Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

The effectiveness of influenza vaccination in preventing hospitalisations of elderly individuals in two influenza seasons: a multicentre case-control study, Spain, 2013/14 and 2014/15.

PubMed

Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Espejo, Elena; Fernandez, Maria Amelia; Mayoral, José María; Castilla, Jesús; Egurrola, Mikel; Tamames, Sonia; Astray, Jenaro; Morales-Suárez-Varela, María

2017-08-24

Influenza vaccination may limit the impact of influenza in the community. The aim of this study was to assess the effectiveness of influenza vaccination in preventing hospitalisation in individuals aged ≥ 65 years in Spain. A multicentre case-control study was conducted in 20 Spanish hospitals during 2013/14 and 2014/15. Patients aged ≥ 65 years who were hospitalised with laboratory-confirmed influenza were matched with controls according to sex, age and date of hospitalisation. Adjusted vaccine effectiveness (VE) was calculated by multivariate conditional logistic regression. A total of 728 cases and 1,826 matched controls were included in the study. Overall VE was 36% (95% confidence interval (CI): 22-47). VE was 51% (95% CI: 15-71) in patients without high-risk medical conditions and 30% (95% CI: 14-44) in patients with them. VE was 39% (95% CI: 20-53) in patients aged 65-79 years and 34% (95% CI: 11-51) in patients aged ≥ 80 years, and was greater against the influenza A(H1N1)pdm09 subtype than the A(H3N2) subtype. Influenza vaccination was effective in preventing hospitalisations of elderly individuals. This article is copyright of The Authors, 2017.

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

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

PubMed

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

2015-11-17

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

HPV and cofactors for invasive cervical cancer in Morocco: a multicentre case-control study.

PubMed

Berraho, Mohamed; Amarti-Riffi, Afaf; El-Mzibri, Mohammed; Bezad, Rachid; Benjaafar, Noureddine; Benideer, Abdelatif; Matar, Noureddine; Qmichou, Zinab; Abda, Naima; Attaleb, Mohammed; Znati, Kaoutar; El Fatemi, Hind; Bendahhou, Karima; Obtel, Majdouline; Filali Adib, Abdelhai; Mathoulin-Pelissier, Simone; Nejjari, Chakib

2017-06-20

Limited national information is available in Morocco on the prevalence and distribution of HPV-sub-types of cervical cancer and the role of other risk factors. The aim was to determine the frequency of HPV-sub-types of cervical cancer in Morocco and investigate risk factors for this disease. Between November 2009 and April 2012 a multicentre case-control study was carried out. A total of 144 cases of cervical cancer and 288 age-matched controls were included. Odds-ratios and corresponding confidence-intervals were computed by conditional logistic regression models. Current HPV infection was detected in 92.5% of cases and 13.9% of controls. HPV16 was the most common type for both cases and controls. Very strong associations between HPV-sub-types and cervical cancer were observed: total-HPV (OR = 39), HPV16 (OR = 49), HPV18 (OR = 31), and multiple infections (OR = 13). Education, high parity, sexual intercourse during menstruation, history of sexually transmitted infections, and husband's multiple sexual partners were also significantly associated with cervical cancer in the multivariate analysis. Our results could be used to establish a primary prevention program and to prioritize limited screening to women who have specific characteristics that may put them at an increased risk of cervical cancer.

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial.

PubMed

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-12-11

Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Randomised multicentre clinical trial. Post hoc analyses of the DASH-Sodium trial in the USA. In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. NCT00000608. 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.

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial

PubMed Central

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-01-01

Objectives Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Design Randomised multicentre clinical trial. Setting Post hoc analyses of the DASH-Sodium trial in the USA. Participants In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Outcome measures Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. Results The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. Conclusions A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. Trial registration number NCT00000608. PMID:25500372

The new system of review by multicentre research ethics committees: prospective study

PubMed Central

Tully, Joanna; Ninis, Nelly; Booy, Robert; Viner, Russell

2000-01-01

Objective To assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed. Design Prospectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited. Setting A single multicentre research ethics committee and 125 local ethics committees from six regions of England. Main outcome measures Time to reply, time to approval, and number of non-local changes to the application requested. Results Only 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested. Conclusions The new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims. PMID:10784541

Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis.

PubMed

Xu, Jane; Liu, Yingrui Cyril; Adams, Susan; Karpelowsky, Jonathan

2016-12-21

This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ 2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. NCT02795793; ACTRN12616000788471. 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/.

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

Oxidative stress in dogs with multicentric lymphoma: Effect of chemotherapy on oxidative and antioxidant biomarkers.

PubMed

Bottari, Nathieli B; Munhoz, Thiago D; Torbitz, Vanessa D; Tonin, Alexandre A; Anai, Letícia A; Semolin, Lívia M S; Jark, Paulo C; Bollick, Yãnaí S; Moresco, Rafael N; França, Raqueli T; Lopes, Sonia T A; Stefani, Lenita M; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

2015-01-01

Lymphoma is one of the most common types of cancer in dogs, characterized by the proliferation of lymphoid cells. The treatment of this type of cancer is usually based on drugs with high toxicity, which can cause severe side effects. Therefore, the aim of this study was to measure the levels of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), and ferric reducing antioxidant power (FRAP) in dogs with multicentric lymphoma before and after chemotherapy. For this purpose, serum samples of 25 dogs diagnosed with multicentric lymphoma and 15 healthy dogs were used. The animals were exposed to CHOP chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisone) and serum samples were collected 5 weeks after treatment. High levels of TBARS, AOPP, and FRAP were observed in sera of dogs with multicentric lymphoma when compared to healthy dogs (P < 0.01), and even higher levels (TBARS and AOPP) were found after chemotherapy i.e. treatment exacerbated the oxidative stress levels. On the other hand, FRAP levels did not differ statistically between animals with lymphoma before and after treatment (P > 0.05). Exacerbated oxidative stress was observed in dogs with multicentric lymphoma Group II (Stage IV-V: involvement of lymph nodes and organs) compared to those in Group I (Stage I-III: only affected lymph nodes) of the disease, as well as the dogs with clinical signs and T immunophenotype. Another important result was observed after chemotherapy, where FRAP levels were higher in dogs that showed complete disease remission compared to animals with progressive disease. Therefore, dogs with lymphoma showed protein oxidation and lipid peroxidation, as well as increased total antioxidants before and after chemotherapy compared to the control group.

Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases.

PubMed

Moreno, C; Cuesta-Herranz, J; Fernández-Távora, L; Alvarez-Cuesta, E

2004-04-01

The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17,526 administered doses, 17,368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.

Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study)

PubMed Central

2014-01-01

Background Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure. Methods/Design In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia. Trail registration number NCT01927497 (Clinicaltrial.gov). PMID:25163547

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Energy and nutrient intake of patients with mild-to-moderate chronic renal failure compared with healthy children: an Italian multicentre study.

PubMed

Rätsch, I M; Catassi, C; Verrina, E; Gusmano, R; Appiani, A; Bettinelli, A; Picca, S; Rizzoni, G; Fabian-Bach, C; Wingen, A M

1992-09-01

Nutritional counselling is important in the management of children with chronic renal failure (CRF). In 1988, a controlled European multicentre study was started to evaluate the effects of a low-protein diet on the progression of CRF in children. To assess the energy, macro- and micronutrient intake, 4-day weighed dietary records were obtained from 50 children with low to moderate CRF (creatinine clearance 65 to 15 ml/min per 1.73 m2) and from 93 healthy children. The mean energy intake was 90%-93% of the recommended dietary allowance for Italian children in controls and 76%-88% in CRF patients. The mean protein intake was 2.1-3.1 g/kg per day in controls and 1.6-2.7 g/kg per day in CRF patients. Overall, the energy intake was 10% and the protein intake 33% lower in CRF patients than in healthy children. Children with CRF consumed less cholesterol, calcium and phosphorus than healthy children. The lower spontaneous intake of energy, protein and other nutrients should be taken into account when planning the nutrition of children with CRF.

Assessing treatment-as-usual provided to control groups in adherence trials: Exploring the use of an open-ended questionnaire for identifying behaviour change techniques.

PubMed

Oberjé, Edwin J M; Dima, Alexandra L; Pijnappel, Frank J; Prins, Jan M; de Bruin, Marijn

2015-01-01

Reporting guidelines call for descriptions of control group support in equal detail as for interventions. However, how to assess the active content (behaviour change techniques (BCTs)) of treatment-as-usual (TAU) delivered to control groups in trials remains unclear. The objective of this study is to pre-test a method of assessing TAU in a multicentre cost-effectiveness trial of an HIV-treatment adherence intervention. HIV-nurses (N = 21) completed a semi-structured open-ended questionnaire enquiring about TAU adherence counselling. Two coders independently coded BCTs. Completeness and clarity of nurse responses, inter-coder reliabilities and the type of BCTs reported were examined. The clarity and completeness of nurse responses were adequate. Twenty-three of the 26 identified BCTs could be reliably coded (mean κ = .79; mean agreement rate = 96%) and three BCTs scored below κ = .60. Total number of BCTs reported per nurse ranged between 7 and 19 (M = 13.86, SD = 3.35). This study suggests that the TAU open-ended questionnaire is a feasible and reliable tool to capture active content of support provided to control participants in a multicentre adherence intervention trial. Considerable variability in the number of BCTs provided to control patients was observed, illustrating the importance of reliably collecting and accurately reporting control group support.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials.

PubMed

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials.

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

PubMed

Vickerstaff, Victoria; Ambler, Gareth; Bunce, Catey; Xing, Wen; Gazzard, Gus

2015-11-11

The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 .

Multiple intraosseous hemangiomas-investigation and role of N-butylcyanoacrylate in management.

PubMed

Syal, Rajan; Tyagi, Isha; Goyal, Amit; Barai, Sukanto; Parihar, Anit

2007-05-01

Primary intraosseous hemangiomas are rare (0.7% of all osseous neoplasms), benign, slow-growing neoplasms. These lesions are usually solitary. We are reporting a case of multicentric intraosseous hemangiomas. Investigation, treatment options, and role of N-butylcyanoacrylate (NBCA) in management will be discussed. A 20-year-old man had multicentric intraosseous hemangiomas involving the skull bones, mandible, vertebra, pelvic bone, and tibial tuberosity. N-butylcyanoacrylate was used by direct puncture technique using a transosseous transcutaneous route to control profuse bleeding from the retromolar region. To the best of our knowledge, this is the first reported case with such extensive multicentric intraosseous hemangiomas. N-butylcyanoacrylate by direct puncture technique can be an effective method to devascularize and stabilize low-flow intraosseous vascular tumors. (c) 2007 Wiley Periodicals, Inc.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

Johnson, Julie K; Barach, Paul; Vernooij-Dassen, Myrra

2012-12-01

A multicentre, multinational research study requires careful planning and coordination to accomplish the aims of the study and to ensure systematic and rigorous examination of all project methods and data collected. The aim of this paper is to describe the approach we used during the HANDOVER Project to develop a multicentre, multinational research project for studying transitions of patient care while creating a community of practice for the researchers. We highlight the process used to assure the quality of a multicentre qualitative study and to create a codebook for data analysis as examples of attending to the community of practice while conducting rigorous qualitative research. Essential elements for the success of this multinational, multilanguage research project included recruiting a strong research team, explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalise upon those differences. Although not commonly discussed in reports of large research projects, there is an underlying, concurrent stream of activities to develop a cohesive team that trusts and respects one another's skills and that engage independent researchers in a group process that contributes to achieving study goals. We discuss other lessons learned and offer recommendations for other teams planning multicentre research.

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

PubMed

Riccardi, G; Giacco, R; Parillo, M; Turco, S; Rivellese, A A; Ventura, M R; Contadini, S; Marra, G; Monteduro, M; Santeusanio, F; Brunetti, P; Librenti, M C; Pontiroli, A E; Vedani, P; Pozza, G; Bergamini, L; Bianchi, C

1999-03-01

The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed Central

1984-01-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide. PMID:6383234

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed

1984-08-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide.

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

PubMed

Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials

PubMed Central

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

Purpose This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. Methods The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. Results The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Conclusion Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials. PMID:27467882

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64.

PubMed

Miller, Julie M; Dewey, Marc; Vavere, Andrea L; Rochitte, Carlos E; Niinuma, Hiroyuki; Arbab-Zadeh, Armin; Paul, Narinder; Hoe, John; de Roos, Albert; Yoshioka, Kunihiro; Lemos, Pedro A; Bush, David E; Lardo, Albert C; Texter, John; Brinker, Jeffery; Cox, Christopher; Clouse, Melvin E; Lima, João A C

2009-04-01

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective "CORE-64" trial ("Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors"). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Treating KSHV-Associated Multicentric Castleman Disease

Cancer.gov

In this study, patients with KSHV-associated multicentric Castleman disease will receive IV tocilizumab every other week for up to 12 weeks. Patients who do not benefit may go on to receive high-dose AZT and valganciclovir as well.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

PubMed

Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

2016-05-01

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study

PubMed Central

Yuan, Ziwen; Wang, Bo; Li, Feijiang; Wang, Jing; Zhi, Jin; Luo, Erping; Liu, Zhirong; Zhao, Gang

2015-01-01

Introduction The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. Methods and analysis This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. Ethics and dissemination The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. Trial registration number NCT02088346 (12 March 2014). PMID:25979867

CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.

PubMed

Carling, Anna; Forsberg, Anette; Gunnarsson, Martin; Nilsagård, Ylva

2017-09-01

Imbalance leading to falls is common in people with multiple sclerosis (PwMS). To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5). A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up. Post-intervention, the exercise group showed statistically significant improvement ( p = 0.015) in BBS and borderline significant improvement in MS Walking Scale ( p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before ( p < 0.001; p < 0.004). This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.

Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

PubMed

Gathani, Toral; Barnes, Isobel; Ali, Raghib; Arumugham, Rajkumar; Chacko, Raju; Digumarti, Raghunadharao; Jivarajani, Parimal; Kannan, Ravi; Loknatha, Dasappa; Malhotra, Hemant; Mathew, Beela S

2017-01-18

The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

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.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

PubMed

Fuentes Camps, Inmaculada; Rodríguez, Alexis; Agustí, Antonia

2018-06-01

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value. © 2018 The British Pharmacological Society.

The psychosocial burden of hand eczema: Data from a European dermatological multicentre study.

PubMed

Marron, Servando E; Tomas-Aragones, Lucia; Navarro-Lopez, Jorge; Gieler, Uwe; Kupfer, Jörg; Dalgard, Florence J; Lien, Lars; Finlay, Andrew Y; Poot, Françoise; Linder, Dennis; Szepietowski, Jacek C; Misery, Laurent; Jemec, Gregor B E; Romanov, Dmitry; Sampogna, Francesca; Szabo, Csanad; Altunay, Ilknur K; Spillekom-van Koulil, Saskia; Balieva, Flora; Ali, Faraz M; Halvorsen, Jon A; Marijuan, Pedro C

2018-06-01

The essential physical role, visibility and social importance of the hands place a major psychological burden on patients with hand eczema. The aim of this study was to identify the psychological, social and clinical characteristics of patients with hand eczema, in particular the prevalences of depression, anxiety, suicidal ideation, and comorbidities. Data on patients with hand eczema were analysed from a large European multicentre study conducted with dermatology outpatients from 13 countries. Groups of patients and controls were compared to analyse the psychological burden of hand eczema. Female patients with hand eczema had higher Hospital Anxiety and Depression Scale (HADS) scores for anxiety (n = 86, median = 7.0) than controls (n = 900, median = 5.0, P = .02), and for depression (median = 4.0) than controls (3.0, P < .001). Patients with high suicidal ideation, with low socioeconomic status and who were widowed or divorced were more likely to fulfil the HADS criteria for anxiety [odds ratio (OR) > 1, P = .038, P < .001, and P < .001, respectively]. The median Dermatology Life Quality Index score was 7.0 (n = 68). This study identifies a specific psychological burden experienced by hand eczema patients, highlighting the need for focused psychosocial interventions. Physicians in particular should be aware of the need to identify anxiety and depression in female patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fluid balance and chloride load in the first 24h of ICU admission and its relation with renal replacement therapies through a multicentre, retrospective, case-control study paired by APACHE-II.

PubMed

González-Castro, A; Ortiz-Lasa, M; Leizaola, O; Salgado, E; Irriguible, T; Sánchez-Satorra, M; Lomas-Fernández, C; Barral-Segade, P; Cordero-Vallejo, M; Rodrigo-Calabia, E; Dierssen-Sotos, T

2017-05-01

To analyse the association between water balance during the first 24h of admission to ICU and the variables related to chloride levels (chloride loading, type of fluid administered, hyperchloraemia), with the development of acute kidney injury renal replacement therapy (AKI-RRT) during patients' admission to ICU. Multicentre case-control study. Hospital-based, national, carried out in 6 ICUs. Cases were patients older than 18 years who developed an AKI-RRT. Controls were patients older than 18 years admitted to the same institutions during the study period, who did not develop AKI-RRT during ICU admission. Pairing was done by APACHE-II. An analysis of unconditional logistic regression adjusted for age, sex, APACHE-II and water balance (in evaluating the type of fluid). We analysed the variables of 430 patients: 215 cases and 215 controls. An increase of 10% of the possibility of developing AKI-RRT per 500ml of positive water balance was evident (OR: 1.09 [95% CI: 1.05 to 1.14]; P<.001). The study of mean values of chloride load administered did not show differences between the group of cases and controls (299.35±254.91 vs. 301.67±234.63; P=.92). The water balance in the first 24h of ICU admission relates to the development of IRA-TRR, regardless of chloraemia. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

[Multicenter randomized trial of amnioinfusion].

