitis (PEP) including three RCTs conducted in Italy and one in China. All of the four RCTs were of high quality. When the RCTs were analyzed, odds ratios (OR) for gabexate mesilate were 0.67 [95% CI (0.31 to approximately 1.47), p = 0.32] for PEP, 3.78 [95% CI (0.62 to approximately 22.98), p = 0.15] for severe PEP, 0.68 [95% CI (0.19 to approximately 2.43), p = 0.56] for the case-fatality of PEP, 0.88 [95% CI (0.72 to approximately 1.07), p = 0.20] for post-ERCP hyperamylasemia, 0.69 [95% CI (0.39 to approximately 1.21), p = 0.19] for post-ERCP abdominal pain, thus indicating no beneficial effects of gabexate on acute pancreatitis, the death rate of PEP, hyperamylasemia and abdominal pain. No evidence of publication bias was found. Gabexate mesilate can not prevent the pancreatic injury after ERCP. It is not recommended for the use of gabexate mesilate in the prophylaxis of PEP.

The fate of prospective spine studies registered on www.ClinicalTrials.gov.

PubMed

Ohnmeiss, Donna D

2015-03-01

There has been concern expressed about research ethics with respect to not fully reporting data collected during clinical studies. One site available for all clinical trials is ClinicalTrials.gov. The original purpose of this site was to facilitate patients seeking a trial for the treatment of their particular condition. The internationally available site offers general information about the study, sponsor name, principal investigator, patient selection criteria, enrollment goal, study design, outcome measures, participating centers, initiation date, date posted, date completed, and other pertinent data. The site can be used to identify studies conducted for a particular condition or intervention. The purpose of this study was to investigate the fate of spine-related studies registered on www.ClinicalTrials.gov, with particular focus on the publication rate of completed trials. Analysis and classification of clinical studies posted on an international research registry Web page and literature search for related publications. Not applicable. The primary outcome measure was publication of the study registered on ClinicalTrials.gov. Multiple searches were conducted on ClinicalTrials.gov Web site to identify studies related to commonly treated spinal conditions, including herniated disc, degenerative disc disease, stenosis, and spondylolisthesis. Studies related to tumors, fractures, or that included nonspine conditions were not included. For studies classified as completed more than 18 months before this review, literature searches were conducted to determine if the results of the study had been published and factors related to publication. The author has no financial conflict related to this work. There were 263 spine-related studies identified from searches on the ClinicalTrials.gov site. Data on the site had the studies classified as follows: 72 completed, 70 active, not recruiting (generally indicates collecting follow-up data), 74 recruiting, 11 recruiting by invitation, 13 not yet recruiting, 18 terminated, 4 withdrawn, and 1 suspended. Among the 72 studies indicated to be completed, 28 (38.9%) have been published. The mean time to publish was 27.9 months from the date of completion. Among unpublished studies, the mean length of time from study completion to the preparation of this article was 62.0 months. There was no difference in the likelihood of publication based on the geographic region of study origin or whether the study was registered before or after initiation. There were statistically significant relationships between the publication rate and the funding type as well as the research type (p<.05) with industrial-funded studies and those evaluating devices having a lower publication rate and those that were funded by a federal agency and comparing surgery to nonoperative care had the highest publication rates. Although the 38.9% publication rate for spine-related studies found in this study appears low, it is in line with other studies reporting a 22.8% publication rate for arthroplasty trials and 43.2% for orthopedic trauma trials. In addition to ClinicalTrials.gov Web site fulfilling its original goal of providing patients information about clinical studies, it can also provide a means of tracking publication of prospective studies, changes to protocols, matching publication content to posted study design, and others and raise queries concerning the reasons for not publishing what appear to be well-designed studies. The posting of spine studies before initiation can increase transparency and ability to evaluate clinical trials in spine. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluating Adaptation of a Cancer Clinical Trial Decision Aid for Rural Cancer Patients: A Mixed-Methods Approach.

PubMed

Pathak, Swati; George, Nerissa; Monti, Denise; Robinson, Kathy; Politi, Mary C

2018-06-03

Rural-residing cancer patients often do not participate in clinical trials. Many patients misunderstand cancer clinical trials and their rights as participant. The purpose of this study is to modify a previously developed cancer clinical trials decision aid (DA), incorporating the unique needs of rural populations, and test its impact on knowledge and decision outcomes. The study was conducted in two phases. Phase I recruited 15 rural-residing cancer survivors in a qualitative usability study. Participants navigated the original DA and provided feedback regarding usability and implementation in rural settings. Phase II recruited 31 newly diagnosed rural-residing cancer patients. Patients completed a survey before and after using the revised DA, R-CHOICES. Primary outcomes included decisional conflict, decision self-efficacy, knowledge, communication self-efficacy, and attitudes towards and willingness to consider joining a trial. In phase I, the DA was viewed positively by rural-residing cancer survivors. Participants provided important feedback about factors rural-residing patients consider when thinking about trial participation. In phase II, after using R-CHOICES, participants had higher certainty about their choice (mean post-test = 3.10 vs. pre-test = 2.67; P = 0.025) and higher trial knowledge (mean percentage correct at post-test = 73.58 vs. pre-test = 57.77; P < 0.001). There was no significant change in decision self-efficacy, communication self-efficacy, and attitudes towards or willingness to join trials. The R-CHOICES improved rural-residing patients' knowledge of cancer clinical trials and reduced conflict about making a trial decision. More research is needed on ways to further support decisions about trial participation among this population.

Program to Optimize Simulated Trajectories II (POST2) Surrogate Models for Mars Ascent Vehicle (MAV) Performance Assessment

NASA Technical Reports Server (NTRS)

Zwack, M. R.; Dees, P. D.; Thomas, H. D.; Polsgrove, T. P.; Holt, J. B.

2017-01-01

The primary purpose of the multiPOST tool is to enable the execution of much larger sets of vehicle cases to allow for broader trade space exploration. However, this exploration is not achieved solely with the increased case throughput. The multiPOST tool is applied to carry out a Design of Experiments (DOE), which is a set of cases that have been structured to capture a maximum amount of information about the design space with minimal computational effort. The results of the DOE are then used to fit a surrogate model, ultimately enabling parametric design space exploration. The approach used for the MAV study includes both DOE and surrogate modeling. First, the primary design considerations for the vehicle were used to develop the variables and ranges for the multiPOST DOE. The final set of DOE variables were carefully selected in order to capture the desired vehicle trades and take into account any special considerations for surrogate modeling. Next, the DOE sets were executed through multiPOST. Following successful completion of the DOE cases, a manual verification trial was performed. The trial involved randomly selecting cases from the DOE set and running them by hand. The results from the human analyst's run and multiPOST were then compared to ensure that the automated runs were being executed properly. Completion of the verification trials was then followed by surrogate model fitting. After fits to the multiPOST data were successfully created, the surrogate models were used as a stand-in for POST2 to carry out the desired MAV trades. Using the surrogate models in lieu of POST2 allowed for visualization of vehicle sensitivities to the input variables as well as rapid evaluation of vehicle performance. Although the models introduce some error into the output of the trade study, they were very effective at identifying areas of interest within the trade space for further refinement by human analysts. The next section will cover all of the ground rules and assumptions associated with DOE setup and multiPOST execution. Section 3.1 gives the final DOE variables and ranges, while section 3.2 addresses the POST2 specific assumptions. The results of the verification trials are given in section 4. Section 5 gives the surrogate model fitting results, including the goodness-of-fit metrics for each fit. Finally, the MAV specific results are discussed in section 6.

Lavender-thymol as a new topical aromatherapy preparation for episiotomy: A randomised clinical trial.

PubMed

Marzouk, T; Barakat, R; Ragab, A; Badria, F; Badawy, A

2015-01-01

The objective of this study was to evaluate the effectiveness of topical lavender-thymol in promoting episiotomy healing. This placebo-controlled, single-blinded, randomised clinical trial involved 60 primiparous women. REEDA score was used to evaluate the outcome of the trial. On the 7th post-partum day, women in Placebo-treated group had worse Redness, Edema, Ecchymosis, Discharge and Approximation (REEDA) score of 3.93 ± 3.65 compared with those in Lavender-thymol-treated group (2.03 ± 1.7) with significant difference (P = 0.013). Visual analogue Scale (VAS) score for pain at episiotomy in Lavender-thymol-treated group was 3.5 ± 1.9, whereas in Placebo-treated group it was 2.1 ± 2.2 (p = 0.011) for dyschezia, 3.8 ± 1.7 and 2.8 ± 1.6 in Placebo- and Lavender-thymol-treated women, respectively (p = 0.023). At 7th post-partum week, dyspareunia was more severe in Placebo-treated group compared with that in Lavender-thymol-treated group (5.3 ± 2.7 vs 2.7 ± 1.5 and p < 0.001). Topical aromatherapy using lavender-thymol was highly effective, suitable and safe for episiotomy wound care with little or no expected side effects compared with that using placebo.

Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial.

PubMed

Chua, Seng; Gupta, Sarika; Curnow, Jennifer; Gidaszewski, Beata; Khajehei, Marjan; Diplock, Hayley

2017-12-19

Acute post-partum anaemia can be associated with significant morbidity including a predisposition for postnatal depression. Lack of clear practice guidelines means a number of women are treated with multiple blood transfusions. Intravenous iron has the potential to limit the need for multiple blood transfusions but its role in the post-partum setting is unclear. IIBAPPA is a multi-centre randomised non-inferiority trial. Women with a primary post-partum haemorrhage (PPH) >1000 mL and resultant haemoglobin (Hb) 5.5-8.0 g/dL after resuscitation with ongoing symptomatic anaemia who are otherwise stable (no active bleeding) are eligible to participate. Patients with sepsis or conditions necessitating rapid Hb restoration are excluded. Eligible participants are randomised to receive a blood transfusion or a single dose of intravenous iron polymaltose calculated using the Ganzoni formula. Primary outcome measures include Hb, Ferritin and C-Reactive Protein levels on Day 7. Secondary outcomes evaluate (i) Hb, Ferritin and CRP levels on Day 14, 28, (ii) anaemia symptoms on Day 0, 7, 14 and 28 using structured health related quality of life questionnaires, (iii) treatment safety by assessing adverse reactions and infection endpoints and (iv) the quantitative impact of anaemia on breast feeding quality using a hospital designed questionnaire. If equivalence in Hb and ferritin levels, symptom scores and safety endpoints is demonstrated, intravenous iron may become the preferred treatment for women with acute post-partum anaemia to minimise transfusion reactions and costs. Australian and New Zealand Clinical Trials Registry: ACTRN12615001370594 on 16th December, 2015 (prospective approval).

En Route Air Traffic Control Input Devices for the Next Generation

NASA Technical Reports Server (NTRS)

Mainini, Matthew J.

2010-01-01

The purpose of this study was to investigate the usefulness of different input device configurations when trial planning new routes for aircraft in an advanced simulation of the en route workstation. The task of trial planning is one of the futuristic tools that is performed by the graphical manipulation of an aircraft's trajectory to reroute the aircraft without voice communication. In this study with two input devices, the FAA's current trackball and a basic optical computer mouse were evaluated with "pick" button in a click-and-hold state and a click-and-release state while the participant dragged the trial plan line. The trial plan was used for three different conflict types: Aircraft Conflicts, Weather Conflicts, and Aircraft + Weather Conflicts. Speed and accuracy were the primary dependent variables. Results indicate that the mouse conditions were significantly faster than the trackball conditions overall with no significant loss of accuracy. Several performance ratings and preference ratings were analyzed from post-run and post-simulation questionnaires. The release conditions were significantly more useful and likable than the hold conditions. The results suggest that the mouse in the release button state was the fastest and most well liked device configuration for trial planning in the en route workstation. Keywords-input devices, en route, controller, workstation, mouse, trackball, NextGen

Impact on learning of an e-learning module on leukaemia: a randomised controlled trial.

PubMed

Morgulis, Yuri; Kumar, Rakesh K; Lindeman, Robert; Velan, Gary M

2012-05-28

e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group's evaluation of the module was overwhelmingly positive. A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

Oncology trial abstracts showed suboptimal improvement in reporting: a comparative before-and-after evaluation using CONSORT for Abstract guidelines.

PubMed

Ghimire, Saurav; Kyung, Eunjung; Lee, Heeyoung; Kim, Eunyoung

2014-06-01

The aims of this study were to evaluate the quality of randomized controlled trial (RCT) abstracts published in the field of oncology and identify characteristics associated with better reporting quality. All phase III trials published during 2005-2007 [before Consolidated Standards of Reporting Trials (CONSORT)] and 2010-2012 (after CONSORT) were searched electronically in MEDLINE/PubMed and retrieved for review using an 18-point overall quality score (OQS) for reporting based on the CONSORT for Abstract guidelines. Descriptive statistics followed by multivariate linear regression were used to identify features associated with improved reporting quality. The mean OQS was 8.2 (range: 5-13; 95% confidence interval (CI): 8.0, 8.3) and 9.9 (range: 5-18; 95% CI: 9.7, 10.2) in the pre- and post-CONSORT periods, respectively. The method for random sequence generation, allocation concealment, blinding details, and funding sources were missing in pre-CONSORT abstracts and insufficiently reported (<20%) in post-CONSORT abstracts. A high impact factor (P < 0.001) and the journal of publication (P < 0.001) were independent factors that were significantly associated with higher reporting quality on multivariate analysis. The reporting quality of RCT abstracts in oncology showed suboptimal improvement over time. Thus, stricter adherence to the CONSORT for Abstract guidelines is needed to improve the reporting quality of RCT abstracts published in oncology. Copyright © 2014 Elsevier Inc. All rights reserved.

Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

PubMed

Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

2016-02-01

We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pilot randomized controlled trial of dialectical behavior therapy group skills training for ADHD among college students.

PubMed

Fleming, Andrew P; McMahon, Robert J; Moran, Lyndsey R; Peterson, A Paige; Dreessen, Anthony

2015-03-01

ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications.

Is the large simple trial design used for comparative, post-approval safety research? A review of a clinical trials registry and the published literature.

PubMed

Reynolds, Robert F; Lem, Joanna A; Gatto, Nicolle M; Eng, Sybil M

2011-10-01

Post-approval, observational drug safety studies face well known difficulties in controlling for confounding, particularly confounding by indication for drug use. A study design that addresses confounding by indication is the large simple trial (LST). LSTs are characterized by large sample sizes, often in the thousands; broad entry criteria consistent with the approved medication label; randomization based on equipoise, i.e. neither physician nor patient believes that one treatment option is superior; minimal, streamlined data collection requirements; objectively-measured endpoints (e.g. death, hospitalization); and follow-up that minimizes interventions or interference with normal clinical practice. In theory then, the LST is a preferred study design for drug and vaccine safety research because it controls for biases inherent to observational research while still providing results that are generalizable to 'real-world' use. To evaluate whether LSTs are used for comparative safety evaluation and if the design is, in fact, advantageous compared with other designs, we conducted a review of the published literature (1949 through 31 December 2010) and the ClinicalTrials.gov registry (2000 through 31 December 2010). Thirteen ongoing or completed safety LSTs were identified. The design has rarely been used in comparative drug safety research, which is due to the operational, financial and scientific hurdles of implementing the design. The studies that have been completed addressed important clinical questions and, in some cases, led to re-evaluation of medical practice. We conclude the design has demonstrated utility for comparative safety research of medicines and vaccines if the necessary scientific and operational conditions for its use are met.

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.

Rehab-let: touchscreen tablet for self-training impaired dexterity post stroke: study protocol for a pilot randomized controlled trial.

PubMed

Rand, Debbie; Zeilig, Gabi; Kizony, Rachel

2015-06-18

Impaired dexterity of the weaker upper extremity is common post stroke and it is recommended that these individuals practice many repetitions of movement to regain function. However, stroke rehabilitation methods do not achieve the required intensity to be effective. Touchscreen tablet technology may be used as a motivating tool for self-training impaired dexterity of the weaker upper extremity post stroke. Rehab-let is a self-training protocol utilizing game apps on a touchscreen for practicing movement of the weaker upper extremity. We will conduct a pilot randomized controlled trial to assess Rehab-let compared to traditional self-training to improve dexterity of the weaker hand, and to increase self-training time and satisfaction in individuals with subacute stroke. Forty individuals with stroke undergoing subacute rehabilitation will be randomly allocated to Rehab-let or a traditional self-training program using therapeutic aids such as balls, blocks and pegs. All participants will be requested to perform self-training for 60 minutes a day, 5 times a week for 4 weeks. Dexterity assessed by The Nine Hole Peg Test is the main outcome measure. Assessments will be administered pre and post the self-training intervention by assessors blind to the group allocation. The outcomes of this study will inform the design of a fully powered randomized controlled trial to evaluate the effectiveness of Rehab-let. If found to be effective, Rehab-let can be used during subacute rehabilitation to increase treatment intensity and improve dexterity. Potentially, Rehab-let can also be used after discharge and might be ideal for individuals with mild stroke who are often not referred to formal rehabilitation. Current Controlled Trials NCT02136433 registered on 17 September 2014.

The effect of post-exercise hydrotherapy on subsequent exercise performance and heart rate variability.

PubMed

Stanley, Jamie; Buchheit, Martin; Peake, Jonathan M

2012-03-01

We investigated the effect of hydrotherapy on time-trial performance and cardiac parasympathetic reactivation during recovery from intense training. On three occasions, 18 well-trained cyclists completed 60 min high-intensity cycling, followed 20 min later by one of three 10-min recovery interventions: passive rest (PAS), cold water immersion (CWI), or contrast water immersion (CWT). The cyclists then rested quietly for 160 min with R-R intervals and perceptions of recovery recorded every 30 min. Cardiac parasympathetic activity was evaluated using the natural logarithm of the square root of mean squared differences of successive R-R intervals (ln rMSSD). Finally, the cyclists completed a work-based cycling time trial. Effects were examined using magnitude-based inferences. Differences in time-trial performance between the three trials were trivial. Compared with PAS, general fatigue was very likely lower for CWI (difference [90% confidence limits; -12% (-18; -5)]) and CWT [-11% (-19; -2)]. Leg soreness was almost certainly lower following CWI [-22% (-30; -14)] and CWT [-27% (-37; -15)]. The change in mean ln rMSSD following the recovery interventions (ln rMSSD(Post-interv)) was almost certainly higher following CWI [16.0% (10.4; 23.2)] and very likely higher following CWT [12.5% (5.5; 20.0)] compared with PAS, and possibly higher following CWI [3.7% (-0.9; 8.4)] compared with CWT. The correlations between performance, ln rMSSD(Post-interv) and perceptions of recovery were unclear. A moderate correlation was observed between ln rMSSD(Post-interv) and leg soreness [r = -0.50 (-0.66; -0.29)]. Although the effects of CWI and CWT on performance were trivial, the beneficial effects on perceptions of recovery support the use of these recovery strategies.

Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients

PubMed Central

Morel, Véronique; Joly, Dominique; Villatte, Christine; Dubray, Claude; Durando, Xavier; Daulhac, Laurence; Coudert, Catherine; Roux, Delphine; Pereira, Bruno; Pickering, Gisèle

2016-01-01

Background Neuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life. Method A randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy. Results Data analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported. Conclusions This study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy. Trial Registration Clinicaltrials.gov NCT01536314 PMID:27050431

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial

PubMed Central

Rushton, Alison; Goodwin, Peter C.

2015-01-01

Objectives To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. Design and Setting A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. Participants Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. Interventions Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. Main Outcome Measures Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. Results At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. Conclusions Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome. Trial Registration ISRCTN registry 33808269 PMID:26562660

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

Evaluating a multicomponent social behaviour change communication strategy to reduce intimate partner violence among married couples: study protocol for a cluster randomized trial in Nepal.

PubMed

Clark, Cari Jo; Spencer, Rachael A; Shrestha, Binita; Ferguson, Gemma; Oakes, J Michael; Gupta, Jhumka

2017-01-13

Intimate partner violence (IPV) is a significant public health issue that affects 1 in 3 women globally and a similarly large number of women in Nepal. Over the past decade, important policy and programmatic steps have been taken to address violence against women in Nepal. There remains a dearth of evidence on the effectiveness of primary violence prevention strategies. The Change Starts at Home study begins to fill this gap by utilizing a multi-component social behaviour change communication (SBCC) strategy involving a radio drama and community mobilization to shift attitudes, norms and behaviours that underpin IPV perpetration in Nepal. The study uses a concurrent mixed-methods design. The quantitative aspect of the evaluation is a pair-matched, repeated cross-sectional 2-armed, single-blinded cluster trial (RCT: N = 36 clusters, 1440 individuals), comparing a social behaviour change communication (SBCC) strategy to radio programming alone for its impact on physical and / or sexual IPV at the end of programming (12 months' post-baseline) and 6-months post the cessation of project activities (18-months post baseline). The qualitative aspects of the design include several longitudinal approaches to understand the impact of the intervention and to examine mechanisms of change including in-depth interviews with participants (N = 18 couples), and focus group discussions with community leaders (N = 3 groups), and family members of participants (N = 12 groups). Treatment effects will be estimated with generalized logistic mixed models specified to compare differences in primary outcome from baseline to 12-month follow-up, and baseline to 18-months follow-up in accordance with intention-to-treat principles. The study rigorously evaluates the effectiveness of a promising strategy to prevent IPV. The results of the trial will be immediately useful for governmental, nongovernmental, and donor funded programs targeting partner violence or social norms that underpin it. Findings of the study will also contribute to global knowledge on the effectiveness of media and community engagement as a primary prevention strategy for IPV. Trial was registered in clinicaltrials.gov, NCT02942433 , 10/13/2016, retrospectively registered.

Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors.

PubMed

Corbett, Teresa; Devane, Declan; Walsh, Jane C; Groarke, AnnMarie; McGuire, Brian E

2015-12-04

Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. Some evidence has been reported for interventions for fatigue during active treatment. However, to date, there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer. This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database. We will search the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and relevant sources of grey literature. Randomised controlled trials (RCTs) which have evaluated psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, will be included. Two review authors will independently extract data from the selected studies and assess the methodological quality using the Cochrane Collaboration Risk of Bias Tool. Most existing evidence on cancer-related fatigue is from those in active cancer treatment. This systematic review and meta-analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment. With the growing need for stage-specific research in cancer, this review seeks to highlight a gap in current practice and to strengthen the evidence base of randomised controlled trials in the area. PROSPERO CRD42014015219.

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

PubMed

Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

2017-10-01

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

Post-trial dopaminergic modulation of conditioned catalepsy: A single apomorphine induced increase/decrease in dopaminergic activation immediately following a conditioned catalepsy response can reverse/enhance a haloperidol conditioned and sensitized catalepsy response.

PubMed

Oliveira, Lucas Rangel; Dias, Flávia Regina Cruz; Santos, Breno Garone; Silva, Jade Leal Loureiro; Carey, Robert J; Carrera, Marinete Pinheiro

2016-09-15

Haloperidol can induce catalepsy and this drug effect can be conditioned as well as sensitized to contextual cues. We used a paired/unpaired Pavlovian conditioning protocol to establish haloperidol catalepsy conditioned and sensitized responses. Groups of rats were given 10 daily catalepsy tests following administration of vehicle (n=24) or haloperidol (1.0mg/kg) either paired (n=18) or unpaired (n=18) to testing. Subsequently, testing for conditioning was conducted and conditioning and sensitization of catalepsy were observed selectively in the paired group. Immediately following a second test for catalepsy conditioning, the groups were subdivided into 4 vehicle groups, 3 unpaired haloperidol groups and 3 paired haloperidol groups and were given one of three post-trial treatments (vehicle, 0.05mg/kg or 2.0mg/kg apomorphine). One day later the conditioned catalepsy test 3 was carried out and on the next day, a haloperidol challenge test was performed. The post-trial apomorphine treatments had major effects on the paired groups upon both conditioning and the haloperidol challenge test. The low dose apomorphine post-trial treatment enhanced both the conditioned and the haloperidol sensitized catalepsy responses. The high dose apomorphine post-trial treatment eliminated conditioned catalepsy and eliminated the initial acute catalepsy response to haloperidol that was induced in the vehicle control groups. These results demonstrate the sensitivity of conditioned drug cues to modification by increases/decreases in activity of the dopamine system in the immediate post-trial interval after a conditioning trial. This demonstration that post-trial dopaminergic drug treatments can modify conditioned drug behavior has broad implications for conditioned drug effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of post-remission therapy in patients aged 65–70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

PubMed Central

Itzykson, Raphael; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigne, Sylvie; Dombret, Hervé; Boissel, Nicolas

2011-01-01

Background There is no standard post-remission therapy in older patients with acute myeloid leukemia. Design and Methods From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy. Results Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy. Conclusions In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025) PMID:21459791

Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria.

PubMed

Itzykson, Raphael; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigne, Sylvie; Dombret, Hervé; Boissel, Nicolas

2011-06-01

There is no standard post-remission therapy in older patients with acute myeloid leukemia. From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy. Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy. In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025).

Low degree of satisfactory individual pain relief in post-operative pain trials.

PubMed

Geisler, A; Dahl, J B; Karlsen, A P H; Persson, E; Mathiesen, O

2017-01-01

The majority of clinical trials regarding post-operative pain treatment focuses on the average analgesic efficacy, rather than on efficacy in individual patients. It has been argued, that in acute pain trials, the underlying distributions are often skewed, which makes the average unfit as the only way to measure efficacy. Consequently, dichotomised, individual responder analyses using a predefined 'favourable' response, e.g. Visual Analogue Scale (VAS) pain scores ≤ 30, have recently been suggested as a more clinical relevant outcome. We re-analysed data from 16 randomised controlled trials of post-operative pain treatment and from meta-analyses of a systematic review regarding hip arthroplasty. The predefined success criterion was that at least 80% of patients in active treatment groups should obtain VAS < 30 at 6 and 24 h post-operatively. In the analysis of data from the randomised controlled trials, we found that at 6 h post-operatively, 50% (95% CI: 31-69) of patients allocated to active treatment reached the success criterion for pain at rest and 14% (95% CI: 5-34) for pain during mobilisation. At 24 h post-operatively, 60% (95% CI: 38-78) of patients allocated to active treatment reached the success criterion for pain at rest, and 15% (95% CI: 5-36) for pain during mobilisation. Similar results were found for trials from the meta-analyses. Our results indicate that for conventional, explanatory trials of post-operative pain, individual patient's achievement of a favourable response to analgesic treatment is rather low. Future pragmatic clinical trials should focus on both average pain levels and individual responder analyses in order to promote effective pain treatment at the individually patient level. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Registration status and outcome reporting of trials published in core headache medicine journals.

PubMed

Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy

NASA Astrophysics Data System (ADS)

Wangerin, Kristen A.; Muzi, Mark; Peterson, Lanell M.; Linden, Hannah M.; Novakova, Alena; Mankoff, David A.; E Kinahan, Paul

2017-05-01

We developed a method to evaluate variations in the PET imaging process in order to characterize the relative ability of static and dynamic metrics to measure breast cancer response to therapy in a clinical trial setting. We performed a virtual clinical trial by generating 540 independent and identically distributed PET imaging study realizations for each of 22 original dynamic fluorodeoxyglucose (18F-FDG) breast cancer patient studies pre- and post-therapy. Each noise realization accounted for known sources of uncertainty in the imaging process, such as biological variability and SUV uptake time. Four definitions of SUV were analyzed, which were SUVmax, SUVmean, SUVpeak, and SUV50%. We performed a ROC analysis on the resulting SUV and kinetic parameter uncertainty distributions to assess the impact of the variability on the measurement capabilities of each metric. The kinetic macro parameter, K i , showed more variability than SUV (mean CV K i   =  17%, SUV  =  13%), but K i pre- and post-therapy distributions also showed increased separation compared to the SUV pre- and post-therapy distributions (mean normalized difference K i   =  0.54, SUV  =  0.27). For the patients who did not show perfect separation between the pre- and post-therapy parameter uncertainty distributions (ROC AUC  <  1), dynamic imaging outperformed SUV in distinguishing metabolic change in response to therapy, ranging from 12 to 14 of 16 patients over all SUV definitions and uptake time scenarios (p  <  0.05). For the patient cohort in this study, which is comprised of non-high-grade ER+  tumors, K i outperformed SUV in an ROC analysis of the parameter uncertainty distributions pre- and post-therapy. This methodology can be applied to different scenarios with the ability to inform the design of clinical trials using PET imaging.

Adaptation of feedforward movement control is abnormal in patients with cervical dystonia and tremor.

PubMed

Avanzino, Laura; Ravaschio, Andrea; Lagravinese, Giovanna; Bonassi, Gaia; Abbruzzese, Giovanni; Pelosin, Elisa

2018-01-01

It is under debate whether the cerebellum plays a role in dystonia pathophysiology and in the expression of clinical phenotypes. We investigated a typical cerebellar function (anticipatory movement control) in patients with cervical dystonia (CD) with and without tremor. Twenty patients with CD, with and without tremor, and 17 healthy controls were required to catch balls of different load: 15 trials with a light ball, 25 trials with a heavy ball (adaptation) and 15 trials with a light ball (post-adaptation). Arm movements were recorded using a motion capture system. We evaluated: (i) the anticipatory adjustment (just before the impact); (ii) the extent and rate of the adaptation (at the impact) and (iii) the aftereffect in the post-adaptation phase. The anticipatory adjustment was reduced during adaptation in CD patients with tremor respect to CD patients without tremor and controls. The extent and rate of adaptation and the aftereffect in the post-adaptation phase were smaller in CD with tremor than in controls and CD without tremor. Patients with cervical dystonia and tremor display an abnormal predictive movement control. Our findings point to a possible role of cerebellum in the expression of a clinical phenotype in dystonia. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Hydrotherapy as a recovery strategy after exercise: a pragmatic controlled trial.

PubMed

Cuesta-Vargas, Antonio I; Travé-Mesa, Alvaro; Vera-Cabrera, Alberto; Cruz-Terrón, Dario; Castro-Sánchez, Adelaida M; Fernández-de-las-Peñas, Cesar; Arroyo-Morales, Manuel

2013-07-18

Our aim was to evaluate the recovery effects of hydrotherapy after aerobic exercise in cardiovascular, performance and perceived fatigue. A pragmatic controlled repeated measures; single-blind trial was conducted. Thirty-four recreational sportspeople visited a Sport-Centre and were assigned to a Hydrotherapy group (experimental) or rest in a bed (control) after completing a spinning session. Main outcomes measures including blood pressure, heart rate, handgrip strength, vertical jump, self-perceived fatigue, and body temperature were assessed at baseline, immediately post-exercise and post-recovery. The hypothesis of interest was the session*time interaction. The analysis revealed significant session*time interactions for diastolic blood pressure (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy resulted in recovered heart rate and diastolic blood pressure similar to baseline values after the spinning session. Further, hydrotherapy resulted in decreased self-perceived fatigue after the spinning session. Our results support that hydrotherapy is an adequate strategy to facilitate cardiovascular recovers and perceived fatigue, but not strength, after spinning exercise. ClinicalTrials.gov Identifier: NCT01765387.

[Declaration of the Chilean Academy of Medicine of Law 20.850 "On clinical trials of pharmaceutical products and medical devices" and of the bylaw that will regulate its application].

PubMed

López, Gloría; Valdés, Gloría; Roessler, Emilio; Valdivieso, Vicente

2017-04-01

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1) The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2) The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3) Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians' interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients' ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.

Mechanochemical endovenous ablation versus radiofrequency ablation in the treatment of primary small saphenous vein insufficiency (MESSI trial): study protocol for a randomized controlled trial.

PubMed

Boersma, Doeke; van Eekeren, Ramon R J P; Kelder, Hans J C; Werson, Debora A B; Holewijn, Suzanne; Schreve, Michiel A; Reijnen, Michel M P J; de Vries, Jean Paul P M

2014-10-29

Minimally invasive endothermal techniques, for example, radiofrequency ablation (RFA), have revolutionized the treatment of insufficient truncal veins and are associated with an excellent outcome. The use of thermal energy requires the instillation of tumescent anesthesia around the vein. Mechanochemical endovenous ablation (MOCA™) combines mechanical endothelial damage, using a rotating wire, with simultaneous infusion of a liquid sclerosans. Tumescent anesthesia is not required as no heat is used. Prospective studies using MOCA™ in both great and small saphenous veins showed good anatomical and clinical results with fast postoperative recovery. The MESSI trial (Mechanochemical Endovenous ablation versus radiofrequency ablation in the treatment of primary Small Saphenous vein Insufficiency) is a multicenter randomized controlled trial in which a total of 160 patients will be randomized (1:1) to MOCA™ or RFA. Consecutive patients with primary small saphenous vein incompetence, who meet the eligibility criteria, will be invited to participate in this trial. The primary endpoint is anatomic success, defined as occlusion of the treated veins objectified with duplex ultrasonography at 1 year follow-up. Secondary endpoints are post-procedural pain, initial technical success, clinical success, complications and the duration of the procedure. Initial technical success is defined as the ability to position the device adequately, treat the veins as planned and occlude the treated vein directly after the procedure has been proven by duplex ultrasonography. Clinical success is defined as an objective improvement of clinical outcome after treatment, measured with the Venous Clinical Severity Score (VCSS). Power analyses are conducted for anatomical success and post-procedural pain.Both groups will be evaluated on an intention-to-treat principle. The hypothesis of the MESSI trial is that the anatomic success rate of MOCA™ is not inferior to RFA. The second hypothesis is that post-procedural pain is significantly less after MOCA compared to RFA. NTR4613 Date of trial registration: 28 May 2014.

Applying quantitative bias analysis to estimate the plausible effects of selection bias in a cluster randomised controlled trial: secondary analysis of the Primary care Osteoarthritis Screening Trial (POST).

PubMed

Barnett, L A; Lewis, M; Mallen, C D; Peat, G

2017-12-04

Selection bias is a concern when designing cluster randomised controlled trials (c-RCT). Despite addressing potential issues at the design stage, bias cannot always be eradicated from a trial design. The application of bias analysis presents an important step forward in evaluating whether trial findings are credible. The aim of this paper is to give an example of the technique to quantify potential selection bias in c-RCTs. This analysis uses data from the Primary care Osteoarthritis Screening Trial (POST). The primary aim of this trial was to test whether screening for anxiety and depression, and providing appropriate care for patients consulting their GP with osteoarthritis would improve clinical outcomes. Quantitative bias analysis is a seldom-used technique that can quantify types of bias present in studies. Due to lack of information on the selection probability, probabilistic bias analysis with a range of triangular distributions was also used, applied at all three follow-up time points; 3, 6, and 12 months post consultation. A simple bias analysis was also applied to the study. Worse pain outcomes were observed among intervention participants than control participants (crude odds ratio at 3, 6, and 12 months: 1.30 (95% CI 1.01, 1.67), 1.39 (1.07, 1.80), and 1.17 (95% CI 0.90, 1.53), respectively). Probabilistic bias analysis suggested that the observed effect became statistically non-significant if the selection probability ratio was between 1.2 and 1.4. Selection probability ratios of > 1.8 were needed to mask a statistically significant benefit of the intervention. The use of probabilistic bias analysis in this c-RCT suggested that worse outcomes observed in the intervention arm could plausibly be attributed to selection bias. A very large degree of selection of bias was needed to mask a beneficial effect of intervention making this interpretation less plausible.

Surgery for post-vitrectomy cataract

PubMed Central

Do, Diana V; Gichuhi, Stephen; Vedula, Satyanarayana S; Hawkins, Barbara S

2014-01-01

Background Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery. Objectives The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 May 2013. Selection criteria We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy. Data collection and analysis Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration. Main results We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery. Authors' conclusions There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined. PMID:24357418

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.

The impact of an alcohol harm reduction intervention on interpersonal violence and engagement in sex work among female sex workers in Mombasa, Kenya: Results from a randomized controlled trial.

PubMed

Parcesepe, Angela M; L Engle, Kelly L; Martin, Sandra L; Green, Sherri; Sinkele, William; Suchindran, Chirayath; Speizer, Ilene S; Mwarogo, Peter; Kingola, Nzioki

2016-04-01

To evaluate whether an alcohol harm reduction intervention was associated with reduced interpersonal violence or engagement in sex work among female sex workers (FSWs) in Mombasa, Kenya. Randomized controlled trial. HIV prevention drop-in centers in Mombasa, Kenya. 818 women 18 or older in Mombasa who visited HIV prevention drop-in centers, were moderate-risk drinkers and engaged in transactional sex in past six months (410 and 408 in intervention and control arms, respectively). 6 session alcohol harm reduction intervention. 6 session non-alcohol related nutrition intervention. In-person interviews were conducted at enrollment, immediately post-intervention and 6-months post-intervention. General linear mixed models examined associations between intervention assignment and recent violence (physical violence, verbal abuse, and being robbed in the past 30 days) from paying and non-paying sex partners and engagement in sex work in the past 30 days. The alcohol intervention was associated with statistically significant decreases in physical violence from paying partners at 6 months post-intervention and verbal abuse from paying partners immediately post-intervention and 6-months post-intervention. Those assigned to the alcohol intervention had significantly reduced odds of engaging in sex work immediately post-intervention and 6-months post-intervention. The alcohol intervention was associated with reductions in some forms of violence and with reductions in engagement in sex work among FSWs in Mombasa, Kenya. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stroke Survivors' Evaluations of a Stroke Workbook-Based Intervention Designed to Increase Perceived Control over Recovery

ERIC Educational Resources Information Center

Joice, Sara; Johnston, Marie; Bonetti, Debbie; Morrison, Val; MacWalter, Ron

2012-01-01

Objective: To report stroke survivors' experiences and perceived usefulness of an effective self-help workbook-based intervention. Design: A cross-sectional study involving the intervention group of an earlier randomized controlled trial. Setting: At the participants' homes approximately seven weeks post-hospital discharge. Method: Following the…

Provider training to screen and initiate evidence-based pediatric obesity treatment in routine practice settings: A randomized pilot trial

PubMed Central

Kolko, Rachel P.; Kass, Andrea E.; Hayes, Jacqueline F.; Levine, Michele D.; Garbutt, Jane M.; Proctor, Enola K.; Wilfley, Denise E.

2016-01-01

Introduction This randomized pilot trial evaluated two training modalities for first-line, evidence-based pediatric obesity services (screening and goal-setting) among nursing students. Method Participants (N=63) were randomized to Live Interactive Training (Live) or Web-facilitated Self-study Training (Web). Pre-training, post-training, and one-month follow-up assessments evaluated training feasibility, acceptability, and impact (knowledge, and skill via simulation). Moderator (previous experience) and predictor (content engagement) analyses were conducted. Results Nearly-all (98%) participants completed assessments. Both trainings were acceptable, with higher ratings for Live and participants with previous experience (p’s<.05). Knowledge and skill improved from pre-training to post-training and follow-up in both conditions (p’s<.001). Live demonstrated greater content engagement (p’s<.01). Conclusions The training package was feasible, acceptable, and efficacious among nursing students. Given that Live had higher acceptability and engagement, and online training offers greater scalability, integrating interactive Live components within Web-based training may optimize outcomes, which may enhance practitioners’ delivery of pediatric obesity services. PMID:26873293

A cluster-randomized controlled trial evaluating the effects of delaying onset of adolescent substance abuse on cognitive development and addiction following a selective, personality-targeted intervention programme: the Co-Venture trial.

PubMed

O'Leary-Barrett, Maeve; Mâsse, Benoit; Pihl, Robert O; Stewart, Sherry H; Séguin, Jean R; Conrod, Patricia J

2017-10-01

Substance use and binge drinking during early adolescence are associated with neurocognitive abnormalities, mental health problems and an increased risk for future addiction. The trial aims to evaluate the protective effects of an evidence-based substance use prevention programme on the onset of alcohol and drug use in adolescence, as well as on cognitive, mental health and addiction outcomes over 5 years. Thirty-eight high schools will be recruited, with a final sample of 31 schools assigned to intervention or control conditions (3826 youth). Brief personality-targeted interventions will be delivered to high-risk youth attending intervention schools during the first year of the trial. Control school participants will receive no intervention above what is offered to them in the regular curriculum by their respective schools. Public/private French and English high schools in Montreal (Canada). All grade 7 students (12-13 years old) will be invited to participate. High-risk youth will be identified as those scoring one standard deviation or more above the school mean on one of the four personality subscales of the Substance Use Risk Profile Scale (40-45% youth). Self-reported substance use and mental health symptoms and cognitive functioning measured annually throughout 5 years. Primary outcomes are the onset of substance use disorders at 4 years post-intervention (year 5). Secondary intermediate outcomes are the onset of alcohol and substance use 2 years post-intervention and neuropsychological functions; namely, the protective effects of substance use prevention on cognitive functions generally, and executive functions and reward sensitivity specifically. This longitudinal, cluster-randomized controlled trial will investigate the impact of a brief personality-targeted intervention program on reducing the onset of addiction 4 years-post intervention. Results will tease apart the developmental sequences of uptake and growth in substance use and cognitive development in adolescence using developmentally sensitive neuropsychological measures. © 2017 Society for the Study of Addiction.

ESCAPS study protocol: a feasibility randomised controlled trial of ‘Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm’

PubMed Central

Fletcher-Smith, Joanna C; Walker, Dawn-Marie; Sprigg, Nikola; James, Marilyn; Walker, Marion F; Allatt, Kate; Mehta, Rajnikant; Pandyan, Anand D

2016-01-01

Introduction Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb. Methods and analysis This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments. Ethics and dissemination This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences. Trial registration number ISRCTN1648908; Pre-results. Clinicaltrials.gov ID: NCT02324634. PMID:26729394

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial

PubMed Central

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-01-01

Background: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. Aims: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. Patients: One hundred patients (aged 6 months–15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. Methods: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children ⩾6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. Results: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. Conclusions: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation. PMID:15479678

Feasibility trial of a film-based educational intervention for increasing boys’ and girls’ intentions to avoid teenage pregnancy: Study protocol☆

PubMed Central

Lohan, Maria; Aventin, Áine; Maguire, Lisa; Clarke, Mike; Linden, Mark; McDaid, Lisa

2014-01-01

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers’ intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs. PMID:25284956

Feasibility trial of a film-based educational intervention for increasing boys' and girls' intentions to avoid teenage pregnancy: Study protocol.

PubMed

Lohan, Maria; Aventin, Aine; Maguire, Lisa; Clarke, Mike; Linden, Mark; McDaid, Lisa

2014-01-01

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs.

Protocol for process evaluation of a randomised controlled trial of family-led rehabilitation post stroke (ATTEND) in India

PubMed Central

Liu, Hueiming; Lindley, Richard; Alim, Mohammed; Felix, Cynthia; Gandhi, Dorcas B C; Verma, Shweta J; Tugnawat, Deepak Kumar; Syrigapu, Anuradha; Ramamurthy, Ramaprabhu Krishnappa; Pandian, Jeyaraj D; Walker, Marion; Forster, Anne; Anderson, Craig S; Langhorne, Peter; Murthy, Gudlavalleti Venkata Satyanarayana; Shamanna, Bindiganavale Ramaswamy; Hackett, Maree L; Maulik, Pallab K; Harvey, Lisa A; Jan, Stephen

2016-01-01

Introduction We are undertaking a randomised controlled trial (fAmily led rehabiliTaTion aftEr stroke in INDia, ATTEND) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability; as a potentially affordable, culturally acceptable and effective intervention for use in India. A process evaluation is needed to understand how and why this complex intervention may be effective, and to capture important barriers and facilitators to its implementation. We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting. Methods and analysis The realist and RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) frameworks informed the design. Mixed methods include semistructured interviews with health providers, patients and their carers, analysis of quantitative process data describing fidelity and dose of intervention, observations of trial set up and implementation, and the analysis of the cost data from the patients and their families perspective and programme budgets. These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial, and then triangulated with the results from the primary outcome evaluation. Ethics and dissemination The process evaluation has received ethical approval for all sites in India. In low-income and middle-income countries, the available human capital can form an approach to reducing the evidence practice gap, compared with the high cost alternatives available in established market economies. This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale. Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred, cost-effective and sustainable models of stroke rehabilitation. Trial registration number CTRI/2013/04/003557. PMID:27633636

Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: An efficacy trial conducted in the real world

PubMed Central

Winhusen, Theresa; Brady, Kathleen T.; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; VanVeldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene

2012-01-01

Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance-abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention. PMID:22613054

Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted in the real world.

PubMed

Winhusen, Theresa; Brady, Kathleen T; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; Vanveldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene

2012-09-01

Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors.

PubMed

Kaufmann, Jost; Roth, Bernhard; Engelhardt, Thomas; Lechleuthner, Alex; Laschat, Michael; Hadamitzky, Christoph; Wappler, Frank; Hellmich, Martin

2018-01-01

Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre-post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patient's weight. Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p < 0.001). All administrations of epinephrine occurred excessive (DRD > 300%) in pre-interventional and none in post-interventional patients (p < 0.001). The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors.

Psychological interventions for post-traumatic stress disorder in people living with HIV in Resource poor settings: a systematic review.

PubMed

Verhey, Ruth; Chibanda, Dixon; Brakarsh, Jonathan; Seedat, Soraya

2016-10-01

Post-traumatic stress disorder is pervasive in low- and middle-income countries. There is evidence to suggest that post-traumatic stress disorder is more common among people living with HIV than non-infected matched controls. We carried out a systematic review of interventions for adult post-traumatic stress disorder from resource poor settings with a focus on people living with HIV. We included all studies that investigated interventions for adult post-traumatic stress disorder from resource poor settings with a focus on interventions that were either randomised controlled trials or observational cohort studies carried out from 1980 to May 2015. Of the 25 articles that were identified for full review, two independent reviewers identified seven studies that met our study inclusion criteria. All randomised controlled trials (RCT) (n = 6) used cognitive behavioural therapy-based interventions and focused on people living with HIV in resource poor settings. There was only one study focusing on the use of lay counsellors to address post-traumatic stress disorder but core competencies were not described. There were no intervention studies from Africa, only an observational cohort study from Rwanda. Rigorously evaluated interventions for adult post-traumatic stress disorder in people living with HIV are rare. Most were undertaken in resource poor settings located in high-income countries. There is a need for research on the development and implementation of appropriate interventions for post-traumatic stress disorder in people living with HIV in low- and middle-income countries. © 2016 John Wiley & Sons Ltd.

Lack of benefit from percutaneous intervention of persistently occluded infarct arteries after the acute phase of myocardial infarction is time independent: insights from Occluded Artery Trial

PubMed Central

Menon, Venu; Pearte, Camille A.; Buller, Christopher E.; Steg, Ph.Gabriel; Forman, Sandra A.; White, Harvey D.; Marino, Paolo N.; Katritsis, Demosthenes G.; Caramori, Paulo; Lasevitch, Ricardo; Loboz-Grudzien, Krystyna; Zurakowski, Aleksander; Lamas, Gervasio A.; Hochman, Judith S.

2009-01-01

Aims The Occluded Artery Trial (OAT) (n = 2201) showed no benefit for routine percutaneous intervention (PCI) (n = 1101) over medical therapy (MED) (n = 1100) on the combined endpoint of death, myocardial infarction (MI), and class IV heart failure (congestive heart failure) in stable post-MI patients with late occluded infarct-related arteries (IRAs). We evaluated the potential for selective benefit with PCI over MED for patients enrolled early in OAT. Methods and results We explored outcomes with PCI over MED in patients randomized to the ≤3 calendar days and ≤7 calendar days post-MI time windows. Earlier, times to randomization in OAT were associated with higher rates of the combined endpoint (adjusted HR 1.04/day: 99% CI 1.01–1.06; P < 0.001). The 48-month event rates for ≤3 days, ≤7 days post-MI enrolled patients were similar for PCI vs. MED for the combined and individual endpoints. There was no interaction between time to randomization defined as a continuous (P = 0.55) or categorical variable with a cut-point of 3 days (P = 0.98) or 7 days (P = 0.64) post-MI and treatment effect. Conclusion Consistent with overall OAT findings, patients enrolled in the ≤3 day and ≤7 day post-MI time windows derived no benefit with PCI over MED with no interaction between time to randomization and treatment effect. Our findings do not support routine PCI of the occluded IRA in trial-eligible patients even in the earliest 24–72 h time window. PMID:19028780

Pilot Randomized Controlled Trial of Internet-delivered Cognitive-Behavioral Treatment for Pediatric Headache

PubMed Central

Law, Emily F.; Beals-Erickson, Sarah E.; Noel, Melanie; Claar, Robyn; Palermo, Tonya M.

2015-01-01

Objective To evaluate the feasibility and preliminary effectiveness of an Internet-delivered cognitive-behavioral therapy (CBT) intervention for adolescents with chronic headache. Background Headache is among the most common pain complaints of childhood. Cognitive-behavioral interventions are efficacious for improving pain among youth with headache. However, many youth do not receive psychological treatment for headache due to poor access, which has led to consideration of alternative delivery modalities such as the Internet. Methods We used a parallel arm randomized controlled trial design to evaluate the feasibility and preliminary effectiveness of an Internet-delivered family-based CBT intervention, Web-Based Management of Adolescent Pain (Web-MAP). Adolescents were eligible for the trial if they were a new patient being evaluated in a specialized headache clinic, between the ages of 11–17 years old, and had recurrent headache for three months or more as diagnosed by a pediatric neurologist. Eighty-three youth enrolled in the trial. An online random number generator was used to randomly assign participants to receive Internet CBT adjunctive to specialized headache treatment (n = 44) or specialized headache treatment alone (n = 39). The primary treatment outcome was headache days. Results Youth and parents in the Internet CBT group demonstrated high levels of engagement with the web program and reported satisfaction with the intervention. Multi-level modeling was used to conduct hypothesis testing for continuous outcomes. For our primary treatment outcome of headache days, adolescents reported a statistically significant reduction in headache days from baseline to post-treatment and baseline to three-month follow-up in both treatment conditions (main effect for time F(2, 136) = 19.70, p < .001). However, there was no statistically significant difference between the Internet CBT group and the specialized headache treatment group at post-treatment or follow-up (group x time interaction F(2, 134) = .94, p = .395). For our secondary treatment outcomes, findings from multilevel modeling (MLM) showed that adolescents in both groups demonstrated statistically significant improvement headache pain intensity, activity limitations, depressive symptoms and parent protective behaviors from baseline to post-treatment and these gains were maintained at three-month follow-up. Adolescent anxiety symptoms and sleep did not change during the study period for either group. There were no statistically significant group differences on any secondary outcomes at post-treatment or follow-up (p > 0.05 for all outcomes). No adverse events were reported. Conclusion Although adjunctive Internet CBT did not lead to additional benefit in this population, future research should evaluate whether it is an effective intervention for adolescents with headache who are unable to access specialized headache treatment. PMID:26316194

Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.

PubMed

Gingnell, Malin; Frick, Andreas; Engman, Jonas; Alaie, Iman; Björkstrand, Johannes; Faria, Vanda; Carlbring, Per; Andersson, Gerhard; Reis, Margareta; Larsson, Elna-Marie; Wahlstedt, Kurt; Fredrikson, Mats; Furmark, Tomas

2016-09-01

Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination. To evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD. Double-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928). Escitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders. Adding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response. © The Royal College of Psychiatrists 2016.

The role of physician characteristics in clinical trial acceptance: testing pathways of influence.

PubMed

Curbow, Barbara; Fogarty, Linda A; McDonnell, Karen A; Chill, Julia; Scott, Lisa Benz

2006-03-01

Eight videotaped vignettes were developed that assessed the effects of three physician-related experimental variables (in a 2 x 2 x 2 factorial design) on clinical trial (CT) knowledge, video knowledge, information processing, CT beliefs, affective evaluations (attitudes), and CT acceptance. It was hypothesized that the physician variables (community versus academic-based affiliation, enthusiastic versus neutral presentation of the trial, and new versus previous relationship with the patient) would serve as communication cues that would interrupt message processing, leading to lower knowledge gain but more positive beliefs, attitudes, and CT acceptance. A total of 262 women (161 survivors and 101 controls) participated in the study. The manipulated variables primarily influenced the intermediary variables of post-test CT beliefs and satisfaction with information rather than knowledge or information processing. Multiple regression results indicated that CT acceptance was associated with positive post-CT beliefs, a lower level of information processing, satisfaction with information, and control status. Based on these results, CT acceptance does not appear to be based on a rational decision-making model; this has implications for both the ethics of informed consent and research conceptual models.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial

PubMed Central

Nair, Velu; Madan, Hemant; Sofat, Sunil; Ganguli, Prosenjit; Jacob, M.J.; Datta, Rajat; Bharadwaj, Prashant; Sarkar, R.S.; Pandit, A.J.; Nityanand, Soniya; Goel, Pravin K.; Garg, Naveen; Gambhir, Sanjay; George, Paul V.; Chandy, Sunil; Mathews, Vikram; George, Oomen K.; Talwar, K.K.; Bahl, Ajay; Marwah, Neelam; Bhatacharya, Anish; Bhargava, Balram; Airan, Balram; Mohanty, Sujata; Patel, Chetan D.; Sharma, Alka; Bhatnagar, Shinjini; Mondal, A.; Jose, Jacob; Srivastava, A.

2015-01-01

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 × 108(n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials. PMID:26354213

A comparison of two treatments for childhood apraxia of speech: methods and treatment protocol for a parallel group randomised control trial

PubMed Central

2012-01-01

Background Childhood Apraxia of Speech is an impairment of speech motor planning that manifests as difficulty producing the sounds (articulation) and melody (prosody) of speech. These difficulties may persist through life and are detrimental to academic, social, and vocational development. A number of published single subject and case series studies of speech treatments are available. There are currently no randomised control trials or other well designed group trials available to guide clinical practice. Methods/Design A parallel group, fixed size randomised control trial will be conducted in Sydney, Australia to determine the efficacy of two treatments for Childhood Apraxia of Speech: 1) Rapid Syllable Transition Treatment and the 2) Nuffield Dyspraxia Programme – Third edition. Eligible children will be English speaking, aged 4–12 years with a diagnosis of suspected CAS, normal or adjusted hearing and vision, and no comprehension difficulties or other developmental diagnoses. At least 20 children will be randomised to receive one of the two treatments in parallel. Treatments will be delivered by trained and supervised speech pathology clinicians using operationalised manuals. Treatment will be administered in 1-hour sessions, 4 times per week for 3 weeks. The primary outcomes are speech sound and prosodic accuracy on a customised 292 item probe and the Diagnostic Evaluation of Articulation and Phonology inconsistency subtest administered prior to treatment and 1 week, 1 month and 4 months post-treatment. All post assessments will be completed by blinded assessors. Our hypotheses are: 1) treatment effects at 1 week post will be similar for both treatments, 2) maintenance of treatment effects at 1 and 4 months post will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment, and 3) generalisation of treatment effects to untrained related speech behaviours will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment. This protocol was approved by the Human Research Ethics Committee, University of Sydney (#12924). Discussion This will be the first randomised control trial to test treatment for CAS. It will be valuable for clinical decision-making and providing evidence-based services for children with CAS. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12612000744853 PMID:22863021

Post Hoc Analyses of ApoE Genotype-Defined Subgroups in Clinical Trials.

PubMed

Kennedy, Richard E; Cutter, Gary R; Wang, Guoqiao; Schneider, Lon S

2016-01-01

Many post hoc analyses of clinical trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are in small Phase 2 trials. Subject heterogeneity may lead to statistically significant post hoc results that cannot be replicated in larger follow-up studies. We investigated the extent of this problem using simulation studies mimicking current trial methods with post hoc analyses based on ApoE4 carrier status. We used a meta-database of 24 studies, including 3,574 subjects with mild AD and 1,171 subjects with MCI/prodromal AD, to simulate clinical trial scenarios. Post hoc analyses examined if rates of progression on the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) differed between ApoE4 carriers and non-carriers. Across studies, ApoE4 carriers were younger and had lower baseline scores, greater rates of progression, and greater variability on the ADAS-cog. Up to 18% of post hoc analyses for 18-month trials in AD showed greater rates of progression for ApoE4 non-carriers that were statistically significant but unlikely to be confirmed in follow-up studies. The frequency of erroneous conclusions dropped below 3% with trials of 100 subjects per arm. In MCI, rates of statistically significant differences with greater progression in ApoE4 non-carriers remained below 3% unless sample sizes were below 25 subjects per arm. Statistically significant differences for ApoE4 in post hoc analyses often reflect heterogeneity among small samples rather than true differential effect among ApoE4 subtypes. Such analyses must be viewed cautiously. ApoE genotype should be incorporated into the design stage to minimize erroneous conclusions.

Results of the post-market Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE).

PubMed

Strueber, Martin; Larbalestier, Robert; Jansz, Paul; Zimpfer, Daniel; Fiane, Arnt E; Tsui, Steven; Simon, André; Schmitto, Jan D; Khaghani, Asghar; Wieselthaler, George M; Najarian, Kevin; Schueler, Stephan

2014-05-01

The post-market Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE) is an investigator-initiated registry established to collect post-CE Mark Trial clinical data on patients receiving a HeartWare ventricular assist device (HVAD) in the European Union and Australia. The ReVOLVE is a multi-center, prospective, single-arm registry performed at seven centers in Europe and two in Australia. Herein we describe a total of 254 commercial HVAD implants according to labeled indications between February 2009 and November 2012. Summary statistics included patients' demographics, adverse events, length of support and outcomes. Compared with the clinical trial supporting the CE Mark of the HeartWare system, patient selection differed in that patients were older, and there were higher proportions of females and patients with idiopathic cardiomyopathies in the ReVOLVE cohort. Duration of support ranged from 1 to 1,057 days, with a mean of 363 ± 280 days (median 299.5 days). Transplantation was done in 56 patients (22%), explant for recovery was performed in 3 patients (1%), 43 died while on support (17%), and 152 (60%) remain on the device. Success in patients with the HeartWare system was 87% at 6 months, 85% at 1 year, 79% at 2 years and 73% at 3 years. Adverse event rates were low, comparable or improved when compared to the CE Mark Trial. Real-world use of the HeartWare system continues to demonstrate excellent clinical outcomes in patients supported with the device. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments

PubMed Central

2011-01-01

Background No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes - the "sentinel lesion approach". Methods/design MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Results Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. Conclusions In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability. Trial registration ClinicalTrials.gov (NCT00395200). PMID:21366911

Rectal indomethacin versus placebo to reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography: results of a controlled clinical trial.

PubMed

Andrade-Dávila, Víctor Fernando; Chávez-Tostado, Mariana; Dávalos-Cobián, Carlos; García-Correa, Jesús; Montaño-Loza, Alejandro; Fuentes-Orozco, Clotilde; Macías-Amezcua, Michel Dassaejv; García-Rentería, Jesús; Rendón-Félix, Jorge; Cortés-Lares, José Antonio; Ambriz-González, Gabriela; Cortés-Flores, Ana Olivia; Alvarez-Villaseñor, Andrea del Socorro; González-Ojeda, Alejandro

2015-07-21

Acute pancreatitis is the most common major complication after endoscopic retrograde cholangiopancreatography (ERCP). Many drugs have been evaluated for prophylaxis, including nonsteroidal anti-inflammatory drugs (NSAIDs), which are potent inhibitors of phospholipase A2 and play a role in the pathogenesis of acute pancreatitis. Rectal NSAIDs have been shown in prospective studies to decrease the incidence of this complication, but the indication is not generalized in clinical practice. The aim of this study was to evaluate the efficacy of rectal administration of indomethacin in reducing the incidence of post-ERCP pancreatitis in high-risk patients. This was a controlled clinical trial where patients with an elevated risk of developing post-ERCP pancreatitis were assigned to receive 100 mg of rectal indomethacin or a 2.6 g suppository of glycerin immediately after ERCP, without placement of a pancreatic stent. The patients were determined to be at high risk based on validated patient- and procedure-related risk factors. Post-ERCP pancreatitis was defined as the presence of new upper abdominal pain, hyperamylasemia/hyperlipasemia (at least three times the upper limit) 2 hours after the procedure and hospitalization at least 48 hours because of the complication. Pancreatitis severity was defined according to Cotton's criteria. One hundred sixty-six patients were included; 82 in the study group and 84 in the placebo group. Patients had at least one major and/or two minor risk factors for developing post-ERCP pancreatitis. The incidence of the complication was 4.87% (4/82) in the study group and 20.23% (17/84) in the placebo group; this difference was significant (P = 0.01). According to Cotton's criteria, 17 patients (80.9%) developed mild pancreatitis and 4 (19.1%) had moderate pancreatitis; 3 of these 4 patients belonged to the placebo group (P = 0.60). Based on these results, an absolute risk reduction of 0.15 (15%), a relative risk reduction of 0.75 (75%) and a number needed to treat of 6.5 patients were calculated to prevent an episode of post-ERCP pancreatitis. There was no mortality. Rectal indomethacin reduced the incidence of post-ERCP pancreatitis among patients at high risk of developing this complication. National Clinical Trials NCT02110810. Date April 7, 2014.

A Translational Worksite Diabetes Prevention Trial Improves Psychosocial Status, Dietary Intake, and Step Counts among Employees with Prediabetes: A Randomized Controlled Trial.

PubMed

Miller, Carla K; Weinhold, Kellie; Marrero, David G; Nagaraja, Haikady N; Focht, Brian C

Few worksite trials have examined the impact of diabetes prevention interventions on psychological and behavioral outcomes. Thus, the impact of a worksite lifestyle intervention on psychosocial outcomes, food group intake, and step counts for physical activity (PA) was evaluated. A randomized pretest/posttest control group design with 3-month follow-up was employed from October 2012 to May 2014 at a U.S. university worksite among employees with prediabetes. The experimental group (n=35) received a 16-week group-based intervention while the control group received usual care (n=33). Repeated measures analysis of variance compared the change in outcomes between groups across time. A significant difference occurred between groups post-intervention for self-efficacy associated with eating and PA; goal commitment and difficulty; satisfaction with weight loss and physical fitness; peer social support for healthful eating; generation of alternatives for problem solving; and intake of fruits, meat, fish, poultry, nuts, and seeds (all ps < .05). The experimental group significantly increased step counts post-intervention (p = .0279) and were significantly more likely to report completing their work at study end (p = .0231). The worksite trial facilitated improvement in modifiable psychosocial outcomes, dietary patterns, and step counts; the long-term impact on diabetes prevention warrants further investigation. ClinicalTrials.gov identifier: NCT01682954.

Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

PubMed Central

2012-01-01

Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines. PMID:22640463

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): rationale and study design of the randomized TWENTE III multicenter trial.

PubMed

Lam, Ming Kai; Sen, Hanim; Tandjung, Kenneth; van Houwelingen, K Gert; de Vries, Arie G; Danse, Peter W; Schotborgh, Carl E; Scholte, Martijn; Löwik, Marije M; Linssen, Gerard C M; Ijzerman, Maarten J; van der Palen, Job; Doggen, Carine J M; von Birgelen, Clemens

2014-04-01

To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Comprehensive behavioral-motivational nutrition education improves depressive symptoms following bariatric surgery: a randomized, controlled trial of obese Hispanic Americans.

PubMed

Petasne Nijamkin, Monica; Campa, Adriana; Samiri Nijamkin, Shani; Sosa, Jorge

2013-01-01

To evaluate the effect of 2 post-bariatric support interventions on depressive symptoms of Hispanic Americans treated with gastric bypass for morbid or severe obesity. Prospective randomized, controlled trial conducted in a laparoscopic institution. During the Phase 1 clinical trial (from preoperative evaluation to 6 months after surgery), all participants received standard care. During Phase 2 (6-12 months after surgery), participants were randomly assigned to receive either standard care (n = 72) or comprehensive support (n = 72). Comprehensive group participants received 6 educational sessions focused on behavior change strategies and motivation with nutrition counseling. Depression scores and weight change over time. Independent samples t tests and regression analysis assessed relationships among depression scores and excess weight loss. Participants receiving behavioral-motivational intervention scored significantly lower on Beck's Depression Inventory questionnaire scores than those receiving standard care. For those with depressive symptoms at randomization, 24% of participants who received the comprehensive intervention reported no depressive symptoms at 12 months after surgery, compared with 6% of those who received standard care (P < .001). Patients' depressive mood improvement was significantly and positively associated with excess weight loss and attendance at educational sessions (P < .001). Findings support the importance of post-bariatric comprehensive behavioral-motivational nutrition education for decreasing risk for depression and improving weight loss. Copyright © 2013 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

77 FR 48755 - Office Patent Trial Practice Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Trial and Appeal Board (Board) including inter partes review, post-grant review, the transitional... proceedings. DATES: Effective Date: This practice guide applies to inter partes review, post-grant review, and... proceedings to be conducted by the Board including: (1) Inter partes review (IPR); (2) post-grant review (PGR...

From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke.

PubMed

Graven, Christine; Brock, Kim; Hill, Keith; Ames, David; Cotton, Susan; Joubert, Lynette

2011-06-18

There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined. Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy. The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000042347.

A controlled trial of trauma-focused therapy versus problem-solving in Islamic children affected by civil conflict and disaster in Aceh, Indonesia.

PubMed

Dawson, Katie; Joscelyne, Amy; Meijer, Catherine; Steel, Zachary; Silove, Derrick; Bryant, Richard A

2018-03-01

To evaluate the relative efficacies of trauma-focused cognitive behavior therapy and problem-solving therapy in treating post-traumatic stress disorder in children affected by civil conflict in Aceh, Indonesia. A controlled trial of children with post-traumatic stress disorder ( N = 64) randomized children to either five individual weekly sessions of trauma-focused cognitive behavior therapy or problem-solving therapy provided by lay-counselors who were provided with brief training. Children were assessed by blind independent assessors at pretreatment, posttreatment and 3-month follow-up on post-traumatic stress disorder, depression and anger, as well as caregiver ratings of the child's post-traumatic stress disorder levels. Intent-to-treat analyses indicated no significant linear time × treatment condition interaction effects for post-traumatic stress disorder at follow-up ( t(129.05) = -0.55, p = 0.58), indicating the two conditions did not differ. Across both conditions, there were significant reductions in post-traumatic stress disorder on self-reported ( t(131.26) = -9.26, p < 0.001) and caregiver-reported ( t(170.65) = 3.53, p = 0.001) measures and anger ( t(127.66) = -7.14, p < 0.001). Across both conditions, there was a large effect size for self-reported post-traumatic stress disorder (cognitive behavior therapy: 3.73, 95% confidence interval = [2.75, 3.97]; problem-solving: 2.68, 95% confidence interval = [2.07, 3.29]). These findings suggest that trauma-focused cognitive behavior therapy and problem-solving approaches are comparably successful in reducing post-traumatic stress disorder and anger in treating mental health in children in a post-conflict setting. This pattern may reflect the benefits of non-specific therapy effects or gains associated with trauma-focused or problem-solving approaches.

The Benefits of Early Book Sharing (BEBS) for child cognitive and socio-emotional development in South Africa: study protocol for a randomised controlled trial.

PubMed

Dowdall, Nicholas; Cooper, Peter J; Tomlinson, Mark; Skeen, Sarah; Gardner, Frances; Murray, Lynne

2017-03-09

Children in low and middle-income countries (LMICs) are at risk for problems in their cognitive, social and behavioural development. Factors such as a lack of cognitive stimulation, harsh parenting practices, and severe and persistent aggression in early childhood are central to the genesis of these problems. Interventions that target the intersection between early childhood development, parenting, and early violence prevention are required in order to meaningfully address these problems. We are conducting a randomised controlled trial to evaluate a parenting intervention for caregivers of children aged between 23 and 27 months, designed to promote child cognitive and socioemotional development in Khayelitsha, a low-income peri-urban township in South Africa. Families are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, we train caregivers in supportive book-sharing with young children. Training is carried out in small groups over a period of 8 weeks. Data are collected at baseline, post intervention and at 6 months post intervention. In addition to targeting child cognitive development, the intervention aims to improve child socioemotional functioning. The Benefits of Early Book Sharing (BEBS) trial aims to evaluate the impact of an early parenting intervention on several key risk factors for the development of violence, including aspects of parenting and child cognition, prosocial behaviour, aggression, and socioemotional functioning. The study is being carried out in a LMIC where violence constitutes a major social and health burden. Since the intervention is brief and, with modest levels of training, readily deliverable in LMIC contexts, a demonstration that it is of benefit to both child cognitive and socioemotional development would be of significance. The BEBS trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN71109104 . Registered on 9 February 2016. This is version 1 of the protocol for the BEBS trial.

Comparison of outcome measures and complication rates following three different approaches for primary total hip arthroplasty: a pragmatic randomised controlled trial.

PubMed

Talia, Adrian J; Coetzee, Cassandra; Tirosh, Oren; Tran, Phong

2018-01-08

Total hip arthroplasty is one of the most commonly performed surgical procedures worldwide. There are a number of surgical approaches for total hip arthroplasty and no high-level evidence supporting one approach over the other. Each approach has its unique benefits and drawbacks. This trial aims to directly compare the three most common surgical approaches for total hip arthroplasty. This is a single-centre study conducted at Western Health, Melbourne, Australia; a large metropolitan centre. It is a pragmatic, parallel three-arm, randomised controlled trial. Sample size will be 243 participants (81 in each group). Randomisation will be secure, web-based and managed by an independent statistician. Patients and research team will be blinded pre-operatively, but not post-operatively. Intervention will be either direct anterior, lateral or posterior approach for total hip arthroplasty, and the three arms will be directly compared. Participants will be aged over 18 years, able to provide informed consent and recruited from our outpatients. Patients who are having revision surgery or have indications for hip replacement other than osteoarthritis (i.e., fracture, malignancy, development dysplasia) will be excluded from the trial. The Oxford Hip Score will be determined for patients pre-operatively and 6 weeks, 6, 12 and 24 months post-operatively. The Oxford Hip Score at 24 months will be the primary outcome measure. Secondary outcome measures will be dislocation, infection, intraoperative and peri-prosthetic fracture rate, length of hospital stay and pain level, reported using a visual analogue scale. Many studies have evaluated approaches for total hip arthroplasty and arthroplasty registries worldwide are now collecting this data. However no study to date has compared these three common approaches directly in a randomised fashion. No trial has used patient-reported outcome measures to evaluate success. This pragmatic study aims to identify differences in patient perception of total hip arthroplasty depending on surgical approach. Australian New Zealand Clinical Trials Registry, ACTRN12617000272392 . Registered on 22 February 2017.

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

STROKE OUTCOMES AMONG PARTICIPANTS RANDOMIZED TO CHLORTHALIDONE, AMLODIPINE OR LISINOPRIL IN ALLHAT

PubMed Central

Yamal, José-Miguel; Oparil, Suzanne; Davis, Barry R.; Alderman, Michael H.; Calhoun, David A.; Cushman, William C.; Fendley, Herbert F.; Franklin, Stanley S.; Habib, Gabriel B.; Pressel, Sara L.; Probstfield, Jeffrey L.; Sastrasinh, Sithiporn

2014-01-01

Background The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. Methods and Results ALLHAT compared cardiovascular disease outcomes in participants initially treated with angiotensin-converting enzyme inhibitor (lisinopril), calcium channel blocker (amlodipine), or thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for total follow-up of 8–13 years. Stroke rates were higher with lisinopril (6-year rate/100=6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100=13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In- trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P=0.005, race-by-amlodipine/lisinopril interaction P=0.012) and gender (gender-by-lisinopril/amlodipine interaction P=0.041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Conclusions Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period. PMID:25455006

Treatment of depression with Chai Hu Shu Gan San: a systematic review and meta-analysis of 42 randomized controlled trials.

PubMed

Sun, Yan; Xu, Xia; Zhang, Jinping; Chen, Yuanyuan

2018-02-17

Depression is a common mental disorder. Chai Hu Shu Gan San, a traditional Chinese medicine, is used to treat depression empirically. We present a systematic review and meta-analysis of the therapeutic efficacy and safety of Chai Hu Shu Gan San in treating depression. Several databases, including PubMed, China National Knowledge Internet, Wanfang, Chongqing VIP, and the Cochrane library, were systematically searched from their date of foundation to January 1, 2017. In this review, wehave included randomized control trials that compared Chai Hu Shu Gan San (or its combination with a regular Western medicine) with a regular Western medicine alone for the treatment of depression. Two investigators independently extracted and analyzed the data using RevMan 5.2.0 software. Mean difference (with a 95% confidence interval) was used as efficacy indices for outcomes. We included 42 studies involving 3234 patients with depression in 15 different types of diseases. Meta analyses showed better effect of Chai Hu Shu Gan San than fluoxetine for pure depression (MD = - 1.59, from - 2.82 to - 0.37, 4 trials, I 2  = 26%), for post-stroke depression (MD = - 4.20, from - 6.20 to - 2.19, 7 trials, I 2  = 96%), and for postpartum depression (MD = - 4.10, from - 7.48 to - 0.72 7 trials, I 2  = 86%). None of the articles reported severe adverse events of oral administration of Chai Hu Shu Gan San. Furthermore, any adverse effects of using Chai Hu Shu Gan San alone were fewer than those of regular Western medicines. This review found that Chai Hu Shu Gan San has some advantages in treating depression, especially post-stroke depression and post-partum depression. A meticulously designed and conducted randomized control trial is needed for further evaluation.

An intervention to support stroke survivors and their carers in the longer term (LoTS2Care): study protocol for a cluster randomised controlled feasibility trial.

PubMed

Forster, Anne; Hartley, Suzanne; Barnard, Lorna; Ozer, Seline; Hardicre, Natasha; Crocker, Tom; Fletcher, Marie; Moreau, Lauren; Atkinson, Ross; Hulme, Claire; Holloway, Ivana; Schmitt, Laetitia; House, Allan; Hewison, Jenny; Richardson, Gillian; Farrin, Amanda

2018-06-11

Despite the evidence that many stroke survivors report longer term unmet needs, the provision of longer term care is limited. To address this, we are conducting a programme of research to develop an evidence-based and replicable longer term care strategy. The developed complex intervention (named New Start), which includes needs identification, exploration of social networks and components of problem solving and self-management, was designed to improve quality of life by addressing unmet needs and increasing participation. A multicentre, cluster randomised controlled feasibility trial designed to inform the design of a possible future definitive cluster randomised controlled trial (cRCT) and explore the potential clinical and cost-effectiveness of New Start. Ten stroke services across the UK will be randomised on a 1:1 basis either to implement New Start or continue with usual care only. New Start will be delivered by trained facilitators and will be offered to all stroke survivors within the services allocated to the intervention arm. Stroke survivors will be eligible for the trial if they are 4-6 months post-stroke and residing in the community. Carers (if available) will also be invited to take part. Invitation to participate will be initiated by post and outcome measures will be collected via postal questionnaires at 3, 6 and 9 months after recruitment. Outcome data relating to perceived health and disability, wellbeing and quality of life as well as unmet needs will be collected. A 'study within a trial' (SWAT) is planned to determine the most acceptable format in which to provide the postal questionnaires. Details of health and social care service usage will also be collected to inform the economic evaluation. The feasibility of recruiting services and stroke survivors to the trial and of collecting postal outcomes will be assessed and the potential for effectiveness will be investigated. An embedded process evaluation (reported separately) will assess implementation fidelity and explore and clarify causal assumptions regarding implementation. This feasibility trial with embedded process evaluation will allow us to gather important and detailed data regarding methodological and implementation issues to inform the design of a possible future definitive cRCT of this complex intervention. ISRCTN38920246 . Registered 22 June 2016.

The post-trial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization

PubMed Central

Balkus, Jennifer E.; Jaoko, Walter; Mandaliya, Kishorchandra; Richardson, Barbra A.; Masese, Linnet; Gitau, Ruth; Kiarie, James; Marrazzo, Jeanne; Farquhar, Carey; McClelland, R. Scott

2012-01-01

Background We previously demonstrated a decrease in bacterial vaginosis (BV) and an increase in Lactobacillus colonization among randomized controlled trial (RCT) participants who received monthly oral periodic presumptive treatment (PPT) [2g metronidazole + 150mg fluconazole]. Post-trial data were analyzed to test the hypothesis that the treatment effect would persist following completion of one year of PPT. Methods Data were obtained from women who completed all 12 RCT visits and attended ≥1 post-trial visit within 120 days following completion of the RCT. We used Andersen-Gill proportional hazards models to estimate the post-trial effect of the intervention on the incidence of BV by Gram stain and detection of Lactobacillus species by culture. Results The analysis included 165 subjects (83 active and 82 placebo). The post-trial incidence of BV was 260 per 100 person-years in the intervention arm versus 358 per 100 person-years in the placebo arm (hazard ratio [HR]=0.76; 95% confidence interval [CI]: 0.51–1.12). The post-trial incidence of Lactobacillus colonization was 180 per 100 person-years in the intervention arm versus 127 per 100 person-years in the placebo arm (HR=1.42; 95% CI: 0.85–2.71). Conclusions Despite a decrease in BV and an increase in Lactobacillus colonization during the RCT, the effect of PPT was not sustained at the same level following cessation of the intervention. New interventions that reduce BV recurrence and promote Lactobacillus colonization without the need for ongoing treatment are needed. PMID:22504600

Decline in Frozen Section Diagnosis for Axillary Sentinel Lymph Nodes as a Result of the American College of Surgeons Oncology Group Z0011 Trial.

PubMed

Bishop, Julie Anne; Sun, Jihong; Ajkay, Nicolas; Sanders, Mary Ann G

2016-08-01

-Results of the American College of Surgeons Oncology Group Z0011 trial showed that patients with early-stage breast cancer and limited sentinel node metastasis treated with breast conservation and systemic therapy did not benefit from axillary lymph node dissection. Subsequently, most pathology departments have likely seen a decrease in frozen section diagnosis of sentinel lymph nodes. -To determine the effect of the Z0011 trial on pathology practice and to examine the utility of intraoperative sentinel lymph node evaluation for this subset of patients. -Pathology reports from cases of primary breast cancer that met Z0011 clinical criteria and were initially treated with lumpectomy and sentinel lymph node biopsy from 2009 to 2015 were collected. Clinicopathologic data were recorded. -Sentinel lymph node biopsies sent for frozen section diagnosis occurred in 22 of 22 cases (100%) in 2009 and 15 of 22 cases (68%) in 2010 during the pre-Z0011 years, and in 3 of 151 cases (2%) collected in 2011 through 2015, considered to be post-Z0011 years. Of the 151 post-Z0011 cases, 28 (19%) had sentinel lymph nodes with metastasis, and 147 (97%) were spared axillary lymph node dissection. -Following Z0011, intraoperative sentinel lymph node evaluation has significantly decreased at our institution. Prior to surgery, all patients had clinically node-negative disease. After sentinel lymph node evaluation, 97% (147 of 151) of the patients were spared axillary lymph node dissection. Therefore, routine frozen section diagnosis for sentinel lymph node biopsies can be avoided in these patients.

Efficacy of interpersonal therapy-group format adapted to post-traumatic stress disorder: an open-label add-on trial.

PubMed

Campanini, Rosaly F B; Schoedl, Aline F; Pupo, Mariana C; Costa, Ana Clara H; Krupnick, Janice L; Mello, Marcelo F

2010-01-01

Post-traumatic stress disorder (PTSD) is a highly prevalent condition, yet available treatments demonstrate only modest efficacy. Exposure therapies, considered by many to be the "gold-standard" therapy for PTSD, are poorly tolerated by many patients and show high attrition. We evaluated interpersonal therapy, in a group format, adapted to PTSD (IPT-G PTSD), as an adjunctive treatment for patients who failed to respond to conventional psychopharmacological treatment. Research participants included 40 patients who sought treatment through a program on violence in the department of psychiatry of Federal University of São Paulo (UNIFESP). They had received conventional psychopharmacological treatment for at least 12 weeks and failed to have an adequate clinical response. After signing an informed consent, approved earlier by the UNIFESP Ethics Review Board, they received a semi-structured diagnostic interview (SCID-I), administered by a trained mental health worker, to confirm the presence of a PTSD diagnosis according to DSM-IV criteria. Other instruments were administered, and patients completed out self-report instruments at baseline, and endpoint to evaluate clinical outcomes. Thirty-three patients completed the trial, but all had at least one second outcome evaluation. There were significant improvements on all measures, with large effect sizes. IPT-G PTSD was effective not only in decreasing symptoms of PTSD, but also in decreasing symptoms of anxiety and depression. It led to significant improvements in social adjustment and quality of life. It was well tolerated and there were few dropouts. Our results are very preliminary; they need further confirmation through randomized controlled clinical trials.

Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation of a Randomized Controlled Trial.

PubMed

Voorn, Eric L; Koopman, Fieke S; Brehm, Merel A; Beelen, Anita; de Haan, Arnold; Gerrits, Karin H L; Nollet, Frans

2016-01-01

To explore reasons for the lack of efficacy of a high intensity aerobic exercise program in post-polio syndrome (PPS) on cardiorespiratory fitness by evaluating adherence to the training program and effects on muscle function. A process evaluation using data from an RCT. Forty-four severely fatigued individuals with PPS were randomized to exercise therapy (n = 22) or usual care (n = 22). Participants in the exercise group were instructed to exercise 3 times weekly for 4 months on a bicycle ergometer (60-70% heart rate reserve). The attendance rate was high (median 89%). None of the participants trained within the target heart rate range during >75% of the designated time. Instead, participants exercised at lower intensities, though still around the anaerobic threshold (AT) most of the time. Muscle function did not improve in the exercise group. Our results suggest that severely fatigued individuals with PPS cannot adhere to a high intensity aerobic exercise program on a cycle ergometer. Despite exercise intensities around the AT, lower extremity muscle function nor cardiorespiratory fitness improved. Improving the aerobic capacity in PPS is difficult through exercise primarily focusing on the lower extremities, and may require a more individualized approach, including the use of other large muscle groups instead. Netherlands National Trial Register NTR1371.

Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing evaluation: Rationale and best practices. A report from the cardiac safety research consortium.

PubMed

Seltzer, Jonathan H; Heise, Ted; Carson, Peter; Canos, Daniel; Hiatt, Jo Carol; Vranckx, Pascal; Christen, Thomas; Cutlip, Donald E

2017-08-01

This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence. Copyright © 2017. Published by Elsevier Inc.

"Healthy Habits, Healthy Girls-Brazil": an obesity prevention program with added focus on eating disorders.

PubMed

Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva; Thompson, Debbe; Nicklas, Theresa; Baranowski, Tom

2018-05-05

To evaluate the immediate post-intervention and 6-month post-intervention effects of a Brazilian school-based randomized controlled trial for girls targeting shared risk factors for obesity and disordered eating. Total of 253 girls, mean of 15.6 (0.05) years from 1st to 3rd grades of high school participated in this 6-month school-based cluster randomized controlled trial. "Healthy Habits, Healthy Girls-Brazil (H3G-Brazil)", originally developed in Australia, emphasized 10 key nutrition and physical activity (PA) messages delivered over 6 months. Disordered eating prevention procedures, i.e., prevention of weight-teasing, body satisfaction, and unhealthy weight control behavior, were added to the intervention. Body dissatisfaction, unhealthy weight control behaviors and social cognitive-related diet, and physical activity variables were assessed at baseline, immediate post-intervention, and 6-month post-intervention. Intervention effects were determined by one-way analysis of covariance or logistic regression, after checking for the clustering effects of school. The control group did not receive intervention prior to follow-up assessment. A conservative significance level was set at p < 0.01. Beneficial effects were detected for PA social support (F = 6.005, p = 0.01), and healthy eating strategies (F = 6.08, p = 0.01) immediate post-intervention; and healthy eating social support (F = 14.731, p = 0.00) and healthy eating strategies (F = 5.812, p = 0.01) at 6-month post-intervention. Intervention group was more likely to report unhealthy weight control behaviors (OR = 1.92, 95% CI 1.15-3.21, p = 0.01) at 6-month post-intervention. No other significant immediate or 6-month post effects were detected. H3G-Brazil demonstrated positive 6-month effects on some social cognitive variables but an adverse effect on unhealthy weight control behaviors. Thus, this study was not able to achieve synergy by combining obesity and disordered eating prevention procedures in an intervention among low-income girls in Brazil. Level I: cluster randomized controlled trial.

What work has to be done to implement collaborative care for depression? Process evaluation of a trial utilizing the Normalization Process Model

PubMed Central

2010-01-01

Background There is a considerable evidence base for 'collaborative care' as a method to improve quality of care for depression, but an acknowledged gap between efficacy and implementation. This study utilises the Normalisation Process Model (NPM) to inform the process of implementation of collaborative care in both a future full-scale trial, and the wider health economy. Methods Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory randomised controlled trial of a collaborative model of care for depression. Results Findings are presented as they relate to the four factors of the NPM (interactional workability, relational integration, skill-set workability, and contextual integration) and a number of necessary tasks are identified. Using the model, it was possible to observe that predictions about necessary work to implement collaborative care that could be made from analysis of the pre-trial data relating to the four different factors of the NPM were indeed borne out in the post-trial data. However, additional insights were gained from the post-trial interview participants who, unlike those interviewed before the trial, had direct experience of a novel intervention. The professional freedom enjoyed by more senior mental health workers may work both for and against normalisation of collaborative care as those who wish to adopt new ways of working have the freedom to change their practice but are not obliged to do so. Conclusions The NPM provides a useful structure for both guiding and analysing the process by which an intervention is optimized for testing in a larger scale trial or for subsequent full-scale implementation. PMID:20181163

A randomized trial testing the superiority of a post-discharge care management model for stroke survivors

PubMed Central

Allen, Kyle; Hazelett, Susan; Jarjoura, David; Hua, Keding; Wright, Kathy; Weinhardt, Janice; Kropp, Denise

2009-01-01

Objective To evaluate whether comprehensive post-discharge care management for stroke survivors is superior to organized acute stroke unit care with enhanced discharge planning in improving a profile of health and well-being. Methods This was a randomized trial of a comprehensive post-discharge care management intervention for ischemic stroke patients with NIH Stroke Scale scores ≥1 discharged from an acute stroke unit. An Advanced Practice Nurse (APN) performed an in-home assessment for the intervention group from which an Interdisciplinary Team developed patient-specific care plans. The APN worked with the primary care physician (PCP) and patient to implement the plan over the next 6 months. Main outcome measures The intervention and usual care groups were compared using a global and closed hypothesis testing strategy. Outcomes fell into 5 domains: 1) Neuromotor Function, 2) Institution Time or Death, 3) Quality of Life, 4) Management of Risk, and 5) Stroke Knowledge and Lifestyle. Results Treatment effect was near zero standard deviations for all but the stroke knowledge and lifestyle domain which showed a significant effect of the intervention (p=0.0003). Conclusions Post discharge care management was not more effective than organized stroke unit care with enhanced discharge planning in most domains in this population. The intervention did, however, fill a post-discharge knowledge gap. PMID:19900646

Pharmaceutical companies vs. the State: who is responsible for post-trial provision of drugs in Brazil?

PubMed

Wang, Daniel Wei L; Ferraz, Octavio Luiz Motta

2012-01-01

This paper discusses the post-trial access to drugs for patients who participated in clinical trials in Brazil. The ethical guidance for clinical trials in Brazil is arguably one of the clearest in the world in attributing to research sponsors the responsibility for providing post-trial drugs to patients who participated in their experiments. The Federal Constitution recognizes health as a fundamental right to be fulfilled by the State. Based on the Brazilian constitution and on the National Health Council resolutions, courts have been accepting patients' claims and ordering the State and the pharmaceutical companies to provide these patients with the tested treatment in the quantity and duration they need it. This generous interpretation of the duties of the pharmaceutical companies and the State makes the Brazilian model for post-trial access unique when compared to the experience of other countries and thus should be followed with attention by future research in order to assess its consequences for patients, research sponsors, and the public health system. © 2012 American Society of Law, Medicine & Ethics, Inc.

Treatment of traumatized refugees with sertraline versus venlafaxine in combination with psychotherapy - study protocol for a randomized clinical trial.

PubMed

Sonne, Charlotte; Carlsson, Jessica; Elklit, Ask; Mortensen, Erik Lykke; Ekstrøm, Morten

2013-05-11

Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. This study will include approximately 150 patients, randomized into two different groups treated with either sertraline or venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. ClinicalTrials.gov NCT01569685.

Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients.

PubMed

Morel, Véronique; Joly, Dominique; Villatte, Christine; Dubray, Claude; Durando, Xavier; Daulhac, Laurence; Coudert, Catherine; Roux, Delphine; Pereira, Bruno; Pickering, Gisèle

2016-01-01

Neuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life. A randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0-10) numerical rating scale at three months post-mastectomy. Data analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported. This study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy. Clinicaltrials.gov NCT01536314.

The Primary Prevention of PTSD in Firefighters: Preliminary Results of an RCT with 12-Month Follow-Up

PubMed Central

Rees, Clare S.; Mazzucchelli, Trevor G.; Kane, Robert T.

2016-01-01

Aim To develop and evaluate an evidence-based and theory driven program for the primary prevention of Post-traumatic Stress Disorder (PTSD). Design A pre-intervention / post-intervention / follow up control group design with clustered random allocation of participants to groups was used. The “control” group received “Training as Usual” (TAU). Method Participants were 45 career recruits within the recruit school at the Department of Fire and Emergency Services (DFES) in Western Australia. The intervention group received a four-hour resilience training intervention (Mental Agility and Psychological Strength training) as part of their recruit training school curriculum. Data was collected at baseline and at 6- and 12-months post intervention. Results We found no evidence that the intervention was effective in the primary prevention of mental health issues, nor did we find any significant impact of MAPS training on social support or coping strategies. A significant difference across conditions in trauma knowledge is indicative of some impact of the MAPS program. Conclusion While the key hypotheses were not supported, this study is the first randomised control trial investigating the primary prevention of PTSD. Practical barriers around the implementation of this program, including constraints within the recruit school, may inform the design and implementation of similar programs in the future. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001362583 PMID:27382968

Designing and evaluating the effectiveness of a serious game for safe administration of blood transfusion: A randomized controlled trial.

PubMed

Tan, Apphia Jia Qi; Lee, Cindy Ching Siang; Lin, Patrick Yongxing; Cooper, Simon; Lau, Lydia Siew Tiang; Chua, Wei Ling; Liaw, Sok Ying

2017-08-01

Preparing nursing students for the knowledge and skills required for the administration and monitoring of blood components is crucial for entry into clinical practice. Serious games create opportunities to develop this competency, which can be used as a self-directed learning strategy to complement existing didactic learning and simulation-based strategies. To describe the development and evaluation of a serious game to improve nursing students' knowledge, confidence, and performance in blood transfusion. An experiential gaming model was applied to guide the design of the serious game environment. A clustered, randomized controlled trial was conducted with 103 second-year undergraduate nursing students who were randomized into control or experimental groups. After a baseline evaluation of the participants' knowledge and confidence on blood transfusion procedure, the experimental group undertook a blood transfusion serious game and completed a questionnaire to evaluate their learning experience. All participants' clinical performances were evaluated in a simulated environment. The post-test knowledge and confidence mean scores of the experimental group improved significantly (p<0.001) after the serious game intervention compared to pre-test mean scores and to post-test mean scores of the control group (p<0.001). However, no significance difference (p=0.11) was found between the experimental and control groups on the post-test performance mean scores. The participants evaluated the serious game positively. The study provided evidence on the effectiveness of a serious game in improving the knowledge and confidence of nursing students on blood transfusion practice. The features of this serious game could be further developed to incorporate additional scenarios with repetitive exercises and feedback to enhance the impact on clinical performance. Given the flexibility, practicality, and scalability of such a game, they can serve as a promising approach to optimize learning when blended with high-fidelity simulation. Copyright © 2017. Published by Elsevier Ltd.

A five-city trial of a behavioural intervention to reduce sexually transmitted disease/HIV risk among sex workers in China.

PubMed

Rou, Keming; Wu, Zunyou; Sullivan, Sheena G; Li, Fan; Guan, Jihui; Xu, Chen; Liu, Wei; Liu, Dahua; Yin, Yueping

2007-12-01

To explore and evaluate a sexually transmitted disease (STD)/HIV intervention program targeting female sex workers working in entertainment establishments in five different settings in China. A prospective, community-based, pre/post, intervention trial set in entertainment establishments (karaoke bars, massage parlours, dance halls, beauty parlours) where sex workers operate at sites in five provinces of China: Anhui, Beijing, Fujian, Guangxi and Xinjiang. The participants were all sex workers working in targeted entertainment establishments. A Women's Health Clinic was set up near participants' places of work at each site. Clinic-based outreach activities, including awareness-raising, condom promotion, and sexual health care, were developed and delivered to sex workers. Cross-sectional surveys at baseline and post-intervention were used to evaluate changes in condom use with the last three clients, and the prevalence of chlamydia and gonorrhoea. In total, 907 sex workers were surveyed at baseline and 782 at 12 months post-intervention. Outreach teams made 2552 visits to the target entertainment establishments, approached 13,785 female sex workers, and distributed 33,575 copies of education material and 5102 packets of condoms. The rate of condom use with the most recent three clients increased from 55.2% at baseline to 67.5% at 12 months evaluation. The prevalence of gonorrhoea fell from 26% at baseline to 4% after intervention, and that of chlamydia fell from about 41 to 26%. The intervention was effective for increasing condom use and reducing STD among sex workers. The results were used to develop national guidelines on sex worker interventions for nationwide scale up.

A parent-based intervention to promote healthy eating and active behaviours in pre-school children: evaluation of the MEND 2-4 randomized controlled trial.

PubMed

Skouteris, H; Hill, B; McCabe, M; Swinburn, B; Busija, L

2016-02-01

There is a paucity of studies evaluating targeted obesity prevention interventions in pre-school children. We conducted a randomized controlled trial to evaluate the efficacy of a parent-based obesity prevention intervention for pre-schoolers - MEND (Mind, Exercise, Nutrition … Do It!) 2-4 on child diet, eating habits, physical activity/sedentary behaviours, and body mass index (BMI). Parent-child dyads attended 10 weekly 90-min workshops relating to nutrition, physical activity and behaviours, including guided active play and healthy snack time. Assessments were conducted at baseline, immediately post-intervention, and 6 and 12 months post-intervention; child intake of vegetables, fruit, beverages, processed snack foods, fussiness, satiety responsiveness, physical activity, sedentary behaviour and neophobia were assessed via parent proxy report. Parent and child height and weight were measured. Two hundred one parent-child dyads were randomized to intervention (n = 104) and control (n = 97). Baseline mean child age was 2.7 (standard deviation [SD] 0.6) years, and child BMI-for-age z-score (World Health Organization) was 0.66 (SD 0.88). We found significant positive group effects for vegetable (P = 0.01) and snack food (P = 0.03) intake, and satiety responsiveness (P = 0.047) immediately post-intervention. At 12 months follow-up, intervention children exhibited less neophobia (P = 0.03) than controls. Future research should focus on additional strategies to support parents to continue positive behaviour change. ACTRN12610000200088. © 2015 World Obesity.

Descriptive analysis of a 1:1 physiotherapy outpatient intervention post primary lumbar discectomy: one arm of a small-scale parallel randomised controlled trial across two UK sites.

PubMed

Rushton, A; Calcutt, A; Heneghan, N; Heap, A; White, L; Calvert, M; Goodwin, P

2016-11-09

There is a lack of high-quality evidence for physiotherapy post lumbar discectomy. Substantial heterogeneity in treatment effects may be explained by variation in quality, administration and components of interventions. An optimised physiotherapy intervention may reduce heterogeneity and improve patient benefit. The objective was to describe, analyse and evaluate an optimised 1:1 physiotherapy outpatient intervention for patients following primary lumbar discectomy, to provide preliminary insights. A descriptive analysis of the intervention embedded within an external pilot and feasibility trial. Two UK spinal centres. Participants aged ≥18; post primary, single level, lumbar discectomy were recruited. The intervention encompassed education, advice, mobility and core stability exercises, progressive exercise, and encouragement of early return to work/activity. Patients received ≤8 sessions for ≤8 weeks, starting 4 weeks post surgery (baseline). Blinded outcome assessment at baseline and 12 weeks (post intervention) included the Roland Morris Disability Questionnaire. STarT Back data were collected at baseline. Statistical analyses summarised participant characteristics and preplanned descriptive analyses. Thematic analysis grouped related data. Twenty-two of 29 allocated participants received the intervention. STarT Back categorised n=16 (55%) participants 'not at low risk'. Physiotherapists identified reasons for caution for 8 (36%) participants, commonly risk of overdoing activity (n=4, 18%). There was no relationship between STarT Back and physiotherapists' evaluation of caution. Physiotherapists identified 154 problems (mean (SD) 5.36 (2.63)). Those 'not at low risk', and/or requiring caution presented with more problems, and required more sessions (mean (SD) 3.14 (1.16)). Patients present differently and therefore require tailored interventions. These differences may be identified using clinical reasoning and outcome data. ISRCTN33808269; post 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/.

Evaluation of the relative efficacy of a couple cognitive-behaviour therapy (CBT) for Premenstrual Disorders (PMDs), in comparison to one-to-one CBT and a wait list control: A randomized controlled trial.

PubMed

Ussher, Jane M; Perz, Janette

2017-01-01

A randomised control trial (RCT) was conducted to examine the efficacy of couple-based cognitive behaviour therapy (CBT) for Premenstrual Disorders (PMDs), in comparison to one-to-one CBT and a wait-list control. Triangulation of quantitative and qualitative outcome measures evaluated changes pre-post intervention. Eighty three women were randomly allocated across three conditions, with 63 completing post-intervention measures, a retention rate of 76%. Repeated measures analysis of variance found a significant time by group interaction identifying that women in the two CBT conditions reported lower total premenstrual symptoms, emotional reactivity/mood, and premenstrual distress, in comparison to the wait list control. Significantly higher active behavioural coping post-intervention was found in the couple condition than in the one-to-one and wait list control groups. Qualitative analysis provided insight into the subjective experience of PMDs and participation in the intervention study. Across groups, women reported increased awareness and understanding of premenstrual change post-intervention. A larger proportion of women in the CBT conditions reported reduction in intensity and frequency of negative premenstrual emotional reactivity, increased communication and help-seeking, increased understanding and acceptance of embodied change, and the development of coping skills, post-intervention. Increased partner understanding and improved relationship post-intervention was reported by a greater proportion of participants in the CBT conditions, most markedly in the couple condition. These findings suggest that one-to-one and couple CBT interventions can significantly reduce women's premenstrual symptomatology and distress, and improve premenstrual coping. Couple based CBT interventions may have a greater positive impact upon behavioural coping and perceptions of relationship context and support. This suggests that CBT should be available for women reporting moderate-severe PMDs, with couple-based CBT offering additional benefits to a one-to-one modality.

A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

PubMed

Lim, Keane; See, Yuen Mei; Lee, Jimmy

2017-11-30

The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer's disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington's disease, Parkinson's disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in Parkinson's disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.

Effect of manual therapy versus proprioceptive neuromuscular facilitation in dynamic balance, mobility and flexibility in field hockey players. A randomized controlled trial.

PubMed

Espí-López, Gemma V; López-Martínez, Susana; Inglés, Marta; Serra-Añó, Pilar; Aguilar-Rodríguez, Marta

2018-04-22

To compare the effectiveness of a specific Manual Therapy (MT) protocol applied to field hockey players (FHP), versus a Proprioceptive Neuromuscular Facilitation (PNF) protocol, in the improvement of dynamic balance, active range of movement and lumbar flexibility one-week and four-weeks after the treatment. Randomized controlled trial. Participants were assigned to 2 groups: MT and PNF. 30 min' sessions were performed once a week for three weeks. Three evaluations were performed: basal, one-week and four-weeks post-treatment. University of Valencia (Spain). 22 in MT group and 20 in PNF group. Dynamic Balance, measured with Star Excursion Balance Test; Active Range of Motion (ROM), using a manual goniometer and Lumbar Flexibility, assessed with Fingertip-to-floor test. Both groups significantly improved in lateral and medial dynamic balance one-week post-treatment (p < 0.05); but the improvement in the MT group lasted until the fourth-week after treatment in both reaches (lateral and medial) (p < 0.05). MT group also obtained significant improvements in dorsal flexion of the ankle in the fourth-week post-treatment (p < 0.05) and in lumbar flexibility one-week post-treatment (p < 0.05). MT and PNF improve dynamic balance one-week post-treatment; however, the improvement obtained through MT is maintained four-weeks later. Only MT improves dorsal flexion of the ankle four-weeks post-treatment and lumbar flexibility one-week post-treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impact of an alcohol harm reduction intervention on interpersonal violence and engagement in sex work among female sex workers in Mombasa, Kenya: Results from a randomized controlled trial*

PubMed Central

Parcesepe, Angela M.; L'Engle, Kelly L.; Martin, Sandra L.; Green, Sherri; Sinkele, William; Suchindran, Chirayath; Speizer, Ilene S.; Mwarogo, Peter; Kingola, Nzioki

2016-01-01

Aims To evaluate whether an alcohol harm reduction intervention was associated with reduced interpersonal violence or engagement in sex work among female sex workers (FSWs) in Mombasa, Kenya. Design Randomized controlled trial. Setting HIV prevention drop-in centers in Mombasa, Kenya. Participants 818 women 18 or older in Mombasa who visited HIV prevention drop-in centers, were moderate-risk drinkers and engaged in transactional sex in past six months (410 and 408 in intervention and control arms, respectively). Intervention 6 session alcohol harm reduction intervention. Comparator 6 session non-alcohol related nutrition intervention. Measurements In-person interviews were conducted at enrollment, immediately post-intervention and 6-months post-intervention. General linear mixed models examined associations between intervention assignment and recent violence (physical violence, verbal abuse, and being robbed in the past 30 days) from paying and non-paying sex partners and engagement in sex work in the past 30 days. Findings The alcohol intervention was associated with statistically significant decreases in physical violence from paying partners at 6 months post-intervention and verbal abuse from paying partners immediately post-intervention and 6-months post-intervention. Those assigned to the alcohol intervention had significantly reduced odds of engaging in sex work immediately post-intervention and 6-months post-intervention. Conclusions The alcohol intervention was associated with reductions in some forms of violence and with reductions in engagement in sex work among FSWs in Mombasa, Kenya. PMID:26872880

Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac arrest syndrome patients: study protocol for a randomized controlled trial.