PubMed

Fraser, W; Marcoux, S; Prendiville, W; Petrou, S; Hofmeyr, J; Reinharz, D; Goulet, C; Ohlsson, A

2000-05-01

Meconium staining of the amniotic fluid in labor is a frequent problem that is associated with an increase in the risk of neonatal and maternal morbidity. Amnioinfusion is a simple technique that is designed to prevent neonatal and maternal morbidity associated with meconium. Preliminary studies indicate that amnioinfusion is a promising approach to the prevention of such complications of labor. However, further research is required. The primary objective of this multi-centre randomized controlled study is to determine if amnioinfusion for thick meconium stained amniotic fluid results in a reduction in perinatal death or moderate to severe meconium aspiration syndrome. We will also assess the effects of amnioinfusion on other indicators of neonatal morbidity and on cesarean section. The study includes an evaluation of womens views on their childbirth experience and an economic evaluation of a policy of amnioinfusion The study will be achieved with the collaboration of approximately 50 obstetrical centres from across Canada, US, Europe, South America and South Africa. This multicentre trial will provide urgently needed information on the efficacy and effectiveness of amniofusion for the indication of meconium stained amniotic fluid.

CADASIL: Treatment and Management Options.

PubMed

Bersano, Anna; Bedini, Gloria; Oskam, Joshua; Mariotti, Caterina; Taroni, Franco; Baratta, Silvia; Parati, Eugenio Agostino

2017-09-01

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

Maintenance Cognitive Stimulation Therapy (CST) for dementia: A single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia

PubMed Central

2010-01-01

Background Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. Methods/Design This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks. The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. Discussion A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors. Trial Registration ISRCTN26286067 PMID:20426866

Maintenance Cognitive Stimulation Therapy (CST) for dementia: a single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia.

PubMed

Aguirre, Elisa; Spector, Aimee; Hoe, Juanita; Russell, Ian T; Knapp, Martin; Woods, Robert T; Orrell, Martin

2010-04-28

Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks.The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors.

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years.

PubMed

Willett, Keith; Keene, David J; Morgan, Lesley; Gray, Bridget; Handley, Robert; Chesser, Tim; Pallister, Ian; Tutton, Elizabeth; Knox, Christopher; Lall, Ranjit; Briggs, Andrew; Lamb, Sarah E

2014-03-12

Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Current Controlled Trials ISRCTN04180738.

[Introduction of capillary glycosylated haemoglobin determination in a Primary Care Health Area: Multicentre study of the evolution of patients with type 2 diabetes mellitus].

PubMed

Núñez-Sánchez, M Á; Cervantes-Cuesta, M Á; Brocal-Ibañez, P; Salmeron-Arjona, E; León-Martínez, L P; Cerezo-Sanmartin, M

The aim of this study was to evaluate the efficiency of a joint intervention that included educational components, self-assessment, and information to optimise diabetes control through the introduction of instant capillary glycosylated haemoglobin (HbA1c) determination in Primary Care. A multicentre prospective descriptive study was carried out over 3years in 10Primary Care Centres of the Area VII Murcia East. At the end of the study there were 804 patients with type 2 diabetes (DM2). Patients were divided into 4 groups based on initial values of HbA1c, and if changes in their treatment were needed. HbA1c, body mass index, and blood pressure were monitored. A financial assessment was also performed on the impact of the implementation of a protocol to measure instant capillary RESULTS: A significant reduction was observed in HbA1c values. The initial HbA1c mean value was 7.4±1.4%, which decreased to a final value of 6.9±1.0% (P<.001). At the end of the study, 71.4% of patients included reached diabetic control objectives. In addition, the financial assessment demonstrated that the implementation of this diabetes control system led to a decrease of the 24.7% in spending on glucose strips after the first year of study in Area VII Murcia Health Service. The introduction of capillary HbA1c determination in Primary Care has demonstrated to improve diabetes control and the efficiency of the health personnel. Furthermore, a reduction in the health costs of patients with DM2 was also shown. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Epidemiological multicentre study on the education provided to patients with type 2 diabetes mellitus in the Spanish Health Care System. The Forma2 study.

PubMed

García-Donaire, J A; Franch-Nadal, J; Rodríguez-Fortúnez, P; Labrador-Barba, E; Orera-Peña, M L; Rodríguez de Miguel, M

The purpose of the present study was to characterize the education that patients with type 2 diabetes mellitus receive, and to identify differences as regards the presence of insulin therapy or not. This crossover, multicentre and descriptive study involved 1066 Spanish physicians who completed a questionnaire on Internet. The physicians that responded had a mean of 26.0 years of experience in healthcare, and mainly worked in a walk-in clinic in an urban area. Physicians rated the level of patient knowledge about their disease on a 5.0 point-scale. Fifty percent of them indicated that they spent between 15 and 30min in educating patients at the time of diagnosis. Previous control with HbA1c>9%, presence of microvascular complications, and a low socio-cultural level, were factors associated with spending more time in education. This is the first study designed to evaluate the education provided to patients with type 2 diabetes mellitus from Spain. The time spent and the individualization of the education are important factors associated with better long-term control of the disease, and thus with the effectiveness of the clinical management. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Is screening for fetal anomalies reliable in HIV-infected pregnant women? A multicentre study.

PubMed

Brossard, Philippe; Boulvain, Michel; Coll, Oriol; Barlow, Patricia; Aebi-Popp, Karoline; Bischof, Paul; Martinez de Tejada, Begoña

2008-10-01

To assess the impact of HIV infection on the reliability of the first-trimester screening for Down syndrome, using free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency, and of the second-trimester screening for neural tube defects, using alpha-fetoprotein. Multicentre study comparing the multiples of the median of markers for Down syndrome and neural tube defect screening among 214 HIV-infected pregnant women and 856 HIV-negative controls undergoing a first-trimester Down syndrome screening test, and 209 HIV-positive women and 836 HIV-negative controls with a risk evaluation for neural tube defect. The influence of treatment, chronic hepatitis and HIV disease characteristics were also evaluated. Multiples of the median medians for pregnancy-associated plasma protein-A and beta-human chorionic gonadotrophin were lower in HIV-positive women than controls (0.88 vs. 1.05 and 0.84 vs. 1.09, respectively; P < 0.005), but these differences had no impact on risk estimation; no differences were observed for the other markers. No association was found between HIV disease characteristics, antiretroviral treatment use at the time of screening or chronic hepatitis and marker levels. Screening for Down syndrome during the first trimester and for neural tube defect during the second trimester is accurate for HIV-infected women and should be offered, similar to HIV-negative women.

Work productivity and activity impairment in gastroesophageal reflux disease in Korean full-time employees: a multicentre study.

PubMed

Shin, Woon Geon; Kim, Heung Up; Kim, Sang Gyun; Kim, Gwang Ha; Shim, Ki-Nam; Kim, Jeong Wook; Kim, Jin Il; Kim, Jae Gyu; Kim, Jae J; Yim, Da-Hae; Park, Sue K; Park, Soo-Heon

2012-04-01

The costs of gastroesophageal reflux disease have not been assessed in Asia, even though the prevalence of gastroesophageal reflux disease is gradually increasing. We evaluated work presenteeism and absenteeism as indirect costs of gastroesophageal reflux disease in Korea. This was a cross-sectional and multicentre study using patient-reported outcome instruments. A total of 1009 full-time employees who visited the gastrointestinal department for any reason (281 patients with gastroesophageal reflux disease and 728 controls) were included. Main outcomes were presenteeism and absenteeism measured as work productivity loss and monetary cost per week. Absenteeism and presenteeism were significantly higher in the gastroesophageal reflux disease than the control group (1.49% vs. 0.46%, P=0.0010; 34.13% vs. 9.23%, P<0.0001). Loss of work productivity was significantly greater in the gastroesophageal reflux disease than the control group (33.09% vs. 9.02%; P<0.0001). This loss of work productivity difference between the two groups represented an additional productivity loss of 11.7h/week in the gastroesophageal reflux disease group compared with the control group. Assuming average hourly wages of $14.12, the weekly burden of gastroesophageal reflux disease reached $165.07 per person. Gastroesophageal reflux disease was associated with substantial work productivity loss, mainly due to presenteeism rather than absenteeism, in Korean full-time employees. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Impact of rapid antigen detection testing on antibiotic prescription in acute pharyngitis in adults. FARINGOCAT STUDY: a multicentric randomized controlled trial

PubMed Central

2010-01-01

Background Acute pharyngitis is one of the most frequent consultations to the general practitioner and in most of the cases an antibiotic is prescribed in primary care in Spain. Bacterial etiology, mainly by group A beta-hemolytic streptococcus (GABHS), accounts for 10-20% of all these infections in adults. The purpose of this study is to assess the impact of rapid antigen detection testing (RADT) to identify GABHS in acute pharyngitis on the utilization of antibiotics in primary care. Methods/design Multicentric randomized controlled trial in which antibiotic prescription between two groups of patients with acute pharyngitis will be compared. The trial will include two arms, a control and an intervention group in which RADT will be performed. The primary outcome measure will be the proportion of inappropriate antibiotic prescription in each group. Two hundred seventy-six patients are required to detect a reduction in antibiotic prescription from 85% in the control group to 75% in the intervention group with a power of 90% and a level of significance of 5%. Secondary outcome measures will be specific antibiotic treatment, antibiotic resistance rates, secondary effects, days without working, medical visits during the first month and patient satisfaction. Discussion The implementation of RADT would allow a more rational use of antibiotics and would prevent adverse effects of antibiotics, emergence of antibiotic resistance and the growth of inefficient health expenses. Trial registration ISRCTN23587778 PMID:20331895

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

PubMed

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-12-21

Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

[Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized].

PubMed

Glinski, W; Chodynicka, B; Roszkiewicz, J; Bogdanowski, T; Lecewicz-Torun, B; Kaszuba, A; Bowszyc, J; Nowak, A; Wnorowski, J; Wasik, F; Glinska-Ferenz, M; Blaszczyk, M; Strzyga, P; Pachocki, R

2001-04-01

To determine the increase in healing rate of venous ulcer in patients receiving a micronised purified flavonoid fraction (MPFF) as supplementation to standard local care. A randomised, open, controlled, multicentre study. Departments of Dermatology and University Outpatients Clinics. One hundred and forty patients with chronic venous insufficiency and venous ulcers. PATIENTS received standard compressive therapy plus external treatment alone or 2 tablets of MPFF daily in addition to the above treatment for 24 weeks. Healing of ulcers and their reduction in size after 24 weeks of treatment. The percentage of patients whose ulcers healed completely was found to be markedly higher in those receiving MPFF in addition to standard external and compressive treatment than in those treated with conventional therapy alone (46.5% vs 27.5%; p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of patients in the MPFF group and in 50% of patients in the control group, whereas ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients (p<0.05), respectively. The mean reduction in ulcer size was also found to be greater in patients treated with MPFF (80%) than in the control group (65%) (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group was 1026.2 compared with 1871.8 in the control group. These results indicate that MPFF significantly improves the cure rate in patients with chronic venous insufficiency.

Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study

PubMed Central

Diav-Citrin, Orna; Shechtman, Svetlana; Weinbaum, Dafna; Wajnberg, Rebecka; Avgil, Meytal; Di Gianantonio, Elena; Clementi, Maurizio; Weber-Schoendorfer, Corinna; Schaefer, Christof; Ornoy, Asher

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT In recent years there has been concern regarding the possibility that selective serotonin reuptake inhibitors (SSRIs) cause an increased rate of congenital cardiovascular anomalies. As of today, there is still debate in the literature as to the possible effects of paroxetine and fluoxetine on the embryonic cardiovascular system. WHAT THIS STUDY ADDS Based on prospective data from three Teratogen Information Services, we have demonstrated an increased rate of congenital cardiovascular anomalies among the offspring of fluoxetine- and paroxetine-treated mothers. AIMS Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine. METHODS This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens. RESULTS We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of ≥10 cigarettes day−1 and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. CONCLUSION This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. PMID:18754846

The Plasma-Lyte 148 v Saline (PLUS) study protocol: a multicentre, randomised controlled trial of the effect of intensive care fluid therapy on mortality.

PubMed

Hammond, Naomi E; Bellomo, Rinaldo; Gallagher, Martin; Gattas, David; Glass, Parisa; Mackle, Diane; Micallef, Sharon; Myburgh, John; Saxena, Manoj; Taylor, Colman; Young, Paul; Finfer, Simon

2017-09-01

0.9% sodium chloride (saline) is the most commonly administered resuscitation fluid on a global basis but emerging evidence suggests that its high chloride content may have important adverse effects. To describe the study protocol for the Plasma- Lyte 148 v Saline study, which will test the hypothesis that in critically ill adult patients the use of Plasma-Lyte 148 (a buffered crystalloid solution) for fluid therapy results in different 90-day all-cause mortality when compared with saline. We will conduct this multicentre, blinded, randomised controlled trial in approximately 50 intensive care units in Australia and New Zealand. We will randomly assign 8800 patients to either Plasma-Lyte 148 or saline for all resuscitation fluid, maintenance fluid and compatible drug dilution therapy while in the ICU for up to 90 days after randomisation. The primary outcome is 90-day all-cause mortality; secondary outcomes include mean and peak creatinine concentration, incidence of renal replacement therapy, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, ICU and hospital length of stay, and quality of life and health services use at 6 months. The PLUS study will provide high-quality data on the comparative safety and efficacy of Plasma-Lyte 148 compared with saline for resuscitation and compatible crystalloid fluid therapy in critically ill adult patients.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case–control study in the UK

PubMed Central

Pallawela, S N S; Sullivan, A K; Macdonald, N; French, P; White, J; Dean, G; Smith, A; Winter, A J; Mandalia, S; Alexander, S; Ison, C; Ward, H

2014-01-01

Objective Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the UK in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. Design A prospective multicentre case–control study was conducted at six UK hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Methods Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Results Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. Conclusions This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. PMID:24687130

The burden of common skin diseases assessed with the EQ5D™: a European multicentre study in 13 countries.

PubMed

Balieva, F; Kupfer, J; Lien, L; Gieler, U; Finlay, A Y; Tomás-Aragonés, L; Poot, F; Misery, L; Sampogna, F; van Middendorp, H; Halvorsen, J A; Szepietowski, J C; Lvov, A; Marrón, S E; Salek, M S; Dalgard, F J

2017-05-01

Generic instruments measuring health-related quality of life (HRQoL), like EQ5D™, enable comparison of skin diseases with healthy populations and nondermatological medical conditions, as well as calculation of utility data. To measure HRQoL in patients with common skin diseases and healthy controls across Europe using the EQ5D. This multicentre observational cross-sectional study was conducted in 13 European countries. Each dermatology clinic recruited at least 250 consecutive adult outpatients to complete questionnaires, including the EQ5D. There were 5369 participants (4010 patients and 1359 controls). Mean ± SD self-rated health state reported by patients was 69·9 ± 19·7; for controls it was 82·2 ± 15·5. When adjusted for confounding factors, including comorbidity, mean patient EQ visual analogue scores were 10·5 points lower than for controls (standardized β = -0·23). Odds ratio with 95% confidence interval for impairment in all five dimensions of EQ5D adjusted for confounders was doubled for patients compared with controls. Patients with hidradenitis suppurativa (HS), blistering conditions, leg ulcers, psoriasis and eczemas had the highest risk for reduction in HRQoL in most dimensions (2-10-fold). Data on differences of impairment by dimensions offer new insights. This study confirms the large impact skin conditions have on patients' well-being, differentiating between aspects of HRQoL. Patients with HS, blistering diseases, leg ulcers, infections and most chronic skin diseases reported reduced HRQoL compared with patients with chronic obstructive lung disease, diabetes mellitus, cardiovascular disease and cancers. These findings are important in the prioritization of resource allocation between medical fields and within dermatological subspecialities. © 2016 British Association of Dermatologists.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

PubMed

Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-08-01

This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study

PubMed Central

Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-01-01

Objectives This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. Design A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. Results In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74–1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43–0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5–3.0). Conclusion Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925. PMID:24917966

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

PubMed

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

2016-10-01

Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO 2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

Impact of tailored patient education on adherence of patients with chronic myeloid leukaemia to tyrosine kinase inhibitors: a randomized multicentre intervention study.

PubMed

Kekäle, Meri; Söderlund, Tim; Koskenvesa, Perttu; Talvensaari, Kimmo; Airaksinen, Marja

2016-09-01

The aim of this study was to evaluate the influence of tailored patient education on adherence to tyrosine kinase inhibitor medication among patients with chronic myeloid leukaemia. Management of chronic myeloid leukaemia has changed dramatically during the last decade. While medication adherence is crucial to clinical response, little is known about how to improve patients' adherence. Randomized multicentre intervention study. The study was conducted between June 2012-August 2014. Eighty-six patients with chronic myeloid leukaemia who had been on tyrosine kinase inhibitor medication for at least six months from eight hospitals were randomized into intervention and control groups. Intervention combined nurse-conducted medication counselling, an information booklet, video and website and text message reminders. Patients were interviewed to assess medication adherence using Morisky's 8-Item Medication Adherence Scale at baseline and nine months. Medication adherence improved with the adherence aids used. At nine months, 51% of patients were highly adherent in the intervention group, compared with 21% in the control group. Adherence improved for a higher proportion of patients in the intervention group than the control group (49% vs. 18%). Morisky's score decreased in almost half of control group cases. Patients were most satisfied with face-to-face counselling (86%) and the information booklet (83%) and least satisfied with text messages (9%). Tailored patient education improved the medication adherence of patients with chronic myeloid leukaemia. Without this, adherence behaviour tended to decline. Personal communication with a nurse proved to be an essential part of adherence support and should not be ignored. © 2016 John Wiley & Sons Ltd.