PubMed

Meyer, Anna Sina P; Ostrowski, Sisse R; Kjaergaard, Jesper; Johansson, Pär I; Hassager, Christian

2016-08-02

Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery and AMI. Thus, a study is pertinent to investigate if prostacyclin infusion as a therapeutic intervention reduces endothelial damage without compromising, or even improving, the hemostatic competence in resuscitated cardiac arrest patients. Post-cardiac arrest patients frequently have a need for vasopressor therapy (catecholamines) to achieve the guideline-supported blood pressure goals. To evaluate a possible catecholamine interaction with the primary endpoints of this study, included patients will be randomized into two different blood pressure goals within guideline-recommended targets. A randomized, placebo-controlled, double-blind investigator-initiated pilot trial in 40 out-of-hospital-cardiac-arrest (OHCA) patients will be conducted. Patients will be randomly assigned to either the active treatment group (48 hours of active study drug (iloprost, 1 ng/kg/min) or to the control group [placebo (saline) infusion]. Target mean blood pressure levels will be allocated 1:1 to 65 mmHg or approximately 75 mmHg, which gives four different permutations, namely: (i) iloprost/65 mHg, (ii) iloprost/75 mmHg, (iii) placebo/65 mmHg, and (iv) placebo/75 mmHg. All randomized patients will be treated in accordance with state-of-the art therapy including targeted temperature management. The primary endpoint of this study is change in biomarkers indicative of endothelial activation and damage, [soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), nucleosomes] and sympathoadrenal over activation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization. The secondary endpoints of this trial will include: (1) the hemostatic profile [change in functional hemostatic blood test (thrombelastography (TEG) and whole blood platelet aggregometry (multiplate)) blood cell and endothelial cell-derived microparticles]; (2) feasibility of blood pressure target intervention (target 90 %); (3) interaction of primary endpoints and blood pressure target; (4) levels of neuron-specific enolase at 48 hours post-inclusion according to blood pressure targets. The ENDO-RCA study is a pilot study trial that investigates safety and efficacy of low-dose infusion of prostacyclin administration as compared to standard therapy in post-cardiac arrest syndrome patients. Trial registration at ClinicalTrials.gov (identifier NCT02685618 ) on 18 February 2016.

Resident Work Hour Restrictions and Change Management: A Cautionary Tale.

PubMed

Fang, Z Amy; Hudson, Darren

2015-01-01

Residents are a significant part of coverage in many hospitals. Resident associations are negotiating work hour limits to prevent fatigue-induced medical errors. Our intensive care unit experienced an unexpected resident shortage and used the opportunity to trial a shift schedule for one month. Post-surveys were sent to nurses, attending physicians and residents to evaluate the effects on staff interactions, patient safety and education quality. The trial was clearly a failure on all fronts. Work hour restrictions are a reality in medical education, and administrators need to start considering alternative staffing models and discussing alternative schedules with their medicine faculty.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial

PubMed Central

Bradley, John; Knight, Philip; Stone, William; Osoti, Victor; Makori, Euniah; Owaga, Chrispin; Odongo, Wycliffe; China, Pauline; Shagari, Shehu; Doumbo, Ogobara K.; Sauerwein, Robert W.; Kariuki, Simon; Drakeley, Chris; Stevenson, Jennifer; Cox, Jonathan

2016-01-01

Background Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities. Methods and Findings Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June–6 July 2012) and 16 wk (21 August–10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons. Conclusions Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear. Trial registration ClinicalTrials.gov NCT01575613 PMID:27071072

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

PubMed Central

Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

2016-01-01

Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287 PMID:27490698

Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections.

PubMed

Haas, David M; Morgan, Sarah; Contreras, Karenrose

2014-09-09

Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman's return to normal function and her ability to care for her baby. Despite the widespread use of prophylactic antibiotics, postoperative infectious morbidity still complicates cesarean deliveries. To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities, including endometritis and wound complications. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 July 2014). We included randomized and quasi-randomized trials assessing the impact of vaginal cleansing immediately before cesarean delivery with any type of antiseptic solution versus a placebo solution/standard of care on post-cesarean infectious morbidity. We independently assessed eligibility and quality of the studies. Five trials randomizing 1946 women (1766 analyzed) evaluated the effects of vaginal cleansing (all with povidone-iodine) on post-cesarean infectious morbidity. The risk of bias was generally low, with the quality of most of the studies being high. Vaginal preparation immediately before cesarean delivery significantly reduced the incidence of post-cesarean endometritis from 7.2% in control groups to 3.6% in vaginal cleansing groups (average risk ratio (RR) 0.39, 95% confidence interval (CI) 0.16 to 0.97, five trials, 1766 women). The risk reduction was particularly strong for women with ruptured membranes (1.4% in the vaginal cleansing group versus 15.4% in the control group; RR 0.13, 95% CI 0.02 to 0.66, two trials, 148 women). No other outcomes realized statistically significant differences between the vaginal cleansing and control groups. No adverse effects were reported with the povidone-iodine vaginal cleansing.The quality of the evidence using GRADE was low for post-cesarean endometritis, moderate for postoperative fever, and low for wound infection. Vaginal preparation with povidone-iodine solution immediately before cesarean delivery reduces the risk of postoperative endometritis. This benefit is particularly realized for women undergoing cesarean delivery with ruptured membranes. As a simple, generally inexpensive intervention, providers should consider implementing preoperative vaginal cleansing with povidone-iodine before performing cesarean deliveries.

Variability in Post-Error Behavioral Adjustment Is Associated with Functional Abnormalities in the Temporal Cortex in Children with ADHD

ERIC Educational Resources Information Center

Spinelli, Simona; Vasa, Roma A.; Joel, Suresh; Nelson, Tess E.; Pekar, James J.; Mostofsky, Stewart H.

2011-01-01

Background: Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral…

Nutrient-enriched formula versus standard term formula for preterm infants following hospital discharge.

PubMed

Henderson, G; Fahey, T; McGuire, W

2007-10-17

Preterm infants are often growth-restricted at hospital discharge. Feeding infants after hospital discharge with nutrient-enriched formula rather than standard term formula might facilitate "catch-up" growth and improve development. To determine the effect of feeding nutrient-enriched formula compared with standard term formula on growth and development for preterm infants following hospital discharge. The standard search strategy of the Cochrane Neonatal Review Group were used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - May 2007), EMBASE (1980 - May 2007), CINAHL (1982 - May 2007), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared the effect of feeding preterm infants following hospital discharge with nutrient-enriched formula compared with standard term formula. Data was extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis of data using weighted mean difference and a fixed effects model for meta-analysis. Seven trials were found that were eligible for inclusion. These recruited a total of 631 infants and were generally of good methodological quality. The trials found little evidence that feeding with nutrient-enriched formula milk affected growth and development. Because of differences in the way individual trials measured and presented outcomes, data synthesis was limited. Growth data from two trials found that, at six months post-term, infants fed with nutrient-enriched formula had statistically significantly lower weights [weighted mean difference: -601 (95% confidence interval -1028, -174) grams], lengths [-18.8 (-30.0, -7.6) millimetres], and head circumferences [-10.2 ( -18.0, -2.4) millimetres], than infants fed standard term formula. At 12 to 18 months post-term, meta-analyses of data from three trials did not find any statistically significant differences in growth parameters. However, examination of these meta-analyses demonstrated statistical heterogeneity. Meta-analyses of data from two trials did not reveal a statistically significant difference in Bayley Mental Development or Psychomotor Development Indices. There are not yet any data on growth or development through later childhood. The available data do not provide strong evidence that feeding preterm infants following hospital discharge with nutrient-enriched formula compared with standard term formula affects growth rates or development up to 18 months post-term.

The Seamless Transfer-of-Care Protocol: a randomized controlled trial assessing the efficacy of an electronic transfer-of-care communication tool.

PubMed

Okoniewska, Barbara M; Santana, Maria J; Holroyd-Leduc, Jayna; Flemons, Ward; O'Beirne, Maeve; White, Deborah; Clement, Fiona; Forster, Alan; Ghali, William A

2012-11-21

The transition between acute care and community care represents a vulnerable period in health care delivery. The vulnerability of this period has been attributed to changes to patients' medication regimens during hospitalization, failure to reconcile discrepancies between admission and discharge and the burdening of patients/families to take over care responsibilities at discharge and to relay important information to the primary care physician. Electronic communication platforms can provide an immediate link between acute care and community care physicians (and other community providers), designed to ensure consistent information transfer. This study examines whether a transfer-of-care (TOC) communication tool is efficacious and cost-effective for reducing hospital readmission, adverse events and adverse drug events as well as reducing death. A randomized controlled trial conducted on the Medical Teaching Unit of a Canadian tertiary care centre will evaluate the efficacy and cost-effectiveness of a TOC communication tool. Medical in-patients admitted to the unit will be considered for this study. Data will be collected upon admission, and a total of 1400 patients will be randomized. The control group's acute care stay will be summarized using a traditional dictated summary, while the intervention group will have a summary generated using the TOC communication tool. The primary outcome will be a composite, at 3 months, of death or readmission to any Alberta acute-care hospital. Secondary outcomes will be the occurrence of post-discharge adverse events and adverse drug events at 1 month post discharge. Patients with adverse outcomes will have their cases reviewed by two Royal College certified internists or College-certified family physicians, blinded to patients' group assignments, to determine the type, severity, preventability and ameliorability of all detected adverse outcomes. An accompanying economic evaluation will assess the cost per life saved, cost per readmission avoided and cost per QALY gained with the TOC communication tool compared to traditional dictation summaries. This paper outlines the study protocol for a randomized controlled trial evaluating an electronic transfer-of-care communication tool, with sufficient statistical power to assess the impact of the tool on the significant outcomes of post-discharge death or readmission. The study findings will inform health systems around the world on the potential benefits of such tools, and the value for money associated with their widespread implementation. ClinicalTrials.gov NCT01402609.

Analysing Time to Event Data in Dementia Prevention Trials: The Example of the GuidAge Study of EGb761.

PubMed

Scherrer, B; Andrieu, S; Ousset, P J; Berrut, G; Dartigues, J F; Dubois, B; Pasquier, F; Piette, F; Robert, P; Touchon, J; Garnier, P; Mathiex-Fortunet, H; Vellas, B

2015-12-01

Time-to-event analysis is frequently used in medical research to investigate potential disease-modifying treatments in neurodegenerative diseases. Potential treatment effects are generally evaluated using the logrank test, which has optimal power and sensitivity when the treatment effect (hazard ratio) is constant over time. However, there is generally no prior information as to how the hazard ratio for the event of interest actually evolves. In these cases, the logrank test is not necessarily the most appropriate to use. When the hazard ratio is expected to decrease or increase over time, alternative statistical tests such as the Fleming-Harrington test, provide a better sensitivity. An example of this comes from a large, five-year randomised, placebo-controlled prevention trial (GuidAge) in 2854 community-based subjects making spontaneous memory complaints to their family physicians, which evaluated whether treatment with EGb761 can modify the risk of developing AD. The primary outcome measure was the time to conversion from memory complaint to Alzheimer's type dementia. Although there was no significant difference in the hazard function of conversion between the two treatment groups according to the preplanned logrank test, a significant treatment-by-time interaction for the incidence of AD was observed in a protocol-specified subgroup analysis, suggesting that the hazard ratio is not constant over time. For this reason, additional post hoc analyses were performed using the Fleming-Harrington test to evaluate whether there was a signal of a late effect of EGb761. Applying the Fleming-Harrington test, the hazard function for conversion to dementia in the placebo group was significantly different from that in the EGb761 treatment group (p = 0.0054), suggesting a late effect of EGb761. Since this was a post hoc analysis, no definitive conclusions can be drawn as to the effectiveness of the treatment. This post hoc analysis illustrates the interest of performing another randomised clinical trial of EGb761 explicitly testing the hypothesis of a late treatment effect, as well as of using of better adapted statistical approaches for long term preventive trials when it is expected that prevention cannot have an immediate effect but rather a delayed effect that increases over time.

Mechanism evaluation of a lifestyle intervention for patients with musculoskeletal pain who are overweight or obese: protocol for a causal mediation analysis

PubMed Central

Lee, Hopin; Wiggers, John; Kamper, Steven J; Williams, Amanda; O'Brien, Kate M; Hodder, Rebecca K; Yoong, Sze Lin; Campbell, Elizabeth; Haskins, Robin; Robson, Emma K; McAuley, James H; Williams, Christopher M

2017-01-01

Introduction Low back pain (LBP) and knee osteoarthritis (OA) are highly prevalent and disabling conditions that cause societal and economic impact worldwide. Two randomised controlled trials (RCTs) will evaluate the effectiveness of a multicomponent lifestyle intervention for patients with LBP and knee OA who are overweight or obese. The key targets of this intervention are to improve physical activity, modify diet and correct pain beliefs. These factors may explain how a lifestyle intervention exerts its effects on key patient-relevant outcomes: pain, disability and quality of life. The aim of this protocol is to describe a planned analysis of a mechanism evaluation for a lifestyle intervention for overweight or obese patients with LBP and knee OA. Methods and analysis Causal mediation analyses of 2 two-armed RCTs. Both trials are part of a cohort-multiple RCT, embedded in routine health service delivery. In each respective trial, 160 patients with LBP and 120 patients with knee OA waiting for orthopaedic consultation will be randomised to a lifestyle intervention, or to remain part of the original cohort. The intervention consists of education and advice about the benefits of weight loss and physical activity, and the Australian New South Wales Get Healthy Service. All outcome measures including patient characteristics, primary and alternative mediators, outcomes, and potential confounders will be measured at baseline (T0). The primary mediator, weight, will be measured at 6 months post randomisation; alternative mediators including diet, physical activity and pain beliefs will be measured at 6 weeks post randomisation. All outcomes (pain, disability and quality of life) will be measured at 6 months post randomisation. Data will be analysed using causal mediation analysis with sensitivity analyses for sequential ignorability. All mediation models were specified a priori before completing data collection and without prior knowledge about the effectiveness of the intervention. Ethics and dissemination The study is approved by the Hunter New England Health Human Research Ethics Committee (13/12/11/5.18) and the University of Newcastle Human Research Ethics Committee (H-2015–0043). The results will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration number ACTRN12615000490572 and ACTRN12615000478516; Pre-results. PMID:28674135

A Randomized Controlled Trial of Mindfulness Meditation for Chronic Insomnia

PubMed Central

Ong, Jason C.; Manber, Rachel; Segal, Zindel; Xia, Yinglin; Shapiro, Shauna; Wyatt, James K.

2014-01-01

Study Objectives: To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. Design: Three-arm, single-site, randomized controlled trial. Setting: Academic medical center. Participants: Fifty-four adults with chronic insomnia. Interventions: Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. Measurements and Results: Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. Conclusions: Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. Trial Registration: Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781 Citation: Ong JC, Manber R, Segal Z, Xia Y, Shapiro S, Wyatt JK. A randomized controlled trial of mindfulness meditation for chronic insomnia. SLEEP 2014;37(9):1553-1563. PMID:25142566

A Randomized Controlled Trial of Team-Based Learning Versus Lectures with Break-Out Groups on Knowledge Retention.

PubMed

Thrall, Grace C; Coverdale, John H; Benjamin, Sophiya; Wiggins, Anna; Lane, Christianne Joy; Pato, Michele T

2016-10-01

This goal of this study was to evaluate the efficacy of team-based learning (TBL) on knowledge retention compared to traditional lectures with small break-out group discussion (teaching as usual (TAU)) using a randomized controlled trial. This randomized controlled trial was conducted during a daylong conference for psychiatric educators on attention-deficit hyperactivity disorder and the research literacy topic of efficacy versus effectiveness trials. Learners (n = 115) were randomized with concealed allocation to either TBL or TAU. Knowledge was measured prior to the intervention, immediately afterward, and 2 months later via multiple-choice tests. Participants were necessarily unblinded. Data enterers, data analysts, and investigators were blinded to group assignment in data analysis. Per-protocol analyses of test scores were performed using change in knowledge from baseline. The primary endpoint was test scores at 2 months. At baseline, there were no statistically significant differences between groups in pre-test knowledge. At immediate post-test, both TBL and TAU groups showed improved knowledge scores compared with their baseline scores. The TBL group performed better statistically on the immediate post-test than the TAU group (Cohen's d = 0.73; p < 0.001), although the differences in knowledge scores were not educationally meaningful, averaging just one additional test question correct (out of 15). On the 2-month remote post-test, there were no group differences in knowledge retention among the 42 % of participants who returned the 2-month test. Both TBL and TAU learners acquired new knowledge at the end of the intervention and retained knowledge over 2 months. At the end of the intervention day and after 2 months, knowledge test scores were not meaningfully different between TBL and TAU completers. In conclusion, this study failed to demonstrate the superiority of TBL over TAU on the primary outcome of knowledge retention at 2 months post-intervention.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

PubMed

Protic, Mladjan; Veljkovic, Radovan; Bilchik, Anton J; Popovic, Ana; Kresoja, Milana; Nissan, Aviram; Avital, Itzhak; Stojadinovic, Alexander

2017-02-01

Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. This study was designed as single-blinded PRCT. This study was conducted in an academic medical center. Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Chest closure without drainage after open patent ductus arteriosus ligation in Ugandan children: A non blinded randomized controlled trial.

PubMed

Kebba, Naomi; Mwambu, Tom; Oketcho, Michael; Izudi, Jonathan; Obuku, Ekwaro A

2016-09-29

There is clinical equipoise regarding post-operative management of patients with patent ductus arteriosus (PDA) without insertion of a chest drain. This study evaluated post operative outcomes of chest closure with or without a drain following Patent Ductus Arteriosus ligation among childen at Uganda Heart Instritute (UHI). This was an open label randomized controlled trial of 62 children 12 years of age and below diagnosed with patent ductus arteriosus at Mulago National Teaching and Referral Hospital, Uganda. Participants were randomized in the ratio of 1:1 with surgical ligation of patent ductus arteriosus to either thoracotomy closure with a chest tube or without a chest tube. All participants received standard care and were monitored hourly for 24 hours then until hospital discharge. The combined primary endpoint consisted of significant pleural space accumulation of fluid or air, higher oxygen need or infection of the surgical site. Analysis was conducted by multivariable logistic regression analysis at 5 % significance level. We enrolled 62 participants, 46 (74 %) of whom were females. Their median age was 12 months (IQR: 8-36). Participants in the no-drain arm significantly had less post-operative complications compared to the drain arm (Unadjusted odds ratio [uOR]: 0.21, 95 % CI: 0.06-0.73, p = 0.015). This "protective effect" remained without statistical significance in the multivariable regression model (Adjusted odds ratio [aOR]: 0.07, 95 % CI: 0.00-2.50, p = 0.144). Children aged below 6 years with patent ductus arterious can safely and effectively have thoracotomy closure without using a drain in uncomplicated surgical ligation of the PDA. Chest drain was associated with post-operative complications. The trial was registered in the Pan African Clinical Trials registry on 1st/July/2012, retrospectively registered. Identifier number PACTR201207000395469 .

Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial.

PubMed

Weaver, Lindell K; Wilson, Steffanie H; Lindblad, Anne S; Churchill, Susan; Deru, Kayla; Price, Robert C; Williams, Chris S; Orrison, William W; Walker, James M; Meehan, Anna; Mirow, Susan

2018-01-01

In prior military randomized trials, participants with persistent symptoms after mild traumatic brain injury (TBI) reported improvement regardless of receiving hyperbaric oxygen (HBO₂) or sham intervention. This study's objectives were to identify outcomes for future efficacy trials and describe changes by intervention. This Phase II, randomized, double-blind, sham-controlled trial enrolled military personnel with mild TBI and persistent post-concussive symptoms. Participants were randomized to receive 40 HBO₂ (1.5 atmospheres absolute (ATA), ⟩99% oxygen, 60 minutes) or sham chamber sessions (1.2 ATA, room air, 60 minutes) over 12 weeks. Participants and evaluators were blinded to allocation. Outcomes assessed at baseline, 13 weeks and six months included symptoms, quality of life, neuropsychological, neurological, electroencephalography, sleep, auditory, vestibular, autonomic, visual, neuroimaging, and laboratory testing. Participants completed 12-month questionnaires. Intention-to-treat results are reported. From 9/11/2012 to 5/19/2014, 71 randomized participants received HBO₂ (n=36) or sham (n=35). At baseline, 35 participants (49%) met post-traumatic stress disorder (PTSD) criteria. By the Neurobehavioral Symptom Inventory, the HBO₂ group had improved 13-week scores (mean change -3.6 points, P=0.03) compared to sham (+3.9 points). In participants with PTSD, change with HBO₂ was more pronounced (-8.6 vs. +4.8 points with sham, P=0.02). PTSD symptoms also improved in the HBO₂ group, and more so in the subgroup with PTSD. Improvements regressed at six and 12 months. Hyperbaric oxygen improved some cognitive processing speed and sleep measures. Participants with PTSD receiving HBO₂ had improved functional balance and reduced vestibular complaints at 13 weeks. By 13 weeks, HBO₂ improved post-concussive and PTSD symptoms, cognitive processing speed, sleep quality, and balance function, most dramatically in those with PTSD. Changes did not persist beyond six months. Several outcomes appeared sensitive to change; additional studies are warranted. Copyright© Undersea and Hyperbaric Medical Society.

[Declaration of the Chilean Academy of Medicine of Law 20.850 “On clinical trials of pharmaceutical products and medical devices” and of the bylaw that will regulate its application].

PubMed

López S, Gloria; Valdés S, Gloria; Roessler B, Emilio; Valdivieso D, Vicente

2017-03-01

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1. The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2.The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3. Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians’ interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients’ ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.

Doing Anger Differently: Two Controlled Trials of Percussion Group Psychotherapy for Adolescent Reactive Aggression

ERIC Educational Resources Information Center

Currie, Michael; Startup, Mike

2012-01-01

This study evaluates efficacy and effectiveness of "Doing Anger Differently" (DAD), a group treatment for reactively aggressive 12-15 year old males. DAD uses percussion exercises to aid treatment. Study 1 compared a ten-week treatment with a waitlist control at pre, post and 6 month (treatment group only) follow-up. Study 2 replicated Study 1,…

Programs for Prevention of Externalizing Problems in Children: Limited Evidence for Effect beyond 6 Months Post Intervention

ERIC Educational Resources Information Center

Smedler, Ann-Charlotte; Hjern, Anders; Wiklund, Stefan; Anttila, Sten; Pettersson, Agneta

2015-01-01

Background: Preventing externalizing problems in children is a major societal concern, and a great number of intervention programs have been developed to this aim. To evaluate their preventive effects, well-controlled trials including follow-up assessments are necessary. Methods: This is a systematic review of the effect of prevention programs…

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial.

PubMed

Norman, Wendy V; Kaczorowski, Janusz; Soon, Judith A; Brant, Rollin; Bryan, Stirling; Trouton, Konia J; Dicus, Lyda

2011-06-14

We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion.

Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

PubMed

Deck, Daniel H; Jordan, Jennifer M; Holland, Thomas L; Fan, Weihong; Wikler, Matthew A; Sulham, Katherine A; Ralph Corey, G

2016-09-01

Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. The Medicines Company, Parsippany, NJ, USA. ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II).

Provider Training to Screen and Initiate Evidence-Based Pediatric Obesity Treatment in Routine Practice Settings: A Randomized Pilot Trial.

PubMed

Kolko, Rachel P; Kass, Andrea E; Hayes, Jacqueline F; Levine, Michele D; Garbutt, Jane M; Proctor, Enola K; Wilfley, Denise E

This randomized pilot trial evaluated two training modalities for first-line, evidence-based pediatric obesity services (screening and goal setting) among nursing students. Participants (N = 63) were randomized to live interactive training or Web-facilitated self-study training. Pretraining, post-training, and 1-month follow-up assessments evaluated training feasibility, acceptability, and impact (knowledge and skill via simulation). Moderator (previous experience) and predictor (content engagement) analyses were conducted. Nearly all participants (98%) completed assessments. Both types of training were acceptable, with higher ratings for live training and participants with previous experience (ps < .05). Knowledge and skill improved from pretraining to post-training and follow-up in both conditions (ps < .001). Live training demonstrated greater content engagement (p < .01). The training package was feasible, acceptable, and efficacious among nursing students. Given that live training had higher acceptability and engagement and online training offers greater scalability, integrating interactive live training components within Web-based training may optimize outcomes, which may enhance practitioners' delivery of pediatric obesity services. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

A crossover trial evaluating an educational-behavioural joint protection programme for people with rheumatoid arthritis.

PubMed

Hammond, A; Lincoln, N; Sutcliffe, L

1999-05-01

Joint protection (JP) is a self-management technique widely taught to people with rheumatoid arthritis (RA). JP education aims to enable people with RA to reduce pain, inflammation, joint stress and reduce risks of deformity through using assistive devices and alternative movement patterns of affected joints to perform everyday activities. Previous studies evaluating JP education methods common in the UK have identified JP adherence is poor. A group education programme was developed using the Health Belief Model and Self-efficacy Theory. Strategies used to maximise JP adherence included goal-setting, contracting, modelling, homework programmes, motor learning theory, recall enhancing methods and mental practice. A crossover trial (n = 35) was conducted. Adherence with JP was measured using an objective observational test (the Joint Protection Behaviour Assessment). Significant improvements in use of JP were recorded at 12 and 24 weeks post-education (P < 0.01). No significant changes in measures of pain, functional disability, grip strength, self-efficacy or helplessness occurred post-education, although this may have been due to the small sample size recruited. In conclusion, JP adherence can be facilitated through the use of educational-behavioural strategies, suggesting this approach should be more widely adopted in clinical practice.

Getting clinical trial results into practice: design, implementation, and process evaluation of the ALLHAT Dissemination Project

PubMed Central

Bartholomew, L Kay; Cushman, William C; Cutler, Jeffrey A; Davis, Barry R; Dawson, Glenna; Einhorn, Paula T; Graumlich, James F; Piller, Linda B; Pressel, Sara; Roccella, Edward J; Simpson, Lara; Whelton, Paul K; Williard, Angela

2009-01-01

Background Conventional dissemination of clinical trial results has inconsistent impact on physician practices. A more comprehensive plan to influence determinants of prescribing practices is warranted. Purpose To report the response from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial to the National Heart, Lung, and Blood Institute’s requirement for dissemination and evaluation of trials with potential immediate public health applicability. Methods ALLHAT’s dissemination plan had two-components: 1) a traditional approach of media coverage, scientific presentation and publication; and 2) a theory-based approach targeting determinants of clinician behavior. Strategies included (1) academic detailing, in which physicians approach colleagues regarding blood pressure management, (2) direct patient messages to stimulate communication with physicians regarding blood pressure control, (3) approaches to formulary systems to use educational and economic incentives for evidence-based prescription, and (4) direct professional organization appeals to clinicians. Results One hundred and forty-seven Investigator Educators reported 1698 presentations to 18,524 clinicians in 41 states and the District of Columbia. The pre- and post-test responses of 1709 clinicians in the face-to-face meetings indicated significant changes in expectations for positive patient outcomes and intention to prescribe diuretics. Information was mailed to 55 individuals representing 20 professional organizations and to eight formulary systems. Direct-to-patient messages were provided to 14 sites that host patient newsletters and Web sites such as health plans and insurance companies, 62 print mass media outlets, and 12 broadcast media sites. Limitations It was not within the scope of the project to conduct a randomized trial of the impact of the dissemination. However, impact evaluation using quasi-experimental designs is ongoing. Conclusions A large multi-method dissemination of clinical trial results is feasible. Planning for dissemination efforts, including evaluation research, should be considered as a part of the funding and design of the clinical trial and should begin early in trial planning. PMID:19587068

Getting clinical trial results into practice: design, implementation, and process evaluation of the ALLHAT Dissemination Project.

PubMed

Bartholomew, L Kay; Cushman, William C; Cutler, Jeffrey A; Davis, Barry R; Dawson, Glenna; Einhorn, Paula T; Graumlich, James F; Piller, Linda B; Pressel, Sara; Roccella, Edward J; Simpson, Lara; Whelton, Paul K; Williard, Angela; Allhat Collaborative Research Group

2009-08-01

Conventional dissemination of clinical trial results has inconsistent impact on physician practices. A more comprehensive plan to influence determinants of prescribing practices is warranted. To report the response from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial to the National Heart, Lung, and Blood Institute's requirement for dissemination and evaluation of trials with potential immediate public health applicability. ALLHAT's dissemination plan had two-components: (1) a traditional approach of media coverage, scientific presentation, and publication; and (2) a theory-based approach targeting determinants of clinician behavior. Strategies included: (1) academic detailing, in which physicians approach colleagues regarding blood pressure management, (2) direct patient messages to stimulate communication with physicians regarding blood pressure control, (3) approaches to formulary systems to use educational and economic incentives for evidence-based prescription, and (4) direct professional organization appeals to clinicians. One hundred and forty-seven Investigator Educators reported 1698 presentations to 18,524 clinicians in 41 states and the District of Columbia. The pre- and post-test responses of 1709 clinicians in the face-to-face meetings indicated significant changes in expectations for positive patient outcomes and intention to prescribe diuretics. Information was mailed to 55 individuals representing 20 professional organizations and to eight formulary systems. Direct-to-patient messages were provided to 14 sites that host patient newsletters and Web sites such as health plans and insurance companies, 62 print mass media outlets, and 12 broadcast media sites. It was not within the scope of the project to conduct a randomized trial of the impact of the dissemination. However, impact evaluation using quasi-experimental designs is ongoing. A large multi-method dissemination of clinical trial results is feasible. Planning for dissemination efforts, including evaluation research, should be considered as a part of the funding and design of the clinical trial and should begin early in trial planning.

A Preliminary Study of the Effectiveness of Chinese Therapeutic Food on Regulating Female Reproductive Hormones

PubMed Central

Fu, Lulu; Xu, Hong

2011-01-01

This study investigated the effectiveness of Chinese therapeutic food on female reproductive hormones in a double-blind, placebo-controlled clinical trial. Chinese kiwi fruit extract (Hong En No. 1) was provided for Australian peri-menopausal women for one month. Chinese medical assessment and urinary 2-hydroxyestrone (2-OHE) and 16alpha-hydroxyestrone (16alpha-OHE) tests were conducted. Twenty-six urinary samples (pre and post-trial) which met the requirement of testing were analysed, the ratio 2-OHE:16alpha-OHE of pre-trial (1.18 ± 0.34) and post-trial (0.97 ± 0.29) in the control group (n = 6) decreased but showed no significant change, this ratio of pre-trial (1.44 ± 0.16) and post-trial (1.65 ± 0.21) in the treatment group (n = 7) indicated an improvement (P = 0.066), which results in beneficial hormone regulation. The Chinese medicine assessment indicated that the patterns of disharmony mainly include Liver Qi stagnation and Liver-Kidney Yin deficiency patterns. No significant change observed in the control group, significant score reduction of the patterns of disharmony was achieved at post-trial in the treatment group, which indicates an improvement of general health condition. PMID:21614163

The impact of standalone call centres and GP cooperatives on access to after hours GP care: a before and after study adjusted for secular trend.

PubMed

Dunt, David; Day, Susan E; Kelaher, Margaret; Montalto, Michael

2006-08-01

The After Hours Primary Medical Trials were initiated by the Australian government to redress difficulties in after hours (AH) GP care in areas of high need. The study's objective is to study the impact of two standalone call centres and one GP cooperative offering comprehensive services, in improving consumer access to services for residents of a defined geographic area. A pre-post design was used to evaluate their impact after adjusting for secular trend at a national level. Access was considered in terms of availability, accessibility, affordability, acceptability and responsiveness of care. Unmet need and ease of obtaining AH telephone professional medical advice were also considered. Pre-trial and post-trial telephone surveys of two separate random samples of approximately 350 households using AH services in each trial area as well as in a national sample outside the trial areas. Consumer acceptability and affordability increased in residents in the area served by the GP cooperative. Access, however measured, did not improve in either of the standalone call centre areas. Reduction in unmet need approached but did not achieve statistical significance in most but not all trial areas. Improvements in access in the GP cooperative conformed to expectations based on current and pre-existing AH care arrangements put in place. Absence of improvements in access in the standalone call centres did not conform to expectations but may be partly explained by the reductions in consumer acceptability, following introduction of telephone triage systems reported elsewhere.

Beneficial effects of citrus juice fermented with Lactobacillus plantarum YIT 0132 on atopic dermatitis: results of daily intake by adult patients in two open trials.

PubMed

Harima-Mizusawa, Naomi; Kamachi, Keiko; Kano, Mitsuyoshi; Nozaki, Daisuke; Uetake, Tatsuo; Yokomizo, Yuji; Nagino, Takayuki; Tanaka, Akira; Miyazaki, Kouji; Nakamura, Shinichiro

2016-01-01

This study aimed to examine whether daily intake of citrus juice containing heat-killed Lactobacillus plantarum YIT 0132 (LP0132-fermented juice) alleviates symptoms of atopic dermatitis. This was a natural extension of our previous study in which LP0132 was shown to enhance IL-10 production in vitro and LP0132-fermented juice was found to alleviate symptoms and enhance quality of life (QOL) in patients with Japanese cedar pollinosis. In two open trials, Trial 1 and Trial 2, 32 and 18 adult patients with mild to moderate atopic dermatitis consumed LP0132-fermented juice for 8 weeks. Skin conditions and QOL were subjectively evaluated using Skindex-16 before intake of the juice (Pre-treatment), 8 weeks after starting intake (Treatment) and 8 weeks after termination of intake (Post-treatment). Blood parameters were also analyzed. Comparison of the Treatment and Post-treatment time points with the Pre-treatment time point revealed significant reductions in the Skindex-16 overall score and the 3 domain subscores (symptoms, emotions, and functioning domains) in both trials. Moreover, blood levels of eosinophil cationic protein (ECP), total immunoglobulin E (IgE) and specific IgEs for Japanese cedar and cypress pollen were significantly attenuated in Trial 2. The findings suggest that daily intake of citrus fermented juice containing heat-killed LP0132 has beneficial effects on symptoms and QOL in patients with mild to moderate atopic dermatitis due to an immunomodulatory effect via attenuation of IgE and ECP.

Beneficial effects of citrus juice fermented with Lactobacillus plantarum YIT 0132 on atopic dermatitis: results of daily intake by adult patients in two open trials

PubMed Central

HARIMA-MIZUSAWA, Naomi; KAMACHI, Keiko; KANO, Mitsuyoshi; NOZAKI, Daisuke; UETAKE, Tatsuo; YOKOMIZO, Yuji; NAGINO, Takayuki; TANAKA, Akira; MIYAZAKI, Kouji; NAKAMURA, Shinichiro

2015-01-01

This study aimed to examine whether daily intake of citrus juice containing heat-killed Lactobacillus plantarum YIT 0132 (LP0132-fermented juice) alleviates symptoms of atopic dermatitis. This was a natural extension of our previous study in which LP0132 was shown to enhance IL-10 production in vitro and LP0132-fermented juice was found to alleviate symptoms and enhance quality of life (QOL) in patients with Japanese cedar pollinosis. In two open trials, Trial 1 and Trial 2, 32 and 18 adult patients with mild to moderate atopic dermatitis consumed LP0132-fermented juice for 8 weeks. Skin conditions and QOL were subjectively evaluated using Skindex-16 before intake of the juice (Pre-treatment), 8 weeks after starting intake (Treatment) and 8 weeks after termination of intake (Post-treatment). Blood parameters were also analyzed. Comparison of the Treatment and Post-treatment time points with the Pre-treatment time point revealed significant reductions in the Skindex-16 overall score and the 3 domain subscores (symptoms, emotions, and functioning domains) in both trials. Moreover, blood levels of eosinophil cationic protein (ECP), total immunoglobulin E (IgE) and specific IgEs for Japanese cedar and cypress pollen were significantly attenuated in Trial 2. The findings suggest that daily intake of citrus fermented juice containing heat-killed LP0132 has beneficial effects on symptoms and QOL in patients with mild to moderate atopic dermatitis due to an immunomodulatory effect via attenuation of IgE and ECP. PMID:26858928

An acceptance-oriented cognitive-behavioral therapy in multimodal rehabilitation: a pre-post test evaluation in highly distressed patients with rheumatic diseases.

PubMed

Vriezekolk, Johanna E; Eijsbouts, Agnes M M; van Lankveld, Wim G J M; Beenackers, Hanneke; Geenen, Rinie; van den Ende, Cornelia H M

2013-06-01

To examine the potential effectiveness of a multimodal rehabilitation program including an acceptance-oriented cognitive-behavioral therapy for highly distressed patients with rheumatic diseases. An observational study employing a one-group pre-post test design (N=25). The primary outcome was psychological distress. Secondary outcomes were quality of life, illness acceptance, and coping flexibility. Group pre-to-post and pre-to-12 months follow-up treatment changes were evaluated by paired-samples t-tests and Cohen's effect sizes (d). Individual changes were evaluated by the reliable change index (RCI) and clinically significant change (CSC) parameters. Significant effects were found post-treatment and maintained at 12 months in psychological distress (d>0.80), illness acceptance (d=1.48) and the SF-36 subscales role physical, vitality, and mental health (d ≥ 0.65). No significant effects were found for coping flexibility and the SF-36 subscales physical functioning, bodily pain, social functioning, and role emotional. Both a reliable (RCI) and clinically significant (CSC) improvement was observed for almost half of the highly distressed patients. The patients enrolled in the multimodal rehabilitation program showed improved psychological health status from pre to post-treatment. A randomized clinical trial is needed to confirm or refute the added value of an acceptance-oriented cognitive-behavioral therapy for highly distressed patients in rehabilitation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Home-Based Older People's Exercise (HOPE) trial: study protocol for a randomised controlled trial

PubMed Central

2011-01-01

Background Frailty is common in older age, and is associated with important adverse health outcomes including increased risk of disability and admission to hospital or long-term care. Exercise interventions for frail older people have the potential to reduce the risk of these adverse outcomes by increasing muscle strength and improving mobility. Methods/Design The Home-Based Older People's Exercise (HOPE) trial is a two arm, assessor blind pilot randomised controlled trial (RCT) to assess the effectiveness of a 12 week exercise intervention (the HOPE programme) designed to improve the mobility and functional abilities of frail older people living at home, compared with usual care. The primary outcome is the timed-up-and-go test (TUGT), measured at baseline and 14 weeks post-randomisation. Secondary outcomes include the Barthel Index of activities of daily living (ADL), EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life measure and the geriatric depression scale (GDS), measured at baseline and 14 weeks post-randomisation. We will record baseline frailty using the Edmonton Frail Scale (EFS), record falls and document muscle/joint pain. We will test the feasibility of collection of data to identify therapy resources required for delivery of the intervention. Discussion The HOPE trial will explore and evaluate a home-based exercise intervention for frail older people. Although previous RCTs have used operationalised, non-validated methods of measuring frailty, the HOPE trial is, to our knowledge, the first RCT of an exercise intervention for frail older people that includes a validated method of frailty assessment at baseline. Trial registration ISRCTN: ISRCTN57066881 PMID:21651805

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

PubMed

Schulman, Gerald; Berl, Tomas; Beck, Gerald J; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami

2016-09-30

The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. ClinicalTrials.gov NCT00500682 ; NCT00501046 .

Outcome Evaluation of Family Eats.

PubMed

Cullen, Karen Weber; Thompson, Debbe; Chen, Tzu-An

2017-02-01

This article presents the results of a randomized clinical trial evaluating the eight-session Family Eats web-based intervention promoting healthy home food environments for African American families. African American families ( n = 126) with 8- to 12-year-old children completed online baseline questionnaires and were randomized into intervention or control groups. Data collection occurred at baseline, immediately postintervention (Post 1), and 4 months later (Post 2), for parents and children, separately. There were two group by time intervention effects: Control group parents reported a significantly greater frequency of drinking 100% fruit juice at Post 1 compared with intervention group parents. Parent menu planning skills were significantly higher at Post 2 for the intervention group compared with the control group. Significant positive changes overtime were noted for both groups for home fruit/vegetable availability, food preparation practices, and healthy restaurant selection. Intervention group children reported a significant increase in home juice availability at Post 1 compared with the control group; home fruit availability improved for both groups. There was no difference in log on rates by group: 84% and 86% for those who completed Post 1 and Post 2 measurements, respectively. Sixty-four participants completed the evaluation survey: 17 control (50%) and 47 intervention (51%) participants. All participants reported liking the program components; all but one gave it an A or B grade. An Internet-delivered nutrition intervention for families was successful in achieving change in some mediating variables, with good log on rates. Future research with Family Eats should include larger sample sizes, with longer follow-up and a more objective measure of diet.

Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial.

PubMed

Willmott, C; Ponsford, J

2009-05-01

Most previous studies evaluating the use of methylphenidate following traumatic brain injury (TBI) have been conducted many years post-injury. This study evaluated the efficacy of methylphenidate in facilitating cognitive function in the inpatient rehabilitation phase. 40 participants with moderate-severe TBI (mean 68 days post-injury) were recruited into a randomised, crossover, double blind, placebo controlled trial. Methylphenidate was administered at a dose of 0.3 mg/kg twice daily and lactose in identical capsules served as placebo. Methylphenidate and placebo administration was randomised in a crossover design across six sessions over a 2 week period. Primary efficacy outcomes were neuropsychological tests of attention. No participants were withdrawn because of side effects or adverse events. Methylphenidate significantly increased speed of information processing on the Symbol Digit Modalities Test (95% CI 0.30 to 2.95, Cohen's d = 0.39, p = 0.02), Ruff 2 and 7 Test-Automatic Condition (95% CI 1.38 to 6.12, Cohen's d = 0.51, p = 0.003), Simple Selective Attention Task (95% CI -58.35 to -17.43, Cohen's d = 0.59, p = 0.001) and Dissimilar Compatible (95% CI -70.13 to -15.38, Cohen's d = 0.51, p = 0.003) and Similar Compatible (95% CI -74.82 to -19.06, Cohen's d = 0.55, p = 0.002) conditions of the Four Choice Reaction Time Task. Those with more severe injuries and slower baseline information processing speed demonstrated a greater drug response. Methylphenidate enhances information processing speed in the inpatient rehabilitation phase following TBI. This trial is registered with the Australian New Zealand Clinical Trials Registry (12607000503426).

A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms

PubMed Central

2009-01-01

Background This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. Methods Sixty-one adults were enrolled (age 36.5 ± 12.6 years; height 165.1 ± 9.2 cm; weight 75.4 ± 17.3 kg) and randomized to either Digestive Advantage™ Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use. Results Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. Conclusion In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. Trial Registration ClinicalTrials.gov Identifier: NCT00881322 PMID:19922649

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.

PubMed

Connick, Peter; Kolappan, Madhan; Patani, Rickie; Scott, Michael A; Crawley, Charles; He, Xiao-Ling; Richardson, Karen; Barber, Kelly; Webber, Daniel J; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; Samson, Rebecca S; Thomas, David L; Du, Ming-Qing; Luan, Shi L; Michell, Andrew W; Altmann, Daniel R; Thompson, Alan J; Miller, David H; Compston, Alastair; Chandran, Siddharthan

2011-03-02

No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach". MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS--the sentinel lesion approach--serving as proof of principle for its future wider applicability. ClinicalTrials.gov (NCT00395200).

Effects of acupuncture and computer-assisted cognitive training for post-stroke attention deficits: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; McCaskey, Michael A; Yang, Shanli; Ye, Haicheng; Tao, Jing; Jiang, Cai; Schuster-Amft, Corina; Balzer, Christian; Ettlin, Thierry; Schupp, Wilfried; Kulke, Hartwig; Chen, Lidian

2015-12-02

A majority of stroke survivors present with cognitive impairments. Attention disturbance, which leads to impaired concentration and overall reduced cognitive functions, is strongly associated with stroke. The clinical efficacy of acupuncture with Baihui (GV20) and Shenting (GV24) as well as computer-assisted cognitive training in stroke and post-stroke cognitive impairment have both been demonstrated in previous studies. To date, no systematic comparison of these exists and the potential beneficial effects of a combined application are yet to be examined. The main objective of this pilot study is to evaluate the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The second objective is to test the effects of a combined cognitive intervention that incorporates computer-assisted cognitive training and acupuncture (ACoTrain). An international multicentre, single-blinded, randomised controlled pilot trial will be conducted. In a 1:1:1 ratio, 60 inpatients with post-stroke cognitive dysfunction will be randomly allocated into either the acupuncture group, the computer-assisted cognitive training group, or the ACoTrain group in addition to their individual rehabilitation programme. The intervention period of this pilot trial will last 4 weeks (30 minutes per day, 5 days per week, Monday to Friday). The primary outcome is the test battery for attentional performance. The secondary outcomes include the Trail Making Test, Test des Deux Barrages, National Institute of Health Stroke Scale, and Modified Barthel Index for assessment of daily life competence, and the EuroQol Questionnaire for health-related quality of life. This trial mainly focuses on evaluating the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The results of this pilot trial are expected to provide new insights on how Eastern and Western medicine can complement one another and improve the treatment of cognitive impairments in early stroke rehabilitation. Including patients with different cultural backgrounds allows a more generalisable interpretation of the results but also poses risks of performance bias. Using standardised and well-described assessments, validated for each region, is pivotal to allow pooling of the data. Clinical Trails.gov ID: NCT02324959 (8 December 2014).

A Randomized Controlled Trial of Cognitive-Behavior Therapy Plus Bright Light Therapy for Adolescent Delayed Sleep Phase Disorder

PubMed Central

Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L.; Weaver, Edward; Trenowden, Sophie

2011-01-01

Objective: To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Design: Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Setting: Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. Patients: 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs WL: N = 17). Interventions: CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. Measurements and Results: DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P < 0.0001), yet 13% still met DSPD criteria at the 6-month follow-up. Conclusions: CBT plus BLT for adolescent DSPD is effective for improving multiple sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Clinical Trial Information: Australia – New Zealand Trials Registry Number: ACTRN12610001041044. Citation: Gradisar M; Dohnt H; Gardner G; Paine S; Starkey K; Menne A; Slater A; Wright H; Hudson JL; Weaver E; Trenowden S. A randomized controlled trial of cognitive-behavior therapy plus bright light therapy for adolescent delayed sleep phase disorder. SLEEP 2011;34(12):1671-1680. PMID:22131604

Learning before leaping: integration of an adaptive study design process prior to initiation of BetterBirth, a large-scale randomized controlled trial in Uttar Pradesh, India.

PubMed

Hirschhorn, Lisa Ruth; Semrau, Katherine; Kodkany, Bhala; Churchill, Robyn; Kapoor, Atul; Spector, Jonathan; Ringer, Steve; Firestone, Rebecca; Kumar, Vishwajeet; Gawande, Atul

2015-08-14

Pragmatic and adaptive trial designs are increasingly used in quality improvement (QI) interventions to provide the strongest evidence for effective implementation and impact prior to broader scale-up. We previously showed that an on-site coaching intervention focused on the World Health Organization Safe Childbirth Checklist (SCC) improved performance of essential birth practices (EBPs) in one facility in Karnataka, India. We report on the process and outcomes of adapting the intervention prior to larger-scale implementation in a randomized controlled trial in Uttar Pradesh (UP), India. Initially, we trained a local team of physicians and nurses to coach birth attendants in SCC use at two public facilities for 4-6 weeks. Trained observers evaluated adherence to EBPs before and after coaching. Using mixed methods and a systematic adaptation process, we modified and strengthened the intervention. The modified intervention was implemented in three additional facilities. Pre/post-change in EBP prevalence aggregated across facilities was analyzed. In the first two facilities, limited improvement was seen in EBPs with the exception of post-partum oxytocin. Checklists were used <25 % of observations. We identified challenges in physicians coaching nurses, need to engage district and facility leadership to address system gaps, and inadequate strategy for motivating SCC uptake. Revisions included change to peer-to-peer coaching (nurse to nurse, physician to physician); strengthened coach training on behavior and system change; adapted strategy for effective leadership engagement; and an explicit motivation strategy to enhance professional pride and effectiveness. These modifications resulted in improvement in multiple EBPs from baseline including taking maternal blood pressure (0 to 16 %), post-partum oxytocin (36 to 97 %), early breastfeeding initiation (3 to 64 %), as well as checklist use (range 32 to 88 %), all p < 0.01. Further adaptations were implemented to increase the effectiveness prior to full trial launch. The adaptive study design of implementation, evaluation, and feedback drove iterative redesign and successfully developed a SCC-focused coaching intervention that improved EBPs in UP facilities. This work was critical to develop a replicable BetterBirth package tailored to the local context. The multi-center pragmatic trial is underway measuring impact of the BetterBirth program on EBP and maternal-neonatal morbidity and mortality. NCT02148952 .

The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolonged exercise.

PubMed

Davison, Glen; Callister, Robin; Williamson, Gary; Cooper, Karen A; Gleeson, Michael

2012-02-01

Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise. Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design. DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function. Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.

Carers' assessment, skills and information sharing: theoretical framework and trial protocol for a randomised controlled trial evaluating the efficacy of a complex intervention for carers of inpatients with anorexia nervosa.

PubMed

Goddard, Elizabeth; Raenker, Simone; Macdonald, Pamela; Todd, Gillian; Beecham, Jennifer; Naumann, Ulrike; Bonin, Eva-Maria; Schmidt, Ulrike; Landau, Sabine; Treasure, Janet

2013-01-01

Experienced Carers Helping Others (ECHO) is a guided self-help intervention for carers of people with eating disorders to reduce distress and ameliorate interpersonal maintaining factors to improve patient outcomes. The aim of this paper is to describe the theoretical background and protocol of a randomised controlled trial that will establish whether ECHO has a significant beneficial effect for carers and the person they care for. Individuals with anorexia nervosa and carers will be recruited from eating disorder inpatient/day patient hospital services in the UK. Primary outcomes are time until relapse post-discharge (patient) and distress (carer) at 12 months post-discharge. Secondary outcomes are body mass index, eating disorder symptoms, psychosocial measures and health economic data for patients and carers. Carers will be randomised (stratified by site and illness severity) to receive ECHO (in addition to treatment as usual) or treatment as usual only. Potential difficulties in participant recruitment and delivery of the intervention are discussed. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.

Effects of exercise training using resistance bands on glycaemic control and strength in type 2 diabetes mellitus: a meta-analysis of randomised controlled trials.