Risk and protective factors for falls on stairs in young children: multicentre case–control study

PubMed Central

Kendrick, D; Zou, K; Ablewhite, J; Watson, M; Coupland, C; Kay, B; Hawkins, A; Reading, R

2016-01-01

Aim To investigate risk and protective factors for stair falls in children aged <5 years. Methods Multicentre case–control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated. Results Cases’ most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%). Conclusion Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries. PMID:26662926

Risk and protective factors for falls on one level in young children: multicentre case-control study.

PubMed

Benford, P; Young, B; Coupland, C; Watson, M; Hindmarch, P; Hayes, M; Goodenough, T; Majsak-Newman, G; Kendrick, D

2015-12-01

Childhood falls are an important global public health problem, but there is lack of evidence about their prevention. Falls on one level result in considerable morbidity and they are costly to health services. To estimate ORs for falls on one level in children aged 0-4 years for a range of safety behaviours, safety equipment use and home hazards. Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Participants included 582 children less than 5 years of age with a medically attended fall injury occurring at home and 2460 controls matched on age, sex, calendar time and study centre. Fall on one level. Cases' most common injuries were bangs on the head (52%), cuts or grazes not needing stitches (29%) or cuts or grazes needing stitches (17%). Comparing cases to community controls in the adjusted analyses, significant findings were observed for only two exposures. Injured children were significantly less likely to live in a household without furniture corner covers (adjusted OR (AOR) 0.72, 95% CI 0.55 to 0.95), or without rugs and carpets firmly fixed to the floor (AOR 0.76, 95% CI 0.59 to 0.98). We did not find any safety practices, use of safety equipment or home hazards associated with a reduced risk of fall on one level. Our findings do not provide evidence to support changes to current injury prevention practice. 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/

Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.

PubMed

Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E; Mazor, Tali; Jones, Lindsey E; Wood, Matthew D; Walsh, Kyle M; Bengtsson, Henrik; Hong, Chibo; Oberndorfer, Stefan; Roetzer, Thomas; Smirnov, Ivan V; Clarke, Jennifer L; Aghi, Manish K; Chang, Susan M; Nelson, Sarah J; Woehrer, Adelheid; Phillips, Joanna J; Solomon, David A; Costello, Joseph F

2018-04-09

Rare multicentric lower-grade gliomas (LGGs) represent a unique opportunity to study the heterogeneity among distinct tumor foci in a single patient and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology, and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the 2 lesions. One patient was diagnosed with multicentric isocitrate dehydrogenase 1 (IDH1) mutated diffuse astrocytomas harboring distinct IDH1 mutations, R132H and R132C; the latter mutation has been associated with Li-Fraumeni syndrome, which was subsequently confirmed in the patient's germline DNA and shown in additional cases with The Cancer Genome Atlas data. In another patient, phylogenetic analysis of synchronously arising grade II and grade III diffuse astrocytomas demonstrated a single shared mutation, IDH1 R132H, and revealed convergent evolution via non-overlapping mutations in ATRX and TP53. In 2 cases, there was divergent evolution of IDH1-mutated and 1p/19q-codeleted oligodendroglioma and IDH1-mutated and 1p/19q-intact diffuse astrocytoma, occurring synchronously in one case and metachronously in a second. Each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors. Comprehensive sampling of these lesions can therefore significantly alter diagnosis and management. Additionally, somatic IDH1 R132C mutation in either multicentric or solitary LGG identifies unsuspected germline TP53 mutation, validating the limited number of published cases.

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial.

PubMed

van de Ven, J; Fransen, A F; Schuit, E; van Runnard Heimel, P J; Mol, B W; Oei, S G

2017-09-01

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time. Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy. During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter. The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or implemented, repetitive training sessions every three months seem therefore recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Glutamine--from conditionally essential to totally dispensable?

PubMed

Wernerman, Jan

2014-07-02

Recently a large multicentre randomised controlled trial in critically ill patients reported harm to the patients given supplementary glutamine. In the original publication, no explanation was offered for why this result was obtained; a large number of studies have reported beneficial effects or no effect, but never before reported harm. These results have been commented upon in a number of communications. Now some of the authors of the multicentre randomised controlled trial present a review and meta-analysis of glutamine supplementation, and the discrepancy of results is suggested to relate to intravenous administration to patients of supplementary glutamine via parenteral nutrition or a combination of enteral and parenteral nutrition in contrast to enteral administration of supplementation or a combination of enteral and parenteral supplementation. To explain results by epidemiological means only, by combining results into a meta-analysis, is perhaps not the best way to explain mechanisms behind results. Meta-analyses are primarily hypothesis generating. Launching treatment without a solid mechanistic explanation is always risky. Glutamine supplementation of the critically ill comes into that category. Now we will all have to do our homework and try to understand whether supplementation or omission of glutamine for patients fed parenterally is a good idea or not.

Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study.

PubMed

Mitrovic, Nikola; Delic, Dragan; Markovic-Denic, Ljiljana; Jovicic, Milica; Popovic, Natasa; Bojovic, Ksenija; Simonovic Babic, Jasmina; Svirtlih, Neda

2015-07-01

The epidemiological characteristics of hepatitis C virus (HCV) infection have not yet been described in Serbia. To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. A multicentre case-control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Ultrasound-guided breast-sparing surgery to improve cosmetic outcomes and quality of life. A prospective multicentre randomised controlled clinical trial comparing ultrasound-guided surgery to traditional palpation-guided surgery (COBALT trial)

PubMed Central

2011-01-01

Background Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life. Methods/design In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described. Conclusion The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life. Trial Registration Number Netherlands Trial Register (NTR): NTR2579 PMID:21410949

Poison prevention practices and medically attended poisoning in young children: multicentre case-control study.

PubMed

Kendrick, Denise; Majsak-Newman, Gosia; Benford, Penny; Coupland, Carol; Timblin, Clare; Hayes, Mike; Goodenough, Trudy; Hawkins, Adrian; Reading, Richard

2017-04-01

Childhood poisonings are common, placing a substantial burden on health services. Case-control studies have found inconsistent evidence about modifiable risk factors for poisonings among children aged 0-4 years. This study quantifies associations between poison prevention practices and medically attended poisonings in children aged 0-4 years. Multicentre case-control study conducted at hospitals, minor injury units and family practices from four study centres in England between 2010 and 2013. Participants comprised 567 children presenting with unintentional poisoning occurring at home and 2320 community control participants matched on age, sex, date of event and study centre. Parents/caregivers provided data on safety practices, safety equipment use, home hazards and potential confounders by means of self-completion questionnaires. Data were analysed using conditional logistic regression. Compared with community controls, parents of poisoned children were significantly more likely not to store medicines out of reach (adjusted OR (AOR) 1.59; 95% CI 1.21 to 2.09; population attributable fraction (PAF) 15%), not to store medicines safely (locked or out of reach (AOR 1.83; 95% CI 1.38 to 2.42; PAF 16%) and not to have put all medicines (AOR 2.11; 95% CI 1.54 to 2.90; PAF 20%) or household products (AOR 1.79, 95% CI 1.29 to 2.48; PAF 11%) away immediately after use. Not storing medicines out of reach or locked away and not putting medicines and household products away immediately after use increased the odds of secondary care attended poisonings in children aged 0-4 years. If associations are causal, implementing these poison prevention practices could each prevent between 11% and 20% of poisonings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial.

PubMed

Li, Yanping; Hu, Xiaoqi; Zhang, Qian; Liu, Ailing; Fang, Hongyun; Hao, Linan; Duan, Yifan; Xu, Haiquan; Shang, Xianwen; Ma, Jun; Xu, Guifa; Du, Lin; Li, Ying; Guo, Hongwei; Li, Tingyu; Ma, Guansheng

2010-05-02

Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity. The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure. Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

Cycle control and side effects of a new combiphasic oral contraceptive regimen.

PubMed

Dieben, T O; op ten Berg, M T; Coelingh Bennink, H J

1994-07-01

In a multicentre study 882 women were treated during a total of 12,850 cycles with a new combiphasic contraceptive: CTR 24. The study period was 18 cycles. The combiphasic preparation CTR 24 contains 25 micrograms desogestrel (CAS 54024-22-5) plus 40 micrograms ethinylestradiol (CAS 57-63-6) daily for the first 7 days followed by the combination of 125 micrograms desogestrel and 30 micrograms ethinyl-estradiol daily for the subsequent 15 days. The bleeding patterns were analysed over pill cycles and a comparison was made between starters and switchers. The cycle control of the combination was very good. The side effect profile was favourable.

Medicine in spine exercise (MiSpEx) for nonspecific low back pain patients: study protocol for a multicentre, single-blind randomized controlled trial.

PubMed

Niederer, Daniel; Vogt, Lutz; Wippert, Pia-Maria; Puschmann, Anne-Katrin; Pfeifer, Ann-Christin; Schiltenwolf, Marcus; Banzer, Winfried; Mayer, Frank

2016-10-20

Arising from the relevance of sensorimotor training in the therapy of nonspecific low back pain patients and from the value of individualized therapy, the present trial aims to test the feasibility and efficacy of individualized sensorimotor training interventions in patients suffering from nonspecific low back pain. A multicentre, single-blind two-armed randomized controlled trial to evaluate the effects of a 12-week (3 weeks supervised centre-based and 9 weeks home-based) individualized sensorimotor exercise program is performed. The control group stays inactive during this period. Outcomes are pain, and pain-associated function as well as motor function in adults with nonspecific low back pain. Each participant is scheduled to five measurement dates: baseline (M1), following centre-based training (M2), following home-based training (M3) and at two follow-up time points 6 months (M4) and 12 months (M5) after M1. All investigations and the assessment of the primary and secondary outcomes are performed in a standardized order: questionnaires - clinical examination - biomechanics (motor function). Subsequent statistical procedures are executed after the examination of underlying assumptions for parametric or rather non-parametric testing. The results and practical relevance of the study will be of clinical and practical relevance not only for researchers and policy makers but also for the general population suffering from nonspecific low back pain. Identification number DRKS00010129. German Clinical Trial registered on 3 March 2016.

Reliability of intra-oral quantitative sensory testing (QST) in patients with atypical odontalgia and healthy controls - a multicentre study.

PubMed

Baad-Hansen, L; Pigg, M; Yang, G; List, T; Svensson, P; Drangsholt, M

2015-02-01

The reliability of comprehensive intra-oral quantitative sensory testing (QST) protocol has not been examined systematically in patients with chronic oro-facial pain. The aim of the present multicentre study was to examine test-retest and interexaminer reliability of intra-oral QST measures in terms of absolute values and z-scores as well as within-session coefficients of variation (CV) values in patients with atypical odontalgia (AO) and healthy pain-free controls. Forty-five patients with AO and 68 healthy controls were subjected to bilateral intra-oral gingival QST and unilateral extratrigeminal QST (thenar) on three occasions (twice on 1 day by two different examiners and once approximately 1 week later by one of the examiners). Intra-class correlation coefficients and kappa values for interexaminer and test-retest reliability were computed. Most of the standardised intra-oral QST measures showed fair to excellent interexaminer (9-12 of 13 measures) and test-retest (7-11 of 13 measures) reliability. Furthermore, no robust differences in reliability measures or within-session variability (CV) were detected between patients with AO and the healthy reference group. These reliability results in chronic orofacial pain patients support earlier suggestions based on data from healthy subjects that intra-oral QST is sufficiently reliable for use as a part of a comprehensive evaluation of patients with somatosensory disturbances or neuropathic pain in the trigeminal region. © 2014 John Wiley & Sons Ltd.

Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

PubMed

Mohanty, D; Colah, R B; Gorakshakar, A C; Patel, R Z; Master, D C; Mahanta, J; Sharma, S K; Chaudhari, U; Ghosh, M; Das, S; Britt, R P; Singh, S; Ross, C; Jagannathan, L; Kaul, R; Shukla, D K; Muthuswamy, V

2013-01-01

The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA(2), HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of β-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of β-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δβ-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE β-thalassemia as well as HbS homozygous and HbS-β-thalassemia (<1 %) were also identified. This is the first large multicentre study covering cities from different regions of the country for screening for β-thalassemia carriers and other haemoglobinopathies where uniform protocols and methodology was followed and quality control ensured by the co-ordinating centre. This study also shows that establishment of centres for screening for β-thalassemia and other haemoglobinopathies is possible in medical colleges. Creating awareness, screening and counselling can be done at these centres. This experience will help to formulate a national thalassemia control programme in India.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

PubMed

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study

PubMed Central

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Background Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. Methods In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. Results The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Conclusions Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients. PMID:26418536

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

PubMed

Zhang, Qin-hong; Yue, Jin-huan; Li, Chao-ran; Sun, Zhong-ren

2014-12-30

Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. ChiCTR-TRC-13003959. 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.

Reappraisal of known malaria resistance loci in a large multi-centre study

PubMed Central

Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

2015-01-01

Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933

Does cataract surgery alleviate poverty? Evidence from a multi-centre intervention study conducted in Kenya, the Philippines and Bangladesh.

PubMed

Kuper, Hannah; Polack, Sarah; Mathenge, Wanjiku; Eusebio, Cristina; Wadud, Zakia; Rashid, Mamunur; Foster, Allen

2010-11-09

Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh: $16 vs $24 p = 0.004, Philippines: $24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh: $23 vs $23 p = 0.20, Philippines: $45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals.

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.

PubMed

van Rhee, Frits; Casper, Corey; Voorhees, Peter M; Fayad, Luis E; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle

2015-10-06

Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥ 3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥ 3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab.

Are power calculations useful? A multicentre neuroimaging study

PubMed Central

Suckling, John; Henty, Julian; Ecker, Christine; Deoni, Sean C; Lombardo, Michael V; Baron-Cohen, Simon; Jezzard, Peter; Barnes, Anna; Chakrabarti, Bhismadev; Ooi, Cinly; Lai, Meng-Chuan; Williams, Steven C; Murphy, Declan GM; Bullmore, Edward

2014-01-01

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources. PMID:24644267

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years

PubMed Central

2014-01-01

Background Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. Methods/Design This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. Discussion This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Trial registration Current Controlled Trials ISRCTN04180738. PMID:24621174

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut.

PubMed

van der Valk, Johanna P M; Gerth van Wijk, Roy; Dubois, Anthony E J; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F J; Wichers, Harry J; de Jong, Nicolette W

2016-01-01

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. A total of 179 children were included (median age 9.0 years; range 2-17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. www.ncbi.nlm.nih.gov/pubmed NTR3572.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

PubMed Central

van der Valk, Johanna P. M.; Gerth van Wijk, Roy; Dubois, Anthony E. J.; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F. J.; Wichers, Harry J.; de Jong, Nicolette W.

2016-01-01

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. Trial Registration www.ncbi.nlm.nih.gov/pubmed NTR3572 PMID:26967158

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

[Sentinel node biopsy in patients with multifocal and multicentric breast cancer: A 5-year follow-up].

PubMed

Blanco Saiz, I; López Carballo, M T; Martínez Fernández, J; Carrión Maldonado, J; Cabrera Pereira, A; Moral Alvarez, S; Santamaría Girón, L; Cantero Cerquella, F; López Secades, A; Díaz González, D; Llaneza Folgueras, A; Aira Delgado, F J

2014-01-01

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months). Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Measurement of HbA1c in multicentre diabetes trials - should blood samples be tested locally or sent to a central laboratory: an agreement analysis.

PubMed

Arch, Barbara N; Blair, Joanne; McKay, Andrew; Gregory, John W; Newland, Paul; Gamble, Carrol

2016-10-24

Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For multicentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a central laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up data collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes. HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and 12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of agreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of error between measurements was subjectively set as ±10 % for HbA1c. The percentage of pairs of measurements that were classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within centres. Treatment group was not considered. Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four follow-up time points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD = 4.5, 95 % CI -0.2 to 0.5) higher than central. The 95 % limits of agreement were -8.6 to 9.0 mmol/mol (local minus central). Eighty percent of local measurements were within ±10 % of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias. Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected and standard deviations were similar. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements. We recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting. Eudract No. 2010-023792-25 , registered on 4 November 2010.

Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study.

PubMed

Ebner, Thomas; Montag, Markus; Montag, M; Van der Ven, K; Van der Ven, H; Ebner, T; Shebl, O; Oppelt, P; Hirchenhain, J; Krüssel, J; Maxrath, B; Gnoth, C; Friol, K; Tigges, J; Wünsch, E; Luckhaus, J; Beerkotte, A; Weiss, D; Grunwald, K; Struller, D; Etien, C

2015-04-01

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles (P < 0.001). Further splitting of the historical control group into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed that all groups significantly benefitted (P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

[Local approval procedures act as a brake on RCTs].

PubMed

van der Stok, E P; Huiskens, J; Hemmes, B; Grünhagen, D J; van Gulik, T M; Verhoef, C; Punt, C J A

2016-01-01

Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. Retrospective, descriptive. All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from € 0-€ 1750, and amounted to € 8575 for all procedures combined. No costs were charged by the majority of the centres. The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context.

Effects of an alert system on implantable cardioverter defibrillator-related anxiety: rationale, design, and endpoints of the PANORAMIC multicentre trial.