PubMed

McGinley, Samantha K; Armstrong, Marni J; Boulé, Normand G; Sigal, Ronald J

2015-04-01

Resistance exercise using free weights or weight machines improves glycaemic control and strength in people with type 2 diabetes. Resistance band training is potentially less expensive and more accessible, but the effects of resistance band training on glycaemic control and strength in this population are not well understood. This paper aims to systematically review and meta-analyse the effect of resistance band training on haemoglobin A1c (HbA1c) and strength in adults with type 2 diabetes. Database searches were performed in August 2013 (MEDLINE, SPORTDiscus, EMBASE, and CINAHL). Reference lists of eligible articles were hand-searched for additional studies. Randomised trials evaluating the effects of resistance band training in adults with type 2 diabetes on HbA1c or objectively measured strength were selected. Baseline and post-intervention HbA1c and strength were extracted for the intervention and control groups. Details of the exercise interventions and methodological quality were collected. Seven trials met inclusion criteria. Post-intervention-weighted mean HbA1c was nonsignificantly lower in exercise groups compared to control groups [weighted mean difference (WMD) = -0.18 percentage points (-1.91 mmol/mol); P = 0.27]. Post-intervention strength was significantly higher in the exercise groups compared to the control groups in the lower extremities (WMD = 21.90 kg; P < 0.0001), but not in the upper extremities (WMD = 2.27 kg; P = 0.13) or handgrip (WMD = 1.98 kg; P = 0.46). All trials were small and had methodological limitations. Resistance band training did not significantly affect HbA1c, upper extremity, or handgrip strength but significantly increased the strength of the lower extremities in people with type 2 diabetes.

Pasteuria penetrans for Control of Meloidogyne incognita on Tomato and Cucumber, and M. arenaria on Snapdragon.

PubMed

Kokalis-Burelle, Nancy

2015-09-01

Meloidogyne incognita and Meloidogyne arenaria are important parasitic nematodes of vegetable and ornamental crops. Microplot and greenhouse experiments were conducted to test commercial formulations of the biocontrol agent Pasteuria penetrans for control of M. incognita on tomato and cucumber and M. arenaria on snapdragon. Three methods of application for P. penetrans were assessed including seed, transplant, and post-plant treatments. Efficacy in controlling galling and reproduction of the two root-knot nematode species was evaluated. Seed treatment application was assessed only for M. incognita on cucumber. Pasteuria treatment rates of a granular transplant formulation ranged from 1.5 × 10(5) endospores/cm(3) to 3 × 10(5) endospores/cm(3) of transplant mix applied at seeding. Additional applications of 1.5 × 10(5) endospores/cm(3) of soil were applied as a liquid formulation to soil post-transplant for both greenhouse and microplot trials. In greenhouse cucumber trials, all Pasteuria treatments were equivalent to steamed soil for reducing M. incognita populations in roots and soil, and reducing nematode reproduction and galling. In cucumber microplot trials there were no differences among treatments for M. incognita populations in roots or soil, eggs/g root, or root condition ratings. Nematode reproduction on cucumber was low with Telone II and with the seed treatment plus post-plant application of Pasteuria, which had the lowest nematode reproduction. However, galling for all Pasteuria treatments was higher than galling with Telone II. Root-knot nematode control with Pasteuria in greenhouse and microplot trials varied on tomato and snapdragon. Positive results were achieved for control of M. incognita with the seed treatment application on cucumber.

Pasteuria penetrans for Control of Meloidogyne incognita on Tomato and Cucumber, and M. arenaria on Snapdragon

PubMed Central

Kokalis-Burelle, Nancy

2015-01-01

Meloidogyne incognita and Meloidogyne arenaria are important parasitic nematodes of vegetable and ornamental crops. Microplot and greenhouse experiments were conducted to test commercial formulations of the biocontrol agent Pasteuria penetrans for control of M. incognita on tomato and cucumber and M. arenaria on snapdragon. Three methods of application for P. penetrans were assessed including seed, transplant, and post-plant treatments. Efficacy in controlling galling and reproduction of the two root-knot nematode species was evaluated. Seed treatment application was assessed only for M. incognita on cucumber. Pasteuria treatment rates of a granular transplant formulation ranged from 1.5 × 105 endospores/cm3 to 3 × 105 endospores/cm3 of transplant mix applied at seeding. Additional applications of 1.5 × 105 endospores/cm3 of soil were applied as a liquid formulation to soil post-transplant for both greenhouse and microplot trials. In greenhouse cucumber trials, all Pasteuria treatments were equivalent to steamed soil for reducing M. incognita populations in roots and soil, and reducing nematode reproduction and galling. In cucumber microplot trials there were no differences among treatments for M. incognita populations in roots or soil, eggs/g root, or root condition ratings. Nematode reproduction on cucumber was low with Telone II and with the seed treatment plus post-plant application of Pasteuria, which had the lowest nematode reproduction. However, galling for all Pasteuria treatments was higher than galling with Telone II. Root-knot nematode control with Pasteuria in greenhouse and microplot trials varied on tomato and snapdragon. Positive results were achieved for control of M. incognita with the seed treatment application on cucumber. PMID:26527842

Evaluating the efficacy of an integrated motivational interviewing and multi-modal exercise intervention for youth with major depression: Healthy Body, Healthy Mind randomised controlled trial protocol.

PubMed

Nasstasia, Yasmina; Baker, Amanda L; Halpin, Sean A; Hides, Leanne; Lewin, Terry J; Kelly, Brian J; Callister, Robin

2018-03-01

Recent meta-analytic reviews suggest exercise can reduce depression severity among adults with major depressive disorder (MDD); however, efficacy studies with depressed youth are limited. Few studies have investigated the efficacy of multi-modal exercise interventions in this population, addressed treatment engagement, or explored the differential effects of exercise on depressive symptom profiles. This paper describes the study protocol and recruitment pattern for an assessor blinded, two-arm randomised controlled trial investigating the efficacy of an integrated motivational interviewing (MI) and multi-modal exercise intervention in youth diagnosed with MDD. Associations between depressive symptom profiles (cognitive, somatic and affective) and psychological, physiological (fitness), and biological (blood biomarker) outcomes will also be examined. Participants aged 15-25 years with current MDD were recruited. Eligible participants were randomised and stratified according to gender and depression severity to either an immediate or delayed (control) group. The immediate group received a brief MI intervention followed by a 12-week small group exercise intervention (3 times per week for 1 h), all delivered by personal trainers. The delayed control group received the same intervention 12-weeks later. Both groups were reassessed at mid-treatment or mid-control, post-treatment or post-control, and follow-up (12 weeks post-treatment). 68 participants were recruited and randomly allocated to an intervention group. This trial will increase our understanding of the efficacy of multi-modal exercise interventions for depression and the specific effects of exercise on depressive symptom profiles. It also offers a novel contribution by addressing treatment engagement in exercise efficacy trials in youth with MDD.

Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

PubMed

Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

2016-01-01

Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

An integrated intervention to reduce intimate partner violence and psychological distress with refugees in low-resource settings: study protocol for the Nguvu cluster randomized trial.

PubMed

Tol, Wietse A; Greene, M Claire; Likindikoki, Samuel; Misinzo, Lusia; Ventevogel, Peter; Bonz, Ann G; Bass, Judith K; Mbwambo, Jessie K K

2017-05-18

Intimate partner violence (IPV) is a critical public health and human rights concern globally, including for refugee women in low-resource settings. Little is known about effective interventions for this population. IPV and psychological distress have a bi-directional relationship, indicating the potential benefit of a structured psychological component as part of efforts to reduce IPV for women currently in violent relationships. This protocol describes a cluster randomized controlled trial aimed at evaluating an 8-session integrated psychological and advocacy intervention (Nguvu) with female adult survivors of past-year IPV displaying moderate to severe psychological distress. Outcomes are reductions in: recurrence of IPV; symptoms of anxiety, depression and post-traumatic stress (primary); and functional impairment (secondary). Hypothesized mediators of the intervention are improvements in social support, coping skills and support seeking. We will recruit 400 participants from existing women's support groups operating within villages in Nyarugusu refugee camp, Tanzania. Women's groups will be randomized to receive the intervention (Nguvu and usual care) or usual care alone. All eligible women will complete a baseline assessment (week 0) followed by a post-treatment (week 9) and a 3-month post-treatment assessment (week 20). The efficacy of the intervention will be determined by between-group differences in the longitudinal trajectories of primary outcomes evaluated using mixed-effects models. Study procedures have been approved by Institutional Review Boards in the United States and Tanzania. This trial will provide evidence on the efficacy of a novel integrated group intervention aimed at secondary prevention of IPV that includes a structured psychological component to address psychological distress. The psychological and advocacy components of the proposed intervention have been shown to be efficacious for their respective outcomes when delivered in isolation; however, administering these approaches through a single, integrated intervention may result in synergistic effects given the interrelated, bidirectional relationship between IPV and mental health. Furthermore, this trial will provide information regarding the feasibility of implementing a structured intervention for IPV and mental health in a protracted humanitarian setting. ISRCTN65771265 , June 27, 2016.

Study Protocol: Evaluation of a DVD intervention designed to meet the informaton needs of patients with head and neck cancer and their partner, carer and families.

PubMed

Parker, Vicki; Bennett, Leearna; Bellamy, Douglas; Britton, Benjamin; Lambert, Sylvia

2016-11-22

Patients who undergo surgery for cancer of the head and neck and their families face complex and difficult challenges and are at risk of anxiety and depression and inability to cope with symptom and treatment burden. Information available to support them is not flexible enough to adjust to individual need. A randomised clinical trial pre and post intervention design, comparing the use of a tailored DVD intervention, provided preoperatively and used throughout the post- operative period, with usual treatment. One hundred fifty-six individuals or partner couples will be randomly recruited into either the intervention or control group. A survey will be administered at three time points, preoperatively, post operatively and 3 months post-surgery. Anxiety and empowerment are the primary outcome measures. Qualitative data about use of the resource will be gathered by phone interview. This is the first study to rigorously evaluate the impact of a DVD intervention for this group of patients and their family members. The study will help to understand the impact of information usage on patient and family well- being and test a means by which to evaluate information and education resources for this and other cancer patient groups. ACTRN12614001104640 . Date registered: 17/10/2014.

Prevention of generalized anxiety disorder using a web intervention, iChill: randomized controlled trial.

PubMed

Christensen, Helen; Batterham, Philip; Mackinnon, Andrew; Griffiths, Kathleen M; Kalia Hehir, Kanupriya; Kenardy, Justin; Gosling, John; Bennett, Kylie

2014-09-02

Generalized Anxiety Disorder (GAD) is a high prevalence, chronic disorder. Web-based interventions are acceptable, engaging, and can be delivered at scale. Few randomized controlled trials evaluate the effectiveness of prevention programs for anxiety, or the factors that improve effectiveness and engagement. The intent of the study was to evaluate the effectiveness of a Web-based program in preventing GAD symptoms in young adults, and to determine the role of telephone and email reminders. A 5-arm randomized controlled trial with 558 Internet users in the community, recruited via the Australian Electoral Roll, was conducted with 6- and 12-month follow-up. Five interventions were offered over a 10-week period. Group 1 (Active website) received a combined intervention of psycho-education, Internet-delivered Cognitive Behavioral Therapy (ICBT) for anxiety, physical activity promotion, and relaxation. Group 2 (Active website with telephone) received the identical Web program plus weekly telephone reminder calls. Group 3 (Active website with email) received the identical Web program plus weekly email reminders. Group 4 (Control) received a placebo website. Group 5 (Control with telephone) received the placebo website plus telephone calls. Main outcome measures were severity of anxiety symptoms as measured by the GAD 7-item scale (GAD-7) (at post-test, 6, and 12 months). Secondary measures were GAD caseness, measured by the Mini International Neuropsychiatric Interview (MINI) at 6 months, Centre for Epidemiologic Studies-Depression scale (CES-D), Anxiety Sensitivity Index (ASI), Penn State Worry Questionnaire (PSWQ), and Days out of Role. GAD-7 symptoms reduced over post-test, 6-month, and 12-month follow-up. There were no significant differences between Group 4 (Control) and Groups 1 (Active website), 2 (Active website with telephone), 3 (Active website with email), or 5 (Control with telephone) at any follow-up. A total of 16 cases of GAD were identified at 6 months, comprising 6.7% (11/165) from the Active groups (1, 2, 3) and 4.5% (5/110) from the Control groups (4, 5), a difference that was not significant. CES-D, ASI, and PSWQ scores were significantly lower for the active website with email reminders at post-test, relative to the control website condition. Indicated prevention of GAD was not effective in reducing anxiety levels, measured by GAD-7. There were significant secondary effects for anxiety sensitivity, worry, and depression. Challenges for indicated prevention trials are discussed. International Standard Randomized Controlled Trial Number (ISRCTN): 76298775; http://www.controlled-trials.com/ISRCTN76298775 (Archived by WebCite at http://www.webcitation.org/6S9aB5MAq).

Rho Inhibitor VX-210 in Acute Traumatic Subaxial Cervical Spinal Cord Injury: Design of the SPinal Cord Injury Rho INhibition InvestiGation (SPRING) Clinical Trial.

PubMed

Fehlings, Michael G; Kim, Kee D; Aarabi, Bizhan; Rizzo, Marco; Bond, Lisa M; McKerracher, Lisa; Vaccaro, Alexander R; Okonkwo, David O

2018-05-01

Traumatic spinal cord injury (SCI) is associated with a lifetime of disability stemming from loss of motor, sensory, and autonomic functions; these losses, along with increased comorbid sequelae, negatively impact health outcomes and quality of life. Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI. After an SCI, the enzyme, Rho, is activated by growth-inhibitory factors and regulates events that culminate in collapse of the neuronal growth cone, failure of axonal regeneration, and, ultimately, failure of motor and functional recovery. Inhibition of Rho activation is a potential treatment for injuries such as traumatic SCI. VX-210, an investigational agent, inhibits Rho. When administered extradurally after decompression (corpectomy or laminectomy) and stabilization surgery in a phase 1/2a study, VX-210 was well tolerated. Here, we describe the design of the SPRING trial, a multicenter, phase 2b/3, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of VX-210 (NCT02669849). A subset of patients with acute traumatic cervical SCI is currently being enrolled in the United States and Canada. Medical, neurological, and functional changes are evaluated at 6 weeks and at 3, 6, and 12 months after VX-210 administration. Efficacy will be assessed by the primary outcome measure, change in upper extremity motor score at 6 months post-treatment, and by secondary outcomes that include question-based and task-based evaluations of functional recovery.

Shortened dental arch and prosthetic effect on oral health-related quality of life: a systematic review and meta-analysis.

PubMed

Fueki, K; Baba, K

2017-07-01

This systematic review aimed to compare oral health-related quality of life (OHRQoL) between two tooth replacement strategies - the shortened dental arch (SDA) concept and conventional treatment with removable partial dental prosthesis (RPDP) or implant-supported fixed partial dental prosthesis (IFPDP) - for distal extension of edentulous space in the posterior area. We retrieved eligible randomised controlled trials (RCTs) and non-RCTs published between 1980 and November 2016 retrieved from MEDLINE and the Cochrane Central Register of Controlled Trials. The primary outcome was OHRQoL evaluated using validated questionnaires. Two reviewers independently screened and selected the articles, evaluated the risk of bias and determined the standardised weighted mean difference (SWMD) in OHRQoL scores between the two strategies using a random effects model. Two RCTs and one non-RCT involving 516 participants were included in this review. All studies employed the oral health impact profile (OHIP) for evaluation of OHRQoL. There was no statistically significant difference in OHIP summary scores between SDA and RPDP at 6 (SWMD = 0·24) or 12 (SWMD = 0·40) months post-treatment. Only one non-RCT had reported higher OHRQoL with IFPDP than with SDA; however, because of the small sample size, there was no significant difference in OHIP summary scores between the two strategies at 6 (SWMD = -0·59) or 12 (SWMD = -0·67) months post-treatment. In terms of OHRQoL in partially dentate patients, the SDA concept appears to be as feasible as RPDP restoration. Further clinical trials are required to clarify the effect of IFPDP restoration on OHRQoL. © 2017 John Wiley & Sons Ltd.

Cognitive behavioural therapy for psychopathology in relatives of missing persons: study protocol for a pilot randomised controlled trial.

PubMed

Lenferink, Lonneke I M; Wessel, Ineke; de Keijser, Jos; Boelen, Paul A

2016-01-01

It is hypothesized that the grieving process of relatives of missing persons is complicated by having to deal with uncertainty about the fate of their loved one. We developed a cognitive behavioural therapy (CBT) with mindfulness that focuses on dealing with this uncertainty. In this article, we elucidate the rationale of a pilot randomised controlled trial (RCT) for testing the feasibility and potential effectiveness of this CBT for reducing symptoms of psychopathology in relatives of missing persons. A pilot RCT comparing participants of the CBT condition ( n  = 15) with waiting list controls ( n  = 15) will be executed. Individuals suffering from psychopathology related to the long-term disappearance of a loved one are eligible to participate. The treatment consists of eight individual sessions. Questionnaires tapping psychological constructs will be administered before, during, and after the treatment. The feasibility of the treatment will be evaluated using descriptive statistics (e.g., attrition rate). The primary analysis consists of a within-group analysis of changes in mean scores of persistent complex bereavement disorder from baseline to immediately post-treatment and follow-up (12 and 24 weeks post-treatment). A significant number of people experience the disappearance of a loved one. Surprisingly, an RCT to evaluate a treatment for psychopathology among relatives of missing persons has never been conducted. Knowledge about treatment effects is needed to improve treatment options for those in need of help. The strengths of this study are the development of a tailored treatment for relatives of missing persons and the use of a pilot design before exposing a large sample to a treatment that has yet to be evaluated. Future research could benefit from the results of this study. NTR4732 (The Netherlands National Trial Register (NTR)).

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma.

PubMed

Deniger, Drew C; Kwong, Mei Li M; Pasetto, Anna; Dudley, Mark E; Wunderlich, John R; Langhan, Michelle M; Lee, Chyi-Chia Richard; Rosenberg, Steven A

2017-01-15

This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF V600 mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Metastases resected prior to and after 2 weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation, and recognition of autologous tumor. The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response, and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TILs and peripheral blood T cells were inhibited in vitro by research-grade vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality, and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TILs grown from pre- and post-vemurafenib metastases. Coadministration of vemurafenib and TILs was safe and feasible and generated objective clinical responses in this small pilot clinical trial. Clin Cancer Res; 23(2); 351-62. ©2016 AACRSee related commentary by Cogdill et al., p. 327. ©2016 American Association for Cancer Research.

Efficacy of preparation solutions and cleansing techniques on contamination of the skin in foot and ankle surgery: A systematic review and meta-analysis.

PubMed

Yammine, K; Harvey, A

2013-04-01

We report a systematic review and meta-analysis of published randomised and quasi-randomised trials evaluating the efficacy of pre-operative skin antisepsis and cleansing techniques in reducing foot and ankle skin flora. The post-preparation culture number (Post-PCN) was the primary outcome. The data were evaluated using a modified version of the Cochrane Collaboration’s tool. We identified eight trials (560 participants, 716 feet) that met the inclusion criteria. There was a significant difference in the proportions of Post-PCN between hallux nailfold (HNF) and toe web spaces (TWS) sites: 0.47 vs 0.22, respectively (95% confidence interval (CI) 0.182937 to 0.304097; p < 0.0001). Meta-analyses showed that alcoholic chlorhexidine had better efficacy than alcoholic povidone-iodine (PI) at HNF sites (risk difference 0.19 (95% CI 0.08 to 0.30); p = 0.0005); a two-step intervention using PI scrub and paint (S&P) followed by alcohol showed significantly better efficacy over PI (S&P) alone at TWS sites (risk difference 0.13 (95% CI 0.02 to 0.24); p = 0.0169); and a two-step intervention using chlorhexidine scrub followed by alcohol showed significantly better efficacy over PI (S&P) alone at the combined (HNF with TWS) sites (risk difference 0.27 (95% CI 0.13 to 0.40); p < 0.0001). No significant difference was found between cleansing techniques.

Dissonance-based prevention of eating disorder risk factors in middle school girls: results from two pilot trials.

PubMed

Rohde, Paul; Auslander, Beth A; Shaw, Heather; Raineri, Kate M; Gau, Jeff M; Stice, Eric

2014-07-01

Although several eating disorder prevention programs reduce eating disorder risk factors and symptoms for female high school and college students, few efficacious prevention programs exist for female middle school students, despite the fact that body image and eating disturbances often emerge then. Two pilot trials evaluated a new dissonance-based eating disorder prevention program for middle school girls with body image concerns. Female middle school students with body dissatisfaction from two sites [Study 1: N = 81, M age = 12.1, standard deviation (SD) = 0.9; Study 2: N = 52, M age = 12.5, SD = 0.8] were randomized to a dissonance intervention (MS Body Project) or educational brochure control; Study 2 included a 3-month follow-up. Intervention participants showed significant post-test reductions in only one of the six variables with both Studies 1 and 2 (i.e., pressure to be thin and negative affect, respectively), though post-test effect sizes suggested medium reductions in eating disorder risk factors and symptoms (Study 1: M d = .40; Study 2: M d = .65); reductions at 3-month follow-up in Study 2 were not evident (M d = .19). Results suggest that this new middle school version of the Body Project is producing medium magnitude reductions in eating disorder risk factors at post-test but that effects are showing limited persistence. Continued refinement and evaluation of this intervention appears warranted to develop more effective prevention programs for this age group. © 2014 Wiley Periodicals, Inc.

A randomized controlled trial of an intervention program to Brazilian mothers who use corporal punishment.

PubMed

Santini, Paolla Magioni; Williams, Lucia C A

2017-09-01

This study evaluated a positive parenting program to Brazilian mothers who used corporal punishment with their children. The intervention was conducted in four agencies serving vulnerable children, and at a home replica laboratory at the University. Mothers who admitted using corporal punishment were randomly assigned between experimental (n=20) and control group (n=20). The program consisted of 12 individual sessions using one unit from Projeto Parceria (Partnership Project), with specific guidelines and materials on positive parenting, followed by observational sessions of mother-child interaction with live coaching and a video feedback session in the lab. The study used an equivalent group experimental design with pre/post-test and follow-up, in randomized controlled trials. Measures involved: Initial Interview; Strengths and Difficulties Questionnaire (SDQ) - parent and child versions; Beck Depression Inventory (BDI); observational sessions with a protocol; and a Program Evaluation by participants. Analysis of mixed models for repeated measures revealed significant positive effects on the BDI and SDQ total scores, as well as less Conduct problems and Hyperactivity in SDQ measures from the experimental group mothers, comparing pre with post-test. Observational data also indicated significant improvement in positive interaction from the experimental group mothers at post-test, in comparison with controls. No significant results were found, however, in children's observational measures. Limitations of the study involved using a restricted sample, among others. Implications for future research are suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acceptability and feasibility of an e-mental health intervention for parents of childhood cancer survivors: "Cascade".

PubMed

Wakefield, Claire E; Sansom-Daly, Ursula M; McGill, Brittany C; Ellis, Sarah J; Doolan, Emma L; Robertson, Eden G; Mathur, Sanaa; Cohn, Richard J

2016-06-01

The aim of this study was to evaluate the feasibility and acceptability of "Cascade": an online, group-based, cognitive behavioral therapy intervention, delivered "live" by a psychologist, to assist parents of children who have completed cancer treatment. Forty-seven parents were randomized to Cascade (n = 25) or a 6-month waitlist (n = 22). Parents completed questionnaires at baseline, 1-2 weeks and 6 months post-intervention. Thirty parents completed full evaluations of the Cascade program (n = 21 randomized to Cascade, n = 9 completed Cascade post-waitlist). Ninety-six percent of Cascade participants completed the intervention (n = 24/25). Eighty percent of parents completed every questionnaire (mean completion time 25 min (SD = 12)). Cascade was described as at least "somewhat" helpful by all parents. None rated Cascade as "very/quite" burdensome. Parents reported that the "online format was easy to use" (n = 28, 93.3 %), "I learnt new skills" (n = 28, 93.3 %), and "I enjoyed talking to others" (n = 29, 96.7 %). Peer-to-peer benefits were highlighted by good group cohesion scores. Cascade is highly acceptable and feasible. Its online delivery mechanism may address inequities in post-treatment support for parents, a particularly acute concern for rural/remote families. Future research needs to establish the efficacy of the intervention. ACTRN12613000270718, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12613000270718.

A cluster randomised controlled trial of the Climate Schools: Ecstasy and Emerging Drugs Module in Australian secondary schools: study protocol

PubMed Central

2013-01-01

Background The use of ecstasy is a public health problem and is associated with a range of social costs and harms. In recent years, there has been growing concern about the availability and misuse of new and emerging drugs designed to mimic the effects of illicit drugs, including ecstasy. This, coupled with the fact that the age of use and the risk factors for using ecstasy and emerging drugs are similar, provides a compelling argument to implement prevention for these substances simultaneously. The proposed study will evaluate whether a universal Internet-based prevention program, known as the Climate Schools: Ecstasy and Emerging Drugs Module, can address and prevent the use of ecstasy and emerging drugs among adolescents. Methods A cluster randomised controlled trial will be conducted among Year 10 students (aged 15–16 years) from 12 secondary schools in Sydney, Australia. Schools will be randomly assigned to either the Climate Schools intervention group or the control group. All students will complete a self-report questionnaire at baseline, immediately post-intervention, and 6-, 12- and 24-months post-baseline. The primary outcome measures will include ecstasy and emerging drug-related knowledge, intentions to use these substances in the future, and the patterns of use of ecstasy and emerging drugs. A range of secondary outcomes will also be assessed, including beliefs and attitudes about ecstasy and emerging drugs, peer pressure resistance, other substance use and mental health outcomes. Discussion To our knowledge, this will be the first evaluation of an Internet-based program designed to specifically target ecstasy and NED use among adolescents. If deemed effective, the Climate Schools: Ecstasy and Emerging Drugs Module will provide schools with an interactive and novel prevention program for ecstasy and emerging drugs that can be readily implemented by teachers. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000708752. PMID:24330505

The efficacy and safety of Jiedu Tongluo granules for treating post-stroke depression with qi deficiency and blood stasis syndrome: study protocol for a randomized controlled trial.

PubMed

Zhao, Ai-Mei; Qiu, Wen-Ran; Mao, Li-Jun; Ren, Jun-Guo; Xu, Li; Yao, Ming-Jiang; Bilinksi, Kellie; Chang, Dennis; Liu, Jian-Xun

2018-05-10

Post-stroke depression (PSD) is the most common psychiatric complication after a stroke. The most frequently used antidepressants are selective serotonin receptor inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), however, these exhibit a series of side effects. Traditional Chinese medicine has been used to treat PSD with few side effects. The aim of this study is to evaluate the efficacy and safety of Jiedu Tongluo granules for treating PSD with qi deficiency and blood stasis syndrome. The planned study is a double-blind, randomized, placebo-controlled pilot trial. Eighty participants will be randomly assigned to receive either treatment or placebo. The treatment group will receive Jiedu Tongluo granules (JDTLG) with conventional treatment, and the placebo group will receive placebo with conventional treatment for 8 weeks. The primary outcome is the effectiveness of JDTLG on depression after 8 weeks treatment, which is defined as a decrease of 50% or more in 17-item Hamilton Depression Scale (HAMD-17) score or clinical recovery (score < 7). Secondary outcomes are improvement in neurological function, degree of independence, activities of daily living, and TCM syndrome at each visit, which will be measured with National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and TCM scale, respectively. Interleukin (IL)-6, IL-8, and small-molecule metabolites will be monitored to explore the mechanism of action of JDTLG on PSD. Safety measures include vital signs, results of electrocardiography, laboratory index (full blood count, kidney and liver function tests) and adverse events. The purpose of this trial is to evaluate the therapeutic effects and safety of JDTLG in individuals with PSD with concomitant qi deficiency and blood stasis syndrome. If successful, the outcome of this trial will provide a viable treatment option for PSD patients. ClinicalTrials.gov ID: NCT03147053 . Registered on 27 April 2017.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

PubMed

Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

2016-03-01

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

PubMed

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

Electrocardiographic effects of hawthorn (Crataegus oxyacantha) in healthy volunteers: A randomized controlled trial.

PubMed

Trexler, Stephanie E; Nguyen, Elaine; Gromek, Samantha M; Balunas, Marcy J; Baker, William L

2018-04-19

The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated. The primary endpoint was the change in corrected (Fridericia) QT intervals (QT c I) at 4 and 6 hr. Maximum post-dose QT c I and changes in PR and QRS intervals were measured. No significant differences in 4- or 6-hr QT c I were seen between hawthorn and placebo. Maximum post-dose QT c I in the hawthorn and placebo groups were similar (346 ± 35 vs 346 ± 40 ms; p = .979). No significant adverse events were seen. In conclusion, a single dose of oral hawthorn had no effect on electrocardiographic parameters in healthy volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

PubMed Central

Epperla, Narendranath; Fenske, Timothy S; Hari, Parameswaran N; Hamadani, Mehdi

2015-01-01

Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT. PMID:26421260

Feasibility of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Post-Acute Myocardial Infarction Patients and Refractory Angina Pectoris Patients.

PubMed

Myojo, Masahiro; Ando, Jiro; Uehara, Masae; Daimon, Masao; Watanabe, Masafumi; Komuro, Issei

2017-04-06

Extracorporeal shockwave myocardial revascularization (ESMR) is one of the new treatment options for refractory angina pectoris (RAP), and some studies have indicated its effectiveness. A single-arm prospective trial to assess the feasibility of ESMR using Cardiospec for patients with post-acute myocardial infarction (AMI) and RAP was designed and performed. The patients were treated with 9 sessions of ESMR to the ischemic areas for 9 weeks. The feasibility measures included echocardiography; cardiac magnetic resonance imaging; troponin T, creatine kinase-MB (CK-MB), and brain natriuretic peptide testing; and a Seattle Angina Questionnaire (SAQ) survey. Three post-AMI patients and 3 RAP patients were enrolled. The post-AMI patients had already undergone revascularization with percutaneous coronary intervention (PCI) in the acute phase. In two patients, adverse events requiring admission occurred: one a lumbar disc hernia in a post-AMI patient and the other congestive heart failure resulting in death in an RAP patient. No apparent elevations in CK-MB and troponin T levels during the trial were observed. Echocardiography revealed no remarkable changes of ejection fraction; however, septal E/E' tended to decrease after treatments (11.6 ± 4.8 versus 9.2 ± 2.8, P = 0.08). Concerning the available SAQ scores for two RAP patients, one patient reported improvements in angina frequency and treatment satisfaction and the other reported improvements in physical limitations and angina stability. In this feasibility study, ESMR seems to be a safe treatment for both post-AMI patients and RAP patients. The efficacy of ESMR for post-AMI patients remains to be evaluated with additional studies.

Effectiveness of Prophylactic Antibiotics against Post-Ureteroscopic Lithotripsy Infections: Systematic Review and Meta-Analysis.

PubMed

Lo, Chi-Wen; Yang, Stephen Shei-Dei; Hsieh, Cheng-Hsing; Chang, Shang-Jen

2015-08-01

To evaluate the effectiveness of prophylactic antibiotic therapy in reducing the incidence of post-ureteroscopic lithotripsy (URL) infections. A systemic search of PubMED was performed to identify all randomized trials that compared the incidence of post-operative infections in patients without pre-operative urinary tract infections who underwent URL with and without a single dose of prophylactic antibiotics. The data were analyzed using Cochrane Collaboration Review Manager (RevMan, version 5.2). The endpoints of the analysis were pyuria (>10 white blood cells/high-power field), bacteriuria (urine culture with bacteria >10(5) colony-forming units/mL), and febrile urinary tract infections (fUTIs), defined as a body temperature of >38°C with pyuria or meaningful bacteriuria within 1 wk after the operation. In total, four trials enrolling 500 patients met the inclusion criteria and were subjected to meta-analysis. Prophylactic antibiotics significantly reduced post-URL pyuria (risk ratios [RR] 0.65; 95% confidence interval [CI] 0.51-0.82) and bacteriuria (RR 0.26; 95% CI 0.12-0.60; p=0.001). Patients who received prophylactic antibiotics tended to have lower rates of fUTI, although the difference was not statistically significant. Prophylactic antibiotic therapy can reduce the incidence of pyuria and bacteriuria after URL. However, because of the low incidence of post-URL fUTIs, we failed to show that a single dose of prophylactic antibiotics can reduce the rate of such infections significantly.

Early motion and directed exercise (EMADE) versus usual care post ankle fracture fixation: study protocol for a pragmatic randomised controlled trial.

PubMed

Matthews, Paul A; Scammell, Brigitte E; Ali, Arfan; Coughlin, Timothy; Nightingale, Jessica; Khan, Tanvir; Ollivere, Ben J

2018-05-31

Following surgical fixation of ankle fractures, the traditional management has included immobilisation for 6 weeks in a below-knee cast. However, this can lead to disuse atrophy of the affected leg and joint stiffness. While early rehabilitation from 2 weeks post surgery is viewed as safe, controversy remains regarding its benefits. We will compare the effectiveness of early motion and directed exercise (EMADE) ankle rehabilitation, against usual care, i.e. 6 weeks' immobilisation in a below-knee cast. We have designed a pragmatic randomised controlled trial (p-RCT) to compare the EMADE intervention against usual care. We will recruit 144 independently living adult participants, absent of tissue-healing comorbidities, who have undergone surgical stabilisation of isolated Weber B ankle fractures. The EMADE intervention consists of a non-weight-bearing progressive home exercise programme, complemented with manual therapy and education. Usual care consists of immobilisation in a non-weight-bearing below-knee cast. The intervention period is between week 2 and week 6 post surgery. The primary outcome is the Olerud and Molander Ankle Score (OMAS) patient-reported outcome measure (PROM) at 12 weeks post surgery. Secondary PROMs include the EQ-5D-5 L questionnaire, return to work and return to driving, with objective outcomes including ankle range of motion. Analysis will be on an intention-to-treat basis. An economic evaluation will be included. The EMADE intervention is a package of care designed to address the detrimental effects of disuse atrophy and joint stiffness. An advantage of the OMAS is the potential of meta-analysis with other designs. Within the economic evaluation, the cost-utility analysis, may be used by commissioners, while the use of patient-relevant outcomes, such as return to work and driving, will ensure that the study remains pertinent to patients and their families. As it is being conducted in the clinical environment, this p-RCT has high external validity. Accordingly, if significant clinical benefits and cost-effectiveness are demonstrated, EMADE should become a worthwhile treatment option. A larger-scale, multicentre trial may be required to influence national guidelines. ISRCTN, ID: ISRCTN11212729 . Registered retrospectively on 20 March 2017.

The effects of selected dietary bioflavonoid supplementation on dental caries in young rats fed a high-sucrose diet.

PubMed

Wood, Nelson

2007-12-01

Recent evidence suggests that certain bioflavonoids reduce dental caries and cariogenic bacteria incidence. The present study evaluates two separate, but related, dietary trials -- trial 1, 0.09%, 0.18%, 0.36%, and 0.72% dietary naringenin (NAR) supplementation; and trial 2, 0.57% dietary rutin (R), quercetin (Q), and naringin (N) supplementation-on dental caries formation in 40 different male albino rats, at the expense of dextrose, for periods of 42 days. All rats were fed 40% sucrose. In dietary trial 1, rats were evaluated for dental caries, dental plaque accumulation, and saliva flow rates using oneway analysis of variance, post hoc Tukey's test, Kruskal-Wallis test, and Spearman's correlations. In dietary trial 2, rats were evaluated for occlusal dental caries only using a Kruskal-Wallis H test and analysis of variance. A 5% level of statistical significance was adopted throughout. In dietary trial 1, NAR showed a statistically significant effect on dental caries, plaque, and saliva flow rate reduction compared with the control group (P < .05-.01). An inverse dose-dependent relationship was established among the NAR experimental groups and control group. Dietary NAR supplementation significantly reduced dental caries formation, possibly because of reduced dental plaque accumulation. In dietary trial 2, statistically significant reductions in occlusal caries were observed for R, Q, and N in the maxillary molars and for Q and N in the mandibular molars compared with the control group (P < .05). Significant associations were observed among the experimental groups and maxillary (P < .05) and mandibular (P < .01) occlusal dental caries. Hence, selected bioflavonoids may show promise as an alternative means of reducing dental caries.

Cardiac Autonomic and Blood Pressure Responses to an Acute Foam Rolling Session.

PubMed

Lastova, Kevin; Nordvall, Michael; Walters-Edwards, Michelle; Allnutt, Amy; Wong, Alexei

2018-03-22

Foam Rolling (FR) is a self-myofascial release method that has become extremely popular among athletes and fitness enthusiasts for its ability to improve flexibility and range of motion and alleviate delayed onset muscle soreness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute FR session are currently unknown. The present study evaluated the effects of an acute session of FR exercise on heart rate variability (HRV) and BP responses in healthy individuals. Fifteen (M=8, F=7) healthy subjects completed either a FR or non-exercise control trial in randomized order. HRV and BP measurements were collected at baseline, 10 and 30 min after each trial. There were significant increases (P < 0.01) in markers of vagal tone (nHF) for 30 min after the FR trial, while no changes from baseline were observed following control. There were also significant decreases (P < 0.05) in markers of sympathetic activity (nLF), sympathovagal balance (nLF/nHF), systolic BP and diastolic BP at 10 and 30 min after the trial KB trial while no changes from baseline were observed after the control trial. Our findings indicate that FR decreases sympathovagal balance for 30 min post-intervention which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential cardiovascular protective effects of FR in diverse populations.

Nutrient-enriched formula versus standard formula for preterm infants following hospital discharge.

PubMed

Young, Lauren; Embleton, Nicholas D; McGuire, William

2016-12-13

Preterm infants are often growth-restricted at hospital discharge. Feeding nutrient-enriched formula rather than standard formula to infants after hospital discharge might facilitate 'catch-up' growth and might improve development. To compare the effects of nutrient-enriched formula versus standard formula on growth and development of preterm infants after hospital discharge. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (2016, Issue 8) in the Cochrane Library, MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; to 8 September 2016), as well as conference proceedings and previous reviews. Randomised and quasi-randomised controlled trials that compared the effects of feeding nutrient-enriched formula (postdischarge formula or preterm formula) versus standard term formula to preterm infants after hospital discharge . Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity by performing sensitivity analyses. We assessed quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 16 eligible trials with a total of 1251 infant participants. Trials were of variable methodological quality, with lack of allocation concealment and incomplete follow-up identified as major potential sources of bias. Trials (N = 11) that compared feeding infants with 'postdischarge formula' (energy density about 74 kcal/100 mL) versus standard term formula (about 67 kcal/100 mL) did not find consistent evidence of effects on growth parameters up to 12 to 18 months post term. GRADE assessments indicated that evidence was of moderate quality, and that inconsistency within pooled estimates was the main quality issue.Trials (N = 5) that compared feeding with 'preterm formula' (about 80 kcal/100 mL) versus term formula found evidence of higher rates of growth throughout infancy (weighted mean differences at 12 to 18 months post term: about 500 g in weight, 5 to 10 mm in length, 5 mm in head circumference). GRADE assessments indicated that evidence was of moderate quality, and that imprecision of estimates was the main quality issue.Few trials assessed neurodevelopmental outcomes, and these trials did not detect differences in developmental indices at 18 months post term. Data on growth or development through later childhood have not been provided. Recommendations to prescribe 'postdischarge formula' for preterm infants after hospital discharge are not supported by available evidence. Limited evidence suggests that feeding 'preterm formula' (which is generally available only for in-hospital use) to preterm infants after hospital discharge may increase growth rates up to 18 months post term.

Bioresorbable Scaffold for Treatment of Coronary Artery Lesions: Intravascular Ultrasound Results From the ABSORB Japan Trial.

PubMed

Okada, Kozo; Honda, Yasuhiro; Kitahara, Hideki; Otagiri, Kyuhachi; Tanaka, Shigemitsu; Hollak, M Brooke; Yock, Paul G; Popma, Jeffrey J; Kusano, Hajime; Cheong, Wai-Fung; Sudhir, Krishnankutty; Fitzgerald, Peter J; Kimura, Takeshi

2018-04-09

The aim of this study was to characterize post-procedural intravascular ultrasound (IVUS) findings in the ABSORB Japan trial, specifically stratified by the size of target coronary arteries. Despite overall noninferiority confirmed in recent randomized trials comparing bioresorbable vascular scaffolds (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting metallic stents (CoCr-EES), higher event rates of Absorb BVS have been reported with suboptimal deployment, especially in small coronary arteries. In the ABSORB Japan trial, 150 patients (2:1 randomization) were scheduled in the IVUS cohort. Small vessel was defined as mean reference lumen diameter <2.75 mm. Tapered-vessel lesions were defined as tapering index (proximal/distal reference lumen diameter) ≥1.2. Overall, IVUS revealed that the Absorb BVS arm had smaller device expansion than the CoCr-EES arm did, which was particularly prominent in small- and tapered-vessel lesions. Higher tapering index was also associated with higher rates of incomplete strut apposition in Absorb BVS, but not in CoCr-EES. With respect to procedural techniques, small-vessel lesions were treated more frequently with noncompliant balloons at post-dilatation but using significantly lower pressure in the Absorb BVS arm. In contrast, tapered-vessel lesions were post-dilated at equivalent pressure but with significantly smaller balloon catheters in the Absorb BVS arm, compared with the CoCr-EES arm. The significantly smaller device expansion especially in small vessels may account for the poorer outcomes of Absorb BVS in this lesion type. Appropriate optimization strategy, possibly different between polymeric and metallic devices, needs to be established for bioresorbable scaffold technology. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 Absorb™ BVS) in Japanese Population [ABSORB JAPAN]; NCT01844284). Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Tracheal intubation in critically ill patients: a comprehensive systematic review of randomized trials.

PubMed

Cabrini, Luca; Landoni, Giovanni; Baiardo Radaelli, Martina; Saleh, Omar; Votta, Carmine D; Fominskiy, Evgeny; Putzu, Alessandro; Snak de Souza, Cézar Daniel; Antonelli, Massimo; Bellomo, Rinaldo; Pelosi, Paolo; Zangrillo, Alberto

2018-01-20

We performed a systematic review of randomized controlled studies evaluating any drug, technique or device aimed at improving the success rate or safety of tracheal intubation in the critically ill. We searched PubMed, BioMed Central, Embase and the Cochrane Central Register of Clinical Trials and references of retrieved articles. Finally, pertinent reviews were also scanned to detect further studies until May 2017. The following inclusion criteria were considered: tracheal intubation in adult critically ill patients; randomized controlled trial; study performed in Intensive Care Unit, Emergency Department or ordinary ward; and work published in the last 20 years. Exclusion criteria were pre-hospital or operating theatre settings and simulation-based studies. Two investigators selected studies for the final analysis. Extracted data included first author, publication year, characteristics of patients and clinical settings, intervention details, comparators and relevant outcomes. The risk of bias was assessed with the Cochrane Collaboration's Risk of Bias tool. We identified 22 trials on use of a pre-procedure check-list (1 study), pre-oxygenation or apneic oxygenation (6 studies), sedatives (3 studies), neuromuscular blocking agents (1 study), patient positioning (1 study), video laryngoscopy (9 studies), and post-intubation lung recruitment (1 study). Pre-oxygenation with non-invasive ventilation (NIV) and/or high-flow nasal cannula (HFNC) showed a possible beneficial role. Post-intubation recruitment improved oxygenation , while ramped position increased the number of intubation attempts and thiopental had negative hemodynamic effects. No effect was found for use of a checklist, apneic oxygenation (on oxygenation and hemodynamics), videolaryngoscopy (on number and length of intubation attempts), sedatives and neuromuscular blockers (on hemodynamics). Finally, videolaryngoscopy was associated with severe adverse effects in multiple trials. The limited available evidence supports a beneficial role of pre-oxygenation with NIV and HFNC before intubation of critically ill patients. Recruitment maneuvers may increase post-intubation oxygenation. Ramped position increased the number of intubation attempts; thiopental had negative hemodynamic effects and videolaryngoscopy might favor adverse events.

A Pilot RCT of Psychodynamic Group Art Therapy for Patients in Acute Psychotic Episodes: Feasibility, Impact on Symptoms and Mentalising Capacity

PubMed Central

Montag, Christiane; Haase, Laura; Seidel, Dorothea; Bayerl, Martin; Gallinat, Jürgen; Herrmann, Uwe; Dannecker, Karin

2014-01-01

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function. Trial Registration ClinicalTrials.gov NCT01622166 PMID:25393414

Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System.

PubMed

Steinvil, Arie; Rogers, Toby; Torguson, Rebecca; Waksman, Ron

2016-09-12

This study aims to describe the discussions and recommendations made during the U.S. Food and Drug Administration (FDA) Circulatory System Device Panel pre-market approval application for the Absorb Bioresorbable Vascular Scaffold (BVS) System. The Absorb BVS System is a first-of-its-kind fully bioresorbable percutaneous coronary intervention technology. The absorb BVS was studied in the ABSORB III (A Clinical Evaluation of Absorb BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects with de Novo Native Coronary Artery Lesions) trial, the pivotal U.S. investigational device exemption trial. Observational report of the FDA Circulatory System Device Panel pre-market approval application meeting held on March 15, 2016. The U.S. FDA Circulatory System Device Panel members reviewed the ABSROB III trial outcomes and additional post hoc analyses presented by the sponsor and the FDA. The ABSORB III trial met the primary endpoint of noninferiority of Absorb BVS compared with the control, XIENCE drug-eluting stent, for target lesion failure at 1 year. Although a higher numerical trend for adverse outcomes was reported for the Absorb BVS, there were no statistical differences between Absorb BVS and XIENCE for any safety or effectiveness components for target lesion failure or for the secondary pre-specified outcomes. Panel members raised concerns with regard to the ABSORB III results and post hoc analyses focusing mainly on the noninferiority design of the trial, the apparent safety issues of the Absorb BVS in small vessels, the mismatch of visually versus intravascular imaging assessed vessel size found in ABSORB III and its implications on the adequate device labeling, the safety of Absorb BVS in specific patient and lesion subsets, and the post-approval commitments of the sponsor. Following panel discussions and the evidence presented, the panel voted for approval of the device. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Treatment of Post-Traumatic Stress Disorders with the Alpha-1 Adrenergic Antagonist Prazosin.

PubMed

Simon, Philippe Yves Rémy; Rousseau, Pierre-François

2017-03-01

The present review aims to assess the clinical efficacy and safety of the α-1-adrenergic antagonist prazosin as primary pharmacologic treatment for post-traumatic stress disorder (PTSD). A systematic review was performed using keywords (i.e., prazosin, α-1-adrenergic antagonist, α-1-blocker, post-traumatic stress disorder) in the databases PubMed/Medline (1966-May 2016), Embase (1966-May 2016), ScienceDirect (1823-May 2016), OvidSP (1946-May 2016) and Nature (1845-May 2016). To be considered for inclusion, studies had to test the efficacy of prazosin either alone or added to ongoing treatment in adults with PTSD, use validated tools to assess and monitor the disorders, allow comparisons on the basis of univariate analyses (i.e., p-values of t-tests and effect sizes) and list the identified adverse reactions. 12 studies were included: 5 randomized controlled trials, 4 open-label prospective trials and 3 retrospective file reviews. The evaluation concerned 276 patients exposed to civilian trauma (19%) or war trauma (81%). Prazosin significantly decreases trauma nightmares, avoidance, hypervigilance and improves patient status in all studies. No significant difference of blood pressure was observed at the end of trials. Beyond the methodological and clinical biases of these studies, the present review not only confirms the effectiveness and good tolerability of prazosin, but also suggests its possible use as primary pharmacologic treatment for PTSD. Uncertainties remain, however, regarding the prescription modalities and dosages.

Evaluating the implementation of a school-based emotional well-being programme: a cluster randomized controlled trial of Zippy's Friends for children in disadvantaged primary schools.

PubMed

Clarke, Aleisha M; Bunting, Brendan; Barry, Margaret M

2014-10-01

Schools are recognized as one of the most important settings for promoting social and emotional well-being among children and adolescents. This clustered randomized controlled trial evaluated Zippy's Friends, an international school-based emotional well-being programme, with 766 children from designated disadvantaged schools. The purpose of this study was to evaluate the immediate and long term impact of the programme and to determine the impact of implementation fidelity on programme outcomes. Teachers reported emotional literacy outcomes using the Emotional Literacy Checklist, and emotional and behavioural outcomes using the Strengths and Difficulties Questionnaire. Controlling for the hierarchical structure of the data, path analysis using structural equation modelling revealed that the programme had a significant positive impact on the children's emotional literacy scores including significant improvements in the subscale scores of self-awareness (P < 0.001), self-regulation (P < 0.01), motivation (P < 0.001) and social skills (P < 0.001) at post-intervention. These results were maintained at 12-month follow-up (P < 0.01). The programme, however, did not have a significant impact on children's emotional and behavioural problems. Analysis of programme fidelity indicated that high fidelity was directly related to improved emotional literacy scores at post-intervention. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prevention and treatment of long-term social disability amongst young people with emerging severe mental illness with social recovery therapy (The PRODIGY Trial): study protocol for a randomised controlled trial.

PubMed

Fowler, David; French, Paul; Banerjee, Robin; Barton, Garry; Berry, Clio; Byrne, Rory; Clarke, Timothy; Fraser, Rick; Gee, Brioney; Greenwood, Kathryn; Notley, Caitlin; Parker, Sophie; Shepstone, Lee; Wilson, Jon; Yung, Alison R; Hodgekins, Joanne

2017-07-11

Young people who have social disability associated with severe and complex mental health problems are an important group in need of early intervention. Their problems often date back to childhood and become chronic at an early age. Without intervention, the long-term prognosis is often poor and the economic costs very large. There is a major gap in the provision of evidence-based interventions for this group, and therefore new approaches to detection and intervention are needed. This trial provides a definitive evaluation of a new approach to early intervention with young people with social disability and severe and complex mental health problems using social recovery therapy (SRT) over a period of 9 months to improve mental health and social recovery outcomes. This is a pragmatic, multi-centre, single blind, superiority randomised controlled trial. It is conducted in three sites in the UK: Sussex, Manchester and East Anglia. Participants are aged 16 to 25 and have both persistent and severe social disability (defined as engaged in less than 30 hours per week of structured activity) and severe and complex mental health problems. The target sample size is 270 participants, providing 135 participants in each trial arm. Participants are randomised 1:1 using a web-based randomisation system and allocated to either SRT plus optimised treatment as usual (enhanced standard care) or enhanced standard care alone. The primary outcome is time use, namely hours spent in structured activity per week at 15 months post-randomisation. Secondary outcomes assess typical mental health problems of the group, including subthreshold psychotic symptoms, negative symptoms, depression and anxiety. Time use, secondary outcomes and health economic measures are assessed at 9, 15 and 24 months post-randomisation. This definitive trial will be the first to evaluate a novel psychological treatment for social disability and mental health problems in young people presenting with social disability and severe and complex non-psychotic mental health problems. The results will have important implications for policy and practice in the detection and early intervention for this group in mental health services. Trial Registry: International Standard Randomised Controlled Trial Number (ISRCTN) Registry. ISRCTN47998710 (registered 29/11/2012).

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data.

PubMed

Endrikat, J; Schwenke, C; Prince, M R

2015-07-01

To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18-64 years. Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. Copyright © 2015 The Royal College of Radiologists. All rights reserved.

Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance

PubMed Central

Pushkin, Richard; Barriere, Steven L.; Corey, G. Ralph; Stryjewski, Martin E.

2015-01-01

Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. This post hoc analysis included patients with lesion sizes of ≥75 cm2 and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of −4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, −0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin. PMID:26248356

Evaluation of skin pathologies by RGB autofluorescence imaging

NASA Astrophysics Data System (ADS)

Lihachev, Alexey; Plorina, Emilija V.; Derjabo, Alexander; Lange, Marta; Lihacova, Ilze

2017-12-01

A clinical trial on autofluorescence imaging of malignant and non-malignant skin pathologies comprising 32 basal cell carcinomas (BCC), 4 malignant melanomas (MM), 1 squamous cell carcinoma (SCC), 89 nevi, 14 dysplastic nevi, 20 hemangiomas, 23 seborrheic keratoses, 4 hyperkeratoses, 3 actinic keratoses, 3 psoriasis, 1 dematitis, 2 dermatofibromas, 5 papillofibromas, 12 lupus erythematosus, 7 purpura, 6 bruises, 5 freckles, 3 fungal infections, 1 burn, 1 tattoo, 1 age spot, 1 vitiligo, 32 postoperative scars, 8 post cream therapy BCCs, 4 post radiation therapy scars, 2 post laser therapy scars, 1 post freezing scar as well as 114 reference images of healthy skin was performed. The sequence of autofluorescence images of skin pathologies were recorded by smartphone RGB camera under continuous 405 nm LED excitation during 20 seconds with 0.5 fps. Obtained image sequences further were processed with subsequent extraction of autofluorescence intensity and photobleaching parameters.

Post-licence driver education for the prevention of road traffic crashes: a systematic review of randomised controlled trials.

PubMed

Ker, Katharine; Roberts, Ian; Collier, Timothy; Beyer, Fiona; Bunn, Frances; Frost, Chris

2005-03-01

The effectiveness of post-licence driver education for preventing road traffic crashes was quantified using a systematic review and meta-analyses of randomised controlled trials. Searches of appropriate electronic databases, the Internet and reference lists of relevant papers were conducted. The searches were not restricted by language or publication status. Data were pooled from 21 randomised controlled trials, including over 300,000 full licence-holding drivers of all ages. Nineteen trials reported subsequent traffic offences, with a pooled relative risk of 0.96 (95% confidence interval 0.94, 0.98). Fifteen trials reported traffic crashes with a pooled relative risk of 0.98 (0.96, 1.01). Four trials reported injury crashes with a pooled relative risk of 1.12 (0.88, 1.41). The results provide no evidence that post-licence driver education is effective in preventing road injuries or crashes. Although the results are compatible with a small reduction in the occurrence of traffic crashes, this may be due to selection biases or bias in the included trials.

Respecting and Fulfilling the Right of Post-Primary Pupils to Consent to Participate in Trials and Evaluative Research: A Discussion Paper

ERIC Educational Resources Information Center

Maguire, Lisa K.; Byrne, Bronagh; Kehoe, Susan

2018-01-01

This paper provides an introduction to issues surrounding the participation rights of young people in research and the implications of their growing involvement in research as well as providing a discourse on the ethical implications related to consent. The unique contribution of this paper is that it considers children's rights in respect to the…

Modeling Post-Accident Vehicle Egress

DTIC Science & Technology

2013-01-01

interest for military situations may involve rolled-over vehicles for which detailed movement data are not available. In the current design process...test trials. These evaluations are expensive and time-consuming, and are often performed late in the design process when it is too difficult to...alter the design if weaknesses are discovered. Yet, due to the limitations of current software tools, digital human models (DHMs) are not yet widely

Percutaneous Coronary Intervention of Left Main Disease: Pre- and Post-EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) Era.

PubMed

Park, Duk-Woo; Park, Seung-Jung

2017-06-01

For nearly half a century, coronary artery bypass grafting has been the standard treatment for patients with obstructive left main coronary artery (LMCA) disease. However, there has been considerable evolution in the field of percutaneous coronary intervention, and especially, percutaneous coronary intervention for LMCA disease has been rapidly expanded with adoption of drug-eluting stents. Some, but not all randomized trials, have shown that percutaneous coronary intervention with drug-eluting stents might be a suitable alternative for selected patients with LMCA disease instead of bypass surgery. However, none of previous trials involving early-generation drug-eluting stents was sufficiently powered and comparative trials using contemporary drug-eluting stents were limited. Recently, primary results of 2 new trials of EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) were reported. However, these trials showed conflicting results, which might pose uncertainty on the optimal revascularization strategy for LMCA disease. In this article, with the incorporation of a key review on evolution of LMCA treatment, we summarize the similarity or disparity of the EXCEL and NOBLE trials, focus on how they relate to previous trials in the field, and finally speculate on how the treatment strategy may be changed or recommended for LMCA treatment. © 2017 American Heart Association, Inc.

Identifying Important Gaps in Randomized Controlled Trials of Adult Cardiac Arrest Treatments: A Systematic Review of the Published Literature

PubMed Central

Sinha, Shashank S.; Sukul, Devraj; Lazarus, John J.; Polavarapu, Vivek; Chan, Paul S.; Neumar, Robert W.; Nallamothu, Brahmajee K.

2016-01-01

Background Cardiac arrests are a major public health concern worldwide. The extent and types of randomized controlled trials (RCTs) – our most reliable source of clinical evidence – conducted in these high-risk patients over recent years are largely unknown. Methods and Results We performed a systematic review, identifying all RCTs published in PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library from 1995 to 2014 that focused on acute treatment of non-traumatic cardiac arrest in adults. We then extracted data on the setting of study populations, types and timing of interventions studied, risk of bias, outcomes reported and how these factors have changed over time. Over this twenty-year period, 92 RCTs were published containing 64,309 patients (median, 225.5 per trial). Of these, 81 RCTs (88.0%) involved out-of-hospital cardiac arrest whereas 4 (4.3%) involved in-hospital cardiac arrest and 7 (7.6%) included both. Eighteen RCTs (19.6%) were performed in the U.S., 68 (73.9%) were performed outside the U.S., and 6 (6.5%) were performed in both settings. Thirty-eight RCTs (41.3%) evaluated drug therapy, 39 (42.4%) evaluated device therapy, and 15 (16.3%) evaluated protocol improvements. Seventy-four RCTs (80.4%) examined interventions during the cardiac arrest, 15 (16.3%) examined post-cardiac arrest treatment, and 3 (3.3%) studied both. Overall, reporting of risk of bias was limited. The most common outcome reported was ROSC: 86 (93.5%) with only 22 (23.9%) reporting survival beyond 6 months. Fifty-three RCTs (57.6%) reported global ordinal outcomes whereas 15 (16.3%) reported quality-of-life. RCTs in the last 5 years were more likely to be focused on protocol improvement and post-cardiac arrest care. Conclusions Important gaps in RCTs of cardiac arrest treatments exist, especially those examining in-hospital cardiac arrest, protocol improvement, post-cardiac arrest care, and long-term or quality-of-life outcomes. PMID:27756794

Study protocol: the Fueling Learning through Exercise (FLEX) study - a randomized controlled trial of the impact of school-based physical activity programs on children's physical activity, cognitive function, and academic achievement.

PubMed

Wright, Catherine M; Duquesnay, Paula J; Anzman-Frasca, Stephanie; Chomitz, Virginia R; Chui, Kenneth; Economos, Christina D; Langevin, Elizabeth G; Nelson, Miriam E; Sacheck, Jennifer M

2016-10-13

Physical activity (PA) is critical to preventing childhood obesity and contributes to children's overall physical and cognitive health, yet fewer than half of all children achieve the recommended 60 min per day of moderate-to-vigorous physical activity (MVPA). Schools are an ideal setting to meeting PA guidelines, but competing demands and limited resources have impacted PA opportunities. The Fueling Learning through Exercise (FLEX) Study is a randomized controlled trial that will evaluate the impact of two innovative school-based PA programs on children's MVPA, cognitive function, and academic outcomes. Twenty-four public elementary schools from low-income, ethnically diverse communities around Massachusetts were recruited and randomized to receive either 100 Mile Club® (walking/running program) or Just Move™ (classroom-based PA program) intervention, or control. Schoolchildren (grades 3-4, approximately 50 per school) were recruited to participate in evaluation. Primary outcome measures include PA via 7-day accelerometry (Actigraph GT3X+ and wGT3X-BT), cognitive assessments, and academic achievement via state standardized test scores. Additional measures include height and weight, surveys assessing psycho-social factors related to PA, and dietary intake. School-level surveys assess PA infrastructure and resources and intervention implementation. Data are collected at baseline, mid-point (5-6 months post-baseline), and post-intervention (approximately 1.5 years post-baseline). Demographic data were collected by parents/caregivers at baseline. Mixed-effect models will test the short- and long-term effects of both programs on minutes spent in MVPA, as well as secondary outcomes including cognitive and academic outcomes. The FLEX study will evaluate strategies for increasing children's MVPA through two innovative, low-cost, school-based PA programs as well as their impact on children's cognitive functioning and academic success. Demonstration of a relationship between school-based MVPA with neutral or improved, rather than diminished, academic outcomes in a naturalistic environment has the potential to positively influence investment in school PA programs and initiatives. ClinicalTrials.gov Identifier: NCT02810834 . Registered May 11, 2015. (Retrospectively registered).

Treatment of child anxiety disorders via guided parent-delivered cognitive-behavioural therapy: randomised controlled trial.

PubMed

Thirlwall, Kerstin; Cooper, Peter J; Karalus, Jessica; Voysey, Merryn; Willetts, Lucy; Creswell, Cathy

2013-12-01

Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings. To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders. A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group (trial registration: ISRCTN92977593). Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression - Improvement scale), and change in child anxiety symptoms (Spence Children's Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment. Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was unrelated to child outcome. Full guided parent-delivered CBT is an effective and inexpensive first-line treatment for child anxiety.

Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review

PubMed Central

Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2015-01-01

Objectives We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. Participants Men and women from 30 to 74 years of age. Setting Randomised trials on cancer screening. Design For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. Main outcome measures Relative risk of cancer death. Results In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. Conclusions The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups. PMID:26152677

A cluster randomized control field trial of the ABRACADABRA web-based reading technology: replication and extension of basic findings

PubMed Central

Piquette, Noella A.; Savage, Robert S.; Abrami, Philip C.

2014-01-01

The present paper reports a cluster randomized control trial evaluation of teaching using ABRACADABRA (ABRA), an evidence-based and web-based literacy intervention (http://abralite.concordia.ca) with 107 kindergarten and 96 grade 1 children in 24 classes (12 intervention 12 control classes) from all 12 elementary schools in one school district in Canada. Children in the intervention condition received 10–12 h of whole class instruction using ABRA between pre- and post-test. Hierarchical linear modeling of post-test results showed significant gains in letter-sound knowledge for intervention classrooms over control classrooms. In addition, medium effect sizes were evident for three of five outcome measures favoring the intervention: letter-sound knowledge (d= +0.66), phonological blending (d = +0.52), and word reading (d = +0.52), over effect sizes for regular teaching. It is concluded that regular teaching with ABRA technology adds significantly to literacy in the early elementary years. PMID:25538663

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial.

PubMed

Loughney, Lisa; West, Malcolm A; Kemp, Graham J; Rossiter, Harry B; Burke, Shaunna M; Cox, Trevor; Barben, Christopher P; Mythen, Michael G; Calverley, Peter; Palmer, Daniel H; Grocott, Michael P W; Jack, Sandy

2016-01-13

The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondrial content and improved oxygen uptake capacity, both of which are contributors to physical fitness. The aims of the EMPOWER trial are to assess the effects of neoadjuvant CRT and an in-hospital exercise training programme on physical fitness, health-related quality of life (HRQoL), and physical activity levels, as well as post-operative morbidity and cancer staging. The EMPOWER Trial is a randomised controlled trial with a planned recruitment of 46 patients with locally advanced rectal cancer and who are undergoing neoadjuvant CRT and surgery. Following completion of the neoadjuvant CRT (week 0) prior to surgery, patients are randomised to an in-hospital exercise training programme (aerobic interval training for 6 to 9 weeks) or a usual care control group (usual care and no formal exercise training). The primary endpoint is oxygen uptake at lactate threshold ([Formula: see text] at [Formula: see text]) measured using cardiopulmonary exercise testing assessed over several time points throughout the study. Secondary endpoints include HRQoL, assessed using semi-structured interviews and questionnaires, and physical activity levels assessed using activity monitors. Exploratory endpoints include post-operative morbidity, assessed using the Post-Operative Morbidity Survey (POMS), and cancer staging, assessed by using magnetic resonance tumour regression grading. The EMPOWER trial is the first randomised controlled trial comparing an in-hospital exercise training group with a usual care control group in patients with locally advanced rectal cancer. This trial will allow us to determine whether exercise training following neoadjuvant CRT can improve physical fitness and activity levels, as well as other important clinical outcome measures such as HRQoL and post-operative morbidity. These results will aid the design of a large, multi-centre trial to determine whether an increase in physical fitness improves clinically relevant post-operative outcomes. ClinicalTrials.gov NCT01914068 (received: 7 June 2013). University Hospital Southampton NHS Foundation Trust.

Methodological issues in evaluating cost effectiveness of adjuvant aromatase inhibitors in early breast cancer: a need for improved modelling to aid decision making.

PubMed

Annemans, Lieven

2008-01-01

The optimal adjuvant hormonal strategy in post-menopausal women with early breast cancer is a subject of ongoing debate. Aromatase inhibitors (AIs) have been successfully evaluated in clinical trials that have compared them with a standard treatment of 5 years of tamoxifen. However, several options are available in terms of treatment schedule and selected drug. Systematic reviews of clinical trials and health economic evaluations attempt to contribute to the debate. The objective of this paper is to provide a critical review of existing health economic evaluations with a focus on those parameters and assumptions with the largest impact on final outcomes.A wide range of different inputs and assumptions exist, which make a comparison of results difficult, if not impossible. In particular, the modelling of recurrence rates over longer time horizons than those observed in clinical trials, a cornerstone of health economic modelling, is subject to quite different approaches. The practice of indirect comparison of different AIs without sufficiently acknowledging population differences is also bothersome. A list of key features (related to time horizon, clinical data input, patient subtypes, budget impact and model calibration) that an ideal model should have in order to better assist decision makers in this field is proposed.

Regional Lymph Node Uptake of [{sup 18}F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.

2015-11-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculatedmore » from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.« less

Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial.

PubMed

Ang, Marcus; Tan, Donald; Mehta, Jodhbir S

2012-05-31

Small incision lenticule extraction or SMILE is a novel form of 'flapless' corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively. Single tertiary center, parallel group, single-masked, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> -3.00 diopter (D)) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> -3.00 D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 D of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-masked trial, subjects and their caregivers will be masked to the assigned treatment in each eye. This novel trial will provide information on whether SMILE has comparable, if not superior, refractive outcomes compared to the established LASIK for myopia, thus providing evidence for translation into clinical practice. Clinicaltrials.gov NCT01216475.

A Randomized Clinical Trial of Cognitive-Behavioral Treatment for PTSD in Women

DTIC Science & Technology

2003-10-01

Post Traumatic Stress Disorder ( PTSD ) in 384 female veterans and active duty personnel at 11 sites. This is a VA Cooperative Study. Walter...14. SUBJECT TERMS 15. NUMBER OF PAGES Post - Traumatic Stress Disorder 6 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19...Clinical Trial of Cognitive-Behavioral Treatment for Post Traumatic Stress Disorder in Women for this study, from the protocol Additionally, a new

Breakfast consumption and exercise interact to affect cognitive performance and mood later in the day. A randomized controlled trial.

PubMed

Veasey, R C; Gonzalez, J T; Kennedy, D O; Haskell, C F; Stevenson, E J

2013-09-01

The current study assessed the interactive effect of breakfast and exercise on cognition and mood. Twelve active males completed four trials; no breakfast-rest, breakfast-rest, no breakfast-exercise or breakfast-exercise in a randomized, cross-over design. The trials consisted of; breakfast or fast, a 2h rest, exercise (treadmill run) or equivalent rest, a chocolate milk drink, a 90 min rest and an ad libitum lunch. Cognitive performance and mood were recorded frequently throughout each trial. Data was analysed as pre-exercise/rest, during and immediately post exercise/rest and post-drink. No effects were found prior to consumption of the drink. Post-drink, fasting before exercise increased mental fatigue compared to consuming breakfast before exercise and fasting before rest. Tension increased when breakfast was consumed at rest and when exercise was undertaken fasted compared to omitting breakfast before rest. Breakfast before rest decreased rapid visual information processing task speed and impaired Stroop performance. Breakfast omission improved Four Choice Reaction Time performance. To conclude, breakfast before exercise appeared beneficial for post-exercise mood even when a post-exercise snack was consumed. Exercise reversed post-breakfast cognitive impairment in active males. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pilot randomized controlled trial of a mindfulness-based group intervention in adolescent girls at risk for type 2 diabetes with depressive symptoms.

PubMed

Shomaker, Lauren B; Bruggink, Stephanie; Pivarunas, Bernadette; Skoranski, Amanda; Foss, Jillian; Chaffin, Ella; Dalager, Stephanie; Annameier, Shelly; Quaglia, Jordan; Brown, Kirk Warren; Broderick, Patricia; Bell, Christopher

2017-06-01

(1) Evaluate feasibility and acceptability of a mindfulness-based group in adolescent girls at-risk for type 2 diabetes (T2D) with depressive symptoms, and (2) compare efficacy of a mindfulness-based versus cognitive-behavioral group for decreasing depressive symptoms and improving insulin resistance. Parallel-group, randomized controlled pilot trial conducted at a university. Thirty-three girls 12-17y with overweight/obesity, family history of diabetes, and elevated depressive symptoms were randomized to a six-week mindfulness-based (n=17) or cognitive-behavioral program (n=16). Both interventions included six, one-hour weekly group sessions. The mindfulness-based program included guided mindfulness awareness practices. The cognitive-behavioral program involved cognitive restructuring and behavioral activation. Adolescents were evaluated at baseline, post-intervention, and six-months. Feasibility/acceptability were measured by attendance and program ratings. Depressive symptoms were assessed by validated survey. Insulin resistance was determined from fasting insulin and glucose, and dual energy x-ray absorptiometry was used to assess body composition. Most adolescents attended ≥80% sessions (mindfulness: 92% versus cognitive-behavioral: 87%, p=1.00). Acceptability ratings were strong. At post-treatment and six-months, adolescents in the mindfulness condition had greater decreases in depressive symptoms than adolescents in the cognitive-behavioral condition (ps<.05). Compared to the cognitive-behavioral condition, adolescents in the mindfulness-based intervention also had greater decreases in insulin resistance and fasting insulin at post-treatment, adjusting for fat mass and other covariates (ps<.05). A mindfulness-based intervention shows feasibility and acceptability in girls at-risk for T2D with depressive symptoms. Compared to a cognitive-behavioral program, after the intervention, adolescents who received mindfulness showed greater reductions in depressive symptoms and better insulin resistance. ClinicalTrials.gov identifier: NCT02218138 clinicaltrials.gov. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prospective evaluation of the molecular effects of metformin on the endometrium in women with newly diagnosed endometrial cancer: A window of opportunity study.

PubMed

Soliman, Pamela T; Zhang, Qian; Broaddus, Russell R; Westin, Shannon N; Iglesias, David; Munsell, Mark F; Schmandt, Rosemarie; Yates, Melinda; Ramondetta, Lois; Lu, Karen H

2016-12-01

Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry. Twenty patients completed the trial. Median age and BMI were 57years (range: 27-67) and 34.5kg/m 2 (range: 21.9-50.0). Median duration of metformin was 9.5days (range: 7-24). A majority of women had endometrioid adenocarcinomas (90%) and were early stage (85%). After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035). Compared to baseline, post-treatment tissue showed decreased phospho-AKT in 18/20 patients (90%, p=0.0002), decreased phospho-S6rp in 14/20 patients (70%, p=0.057), and decreased phospho-p44/42MAPK in 15/18 patients (83.3%, p=0.0038). There was no difference in Ki67, phospho-ACC, or caspase 3. Changes did not correlate with BMI, grade, or KRAS mutation. In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomized controlled trial of cognitive-behavior therapy plus bright light therapy for adolescent delayed sleep phase disorder.

PubMed

Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L; Weaver, Edward; Trenowden, Sophie

2011-12-01

To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs. WL: N = 17). CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P < 0.0001), yet 13% still met DSPD criteria at the 6-month follow-up. CBT plus BLT for adolescent DSPD is effective for improving multiple sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Australia-New Zealand Trials Registry Number: ACTRN12610001041044.

Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial

PubMed Central

2013-01-01

Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. Methods A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Discussion The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). Trial registration ClinicalTrials.gov (http://NCT01558765). PMID:23782510

Strategies to improve retention in randomised trials.

PubMed

Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

2013-12-03

Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi(2) and I(2) statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These were incentives, communication strategies, new questionnaire format, participant case management, behavioural and methodological interventions. For 34 of the included trials, retention was response to postal and electronic questionnaires with or without medical test kits. For four trials, retention was the number of participants remaining in the trial. Included trials were conducted across a spectrum of disease areas, countries, healthcare and community settings. Strategies that improved trial retention were addition of monetary incentives compared with no incentive for return of trial-related postal questionnaires (RR 1.18; 95% CI 1.09 to 1.28, P value < 0.0001), addition of an offer of monetary incentive compared with no offer for return of electronic questionnaires (RR 1.25; 95% CI 1.14 to 1.38, P value < 0.00001) and an offer of a GBP20 voucher compared with GBP10 for return of postal questionnaires and biomedical test kits (RR 1.12; 95% CI 1.04 to 1.22, P value < 0.005). The evidence that shorter questionnaires are better than longer questionnaires was unclear (RR 1.04; 95% CI 1.00 to 1.08, P value = 0.07) and the evidence for questionnaires relevant to the disease/condition was also unclear (RR 1.07; 95% CI 1.01 to 1.14). Although each was based on the results of a single trial, recorded delivery of questionnaires seemed to be more effective than telephone reminders (RR 2.08; 95% CI 1.11 to 3.87, P value = 0.02) and a 'package' of postal communication strategies with reminder letters appeared to be better than standard procedures (RR 1.43; 95% CI 1.22 to 1.67, P value < 0.0001). An open trial design also appeared more effective than a blind trial design for return of questionnaires in one fracture prevention trial (RR 1.37; 95% CI 1.16 to 1.63, P value = 0.0003).There was no good evidence that the addition of a non-monetary incentive, an offer of a non-monetary incentive, 'enhanced' letters, letters delivered by priority post, additional reminders, or questionnaire question order either increased or decreased trial questionnaire response/retention. There was also no evidence that a telephone survey was either more or less effective than a monetary incentive and a questionnaire. As our analyses are based on single trials, the effect on questionnaire response of using offers of charity donations, sending reminders to trial sites and when a questionnaire is sent, may need further evaluation. Case management and behavioural strategies used for trial retention may also warrant further evaluation. Most of the retention trials that we identified evaluated questionnaire response. There were few evaluations of ways to improve participants returning to trial sites for trial follow-up. Monetary incentives and offers of monetary incentives increased postal and electronic questionnaire response. Some other strategies evaluated in single trials looked promising but need further evaluation. Application of the findings of this review would depend on trial setting, population, disease area, data collection and follow-up procedures.

Update to the study protocol, including statistical analysis plan for a randomized clinical trial comparing comprehensive cardiac rehabilitation after heart valve surgery with control: the CopenHeartVR trial.

PubMed

Sibilitz, Kirstine Laerum; Berg, Selina Kikkenborg; Hansen, Tina Birgitte; Risom, Signe Stelling; Rasmussen, Trine Bernholdt; Hassager, Christian; Køber, Lars; Gluud, Christian; Thygesen, Lau Caspar; Lindschou, Jane; Schmid, Jean Paul; Taylor, Rod S; Zwisler, Ann-Dorthe

2015-02-05

Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). Trial registered 16 March 2012; ClinicalTrials.gov ( NCT01558765 ).

[Effects of rectal indomethacin in the prevention of post-ERCP acute pancreatitis].

PubMed

Döbrönte, Zoltán; Toldy, Erzsébet; Márk, Levente; Sarang, Krisztina; Lakner, Lilla

2012-06-24

Recently non-steroidal anti-inflammatory drugs have seemed to reduce the frequency of post-ERCP pancreatitis in some prospective controlled trials, but the results have to be confirmed by further studies. To evaluate the efficacy of rectally administered indomethacin for the reduction of incidence of post-ERCP pancreatitis. A prospective randomized placebo-controlled study was conducted in 228 patients who underwent ERCP. Patients were randomized to receive a suppository containing 100 mg indomethacin or an inert placebo 10 mins before ERCP. Patients were evaluated clinically and biochemically by using serum amylase levels measured 24 h after the procedure. Pancreatitis and hyperamylasemia occurred more frequently in the placebo group, but the difference was not significant. In respect to the rate of pancreatitis, this tendency could particularly be observed in females, in patients older than 60 years and in patients with BMI lower than 25; however, it completely failed in cases with pancreatic duct filling or in those with pancreatic EST. Rectal indomethacin given before ERCP did not prove to be statistically effective in the reduction of the incidence of post-procedure pancreatitis. Further, controlled multicenter studies are required to assess safely the potential efficacy of indomethacin in the prevention of pancreatitis following ERCP.

Post-conflict slowing after incongruent stimuli: from general to conflict-specific.

PubMed

Rey-Mermet, Alodie; Meier, Beat

2017-05-01

Encountering a cognitive conflict not only slows current performance, but it can also affect subsequent performance, in particular when the conflict is induced with bivalent stimuli (i.e., stimuli with relevant features for two different tasks) or with incongruent trials (i.e., stimuli with relevant features for two response alternatives). The post-conflict slowing following bivalent stimuli, called "bivalency effect", affects all subsequent stimuli, irrespective of whether the subsequent stimuli share relevant features with the conflict stimuli. To date, it is unknown whether the conflict induced by incongruent stimuli results in a similar post-conflict slowing. To investigate this, we performed six experiments in which participants switched between two tasks. In one task, incongruent stimuli appeared occasionally; in the other task, stimuli shared no feature with the incongruent trials. The results showed an initial performance slowing that affected all tasks after incongruent trials. On further trials, however, the slowing only affected the task sharing features with the conflict stimuli. Therefore, the post-conflict slowing following incongruent stimuli is first general and then becomes conflict-specific across trials. These findings are discussed within current task switching and cognitive control accounts.

Measuring Stability and Security in Iraq

DTIC Science & Technology

2007-12-01

associated with a nationwide shortage of space for pre-trial detainees are exacerbated by the current lack of available prison (post-trial...capacity. Currently, Iraq is utilizing all of its post-trial prison capacity. Although U.S.-funded construction at December 14, 2007 4 Nasiriyah...Fort Suse and Cham Chamal should provide another 6,000 prison beds by the end of 2009, these will not begin to become available until mid-2008. As a

Effects of analgesia of the digital flexor tendon sheath on pain originating in the sole, distal interphalangeal joint or navicular bursa of horses.

PubMed

Harper, J; Schumacher, John; Degraves, F; Schramme, M; Schumacher, Jim

2007-11-01

Specific analgesic techniques are required in diagnosis of lameness to isolate the exact origin of pain to the many structures of the foot that may be involved. To determine if analgesia of the digital flexor tendon sheath (DFTS) results in anaesthesia of other portions of the foot, such as the sole, distal interphalangeal joint (DIPJ), or navicular bursa (NB). Lameness caused by pain in the dorsal margin or heel region of the sole of the foot was induced in 18 horses by: using set-screws to create solar pressure (Trial 1: n = 5); or administering endotoxin intrasynovially into the DIPJ (Trial 2: n = 6) and NB (Trial 3: n = 7). The gait of each horse was evaluated by examining videotape recorded before and after creation of lameness and after administration of mepivacaine hydrochloride into the DFTS. Median lameness scores in Trial 1 at 10 min post injection of the DFTS were not significantly different from those before administration of local anaesthetic solution into the DFTS (P> or =0.05), but median lameness scores were reduced significantly at 20 min (P< or =0.05). In Trials 2 and 3, median lameness scores were not significantly different at observations made at 10 and 20 min post injection of the DFTS. Analgesia of the DFTS has little effect on lameness caused by pain originating in the sole, DIPJ or NB. Improvement of lameness in horses after intrasynovial analgesia of the DFTS is probably caused by attenuation of pain within the structures contained in the DFTS.

Change in lumen eccentricity and asymmetry after treatment with Absorb bioresorbable vascular scaffolds in the ABSORB cohort B trial: a five-year serial optical coherence tomography imaging study.

PubMed

Suwannasom, Pannipa; Sotomi, Yohei; Asano, Taku; Koon, Jaryl Ng Chen; Tateishi, Hiroki; Zeng, Yaping; Tenekecioglu, Erhan; Wykrzykowska, Joanna J; Foin, Nicolas; de Winter, Robbert J; Ormiston, John A; Serruys, Patrick W; Onuma, Yoshinobu

2017-04-07

The aim of the study was to investigate long-term changes in lumen eccentricity and asymmetry at five years after implantation of the Absorb bioresorbable vascular scaffold (BVS). Out of 101 patients from the ABSORB cohort B trial, 28 patients (29 lesions) with serial optical coherence tomography (OCT) examination at four different time points (cohort B1: post-procedure, six months, two, and five years [n=13]; cohort B2: post-procedure, one, three, and five years [n=16]) were evaluated. The longitudinal variance in lumen diameter was assessed by asymmetry index (AI). An asymmetric lesion was defined as AI >0.3. The circularity of the lumen or scaffold was evaluated by the eccentricity index calculated as minimal divided by maximal luminal or scaffold diameter per cross-section. The lowest lumen eccentricity index within a scaffold segment (EIL) <0.7 was defined as an eccentric lesion. Post procedure, an eccentric lesion was observed in 72.4% and became concentric in 93.1% at five years (post EIL 0.67±0.05 vs. five-year EIL 0.80±0.10, p=0.03) with a modest reduction of the lumen area from baseline to five years by 0.75±0.32 mm2. Asymmetric lumen morphology was observed in 93.1% (n=27) post implantation and persisted until five-year follow-up. On serial OCT analyses, there was a substantial increase in the scaffold EI during the first two years (post 0.70±0.06, six months 0.76±0.08, two years 0.85±0.07); then, it remained stable whereas the lumen circularity improved further. There were no significant differences in major adverse cardiac events regarding the lumen morphology over the five-year follow-up. In patients treated with the Absorb BVS, the cross-sectional circularity improved over five years while the variance in longitudinal diameters remained. Regaining of lumen circularity is mainly caused by reshaping of the scaffold during the first two years.

Effectiveness of Omalizumab in Severe Allergic Asthma: A Retrospective UK Real-World Study

PubMed Central

2013-01-01

Objective. The aim of this study was to evaluate the “real world” effects of the monoclonal antibody omalizumab (OMB) when used to treat severe persistent allergic asthma in UK clinical practice. Methods. A 10-center retrospective observational study was carried out to compare oral corticosteroid (OCS) use and exacerbation frequency in 12 months pre- versus post-OMB initiation in 136 patients aged ≥12 years with severe persistent allergic asthma. All patients received ≥1 dose of OMB. Patients who had received OMB in a clinical trial were excluded. Data were obtained from hospital and if necessary general practitioners’ (GPs’) records on OCS use, lung function, hospital resource use, and routinely used quality of life (QoL) measures at baseline (pre-OMB), 16 weeks, and up to 12 months post-OMB initiation. Results. Mean total quantity of OCS prescribed per year decreased by 34% between the 12 months pre- and post-OMB initiation. During the 12 months post-OMB initiation, 87 patients (64%) stopped/reduced OCS use by 20% or more and 66 (49%) stopped OCS completely. Mean percent predicted forced expiratory volume in one second (FEV1) increased from 66.0% at baseline to 75.2% at week 16 of OMB therapy. The number of asthma exacerbations decreased by 53% during the 12 months post-initiation. Accident and emergency visits reduced by 70% and hospitalizations by 61% in the 12 months post-OMB initiation. Conclusion. This retrospective analysis showed a reduction in exacerbations and improved QoL as per previous studies with OMB. However, the total reduction in annual steroid burden and improved lung function in this severely ill group of patients taking regular or frequent OCS is greater than that seen in previous trials. PMID:23574000

The Secret Agent Society Social-Emotional Skills Program for Children with a High-Functioning Autism Spectrum Disorder: A Parent-Directed Trial

ERIC Educational Resources Information Center

Sofronoff, Kate; Silva, Jenni; Beaumont, Renae

2017-01-01

This study evaluated a parent-delivered social and emotional skills intervention--the Secret Agent Society (SAS) for children with high-functioning autism spectrum disorders (HF-ASD). The study was a pre-post follow-up design with an 8-week baseline period and 6-week follow-up period. Participants were 38 parents and 41 children recruited from…

Early versus delayed post-operative bathing or showering to prevent wound complications.

PubMed

Toon, Clare D; Sinha, Sidhartha; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2015-07-23

Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. We searched The Cochrane Wounds Group Specialised Register (30th June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

Early versus delayed post-operative bathing or showering to prevent wound complications.

PubMed

Toon, Clare D; Sinha, Sidhartha; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2013-10-12

Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. We searched The Cochrane Wounds Group Specialised Register;The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

Sensorimotor Learning of Acupuncture Needle Manipulation Using Visual Feedback

PubMed Central

Jung, Won-Mo; Lim, Jinwoong; Lee, In-Seon; Park, Hi-Joon; Wallraven, Christian; Chae, Younbyoung

2015-01-01

Objective Humans can acquire a wide variety of motor skills using sensory feedback pertaining to discrepancies between intended and actual movements. Acupuncture needle manipulation involves sophisticated hand movements and represents a fundamental skill for acupuncturists. We investigated whether untrained students could improve their motor performance during acupuncture needle manipulation using visual feedback (VF). Methods Twenty-one untrained medical students were included, randomly divided into concurrent (n = 10) and post-trial (n = 11) VF groups. Both groups were trained in simple lift/thrusting techniques during session 1, and in complicated lift/thrusting techniques in session 2 (eight training trials per session). We compared the motion patterns and error magnitudes of pre- and post-training tests. Results During motion pattern analysis, both the concurrent and post-trial VF groups exhibited greater improvements in motion patterns during the complicated lifting/thrusting session. In the magnitude error analysis, both groups also exhibited reduced error magnitudes during the simple lifting/thrusting session. For the training period, the concurrent VF group exhibited reduced error magnitudes across all training trials, whereas the post-trial VF group was characterized by greater error magnitudes during initial trials, which gradually reduced during later trials. Conclusions Our findings suggest that novices can improve the sophisticated hand movements required for acupuncture needle manipulation using sensorimotor learning with VF. Use of two types of VF can be beneficial for untrained students in terms of learning how to manipulate acupuncture needles, using either automatic or cognitive processes. PMID:26406248

[Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes].

PubMed

Ma, Li-xin; Wang, Yu-yi; Li, Xin-xue; Liu, Jian-ping

2012-03-01

Randomized controlled trial (RCT) is considered as the gold standard for the efficacy assessment of medicines. With the increasing number of Chinese patent drugs for treatment of type 2 diabetes, the methodology of post-marketing RCTs evaluating the efficacy and specific effect has become more important. To investigate post-marketing Chinese patent drugs for treatment of type 2 diabetes, as well as the methodological quality of post-marketing RCTs. Literature was searched from the books of Newly Compiled Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the State Food and Drug Administration and the Ministry of Human Resources and Social Security of the People's Republic of China, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period for searching ran from the commencement of each database to August 2011. RCTs of post-marketing Chinese patent drugs for treatment of type 2 diabetes with intervention course no less than 3 months. Two authors independently evaluated the research quality of the RCTs by the checklist of risk bias assessment and the data collection forms based on the CONSORT Statement. Independent double data-extraction was performed. The authors identified a total of 149 Chinese patent drugs for treatment of type 2 diabetes. According to different indicative syndromes, the Chinese patent drugs can be divided into the following types, namely, yin deficiency and interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41 RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor endpoint outcome reports were found. Risk bias analysis showed that 81% of the included studies reported randomization for grouping without sequence generation, 98% of these studies did not report concealment of random numbers, 5% used placebo, 10% reported outcome attrition bias and no study employed the analysis of intention-to-treat and 98% reported the diagnostic criteria for type 2 diabetes. The participants mainly consisted of outpatients without complications (76%). The minimum and maximum sample size was 40 and 300 (106 ± 60), respectively. The inclusion and exclusion criteria and outcome measures did not match the purposes and contents of post-marketing research in the included studies. They also failed to reflect the basic principles of traditional Chinese medicine in the process of diagnosis and treatment. The demographic characteristics of the patients, the indications for medicine and the syndrome differentiation process were not reported sufficiently and transparently. In order to improve the post-marketing research and promote the rational use of Chinese patent drugs, it is recommended that phase IV clinical trials should establish clear research purpose as well as hypothesis first, and choose scientific and evidence-based study design and outcome measures. In addition, guidelines for implementation of post-marketing research should be developed.

A Meta-analytic Review of Non-specific Effects in Randomized Controlled Trials of Cognitive Remediation for Schizophrenia.

PubMed

Radhakrishnan, Rajiv; Kiluk, Brian D; Tsai, Jack

2016-03-01

Cognitive remediation (CR) has been found to improve cognitive performance among adults with schizophrenia in randomized controlled trials (RCTs). However, improvements in cognitive performance are often observed in the control groups of RCTs as well. There has been no comprehensive examination of change in control groups for CR, which may inform trial methodology and improve our understanding of measured outcomes for cognitive remediation. In this meta-analysis, we calculated pre-post change in cognitive test performance within control groups of RCTs in 32 CR trials (n = 794 participants) published between 1970 and 2011, and examined the association between pre-post change and sample size, duration of treatment, type of control group, and participants' age, intelligence, duration of illness, and psychiatric symptoms. Results showed that control groups in CR trials showed small effect size changes (Cohen's d = 0.12 ± 0.16) in cognitive test performance over the trial duration. Study characteristics associated with pre-post change included participant age and sample size. These findings suggest attention to change in control groups may help improve detection of cognitive remediation effects for schizophrenia.

Dynamics of device innovation: implications for assessing value.

PubMed

Gelijns, Annetine C; Russo, Mark J; Hong, Kimberly N; Brown, Lawrence D; Ascheim, Deborah D; Moskowitz, Alan J

2013-10-01

In recent years, there has been growing interest in evaluating the health and economic impact of medical devices. Payers increasingly rely on cost-effectiveness analyses in making their coverage decisions, and are adopting value-based purchasing initiatives. These analytic approaches, however, have been shaped heavily by their use in the pharmaceutical realm, and are ill-adapted to the medical device context. This study focuses on the development and evaluation of left ventricular assist devices (LVADs) to highlight the unique challenges involved in the design and conduct of device trials compared with pharmaceuticals. Devices are moving targets characterized by a much higher degree of post-introduction innovation and "learning by using" than pharmaceuticals. The cost effectiveness ratio of left ventricular assist devices for destination therapy, for example, decreased from around $600,000 per life year saved based on results from the pivotal trial to around $100,000 within a relatively short time period. These dynamics pose fundamental challenges to the evaluation enterprise as well as the policy-making world, which this paper addresses.

The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial.

PubMed

Shakur, Haleema; Roberts, Ian; Edwards, Philip; Elbourne, Diana; Alfirevic, Zarko; Ronsmans, Carine

2016-05-17

Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed. The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk. The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial. Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010).

Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma.

PubMed

Ellingson, Benjamin M; Abrey, Lauren E; Nelson, Sarah J; Kaufmann, Timothy J; Garcia, Josep; Chinot, Olivier; Saran, Frank; Nishikawa, Ryo; Henriksson, Roger; Mason, Warren P; Wick, Wolfgang; Butowski, Nicholas; Ligon, Keith L; Gerstner, Elizabeth R; Colman, Howard; de Groot, John; Chang, Susan; Mellinghoff, Ingo; Young, Robert J; Alexander, Brian M; Colen, Rivka; Taylor, Jennie W; Arrillaga-Romany, Isabel; Mehta, Arnav; Huang, Raymond Y; Pope, Whitney B; Reardon, David; Batchelor, Tracy; Prados, Michael; Galanis, Evanthia; Wen, Patrick Y; Cloughesy, Timothy F

2018-04-05

In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS. A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status. Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

Effectiveness of the first French psychoeducational program on unipolar depression: study protocol for a randomized controlled trial.

PubMed

Ducasse, Déborah; Courtet, Philippe; Sénèque, Maude; Genty, Catherine; Picot, Marie-Christine; Schwan, Raymund; Olié, Emilie

2015-11-17

Major Depressive Disorder (MDD) is highly prevalent and was associated with greater morbidity, mortality (including suicide), and healthcare costs. By 2030, MDD will become the leading cause of disability in high-income countries. Notably, among patients with a previous experience of a major depressive episode, it was indeed estimated that up to 85 % of those patients will suffer from relapse. Two main factors were associated with a significantly higher risk of relapse: poor medication adherence and low self-efficacy in disease management. Interestingly, these issues could become the targets of psychoeducational programs for chronic diseases. Indded psychoeducational program for depression are recommended in international guidelines, but have not yet been proposed in France. We propose to evaluate the first French psychoeducational program for depression "ENVIE" in a multicenter randomized controlled trial. The group intervention will include 9 weekly sessions. Its aim is to educate patients on the latest knowledge on depression and effective treatments through didactic and interactive sessions. Patients will experiment the latest innovating psychological skills (from acceptance and commitment therapy) to cope with depressive symptoms and maintain motivation in behavioral activation. In total, 332 unipolar non-chronic (<2 years) outpatients with moderate to severe depression, without psychotic features, will be randomly allocated to the add-on ENVIE program (N = 166) or to a waiting list (N = 166). The follow-up will last 15 months and include 5 assessment visits. The primary endpoint will be the remission rate of the index episode at 15 months post-inclusion, defined by a Montgomery and Asberg Depression Rating Scale (MADRS) score ≤ 12 over an 8-week period, and without relapse during follow-up. We will also assess the response rate and relapse at 15 months post-inclusion, hospitalization rate and adherence to treatment during the follow-up period, quality of life and global functioning upon inclusion and at 9 and 15 months post inclusion. If the proposed trial shows the effectiveness of the intervention, but also an increased remission rate in depressed outpatients at 15-months post-inclusion, in addition to improved treatment adherence in patients, it will further promotes arguments in favor of a wide dissemination of psychoeducational programs for depression. This trial is registered under number 2015-A00249-40 (PURE clinical trial: NCT02501226 ) (June 30th, 2015).

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).

Modelling variable dropout in randomised controlled trials with longitudinal outcomes: application to the MAGNETIC study.

PubMed

Kolamunnage-Dona, Ruwanthi; Powell, Colin; Williamson, Paula Ruth

2016-04-28

Clinical trials with longitudinally measured outcomes are often plagued by missing data due to patients withdrawing or dropping out from the trial before completing the measurement schedule. The reasons for dropout are sometimes clearly known and recorded during the trial, but in many instances these reasons are unknown or unclear. Often such reasons for dropout are non-ignorable. However, the standard methods for analysing longitudinal outcome data assume that missingness is non-informative and ignore the reasons for dropout, which could result in a biased comparison between the treatment groups. In this article, as a post hoc analysis, we explore the impact of informative dropout due to competing reasons on the evaluation of treatment effect in the MAGNETIC trial, the largest randomised placebo-controlled study to date comparing the addition of nebulised magnesium sulphate to standard treatment in acute severe asthma in children. We jointly model longitudinal outcome and informative dropout process to incorporate the information regarding the reasons for dropout by treatment group. The effect of nebulised magnesium sulphate compared with standard treatment is evaluated more accurately using a joint longitudinal-competing risk model by taking account of such complexities. The corresponding estimates indicate that the rate of dropout due to good prognosis is about twice as high in the magnesium group compared with standard treatment. We emphasise the importance of identifying reasons for dropout and undertaking an appropriate statistical analysis accounting for such dropout. The joint modelling approach accounting for competing reasons for dropout is proposed as a general approach for evaluating the sensitivity of conclusions to assumptions regarding missing data in clinical trials with longitudinal outcomes. EudraCT number 2007-006227-12 . Registration date 18 Mar 2008.

A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms.

PubMed

Kalman, Douglas S; Schwartz, Howard I; Alvarez, Patricia; Feldman, Samantha; Pezzullo, John C; Krieger, Diane R

2009-11-18

This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. Sixty-one adults were enrolled (age 36.5 +/- 12.6 years; height 165.1 +/- 9.2 cm; weight 75.4 +/- 17.3 kg) and randomized to either Digestive Advantage Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use. Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. ClinicalTrials.gov Identifier: NCT00881322.

Comparing nasal packing with trans-septal suturing following septoplasty: a randomized clinical trial.

PubMed

Dadgarnia, Mohammadhossein; Meybodian, Mojtaba; Karbasi, Akbar; Baradaranfar, Mohammadhossein; Atighechi, Saeid; Zand, Vahid; Vaziribozorg, Sedighe

2017-09-01

It has been shown that nasal packing after septoplasty is associated with several complications. Our aim was to compare post-septoplasty nasal packing and trans-septal suturing, in terms of complications and outcome of operation. This randomized clinical trial was performed on patients with deviated nasal septum who were candidates for septoplasty. Patients were visited three times after operation (on the first 48 h, first week, and third post-operative month). Participants were checked for having common complications. Rhinomanometric evaluation was performed to measure nasal air flow and airway resistance, as indicators of operation efficacy, both prior to and after surgery. A total of 72 patients were allocated into the two trial arms. Patients in nasal pack group reported higher pain scores on the first 48 h (P < 0.001) and one week after surgery (P < 0.001). Epiphora (P = 0.028), sleep disturbance (P = 0.012), and dyspnea (P < 0.001) were also more commonly observed in patients using nasal pack. Objective evaluation of bleeding demonstrated that more severe bleeding occurred in patients with trans-septal sutures (P = 0.001). No differences were found comparing the indices of rhinomanometry between the two groups. Using trans-septal sutures after septoplasty compared to nasal packing, might be associated with lower frequencies of several specific complications and a lower rate of patients' discomfort. Nevertheless, increase in the risk of bleeding and hematoma was noted in the trans-septal suture group. No differences were observed between the nasal air flow and resistance of patients in the two groups.

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma

PubMed Central

Deniger, Drew C.; Kwong, Mei Li M.; Pasetto, Anna; Dudley, Mark E.; Wunderlich, John R.; Langhan, Michelle M.; Lee, Chyi-Chia Richard; Rosenberg, Steven A.

2016-01-01

Purpose This pilot feasibility clinical trial evaluated the co-administration of vemurafenib, a small molecule antagonist of BRAFV600 mutations, and tumor infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. Experimental Design A metastatic tumor was resected for growth of TIL and patients were treated with vemurafenib for 2 weeks followed by resection of a second lesion. Patients then received a non-myeloablative pre-conditioning regimen, infusion of autologous TIL and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by RECIST 1.0. Metastases resected prior to and after two weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation and recognition of autologous tumor. Results The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TIL and peripheral blood T cells were inhibited in vitro by vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TIL grown from pre- and post-vemurafenib metastases. Conclusions Co-administration of vemurafenib and TIL was safe, feasible and generated objective clinical responses in this small pilot clinical trial. PMID:28093487

PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.

PubMed

Nuebling, Georg; Hensler, Mira; Paul, Sabine; Zwergal, Andreas; Crispin, Alexander; Lorenzl, Stefan

2016-08-01

To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial.

PubMed

Skvarc, David R; Dean, Olivia M; Byrne, Linda K; Gray, Laura J; Ives, Kathryn; Lane, Stephen E; Lewis, Matthew; Osborne, Cameron; Page, Richard; Stupart, Douglas; Turner, Alyna; Berk, Michael; Marriott, Andrew J

2016-08-09

Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting. This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress. The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial. The PANACEA trial has been registered with the Therapeutic Goods Administration, and the Australian New Zealand Clinical Trials Registry: ACTRN12614000411640 ; registered on 15 April 2014.

Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial

PubMed Central

2012-01-01

Background Small incision lenticule extraction or SMILE is a novel form of ‘flapless’ corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively. Methods/Design Single tertiary center, parallel group, single-masked, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 diopter (D)) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 D of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-masked trial, subjects and their caregivers will be masked to the assigned treatment in each eye. Discussion This novel trial will provide information on whether SMILE has comparable, if not superior, refractive outcomes compared to the established LASIK for myopia, thus providing evidence for translation into clinical practice. Trial registration Clinicaltrials.gov NCT01216475. PMID:22647480

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial

PubMed Central

2010-01-01

Background This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Methods and Design Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms. Discussion This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings. Trial registration ISRCTN24952438 PMID:20964860

Epidural blood patching for preventing and treating post-dural puncture headache.

PubMed

Sudlow, C; Warlow, C

2002-01-01

Dural puncture is a common procedure, but leakage of CSF from the resulting dural defect may cause postural headache after the procedure, and this can be disabling. Injecting an epidural blood patch around the site of the defect may stop this leakage, and so may have a role in preventing or treating post dural puncture headache. To assess the possible benefits and harms of epidural blood patching in both the prevention and the treatment of post-dural puncture headache. We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2000), MEDLINE (January 1994 to December 1998), and EMBASE (January 1980 to December 1998). We also searched the reference lists of relevant articles identified electronically, and asked both the authors of all included trials and colleagues with an interest in this area to let us know of any other potentially relevant studies not already identified. Date of last search: December 2000. We sought all properly randomised, unconfounded trials that compared epidural blood patch versus no epidural blood patch in the prevention or treatment of post-dural puncture headache among all types of patients undergoing dural puncture for any reason. The primary outcome of effectiveness was postural headache. One reviewer extracted details of trial methodology and outcome data from the reports of all trials considered eligible for inclusion. We invited the authors of all such trials both to check the information extracted and to provide any details that were unavailable in the published reports. Intention-to-treat analyses were performed using the Peto O-E method. Information about adverse effects (post-dural puncture backache, epidural infection and lower limb paraesthesia) was also extracted. Three trials (77 patients) were eligible for inclusion. Methodological details were generally incomplete. Although the results of our analyses suggested that both prophylactic and therapeutic epidural blood patching may be of benefit, the very small numbers of patients and outcome events, as well as uncertainties about trial methodology, precluded reliable assessments of the potential benefits and harms of this intervention. Further, adequately powered, randomised trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache.

Summary Protocol for a Multi-Centre Randomised Controlled Trial of Enteral Lactoferrin Supplementation in Newborn Very Preterm Infants (ELFIN).

PubMed

2018-06-11

In a multi-centre randomised controlled trial (RCT), we are assessing whether giving very preterm (i.e., born at < 32 weeks' gestation) infants prophylactic enteral bovine lactoferrin supplementation (150 mg/kg/day) from shortly after birth until 34 weeks' post-menstrual age reduces the incidence of late-onset invasive infection (primary outcome), all-cause mortality, bronchopulmonary dysplasia, necrotising enterocolitis, retinopathy of prematurity, and the duration of antibiotic exposure, intensive care, and hospital admission. The trial is recruiting 2,200 participants from 37 neonatal care centres in the UK over 4 years. We will undertake an economic evaluation within the RCT to evaluate cost-effectiveness and provide an estimate of incremental costs for differences in the pre-specified outcomes in primary and subgroup analyses. If a statistically significant and clinically important effect on the primary outcome is detected, we will seek further funding and approval to assess the impact of enteral lactoferrin supplementation on rates of adverse neuro-developmental outcomes in the participating infants when they are 5 years old. © 2018 S. Karger AG, Basel.

Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

PubMed

Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

2015-02-10

Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections.

PubMed

Haas, David M; Morgan, Sarah; Contreras, Karenrose

2014-12-21

Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman's return to normal function and her ability to care for her baby. Despite the widespread use of prophylactic antibiotics, postoperative infectious morbidity still complicates cesarean deliveries. To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities, including endometritis and wound complications. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (10 December 2014). We included randomized and quasi-randomized trials assessing the impact of vaginal cleansing immediately before cesarean delivery with any type of antiseptic solution versus a placebo solution/standard of care on post-cesarean infectious morbidity. We independently assessed eligibility and quality of the studies. Seven trials randomizing 2816 women (2635 analyzed) evaluated the effects of vaginal cleansing (all with povidone-iodine) on post-cesarean infectious morbidity. The risk of bias was generally low, with the quality of most of the studies being high. Vaginal preparation immediately before cesarean delivery significantly reduced the incidence of post-cesarean endometritis from 8.3% in control groups to 4.3% in vaginal cleansing groups (average risk ratio (RR) 0.45, 95% confidence interval (CI) 0.25 to 0.81, seven trials, 2635 women). The risk reduction was particularly strong for women who were already in labor at the time of the cesarean delivery (7.4% in the vaginal cleansing group versus 13.0% in the control group; RR 0.56, 95% CI 0.34 to 0.95, three trials, 523 women) and for women with ruptured membranes (4.3% in the vaginal cleansing group versus 17.9% in the control group; RR 0.24, 95% CI 0.10 to 0.55, three trials, 272 women). No other outcomes realized statistically significant differences between the vaginal cleansing and control groups. No adverse effects were reported with the povidone-iodine vaginal cleansing.The quality of the evidence using GRADE was low for post-cesarean endometritis, moderate for postoperative fever, and low for wound infection. Vaginal preparation with povidone-iodine solution immediately before cesarean delivery reduces the risk of postoperative endometritis. This benefit is particularly realized for women undergoing cesarean delivery, who are already in labor or who have ruptured membranes. As a simple, generally inexpensive intervention, providers should consider implementing preoperative vaginal cleansing with povidone-iodine before performing cesarean deliveries.

Effects of enzyme-potentiated desensitization in the treatment of pollinosis: a double-blind placebo-controlled trial.

PubMed

Astarita, C; Scala, G; Sproviero, S; Franzese, A

1996-01-01

Several controlled clinical trials have shown that specific immunotherapy (SIT) using incremental injections of allergens can be effective in the treatment of allergic rhinitis and asthma. Nevertheless, the risk of side effects have led to some recommended limitations of SIT. Enzyme-potentiated desensitization (EPD) is a proposed method for immunotherapy with very low doses of mixed allergens plus beta-glucuronidase enzyme, for which irrelevant or no side effects have been claimed. The aim of this study was to determine the clinical efficacy of EPD in the treatment of pollinosis. A double-blind placebo-controlled trial of EPD among 20 patients sensitive to Parietaria and grass pollen was performed. All patients recorded daily symptom scores for nine months following a single intradermal injection of EPD or buffered saline received in February. Symptoms recorded were nasal itching and obstruction, sneezing, rhinorrhea, itchy eyes and excessive tear production. Moreover, total and specific lgE were measured and CD3+, CD4+ and CD8+ peripheral blood lymphocytes were counted at different times. In the same period, ten additional subjects, with an allergic clinical profile similar to the subjects admitted to the double-blind trial, were studied in an open clinical trial in order to evaluate the effects of EPD without enzyme using a mixture of allergens. Symptom scores were higher in the placebo group (p < 0.001), with a similar level of significance for both global symptom score and for each individual symptom. Active-treated patients had a significant post-treatment increase in the mean percentage of T-CD8+ peripheral blood cells and a significant post-seasonal decrease in the mean percentage of Parietaria specific lgE. On the contrary, placebo-treated patients had a borderline significant post-seasonal decrease in the mean percentage of CD8+ circulating cells and a significant seasonal increase in the mean percentage of Parietaria specific lgE with no significant post-seasonal decrease. Finally, clinical results of the mixture of allergens injection were similar to those of the placebo in the double-blind trial. EPD injection caused only an asymptomatic, local wheal and flare lasting about two hours. Two patients (20%) in the active-treated group experienced a delayed, mild, unusual headache lasting about two days. In conclusion, EPD is clinically effective in the treatment of pollinosis. Some immunological modifications observed in the EPD-treated patients suggest an EPD-induced enhancement of tolerogenic mechanisms like "immune deviation."

Dentin-like versus Rigid Endodontic Post: 11-year Randomized Controlled Pilot Trial on No-wall to 2-wall Defects.

PubMed

Naumann, Michael; Sterzenbach, Guido; Dietrich, Thomas; Bitter, Kerstin; Frankenberger, Roland; von Stein-Lausnitz, Manja

2017-11-01

This is the first long-term randomized controlled trial to evaluate dentin-like glass fiber posts (GFPs) compared with rather rigid titanium posts (TPs) for post-endodontic restoration of severely damaged endodontically treated teeth with 2 or fewer remaining cavity walls. Ninety-one subjects in need of post-endodontic restorations were randomly assigned to receive either a tapered GFP (n = 45) or TP (n = 46). Posts were adhesively luted by using self-adhesive resin cement, followed by composite core build-up and preparation of 2-mm ferrule design. Primary end point was loss of restoration for any reason. Kaplan-Meier curves were constructed, and log-rank test was calculated (P < .05). After a follow-up of 132 months, 17 GFP and 20 TP restorations survived, and 19 failed (12 GFP, 7 TP). Failure modes for GFP were root fracture (n = 4), core fracture (n = 1), secondary caries (n = 1), endodontic failure (n = 2), extraction because of tooth mobility grade III associated with insufficient design of removable partial denture (n = 1), tooth fracture (n = 1), and changes in treatment plan (n = 2); failure modes for TP were endodontic failure (n = 5), root fracture (n = 1), and 1 extraction for other reasons. Cumulative survival probability was 58.7% for GFP and 74.2% for TP. When using self-adhesively luted prefabricated posts, resin composite core build-up, and 2-mm ferrule to reconstruct severely damaged endodontically treated teeth, tooth survival is not influenced by post rigidity. Survival decreased rapidly after 8 years of observation in both groups. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The role of quantitative safety evaluation in regulatory decision making of drugs.

PubMed

Chakravarty, Aloka G; Izem, Rima; Keeton, Stephine; Kim, Clara Y; Levenson, Mark S; Soukup, Mat

2016-01-01

Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general.

The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): study protocol for a randomised controlled trial.

PubMed

Onerup, Aron; Angenete, Eva; Bock, David; Börjesson, Mats; Fagevik Olsén, Monika; Grybäck Gillheimer, Elin; Skullman, Stefan; Thörn, Sven-Egron; Haglind, Eva; Nilsson, Hanna

2017-05-08

Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer. We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis. An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results. ClinicalTrials.gov identifier: NCT02299596 . Registered on 17 November 2014.

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

PubMed Central

Duncan, Pamela W; Sullivan, Katherine J; Behrman, Andrea L; Azen, Stanley P; Wu, Samuel S; Nadeau, Stephen E; Dobkin, Bruce H; Rose, Dorian K; Tilson, Julie K

2007-01-01

Background Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention. The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions. Methods/Design We will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks. Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment. LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean difference in gait speed change between the two LTP groups. Discussion The goal of this single-blinded, phase III randomized clinical trial is to provide evidence to guide post-stroke walking recovery programs. Trial registration NCT00243919. PMID:17996052

Evaluating a complex intervention with a single outcome may not be a good idea: an example from a randomised trial of stroke case management.

PubMed

Mayo, Nancy E; Scott, Susan

2011-11-01

to estimate the extent to which a case-management intervention for persons newly discharged into the community following an acute stroke effected a change in stroke outcome in comparison with usual care. a re-analysis of stratified, balanced, randomised clinical trial. five university-affiliated acute-care hospitals in Montreal, Quebec, Canada. a total of 190 persons (mean age 70 years) returning home directly from the acute-care hospital following a first or recurrent stroke with a need for health-care supervision post-discharge because of low function, co-morbidity or isolation. for 6 weeks following discharge a nurse case manager delivered, depending on need, over 50 different nursing interventions (range 2-15 per person), which targeted physical, emotional and psychological impairments, role participation restrictions and health perception. seven of the SF-36 subscales were used to measure the targeted constructs, at the post-intervention and 6 month evaluations. Seven binary response variables were created with a change of 10 points the criterion for individual response. Generalised estimating equations, equivalent to a logistic regression for multiple outcomes, were used. the odds of responding to one or more outcomes was 41% greater in the intervention group than in the control group [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.11-1.79]. an analysis considering the complexity of the intervention and outcomes targeted indicated effectiveness of the nurse case-management post-stroke, whereas the traditional one outcome analysis did not.

SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation.

PubMed

Williams, Annabelle E; Croft, Julie; Napp, Vicky; Corrigan, Neil; Brown, Julia M; Hulme, Claire; Brown, Steven R; Lodge, Jen; Protheroe, David; Jayne, David G

2016-02-01

Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18 months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.

Is There a Role for Arnica and Bromelain in Prevention of Post-Procedure Ecchymosis or Edema? A Systematic Review of the Literature.

PubMed

Ho, Derek; Jagdeo, Jared; Waldorf, Heidi A

2016-04-01

The management of postprocedure skin care is of significant interest to dermatologists and other physicians. Ecchymosis and edema are common temporary postprocedure unwanted effects. Two botanically-derived products, arnica and bromelain, are used internationally by physicians to limit ecchymosis and edema that occur secondary to cosmetic, laser, and surgical skin procedures. The authors review the published literature and provide evidence-based recommendations on arnica and bromelain for prevention and treatment of postprocedure ecchymosis and edema. A search of the computerized bibliographic databases Medline, EMBASE, Scopus, and CINAHL was performed on March 23, 2015. The key terms used were "arnica," and "bromelain." This review contains clinical trials that evaluated prevention and/or treatment of postprocedure ecchymosis or edema with oral arnica (11), topical arnica (2), and oral bromelain (7). No studies on topical bromelain were found. Clinical trials on arnica and bromelain have demonstrated mixed results. Some randomized controlled trials reported improvement postprocedure with arnica (4/13) and bromelain (5/7). Based upon published studies, there is insufficient data to support use of arnica and bromelain post procedure, and the authors recommend additional research to determine the efficacy and safety of arnica and bromelain to prevent and/or treat ecchymosis and edema in patients.

Safety assessment of adjuvanted vaccines: Methodological considerations

PubMed Central

Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

2015-01-01

Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

PubMed

Silva, Ivair R

2018-01-15

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

The personalized reminder information and social management system (PRISM) trial: rationale, methods and baseline characteristics.

PubMed

Czaja, Sara J; Boot, Walter R; Charness, Neil; A Rogers, Wendy; Sharit, Joseph; Fisk, Arthur D; Lee, Chin Chin; Nair, Sankaran N

2015-01-01

Technology holds promise in terms of providing support to older adults. To date, there have been limited robust systematic efforts to evaluate the psychosocial benefits of technology for older people and identify factors that influence both the usability and uptake of technology systems. In response to these issues, we developed the Personal Reminder Information and Social Management System (PRISM), a software application designed for older adults to support social connectivity, memory, knowledge about topics, leisure activities and access to resources. This trail is evaluating the impact of access to the PRISM system on outcomes such as social isolation, social support and connectivity. This paper reports on the approach used to design the PRISM system, study design, methodology and baseline data for the trial. The trial is multi-site randomized field trial. PRISM is being compared to a Binder condition where participants received a binder that contained content similar to that found on PRISM. The sample includes 300 older adults, aged 65-98 years, who lived alone and at risk for being isolated. The primary outcome measures for the trial include indices of social isolation and support and well-being. Secondary outcomes measures include indices of computer proficiency, technology uptake and attitudes towards technology. Follow-up assessments occurred at 6 and 12 months post-randomization. The results of this study will yield important information about the potential value of technology for older adults. The study also demonstrates how a user-centered iterative design approach can be incorporated into the design and evaluation of an intervention protocol. Copyright © 2014 Elsevier Inc. All rights reserved.

The Personalized Reminder Information and Social Management System (PRISM) Trial: Rationale, Methods and Baseline Characteristics

PubMed Central

Czaja, Sara J.; Boot, Walter R.; Charness, Neil; Rogers, Wendy; Sharit, Joseph; Fisk, Arthur D.; Lee, Chin Chin; Nair, Sankaran N.

2014-01-01

Technology holds promise in terms of providing support to older adults. To date there have been limited robust systematic efforts to evaluate the psychosocial benefits of technology for older people and identify factors that influence both the usability and uptake of technology systems. In response to these issues we developed the Personal Reminder Information and Social Management System (PRISM), a software application designed for older adults to support social connectivity, memory, knowledge about topics, leisure activities and access to resources. This trail is evaluating the impact of access to the PRISM system on outcomes such as social isolation, social support and connectivity. This paper reports on the approach used to design the PRISM system, study design, methodology and baseline data for the trial. The trial is multi-site randomized field trial. PRISM is being compared to a Binder condition where participants received a binder that contained content similar to that found on PRISM. The sample includes 300 older adults, aged 65 – 98 years, who lived alone and at risk for being isolated. The primary outcome measures for the trial include indices of social isolation and support and well-being. Secondary outcomes measures include indices of computer proficiency, technology uptake and attitudes towards technology. Follow-up assessments occurred at 6 and 12 months post-randomization. The results of this study will yield important information about the potential value of technology for older adults. The study also demonstrates how a user-centered iterative design approach can be incorporated into the design and evaluation of an intervention protocol. PMID:25460342

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial.

PubMed

Rafiq, Sulman; Johansson, Pär Ingemar; Zacho, Mette; Stissing, Trine; Kofoed, Klaus; Lilleør, Nikolaj Bang; Steinbrüchel, Daniel Andreas

2012-04-27

Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. Clinicaltrials.gov Identifier NCT01046942.

Experience Corps: A dual trial to promote the health of older adults and children's academic success

PubMed Central

Fried, Linda P.; Carlson, Michelle C.; McGill, Sylvia; Seeman, Teresa; Xue, Qian-Li; Frick, Kevin; Tan, Erwin; Tanner, Elizabeth K.; Barron, Jeremy; Frangakis, Constantine; Piferi, Rachel; Martinez, Iveris; Gruenewald, Tara; Martin, Barbara K.; Berry-Vaughn, Laprisha; Stewart, John; Dickersin, Kay; Willging, Paul R.; Rebok, George W.

2014-01-01

Background As the population ages, older adults are seeking meaningful, and impactful, post-retirement roles. As a society, improving the health of people throughout longer lives is a major public health goal. This paper presents the design and rationale for an effectiveness trial of Experience Corps™, an intervention created to address both these needs. This trial evaluates (1) whether senior volunteer roles within Experience Corps™ beneficially impact children's academic achievement and classroom behavior in public elementary schools and (2) impact on the health of volunteers. Methods Dual evaluations of (1) an intention-to-treat trial randomizing eligible adults 60 and older to volunteer service in Experience Corps™, or to a control arm of usual volunteering opportunities, and (2) a comparison of eligible public elementary schools receiving Experience Corps™ to matched, eligible control schools in a 1:1 control:intervention school ratio. Outcomes For older adults, the primary outcome is decreased disability in mobility and Instrumental Activities of Daily Living (IADL). Secondary outcomes are decreased frailty, falls, and memory loss; slowed loss of strength, balance, walking speed, cortical plasticity, and executive function; objective performance of IADLs; and increased social and psychological engagement. For children, primary outcomes are improved reading achievement and classroom behavior in Kindergarten through the 3rd grade; secondary outcomes are improvements in school climate, teacher morale and retention, and teacher perceptions of older adults. Summary This trial incorporates principles and practices of community-based participatory research and evaluates the dual benefit of a single intervention, versus usual opportunities, for two generations: older adults and children. PMID:23680986

Qualities of Sore Throat Index (QuaSTI): measuring descriptors of sore throat in a randomized, placebo-controlled trial.

PubMed

Schachtel, Bernard; Shephard, Adrian; Schachtel, Emily; Lorton, Mary Beth; Shea, Tim; Aspley, Sue

2018-03-01

Patients with pharyngitis often describe various sensory, affective and evaluative pain qualities. Using an 11-word/phrase index, the Qualities of Sore Throat Index (QuaSTI), we characterized throat symptoms and evaluated changes in a randomized controlled trial (NCT01986361). Patients received a single flurbiprofen 8.75 mg (n = 101) or placebo (n = 21) lozenge and rated throat soreness at baseline and regular intervals over 3 h, and the QuaSTI at baseline, 1, 2 and 3 h post-treatment. The QuaSTI distinguished active drug from placebo and detected clinically important (≥2-point) changes over 3 h. Mean change from baseline over 3 h was significantly greater for flurbiprofen (154%) than placebo (p < 0.05). The QuaSTI is a sensitive instrument for measuring therapeutic effects in patients with pharyngitis.

Design and Rationale for a Randomized Controlled Trial to Reduce Readmissions among Patients with Depressive Symptoms

PubMed Central

Mitchell, Suzanne E.; Martin, Jessica M.; Krizman, Katherine; Sadikova, Ekaterina; Culpepper, Larry; Stewart, Sabrina K.; Brown, Jennifer Rose; Jack, Brian W.

2016-01-01

Background The Re-Engineered Discharge (Project RED) reduces 30-day readmission rates by 30 percent. However, our data indicates that for patients displaying depressive symptoms during hospitalization, Project RED is less effective in preventing unplanned readmission. We aim to examine the effectiveness of RED-D, a modified brief Cognitive behavioral therapy (CBT) protocol delivered as a post-discharge extension of the Re-Engineered Discharge, in reducing 30-day readmissions rates and emergency department (ED) use as well as depressive symptoms for medical patients with comorbid depressive symptoms. Methods This paper details the study design and implementation of an ongoing, federally funded randomized controlled trial of our post-discharge mental health intervention, RED-D, compared to the RED plus usual care. This research has two primary objectives: (1) to determine whether RED-D delivered telephonically by a mental health professional immediately following discharge is effective in reducing hospital readmission and emergency department use for patients displaying depressive symptoms during their inpatient stay, and (2) to examine whether this approach yields a clinically significant reduction in depressive symptoms. We intend to recruit 1200 participants randomized to our intervention, RED-D (n=600), and to RED plus usual care (n=600). Conclusions Hospitalized patients with depressive symptoms are at increased risk for 30-day readmission. We aim to conduct a randomized clinical trial to evaluate the comparative effectiveness of RED-D, our post-discharge modified brief CBT intervention compared to RED alone in reducing readmissions and depressive symptoms for this at-risk population. PMID:26343332

Design and rationale for a randomized controlled trial to reduce readmissions among patients with depressive symptoms.

PubMed

Mitchell, Suzanne E; Martin, Jessica M; Krizman, Katherine; Sadikova, Ekaterina; Culpepper, Larry; Stewart, Sabrina K; Brown, Jennifer Rose; Jack, Brian W

2015-11-01

The Re-Engineered Discharge (Project RED) reduces 30-day readmission rates by 30%. However, our data indicates that for patients displaying depressive symptoms during hospitalization, Project RED is less effective in preventing unplanned readmission. We aim to examine the effectiveness of RED-D, a modified brief Cognitive behavioral therapy (CBT) protocol delivered as a post-discharge extension of the Re-Engineered Discharge, in reducing 30-day readmissions rates and emergency department (ED) use as well as depressive symptoms for medical patients with comorbid depressive symptoms. This paper details the study design and implementation of an ongoing, federally funded randomized controlled trial of our post-discharge mental health intervention, RED-D, compared to the RED plus usual care. This research has two primary objectives: (1) to determine whether RED-D delivered telephonically by a mental health professional immediately following discharge is effective in reducing hospital readmission and emergency department use for patients displaying depressive symptoms during their inpatient stay, and (2) to examine whether this approach yields a clinically significant reduction in depressive symptoms. We intend to recruit 1200 participants randomized to our intervention, RED-D (n=600), and to RED plus usual care (n=600). Hospitalized patients with depressive symptoms are at increased risk for 30-day readmission. We aim to conduct a randomized clinical trial to evaluate the comparative effectiveness of RED-D, our post-discharge modified brief CBT intervention compared to RED alone in reducing readmissions and depressive symptoms for this at-risk population. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical feasibility of the Nintendo Wii™ for balance training post-stroke: a phase II randomized controlled trial in an inpatient setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2014-09-01

To investigate the feasibility and potential efficacy of the Nintendo Wii™ for balance rehabilitation after stroke. Phase II, single-blind, randomized controlled trial. Inpatient rehabilitation facility. Thirty adults (mean age 63.6 (14.7) years) undergoing inpatient rehabilitation who were less than three months post-stroke and able to stand unsupported. Participants were allocated to a Balance Group, using the 'Wii Fit Plus' in standing, or Upper Limb Group, using the 'Wii Sports/Sports Resort' in sitting. Both groups undertook three 45 minute sessions per week over two to four weeks in addition to standard care. The primary focus was feasibility, addressed by recruitment, retention, adherence, acceptability and safety. Efficacy was evaluated by balance, mobility and upper limb outcomes. Twenty-one percent of individuals screened were recruited and 86% (n = 30) of eligible people agreed to participate. Study retention and session adherence was 90% and > 99%, respectively, at two weeks; dropping to 70% and 87% at four weeks due to early discharge. All participants reported enjoying the sessions and most felt they were beneficial. No major adverse events occurred. Wii use by the Balance Group was associated with trends for improved balance, with significantly greater improvement in outcomes including the Step Test and Wii Balance Board-derived centre of pressure scores. The Upper Limb Group had larger, non-significant changes in arm function. A Wii-based approach appears feasible and promising for post-stroke balance rehabilitation. A larger randomized controlled trial is recommended to further investigate efficacy. © The Author(s) 2014.

Recruitment strategies for a lung cancer chemoprevention trial involving ex-smokers.

PubMed

Kye, Steve H; Tashkin, Donald P; Roth, Michael D; Adams, Bradley; Nie, Wen-Xian; Mao, Jenny T

2009-09-01

The ability to recruit qualified subjects who are willing to adhere to the study protocol in clinical trials is an essential component of translational research. Such tasks can be particularly challenging for chemoprevention studies when the targeted study population is healthy, at risk individuals who do not have signs or symptoms of the disease, and the study participation involves complex scheduling and invasive procedures such as bronchoscopy. In this report, we describe the recruitment process and evaluated the effectiveness of various recruitment strategies utilized in our National Cancer Institute sponsored lung cancer chemoprevention study with celecoxib. Heavy ex-smokers were recruited into the study through various methods such as radio advertisements, print media, mass mailings, flyers, internet postings and others. The number of inquiries, on-site screenees and randomization generated by each method determined the efficacy of that recruitment strategy. We prescreened 4470 individuals, invited 323 people for on-site screening and randomized 137 subjects. Radio advertisements (ads) generated the most inquiries (71.1%), followed by internet posting (11.8%), print media (6.0%), posted and racked flyers (4.4%), mass mailings (2.7%) and other strategies such as referrals from friends or family members or health care providers (2.3%). Radio ads, although costly, yielded the most subjects for on-site screening and randomization. Moreover, among the various types of radio stations, news radio stations were by far the most successful. Our results suggest that advertising on news radio is a highly effective recruitment method for successful accrual of ex-smokers into lung cancer chemoprevention trials.

A lay patient navigation training curriculum targeting disparities in cancer clinical trials.

PubMed

Bryant, Debbie Chatman; Williamson, Deborah; Cartmell, Kathleen; Jefferson, Melanie

2011-12-01

African-Americans experience a disproportionate share of thoracic cancer burden compared to Whites. Low socioeconomic status (SES) and race are factors in low clinical trial enrollment, accounting for the disparities between African-Americans and Whites. Less than 3% of newly diagnosed cancer patients enroll in clinical trials, and of that number, only 10% represent ethnic minorities. The value of clinical trials research is not generalizable without sufficient representation by ethnic minorities. Patient navigation, an intervention designed to ensure timely and efficient access to healthcare, may improve clinical trial enrollment among African-Americans in lung and esophageal trials by influencing a patient's perception of clinical trials. The lack of navigation programs and training may negatively influence standardization of navigation techniques. The purpose of this project was to deliver and evaluate an evidence-based navigation-training curriculum for "lay" navigators. The primary outcomes measured were confidence in the role as navigator, understanding a navigator's role, and knowledge and perception of clinical trials. The results revealed overall confidence in the role as lay navigators increased from pre-to-post test. Lessons learned included the need for preparatory classes to build the navigator's confidence, and additional training components in death and dying. A larger study is warranted to confirm the findings.

Improving recruitment and retention for an online randomized controlled trial: experience from the Youthnet study.

PubMed

Bull, S S; Vallejos, D; Levine, D; Ortiz, C

2008-09-01

The objective of the study was to present recruitment and retention findings for an Internet based HIV prevention trial evaluated using a randomized controlled design among 15-25-year-olds accessing a website on the Internet. We used a combination of automated electronic and personalized approaches to increase and diversify recruitment, verify participant eligibility and increase retention. We posted 3.5 million banner advertisements, 9354 individuals clicked on the advertisement, 8950 completed an eligibility screener and 3298 a baseline survey; we flagged 675 of these as suspicious and enrolled 2623 individuals. Of these, 2082 (79%) completed a follow-up at one-month and 1398 (53%) completed a two-month follow-up. This retention rate is the highest we have seen for an Internet-based HIV-prevention trial. Our procedures can be replicated in other trials. We stress the importance of using a combination of automated and personalized techniques to increase enrollment, verify eligibility and promote retention.

Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.

PubMed

Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T W; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S; Raman, Pichai; Waanders, Angela J; Resnick, Adam C; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascale; Jones, Chris

2018-05-14

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8 + tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term "HGG" in the pediatric population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

A systematic review of parenting interventions for traumatic brain injury: child and parent outcomes.

PubMed

Brown, Felicity Louise; Whittingham, Koa; Boyd, Roslyn; Sofronoff, Kate

2013-01-01

To evaluate the efficacy of parenting interventions on child and parent behavioral and emotional outcomes for parents of children with traumatic brain injury (TBI). Systematic searches of 5 databases. Included studies were assessed for quality, and relevant data were extracted and collated. Eight articles met inclusion criteria, reporting 6 trials of interventions involving parent training for parents of children with TBI. Only 1 pre-post study trialed a version of a traditional parenting intervention. The remaining studies involved a multicomponent family problem-solving intervention. Each trial found a statistically significant intervention effect for at least 1 outcome measure. Interventions that train parents may be a useful approach to alleviate behavioral and emotional disturbances after pediatric TBI. Some evidence suggests that these interventions may help to improve parenting skill and adjustment. However, all identified studies included interventions with multiple treatment components, so the effects attributable to parent training alone remain undetermined. Further quality trials are needed to assess the unique effectiveness of parenting interventions in this population.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

PubMed

Vorobiof, D A; Rapoport, B L; Chasen, M R; Abratt, R P; Cronje, N; Fourie, L; McMichael, G; Hacking, D

2002-03-01

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

Guidelines for reporting embedded recruitment trials.

PubMed

Madurasinghe, Vichithranie W

2016-01-14

Recruitment to clinical trials is difficult with many trials failing to recruit to target and within time. Embedding trials of recruitment interventions within host trials may provide a successful way to improve this. There are no guidelines for reporting such embedded methodology trials. As part of the Medical Research Council funded Systematic Techniques for Assisting Recruitment to Trials (MRC START) programme designed to test interventions to improve recruitment to trials, we developed guidelines for reporting embedded trials. We followed a three-phase guideline development process: (1) pre-meeting literature review to generate items for the reporting guidelines; (2) face-to-face consensus meetings to draft the reporting guidelines; and (3) post-meeting feedback review, and pilot testing, followed by finalisation of the reporting guidelines. We developed a reporting checklist based on the Consolidated Standards for Reporting Trials (CONSORT) statement 2010. Embedded trials evaluating recruitment interventions should follow the CONSORT statement 2010 and report all items listed as essential. We used a number of examples to illustrate key issues that arise in embedded trials and how best to report them, including (a) how to deal with description of the host trial; (b) the importance of describing items that may differ in the host and embedded trials (such as the setting and the eligible population); and (c) the importance of identifying clearly the point at which the recruitment interventions were embedded in the host trial. Implementation of these guidelines will improve the quality of reports of embedded recruitment trials while advancing the science, design and conduct of embedded trials as a whole.

Increasing the occupational therapy mental health workforce through innovative practice education: a pilot project.

PubMed

Rodger, Sylvia; Thomas, Yvonne; Holley, Sue; Springfield, Elizabeth; Edwards, Ann; Broadbridge, Jacqui; Greber, Craig; McBryde, Cathy; Banks, Rebecca; Hawkins, Rachel

2009-12-01

This paper describes the evaluation of a pilot trial of two innovative placement models in the area of mental health, namely role emerging and collaborative supervision. The Queensland Occupational Therapy Fieldwork Collaborative conducted this trial in response to workforce shortages in mental health. Six occupational therapy students and eight practice educators were surveyed pre- and post-placements regarding implementation of these innovative models. Students participating in these placements reported that they were highly likely to work in mental health upon graduation, and practice educators were positive about undertaking innovative placements in future. An overview of the placement sites, trials, outcomes and limitations of this pilot trial is provided. Though limited by its small sample size, this pilot trial has demonstrated the potential of innovative placement models to provide valuable student learning experiences in mental health. The profession needs to develop expertise in the use of innovative placement models if students are to be adequately prepared to work with the mental health issues of the Australian community now and in the future.

Study design to evaluate cognitive behavioral therapy among a diverse sample of adults with a first-time DUI offense.

PubMed

Chan Osilla, Karen; Watkins, Katherine E; Kulesza, Magdalena; Flórez, Karen; Lara-Greenberg, Marielena; Miles, Jeremy N V

2016-03-31

Driving under the influence (DUI) of alcohol is a major public health concern, and many individuals continue to drink and drive even after being convicted of a DUI offense. Latinos, in particular, are disproportionately likely to be arrested for a DUI, have higher rates of recidivism, and are more likely to die in alcohol-related accidents than non-Latino Whites. Latinos also experience significant disparities in accessing alcohol-related treatment. This study protocol paper describes a randomized trial of cognitive behavioral therapy (CBT) compared to usual care in DUI programs for individuals with a first-time offense and at-risk drinking. We will utilize a two-group randomized design where individuals enrolled in a DUI program with a first-time conviction will be randomized to CBT (n = 150) or usual care (n = 150). Participants will be assessed at baseline, immediately post-treatment, and 6-months post-treatment. Recidivism data will be collected using administrative data within 2 years post-treatment. This project has the potential to benefit a large population of vulnerable individuals who are at risk of DUI recidivism. It also develops a new model of care by providing treatment in DUI programs to reduce disparities associated with poor treatment access. Trial registration NCT02588703.

The Primary Prevention of PTSD in Firefighters: Preliminary Results of an RCT with 12-Month Follow-Up.

PubMed

Skeffington, Petra M; Rees, Clare S; Mazzucchelli, Trevor G; Kane, Robert T

2016-01-01

To develop and evaluate an evidence-based and theory driven program for the primary prevention of Post-traumatic Stress Disorder (PTSD). A pre-intervention / post-intervention / follow up control group design with clustered random allocation of participants to groups was used. The "control" group received "Training as Usual" (TAU). Participants were 45 career recruits within the recruit school at the Department of Fire and Emergency Services (DFES) in Western Australia. The intervention group received a four-hour resilience training intervention (Mental Agility and Psychological Strength training) as part of their recruit training school curriculum. Data was collected at baseline and at 6- and 12-months post intervention. We found no evidence that the intervention was effective in the primary prevention of mental health issues, nor did we find any significant impact of MAPS training on social support or coping strategies. A significant difference across conditions in trauma knowledge is indicative of some impact of the MAPS program. While the key hypotheses were not supported, this study is the first randomised control trial investigating the primary prevention of PTSD. Practical barriers around the implementation of this program, including constraints within the recruit school, may inform the design and implementation of similar programs in the future. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001362583.

Mediation and moderation of treatment effects in randomised controlled trials of complex interventions.

PubMed

Emsley, Richard; Dunn, Graham; White, Ian R

2010-06-01

Complex intervention trials should be able to answer both pragmatic and explanatory questions in order to test the theories motivating the intervention and help understand the underlying nature of the clinical problem being tested. Key to this is the estimation of direct effects of treatment and indirect effects acting through intermediate variables which are measured post-randomisation. Using psychological treatment trials as an example of complex interventions, we review statistical methods which crucially evaluate both direct and indirect effects in the presence of hidden confounding between mediator and outcome. We review the historical literature on mediation and moderation of treatment effects. We introduce two methods from within the existing causal inference literature, principal stratification and structural mean models, and demonstrate how these can be applied in a mediation context before discussing approaches and assumptions necessary for attaining identifiability of key parameters of the basic causal model. Assuming that there is modification by baseline covariates of the effect of treatment (i.e. randomisation) on the mediator (i.e. covariate by treatment interactions), but no direct effect on the outcome of these treatment by covariate interactions leads to the use of instrumental variable methods. We describe how moderation can occur through post-randomisation variables, and extend the principal stratification approach to multiple group methods with explanatory models nested within the principal strata. We illustrate the new methodology with motivating examples of randomised trials from the mental health literature.

Regional differences in baseline disease activity and remission rates following golimumab treatment for RA: results from the GO-MORE trial.

PubMed

Durez, Patrick; Pavelka, Karel; Lazaro, Maria Alicia; Garcia-Kutzbach, Abraham; Moots, Robert J; Amital, Howard; Govoni, Marinella; Vastesaeger, Nathan

2018-05-01

GO-MORE (NCT00975130) was a large open-label, multinational, multicenter, prospective phase 3 trial evaluating add-on therapy with golimumab in biologic-naïve patients with active rheumatoid arthritis (RA). The objective of this post hoc analysis was to examine regional differences in baseline disease activity and remission rates following golimumab treatment for RA. This was a planned, descriptive post hoc analysis of data from the GO-MORE trial. Baseline disease activity and remission were defined as moderate or severe based on EULAR criteria. This analysis included 3280 participants from the GO-MORE trial. All participants included in this analysis had high or moderate disease activity at baseline. At baseline, high disease activity was least common in Europe (71.0%), Canada (77.0%), and the Middle East (78.2%) and most common in Latin America (90.7%), South Africa (91.5%), and Asia (92.5%). Month 6 remission rates were highest in South Africa (29.1%), Europe (27.9%), and the Middle East (27.3%) and lowest in Canada (19.7%), Latin America (17.2%), and Asia (15.0%). Higher rates of remission in each geographical region generally corresponded with lower baseline disease activity. We suspect that access to care and implementation of the treat-to-target strategy were the most important determinants, but this apparent relationship needs to be confirmed in further studies that include a statistical analysis of prognostic indicators.

Use of ultraviolet-fluorescence-based simulation in evaluation of personal protective equipment worn for first assessment and care of a patient with suspected high-consequence infectious disease.

PubMed

Hall, S; Poller, B; Bailey, C; Gregory, S; Clark, R; Roberts, P; Tunbridge, A; Poran, V; Evans, C; Crook, B

2018-06-01

Variations currently exist across the UK in the choice of personal protective equipment (PPE) used by healthcare workers when caring for patients with suspected high-consequence infectious diseases (HCIDs). To test the protection afforded to healthcare workers by current PPE ensembles during assessment of a suspected HCID case, and to provide an evidence base to justify proposal of a unified PPE ensemble for healthcare workers across the UK. One 'basic level' (enhanced precautions) PPE ensemble and five 'suspected case' PPE ensembles were evaluated in volunteer trials using 'Violet'; an ultraviolet-fluorescence-based simulation exercise to visualize exposure/contamination events. Contamination was photographed and mapped. There were 147 post-simulation and 31 post-doffing contamination events, from a maximum of 980, when evaluating the basic level of PPE. Therefore, this PPE ensemble did not afford adequate protection, primarily due to direct contamination of exposed areas of the skin. For the five suspected case ensembles, 1584 post-simulation contamination events were recorded, from a maximum of 5110. Twelve post-doffing contamination events were also observed (face, two events; neck, one event; forearm, one event; lower legs, eight events). All suspected case PPE ensembles either had post-doffing contamination events or other significant disadvantages to their use. This identified the need to design a unified PPE ensemble and doffing procedure, incorporating the most protective PPE considered for each body area. This work has been presented to, and reviewed by, key stakeholders to decide on a proposed unified ensemble, subject to further evaluation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial.

PubMed

Hammond, Simon P; Cross, Jane L; Shepstone, Lee; Backhouse, Tamara; Henderson, Catherine; Poland, Fiona; Sims, Erika; MacLullich, Alasdair; Penhale, Bridget; Howard, Robert; Lambert, Nigel; Varley, Anna; Smith, Toby O; Sahota, Opinder; Donell, Simon; Patel, Martyn; Ballard, Clive; Young, John; Knapp, Martin; Jackson, Stephen; Waring, Justin; Leavey, Nick; Howard, Gregory; Fox, Chris

2017-12-04

Health and social care provision for an ageing population is a global priority. Provision for those with dementia and hip fracture has specific and growing importance. Older people who break their hip are recognised as exceptionally vulnerable to experiencing confusion (including but not exclusively, dementia and/or delirium and/or cognitive impairment(s)) before, during or after acute admissions. Older people experiencing hip fracture and confusion risk serious complications, linked to delayed recovery and higher mortality post-operatively. Specific care pathways acknowledging the differences in patient presentation and care needs are proposed to improve clinical and process outcomes. This protocol describes a multi-centre, feasibility, cluster-randomised, controlled trial (CRCT) to be undertaken across ten National Health Service hospital trusts in the UK. The trial will explore the feasibility of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery intervention (PERFECT-ER), which acknowledges the differences in care needs of confused older patients experiencing hip fracture, with standard care. The trial will also have an integrated process evaluation to explore how PERFECT-ER is implemented and interacts with the local context. The study will recruit 400 hip fracture patients identified as experiencing confusion and will also recruit "suitable informants" (individuals in regular contact with participants who will complete proxy measures). We will also recruit NHS professionals for the process evaluation. This mixed methods design will produce data to inform a definitive evaluation of the intervention via a large-scale pragmatic randomised controlled trial (RCT). The trial will provide a preliminary estimate of potential efficacy of PERFECT-ER versus standard care; assess service delivery variation, inform primary and secondary outcome selection, generate estimates of recruitment and retention rates, data collection difficulties, and completeness of outcome data and provide an indication of potential economic benefits. The process evaluation will enhance knowledge of implementation delivery and receipt. ISRCTN, 99336264 . Registered on 5 September 2016.

Effectiveness evaluation of whole-body electromyostimulation as a post-exercise recovery method.

PubMed

DE LA Camara, Miguel A; Pardos, Ana I; Veiga, Óscar L

2018-01-04

Whole-body electromyostimulation (WB-EMS) devices are now being used in health and sports training, although there are few studies investigating their benefits. The objective of this research was to evaluate the effectiveness of WB-EMS as a post-exercise recovery method, and compare it with other methods like active and passive recovery. The study included nine trained men (age = 21 ± 1years, height = 1.77 ± 0.4 m, mass = 62 ± 7 kg). Three trials were performed in three different sessions, 1 week apart. Each trial, the participants completed the same exercise protocol and a different recovery method each time. A repeated measures design was used to check the basal reestablishing on several physiological variables [lactate, heart rate, percentage of tissue hemoglobin saturation, temperature, and neuromuscular fatigue] and to evaluate the quality of recovery. The non-parametric Wilcoxon and Friedman ANOVA tests were used to examine the differences between recovery methods. The results showed no differences between methods in the physiological and psychological variables analyzed. Although, the blood lactate concentration showed borderline statistical significance between methods (P = 0.050). Likewise, WB-EMS failed to recover baseline blood lactate concentration (P = 0.021) and percentage of tissue hemoglobin saturation (P = 0.023), in contrast to the other two methods. These findings suggest that WB-EMS is not a good recovery method because the power of reestablishing of several physiological and psychological parameters is not superior to other recovery methods like active and passive recovery.

Early intervention to protect the mother-infant relationship following postnatal depression: study protocol for a randomised controlled trial.

PubMed

Milgrom, Jeannette; Holt, Charlene

2014-10-03

At least 13% of mothers experience depression in the first postnatal year, with accompanying feelings of despair and a range of debilitating symptoms. Serious sequelae include disturbances in the mother-infant relationship and poor long-term cognitive and behavioural outcomes for the child. Surprisingly, treatment of maternal symptoms of postnatal depression does not improve the mother-infant relationship for a majority of women. Targeted interventions to improve the mother-infant relationship following postnatal depression are scarce and, of those that exist, the majority are not evaluated in randomised controlled trials. This study aims to evaluate a brief targeted mother-infant intervention, to follow cognitive behavioural therapy treatment of postnatal depression, which has the potential to improve developmental outcomes of children of depressed mothers. The proposed study is a two-arm randomised controlled trial with follow-up to 6 months. One hundred participants will be recruited via referrals from health professionals including maternal and child health nurses and general practitioners, as well as self-referrals from women who have seen promotional materials for the study. Women who meet inclusion criteria (infant aged <12 months, women 18+ years of age) will complete the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV-TR Axis I Disorders. Those with a clinical diagnosis of current major or minor depressive disorder and who do not meet exclusion criteria (that is, currently receiving treatment for depression, significant difficulty with English, medium to high suicide risk, current self-harm, current substance abuse, current post-traumatic stress disorder, current manic/hypomanic episode or psychotic symptoms) will be randomised to receive either a 4-session mother-infant intervention (HUGS: Happiness Understanding Giving and Sharing) or a 4-session attention placebo playgroup (Playtime) following a 12-session postnatal depression group treatment programme. Primary outcome measures are the Parenting Stress Index (self-report measure) and the Parent-child Early Relational Assessment (observational measure coded by a blinded observer). Measurements are taken at baseline, after the postnatal depression programme, post-HUGS/Playtime, and at 6 months post-HUGS/Playtime. This research addresses the need for specific treatment for mother-infant interactional difficulties following postnatal depression. There is a need to investigate interventions in randomised trials to prevent detrimental effects on child development and make available evidence-based treatments. Australia and New Zealand Clinical Trials Register: ACTRN12612001110875. Date Registered: 17 October 2012.

Randomised controlled pilot study to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: TOPIC feasibility study protocol.

PubMed

Yeung, Joyce; Melody, Teresa; Kerr, Amy; Naidu, Babu; Middleton, Lee; Tryposkiadis, Kostas; Daniels, Jane; Gao, Fang

2016-12-01

Open chest surgery (thoracotomy) is considered the most painful of surgical procedures. Forceful wound retraction, costochondral dislocation, posterior costovertebral ligament disruption, intercostal nerve trauma and wound movement during respiration combine to produce an acute, severe postoperative pain insult and persistent chronic pain many months after surgery is common. Three recent systematic reviews conclude that unilateral continuous paravertebral blockade (PVB) provides analgesia at least equivalent to thoracic epidural blockade (TEB) in the postoperative period, has a lower failure rate, and symptom relief that lasted months. Crucially, PVB may reduce the development of subsequent chronic pain by intercostal nerve protection or decreased nociceptive input. The overall aim is to determine in patients who undergo thoracotomy whether perioperative PVB results in reducing chronic post-thoracotomy pain (CPTP) compared with TEB. This pilot study will evaluate feasibility of a substantive trial. TOPIC is a randomised controlled trial comparing the effectiveness of TEB and PVB in reducing CPTP. This is a pilot study to evaluate feasibility of a substantive trial and study processes in 2 adult thoracic centres, Heart of England NHS Foundation Trust (HEFT) and University Hospital of South Manchester NHS Foundation Trust (UHSM). The primary objective is to establish the number of patients randomised as a proportion of those eligible. Secondary objectives include evaluation of study processes. Analyses of feasibility and patient-reported outcomes will primarily take the form of simple descriptive statistics and where appropriate, point estimates of effects sizes and associated 95% CIs. The study has obtained ethical approval from NHS Research Ethics Committee (REC number 14/EM/1280). Dissemination plan includes: informing patients and health professionals; engaging multidisciplinary professionals to support a proposal of a definitive trial and submission for a full HTA application dependent on the success of the study. ISRCTN45041624; Pre-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/.

Is EMDR an effective treatment for people diagnosed with both intellectual disability and post-traumatic stress disorder?

PubMed

Gilderthorp, Rosanna C

2015-03-01

This study aimed to critically review all studies that have set out to evaluate the use of eye movement desensitization and reprocessing (EMDR) for people diagnosed with both intellectual disability (ID) and post-traumatic stress disorder (PTSD). Searches of the online databases Psych Info, The Cochrane Database of Systematic Reviews, The Cochrane Database of Randomized Control Trials, CINAHL, ASSIA and Medline were conducted. Five studies are described and evaluated. Key positive points include the high clinical salience of the studies and their high external validity. Several common methodological criticisms are highlighted, however, including difficulty in the definition of the terms ID and PTSD, lack of control in design and a lack of consideration of ethical implications. Overall, the articles reviewed indicate cause for cautious optimism about the utility of EMDR with this population. The clinical and research implications of this review are discussed. © The Author(s) 2014.

A randomized clinical trial of how to best position retropubic slings for stress urinary incontinence: Development of a study protocol for the mid-urethral sling tensioning (MUST) trial.

PubMed

Brennand, Erin A; Kim-Fine, Shunaha

2016-08-15

The goal of this trial is to compare two techniques for tensioning retropubic midurethral slings: a Mayo scissor between the tape and urethra vs. a Babcock clamp creating a measured loop underneath the urethra. The primary outcome is a composite of abnormal bladder function at 12 months post surgery. Abnormal bladder function is defined as bothersome stress incontinence or worsening over active bladder symptoms, a positive cough stress test, re-treatment of stress urinary incontinence, post-operative urinary retention requiring either catheterization beyond 6 weeks or surgical intervention. Secondary outcomes include the duration of post operative urinary retention, quality of life scores, and physical examination. This article describes the rationale and design of this clinical trial, which will be of interest to those who care for patient with pelvic floor disorders such as stress urinary incontinence.

Caring letters for suicide prevention: implementation of a multi-site randomized clinical trial in the U.S. military and Veteran Affairs healthcare systems.

PubMed

Luxton, David D; Thomas, Elissa K; Chipps, Joan; Relova, Rona M; Brown, Daphne; McLay, Robert; Lee, Tina T; Nakama, Helenna; Smolenski, Derek J

2014-03-01

Caring letters is a suicide prevention intervention that entails the sending of brief messages that espouse caring concern to patients following discharge from treatment. First tested more than four decades ago, this intervention is one of the only interventions shown in a randomized controlled trial to reduce suicide mortality rates. Due to elevated suicide risk among patients following psychiatric hospitalization and the steady increase in suicide rates among the U.S. military personnel, it is imperative to test interventions that may help prevent suicide among high-risk military personnel and veterans. This paper describes the design, methods, study protocol, and regulatory implementation processes for a multi-site randomized controlled trial that aims to evaluate the effectiveness of a caring emails intervention for suicide prevention in the military and VA healthcare systems. The primary outcome is suicide mortality rates to be determined 24 months post-discharge from index hospital stay. Healthcare re-utilization rates will also be evaluated and comprehensive data will be collected regarding suicide risk factors. Recommendations for navigating the military and VA research regulatory processes and implementing a multi-site clinical trial at military and VA hospitals are discussed. Published by Elsevier Inc.

Effectiveness of implementing a wake up and breathe program on sedation and delirium in the ICU.

PubMed

Khan, Babar A; Fadel, William F; Tricker, Jason L; Carlos, W Graham; Farber, Mark O; Hui, Siu L; Campbell, Noll L; Ely, E Wesley; Boustani, Malaz A

2014-12-01

Mechanically ventilated critically ill patients receive significant amounts of sedatives and analgesics that increase their risk of developing coma and delirium. We evaluated the impact of a "Wake-up and Breathe Protocol" at our local ICU on sedation and delirium. A pre/post implementation study design. A 22-bed mixed surgical and medical ICU. Seven hundred two consecutive mechanically ventilated ICU patients from June 2010 to January 2013. Implementation of daily paired spontaneous awakening trials (daily sedation vacation plus spontaneous breathing trials) as a quality improvement project. After implementation of our program, there was an increase in the mean Richmond Agitation Sedation Scale scores on weekdays of 0.88 (p < 0.0001) and an increase in the mean Richmond Agitation Sedation Scale scores on weekends of 1.21 (p < 0.0001). After adjusting for age, race, gender, severity of illness, primary diagnosis, and ICU, the incidence and prevalence of delirium did not change post implementation of the protocol (incidence: 23% pre vs 19.6% post; p = 0.40; prevalence: 66.7% pre vs 55.3% post; p = 0.06). The combined prevalence of delirium/coma decreased from 90.8% pre protocol implementation to 85% postimplementation (odds ratio, 0.505; 95% CI, 0.299-0.853; p = 0.01). Implementing a "Wake Up and Breathe Program" resulted in reduced sedation among critically ill mechanically ventilated patients but did not change the incidence or prevalence of delirium.