PubMed

Duru, Firat; Dorian, Paul; Favale, Stefano; Perings, Christian; Pedersen, Susanne S; Willems, Vincent

2010-05-01

Implantable cardioverter defibrillators (ICD) can prevent sudden cardiac death by delivering high-energy shocks in patients at risk of life-threatening ventricular tachyarrhythmias. Patients may be anxious about receiving inappropriate shocks in case of device or lead system malfunction, or about failing to receive needed therapy for the same reason. New devices include programmable vibrating patient notifiers (PN), which, by warning patients of a possible device dysfunction, might lower device-related anxiety. PAtient NOtifier feature for Reduction of Anxiety: a Multicentre ICD study (PANORAMIC) is a multicentre, randomized, clinical trial designed to examine the effects of the awareness of an active vibrating alert system on device-related anxiety. The trial will randomly assign 356 patients in a 1:1 design to a control group (PN OFF) vs. a treatment group (PN ON). Patients will be followed for 12 months, with visits scheduled at 6 and 12 months. During clinical follow-up visits, the ICD will be interrogated, and all patients will complete the Hospital Anxiety and Depression Scale and a device-related anxiety questionnaire. The sensitivity and specificity of PN, the effect of personality on anxiety, using the Type D scale (DS14), the number of delivered appropriate and inappropriate ICD therapies, changes in anxiety related to the delivery of appropriate or inappropriate shocks, crossovers from the assigned group, the number of hospitalizations, and the mortality rate will also be assessed. ClinicalTrials.gov Identifier: NCT00559559.

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © 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.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study

PubMed Central

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-01-01

Background Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). Methods In-depth semi-structured telephone interviews were conducted in 2003–04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. Results The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. Conclusion This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research. PMID:17184521

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Occupational risk factors for urothelial carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter Urothelial and Renal Cancer.

PubMed

Pesch, B; Haerting, J; Ranft, U; Klimpel, A; Oelschlägel, B; Schill, W

2000-04-01

This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons (PAH), and chlorinated hydrocarbons besides other suspected risk factors. In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age. Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI: 1.1-2.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix: OR = 1.8, 95% CI: 1.2-2.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI: 1.4-3.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution. Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents.

Positive and cost-effectiveness effect of spa therapy on the resumption of occupational and non-occupational activities in women in breast cancer remission: a French multicentre randomised controlled trial.

PubMed

Mourgues, Charline; Gerbaud, Laurent; Leger, Stéphanie; Auclair, Candy; Peyrol, Fleur; Blanquet, Marie; Kwiatkowski, Fabrice; Leger-Enreille, Anne; Bignon, Yves-Jean

2014-10-01

The main aim was to assess the effects of a spa treatment on the resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. A cost-effectiveness analysis (CEA) was also performed. A multicentre randomised controlled trial was carried out between 2008 and 2010 in the University Hospital of Auvergne and two private hospitals in Clermont-Ferrand, France. Eligible patients were women in complete breast cancer remission without contraindication for physical activities or cognitive disorders and a body mass index between 18.5 and 40 kg/m(2). The intervention group underwent spa treatment combined with consultation with dietician whereas the control underwent consultations with the dietician only. Of the 181 patients randomised, 92 and 89 were included in the intervention and the control groups, respectively. The CEA involved 90 patients, 42 from the intervention group and 48 from the control group. The main results showed a higher rate of resumption of occupational activities in the intervention group (p = 0.0025) and a positive effect of the intervention on the women's ability to perform occupational activities 12 months after the beginning of the study (p = 0.0014), and on their ability to perform family activities (p = 0.033). The stay in a thermal centre was cost-effective at 12 months. Spa treatment is a cost-effective strategy to improve resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic Resonance Enterography to Assess Multifocal and Multicentric Bowel Endometriosis.

PubMed

Nyangoh Timoh, Krystel; Stewart, Zelda; Benjoar, Mikhael; Beldjord, Selma; Ballester, Marcos; Bazot, Marc; Thomassin-Naggara, Isabelle; Darai, Emile

To prospectively determine the accuracy of magnetic resonance enterography (MRE) compared with conventional magnetic resonance imaging (MRI) for multifocal (i.e., multiple lesions affecting the same digestive segment) and multicentric (i.e., multiple lesions affecting several digestive segments) bowel endometriosis. A prospective study (Canadian Task Force classification II-2). Tenon University Hospital, Paris, France. Patients with MRI-suspected colorectal endometriosis scheduled for colorectal resection from April 2014 to February 2016 were included. Patients underwent both 1.5-Tesla MRI and MRE as well as laparoscopically assisted and open colorectal resections. The diagnostic performance of MRI and MRE was evaluated for sensitivity, specificity, positive and negative predictive values, accuracy, and positive and negative likelihood ratios (LRs). The interobserver variability of the experienced and junior radiologists was quantified using weighted statistics. Forty-seven patients were included. Twenty-two (46.8%) patients had unifocal lesions, 14 (30%) had multifocal lesions, and 11 (23.4%) had multicentric lesions. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multifocal lesions were 0.29 (6/21), 1.00 (23/24), 15.36, and 0.71 for MRI and 0.57 (12/21), 0.89 (23/25), 4.95, and 0.58 for MRE. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multicentric lesions were 0.18 (1/11), 1.00 (1/1), 15, and 0.80 for MRI and 0.46 (5/11), 0.92 (33/36), 5.45, and 0.60 for MRE. Lower accuracies for MRI compared with MRE to diagnose multicentric (p = .01) and multifocal lesions (p = .004) were noted. The interobserver agreement for MRE was good for both multifocality (κ = 0.80) and multicentricity (κ = 0.61). MRE has better accuracy for diagnosing multifocal and multicentric bowel endometriosis than conventional MRI. Copyright © 2018. Published by Elsevier Inc.

Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy.

PubMed

Chronowski, G M; Ha, C S; Wilder, R B; Cabanillas, F; Manning, J; Cox, J D

2001-08-01

Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Copyright 2001 American Cancer Society.

Multicentric myelolipoma in a dog.

PubMed

Kamiie, Junichi; Fueki, Keisuke; Amagai, Harumi; Ichikawa, Youichiro; Shirota, Kinji

2009-03-01

We report herein a case of multicentric myelolipoma in an 11-year-old beagle dog that presented with vomiting. Laparotomy demonstrated the presence of a large mass adherent to the greater omentum and multiple small white maculae in the spleen. Cytological and histological examinations revealed that the mass and maculae comprised mature adipocytes and hematopoietic elements including granulocytic, erythrocytic and megakaryocytic series in several phases of maturation and macrophages containing hemosiderin deposits, resembling bone marrow. Multicentric myelolipoma was diagnosed. This is first report of multicentric myelolipoma in a dog.

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial

PubMed Central

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-01-01

Introduction The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016–0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. Trial registration number The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. PMID:28801436

Catheter ablation in patients with persistent atrial fibrillation

PubMed Central

Kirchhof, Paulus; Calkins, Hugh

2017-01-01

Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi-centre trials. PMID:27389907

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

PubMed

Kołtowski, Łukasz; Aradi, Daniel; Huczek, Zenon; Tomaniak, Mariusz; Sibbing, Dirk; Filipiak, Krzysztof J; Kochman, Janusz; Balsam, Paweł; Opolski, Grzegorz

2016-01-01

High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. ClinicalTrials.gov: NCT01930773.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol

PubMed Central

García‐Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin‐Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García‐Gutiérrez, Susana

2017-01-01

Abstract Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. PMID:29154427

Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.

PubMed

Nilsagård, Ylva E; Forsberg, Anette S; von Koch, Lena

2013-02-01

The use of interactive video games is expanding within rehabilitation. The evidence base is, however, limited. Our aim was to evaluate the effects of a Nintendo Wii Fit® balance exercise programme on balance function and walking ability in people with multiple sclerosis (MS). A multi-centre, randomised, controlled single-blinded trial with random allocation to exercise or no exercise. The exercise group participated in a programme of 12 supervised 30-min sessions of balance exercises using Wii games, twice a week for 6-7 weeks. Primary outcome was the Timed Up and Go test (TUG). In total, 84 participants were enrolled; four were lost to follow-up. After the intervention, there were no statistically significant differences between groups but effect sizes for the TUG, TUGcognitive and, the Dynamic Gait Index (DGI) were moderate and small for all other measures. Statistically significant improvements within the exercise group were present for all measures (large to moderate effect sizes) except in walking speed and balance confidence. The non-exercise group showed statistically significant improvements for the Four Square Step Test and the DGI. In comparison with no intervention, a programme of supervised balance exercise using Nintendo Wii Fit® did not render statistically significant differences, but presented moderate effect sizes for several measures of balance performance.

Haptic-Based Neurorehabilitation in Poststroke Patients: A Feasibility Prospective Multicentre Trial for Robotics Hand Rehabilitation

PubMed Central

Daud Albasini, Omar A.; Oboe, Roberto; Tonin, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Piron, Lamberto

2013-01-01

Background. Haptic robots allow the exploitation of known motor learning mechanisms, representing a valuable option for motor treatment after stroke. The aim of this feasibility multicentre study was to test the clinical efficacy of a haptic prototype, for the recovery of hand function after stroke. Methods. A prospective pilot clinical trial was planned on 15 consecutive patients enrolled in 3 rehabilitation centre in Italy. All the framework features of the haptic robot (e.g., control loop, external communication, and graphic rendering for virtual reality) were implemented into a real-time MATLAB/Simulink environment, controlling a five-bar linkage able to provide forces up to 20 [N] at the end effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl-Meyer upper extremity scale; nine hold pegboard test) and kinematics (i.e., time; velocity; jerk metric; normalized jerk of standard movements) outcomes were assessed before and after treatment to detect changes in patients' motor performance. Reorganization of cortical activation was detected in one patient by fMRI. Results and Conclusions. All patients showed significant improvements in both clinical and kinematic outcomes. Additionally, fMRI results suggest that the proposed approach may promote a better cortical activation in the brain. PMID:24319496

Haptic-based neurorehabilitation in poststroke patients: a feasibility prospective multicentre trial for robotics hand rehabilitation.

PubMed

Turolla, Andrea; Daud Albasini, Omar A; Oboe, Roberto; Agostini, Michela; Tonin, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Venneri, Annalena; Piron, Lamberto

2013-01-01

Background. Haptic robots allow the exploitation of known motor learning mechanisms, representing a valuable option for motor treatment after stroke. The aim of this feasibility multicentre study was to test the clinical efficacy of a haptic prototype, for the recovery of hand function after stroke. Methods. A prospective pilot clinical trial was planned on 15 consecutive patients enrolled in 3 rehabilitation centre in Italy. All the framework features of the haptic robot (e.g., control loop, external communication, and graphic rendering for virtual reality) were implemented into a real-time MATLAB/Simulink environment, controlling a five-bar linkage able to provide forces up to 20 [N] at the end effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl-Meyer upper extremity scale; nine hold pegboard test) and kinematics (i.e., time; velocity; jerk metric; normalized jerk of standard movements) outcomes were assessed before and after treatment to detect changes in patients' motor performance. Reorganization of cortical activation was detected in one patient by fMRI. Results and Conclusions. All patients showed significant improvements in both clinical and kinematic outcomes. Additionally, fMRI results suggest that the proposed approach may promote a better cortical activation in the brain.

Low social interactions in eating disorder patients in childhood and adulthood: a multi-centre European case control study.

PubMed

Krug, Isabel; Penelo, Eva; Fernandez-Aranda, Fernando; Anderluh, Marija; Bellodi, Laura; Cellini, Elena; di Bernardo, Milena; Granero, Roser; Karwautz, Andreas; Nacmias, Benedetta; Ricca, Valdo; Sorbi, Sandro; Tchanturia, Kate; Wagner, Gudrun; Collier, David; Treasure, Janet

2013-01-01

The objective of this article was to examine lifestyle behaviours in eating disorder (ED) patients and healthy controls. A total of 801 ED patients and 727 healthy controls from five European countries completed the questions related to lifestyle behaviours of the Cross-Cultural Questionnaire (CCQ). For children, the ED sample exhibited more solitary activities (rigorously doing homework [p<0.001] and watching TV [p<0.05] and less socializing with friends [p<0.05]) than the healthy control group and this continued in adulthood. There were minimal differences across ED sub-diagnoses and various cross-cultural differences emerged. Reduced social activities may be an important risk and maintaining factor for ED symptomatology.

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial.

PubMed

Sivaprasad, Sobha; Arden, Geoffrey; Prevost, A Toby; Crosby-Nwaobi, Roxanne; Holmes, Helen; Kelly, Joanna; Murphy, Caroline; Rubin, Gary; Vasconcelos, Joanna; Hykin, Philip

2014-11-22

This study will evaluate hypoxia, as a novel concept in the pathogenesis of diabetic macular oedema (DMO). As the oxygen demand of the eye is maximum during dark-adaptation, we hypothesize that wearing light-masks during sleep will cause regression and prevent the development and progression of DMO. The study protocol comprises both an efficacy and mechanistic evaluation to test this hypothesis. This is a phase III randomised controlled single-masked multicentre clinical trial to test the clinical efficacy of light-masks at preventing dark-adaptation in the treatment of non-central DMO. Three hundred patients with non-centre-involving DMO in at least one eye will be randomised 1:1 to light-masks and control masks (with no light) to be used during sleep at night for a period of 24 months. The primary outcome is regression of non-central oedema by assessing change in the zone of maximal retinal thickness at baseline on optical coherence tomography (SD-OCT). Secondary outcomes will evaluate the prevention of development and progression of DMO by assessing changes in retinal thickness in different regions of the macula, macular volume, refracted visual acuity and level of retinopathy. Safety parameters will include sleep disturbance. Adverse events and measures of compliance will be assessed over 24 months. Participants recruited to the mechanistic sub-study will have additional retinal oximetry, multifocal electroretinography (ERG) and microperimetry to evaluate the role of hypoxia by assessing and comparing changes induced by supplemental oxygen and the light-masks at 12 months. The outcomes of this study will provide insight into the pathogenesis of DMO and provide evidence on whether a simple, non-invasive device in the form of a light-mask can help prevent the progression to centre-involving DMO and visual impairment in people with diabetes.

Electroacupuncture for insomnia disorder: study protocol for a randomized controlled trial.

PubMed

Kim, Sung-Phil; Kim, Joo-Hee; Kim, Bo-Kyung; Kim, Hyeong-Jun; Jung, In Chul; Cho, Jung Hyo; Kim, Jung-Eun; Kim, Mi-Kyung; Kwon, O-Jin; Kim, Ae-Ran; Park, Hyo-Ju; Seo, Bok-Nam

2017-04-13

Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia. In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit. The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder. Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial.

PubMed

Hollands, Kristen L; Pelton, Trudy A; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M; Wing, Alan M; Tyson, Sarah F; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M

2015-01-01

Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services. Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments. Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Clinicaltrials.gov NCT01600391.

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

PubMed

Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina

2018-03-01

Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants. Copyright © 2018.

Association of tobacco use and other determinants with pregnancy outcomes: a multicentre hospital-based case-control study in Karachi, Pakistan.

PubMed

Rozi, Shafquat; Butt, Zahid Ahmad; Zahid, Nida; Wasim, Saba; Shafique, Kashif

2016-09-20

The study aimed to identify the effects of maternal tobacco consumption during pregnancy and other factors on birth outcomes and obstetric complications in Karachi, Pakistan. A multicentre hospital-based case-control study. Four leading maternity hospitals of Karachi. A random sample of 1275 women coming to the gynaecology and obstetric department of selected hospitals for delivery was interviewed within 48 hours of delivery from wards. Cases were women with adverse birth outcomes and obstetric complications, while controls were women who had normal uncomplicated delivery. Adverse birth outcomes (preterm delivery, low birth weight, stillbirth, low Apgar score) and obstetric complications (antepartum haemorrhage, caesarean section, etc). Final multiple logistic regression analysis revealed that with every 1 year increase in age the odds of being a case was 1.03 times as compared with being a control. Tobacco use (adjusted OR (aOR): 2.24; 95% CI 1.56 to 3.23), having no slits in the kitchen (proxy indicator for indoor air pollution) (aOR=1.90; 95% CI 1.05 to 3.43), gravidity (aOR=0.83; 95% CI 0.73 to 0.93), non-booked hospital cases (aOR=1.87; 95% CI 1.38 to 2.74), history of stillbirth (aOR=4.06; 95% CI 2.36 to 6.97), miscarriages (aOR=1.91; 95% CI 1.27 to 2.85) and preterm delivery (aOR=6.04; 95% CI 2.52 to 14.48) were significantly associated with being a case as compared with control. This study suggests that women who had adverse pregnancy outcomes were more likely to have exposure to tobacco, previous history of adverse birth outcomes and were non-booked cases. Engagement of stakeholders in tobacco control for providing health education, incorporating tobacco use in women in the tobacco control policy and designing interventions for tobacco use cessation is warranted. Prenatal care and health education might help in preventing such adverse events. 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/

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

PubMed

Pallawela, S N S; Sullivan, A K; Macdonald, N; French, P; White, J; Dean, G; Smith, A; Winter, A J; Mandalia, S; Alexander, S; Ison, C; Ward, H

2014-06-01

Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. 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.

Results of a multicentre randomised controlled trial of statistical process control charts and structured diagnostic tools to reduce ward-acquired meticillin-resistant Staphylococcus aureus: the CHART Project.