Effects of prednisone on eosinophilic bronchitis in asthma: a systematic review and meta-analysis*,**

PubMed Central

Sakae, Thiago Mamôru; Maurici, Rosemeri; Trevisol, Daisson José; Pizzichini, Marcia Margaret Menezes; Pizzichini, Emílio

2014-01-01

OBJECTIVE: To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis. METHODS: We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV1-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV1. RESULTS: The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (↓8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (↓83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (↓267.60 µg/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV1 (↑8.09%; 95% CI: 5.35-10.83; p < 0.001). CONCLUSIONS: In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV1. PMID:25410844

Induction of labour for improving birth outcomes for women at or beyond term

PubMed Central

Gülmezoglu, A Metin; Crowther, Caroline A; Middleton, Philippa; Heatley, Emer

2014-01-01

Background As a pregnancy continues beyond term the risks of babies dying inside the womb or in the immediate newborn period increase. Whether a policy of labour induction at a predetermined gestational age can reduce this increased risk is the subject of this review. Objectives To evaluate the benefits and harms of a policy of labour induction at term or post-term compared with awaiting spontaneous labour or later induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2012). Selection criteria Randomised controlled trials conducted in women at or beyond term. The eligible trials were those comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour. Cluster-randomised trials and cross-over trials are not included. Quasi-random allocation schemes such as alternation, case record numbers or open random-number lists were not eligible. Data collection and analysis Two review authors independently assessed trials for inclusion. Two review authors independently assessed trial quality and extracted data. Data were checked for accuracy. Outcomes are analysed in two main categories: gestational age and cervix status. Main results We included 22 trials reporting on 9383 women. The trials were generally at moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths: risk ratio (RR) 0.31, 95% confidence interval (CI) 0.12 to 0.88; 17 trials, 7407 women. There was one perinatal death in the labour induction policy group compared with 13 perinatal deaths in the expectant management group. The number needed to treat to benefit (NNTB) with induction of labour in order to prevent one perinatal death was 410 (95% CI 322 to 1492). For the primary outcome of perinatal death and most other outcomes, no differences between timing of induction subgroups were seen; the majority of trials adopted a policy of induction at 41 completed weeks (287 days) or more. Fewer babies in the labour induction group had meconium aspiration syndrome (RR 0.50, 95% CI 0.34 to 0.73; eight trials, 2371 infants) compared with a policy of expectant management. There was no statistically significant difference between the rates of neonatal intensive care unit (NICU) admission for induction compared with expectant management (RR 0.90, 95% CI 0.78 to 1.04; 10 trials, 6161 infants). For women in the policy of induction arms of trials, there were significantly fewer caesarean sections compared with expectant management in 21 trials of 8749 women (RR 0.89, 95% CI 0.81 to 0.97). Authors’ conclusions A policy of labour induction compared with expectant management is associated with fewer perinatal deaths and fewer caesarean sections. Some infant morbidities such as meconium aspiration syndrome were also reduced with a policy of post-term labour induction although no significant differences in the rate of NICU admission were seen. However, the absolute risk of perinatal death is small. Women should be appropriately counselled in order to make an informed choice between scheduled induction for a post-term pregnancy or monitoring without induction (or delayed induction). PMID:22696345

Increasing Access to Modern Multidisciplinary Breast Cancer Care

DTIC Science & Technology

2002-02-01

patient at course completion and 1 year later. A randomized trial of the effect of same-day mammography on patient compliance, utilizing different practice...tests for independent samples are presented. P-values are 2-sided. Table 1 : Training Effects Comparison of Peer Educators Pre- and Post-Test With Peer...Bandura) The numbers of PE projects have grown. 1 The comparatively few published outcomes evaluations of PE interventions suggest that PE are effective

Feasibity of Using a Measure of Heart Rate Change in Human Adults to Signal Occurrence of Tone

DTIC Science & Technology

1977-11-01

clearly with the binaural subjects in the 85 dB free response live trials situation on post-tone offset beat 1. Here, the significant response...seen when comparing the sign test results of post-tone offset beat I in the binaural 15 db motor response live trial situation to the analagous 85 db...subject response consistency. Tills is most evident in the binaural 85 db fret live situation comparison of post-tone offset beat one to

Ear Acupuncture for Post-Operative Pain Associated with Ambulatory Arthroscopic Knee Surgery: A Randomized Controlled Trial

DTIC Science & Technology

2014-01-14

E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH 14 Jan 2014 Final Report Ear acupuncture for post-operative pain associated with ambulatory arthroscopic...DISTRIBUTION A. Approved for public release: distribution unlimited. The purpose of this study is to compare ear acupuncture plus standard therapy versus...3298 Ear Acupuncture for Post-operative Pa111 Assoc1ated With Ambulatory Arthroscopic Knee Surgery A Randomized Controlled Trial ’• V ’’ ’-’ I

Early mobilization of patients who have had a hip or knee joint replacement reduces length of stay in hospital: a systematic review.

PubMed

Guerra, Mark L; Singh, Parminder J; Taylor, Nicholas F

2015-09-01

To systematically review the effect of early mobilization after hip or knee joint replacement surgery on length of stay in an acute hospital. Randomized controlled trials were selected from electronic databases based on inclusion criterion requiring an experimental group mobilizing (sitting out of bed/walking) earlier than a comparison group post joint replacement surgery of the hip or knee in an acute hospital. Clinically homogeneous data were analyzed with meta-analysis. Five randomized controlled trials (totaling 622 participants) were included for review. A meta-analysis of 5 trials found a reduced length of stay of 1.8 days (95% confidence interval 1.1 to 2.6) in favor of the experimental group. In 4 of the 5 trials the experimental group first sat out of bed within 24 hours post operatively. In 4 of the 5 trials the experimental group first walked within 48 hours post operatively. Individual trials reported benefits in range of motion, muscle strength and health-related quality of life in favor of the experimental group. There were no differences in discharge destinations, incidence of negative outcomes or adverse events attributable to early mobilization when compared to the comparison groups. Early mobilization post hip or knee joint replacement surgery can result in a reduced length of stay of about 1.8 days. Trials that reported these positive results showed that early mobilization can be achieved within 24 hours of operation. This positive gain was achieved without an increase in negative outcomes. © The Author(s) 2014.

Honey as a topical treatment for wounds.

PubMed

Jull, Andrew B; Cullum, Nicky; Dumville, Jo C; Westby, Maggie J; Deshpande, Sohan; Walker, Natalie

2015-03-06

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective of this review was to assess the effects of honey compared with alternative wound dressings and topical treatments on the of healing of acute (e.g. burns, lacerations) and/or chronic (e.g. venous ulcers) wounds. For this update of the review we searched the Cochrane Wounds Group Specialised Register (searched 15 October 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9); Ovid MEDLINE (1946 to October Week 1 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October 2014); Ovid EMBASE (1974 to 13 October 2014); and EBSCO CINAHL (1982 to 15 October 2014). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. All data have been subsequently checked by two more authors. We identified 26 eligible trials (total of 3011 participants). Three trials evaluated the effects of honey in minor acute wounds, 11 trials evaluated honey in burns, 10 trials recruited people with different chronic wounds including two in people with venous leg ulcers, two trials in people with diabetic foot ulcers and single trials in infected post-operative wounds, pressure injuries, cutaneous Leishmaniasis and Fournier's gangrene. Two trials recruited a mixed population of people with acute and chronic wounds. The quality of the evidence varied between different comparisons and outcomes. We mainly downgraded the quality of evidence for risk of bias, imprecision and, in a few cases, inconsistency.There is high quality evidence (2 trials, n=992) that honey dressings heal partial thickness burns more quickly than conventional dressings (WMD -4.68 days, 95%CI -5.09 to -4.28) but it is unclear if there is a difference in rates of adverse events (very low quality evidence) or infection (low quality evidence).There is very low quality evidence (4 trials, n=332) that burns treated with honey heal more quickly than those treated with silver sulfadiazine (SSD) (WMD -5.12 days, 95%CI -9.51 to -0.73) and high quality evidence from 6 trials (n=462) that there is no difference in overall risk of healing within 6 weeks for honey compared with SSD (RR 1.00, 95% CI 0.98 to 1.02) but a reduction in the overall risk of adverse events with honey relative to SSD. There is low quality evidence (1 trial, n=50) that early excision and grafting heals partial and full thickness burns more quickly than honey followed by grafting as necessary (WMD 13.6 days, 95%CI 9.82 to 17.38).There is low quality evidence (2 trials, different comparators, n=140) that honey heals a mixed population of acute and chronic wounds more quickly than SSD or sugar dressings.Honey healed infected post-operative wounds more quickly than antiseptic washes followed by gauze and was associated with fewer adverse events (1 trial, n=50, moderate quality evidence, RR of healing 1.69, 95%CI 1.10 to 2.61); healed pressure ulcers more quickly than saline soaks (1 trial, n= 40, very low quality evidence, RR 1.41, 95%CI 1.05 to 1.90), and healed Fournier's gangrene more quickly than Eusol soaks (1 trial, n=30, very low quality evidence, WMD -8.00 days, 95%CI -6.08 to -9.92 days).The effects of honey relative to comparators are unclear for: venous leg ulcers (2 trials, n= 476, low quality evidence); minor acute wounds (3 trials, n=213, very low quality evidence); diabetic foot ulcers (2 trials, n=93, low quality evidence); Leishmaniasis (1 trial, n=100, low quality evidence); mixed chronic wounds (2 trials, n=150, low quality evidence). It is difficult to draw overall conclusions regarding the effects of honey as a topical treatment for wounds due to the heterogeneous nature of the patient populations and comparators studied and the mostly low quality of the evidence. The quality of the evidence was mainly downgraded for risk of bias and imprecision. Honey appears to heal partial thickness burns more quickly than conventional treatment (which included polyurethane film, paraffin gauze, soframycin-impregnated gauze, sterile linen and leaving the burns exposed) and infected post-operative wounds more quickly than antiseptics and gauze. Beyond these comparisons any evidence for differences in the effects of honey and comparators is of low or very low quality and does not form a robust basis for decision making.

Honey as a topical treatment for wounds.

PubMed

Jull, Andrew B; Rodgers, Anthony; Walker, Natalie

2008-10-08

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (burns, lacerations and other traumatic wounds) and chronic wounds (venous ulcers, arterial ulcers, diabetic ulcers, pressure ulcers, infected surgical wounds). We searched the Cochrane Wounds Group Specialised Register (May 2008), CENTRAL (May 2008) and several other electronic databases (May 2008). Bibliographies were searched and manufacturers of dressing products were contacted for unpublished trials. Randomised and quasi randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised using a data extraction sheet by one author and independently verified by a second author. 19 trials (n=2554) were identified that met the inclusion criteria. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and nine trials evaluated the effect the honey in burns. In chronic wounds two trials evaluated the effect of honey in venous leg ulcers and one trial in pressure ulcers, infected post-operative wounds, and Fournier's gangrene respectively. Two trials recruited people with mixed groups of chronic or acute wounds. The poor quality of most of the trial reports means the results should be interpreted with caution, except in venous leg ulcers. In acute wounds, honey may reduce time to healing compared with some conventional dressings in partial thickness burns (WMD -4.68 days, 95%CI -4.28 to -5.09 days). All the included burns trials have originated from a single centre, which may have impact on replicability. In chronic wounds, honey in addition to compression bandaging does not significantly increase healing in venous leg ulcers (RR 1.15, 95%CI 0.96 to 1.38). There is insufficient evidence to determine the effect of honey compared with other treatments for burns or in other acute or chronic wound types. Honey may improve healing times in mild to moderate superficial and partial thickness burns compared with some conventional dressings. Honey dressings as an adjuvant to compression do not significantly increase leg ulcer healing at 12 weeks. There is insufficient evidence to guide clinical practice in other areas.

Protocol for process evaluation of a randomised controlled trial of family-led rehabilitation post stroke (ATTEND) in India.

PubMed

Liu, Hueiming; Lindley, Richard; Alim, Mohammed; Felix, Cynthia; Gandhi, Dorcas B C; Verma, Shweta J; Tugnawat, Deepak Kumar; Syrigapu, Anuradha; Ramamurthy, Ramaprabhu Krishnappa; Pandian, Jeyaraj D; Walker, Marion; Forster, Anne; Anderson, Craig S; Langhorne, Peter; Murthy, Gudlavalleti Venkata Satyanarayana; Shamanna, Bindiganavale Ramaswamy; Hackett, Maree L; Maulik, Pallab K; Harvey, Lisa A; Jan, Stephen

2016-09-15

We are undertaking a randomised controlled trial (fAmily led rehabiliTaTion aftEr stroke in INDia, ATTEND) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability; as a potentially affordable, culturally acceptable and effective intervention for use in India. A process evaluation is needed to understand how and why this complex intervention may be effective, and to capture important barriers and facilitators to its implementation. We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting. The realist and RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) frameworks informed the design. Mixed methods include semistructured interviews with health providers, patients and their carers, analysis of quantitative process data describing fidelity and dose of intervention, observations of trial set up and implementation, and the analysis of the cost data from the patients and their families perspective and programme budgets. These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial, and then triangulated with the results from the primary outcome evaluation. The process evaluation has received ethical approval for all sites in India. In low-income and middle-income countries, the available human capital can form an approach to reducing the evidence practice gap, compared with the high cost alternatives available in established market economies. This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale. Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred, cost-effective and sustainable models of stroke rehabilitation. CTRI/2013/04/003557. 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/

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

Pathways to prevention: protocol for the CAP (Climate and Preventure) study to evaluate the long-term effectiveness of school-based universal, selective and combined alcohol misuse prevention into early adulthood.

PubMed

Newton, Nicola C; Stapinski, Lexine; Slade, Tim; Champion, Katrina E; Barrett, Emma L; Chapman, Catherine; Smout, Anna; Lawler, Siobhan; Mather, Marius; Castellanos-Ryan, Natalie; Conrod, Patricia J; Teesson, Maree

2018-05-21

Alcohol use and associated harms are among the leading causes of burden of disease among young people, highlighting the need for effective prevention. The Climate and Preventure (CAP) study was the first trial of a combined universal and selective school-based approach to preventing alcohol misuse among adolescents. Initial results indicate that universal, selective and combined prevention were all effective in delaying the uptake of alcohol use and binge drinking for up to 3 years following the interventions. However, little is known about the sustainability of prevention effects across the transition to early adulthood, a period of increased exposure to alcohol and other drug use. This paper describes the protocol for the CAP long-term follow-up study which will determine the effectiveness of universal, selective and combined alcohol misuse prevention up to 7 years post intervention, and across the transition from adolescence into early adulthood. A cluster randomized controlled trial was conducted between 2012 and 2015 with 2190 students (mean age: 13.3 yrs) from 26 Australian high schools. Participants were randomized to receive one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). The positive effect of the interventions on alcohol use at 12-, 24- and 36-month post baseline have previously been reported. This study will follow up the CAP study cohort approximately 5- and 7-years post baseline. The primary outcome will be alcohol use and related harms. Secondary outcomes will be cannabis use, alcohol and other drug harms including violent behavior, and mental health symptomatology. Analyses will be conducted using multi-level, mixed effects models within an intention-to-treat framework. This study will provide the first ever evaluation of the long-term effectiveness of combining universal and selective approaches to alcohol prevention and will examine the durability of intervention effects into the longer-term, over a 7-year period from adolescence to early adulthood. This trial was registered in the Australian New Zealand Clinical Trials Registry ( ACTRN12612000026820 ) on January 6th 2012.

Effectiveness of bovine-derived xenograft versus bioactive glass with periodontally accelerated osteogenic orthodontics in adults: a randomized, controlled clinical trial.

PubMed

Bahammam, Maha A

2016-11-30

Periodontally accelerated osteogenic orthodontics (PAOO) combines periodontal therapy with orthodontic therapy, which minimises treatment time. This study compared the effectiveness of a bovine-derived xenograft with that of bioactive glass when combined with PAOO for the treatment of adult patients with moderate crowding of the teeth. In this prospective, single-masked clinical trial, 33 orthodontic patients (20 women, 13 men; mean age 21.2 ± 1.43 [18 - 27] years), were randomly allocated to one of three groups. Group 1 underwent a modified corticotomy technique on the labial side only, whereas group 2 was treated with the same technique combined with PAOO using a bovine-derived xenograft and group 3 was treated in the same way but combining PAOO with bioactive glass. The total treatment duration was recorded from the start of active orthodontic treatment, immediately after corticotomy, and at the time of debonding. Probing depth was evaluated clinically and bone density and root length were evaluated radiographically on the day of surgery (baseline, T1), post-treatment at debonding (T2), and 9 months post-treatment (T3). The duration of orthodontic treatment was markedly reduced to an average of 11.4 ± 0.14 weeks in all groups. All probing depths were < 3 mm, the interdental papillae were well preserved, there was no loss of tooth vitality, and there was no evidence of significant apical root resorption at any time interval. All groups showed a decrease in mean bone density at T2 followed by an increase at T3. The net percentage change that occurred between baseline and 9 months post-treatment was significantly different between the three groups. Groups 2 and 3, where grafts were incorporated, demonstrated a statistically significant greater increase in bone density than group 1 at T3. Combination of orthodontic treatment and periodontal surgery is an effective treatment for adult patients that decreases the duration of active treatment and reduces the risk of root resorption. Use of a bovine-derived xenograft with modified corticotomy provided superior benefits in terms of increased bone density than did the use of bioactive glass. The study was retrospectively registered at ClinicalTrials.gov under Clinical Trial Registration Number: NCT02796911 .

Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

PubMed

Karaarslan, Numan; Yilmaz, Ibrahim; Ozbek, Hanefi; Caliskan, Tezcan; Topuk, Savas; Sirin, Duygu Yasar; Ates, Ozkan

2018-04-06

The aim of this study was to systematically investigate the role of artificial small interfering RNA (siRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and "glioblastoma," either individually or combined (\\"OR\\" and \\"AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. To be able to evaluate the clinical use of siRNAs, there is an urgent need for in-vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis

PubMed Central

Ayton, Lauren N.; Blamey, Peter J.; Guymer, Robyn H.; Luu, Chi D.; Nayagam, David A. X.; Sinclair, Nicholas C.; Shivdasani, Mohit N.; Yeoh, Jonathan; McCombe, Mark F.; Briggs, Robert J.; Opie, Nicholas L.; Villalobos, Joel; Dimitrov, Peter N.; Varsamidis, Mary; Petoe, Matthew A.; McCarthy, Chris D.; Walker, Janine G.; Barnes, Nick; Burkitt, Anthony N.; Williams, Chris E.; Shepherd, Robert K.; Allen, Penelope J.

2014-01-01

Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Trial Registration Clinicaltrials.gov NCT01603576 PMID:25521292

Major publications in the critical care pharmacotherapy literature: January-December 2017.

PubMed

Hammond, Drayton A; Baumgartner, Laura; Cooper, Craig; Donahey, Elisabeth; Harris, Serena A; Mercer, Jessica M; Morris, Mandy; Patel, Mona K; Plewa-Rusiecki, Angela M; Poore, Alia A; Szaniawski, Ryan; Horner, Deanna

2018-06-01

To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2017. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 115 during 2017. Two meta-analyses and eight original research trials were reviewed here from those included in the monthly CCPLU. Meta-analyses on early, goal-directed therapy for septic shock and statin therapy for acute respiratory distress syndrome were summarized. Original research trials that were included evaluate thrombolytic therapy in severe stroke, hyperoxia and hypertonic saline in septic shock, intraoperative ketamine for prevention of post-operative delirium, intravenous ketorolac dosing regimens for acute pain, angiotensin II for vasodilatory shock, dabigatran reversal with idarucizumab, bivalirudin versus heparin monotherapy for myocardial infarction, and balanced crystalloids versus saline fluid resuscitation. This clinical review provides perspectives on impactful critical care pharmacotherapy publications in 2017. Copyright © 2018 Elsevier Inc. All rights reserved.

Laser-assisted subepithelial keratectomy (LASEK) versus photorefractive keratectomy (PRK) for correction of myopia.

PubMed

Li, Shi-Ming; Zhan, Siyan; Li, Si-Yuan; Peng, Xiao-Xia; Hu, Jing; Law, Hua Andrew; Wang, Ning-Li

2016-02-22

Myopia (near-sightedness or short-sightedness) is a condition in which the refractive power of the eye is greater than required. The most frequent complaint of people with myopia is blurred distance vision, which can be eliminated by conventional optical aids such as spectacles or contact lenses, or by refractive surgery procedures such as photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK). PRK uses laser to remove the corneal stroma. Similar to PRK, LASEK first creates an epithelial flap and then replaces it after ablating the corneal stroma. The relative benefits and harms of LASEK and PRK, as shown in different trials, warrant a systematic review. The objective of this review is to compare LASEK versus PRK for correction of myopia by evaluating their efficacy and safety in terms of postoperative uncorrected visual acuity, residual refractive error, and associated complications. We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2015 Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 December 2015. We used the Science Citation Index and searched the reference lists of the included trials to identify relevant trials for this review. We included in this review randomized controlled trials (RCTs) comparing LASEK versus PRK for correction of myopia. Trial participants were 18 years of age or older and had no co-existing ocular or systemic diseases that might affect refractive status or wound healing. Two review authors independently screened all reports and assessed the risk of bias of trials included in this review. We extracted data and summarized findings using risk ratios and mean differences. We used a random-effects model when we identified at least three trials, and we used a fixed-effect model when we found fewer than three trials. We included 11 RCTs with a total of 428 participants 18 years of age or older with low to moderate myopia. These trials were conducted in the Czech Republic, Brazil, Italy, Iran, China, Korea, Mexico, Turkey, USA, and UK. Investigators of 10 out of 11 trials randomly assigned one eye of each participant to be treated with LASEK and the other with PRK, but did not perform paired-eye (matched) analysis. Because of differences in outcome measures and follow-up times among the included trials, few trials contributed data for many of the outcomes we analyzed for this review. Overall, we judged RCTs to be at unclear risk of bias due to poor reporting; however, because of imprecision, inconsistency, and potential reporting bias, we graded the quality of the evidence from very low to moderate for outcomes assessed in this review.The proportion of eyes with uncorrected visual acuity of 20/20 or better at 12-month follow-up was comparable in LASEK and PRK groups (risk ratio (RR) 0.98, 95% confidence interval (95% CI) 0.92 to 1.05). Although the 95% CI suggests little to no difference in effect between groups, we judged the quality of the evidence to be low because only one trial reported this outcome (102 eyes). At 12 months post treatment, data from two trials suggest no difference or a possibly small effect in favor of PRK over LASEK for the proportion of eyes achieving ± 0.50 D of target refraction (RR 0.93, 95% CI 00.84 to 1.03; 152 eyes; low-quality evidence). At 12 months post treatment, one trial reported that one of 51 eyes in the LASEK group lost one line or more best-spectacle corrected visual acuity compared with none of 51 eyes in the PRK group (RR 3.00, 95% CI 0.13 to 71.96; very low-quality evidence).Three trials reported adverse outcomes at 12 months of follow-up or longer. At 12 months post treatment, three trials reported corneal haze score; however, data were insufficient and were inconsistent among the trials, precluding meta-analysis. One trial reported little or no difference in corneal haze scores between groups; another trial reported that corneal haze scores were lower in the LASEK group than in the PRK group; and one trial did not report analyzable data to estimate a treatment effect. At 24 months post treatment, one trial reported a lower, but clinically unimportant, difference in corneal haze score for LASEK compared with PRK (MD -0.22, 95% CI -0.30 to -0.14; 184 eyes; low-quality evidence). Uncertainty surrounds differences in efficacy, accuracy, safety, and adverse effects between LASEK and PRK for eyes with low to moderate myopia. Future trials comparing LASEK versus PRK should follow reporting standards and follow correct analysis. Trial investigators should expand enrollment criteria to include participants with high myopia and should evaluate visual acuity, refraction, epithelial healing time, pain scores, and adverse events.

Laser-assisted subepithelial keratectomy (LASEK) versus photorefractive keratectomy (PRK) for correction of myopia

PubMed Central

Li, Shi-Ming; Zhan, Siyan; Li, Si-Yuan; Peng, Xiao-Xia; Hu, Jing; Law, Hua Andrew; Wang, Ning-Li

2016-01-01

Background Myopia (near-sightedness or short-sightedness) is a condition in which the refractive power of the eye is greater than required. The most frequent complaint of people with myopia is blurred distance vision, which can be eliminated by conventional optical aids such as spectacles or contact lenses, or by refractive surgery procedures such as photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK). PRK uses laser to remove the corneal stroma. Similar to PRK, LASEK first creates an epithelial flap and then replaces it after ablating the corneal stroma. The relative benefits and harms of LASEK and PRK, as shown in different trials, warrant a systematic review. Objectives The objective of this review is to compare LASEK versus PRK for correction of myopia by evaluating their efficacy and safety in terms of postoperative uncorrected visual acuity, residual refractive error, and associated complications. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2015 Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 December 2015. We used the Science Citation Index and searched the reference lists of the included trials to identify relevant trials for this review. Selection criteria We included in this review randomized controlled trials (RCTs) comparing LASEK versus PRK for correction of myopia. Trial participants were 18 years of age or older and had no co-existing ocular or systemic diseases that might affect refractive status or wound healing. Data collection and analysis Two review authors independently screened all reports and assessed the risk of bias of trials included in this review. We extracted data and summarized findings using risk ratios and mean differences. We used a random-effects model when we identified at least three trials, and we used a fixed-effect model when we found fewer than three trials. Main results We included 11 RCTs with a total of 428 participants 18 years of age or older with low to moderate myopia. These trials were conducted in the Czech Republic, Brazil, Italy, Iran, China, Korea, Mexico, Turkey, USA, and UK. Investigators of 10 out of 11 trials randomly assigned one eye of each participant to be treated with LASEK and the other with PRK, but did not perform paired-eye (matched) analysis. Because of differences in outcome measures and follow-up times among the included trials, few trials contributed data for many of the outcomes we analyzed for this review. Overall, we judged RCTs to be at unclear risk of bias due to poor reporting; however, because of imprecision, inconsistency, and potential reporting bias, we graded the quality of the evidence from very low to moderate for outcomes assessed in this review. The proportion of eyes with uncorrected visual acuity of 20/20 or better at 12-month follow-up was comparable in LASEK and PRK groups (risk ratio (RR) 0.98, 95% confidence interval (95% CI) 0.92 to 1.05). Although the 95% CI suggests little to no difference in effect between groups, we judged the quality of the evidence to be low because only one trial reported this outcome (102 eyes). At 12 months post treatment, data from two trials suggest no difference or a possibly small effect in favor of PRK over LASEK for the proportion of eyes achieving ± 0.50 D of target refraction (RR 0.93, 95% CI 00.84 to 1.03; 152 eyes; low-quality evidence). At 12 months post treatment, one trial reported that one of 51 eyes in the LASEK group lost one line or more best-spectacle corrected visual acuity compared with none of 51 eyes in the PRK group (RR 3.00, 95% CI 0.13 to 71.96; very low-quality evidence). Three trials reported adverse outcomes at 12 months of follow-up or longer. At 12 months post treatment, three trials reported corneal haze score; however, data were insufficient and were inconsistent among the trials, precluding meta-analysis. One trial reported little or no difference in corneal haze scores between groups; another trial reported that corneal haze scores were lower in the LASEK group than in the PRK group; and one trial did not report analyzable data to estimate a treatment effect. At 24 months post treatment, one trial reported a lower, but clinically unimportant, difference in corneal haze score for LASEK compared with PRK (MD −0.22, 95% CI −0.30 to −0.14; 184 eyes; low-quality evidence). Authors’ conclusions Uncertainty surrounds differences in efficacy, accuracy, safety, and adverse effects between LASEK and PRK for eyes with low to moderate myopia. Future trials comparing LASEK versus PRK should follow reporting standards and follow correct analysis. Trial investigators should expand enrollment criteria to include participants with high myopia and should evaluate visual acuity, refraction, epithelial healing time, pain scores, and adverse events. PMID:26899152

Subjective safety and self-confidence in prehospital trauma care and learning progress after trauma-courses: part of the prospective longitudinal mixed-methods EPPTC-trial.

PubMed

Häske, David; Beckers, Stefan K; Hofmann, Marzellus; Lefering, Rolf; Grützner, Paul A; Stöckle, Ulrich; Papathanassiou, Vassilios; Münzberg, Matthias

2017-08-14

Prehospital trauma care is stressful and requires multi-professional teamwork. A decrease in the number of accident victims ultimately affects the routine and skills and underlines the importance of effective training. Standardized courses, like PHTLS, are established for health care professionals to improve the prehospital care of trauma patients. The aim of the study was to investigate the subjective safety in prehospital trauma care and learning progress by paramedics in a longitudinal analysis. This was a prospective intervention trial and part of the mixed-method longitudinal EPPTC-trial, evaluating subjective and objective changes among participants and real patient care as a result of PHTLS courses. Participants were evaluated with pre/post questionnaires as well as one year after the course. We included 236 datasets. In the pre/post comparison, an increased performance could be observed in nearly all cases. The result shows that the expectations of the participants of the course were fully met even after one year (p = 0.002). The subjective safety in trauma care is significantly better even one year after the course (p < 0.001). Regression analysis showed that (ABCDE)-structure is decisive (p = 0.036) as well as safety in rare and common skills (both p < 0.001). Most skills are also rated better after one year. Knowledge and specific safety are assessed as worse after one year. The courses meet the expectations of the participants and increase the subjective safety in the prehospital care of trauma patients. ABCDE-structure and safety in skills are crucial. In the short term, both safety in skills and knowledge can be increased, but the courses do not have the power to maintain knowledge and specific subjective safety issues over a year. German Clinical Trials Register, ID DRKS00004713 , registered 14. February 2014.

A cluster randomised controlled trial of the Climate Schools: Ecstasy and Emerging Drugs Module in Australian secondary schools: study protocol.

PubMed

Champion, Katrina E; Teesson, Maree; Newton, Nicola C

2013-12-12

The use of ecstasy is a public health problem and is associated with a range of social costs and harms. In recent years, there has been growing concern about the availability and misuse of new and emerging drugs designed to mimic the effects of illicit drugs, including ecstasy. This, coupled with the fact that the age of use and the risk factors for using ecstasy and emerging drugs are similar, provides a compelling argument to implement prevention for these substances simultaneously. The proposed study will evaluate whether a universal Internet-based prevention program, known as the Climate Schools: Ecstasy and Emerging Drugs Module, can address and prevent the use of ecstasy and emerging drugs among adolescents. A cluster randomised controlled trial will be conducted among Year 10 students (aged 15-16 years) from 12 secondary schools in Sydney, Australia. Schools will be randomly assigned to either the Climate Schools intervention group or the control group. All students will complete a self-report questionnaire at baseline, immediately post-intervention, and 6-, 12- and 24-months post-baseline. The primary outcome measures will include ecstasy and emerging drug-related knowledge, intentions to use these substances in the future, and the patterns of use of ecstasy and emerging drugs. A range of secondary outcomes will also be assessed, including beliefs and attitudes about ecstasy and emerging drugs, peer pressure resistance, other substance use and mental health outcomes. To our knowledge, this will be the first evaluation of an Internet-based program designed to specifically target ecstasy and NED use among adolescents. If deemed effective, the Climate Schools: Ecstasy and Emerging Drugs Module will provide schools with an interactive and novel prevention program for ecstasy and emerging drugs that can be readily implemented by teachers. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000708752.

The sydney playground project: popping the bubblewrap - unleashing the power of play: a cluster randomized controlled trial of a primary school playground-based intervention aiming to increase children's physical activity and social skills

PubMed Central

2011-01-01

Background In the Westernised world, numerous children are overweight and have problems with bullying and mental health. One of the underlying causes for all three is postulated to be a decrease in outdoor free play. The aim of the Sydney Playground Project is to demonstrate the effectiveness of two simple interventions aimed to increase children's physical activity and social skills. Methods/Design This study protocol describes the design of a 3-year cluster randomised controlled trial (CRCT), in which schools are the clusters. The study consists of a 13-week intervention and 1 week each of pre-and post-testing. We are recruiting 12 schools (6 control; 6 intervention), with 18 randomly chosen participants aged 5 to 7 years in each school. The two intervention strategies are: (1) Child-based intervention: Unstructured materials with no obvious play value introduced to the playground; and (2) Adult-based intervention: Risk reframing sessions held with parents and teachers with the aim of exploring the benefits of allowing children to engage in activities with uncertain outcomes. The primary outcome of the study, physical activity as measured by accelerometer counts, is assessed at baseline and post-intervention. Additional assessments include social skills and interactions, self-concept, after school time use and anthropometric data. Qualitative data (i.e., transcriptions of audio recordings from the risk reframing sessions and of interviews with selected teacher and parent volunteers) are analysed to understand their perceptions of risk in play. The control schools have recess as usual. In addition to outcome evaluation, regular process evaluation sessions are held to monitor fidelity to the treatment. Discussion These simple interventions, which could be adopted in every primary school, have the potential of initiating a self-sustaining cycle of prevention for childhood obesity, bullying and mental ill health. Trial registration Australian and New Zealand Clinical Trials Registration Number ACTRN12611000089932. PMID:21884603

Using Screencasting to Promote Database Trials and Library Resources

ERIC Educational Resources Information Center

Emanuel, Michelle

2013-01-01

At the University of Mississippi, screencasting was used to promote a database trial to the ARTStor Digital Library. Using Jing, a free product used for recording and posting screencasts, and a Snowball USB microphone, 11 videos averaging 3 minutes in length were posted to an online topic guide. Screencasting was used as a quick, creative, and…

Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.

PubMed

Esparza-Villalpando, Vicente; Pozos-Guillén, Amaury; Masuoka-Ito, David; Gaitán-Fonseca, César; Chavarría-Bolaños, Daniel

2018-03-01

Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect. © 2017 Wiley Periodicals, Inc.

An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes - the MID-Frail study: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Diabetes, a highly prevalent, chronic disease, is associated with increasing frailty and functional decline in older people, with concomitant personal, social, and public health implications. We describe the rationale and methods of the multi-modal intervention in diabetes in frailty (MID-Frail) study. Methods/Design The MID-Frail study is an open, randomised, multicentre study, with random allocation by clusters (each trial site) to a usual care group or an intervention group. A total of 1,718 subjects will be randomised with each site enrolling on average 14 or 15 subjects. The primary objective of the study is to evaluate, in comparison with usual clinical practice, the effectiveness of a multi-modal intervention (specific clinical targets, education, diet, and resistance training exercise) in frail and pre-frail subjects aged ≥70 years with type 2 diabetes in terms of the difference in function 2 years post-randomisation. Difference in function will be measured by changes in a summary ordinal score on the short physical performance battery (SPPB) of at least one point. Secondary outcomes include daily activities, economic evaluation, and quality of life. Discussion The MID-Frail study will provide evidence on the clinical, functional, social, and economic impact of a multi-modal approach in frail and pre-frail older people with type 2 diabetes. Trial registration ClinicalTrials.gov: NCT01654341. PMID:24456998

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial.

PubMed

Brinkman, Sally A; Johnson, Sarah E; Lawrence, David; Codde, James P; Hart, Michael B; Straton, Judith A Y; Silburn, Sven

2010-10-21

This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms. This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings. ISRCTN24952438.

The effects of acute versus chronic training status on pacing strategies of older men in a hot, humid environment.

PubMed

Chia, Eevon; Cannon, Jack; Marino, Frank E

2015-10-01

The combined effects of age and training on the regulation of exercise performance may be confounded by the additional challenge of thermoregulation. Thus, the objective of this study was to compare the pacing strategy of older men who have recently completed 12 weeks of exercise training (acute) to men who have been regularly (>3 times/week) training for at least 6 months (chronic) in a hot, humid environment and to observe disparity, if any, between acute and chronic exercise training on thermoregulation. Eleven chronically trained men (OT) completed a familiarisation trial before returning after 7-10 days to repeat the protocol. Similarly, eight untrained men (OU-PRE) were familiarised and repeated the protocol before completing 12 weeks of exercise training. Post-training, the eight acutely trained men (OU-POST) returned to the laboratory for a third trial. All trials were conducted on a cycle ergometer at the same time of the day in a climate controlled chamber with a mean dry bulb temperature and relative humidity of 32.0°C and 68%, respectively. OT consumed more water than OU-POST and OU-PRE (P<0.01) whilst no differences were observed in the OU with training. Voluntary activation of the knee extensors decreased by 11.3% (P<0.05) in the OU-PRE after the cycling time trial. However, the decrease in voluntary activation observed in the OU-POST and OT after the cycling time trial were not significant. The OT maintained a higher power output compared with the OU-POST and OU-PRE except for the last sprint, whilst no significant differences in power output were observed between the OU-PRE and OU-POST. The rate of rise in core temperature was significantly higher in the OT compared with OU-POST (P<0.001) and OU-PRE (P<0.001). With more experience in training, the OT used an alternative hydration strategy compared with the OU-POST and OU-PRE to mitigate the effects of possible exercise hyperthermia, ultimately attaining a higher, but non-critical core temperature at the end of the cycling time trial. Twelve weeks of exercise training may not manifest in improved exercise performance per se, but could translate to improved performance of activities of daily and independent living. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effect of Three-Monthly Albendazole Treatment on Malarial Parasitemia and Allergy: A Household-Based Cluster-Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Kaisar, Maria M. M.; May, Linda; Prasetyani, Margaretta A.; Wahyuni, Sitti; Djuardi, Yenny; Ariawan, Iwan; Wibowo, Heri; Lell, Bertrand; Sauerwein, Robert; Brice, Gary T.; Sutanto, Inge; van Lieshout, Lisette; de Craen, Anton J. M.; van Ree, Ronald; Verweij, Jaco J.; Tsonaka, Roula; Houwing-Duistermaat, Jeanine J.; Luty, Adrian J. F.; Sartono, Erliyani; Supali, Taniawati; Yazdanbakhsh, Maria

2013-01-01

Background Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. Methods and Findings A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5–15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35–12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74–1.86) at 9 months or 1.37 (0.93–2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. Conclusions The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. Trial Registration Controlled-Trials.com ISRCTN83830814 PMID:23526959

Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies.

PubMed

Chupp, Geoffrey; Laviolette, Michel; Cohn, Lauren; McEvoy, Charlene; Bansal, Sandeep; Shifren, Adrian; Khatri, Sumita; Grubb, G Mark; McMullen, Edmund; Strauven, Racho; Kline, Joel N

2017-08-01

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More "real-world" clinical outcome data is needed.This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial.279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m -2 ) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day -1 ). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results.The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control. Copyright ©ERS 2017.

Evolutionary cognitive therapy versus standard cognitive therapy for depression: a protocol for a blinded, randomized, superiority clinical trial.

PubMed

Giosan, Cezar; Cobeanu, Oana; Mogoase, Cristina; Muresan, Vlad; Malta, Loretta S; Wyka, Katarzyna; Szentagotai, Aurora

2014-03-19

Depression is estimated to become the leading cause of disease burden globally by 2030. Despite existing efficacious treatments (both medical and psychotherapeutic), a large proportion of patients do not respond to therapy. Recent insights from evolutionary psychology suggest that, in addition to targeting the proximal causes of depression (for example, targeting dysfunctional beliefs by cognitive behavioral therapy), the distal or evolutionary causes (for example, inclusive fitness) should also be addressed. A randomized superiority trial is conducted to develop and test an evolutionary-driven cognitive therapy protocol for depression, and to compare its efficacy against standard cognitive therapy for depression. Romanian-speaking adults (18 years or older) with elevated Beck Depression Inventory (BDI) scores (>13), current diagnosis of major depressive disorder or major depressive episode (MDD or MDE), and MDD with comorbid dysthymia, as evaluated by the Structured Clinical Interview for DSM-IV (SCID), are included in the study. Participants are randomized to one of two conditions: 1) evolutionary-driven cognitive therapy (ED-CT) or 2) cognitive therapy (CT). Both groups undergo 12 psychotherapy sessions, and data are collected at baseline, mid-treatment, post-treatment, and the 3-month follow-up. Primary outcomes are depressive symptomatology and a categorical diagnosis of depression post-treatment. This randomized trial compares the newly proposed ED-CT with a classic CT protocol for depression. To our knowledge, this is the first attempt to integrate insights from evolutionary theories of depression into the treatment of this condition in a controlled manner. This study can thus add substantially to the body of knowledge on validated treatments for depression. Current Controlled Trials ISRCTN64664414The trial was registered in June 2013. The first participant was enrolled on October 3, 2012.

Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial.

PubMed

Sibilitz, Kirstine Laerum; Berg, Selina Kikkenborg; Hansen, Tina Birgitte; Risom, Signe Stelling; Rasmussen, Trine Bernholdt; Hassager, Christian; Køber, Lars; Steinbrüchel, Daniel; Gluud, Christian; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Schmid, Jean Paul; Conraads, Viviane; Brocki, Barbara Christina; Zwisler, Ann-Dorthe

2013-04-22

Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). ClinicalTrials.gov (http://NCT01558765).

Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

PubMed

Leoutsakos, Jeannie-Marie S; Yan, Haijuan; Anderson, William S; Asaad, Wael F; Baltuch, Gordon; Burke, Anna; Chakravarty, M Mallar; Drake, Kristen E; Foote, Kelly D; Fosdick, Lisa; Giacobbe, Peter; Mari, Zoltan; McAndrews, Mary Pat; Munro, Cynthia A; Oh, Esther S; Okun, Michael S; Pendergrass, Jo Cara; Ponce, Francisco A; Rosenberg, Paul B; Sabbagh, Marwan N; Salloway, Stephen; Tang-Wai, David F; Targum, Steven D; Wolk, David; Lozano, Andres M; Smith, Gwenn S; Lyketsos, Constantine G

2018-06-09

Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.

Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: A randomized double-blind placebo-controlled trial.

PubMed

Jahanbakhsh, Seyedeh Pardis; Manteghi, Ali Akhondpour; Emami, Seyed Ahmad; Mahyari, Saman; Gholampour, Beheshteh; Mohammadpour, Amir Hooshang; Sahebkar, Amirhossein

2016-08-01

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that is causally linked to dysregulation of the serotonergic system. The aim of this study is to investigate the efficacy of Withania somnifera (W. somnifera) root extract as an adjunct therapy to standard OCD treatment. Thirty patients with a confirmed diagnosis of OCD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria participated in this randomized double-blind placebo-controlled trial and were randomly assigned to the treatment group (W. somnifera extract, 120mg/day; n=15) or the placebo group (n=15). All patients were under treatment with Selective Serotonin Re-uptake Inhibitors (SSRIs), and were instructed to take 4 capsules of the extract or placebo per day, preferably after meals, for a period of six weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used in order to assess the severity of OCD symptoms at baseline and at the end of the trial. Statistical analyses were performed using SPSS software and Y-BOCS values were presented as median and range (Min-Max). Comparison of the change in Y-BOCS score during the course of the trial revealed a significantly greater effect of W. somnifera (26 (14-40) [pre-treatment] versus 14 (4-40) [post-treatment]; change: -8 (-23 to 0)) versus placebo (18 (11-33) [pre-treatment] versus 16 (10-31) [post-treatment]; change: -2 (-4 to 0)) (P<0.001). The extract was safe and no adverse event was reported during the trial. W. somnifera extract may be beneficial as a safe and effective adjunct to SSRIs in the treatment of OCD. Copyright © 2016. Published by Elsevier Ltd.

Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies

PubMed Central

Laviolette, Michel; Cohn, Lauren; McEvoy, Charlene; Bansal, Sandeep; Shifren, Adrian; Khatri, Sumita; Grubb, G. Mark; McMullen, Edmund; Strauven, Racho; Kline, Joel N.

2017-01-01

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More “real-world” clinical outcome data is needed. This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial. 279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m−2) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day−1). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results. The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control. PMID:28860266

Testing a workplace physical activity intervention: a cluster randomized controlled trial

PubMed Central

2011-01-01

Background Increased physical activity levels benefit both an individuals' health and productivity at work. The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention designed to increase physical activity levels. Methods A total of 1260 participants from 44 UK worksites (based within 5 organizations) were recruited to a cluster randomized controlled trial with worksites randomly allocated to an intervention or control condition. Measurement of physical activity and other variables occurred at baseline, and at 0 months, 3 months and 9 months post-intervention. Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention. The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior, delivered in-house by nominated facilitators. Self-reported physical activity (measured using the IPAQ short-form) and health outcomes were assessed. Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity (from the IPAQ) at any of the follow-up time points controlling for baseline activity. However, the intervention did significantly reduce systolic blood pressure (B = -1.79 mm/Hg) and resting heart rate (B = -2.08 beats) and significantly increased body mass index (B = .18 units) compared to control. The intervention was found not to be cost-effective, however the substantial variability round this estimate suggested that further research is warranted. Conclusions The current study found mixed support for this worksite physical activity intervention. The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale randomized controlled trials in real-world settings. Trial registration Current controlled trials ISRCTN08807396 PMID:21481265

A pilot RCT of psychodynamic group art therapy for patients in acute psychotic episodes: feasibility, impact on symptoms and mentalising capacity.

PubMed

Montag, Christiane; Haase, Laura; Seidel, Dorothea; Bayerl, Martin; Gallinat, Jürgen; Herrmann, Uwe; Dannecker, Karin

2014-01-01

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function. ClinicalTrials.gov NCT01622166.

Physiotherapy Commenced Within the First Four Weeks Post-Spinal Surgery Is Safe and Effective: A Systematic Review and Meta-Analysis.

PubMed

Snowdon, Megan; Peiris, Casey L

2016-02-01

To determine whether physiotherapy commenced within the first 4 weeks post-spinal surgery is safe and effective. Electronic databases CINAHL, MEDLINE, AMED, PubMed, Embase, and PEDro were searched from the earliest date possible through May 2015. An additional trial was identified through reference list scanning. Controlled trials evaluating comprehensive physiotherapy rehabilitation commenced within 4 weeks postoperatively compared with a control group receiving no physiotherapy, standard postoperative care, rest, less active physiotherapy, or sham physiotherapy after spinal surgery of a musculoskeletal etiology. Two reviewers independently applied inclusion and exclusion criteria, with disagreements discussed until consensus could be reached. Searching identified 3162 potentially relevant articles, of which 4 trials with 250 participants met the inclusion criteria. Data were extracted using a predefined data extraction form. Methodological quality of trials was assessed independently by 2 reviewers using the Downs and Black checklist. Pooled analyses were performed using a random-effects model with inverse variance methods to calculate risk differences and 95% confidence intervals (CIs) (dichotomous outcomes), and standardized mean differences (SMDs) and 95% CIs (continuous outcomes). When compared with no or sham physiotherapy, early comprehensive physiotherapy did not increase the risk of adverse events (risk difference, -.01; 95% CI, -.07 to .05; I(2)=0%). In addition, there is moderate-quality evidence demonstrating a reduction in pain by a moderate and significant amount at 12 weeks (SMD=-.38; 95% CI, -.66 to -.10; I(2)=0%) and at 12+ months (SMD=-.30; 95% CI, -.59 to -.02; I(2)=0%). Early comprehensive physiotherapy commenced within the first 4 weeks post-spinal surgery does not increase the potential for an adverse event and leads to a moderate, statistically significant reduction in pain when compared with a control group. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of post-diagnosis treatment in dementia coordinated by Multidisciplinary Memory Clinics in comparison to treatment coordinated by general practitioners: an example of a pragmatic trial.

PubMed

Meeuwsen, E J; German, P; Melis, R J F; Adang, E M; Golüke-Willemse, G A; Krabbe, P F; de Leest, B J; van Raak, F H J M; Schölzel-Dorenbos, C J M; Visser, M C; Wolfs, C A; Vliek, S; Rikkert, M G M Olde

2009-03-01

With the rising number of dementia patients with associated costs and the recognition that there is room for improvement in the provision of dementia care, the question arises on how to efficiently provide high quality dementia care. To describe the design of a study to determine multidisciplinary memory clinics' (MMC) effectiveness and cost-effectiveness in post-diagnosis treatment and care-coordination of dementia patients and their caregivers compared to the post-diagnosis treatment and care-coordination by general practitioners (GP). Next, this article provides the theoretical background of pragmatic trials, often needed in complex interventions, with the AD- Euro study as an example of such a pragmatic approach in a clinical trial. The study is a pragmatic multicentre, randomised clinical trial with an economic evaluation alongside, which aims to recruit 220 independently living patients with a new dementia diagnosis and their informal caregivers. After baseline measurements, patient and caregiver are allocated to the treatment arm MMC or GP and are visited for follow up measurements at 6 and 12 months. Primary outcome measures are Health Related Quality of Life of the patient as rated by the caregiver using the Quality of Life in Alzheimer's Disease instrument (Qol-AD) and self-perceived caregiving burden of the informal caregiver measured using the Sense of Competence Questionnaire (SCQ). To establish cost-effectiveness a cost-utility analysis using utilities generated by the EuroQol instrument (EQ-5D) will be conducted from a societal perspective. Analyses will be done in an intention-to-treat fashion. The inclusion period started in January 2008 and will commence until at least December 2008. After finalising follow up the results of the study are expected to be available halfway through 2010. The study will provide an answer to whether follow-up of dementia patients can best be done in specialised outpatient memory clinics or in primary care settings with regard to quality and costs. It will enable decision making on how to provide good and efficient health care services in dementia. ClinicalTrials.gov Identifier NCT00554047.

Group hypnotherapy versus group relaxation for smoking cessation: an RCT study protocol

PubMed Central

2012-01-01

Background A significant number of smokers would like to stop smoking. Despite the demonstrated efficacy of pharmacological smoking cessation treatments, many smokers are unwilling to use them; however, they are inclined to try alternative methods. Hypnosis has a long-standing reputation in smoking cessation therapy, but its efficacy has not been scientifically proven. We designed this randomised controlled trial to evaluate the effects of group hypnosis as a method for smoking cessation, and we will compare the results of group hypnosis with group relaxation. Methods/Design This is a randomised controlled trial (RCT) to compare the efficacy of a single session of hypnosis with that of relaxation performed in groups of 8-15 smokers. We intend to include at least 220 participants in our trial. The inclusion criteria include smoking at least 5 cigarettes per day, not using other cessation methods and being willing to quit smoking. The intervention is performed by a trained hypnotist/relaxation therapist. Both groups first receive 40 min of mental preparation that is based on motivational interviewing. Then, a state of deep relaxation is induced in the hypnosis condition, and superficial relaxation is induced in the control condition. Suggestions are made in the hypnosis condition that aim to switch the mental self-image of the participants from that of smokers to that of non-smokers. Each intervention lasts for 40 min. The participants also complete questionnaires that assess their smoking status and symptoms of depression and anxiety at baseline, 2 weeks and 6 months post-intervention. In addition, saliva samples are collected to assess cotinine levels at baseline and at 6 months post-intervention. We also assess nicotine withdrawal symptoms at 2 weeks post-intervention. Discussion To the best of our knowledge, this RCT is the first to test the efficacy of group hypnosis versus group relaxation. Issues requiring discussion in the outcome paper include the lack of standardisation of hypnotic interventions in smoking cessation, the debriefing of the participants, the effects of group dynamics and the reasons for dropouts. Trial registration Current Controlled Trials, ISRCTN72839675. PMID:22475087

Engaging adolescents in tuberculosis and clinical trial research through drama.

PubMed

Schmidt, Bey-Marrié; Abrams, Amber; Tameris, Michele

2016-04-06

The South African Tuberculosis Vaccine Initiative is based in Worcester where tuberculosis (TB) is endemic, and incidence rates are amongst the highest nationally. In high TB burden settings after an early childhood peak, incidence rates start to rise again in adolescents, therefore they are an important target group for tuberculosis vaccine research. In 2012, learners from a local school developed a one-off theatrical production out of an educational comic book Carina's Choice, developed by the South African Tuberculosis Vaccine Initiative in 2010. A Wellcome Trust International Engagement grant allowed for this one-off production to be further developed, with input from university students and staff, and rolled out to schools in the Worcester area as an engagement and education intervention. Focus group feedback was used to identify key messages and to develop the play's script. Qualitative methods were used to collect and analyse relevant data. Interviews were conducted with learner-actors, pre- and post-focus group feedback was obtained from a sample of school-going adolescents, and pre- and post-questionnaires were administered to adolescent audience members. From the pre-drama focus group discussions, topics such as TB symptoms, stigma and transmission were identified as areas that needed attention. After the performances, adolescents showed improved knowledge on the identified topics and they discussed TB prevention measures. They highlighted transmission of TB during pregnancy as a further topic to be addressed in future iterations of the drama. Although stigma is a difficult phenomenon to interpret, post-drama participants understood that TB transmission could occur in all individuals. Learner-actors agreed with focus group participants that the play could impact the wider community if it were rolled out. Feedback from the South African Tuberculosis Vaccine Initiative staff verified that recruitment for an upcoming trial was facilitated by the preparedness that the play provided in recruitment areas. The study showed that before and after evaluations provide data on the usefulness of the play as an education tool. Theatre, presented and motivated by adolescent peers, can raise awareness of TB, and assist clinical trial preparedness and further engagement between trial staff and their trial community.

Interferon after surgery for women with advanced (Stage II-IV) epithelial ovarian cancer.

PubMed

Lawal, Aramide O; Musekiwa, Alfred; Grobler, Liesl

2013-06-06

Epithelial ovarian cancer (EOC) is a life-threatening disease. Most often women become symptomatic only in the advanced stages of the disease, increasing the difficulty of treatment. Whilst the disease responds well to surgery and chemotherapy, the relapse rate is high. New treatments to prevent disease recurrence or progression, prolong survival, and increase the quality of life are needed. To assess the effectiveness and safety of interferon after surgery in the treatment of advanced (stage II-IV) EOC. The Cochrane Gynaecological Cancer Review Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2012, MEDLINE and EMBASE were searched to January 2012. Handsearching of conference proceedings was also undertaken. Reference lists of reviews and included trials were screened and experts in the field were contacted for additional trials. Clinical trials registers were searched for ongoing trials. Randomised controlled trials (RCTs) involving participants with advanced EOC that compared post-operative chemotherapy alone with post-operative interferon therapy in combination with chemotherapy or post-operative chemotherapy followed by interferon or observation alone Two review authors (AL and AM) independently screened the search results for relevant trials and extracted pre-specified information from each included trial. Data were managed using Review Manager 5.1. Hazard ratios (HR) were calculated for time-to-event outcomes and risk ratios (RR) for dichotomous outcomes, with corresponding 95% confidence intervals (CI). Five trials, including 1476 participants, were included in the review. Two trials compared interferon with observation alone and three trials compared interferon plus chemotherapy with chemotherapy alone. A meta-analysis of two trials involving 370 participants found no significant difference in both overall survival (HR 1.14, 95% CI 0.84 to 1.55) and progression free survival (HR 0.99, 95% CI 0.79 to 1.24) between the interferon and observation alone groups in post-surgical women who had undergone first-line chemotherapy for advanced EOC. One trial with 293 participants found that while no significant difference was observed in incidence of nausea or vomiting between the two treatment groups, significantly more flu-like symptoms (RR 2.25, 95% CI 1.73 to 2.91) and fatigue (RR 1.54, 95% CI 1.27 to 1.88) were reported in the interferon group. For the second comparison, a meta-analysis of two trials comprising 244 participants found that although there was no significant difference in overall survival between the interferon plus chemotherapy and the chemotherapy alone group (HR 1.14, 95% CI 0.74 to 1.76), women in the interferon plus chemotherapy group had worse progression free survival than those in the chemotherapy alone group (HR 1.43, 95% CI 1.02 to 2.00). Compared to chemotherapy alone, adding interferon to chemotherapy did not alter the incidence of adverse events in post-surgical women with advanced EOC. Implications for practice Based on low quality evidence, the addition of interferon to first-line chemotherapy did not alter the overall survival in post-surgical women with advanced EOC compared with chemotherapy alone. There is low quality evidence to suggest that interferon in combination with chemotherapy worsened the progression free survival in post-surgical women with advanced EOC compared with chemotherapy alone. There is not enough evidence that interferon therapy alone alters overall survival or progression free survival compared to observation alone in post-surgical women who have undergone first-line chemotherapy. Three of the five trials included in this review were stopped early and were, therefore, underpowered to detect any true effect of the intervention. The trials did not report the results of important outcomes in a uniform manner, preventing statistical aggregation of the results. Trial methodology was poorly reported resulting in unclear risk of bias. For clear recommendations to be made regarding the effectiveness of interferon in the treatment of advanced EOC, long-term, well conducted and adequately powered RCTs would be needed. However, the available data do not suggest that interferon has an adequately advantageous effect to warrant further investigation.

The 'Healthy Dads, Healthy Kids' community effectiveness trial: study protocol of a community-based healthy lifestyle program for fathers and their children

PubMed Central

2011-01-01

Background The 'Healthy Dads, Healthy Kids' program was designed to help overweight fathers lose weight and positively influence the health behaviors of their children. The aim of the current study was to evaluate the previously established program in a community setting, in a large effectiveness trial. Methods/Design The Healthy Dads, Healthy Kids community trial consists of three stages: (i) Stage 1 - program refinement and resource development (ii) Stage 2 - community randomized controlled trial (iii) Stage 3 - community effectiveness trial. The program will be evaluated in five Local Government Areas in the Hunter Valley Region of NSW, Australia. For the community randomized controlled trial, 50 overweight/obese men (aged 18-65 years) from one Local Government Area with a child aged between 5-12 years of age will be recruited. Families will be randomized to either the program or a 6-month wait-list control group. Fathers and their children will be assessed at baseline, post-intervention (3-months) and 6-months. Inclusion criteria are: body mass index 25-40 kg/m2; no participation in other weight loss programs during the study; pass a health-screening questionnaire; and access to a computer with Internet facilities. In the community trial, the program will be evaluated using a non-randomized, prospective design in five Local Government Areas. The exclusion criteria is body mass index < 25 kg/m2 or lack of doctor's approval. Measures will be collected at baseline, 3-, 6- and 12-months. The program involves fathers attending seven face-to-face group sessions (three with children) over 3-months. Measures: The primary outcome is fathers' weight. Secondary outcomes for both fathers and children include: waist circumference, blood pressure, resting heart rate, physical activity, sedentary behaviors and dietary intake. Father-only measures include portion size, alcohol consumption, parenting for physical activity and nutrition and parental engagement. Process evaluation will determine the fidelity, dose (delivered and received), reach, recruitment and context of the program. Discussion As a unique approach to reducing obesity prevalence in men and improving lifestyle behaviours in children, our findings will provide important evidence relating to the translation of Healthy Dads, Healthy Kids, which will enable it to be delivered on a larger scale. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000608066 PMID:22099889

Efficiency and effectiveness in case of disaster: a visual damage assessment test

NASA Astrophysics Data System (ADS)

Ooms, Kristien; Åhlén, Julia; Seipel, Stefan

2018-05-01

A user study is conducted to evaluate the efficiency and effectiveness of two types of visualizations to identify damages sites in case of disaster. The test consists out 36 trials (18 for each visualisation) and in each trial an area of 1 × 1 km, located in Ghent, is displayed on a screen. This image shows the combined height information from before and after the disaster. The first visualisation, page flipping, is based on greyscale images with height information from the pre- and post-disaster situation between which users can switch manually. The second visualisation, difference image, is a result of subtracting the heights (before versus after) and assigning a blue-white-red colour ramp. In order to simulate the urgency with which the data is captured, systematic and random imperfections are introduced in the post-disaster data. All participants' mouse and key interactions are logged, which is further complemented by the registration of their eye movements. This give insights the visualizations' efficiency, effectiveness and the overall search strategies of the participants.

Episodic retrieval involves early and sustained effects of reactivating information from encoding.

PubMed

Johnson, Jeffrey D; Price, Mason H; Leiker, Emily K

2015-02-01

Several fMRI studies have shown a correspondence between the brain regions activated during encoding and retrieval, consistent with the view that memory retrieval involves hippocampally-mediated reinstatement of cortical activity. With the limited temporal resolution of fMRI, the precise timing of such reactivation is unclear, calling into question the functional significance of these effects. Whereas reactivation influencing retrieval should emerge with neural correlates of retrieval success, that signifying post-retrieval monitoring would trail retrieval. The present study employed EEG to provide a temporal landmark of retrieval success from which we could investigate the sub-trial time course of reactivation. Pattern-classification analyses revealed that early-onsetting reactivation differentiated the outcome of recognition-memory judgments and was associated with individual differences in behavioral accuracy, while reactivation was also evident in a sustained form later in the trial. The EEG findings suggest that, whereas prior fMRI findings could be interpreted as reflecting the contribution of reinstatement to retrieval success, they could also indicate the maintenance of episodic information in service of post-retrieval evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

Modeling and simulation to support dose selection and clinical development of SC-75416, a selective COX-2 inhibitor for the treatment of acute and chronic pain.

PubMed

Kowalski, K G; Olson, S; Remmers, A E; Hutmacher, M M

2008-06-01

Pharmacokinetic/pharmacodynamic (PK/PD) models were developed and clinical trial simulations were conducted to recommend a study design to test the hypothesis that a dose of SC-75416, a selective cyclooxygenase-2 inhibitor, can be identified that achieves superior pain relief (PR) compared to 400 mg ibuprofen in a post-oral surgery pain model. PK/PD models were developed for SC-75416, rofecoxib, valdecoxib, and ibuprofen relating plasma concentrations to PR scores using a nonlinear logistic-normal model. Clinical trial simulations conducted using these models suggested that 360 mg SC-75416 could achieve superior PR compared to 400 mg ibuprofen. A placebo- and positive-controlled parallel-group post-oral surgery pain study was conducted evaluating placebo, 60, 180, and 360 mg SC-75416 oral solution, and 400 mg ibuprofen. The study results confirmed the hypothesis that 360 mg SC-75416 achieved superior PR relative to 400 mg ibuprofen (DeltaTOTPAR6=3.3, P<0.05) and demonstrated the predictive performance of the PK/PD models.

Fibrin Sealants in Dura Sealing: A Systematic Literature Review

PubMed Central

2016-01-01

Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. Conclusions A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety. PMID:27119993

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

PubMed

Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo

2016-01-01

Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.

Rehabilitation for distal radial fractures in adults.

PubMed

Handoll, Helen H G; Elliott, Joanne

2015-09-25

Fracture of the distal radius is a common clinical problem, particularly in older people with osteoporosis. There is considerable variation in the management, including rehabilitation, of these fractures. This is an update of a Cochrane review first published in 2002 and last updated in 2006. To examine the effects of rehabilitation interventions in adults with conservatively or surgically treated distal radial fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2014; Issue 12), MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker and other databases, trial registers, conference proceedings and reference lists of articles. We did not apply any language restrictions. The date of the last search was 12 January 2015. Randomised controlled trials (RCTs) or quasi-RCTs evaluating rehabilitation as part of the management of fractures of the distal radius sustained by adults. Rehabilitation interventions such as active and passive mobilisation exercises, and training for activities of daily living, could be used on their own or in combination, and be applied in various ways by various clinicians. The review authors independently screened and selected trials, and reviewed eligible trials. We contacted study authors for additional information. We did not pool data. We included 26 trials, involving 1269 mainly female and older patients. With few exceptions, these studies did not include people with serious fracture or treatment-related complications, or older people with comorbidities and poor overall function that would have precluded trial participation or required more intensive treatment. Only four of the 23 comparisons covered by these 26 trials were evaluated by more than one trial. Participants of 15 trials were initially treated conservatively, involving plaster cast immobilisation. Initial treatment was surgery (external fixation or internal fixation) for all participants in five trials. Initial treatment was either surgery or plaster cast alone in six trials. Rehabilitation started during immobilisation in seven trials and after post-immobilisation in the other 19 trials. As well as being small, the majority of the included trials had methodological shortcomings and were at high risk of bias, usually related to lack of blinding, that could affect the validity of their findings. Based on GRADE criteria for assessment quality, we rated the evidence for each of the 23 comparisons as either low or very low quality; both ratings indicate considerable uncertainty in the findings.For interventions started during immobilisation, there was very low quality evidence of improved hand function for hand therapy compared with instructions only at four days after plaster cast removal, with some beneficial effects continuing one month later (one trial, 17 participants). There was very low quality evidence of improved hand function in the short-term, but not in the longer-term (three months), for early occupational therapy (one trial, 40 participants), and of a lack of differences in outcome between supervised and unsupervised exercises (one trial, 96 participants).Four trials separately provided very low quality evidence of clinically marginal benefits of specific interventions applied in addition to standard care (therapist-applied programme of digit mobilisation during external fixation (22 participants); pulsed electromagnetic field (PEMF) during cast immobilisation (60 participants); cyclic pneumatic soft tissue compression using an inflatable cuff placed under the plaster cast (19 participants); and cross-education involving strength training of the non-fractured hand during cast immobilisation with or without surgical repair (39 participants)).For interventions started post-immobilisation, there was very low quality evidence from one study (47 participants) of improved function for a single session of physiotherapy, primarily advice and instructions for a home exercise programme, compared with 'no intervention' after cast removal. There was low quality evidence from four heterogeneous trials (30, 33, 66 and 75 participants) of a lack of clinically important differences in outcome in patients receiving routine physiotherapy or occupational therapy in addition to instructions for home exercises versus instructions for home exercises from a therapist. There was very low quality evidence of better short-term hand function in participants given physiotherapy than in those given either instructions for home exercises by a surgeon (16 participants, one trial) or a progressive home exercise programme (20 participants, one trial). Both trials (46 and 76 participants) comparing physiotherapy or occupational therapy versus a progressive home exercise programme after volar plate fixation provided low quality evidence in favour of a structured programme of home exercises preceded by instructions or coaching. One trial (63 participants) provided very low quality evidence of a short-term, but not persisting, benefit of accelerated compared with usual rehabilitation after volar plate fixation.For trials testing single interventions applied post-immobilisation, there was very low quality evidence of no clinically significant differences in outcome in patients receiving passive mobilisation (69 participants, two trials), ice (83 participants, one trial), PEMF (83 participants, one trial), PEMF plus ice (39 participants, one trial), whirlpool immersion (24 participants, one trial), and dynamic extension splint for patients with wrist contracture (40 participants, one trial), compared with no intervention. This finding applied also to the trial (44 participants) comparing PEMF versus ice, and the trial (29 participants) comparing manual oedema mobilisation versus traditional oedema treatment. There was very low quality evidence from single trials of a short-term benefit of continuous passive motion post-external fixation (seven participants), intermittent pneumatic compression (31 participants) and ultrasound (38 participants). The available evidence from RCTs is insufficient to establish the relative effectiveness of the various interventions used in the rehabilitation of adults with fractures of the distal radius. Further randomised trials are warranted. However, in order to optimise research effort and engender the large multicentre randomised trials that are required to inform practice, these should be preceded by research that aims to identify priority questions.

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics.

PubMed

Garner, Alan A; Fearnside, Michael; Gebski, Val

2013-09-14

The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. ClinicalTrials.gov: NCT00112398.

Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs.

PubMed

Maeda, Kojiro; Kaneko, Masayuki; Narukawa, Mamoru; Arato, Teruyo

2017-08-23

The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future.

Acupuncture for post anaesthetic recovery and postoperative pain: study protocol for a randomised controlled trial.

PubMed

Fleckenstein, Johannes; Baeumler, Petra I; Gurschler, Caroline; Weissenbacher, Tobias; Simang, Michael; Annecke, Thorsten; Geisenberger, Thomas; Irnich, Dominik

2014-07-21

We report on the design and implementation of a study protocol entitled Acupuncture randomised trial for post anaesthetic recovery and postoperative pain - a pilot study (ACUARP) designed to investigate the effectiveness of acupuncture therapy performed in the perioperative period on post anaesthetic recovery and postoperative pain. The study is designed as a randomised controlled pilot trial with three arms and partial double blinding. We will compare (a) press needle acupuncture, (b) no treatment and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy-five patients scheduled for laparoscopic surgery to the uterus or ovaries will be allocated randomly to one of the three trial arms. The total observation period will begin one day before surgery and end on the second postoperative day. Twelve press needles and press plasters are to be administered preoperatively at seven acupuncture points. The primary outcome measure will be time from extubation to 'ready for discharge' from the post anaesthesia care unit (in minutes). The 'ready for discharge' end point will be assessed using three different scores: the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House score. Secondary outcome measures will comprise pre-, intra- and postoperative variables (which are anxiety, pain, nausea and vomiting, concomitant medication). The results of this study will provide information on whether acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture with acupressure will provide insight into potential therapeutic differences between invasive and non-invasive acupuncture techniques. NCT01816386 (First received: 28 October 2012).

The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis

PubMed Central

Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan

2015-01-01

Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

PubMed Central

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

Quantification of myocardium at risk in ST- elevation myocardial infarction: a comparison of contrast-enhanced steady-state free precession cine cardiovascular magnetic resonance with coronary angiographic jeopardy scores.

PubMed

De Palma, Rodney; Sörensson, Peder; Verouhis, Dinos; Pernow, John; Saleh, Nawzad

2017-07-27

Clinical outcome following acute myocardial infarction is predicted by final infarct size evaluated in relation to left ventricular myocardium at risk (MaR). Contrast-enhanced steady-state free precession (CE-SSFP) cardiovascular magnetic resonance imaging (CMR) is not widely used for assessing MaR. Evidence of its utility compared to traditional assessment methods and as a surrogate for clinical outcome is needed. Retrospective analysis within a study evaluating post-conditioning during ST elevation myocardial infarction (STEMI) treated with coronary intervention (n = 78). CE-SSFP post-infarction was compared with angiographic jeopardy methods. Differences and variability between CMR and angiographic methods using Bland-Altman analyses were evaluated. Clinical outcomes were compared to MaR and extent of infarction. MaR showed correlation between CE-SSFP, and both BARI and APPROACH scores of 0.83 (p < 0.0001) and 0.84 (p < 0.0001) respectively. Bias between CE-SSFP and BARI was 1.1% (agreement limits -11.4 to +9.1). Bias between CE-SSFP and APPROACH was 1.2% (agreement limits -13 to +10.5). Inter-observer variability for the BARI score was 0.56 ± 2.9; 0.42 ± 2.1 for the APPROACH score; -1.4 ± 3.1% for CE-SSFP. Intra-observer variability was 0.15 ± 1.85 for the BARI score; for the APPROACH score 0.19 ± 1.6; and for CE-SSFP -0.58 ± 2.9%. Quantification of MaR with CE-SSFP imaging following STEMI shows high correlation and low bias compared with angiographic scoring and supports its use as a reliable and practical method to determine myocardial salvage in this patient population. Clinical trial registration information for the parent clinical trial: Karolinska Clinical Trial Registration (2008) Unique identifier: CT20080014. Registered 04 th January 2008.

Cost-utility analysis of a one-time supervisor telephone contact at 6-weeks post-partum to prevent extended sick leave following maternity leave in The Netherlands: results of an economic evaluation alongside a randomized controlled trial

PubMed Central

2011-01-01

Background Working women of childbearing age are a vital part of the population. Following childbirth, this group of women can experience a myriad of physical and mental health problems that can interfere with their ability to work. Currently, there is little known about cost-effective post-partum interventions to prevent work disability. The purpose of the study was to evaluate whether supervisor telephone contact (STC) during maternity leave is cost-effective from a societal perspective in reducing sick leave and improving quality-adjusted life years (QALYs) compared to common practice (CP). Methods We conducted an economic evaluation alongside a randomized controlled trial. QALYs were measured by the EuroQol 5-D, and sick leave and presenteeism by the Health and work Performance Questionnaire. Resource use was collected by questionnaires. Data were analysed according to intention-to-treat. Missing data were imputed via multiple imputation. Uncertainty was estimated by 95% confidence intervals, cost-utility planes and curves, and sensitivity analyses. Results 541 working women from 15 companies participated. Response rates were above 85% at each measurement moment. At the end of the follow-up, no statistically significant between-group differences in QALYs, mean hours of sick leave or presenteeism or costs were observed. STC was found to be less effective and more costly. For willingness-to-pay levels from €0 through €50,000, the probability that STC was cost-effective compared to CP was 0.2. Overall resource use was low. Mean total costs were €3678 (95% CI: 3386; 3951). Productivity loss costs represented 37% of the total costs and of these costs, 48% was attributable to sick leave and 52% to work presenteeism. The cost analysis from a company's perspective indicated that there was a net cost associated with the STC intervention. Conclusions STC was not cost-effective compared to common practice for a healthy population of working mothers; therefore, implementation is not indicated. The cost-utility of STC for working mothers with more severe post-partum health problems, however, needs to be investigated. Work presenteeism accounted for half of the total productivity loss and warrants attention in future studies. Trial registration number ISRCTN: ISRCTN73119486 PMID:21272325

Mechanism evaluation of a lifestyle intervention for patients with musculoskeletal pain who are overweight or obese: protocol for a causal mediation analysis.

PubMed

Lee, Hopin; Wiggers, John; Kamper, Steven J; Williams, Amanda; O'Brien, Kate M; Hodder, Rebecca K; Wolfenden, Luke; Yoong, Sze Lin; Campbell, Elizabeth; Haskins, Robin; Robson, Emma K; McAuley, James H; Williams, Christopher M

2017-07-03

Low back pain (LBP) and knee osteoarthritis (OA) are highly prevalent and disabling conditions that cause societal and economic impact worldwide. Two randomised controlled trials (RCTs) will evaluate the effectiveness of a multicomponent lifestyle intervention for patients with LBP and knee OA who are overweight or obese. The key targets of this intervention are to improve physical activity, modify diet and correct pain beliefs. These factors may explain how a lifestyle intervention exerts its effects on key patient-relevant outcomes: pain, disability and quality of life. The aim of this protocol is to describe a planned analysis of a mechanism evaluation for a lifestyle intervention for overweight or obese patients with LBP and knee OA. Causal mediation analyses of 2 two-armed RCTs. Both trials are part of a cohort-multiple RCT, embedded in routine health service delivery. In each respective trial, 160 patients with LBP and 120 patients with knee OA waiting for orthopaedic consultation will be randomised to a lifestyle intervention, or to remain part of the original cohort. The intervention consists of education and advice about the benefits of weight loss and physical activity, and the Australian New South Wales Get Healthy Service. All outcome measures including patient characteristics, primary and alternative mediators, outcomes, and potential confounders will be measured at baseline (T0). The primary mediator, weight, will be measured at 6 months post randomisation; alternative mediators including diet, physical activity and pain beliefs will be measured at 6 weeks post randomisation. All outcomes (pain, disability and quality of life) will be measured at 6 months post randomisation. Data will be analysed using causal mediation analysis with sensitivity analyses for sequential ignorability. All mediation models were specified a priori before completing data collection and without prior knowledge about the effectiveness of the intervention. The study is approved by the Hunter New England Health Human Research Ethics Committee (13/12/11/5.18) and the University of Newcastle Human Research Ethics Committee (H-2015-0043). The results will be disseminated in peer-reviewed journals and at scientific conferences. ACTRN12615000490572 and ACTRN12615000478516; 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.

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery

PubMed Central

2010-01-01

Background The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. Methods/Design The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 × 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. Discussion This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period. Trial Registration Current controlled trials ISRCTN46782945 UK CRN ID: 2670 PMID:20102625

Di-tri-octahedral smectite for the prevention of post-operative diarrhea in equids with surgical disease of the large intestine: results of a randomized clinical trial.

PubMed

Hassel, Diana M; Smith, Phoebe A; Nieto, Jorge E; Beldomenico, Pablo; Spier, Sharon J

2009-11-01

The aim of this study was to evaluate the effects of a commercially available di-tri-octahedral (DTO) smectite product on clinical signs and prevalence of post-operative diarrhea in horses with colic associated with disease of the large intestine. Sixty-seven horses with surgical disease of the large intestine were randomly assigned to be treated with DTO smectite (n=37; 0.5 kg via nasogastric intubation every 24 h for 3 days post-operatively) or a placebo (n=30). The effect of treatment on fecal scores and clinical and hematological parameters, including heart rate, mucous membrane color, temperature, total white blood cell count, total neutrophil count and total plasma protein values, were determined. Horses treated with DTO smectite had a significant reduction in the prevalence of post-operative diarrhea (10.8%), compared with controls (41.4%). A significant improvement in mucous membrane color was observed 72 h post-operatively in horses receiving treatment, compared with placebo. Administration of DTO smectite to colic patients with disease of the large intestine reduced the occurrence of diarrhea in the early post-operative period.

A novel cognitive behaviour therapy for bipolar disorders (Think Effectively About Mood Swings or TEAMS): study protocol for a randomized controlled trial.

PubMed

Mansell, Warren; Tai, Sara; Clark, Alexandra; Akgonul, Savas; Dunn, Graham; Davies, Linda; Law, Heather; Morriss, Richard; Tinning, Neil; Morrison, Anthony P

2014-10-24

Existing psychological therapies for bipolar disorders have been found to have mixed results, with a consensus that they provide a significant, but modest, effect on clinical outcomes. Typically, these approaches have focused on promoting strategies to prevent future relapse. An alternative treatment approach, termed 'Think Effectively About Mood Swings' (TEAMS) addresses current symptoms, including subclinical hypomania, depression and anxiety, and promotes long-term recovery. Following the publication of a theoretical model, a range of research studies testing the model and a case series have demonstrated positive results. The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial. A target number of 84 patients with a diagnosis of bipolar I or II disorder, or bipolar disorder not-otherwise-specified are screened, allocated to a baseline assessment and randomized to either 16 sessions of TEAMS therapy plus treatment-as-usual (TAU) or TAU. Patients complete self-report inventories of depression, anxiety, recovery status and bipolar cognitions targeted by TEAMS. Assessments of diagnosis, bipolar symptoms, medication, access to services and quality of life are conducted by assessors blind to treatment condition at 3, 6, 12 and 18 months post-randomization. The main aim is to evaluate recruitment and retention of participants into both arms of the study, as well as adherence to therapy, to determine feasibility and acceptability. It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization. The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety, reduce bipolar cognitions, improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up. The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of TEAMS therapy that will be subject to qualitative analyses to inform future developments of the approach. The design will provide preliminary evidence of efficacy, feasibility, acceptability, uptake, attrition and barriers to treatment to design a definitive trial of this novel intervention compared to treatment as usual. This trial was registered with Current Controlled Trials (ISRCTN83928726) on registered 25 July 2014.

Hypogravity's Effect on the Life Cycle of Japanese Quail

NASA Technical Reports Server (NTRS)

Hester, Patricia Y.

1999-01-01

A series of studies were conducted to determine the effect of activities preceding space-flight and during space-flight on quail embryonic development. While the overall development of the quail embryos was evaluated, the report presented herein, focused on calcium utilization or uptake from eggshells by developing embryos during incubation in space and on earth. In the pre-space trials, fertilized quail eggs were subjected to pre-night dynamics including forces of centrifugation, vibration, or a combination of vibration and centrifugation prior to incubation for 6 or 16 days. In another trial, fertile quail eggs were tested for survivability in a refrigerator stowage kit for eggs (RSKE) which was subsequently used to transport the eggs to space. Eggs in the RSKE were subjected to shuttle launch dynamics including G force and random vibration profiles. In the space- flight trials, 48 fertile quail eggs were launched on space shuttle Flight STS-76 and were subsequently incubated in a Slovakian incubator onboard space station, MIR. Two sets of ground controls each with 48 fertile eggs with and without exposure to launch dynamics were initiated 5 days post-launch. There was a laboratory control (incubated in Lyon RX2 incubator at 37.5 C) and a synchronous control (incubated in Lyon RX2 incubator at 39 - 400 C), which simulated the temperature of the space-flight incubator. Following space-flight trials, post-flight trials were conducted where quail eggs were incubated in Lyon RX2 or Slovakian incubators under various temperatures with or without launch dynamics. Eggshells from all study trials were retrieved and analyzed for calcium content to determine if its utilization by developing quail embryos was affected by activities preceding space-flight or during incubation in space under microgravity. Results from the pre-flight and post-flight showed that pre-flight activities and shuttle launch dynamics had no effect on calcium uptake from the eggshell by developing embryos. However, calcium uptake from the eggshell by developing embryos incubated in micro,aravity was impaired by 12.6% when compared to embryos incubated on earth under laboratory control environment. This impairment was unlikely due to factors other than microgravity. In general, calcium utilization by developing embryos increased with age of incubation with the most increase occurring at day 16 of incubation.

Time course of upper limb function and return-to-work post-radiotherapy in young adults with breast cancer: a pilot randomized control trial on effects of targeted exercise program.

PubMed

Ibrahim, Marize; Muanza, Thierry; Smirnow, Nadia; Sateren, Warren; Fournier, Beatrice; Kavan, Petr; Palumbo, Michael; Dalfen, Richard; Dalzell, Mary-Ann

2017-12-01

Breast cancer (BC) diagnosis in young adults (YA) is rising, and both disease and treatments are aggressive in this population. Evidence supports the use of physical activity in reducing shoulder dysfunction, which is common among BC survivors. A pilot randomized clinical trial was performed to determine the effectiveness of a 12-week post-radiation exercise program in minimizing upper extremity dysfunction in YA with BC. Participants were randomized to either an exercise arm or a control arm receiving standard care. Data was collected over six time points using: the Disability of Arm, Shoulder, and Hand (DASH); the Metabolic Equivalent of Task-hours per week (MET-hours/week), and a post hoc questionnaire on return to work. In total, 59 young women participated in the study (n = 29 exercise; n = 30 control). No statistically significant differences were found in overall DASH results between groups; however, those who underwent total mastectomy had residual upper limb dysfunction (p < 0.05). Both groups returned to pre-diagnosis activity levels by 18 months. Final evaluation showed that 86% of the women returned to work, and 89% resumed prior work activities with a decrease of 8.5 h/week. Although the short-term targeted exercise program had no effect on long-term upper limb function post-radiation, timing and program specificity may require consideration of tissue healing post-radiation and surgery type. The majority of participants returned to work, however not returning to pre-diagnosis work hours. Exercise interventions alone may not reverse the long-term sequelae of breast cancer treatment and allow young adult patients to return to work.

Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies.

PubMed

Balassy, Csilla; Roberts, Donna; Miller, Stephen F

2015-11-01

Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children.

Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial

PubMed Central

2014-01-01

Background Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness. Methods/Design This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated. Discussion We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease. Trial registration ClinicalTrials.gov identifier: NCT01547611 PMID:24502414

Group interventions for co-morbid insomnia and osteoarthritis pain in primary care: the lifestyles cluster randomized trial design.

PubMed

Von Korff, Michael; Vitiello, Michael V; McCurry, Susan M; Balderson, Benjamin H; Moore, Amy L; Baker, Laura D; Yarbro, Patricia; Saunders, Kathleen; Keefe, Francis J; Rybarczyk, Bruce D

2012-07-01

Six weekly sessions of group cognitive-behavioral therapy for insomnia and osteoarthritis pain (CBT-PI), and for osteoarthritis pain alone (CBT-P) were compared to an education only control (EOC). Basic education about pain and sleep was comparable, so EOC controlled for information and group participation. Active interventions differed from EOC in training pain coping skills (CBT-P and CBT-PI) and sleep enhancement techniques (CBT-PI). Persons with osteoarthritis age 60 or older were screened for osteoarthritis pain and insomnia severity via mailed survey. Primary outcomes were pain severity (pain intensity and interference ratings from the Graded Chronic Pain Scale) and insomnia severity (Insomnia Severity Index). Secondary outcomes were arthritis pain (AIMS-2 symptom scale) and sleep efficiency assessed by wrist actigraphy. Ancillary outcomes included: cognitive function, depression, and health care use. A clustered randomized design provided adequate power to identify moderate effects on primary outcomes (effect size>0.35). Modified intent to treat analyses, including all participants who attended the first session, assessed effects across CBT-PI, CBT-P, and EOC groups. Treatment effects were assessed post-intervention (2 months) and at 9 months, with durability of intervention effects evaluated at 18 months. The trial was executed in 6 primary clinics, randomizing 367 participants, with 93.2% of randomized patients attending at least 4 group sessions. Response rates for post-intervention and 9 month assessments were 96.7% and 92.9% respectively. This hybrid efficacy-effectiveness trial design evaluates whether interventions yield specific benefits for clinical and behavioral outcomes relative to an education only control when implemented in a primary care setting. Copyright © 2012 Elsevier Inc. All rights reserved.

Cognitive and Self-regulatory Mechanisms of Obesity Study (COSMOS): Study protocol for a randomized controlled weight loss trial examining change in biomarkers, cognition, and self-regulation across two behavioral treatments.

PubMed

Hawkins, M A W; Colaizzi, Janna; Gunstad, John; Hughes, Joel W; Mullins, Larry L; Betts, Nancy; Smith, Caitlin E; Keirns, Natalie G; Vohs, Kathleen D; Moore, Shirley M; Forman, Evan M; Lovallo, William R

2018-03-01

Obesity is a global epidemic, yet successful interventions are rare. Up to 60% of people fail to achieve clinically meaningful, short-term weight loss (5-10% of start weight), whereas up to 72% are unsuccessful at achieving long-term weight loss (5-10% loss for ≥5years). Understanding how biological, cognitive, and self-regulatory factors work together to promote or to impede weight loss is clearly needed to optimize obesity treatment. This paper describes the methodology of the Cognitive and Self-regulatory Mechanisms of Obesity Study (the COSMOS trial). COSMOS is the first randomized controlled trial to investigate how changes in multiple biopsychosocial and cognitive factors relate to weight loss and one another across two weight loss treatments. The specific aims are to: 1) Confirm that baseline obesity-related physiological dysregulation is linked to cognitive deficits and poorer self-regulation, 2) Evaluate pre- to post-treatment change across time to assess individual differences in biomarkers, cognition, and self-regulation, and 3) Evaluate whether the acceptance-based treatment (ABT) group has greater improvements in outcomes (e.g., greater weight loss and less weight regain, improvements in biomarkers, cognition, and self-regulation), than the standard behavioral treatment group (SBT) from pre- to post-treatment and 1-year follow-up. The results of COSMOS will provide critical information about how dysregulation in biomarkers, cognition, and/or self-regulation is related to weight loss and whether weight loss treatments are differentially associated with these factors. This information will be used to identify promising treatment targets that are informed by biological, cognitive, and self-regulatory factors in order to advance obesity treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Liver Function Assessment Using Technetium 99m-Galactosyl Single-Photon Emission Computed Tomography/CT Fusion Imaging: A Prospective Trial.

PubMed

Okabayashi, Takehiro; Shima, Yasuo; Morita, Sojiro; Shimada, Yasuhiro; Sumiyoshi, Tatsuaki; Sui, Kenta; Iwata, Jun; Iiyama, Tatsuo

2017-12-01

The prediction of postoperative liver function remains a largely subjective practice based on CT volumetric analysis. However, future liver volume after a hepatectomy is not the only factor that contributes to postoperative liver function and outcomes. In this prospective trial, 185 consecutive patients who underwent liver operations between 2014 and 2015 were studied. Volumetric and functional rates of remnant liver were measured using technetium 99m-galactosyl human serum albumin single-photon emission computed tomography/CT fusion imaging to evaluate post-hepatectomy remnant liver function. Remnant indocyanine green clearance rate using galactosyl (KGSA) (KGSA × functional rate) was used to predict future remnant liver function. Hepatectomy was considered safe for patients with remnant KGSA values ≥0.05, and the primary end point was to determine the accuracy and reliability of this criteria. The prediction of the 90-day major complication and mortality rates was assessed. Median hospital stay was 9 days and median ICU stay was 1 day, with only 1 in-hospital death (90-day mortality rate 0.5%). Overall morbidity rate evaluated according to the Clavien-Dindo classification was 9%. For post-hepatectomy liver failure definitions, the International Study Group of Liver Surgery definition was fulfilled in 14 patients (8%), with the majority being grade B (50%), compared with 2 patients (1%) fulfilling the "50-50" criteria, and 0 patients (0%) fulfilling the Peak Bili >7 criteria. Results of this study showed that remnant KGSA provided information that allowed us to predict remnant liver function. This information will be important for surgeons when deciding on a treatment plan for patients with liver diseases. (ClinicalTrials.gov ID: NCT02013895). Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis.

PubMed

Sotoudehmanesh, Rasoul; Eloubeidi, Mohamad Ali; Asgari, Ali Ali; Farsinejad, Maryam; Khatibian, Morteza

2014-06-01

Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

Automatic remote monitoring utilizing daily transmissions: transmission reliability and implantable cardioverter defibrillator battery longevity in the TRUST trial.

PubMed

Varma, Niraj; Love, Charles J; Schweikert, Robert; Moll, Philip; Michalski, Justin; Epstein, Andrew E

2018-04-01

Benefits of automatic remote home monitoring (HM) among implantable cardioverter defibrillator (ICD) patients may require high transmission frequency. However, transmission reliability and effects on battery longevity remain uncertain. We hypothesized that HM would have high transmission success permitting punctual guideline based follow-up, and improve battery longevity. This was tested in the prospective randomized TRUST trial. Implantable cardioverter defibrillator patients were randomized post-implant 2:1 to HM (n = 908) (transmit daily) or to Conventional in-person monitoring [conventional management (CM), n = 431 (HM disabled)]. In both groups, five evaluations were scheduled every 3 months for 15 months. Home Monitoring technology performance was assessed by transmissions received vs. total possible, and number of scheduled HM checks failing because of missed transmissions. Battery longevity was compared in HM vs. CM at 15 months, and again in HM 3 years post-implant using continuously transmitted data. Transmission success per patient was 91% (median follow-up of 434 days). Overall, daily HM transmissions were received in 315 795 of a potential 363 450 days (87%). Only 55/3759 (1.46%) of unsuccessful scheduled evaluations in HM were attributed to transmission loss. Shock frequency and pacing percentage were similar in HM vs. CM. Fifteen month battery longevity was 12% greater in HM (93.2 ± 8.8% vs. 83.5 ± 6.0% CM, P < 0.001). In extended follow-up of HM patients, estimated battery longevity was 50.9 ± 9.1% (median 52%) at 36 months. Automatic remote HM demonstrated robust transmission reliability. Daily transmission load may be sustained without reducing battery longevity. Home Monitoring conserves battery longevity and tracks long term device performance. ClinicalTrials.gov; NCT00336284.

The Impact of Prophylactic Dexamethasone on Nausea and Vomiting after Thyroidectomy: A Systematic Review and Meta-Analysis

PubMed Central

Zou, Zhenhong; Jiang, Yuming; Xiao, Mingjia; Zhou, Ruiyao

2014-01-01

Background We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in patients undergoing thyroidectomy. Methods We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software. Results Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P<0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD –1.17, 95% CI –1.91 to –0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50–0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8–10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25–5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86–1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event. Conclusions Prophylactic dexamethasone 8–10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to define the benefits and risks of prophylactic dexamethasone in potential patients with a high risk for PONV. PMID:25330115

The Sternal Management Accelerated Recovery Trial (S.M.A.R.T) - standard restrictive versus an intervention of modified sternal precautions following cardiac surgery via median sternotomy: study protocol for a randomised controlled trial.

PubMed

Katijjahbe, Md Ali; Denehy, Linda; Granger, Catherine L; Royse, Alistair; Royse, Colin; Bates, Rebecca; Logie, Sarah; Clarke, Sandy; El-Ansary, Doa

2017-06-23

The routine implementation of sternal precautions to prevent sternal complications that restrict the use of the upper limbs is currently worldwide practice following a median sternotomy. However, evidence is limited and drawn primarily from cadaver studies and orthopaedic research. Sternal precautions may delay recovery, prolong hospital discharge and be overly restrictive. Recent research has shown that upper limb exercise reduces post-operative sternal pain and results in minimal micromotion between the sternal edges as measured by ultrasound. The aims of this study are to evaluate the effects of modified sternal precautions on physical function, pain, recovery and health-related quality of life after cardiac surgery. This study is a phase II, double-blind, randomised controlled trial with concealed allocation, blinding of patients and assessors, and intention-to-treat analysis. Patients (n = 72) will be recruited following cardiac surgery via a median sternotomy. Sample size calculations were based on the minimal important difference (two points) for the primary outcome: Short Physical Performance Battery. Thirty-six participants are required per group to counter dropout (20%). All participants will be randomised to receive either standard or modified sternal precautions. The intervention group will receive guidelines encouraging the safe use of the upper limbs. Secondary outcomes are upper limb function, pain, kinesiophobia and health-related quality of life. Descriptive statistics will be used to summarise data. The primary hypothesis will be examined by repeated-measures analysis of variance to evaluate the changes from baseline to 4 weeks post-operatively in the intervention arm compared with the usual-care arm. In all tests to be conducted, a p value <0.05 (two-tailed) will be considered statistically significant, and confidence intervals will be reported. The Sternal Management Accelerated Recovery Trial (S.M.A.R.T.) is a two-centre randomised controlled trial powered and designed to investigate whether the effects of modifying sternal precautions to include the safe use of the upper limbs and trunk impact patients' physical function and recovery following cardiac surgery via median sternotomy. Australian and New Zealand Clinical Trials Registry identifier: ACTRN12615000968572 . Registered on 16 September 2015 (prospectively registered).

Pre-referral rectal artesunate in severe malaria: flawed trial.

PubMed

Hirji, Karim F; Premji, Zulfiqarali G

2011-08-08

Immediate injectable treatment is essential for severe malaria. Otherwise, the afflicted risk lifelong impairment or death. In rural areas of Africa and Asia, appropriate care is often miles away. In 2009, Melba Gomes and her colleagues published the findings of a randomized, placebo-controlled trial of rectal artesunate for suspected severe malaria in such remote areas. Enrolling nearly 18,000 cases, the aim was to evaluate whether, as patients were in transit to a health facility, a pre-referral artesunate suppository blocked disease progression sufficiently to reduce these risks. The affirmative findings of this, the only trial on the issue thus far, have led the WHO to endorse rectal artesunate as a pre-referral treatment for severe malaria. In the light of its public health importance and because its scientific quality has not been assessed for a systematic review, our paper provides a detailed evaluation of the design, conduct, analysis, reporting, and practical features of this trial. We performed a checklist-based and an in-depth evaluation of the trial. The evaluation criteria were based on the CONSORT statement for reporting clinical trials, the clinical trial methodology literature, and practice in malaria research. Our main findings are: The inclusion and exclusion criteria and the sample size justification are not stated. Many clearly ineligible subjects were enrolled. The training of the recruiters does not appear to have been satisfactory. There was excessive between center heterogeneity in design and conduct. Outcome evaluation schedule was not defined, and in practice, became too wide. Large gaps in the collection of key data were evident. Primary endpoints were inconsistently utilized and reported; an overall analysis of the outcomes was not done; analyses of time to event data had major flaws; the stated intent-to-treat analysis excluded a third of the randomized subjects; the design-indicated stratified or multi-variate analysis was not done; many improper subgroups were analyzed in a post-hoc fashion; the analysis and reporting metric was deficient. There are concerns relating to patient welfare at some centers. Exclusion of many cases from data analysis compromised external validity. A bias-controlled reanalysis of available data does not lend support to the conclusions drawn by the authors. This trial has numerous serious deficiencies in design, implementation, and methods of data analysis. Interpretation and manner of reporting are wanting, and the applicability of the findings is unclear. The trial conduct could have been improved to better protect patient welfare. The totality of these problems make it a flawed study whose conclusions remain subject to appreciable doubt.

Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

PubMed

Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

2017-10-09

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

PubMed

Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

2015-02-04

Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

SPIRIT trial: A phase III pragmatic trial of an advance care planning intervention in ESRD.

PubMed

Song, Mi-Kyung; Unruh, Mark L; Manatunga, Amita; Plantinga, Laura C; Lea, Janice; Jhamb, Manisha; Kshirsagar, Abhijit V; Ward, Sandra E

2018-01-01

Advance care planning (ACP) is a central tenet of dialysis care, but the vast majority of dialysis patients report never engaging in ACP discussions with their care providers. Over the last decade, we have developed and iteratively tested SPIRIT (Sharing Patient's Illness Representation to Increase Trust), a theory-based, patient- and family-centered advance care planning intervention. SPIRIT is a six-step, two-session, face-to-face intervention to promote cognitive and emotional preparation for end-of-life decision making for patients with ESRD and their surrogates. In these explanatory trials, SPIRIT was delivered by trained research nurses. Findings consistently revealed that patients and surrogates in SPIRIT showed significant improvement in preparedness for end-of-life decision making, and surrogates in SPIRIT reported significantly improved post-bereavement psychological outcomes after the patient's death compared to a no treatment comparison condition. As a critical next step, we are conducting an effectiveness-implementation study. This study is a multicenter, clinic-level cluster randomized pragmatic trial to evaluate the effectiveness of SPIRIT delivered by dialysis care providers as part of routine care in free-standing outpatient dialysis clinics, compared to usual care plus delayed SPIRIT implementation. Simultaneously, we will evaluate the implementation of SPIRIT, including sustainability. We will recruit 400 dyads of patients at high risk of death in the next year and their surrogates from 30 dialysis clinics in four states. This trial of SPIRIT will generate novel, meaningful insights about improving ACP in dialysis care. ClinicalTrials.govNCT03138564, registered 05/01/2017. Copyright © 2017 Elsevier Inc. All rights reserved.

A comparison of three induction regimens using succinylcholine, vecuronium, or no muscle relaxant: impact on the intraoperative monitoring of the lateral spread response in hemifacial spasm surgery: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Surgical microvascular decompression (MVD) is the curative treatment for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread response (LSR) intraoperatively can predict a successful clinical outcome. However, the rate of the LSR varies between trials, and the reason for this variation is unclear. The aim of our trial is to evaluate the rate of the LSR after intubation following treatment with succinylcholine, vecuronium, or no muscle relaxant. Methods and design This trial is a prospective randomised controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD under general anaesthesia. Patients are randomised to receive succinylcholine, vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be recorded until dural opening. The primary outcome of this study is the rate of the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal symptoms, the rate of difficult intubations, the rate of adverse haemodynamic events and the relationship between the measurement of LSR or not, and clinical success rates at 30 days after surgery. Discussion This study aims to evaluate the impact of muscle relaxants on the rate of the LSR, and the study may provide evidence supporting the use of muscle relaxants before intubation in patients with HFS undergoing MVD surgery. Trials registration http://www.chictr.org/ ChiCTR-TRC-11001504 Date of registration: 24 June, 2011. The date the first patient was randomised: 30 September, 2011. PMID:22958580

Fast-track surgery after gynaecological oncological surgery: study protocol for a prospective randomised controlled trial.

PubMed

Cui, Ling; Shi, Yu; Zhang, G N

2016-12-15

Fast-track surgery (FTS), also known as enhanced recovery after surgery, is a multidisciplinary approach to accelerate recovery, reduce complications, minimise hospital stay without increasing readmission rates, and reduce health care costs, all without compromising patient safety. The advantages of FTS in abdominal surgery most likely extend to gynaecological surgery, but this is an assumption, as FTS in elective gynaecological surgery has not been well studied. No consensus guidelines have been developed for gynaecological oncological surgery although surgeons have attempted to introduce slightly modified FTS programmes for patients undergoing such surgery. To our knowledge, there are no published randomised controlled trials; however, some studies have shown that FTS in gynaecological oncological surgery leads to early hospital discharge with high levels of patient satisfaction. The aim of this study is whether FTS reduces the length of stay in hospital compared to traditional management. The secondary aim is whether FTS is associated with any increase in post-surgical complications compared to traditional management (for both open and laparoscopic surgery). This trial will prospectively compare FTS and traditional management protocols. The primary endpoint is the length of post-operative hospitalisation (days, mean ± standard deviation), defined as the number of days between the date of discharge and the date of surgery. The secondary endpoints are complications in both groups (FTS versus traditional protocol) occurring during the first 3 months post-operatively including infection (wound infection, lung infection, intraperitoneal infection), post-operative nausea and vomiting, ileus, post-operative haemorrhage, post-operative thrombosis, and the Acute Physiology and Chronic Health Enquiry II score. The advantages of FTS most likely extend to gynaecology, although, to our knowledge, there are no randomised controlled trials. The aim of this study is to compare the post-operative length of hospitalisation after major gynaecological or gynaecological oncological surgery and to analyse patients' post-operative complications. This trial may reveal whether FTS leads to early hospital discharge with few complications after gynaecological surgery. NCT02687412 . Approval Number: SCCHEC20160001. Date of registration: registered on 23 February 2016.

Trends in Research with U.S. Military Service Member Participants: A Population-Specific ClinicalTrials.gov Review.

PubMed

Cook, Wendy A; Doorenbos, Ardith Z; Bridges, Elizabeth J

2016-08-15

ClinicalTrials.gov reviews have evaluated research trends for specific conditions and age groups but not for specific populations of research participants. No ClinicalTrials.gov reviews have evaluated research with military service member participants. Study objectives were (a) to use ClinicalTrials.gov to identify trends in biomedical research from 2005 to 2014 in which U.S. military service members actively participated as research participants and (b) to describe a search strategy for adaptation in future ClinicalTrials.gov reviews of specific participant populations. A systematic review of ClinicalTrials.gov was performed to identify studies that included U.S. service members as participants, either exclusively or with other groups of participants. U.S. service members were identified as participants in 512 studies. Service members participated together with other groups in 392 studies, while 120 studies included only service members. The top five conditions of interest were post-traumatic stress disorder, traumatic brain injury, amputations, burns, and ocular injuries/disorders. The number of studies started each year peaked in 2011 and declined from 2012 to 2014. Twenty-five percent of studies exclusive to service members aimed to enroll 500 or more participants. Research exclusive to Guard and Reserve service members during this period was limited. U.S. military service members participate in biomedical research. To address the health needs of U.S. service members, it is important to ensure there is not a prolonged decline in research among this population. The search strategy may be adapted to ClinicalTrials.gov reviews of specific participant populations for which straightforward searches are not possible.

Sleep deficits in the High Arctic summer in relation to light exposure and behaviour: use of melatonin as a countermeasure.

PubMed

Paul, Michel A; Love, Ryan J; Hawton, Andrea; Brett, Kaighley; McCreary, Donald R; Arendt, Josephine

2015-03-01

There are conflicting reports regarding seasonal sleep difficulties in polar regions. Herein we report differences in actigraphic sleep measures between two summer trials (collected at Canadian Forces Station Alert, 82.5°N, in 2012 and 2014) and evaluate exogenous melatonin for preventing/treating circadian phase delay due to nocturnal light exposure. Subjects wore actigraphs continuously to obtain sleep data. Following seven days of actigraphic recording the subjects filled out questionnaires regarding sleep difficulty and psychosocial parameters and subsequently remained in dim light conditions for 24 hours, during which saliva was collected bihourly to measure melatonin. During Trial 2, individuals who reported difficulty sleeping were prescribed melatonin, and a second saliva collection was conducted to evaluate the effect of melatonin on the circadian system. Trial 1 subjects collectively had late dim light melatonin onsets and difficulty sleeping; however, the Trial 2 subjects had normally timed melatonin rhythms, and obtained a good quantity of high-quality sleep. Nocturnal light exposure was significantly different between the trials, with Trial 1 subjects exposed to significantly more light between 2200 and 0200h. Melatonin treatment during Trial 2 led to an improvement in the subjective sleep difficulty between the pre- and post-treatment surveys; however there were no significant differences in the objective measures of sleep. The difference in sleep and melatonin rhythms between research participants in June 2012 and June 2014 is attributed to the higher levels of nocturnal light exposure in 2012. The avoidance of nocturnal light is likely to improve sleep during the Arctic summer. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.

PubMed

Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John; Chiaravalloti, Nancy D

2014-09-01

Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.