PubMed

Curran, E; Harper, P; Loveday, H; Gilmour, H; Jones, S; Benneyan, J; Hood, J; Pratt, R

2008-10-01

Statistical process control (SPC) charts have previously been advocated for infection control quality improvement. To determine their effectiveness, a multicentre randomised controlled trial was undertaken to explore whether monthly SPC feedback from infection control nurses (ICNs) to healthcare workers of ward-acquired meticillin-resistant Staphylococcus aureus (WA-MRSA) colonisation or infection rates would produce any reductions in incidence. Seventy-five wards in 24 hospitals in the UK were randomised into three arms: (1) wards receiving SPC chart feedback; (2) wards receiving SPC chart feedback in conjunction with structured diagnostic tools; and (3) control wards receiving neither type of feedback. Twenty-five months of pre-intervention WA-MRSA data were compared with 24 months of post-intervention data. Statistically significant and sustained decreases in WA-MRSA rates were identified in all three arms (P<0.001; P=0.015; P<0.001). The mean percentage reduction was 32.3% for wards receiving SPC feedback, 19.6% for wards receiving SPC and diagnostic feedback, and 23.1% for control wards, but with no significant difference between the control and intervention arms (P=0.23). There were significantly more post-intervention 'out-of-control' episodes (P=0.021) in the control arm (averages of 0.60, 0.28, and 0.28 for Control, SPC and SPC+Tools wards, respectively). Participants identified SPC charts as an effective communication tool and valuable for disseminating WA-MRSA data.

Study protocol. IDUS - Instrumental delivery & ultrasound: a multi-centre randomised controlled trial of ultrasound assessment of the fetal head position versus standard care as an approach to prevent morbidity at instrumental delivery.

PubMed

Murphy, Deirdre J; Burke, Gerard; Montgomery, Alan A; Ramphul, Meenakshi

2012-09-13

Instrumental deliveries are commonly performed in the United Kingdom and Ireland, with rates of 12 - 17% in most centres. Knowing the exact position of the fetal head is a pre-requisite for safe instrumental delivery. Traditionally, diagnosis of the fetal head position is made on transvaginal digital examination by delineating the suture lines of the fetal skull and the fontanelles. However, the accuracy of transvaginal digital examination can be unreliable and varies between 20% and 75%. Failure to identify the correct fetal head position increases the likelihood of failed instrumental delivery with the additional morbidity of sequential use of instruments or second stage caesarean section. The use of ultrasound in determining the position of the fetal head has been explored but is not part of routine clinical practice. A multi-centre randomised controlled trial is proposed. The study will take place in two large maternity units in Ireland with a combined annual birth rate of 13,500 deliveries. It will involve 450 nulliparous women undergoing instrumental delivery after 37 weeks gestation. The main outcome measure will be incorrect diagnosis of the fetal head position. A study involving 450 women will have 80% power to detect a 10% difference in the incidence of inaccurate diagnosis of the fetal head position with two-sided 5% alpha. It is both important and timely to evaluate the use of ultrasound to diagnose the fetal head position prior to instrumental delivery before routine use can be advocated. The overall aim is to reduce the incidence of incorrect diagnosis of the fetal head position prior to instrumental delivery and improve the safety of instrumental deliveries. Current Controlled Trials ISRCTN72230496.

Risk factors for acquisition of OXA-48-producing Klebsiella pneumonia among contact patients: a multicentre study.

PubMed

Hilliquin, D; Le Guern, R; Thepot Seegers, V; Neulier, C; Lomont, A; Marie, V; Legeay, C; Merrer, J; Lepelletier, D; Rogues, A M; Grandbastien, B; Lucet, J C; Zahar, J R

2018-03-01

Cohorting carbapenemase-producing Enterobacteriaceae (CPE) carriers during hospitalization limits in-hospital spreading. To identify risk factors for CPE acquisition among contacts of an index patient in non-cohorted populations. A multicentre retrospective matched case-control study was conducted in five hospitals. Each contact patient (case) who acquired Klebsiella pneumoniae (KP)-OXA-48 from an index patient was compared to three contact (controls) with the same index patients matched with hospitalization in the same unit and similar exposure times. Fifty-one secondary cases and 131 controls were included. By univariate analysis, exposure time (odds ratio: 1.06; 95% confidence interval: 1.02-1.1; P = 0.006), concomitant infection at admission (3.23; 1.42-7.35; P = 0.005), antimicrobial therapy within the last month before hospitalization (2.88; 1.34-6.2; P = 0.007), antimicrobial therapy during the exposure time (5.36; 2.28-12.6; P < 0.001), use of at least one invasive procedure (2.99; 1.25-7.15; P = 0.014), number of invasive procedures (1.52; 1.05-2.19; P = 0.025), and geographical proximity (2.84; 1.15-7.00; P = 0.023) were associated with CPE acquisition. By multivariate analysis, antimicrobial therapy during the exposure time (odds ratio: 6.36; 95% confidence interval: 2.46-16.44; P < 0.001), at least one invasive procedure (2.92; 1.04-8.17; P = 0.041), and geographical proximity (3.69; 1.15-11.86; P = 0.028) were associated with acquisition. In this study, geographical proximity, invasive procedure, and antimicrobial therapy during exposure time were significantly associated with KP-OXA-48 acquisition. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Patient satisfaction with switching to esomeprazole from existing proton pump inhibitor therapy for gastro-oesophageal reflux disease: an observational, multicentre study.

PubMed

Hoogendoorn, Robert J; Groeneveld, Lex; Kwee, J Andy

2009-01-01

To determine treatment satisfaction in patients with gastro-oesophageal reflux disease (GORD) when switched to esomeprazole. This observational, multicentre study conducted in the Netherlands included primary-care patients being treated with a proton pump inhibitor (PPI) [omeprazole, pantoprazole, rabeprazole or lansoprazole] for GORD who were switched to esomeprazole by their physician. After a median of 28 days' esomeprazole therapy, patients' satisfaction was assessed using a questionnaire. Patients self-rated whether they were 'more satisfied', felt there was 'no difference' or were 'less satisfied' with esomeprazole compared with previous PPI therapy. Symptom control, concomitant medication use and tolerability were also assessed. Overall, 4929 patients were included in this study; of these, only 21.9% were satisfied with PPI treatment at consultation (i.e. prior to switching to esomeprazole). Following switching to esomeprazole therapy, 88.0% of patients were satisfied with therapy and only 26.9% of patients were still experiencing symptoms (vs 84.0% at consultation); 71.3% were more satisfied with esomeprazole than with their previous PPI, most frequently because they had fewer or no symptoms. Among patients who had been using concomitant therapy to control GORD symptoms, 62.0% were no longer using any such medication. Of the 1069 patients who had been satisfied with their previous PPI therapy, 39.4% were even more satisfied with esomeprazole. Esomeprazole was well tolerated; the most commonly reported adverse events were nausea/vomiting and headache, and no treatment-related serious adverse events occurred. Among primary-care patients receiving PPI therapy for GORD, switching to esomeprazole therapy impacts positively on treatment satisfaction and symptom control.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion--a study protocol.

PubMed

Brorsson, Anna Lena; Leksell, Janeth; Viklund, Gunnel; Lindholm Olinder, Anna

2013-12-20

Continuous subcutaneous insulin infusion (CSII) treatment among children with type 1 diabetes is increasing in Sweden. However, studies evaluating glycaemic control in children using CSII show inconsistent results. The distribution of responsibility for diabetes self-management between children and parents is often unclear and needs clarification. There is much published support for continued parental involvement and shared diabetes management during adolescence. Guided Self-Determination (GSD) is an empowerment-based, person-centred, reflection and problem solving method intended to guide the patient to become self-sufficient and develop life skills for managing difficulties in diabetes self-management. This method has been adapted for adolescents and parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate the effect of an intervention with GSD-Y in groups of adolescents starting on insulin pumps and their parents on diabetes-related family conflicts, perceived health and quality of life (QoL), and metabolic control. Here, we describe the protocol and plans for study enrollment. This study is designed as a randomized, controlled, prospective, multicentre study. Eighty patients between 12-18 years of age who are planning to start CSII will be included. All adolescents and their parents will receive standard insulin pump training. The education intervention will be conducted when CSII is to be started and at four appointments in the first 4 months after starting CSII. The primary outcome is haemoglobin A1c levels. Secondary outcomes are perceived health and QoL, frequency of blood glucose self-monitoring and bolus doses, and usage of carbohydrate counting. The following instruments will be used: Disabkids, 'Check your health', the Diabetes Family Conflict Scale and the Swedish Diabetes Empowerment Scale. Outcomes will be evaluated within and between groups by comparing data at baseline, and at 6 and 12 months after starting treatment. In this study, we will assess the effect of starting an CSII together with the model of GSD to determine whether this approach leads to retention of improved glycaemic control, QoL, responsibility distribution and reduced diabetes-related conflicts in the family.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

A cognitive behavioral based group intervention for children with a chronic illness and their parents: a multicentre randomized controlled trial.

PubMed

Scholten, Linde; Willemen, Agnes M; Grootenhuis, Martha A; Maurice-Stam, Heleen; Schuengel, Carlo; Last, Bob F

2011-07-14

Coping with a chronic illness (CI) challenges children's psychosocial functioning and wellbeing. Cognitive-behavioral intervention programs that focus on teaching the active use of coping strategies may prevent children with CI from developing psychosocial problems. Involvement of parents in the intervention program may enhance the use of learned coping strategies in daily life, especially on the long-term. The primary aim of the present study is to examine the effectiveness of a cognitive behavioral based group intervention (called 'Op Koers') 1 for children with CI and of a parallel intervention for their parents. A secondary objective is to investigate why and for whom this intervention works, in order to understand the underlying mechanisms of the intervention effect. This study is a multicentre randomized controlled trial. Participants are children (8 to 18 years of age) with a chronic illness, and their parents, recruited from seven participating hospitals in the Netherlands. Participants are randomly allocated to two intervention groups (the child intervention group and the child intervention combined with a parent program) and a wait-list control group. Primary outcomes are child psychosocial functioning, wellbeing and child disease related coping skills. Secondary outcomes are child quality of life, child general coping skills, child self-perception, parental stress, quality of parent-child interaction, and parental perceived vulnerability. Outcomes are evaluated at baseline, after 6 weeks of treatment, and at a 6 and 12-month follow-up period. The analyses will be performed on the basis of an intention-to-treat population. This study evaluates the effectiveness of a group intervention improving psychosocial functioning in children with CI and their parents. If proven effective, the intervention will be implemented in clinical practice. Strengths and limitations of the study design are discussed. Current Controlled Trials ISRCTN60919570.

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

PubMed

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

2016-10-01

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

A new social-family model for eating disorders: A European multicentre project using a case-control design.

PubMed

Krug, Isabel; Fuller-Tyszkiewicz, Matthew; Anderluh, Marija; Bellodi, Laura; Bagnoli, Silvia; Collier, David; Fernandez-Aranda, Fernando; Karwautz, Andreas; Mitchell, Sarah; Nacmias, Benedetta; Ricca, Valdo; Sorbi, Sandro; Tchanuria, Kate; Wagner, Gudrun; Treasure, Janet; Micali, Nadia

2015-12-01

To examine a new socio-family risk model of Eating Disorders (EDs) using path-analyses. The sample comprised 1264 (ED patients = 653; Healthy Controls = 611) participants, recruited into a multicentre European project. Socio-family factors assessed included: perceived maternal and parental parenting styles, family, peer and media influences, and body dissatisfaction. Two types of path-analyses were run to assess the socio-family model: 1.) a multinomial logistic path-model including ED sub-types [Anorexia Nervosa-Restrictive (AN-R), AN-Binge-Purging (AN-BP), Bulimia Nervosa (BN) and EDNOS)] as the key polychotomous categorical outcome and 2.) a path-model assessing whether the socio-family model differed across ED sub-types and healthy controls using body dissatisfaction as the outcome variable. The first path-analyses suggested that family and media (but not peers) were directly and indirectly associated (through body dissatisfaction) with all ED sub-types. There was a weak effect of perceived parenting directly on ED sub-types and indirectly through family influences and body dissatisfaction. For the second path-analyses, the socio-family model varied substantially across ED sub-types. Family and media influences were related to body dissatisfaction in the EDNOS and control sample, whereas perceived abusive parenting was related to AN-BP and BN. This is the first study providing support for this new socio-family model, which differed across ED sub-types. This suggests that prevention and early intervention might need to be tailored to diagnosis-specific ED profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

A guide to multi-centre ethics for surgical research in Australia and New Zealand.

PubMed

Boult, Maggi; Fitzpatrick, Kate; Maddern, Guy; Fitridge, Robert

2011-03-01

This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

A UK NEQAS ICC and ISH multicentre study using the Kreatech Poseidon HER2 FISH probe: intersite variation can be rigorously controlled using FISH.

PubMed

Bartlett, John M S; Campbell, Fiona M; Ibrahim, Merdol; Thomas, Jeremy; Wencyk, Pete; Ellis, Ian; Kay, Elaine; Connolly, Yvonne; O'Grady, Anthony; Barnett, Sarah; Starczynski, Jane; Cunningham, Paul; Miller, Keith

2010-02-01

To assess a new HER2 fluorescence in situ hybridization (FISH) test and report on multicentre intrasite and intersite variation. HER2 results were scored from 45 breast cancers in eight laboratories using the Kreatech Poseidon HER2 FISH probe (Kreatech Diagnostics, Amsterdam, the Netherlands). Overall, 80.9% of cores were successfully analysed. Mean intrasite variation for HER2 ratio assessment was low (4.74%). Intersite variation in ratio was in line with previous reports (11.9+/-0.8%) for both reference and non-reference laboratories; only one laboratory displayed significantly higher intersite variation (P=0.009) than the remaining seven laboratories. The overall incidence of misclassification of cores was <1.3%, demonstrating an excellent level of concordance (>98.7%) across all eight laboratories, irrespective of whether they were 'reference' or 'routine diagnostic' laboratories. The Kreatech Poseidon HER2 FISH test is robust and reproducible. Highly quantitatively reproducible FISH results were obtained from eight 'diagnostic' and 'reference' laboratories; however, continued quality assessments are essential to good performance.

MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis.

PubMed

Cuevas, Víctor D; Anta, Laura; Samaniego, Rafael; Orta-Zavalza, Emmanuel; Vladimir de la Rosa, Juan; Baujat, Geneviève; Domínguez-Soto, Ángeles; Sánchez-Mateos, Paloma; Escribese, María M; Castrillo, Antonio; Cormier-Daire, Valérie; Vega, Miguel A; Corbí, Ángel L

2017-03-01

Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, whereas the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knockdown of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the coexpression of MAFB and MAFB-target genes in CD163 + tissue-resident and tumor-associated macrophages. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from multicentric carpotarsal osteolysis (Online Mendelian Inheritance in Man #166300), a pathology caused by mutations in the MAFB gene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages. Copyright © 2017 by The American Association of Immunologists, Inc.

Adverse events associated with acupuncture: three multicentre randomized controlled trials of 1968 cases in China.

PubMed

Zhao, Ling; Zhang, Fu-wen; Li, Ying; Wu, Xi; Zheng, Hui; Cheng, Lin-hao; Liang, Fan-rong

2011-03-24

In order to evaluate the safety of acupuncture in China objectively, we investigated the adverse events associated with acupuncture based on three multicentre randomized controlled trials (RCTs) to assess the safety of acupuncture, identifying the common types of acupuncture adverse events, and analysing the related risk factors for their occurrence. This observational study included patients who received acupuncture from three multicentre RCTs respectively for migraine, functional dyspepsia and Bell's palsy. The 1968 patients and their acupuncturists documented adverse events associated with acupuncture after treatment. We collected data about adverse events due to acupuncture treatment from their case report forms. We analysed the incidence and details of the adverse effects, and studied the risk factors for acupuncture adverse events with non-conditional logistic regression analysis. Among the 1968 patients, 74 patients (3.76%) suffered at least one adverse event throughout the treatment period. We did not observe the occurrence of serious adverse events. 73 patients with adverse events recovered within 2 weeks through effective treatment such as physiotherapy or self-treatment. A total of 3 patients withdrew because of adverse events. There were 9 types of adverse events related to acupuncture, including subcutaneous haematoma, bleeding, skin bruising and needle site pain. Subcutaneous haematoma and haemorrhage in the needling points were the most common adverse events. Age and gender were related to the occurrence of acupuncture adverse events. The older the patients were, the higher the risk of adverse events was. In addition, male patients had slightly higher risk of an adverse event than female patients. Acupuncture is a safe therapy with low risk of adverse events in clinical practice. The risk factors for adverse events (AEs) were related to the patients' gender and age and the local anatomical structure of the acupoints. AEs could be reduced and mitigated by improving the medical environment, ensuring a high technical level of the acupuncture practitioners and establishing a good relationship of mutual trust between doctor and patient. ClinicalTrials.gov: NCT00599586, NCT00599677, NCT00608660.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review.

PubMed

Díaz-Delgado, Josué; Pool, Roy; Hoppes, Sharman; Cerezo, Argine; Quesada-Canales, Óscar; Stoica, George

2017-05-18

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

Satisfaction level and asthma control among Malaysian asthma patients on Symbicort Maintenance and Reliever Therapy (SMART) in the primary care setting (SMARTEST study).

PubMed

Liam, Chong-Kin; Pang, Yong-Kek; Chua, Keong-Tiong

2014-06-01

To evaluate Malaysian patients' satisfaction levels and asthma control with Symbicort SMART® in the primary care setting. This is a cross-sectional, multicentre study involving adult patients with persistent asthma who were prescribed only Symbicort SMART in the preceding one month prior to recruitment. Patients' satisfaction with Symbicort SMART and asthma control were evaluated using the self-administered Satisfaction with Asthma Treatment Questionnaire (SATQ) and the Asthma Control Test (ACT). Asthma was controlled (ACT score >20) in 189 (83%) of 228 patients. The mean overall SATQ score for patients with controlled asthma was 5.65 indicating a high satisfaction level, which was positively correlated with high ACT scores. There were differences in asthma control based on ethnicity, number of unscheduled visits and treatment compliance. Symbicort SMART resulted in a high satisfaction level and asthma control among Malaysian patients treated in the primary care setting and it is an effective and appealing treatment for asthmatic patients.

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial

PubMed Central

Bime, Christian; Wei, Christine Y; Holbrook, Janet; Smith, Lewis J; Wise, Robert A

2013-01-01

Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control. PMID:22885561

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

PubMed

de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades; Nijhuis, Harold J A; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P; Lenders, Mathieu W P M

2014-11-01

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

[A national multicentre study on nosocomial infections in PICU].

PubMed

Jordan García, I; Arriourtúa, A Bustinza; Torre, J A Concha; Antón, J Gil; Vicente, J C de Carlos; González, C Téllez

2014-01-01

Nosocomial infection (NI) is a common complication in paediatric critical care units (PICU), with an associated mortality up to 11%. To describe NI epidemiology in the national PICU. To initiate an standard NI control measures to obtain paediatric incidence rates. Multicentre prospective study from 1 to 31 march 2007. Centre Disease Control diagnosis and methodological criteria were used. It was specially analyzed NI related to invasive devices: central venous catheter (CVC), mechanical ventilation (MV), urinary catheter (UC). There were recruited 300 patients from 6 PICU, with 17 NI episodes in 16 patients (5,3% from admitted). NI rates resulted in 13,8 infections/1000 patients-day. Middle age from infected patients was 2,31 years (± 3,43), 9 males. Risk factors were found in 7 cases. NI location was: catheter-related bloodstream infection in 7 patients (6,7/1000 days CVC), ventilator associated pneumonia in 4 (9,4/1000 MV days), urinary-tract infection associated with UC in 4 (5,5/1000 UC days), one case of primary bloodstream infection and one surgical site infection. Isolated microorganisms were: 9 gram negatives bacillus, 4 Candida, 2 plasmocoagulase negative staphylococcus, 1 Haemophilus and 1 Staphylococcus aureus. Seven isolations were resistant microorganisms. There weren't any died related to NI. NI epidemiology was similar to published data in our near countries. NI surveillance, with a standardized method of analysis is essential to the NI correct manage. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Surgical timing after chemoradiotherapy for rectal cancer, analysis of technique (STARRCAT): results of a feasibility multi-centre randomized controlled trial.

PubMed

Foster, J D; Ewings, P; Falk, S; Cooper, E J; Roach, H; West, N P; Williams-Yesson, B A; Hanna, G B; Francis, N K

2016-10-01

The optimal time of rectal resection after long-course chemoradiotherapy (CRT) remains unclear. A feasibility study was undertaken for a multi-centre randomized controlled trial evaluating the impact of the interval after chemoradiotherapy on the technical complexity of surgery. Patients with rectal cancer were randomized to either a 6- or 12-week interval between CRT and surgery between June 2012 and May 2014 (ISRCTN registration number: 88843062). For blinded technical complexity assessment, the Observational Clinical Human Reliability Analysis technique was used to quantify technical errors enacted within video recordings of operations. Other measured outcomes included resection completeness, specimen quality, radiological down-staging, tumour cell density down-staging and surgeon-reported technical complexity. Thirty-one patients were enrolled: 15 were randomized to 6 and 16-12 weeks across 7 centres. Fewer eligible patients were identified than had been predicted. Of 23 patients who underwent resection, mean 12.3 errors were observed per case at 6 weeks vs. 10.7 at 12 weeks (p = 0.401). Other measured outcomes were similar between groups. The feasibility of measurement of operative performance of rectal cancer surgery as an endpoint was confirmed in this exploratory study. Recruitment of sufficient numbers of patients represented a challenge, and a proportion of patients did not proceed to resection surgery. These results suggest that interval after CRT may not substantially impact upon surgical technical performance.

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

PubMed Central

Croall, Iain D.; Lohner, Valerie; Moynihan, Barry; Khan, Usman; Hassan, Ahamad; O’Brien, John T.; Morris, Robin G.; Tozer, Daniel J.; Cambridge, Victoria C.; Harkness, Kirsty; Werring, David J.; Blamire, Andrew M.; Ford, Gary A.; Barrick, Thomas R.

2017-01-01

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies. PMID:28487471

Rates of self-harm presenting to general hospitals: a comparison of data from the Multicentre Study of Self-Harm in England and Hospital Episode Statistics

PubMed Central

Turnbull, Pauline; Hawton, Keith; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Townsend, Ellen; Khundakar, Kazem; Kapur, Nav

2016-01-01

Objective Rates of hospital presentation for self-harm in England were compared using different national and local data sources. Design The study was descriptive and compared bespoke data collection methods for recording self-harm presentations to hospital with routinely collected hospital data. Setting Local area data on self-harm from the 3 centres of the Multicentre Study of Self-harm in England (Oxford, Manchester and Derby) were used along with national and local routinely collected data on self-harm admissions and emergency department attendances from Hospital Episode Statistics (HES). Primary outcome Rate ratios were calculated to compare rates of self-harm generated using different data sources nationally and locally (between 2010 and 2012) and rates of hospital presentations for self-harm were plotted over time (between 2003 and 2012), based on different data sources. Results The total number of self-harm episodes between 2010 and 2012 was 13 547 based on Multicentre Study data, 9600 based on HES emergency department data and 8096 based on HES admission data. Nationally, routine HES data underestimated overall rates of self-harm by approximately 60% compared with rates based on Multicentre Study data (rate ratio for HES emergency department data, 0.41 (95% CI 0.35 to 0.49); rate ratio for HES admission data, 0.42 (95% CI 0.36 to 0.49)). Direct local area comparisons confirmed an overall underascertainment in the HES data, although the difference varied between centres. There was a general increase in self-harm over time according to HES data which contrasted with a fall and then a rise in the Multicentre Study data. Conclusions There was a consistent underestimation of presentations for self-harm recorded by HES emergency department data, and fluctuations in year-on-year figures. HES admission data appeared more reliable but missed non-admitted episodes. Routinely collected data may miss important trends in self-harm and cannot be used in isolation as the basis for a robust national indicator of self-harm. PMID:26883238

Generalisation and extension of a web-based data collection system for clinical studies using Java and CORBA.

PubMed

Eich, H P; Ohmann, C

1999-01-01

Inadequate informatical support of multi-centre clinical trials lead to pure quality. In order to support a multi-centre clinical trial a data collection via WWW and Internet based on Java has been developed. In this study a generalization and extension of this prototype has been performed. The prototype has been applied to another clinical trial and a knowledge server based on C+t has been integrated via CORBA. The investigation and implementation of security aspects of web-based data collection is now under evaluation.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial.

PubMed

Dou, Jingtao; Ma, Jianhua; Liu, Jun; Wang, Changjiang; Johnsson, Eva; Yao, Hui; Zhao, June; Pan, Changyu

2018-03-01

To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%-12.0%). In this multicentre, double-blind, active-controlled study (The START study: NCT02273050, clinicaltrials.gov), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/d over 8 weeks. The primary end point was change in HbA1c from baseline to Week 24. Data from 630 patients (66.5% men; mean age, 50.1 years; mean body mass index, 26.6 kg/m 2 ; mean HbA1c, 9.4%; mean diabetes duration, 0.81 years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (-3.0%) than with saxagliptin plus placebo (-2.1%; P < .001) or metformin plus placebo (-2.8%; P = .034). Changes in mean fasting plasma glucose, 120-minute postprandial glucose, and 180-minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common. Saxagliptin 5 mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment-naïve Chinese patients with type 2 diabetes, and was well tolerated. © 2017 John Wiley & Sons Ltd.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

PubMed

Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

2011-01-01

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

PubMed Central

2011-01-01

Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

PubMed

Borstlap, W A A; Buskens, C J; Tytgat, K M A J; Tuynman, J B; Consten, E C J; Tolboom, R C; Heuff, G; van Geloven, N; van Wagensveld, B A; C A Wientjes, C A; Gerhards, M F; de Castro, S M M; Jansen, J; van der Ven, A W H; van der Zaag, E; Omloo, J M; van Westreenen, H L; Winter, D C; Kennelly, R P; Dijkgraaf, M G W; Tanis, P J; Bemelman, W A

2015-06-28

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. ClincalTrials.gov: NCT02243735 .

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial.

PubMed

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-08-11

The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016-0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. The University Hospital Medical Information Network ID: UMIN000025727 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.

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Thomson, Claire; Doré, Caroline J; Cro, Suzie; Round, Jeff; Molloy, Andrew; Davies, Mark; Karski, Michael; Kim, Louise; Cooke, Paul

2016-01-01

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555. PMID:27601503

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

PubMed

McNamee, J J; Gillies, M A; Barrett, N A; Agus, A M; Beale, R; Bentley, A; Bodenham, A; Brett, S J; Brodie, D; Finney, S J; Gordon, A J; Griffiths, M; Harrison, D; Jackson, C; McDowell, C; McNally, C; Perkins, G D; Tunnicliffe, W; Vuylsteke, A; Walsh, T S; Wise, M P; Young, D; McAuley, D F

2017-05-01

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO 2 R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO 2 R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO 2 R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO 2 R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

NEURAPRO-E study protocol: a multicentre randomized controlled trial of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders.

PubMed

Markulev, Connie; McGorry, Patrick D; Nelson, Barnaby; Yuen, Hok Pan; Schaefer, Miriam; Yung, Alison R; Thompson, Andrew; Berger, Gregor; Mossaheb, Nilufar; Schlögelhofer, Monika; Smesny, Stefan; de Haan, Lieuwe; Riecher-Rössler, Anita; Nordentoft, Merete; Chen, Eric Yu Hai; Verma, Swapna; Hickie, Ian; Amminger, G Paul

2017-10-01

Recent research has indicated that preventative intervention is likely to benefit patients 'at-risk' for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs), coupled with the falling transition rate in ultra high-risk (UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group. This trial is a 6-month, double-blind, randomized placebo-controlled trial of 1.4 g day -1 omega-3 PUFAs in UHR patients aged between 13 and 40 years. The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive-behavioural case management (CBCM) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM. Secondary outcomes will examine symptomatic and functional changes, as well as examine if candidate risk factors predict response to omega-3 PUFA treatment in the UHR group. This is the protocol of the NeuraproE study. Utilizing a large sample, results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders, which may be the strongest avenue for reducing the burden, stigmatization, disability and economic consequences of these disorders. © 2015 Wiley Publishing Asia Pty Ltd.

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Guided Internet-based versus face-to-face clinical care in the management of tinnitus: study protocol for a multi-centre randomised controlled trial.

PubMed

Beukes, Eldré W; Baguley, David M; Allen, Peter M; Manchaiah, Vinaya; Andersson, Gerhard

2017-04-21

Innovative strategies are required to improve access to evidence-based tinnitus interventions. A guided Internet-based cognitive behavioural therapy (iCBT) intervention for tinnitus was therefore developed for a U.K. Initial clinical trials indicated efficacy of iCBT at reducing tinnitus severity and associated comorbidities such as insomnia and depression. The aim of this phase III randomised controlled trial is to compare this new iCBT intervention with an established intervention, namely face-to-face clinical care for tinnitus. This will be a multi-centre study undertaken across three hospitals in the East of England. The design is a randomised, two-arm, parallel-group, non-inferiority trial with a 2-month follow-up. The experimental group will receive the guided iCBT intervention, whereas the active control group will receive the usual face-to-face clinical care. An independent researcher will randomly assign participants, using a computer-generated randomisation schedule, after stratification for tinnitus severity. There will be 46 participants in each group. The primary assessment measure will be the Tinnitus Functional Index. Data analysis will establish whether non-inferiority is achieved using a pre-defined non-inferiority margin. This protocol outlines phase III of a clinical trial comparing a new iCBT with established face-to-face care for tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual tinnitus care, it may be a viable additional management route for individuals with tinnitus. This could increase access to evidence-based effective tinnitus care and reduce the pressures on existing health care systems. ClinicalTrials.gov identifier: NCT02665975 . Registered on 22 January 2016.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

PubMed Central

Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

2015-01-01

Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

The PACT trial: PAtient Centered Telerehabilitation: effectiveness of software-supported and traditional mirror therapy in patients with phantom limb pain following lower limb amputation: protocol of a multicentre randomised controlled trial.

PubMed

Rothgangel, Andreas Stefan; Braun, Susy; Schulz, Ralf Joachim; Kraemer, Matthias; de Witte, Luc; Beurskens, Anna; Smeets, Rob Johannes

2015-01-01

Non-pharmacological interventions such as mirror therapy are gaining increased recognition in the treatment of phantom limb pain; however, the evidence in people with phantom limb pain is still weak. In addition, compliance to self-delivered exercises is generally low. The aim of this randomised controlled study is to investigate the effectiveness of mirror therapy supported by telerehabilitation on the intensity, duration and frequency of phantom limb pain and limitations in daily activities compared to traditional mirror therapy and care as usual in people following lower limb amputation. A three-arm multi-centre randomised controlled trial will be performed. Participants will be randomly assigned to care as usual, traditional mirror therapy or mirror therapy supported by telerehabilitation. During the first 4 weeks, at least 10 individual sessions will take place in every group. After the first 4 weeks, participants will be encouraged to perform self-delivered exercises over a period of 6 weeks. Outcomes will be assessed at 4 and 10 weeks after baseline and at 6 months follow-up. The primary outcome measure is the average intensity of phantom limb pain during the last week. Secondary outcome measures include the different dimensions of phantom limb pain, pain-related limitations in daily activities, global perceived effect, pain-specific self-efficacy, and quality of life. Several questions concerning the study design that emerged during the preparation of this trial will be discussed. This will include how these questions were addressed and arguments for the choices that were made. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Multicentric Evaluation of New Commercial Enzyme Immunoassays for the Detection of Immunoglobulin M and Total Antibodies against Hepatitis A Virus▿

PubMed Central

Arcangeletti, M. C.; Dussaix, E.; Ferraglia, F.; Roque-Afonso, A. M.; Graube, A.; Chezzi, C.

2011-01-01

A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively). PMID:21653739

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma.

PubMed

Rebhun, R B; Kent, M S; Borrofka, S A E B; Frazier, S; Skorupski, K; Rodriguez, C O

2011-03-01

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01). © 2010 Blackwell Publishing Ltd.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review

PubMed Central

DÍAZ-DELGADO, Josué; POOL, Roy; HOPPES, Sharman; CEREZO, Argine; QUESADA-CANALES, Óscar; STOICA, George

2017-01-01

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies. PMID:28331115

Psychological and psychosocial functioning of children with burn scarring using cosmetic camouflage: a multi-centre prospective randomised controlled trial.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2014-02-01

Burns leave patients with long-term physical scarring. Children with scarring are required to face challenges of reintegration into their community, including acceptance of an altered appearance and acceptance by others. This can be difficult given society's preoccupation with physical appearance. Limited research exists investigating validity of cosmetic camouflage as a psychosocial intervention for children with scarring. This study investigated whether using cosmetic camouflage (Microskin™) had a positive impact on health-related quality of life, self-concept and psychopathology for children and adolescents (8-17 years) with burn scarring. A prospective multi-centre randomised controlled trial was conducted across Australian and New Zealand paediatric hospitals. 63 participants (49 females, mean age 12.7 ± 2.1 years) were enrolled. Data points were baseline (Time 1) and at 8 weeks (Time 2) using reliable and valid psychometric measures. Findings indicate there were significant improvements in socialisation, school and appearance scales on the Paediatric Quality of Life Inventory and psychopathology scores particularly peer problems decreased. However self-concept remained stable from baseline throughout intervention use. Cosmetic camouflage appears to have a positive impact on quality of life particularly socialisation. Cosmetic camouflage is a valid tool to assist children with scarring to actively participate socially within their communities. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation.

PubMed

Bourbeau, Jean; Lavoie, Kim L; Sedeno, Maria; De Sousa, Dorothy; Erzen, Damijan; Hamilton, Alan; Maltais, François; Troosters, Thierry; Leidy, Nancy

2016-04-04

Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study. PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies. The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations. NCT02085161. 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/

Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma

PubMed Central

Kong, Doo-Sik; Kim, Jinkuk; Lee, In-Hee; Kim, Sung Tae; Seol, Ho Jun; Lee, Jung-Il; Park, Woong-Yang; Ryu, Gyuha; Wang, Zichen; Ma'ayan, Avi; Nam, Do-Hyun

2016-01-01

We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM. PMID:26863628

Oxygen titration after resuscitation from out-of-hospital cardiac arrest: A multi-centre, randomised controlled pilot study (the EXACT pilot trial).

PubMed

Bray, Janet E; Hein, Cindy; Smith, Karen; Stephenson, Michael; Grantham, Hugh; Finn, Judith; Stub, Dion; Cameron, Peter; Bernard, Stephen

2018-04-21

Recent studies suggest the administration of 100% oxygen to hyperoxic levels following return-of-spontaneous-circulation (ROSC) post-cardiac arrest may be harmful. However, the feasibility and safety of oxygen titration in the prehospital setting is unknown. We conducted a multi-centre, phase-2 study testing whether prehospital titration of oxygen results in an equivalent number of patients arriving at hospital with oxygen saturations SpO2 ≥ 94%. We enrolled unconscious adults with: sustained ROSC; initial shockable rhythm; an advanced airway; and an SpO2 ≥ 95%. Initially (Sept 2015-March 2016) patients were randomised 1:1 to either 2 L/minute (L/min) oxygen (titrated) or >10 L/min oxygen (control) via a bag-valve reservoir. However, one site experienced a high number of desaturations (SpO2 < 94%) in the titrated arm and this arm was changed (April 2016) to an initial reduction of oxygen to 4 L/min then, if tolerated, to 2 L/min, and the desaturation limit was decreased to <90%. We randomised 61 patients to titrated (n = 37: 2L/min = 20 and 2-4 L/min = 17) oxygen or control (n = 24). Patients allocated to titrated oxygen were more likely to desaturate compared to controls ((SpO2 < 94%: 43% vs. 4%, p = 0.001; SpO2 < 90%: 19% vs. 4%, p = 0.09). The majority of desaturations (81%) occurred at 2L/min. On arrival at hospital the majority of patients had a SpO2 ≥ 94% (titrated: 90% vs. control: 100%) and all patients had a SpO2 ≥ 90%. One patient (control) re-arrested. Survival to hospital discharge was similar. Oxygen titration post-ROSC is feasible in the prehospital environment, but incremental titration commencing at 4L/min oxygen flow may be needed to maintain an oxygen saturation >90% (NCT02499042). Copyright © 2018 Elsevier B.V. All rights reserved.

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

Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections.

PubMed

van der Kooi, Tjallie; Sax, Hugo; Pittet, Didier; van Dissel, Jaap; van Benthem, Birgit; Walder, Bernhard; Cartier, Vanessa; Clack, Lauren; de Greeff, Sabine; Wolkewitz, Martin; Hieke, Stefanie; Boshuizen, Hendriek; van de Kassteele, Jan; Van den Abeele, Annemie; Boo, Teck Wee; Diab-Elschahawi, Magda; Dumpis, Uga; Ghita, Camelia; FitzGerald, Susan; Lejko, Tatjana; Leleu, Kris; Martinez, Mercedes Palomar; Paniara, Olga; Patyi, Márta; Schab, Paweł; Raglio, Annibale; Szilágyi, Emese; Ziętkiewicz, Mirosław; Wu, Albert W; Grundmann, Hajo; Zingg, Walter

2018-01-01

To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions. This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

PubMed

Celis-Morales, Carlos; Livingstone, Katherine M; Marsaux, Cyril F M; Forster, Hannah; O'Donovan, Clare B; Woolhead, Clara; Macready, Anna L; Fallaize, Rosalind; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Kolossa, Silvia; Hartwig, Kai; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Daly, E J; Akujobi, Victor; O'Riordan, Rick; Hoonhout, Jettie; Claassen, Arjan; Hoeller, Ulrich; Gundersen, Thomas E; Kaland, Siv E; Matthews, John N S; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Alfredo Martinez, J; Saris, Wim H M; Daniel, Hannelore; Gibney, Mike; Mathers, John C

2015-01-01

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial

PubMed Central

Neubert, Antje; Baarslag, Manuel Alberto; van Dijk, Monique; van Rosmalen, Joost; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

2017-01-01

Introduction Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. Methods and analysis The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Ethics Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial Registration EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results. PMID:28637741

A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

PubMed Central

Cohen, S; Moreland, L; Cush, J; Greenwald, M; Block, S; Shergy, W; Hanrahan, P; Kraishi, M; Patel, A; Sun, G; Bear, M

2004-01-01

Objective: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). Methods: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. Results: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). Conclusions: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone. PMID:15082469

Overcoming the Barriers Experienced in Conducting a Medication Trial in Adults with Aggressive Challenging Behaviour and Intellectual Disabilities

ERIC Educational Resources Information Center

Oliver-Africano, P.; Dickens, S.; Ahmed, Z.; Bouras, N.; Cooray, S.; Deb, S.; Knapp, M.; Hare, M.; Meade, M.; Reece, B.; Bhaumik, S.; Harley, D.; Piachaud, J.; Regan, A.; Ade Thomas, D.; Karatela, S.; Rao, B.; Dzendrowskyj, T.; Lenotre, L.; Watson, J.; Tyrer, P.

2010-01-01

Background: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. Method: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs…

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.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

PubMed

van Roozendaal, L M; Vane, M L G; van Dalen, T; van der Hage, J A; Strobbe, L J A; Boersma, L J; Linn, S C; Lobbes, M B I; Poortmans, P M P; Tjan-Heijnen, V C G; Van de Vijver, K K B T; de Vries, J; Westenberg, A H; Kessels, A G H; de Wilt, J H W; Smidt, M L

2017-07-01

Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

PubMed

Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

2017-09-01

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; 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.

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol

PubMed Central

Dias, Katrin A; Coombes, Jeff S; Green, Daniel J; Gomersall, Sjaan R; Keating, Shelley E; Tjonna, Arnt Erik; Hollekim-Strand, Siri Marte; Hosseini, Mansoureh Sadat; Ro, Torstein Baade; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Ingul, Charlotte B

2016-01-01

Introduction The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. Methods and analysis Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. Ethics and dissemination This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. Trial registration number NCT01991106. PMID:27044585

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

PubMed

Leung, D Y M; Hanifin, J M; Pariser, D M; Barber, K A; Langley, R G; Schlievert, P M; Abrams, B; Hultsch, T

2009-08-01

Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.

PubMed

Gunatilake, Samal; Brims, Fraser J H; Fogg, Carole; Lawrie, Iain; Maskell, Nick; Forbes, Karen; Rahman, Najib; Morris, Steve; Ogollah, Reuben; Gerry, Stephen; Peake, Mick; Darlison, Liz; Chauhan, Anoop J

2014-09-19

Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.

Increasing exercise capacity and quality of life of patients with heart failure through Wii gaming: the rationale, design and methodology of the HF-Wii study; a multicentre randomized controlled trial.

PubMed

Jaarsma, Tiny; Klompstra, Leonie; Ben Gal, Tuvia; Boyne, Josiane; Vellone, Ercole; Bäck, Maria; Dickstein, Kenneth; Fridlund, Bengt; Hoes, Arno; Piepoli, Massimo F; Chialà, Oronzo; Mårtensson, Jan; Strömberg, Anna

2015-07-01

Exercise is known to be beneficial for patients with heart failure (HF), and these patients should therefore be routinely advised to exercise and to be or to become physically active. Despite the beneficial effects of exercise such as improved functional capacity and favourable clinical outcomes, the level of daily physical activity in most patients with HF is low. Exergaming may be a promising new approach to increase the physical activity of patients with HF at home. The aim of this study is to determine the effectiveness of the structured introduction and access to a Wii game computer in patients with HF to improve exercise capacity and level of daily physical activity, to decrease healthcare resource use, and to improve self-care and health-related quality of life. A multicentre randomized controlled study with two treatment groups will include 600 patients with HF. In each centre, patients will be randomized to either motivational support only (control) or structured access to a Wii game computer (Wii). Patients in the control group will receive advice on physical activity and will be contacted by four telephone calls. Patients in the Wii group also will receive advice on physical activity along with a Wii game computer, with instructions and training. The primary endpoint will be exercise capacity at 3 months as measured by the 6 min walk test. Secondary endpoints include exercise capacity at 6 and 12 months, level of daily physical activity, muscle function, health-related quality of life, and hospitalization or death during the 12 months follow-up. The HF-Wii study is a randomized study that will evaluate the effect of exergaming in patients with HF. The findings can be useful to healthcare professionals and improve our understanding of the potential role of exergaming in the treatment and management of patients with HF. NCT01785121. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

A Multi-centric, Double-blind, Placebo-controlled, Randomized, Prospective Study to Evaluate the Efficacy and Safety of Carica papaya Leaf Extract, as Empirical Therapy for Thrombocytopenia associated with Dengue Fever.

PubMed

Kasture, Prabhu Nagnathappa; Nagabhushan, K H; Kumar, Arun

2016-06-01

Dengue is a rapidly expanding global health problem. Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. The management of dengue virus infection is essentially supportive and symptomatic and no specific treatment is available for increasing the fallen platelets, which have a significant role in causing the mortality of dengue patient.This study was conducted to evaluate the platelet increasing efficacy of Carica papaya leaf extract (CPLE) in patients with dengue fever (DF). The administration of Carica papaya leaf extract should significantly increase the platelet count in cases of thrombocytopenia associated with dengue, preventing the patient to go in DHF or DSS conditions. A Multi-centric, Double blind, Placebo controlled, Randomized, prospective study was conducted in 300 patients across 5 centres', to evaluate the Efficacy and Safety of Carica Papaya Leaf Extract, as empirical therapy for thrombocytopenia associated with dengue fever. The subjects were randomized into two groups, as control and intervention group. Both the groups were managed by the standard management guidelines for dengue except steroid administration. In addition to this, the intervention group received CPLE tablet three times daily for five days. All of them were followed daily with platelet monitoring. This study has been registered in the clinical trial registry-India (CTRI Registration number: CTRI/2015/05/005806). The results indicate that CPLE had significant increase(p< 0.01) in the platelet count over the therapy duration, in dengue fever patients, confirming CPLE accelerates the increase in platelet count compared to the control group. There were few adverse events related to GI disturbance like nausea and vomiting which were similar in both groups. Thus this study concluded that Carica papaya leaf extract (CPLE) does significantly increase the platelet count in patients with thrombocytopenia associated with dengue with fewer side effects and good tolerability.

The effect of a perioperative ketamine infusion on the incidence of chronic postsurgical pain-a pilot study.

PubMed

Peyton, P J; Wu, C; Jacobson, T; Hogg, M; Zia, F; Leslie, K

2017-07-01

Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P =0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range, IQR]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.

Nurse-perceived quality of care in intensive care units and associations with work environment characteristics: a multicentre survey study.

PubMed

Stalpers, Dewi; Van Der Linden, Dimitri; Kaljouw, Marian J; Schuurmans, Marieke J

2017-06-01

To examine nurse-perceived quality of care, controlling for overall job satisfaction among critical care nurses and to explore associations with work environment characteristics. Nurse-perceived quality of care and job satisfaction have been positively linked to quality outcomes for nurses and patients. Much evidence exists on factors contributing to job satisfaction. Understanding specific factors that affect nurse-perceived quality potentially enables for improvements of nursing care quality. A multicentre survey study was conducted in three Dutch intensive care units. The Dutch version of the Essentials of Magnetism II questionnaire was used; including the single-item indicators: (i) nurse-perceived quality of care; (ii) overall job satisfaction; and (iii) 58 statements on work environments. Data were collected between October 2013 - June 2014. The majority of 123 responding nurses (response rate 45%) were more than satisfied with quality of care (55%) and with their job (66%). No associations were found with nurse characteristics, besides differences in job satisfaction between the units. After controlling for job satisfaction, nurse-perceived quality was positively associated with the work environment characteristics: adequacy of staffing, patient-centeredness, competent peers and support for education. Patient-centeredness and autonomy were the most important predictors for overall job satisfaction. Factors that contribute to nurse-perceived quality of care in intensive care units, independent from the effects of overall job satisfaction, were identified. Hereby, offering opportunities to maximize high quality of care to critically ill patients. Research in a larger sample is needed to confirm our findings. © 2016 John Wiley & Sons Ltd.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

PubMed

Oyanguren, Juana; García-Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin-Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García-Gutiérrez, Susana

2017-11-01

Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Cost-effectiveness of the Australian Medical Sheepskin for the prevention of pressure ulcers in somatic nursing home patients: study protocol for a prospective multi-centre randomised controlled trial (ISRCTN17553857).

PubMed

Mistiaen, Patriek; Achterberg, Wilco; Ament, Andre; Halfens, Ruud; Huizinga, Janneke; Montgomery, Ken; Post, Henri; Francke, Anneke L

2008-01-07

Pressure ulcers are a major problem, especially in nursing home patients, although they are regarded as preventable and there are many pressure relieving methods and materials. One such pressure relieving material is the recently developed Australian Medical Sheepskin, which has been shown in two randomized controlled trials 12 to be an effective intervention in the prevention of sacral pressure ulcers in hospital patients. However, the use of sheepskins has been debated and in general discouraged by most pressure ulcer working groups and pressure ulcer guidelines, but these debates were based on old forms of sheepskins. Furthermore, nothing is yet known about the (cost-)effectiveness of the Australian Medical sheepskin in nursing home patients. The objective of this study is to assess the effects and costs of the use of the Australian Medical Sheepskin combined with usual care with regard to the prevention of sacral pressure ulcers in somatic nursing home patients, versus usual care only. In a multi-centre randomised controlled trial 750 patients admitted for a primarily somatic reason to one of the five participating nursing homes, and not having pressure ulcers on the sacrum at admission, will be randomized to either usual care only or usual care plus the use of the Australian Medical Sheepskin as an overlay on the mattress. Outcome measures are: incidence of sacral pressure ulcers in the first month after admission; sacrum pressure ulcer free days; costs; patient comfort; and ease of use. The skin of all the patients will be observed once a day from admission on for 30 days. Patient characteristics and pressure risk scores are assessed at admission and at day 30 after it. Additional to the empirical phase, systematic reviews will be performed in order to obtain data for economic weighting and modelling. The protocol is registered in the Controlled Trial Register as ISRCTN17553857.

Long-term integrated telerehabilitation of COPD Patients: a multicentre randomised controlled trial (iTrain).

PubMed

Zanaboni, Paolo; Dinesen, Birthe; Hjalmarsen, Audhild; Hoaas, Hanne; Holland, Anne E; Oliveira, Cristino Carneiro; Wootton, Richard

2016-08-22

Pulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic obstructive pulmonary disease (COPD). However, available resources are often limited, and many patients bear with poor availability of programmes. Sustaining PR benefits and regular exercise over the long term is difficult without any exercise maintenance strategy. In contrast to traditional centre-based PR programmes, telerehabilitation may promote more effective integration of exercise routines into daily life over the longer term and broaden its applicability and availability. A few studies showed promising results for telerehabilitation, but mostly with short-term interventions. The aim of this study is to compare long-term telerehabilitation with unsupervised exercise training at home and with standard care. An international multicentre randomised controlled trial conducted across sites in three countries will recruit 120 patients with COPD. Participants will be randomly assigned to telerehabilitation, treadmill and control, and followed up for 2 years. The telerehabilitation intervention consists of individualised exercise training at home on a treadmill, telemonitoring by a physiotherapist via videoconferencing using a tablet computer, and self-management via a customised website. Patients in the treadmill arm are provided with a treadmill only to perform unsupervised exercise training at home. Patients in the control arm are offered standard care. The primary outcome is the combined number of hospitalisations and emergency department presentations. Secondary outcomes include changes in health status, quality of life, anxiety and depression, self-efficacy, subjective impression of change, physical performance, level of physical activity, and personal experiences in telerehabilitation. This trial will provide evidence on whether long-term telerehabilitation represents a cost-effective strategy for the follow-up of patients with COPD. The delivery of telerehabilitation services will also broaden the availability of PR and maintenance strategies, especially to those living in remote areas and with no access to centre-based exercise programmes. ClinicalTrials.gov: NCT02258646 .

Why did an effective Dutch complex psycho-social intervention for people with dementia not work in the German healthcare context? Lessons learnt from a process evaluation alongside a multicentre RCT.

PubMed

Voigt-Radloff, Sebastian; Graff, Maud; Leonhart, Rainer; Hüll, Michael; Rikkert, Marcel Olde; Vernooij-Dassen, Myrra

2011-08-09

Background The positive effects of the Dutch Community Occupational Therapy in Dementia programme on patients' daily functioning were not found in a multicentre randomised controlled trial (RCT) in Germany. Objectives To evaluate possible effect modification on the primary outcome within the German RCT with regard to (1) participant characteristics, (2) treatment performance and (3) healthcare service utilisation; and (4) to compare the design and primary outcome between the German and the original Dutch study. Methods (1) The impact of participant baseline data on the primary outcome was analysed in exploratory ANCOVA and regression analyses. (2) Therapists completed questionnaires on context and performance problems. The main problems were identified by a qualitative content analysis and focus-group discussion. Associations of the primary outcome with scores of participant adherence and treatment performance were evaluated by regression analysis. (3) Utilisation rates of healthcare services were controlled for significant group differences. (4) Differences in the Dutch and German study design were identified, and the primary outcome was contrasted at the item level. Results (1) Participant characteristics could not explain more than 5% of outcome variance. (2) The treatment performance of some active intervention components was poor but not significantly associated with the primary outcome. (3) There were no significant group differences in the utilisation of healthcare resources. (4) In contrast to the Dutch waiting-control group, the active intervention in the German control group may have reduced group differences in the current RCT. The German patients demonstrated a higher independence at baseline and less improvement in instrumental activities of daily living. Conclusion The differences in outcome may be explained by a more active control treatment, partially poor experimental treatment and less room for improvement in the German sample. Future cross-national transfers should be prepared by pilot studies assessing the applicability of the intervention and patient needs specific to the target country. Trial registration International Clinical Trials Registry Platform, DRKS00000053.

Home safety measures and the risk of unintentional injury among young children: a multicentre case–control study

PubMed Central

LeBlanc, John C.; Pless, I. Barry; King, W. James; Bawden, Harry; Bernard-Bonnin, Anne-Claude; Klassen, Terry; Tenenbein, Milton

2006-01-01

Background Young children may sustain injuries when exposed to certain hazards in the home. To better understand the relation between several childproofing strategies and the risk of injuries to children in the home, we undertook a multicentre case–control study in which we compared hazards in the homes of children with and without injuries. Methods We conducted this case-control study using records from 5 pediatric hospital emergency departments for the 2-year period 1995–1996. The 351 case subjects were children aged 7 years and less who presented with injuries from falls, burns or scalds, ingestions or choking. The matched control subjects were children who presented during the same period with acute non-injury-related conditions. A home visitor, blinded to case-control status, assessed 19 injury hazards at the children's homes. Results Hazards found in the homes included baby walkers (21% of homes with infants), no functioning smoke alarm (17% of homes) and no fire extinguisher (51% of homes). Cases did not differ from controls in the mean proportion of home hazards. After controlling for siblings, maternal education and employment, we found that cases differed from controls for 5 hazards: the presence of a baby walker (odds ratio [OR] 9.0, 95% confidence interval [CI] 1.1–71.0), the presence of choking hazards within a child's reach (OR 2.0, 95% CI 1.0–3.7), no child-resistant lids in bathroom (OR 1.6, 95% CI 1.0–2.5), no smoke alarm (OR 3.2, 95% CI 1.4–7.7) and no functioning smoke alarm (OR 1.7, 95% CI 1.0–2.8). Interpretation Homes of children with injuries differed from those of children without injuries in the proportions of specific hazards for falls, choking, poisoning and burns, with a striking difference noted for the presence of a baby walker. In addition to counselling parents about specific hazards, clinicians should consider that the presence of some hazards may indicate an increased risk for home injuries beyond those directly related to the hazard found. Families with any home hazard may be candidates for interventions to childproof against other types of home hazards. PMID:16998079

Clinical and cost effectiveness of mobile phone supported self monitoring of asthma: multicentre randomised controlled trial.

PubMed

Ryan, Dermot; Price, David; Musgrave, Stan D; Malhotra, Shweta; Lee, Amanda J; Ayansina, Dolapo; Sheikh, Aziz; Tarassenko, Lionel; Pagliari, Claudia; Pinnock, Hilary

2012-03-23

To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies. Multicentre randomised controlled trial with cost effectiveness analysis. UK primary care. 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥ 1.5) from 32 practices. Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring. Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis. There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change -0.02 (95% confidence interval -0.23 to 0.19); KASE-AQ score: mean change -4.4 v -2.4, mean difference 2.0 (-0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring. Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective. Clinical Trials NCT00512837.

Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committee of the Royal College of General Practitioners.

PubMed Central

Wise, P.; Drury, M.

1996-01-01

OBJECTIVE: To assess the outcome of 100 general practice based, multicentre research projects submitted to the ethics committee of the Royal College of General Practitioners by pharmaceutical companies or their agents between 1984 and 1989. DESIGN: Analysis of consecutive submitted protocols for stated objectives, study design, and outcomes; detailed review of committee minutes and correspondence in relation to amendment and approval; assessment of final reports submitted at conclusion of studies. SUBJECTS: 82 finally approved protocols, embracing 34,523 proposed trial subjects and 1195 proposed general practice investigators. MAIN OUTCOME MEASURES: Success at enrolling subjects and investigators; commencement and completion data; validity of final report's assessment of efficacy, safety, tolerability, and acceptability; and method of use and dissemination of findings. RESULTS: 18 studies were not approved and 45 had to be amended. Randomised controlled trials comprised 46 of the original submissions. Remuneration considerations, inadequate information or consent sheets, pregnancy safety, the need to discontinue existing therapy, and suboptimal scientific content were major reasons for rejecting studies or asking for amendments. Of the 82 approved studies 8 were not started. Shortfalls of investigators (of 39%) and trial subjects (of 37%) and an overall 23% withdrawal rate were responsible for a significant incidence of inconclusive results. Within the six year follow up interval, only 19 of the studies had been formally published. CONCLUSIONS: This audit identified substantial ethical concerns in the process of approving multicentre general practice pharmaceutical research. PMID:8939118

Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial.

PubMed

Chamberlain Mitchell, Sarah A F; Garrod, Rachel; Clark, Lynne; Douiri, Abdel; Parker, Sean M; Ellis, Jenny; Fowler, Stephen J; Ludlow, Siobhan; Hull, James H; Chung, Kian Fan; Lee, Kai K; Bellas, H; Pandyan, Anand; Birring, Surinder S

2017-02-01

Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. UKCRN ID 10678 and ISRCTN 73039760; 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/.

Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study.

PubMed

Wallace, Daniel J; Kalunian, Kenneth; Petri, Michelle A; Strand, Vibeke; Houssiau, Frederic A; Pike, Marilyn; Kilgallen, Brian; Bongardt, Sabine; Barry, Anna; Kelley, Lexy; Gordon, Caroline

2014-01-01

To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing.

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

Simulation-based team training for multi-professional obstetric care teams to improve patient outcome: a multicentre, cluster randomised controlled trial.

PubMed

Fransen, A F; van de Ven, J; Schuit, E; van Tetering, Aac; Mol, B W; Oei, S G

2017-03-01

To investigate whether simulation-based obstetric team training in a simulation centre improves patient outcome. Multicentre, open, cluster randomised controlled trial. Obstetric units in the Netherlands. Women with a singleton pregnancy beyond 24 weeks of gestation. Random allocation of obstetric units to a 1-day, multi-professional, simulation-based team training focusing on crew resource management (CRM) in a simulation centre or to no such team training. Intention-to-treat analyses were performed at the cluster level, including a measurement 1 year prior to the intervention. Primary outcome was a composite outcome of obstetric complications during the first year post-intervention, including low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischaemic encephalopathy. Maternal and perinatal mortality were also registered. Each study group included 12 units with a median unit size of 1224 women, combining for a total of 28 657 women. In total, 471 medical professionals received the training course. The composite outcome of obstetric complications did not differ between study groups [odds ratio (OR) 1.0, 95% confidence interval (CI) 0.80-1.3]. Team training reduced trauma due to shoulder dystocia (OR 0.50, 95% CI 0.25-0.99) and increased invasive treatment for severe postpartum haemorrhage (OR 2.2, 95% CI 1.2-3.9) compared with no intervention. Other outcomes did not differ between study groups. A 1-day, off-site, simulation-based team training, focusing on teamwork skills, did not reduce a composite of obstetric complications. 1-day, off-site, simulation-based team training did not reduce a composite of obstetric complications. © 2016 Royal College of Obstetricians and Gynaecologists.

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department.

PubMed

Reynolds, Stacy L; Studnek, Jonathan R; Bryant, Kathleen; VanderHave, Kelly; Grossman, Eric; Moore, Charity G; Young, James; Hogg, Melanie; Runyon, Michael S

2016-09-08

Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. NCT02521415. 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/

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial

PubMed Central

Fan, Qing; Zhang, De-wei; Yang, Da-ye; Li, Hong-wu; Wei, Shi-bo; Yang, Liang; Yang, Fu-quan; Zhang, Shao-jun; Wu, Yao-qiang; An, Wei-de; Dai, Zhong-shu; Jiang, Hui-yong; Wang, Fu-rong; Qiao, Shi-feng; Li, Hang-yu

2017-01-01

Introduction Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as ‘tension’ repair or ‘tension-free’ repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. Methods and analysis This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). Ethics and dissemination This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015–027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number NCT02984917; preresults. PMID:28860228

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

PubMed

Madsbad, S; Kilhovd, B; Lager, I; Mustajoki, P; Dejgaard, A

2001-05-01

To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial

PubMed Central

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-01-01

Introduction Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. Methods and analysis This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics and dissemination Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. Trial registration number NCT02198924. PMID:27609846

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.

PubMed

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-09-08

Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. NCT02198924. 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/

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

PubMed

Lomer, Miranda C E; Grainger, Stephen L; Ede, Roland; Catterall, Adrian P; Greenfield, Simon M; Cowan, Russell E; Vicary, F Robin; Jenkins, Anthony P; Fidler, Helen; Harvey, Rory S; Ellis, Richard; McNair, Alistair; Ainley, Colin C; Thompson, Richard P H; Powell, Jonathan J

2005-03-01

Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

Ethical issues: the multi-centre low-risk ethics/governance review process and AMOSS.

PubMed

Vaughan, Geraldine; Pollock, Wendy; Peek, Michael J; Knight, Marian; Ellwood, David; Homer, Caroline S; Pulver, Lisa Jackson; McLintock, Claire; Ho, Maria T; Sullivan, Elizabeth A

2012-04-01

The Australasian Maternity Outcomes Surveillance System (AMOSS) conducts surveillance and research of rare and serious conditions in pregnancy. This multi-centre population health study is considered low risk with minimal ethical impact. To describe the ethics/governance review pathway undertaken by AMOSS. Prospective, descriptive study during 2009-2011 of the governance/ethical review processes required to gain approval for Australian and New Zealand (ANZ) maternity units with more than 50 births per year (n = 303) to participate in AMOSS. Review processes ranged from a single application for 24 NZ sites, a single application for eligible hospitals in two Australian states, full Health Research Ethics Committee (HREC) applications for individual hospitals, through simple letters of support. As of September 2011, 46 full/expedited ethics applications, 131 site governance applications and 136 letters of support requests were made over 33 months, involving an estimated 3261 hours by AMOSS staff/investigators, and an associated resource burden by participating sites, to obtain approval to receive nonidentifiable data from 291 hospitals. The AMOSS research system provides an important resource to enhance knowledge of conditions that cause rare and serious maternal morbidity. Yet the highly variable ethical approval processes required to implement this study have been excessively repetitive and burdensome. This process jeopardises timely, efficient research project implementation, without corresponding benefits to research participants. The resource burden to establish research governance for AMOSS confirms the urgent need for the Harmonisation of Multi-centre Ethical Review (HoMER) to further streamline ethics/governance review processes for multi-centre research. © 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

PubMed Central

Lawlor, Brian; Kennelly, Sean; O'Dwyer, Sarah; Cregg, Fiona; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Howard, Robert; Murphy, Caroline; Adams, Jessica; Daly, Leslie; Segurado, Ricardo; Gaynor, Siobhan; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Wallin, Anders; Borjesson, Anne; Molloy, William; Tsolaki, Magda; Olde Rikkert, Marcel

2014-01-01

Introduction This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. Trial registration number EUDRACT Reference Number: 2012-002764-27. PMID:25300460

The self-assessed psychological comorbidities of prurigo in European patients: A multi-centre study in 13 countries.

PubMed

Brenaut, Emilie; Halvorsen, Jon Anders; Dalgard, Florence J; Lien, Lars; Balieva, Flora; Sampogna, Francesca; Linder, Dennis; Evers, Andrea W M; Jemec, Gregor B E; Gieler, Uwe; Szepietowski, Jacek; Poot, Françoise; Altunay, Ilknur K; Finlay, Andrew Y; Salek, Sam S; Szabo, Csanad; Lvov, Andrey; Marron, Servando E; Tomas-Aragones, Lucia; Kupfer, Jörg; Misery, Laurent

2018-06-19

Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. The aim of this study was to assess the psychological burden of prurigo in patients of European countries. In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10/27 (37%) suffered from anxiety and 8/27 (29%) from depression. Suicidal ideation was reported by 5/27 (19%) of patients, and for 4 out of these 5 patients, suicidal ideation was related to their skin disease. These frequencies were higher than in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers for example). The impact on quality of life was severe, with a mean DLQI of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study].

PubMed

Torregrosa, Josep V; Morales, Enrique; Díaz, Juan M; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel A; Rodríguez-Benot, Alberto; Rodríguez-García, Minerva; López-Jiménez, Verónica; Gutiérrez-Dalmau, Álex; Jimeno, Luisa; Pérez-Sáez, M José; Romero, Rafael; Gómez-Alamillo, Carlos

2014-01-01

The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2 mg/dl). Patients began treatment with cinacalcet in clinical practice. 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

Implantable hemodynamic monitoring (the Chronicle IHM system): remote telemonitoring for patients with heart failure.

PubMed

Ho, C

2008-01-01

(1) Remote monitoring for ambulatory heart failure patients uses an implantable device to record hemodynamic data and transmit it to a central server for continuous assessment. (2) Preliminary evidence from observational studies suggests a potential for reducing hospitalizations with the use of right ventricle implantable hemodynamic monitoring (IHM). However, although a multicentre, randomized controlled trial (COMPASS-HF) showed a reduction in hospitalizations in the IHM group the results were not statistically significant and the US Food and Drug Administration panel concluded the trial failed to meet its primary efficacy endpoint. (3) In the COMPASS-HF study the most common device-related complication was lead dislodgement. (4) Large randomized controlled trials are needed to demonstrate the clinical utility of IHM, particularly in terms of its impact on reducing hospitalization and improving patient outcomes.

Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial.

PubMed

Carr, Robert; Brocklehurst, Peter; Doré, Caroline J; Modi, Neena

2009-01-17

Systemic sepsis is a major cause of death in preterm neonates. There are compelling theoretical reasons why treatment with haemopoietic colony-stimulating factors might reduce sepsis and improve outcomes, and as a consequence these agents have entered into use in neonatal medicine without adequate evidence. We assessed whether granulocyte-macrophage colony stimulating factor (GM-CSF) administered as prophylaxis to preterm neonates at high risk of neutropenia would reduce sepsis, mortality, and morbidity. We undertook a single-blind, multicentre, randomised controlled trial in 26 centres between June, 2000, and June, 2006. 280 neonates of below or equal to 31 weeks' gestation and below the 10th centile for birthweight were randomised within 72 h of birth to receive GM-CSF 10 microg/kg per day subcutaneously for 5 days or standard management. From recruitment to day 28 a detailed daily clinical record form was completed by the treating clinicians. Primary outcome was sepsis-free survival to 14 days from trial entry. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN42553489. Neutrophil counts after trial entry rose significantly more rapidly in infants treated with GM-CSF than in control infants during the first 11 days (difference between neutrophil count slopes 0.34 x 10(9)/L/day; 95% CI 0.12-0.56). There was no significant difference in sepsis-free survival for all infants (93 of 139 treated infants, 105 of 141 control infants; difference -8%, 95% CI -18 to 3). A meta-analysis of this trial and previous published prophylactic trials showed no survival benefit. Early postnatal prophylactic GM-CSF corrects neutropenia but does not reduce sepsis or improve survival and short-term outcomes in extremely preterm neonates.

[Team Development in Medical Rehabilitation: Concept and Evaluation of a Team Intervention].

PubMed

Körner, M; Luzay, L; Becker, S; Rundel, M; Müller, C; Zimmermann, L

2016-04-01

Interprofessional collaboration is a main precondition of successful treatment in rehabilitation. In order to improve interprofessional collaboration, a clinic-specific, goal- and solution-oriented and systemic team development approach was designed. The aim of the study is the evaluation of this approach. A multi-centre cluster-randomized controlled study with staff questionnaires. The team development could be implemented successfully in 4 of 5 clinics and led to significant improvements in team organisation, willingness to accept responsibility and knowledge integration. The effects are small and are caused by the opposed development of intervention and control group. The team development approach can be recommended for rehabilitation practice. A train-the-trainer approach will be developed and further studies are planned in order to disseminate the approach and to investigate the conditions of implementation. © Georg Thieme Verlag KG Stuttgart · New York.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

PubMed

Murphy, Kellie E; Hannah, Mary E; Willan, Andrew R; Ohlsson, Arne; Kelly, Edmond N; Matthews, Stephen G; Saigal, Saroj; Asztalos, Elizabeth; Ross, Sue; Delisle, Marie-France; Tomat, Laura; Amankwah, Kofi; Guselle, Patricia; Gafni, Amiram; Lee, Shoo K; Armson, B Anthony

2011-09-01

A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Evaluation of postoperative recovery in day surgery patients using a mobile phone application: a multicentre randomized trial.

PubMed

Jaensson, M; Dahlberg, K; Eriksson, M; Nilsson, U

2017-11-01

Many patients undergoing anaesthesia and surgery experience postoperative complications. Our aim was to investigate whether a systematic follow-up smartphone-based assessment, using recovery assessment by phone points (RAPP) compared with standard care, had a positive effect on day surgery patients' postoperative recovery. We also investigated whether there were differences in women and men's recovery and recovery scores. The study was a single-blind, multicentre randomized controlled trial. A total of 997 patients were randomly allocated to either RAPP or standard care. The Swedish web version of a quality of recovery (SwQoR) questionnaire was used to evaluate the patients' postoperative recovery, either on paper or using an application (RAPP) on postoperative days seven and 14. On postoperative day seven the RAPP group reported significantly better values in seven out of 24 items of the SwQoR: sleeping difficulties; not having a general feeling of wellbeing; having difficulty feeling relaxed/comfortable; and dizziness; headache; pain in the surgical wound; and a swollen surgical wound compared with the control group, implying a good postoperative recovery. Both men and women in the RAPP group reported significantly better values (and, hence good postoperative recovery) compared with the control group in the items sleeping difficulties; not having a general feeling of wellbeing and pain in the surgical wound. Measurement of patient-reported outcomes using a smartphone-based application was associated with decreased discomfort from several postoperative symptoms. Systematic e-assessment can thereby increase patients' quality of recovery and identify key areas for improvement in perioperative care. NCT02492191. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

A survey of contemporary opinions and practices of surgical and intensive care specialists towards peri-operative venous thromboembolism prophylaxis in Asia.

PubMed

Lee, L; Liew, N C; Gee, T

2012-12-01

This survey was conducted to determine the opinions and practices of peri-operative venous thromboembolism (VTE) prophylaxis among surgical and intensive care specialists in Asia. A set of questionnaire was distributed to surgeons and intensivists from different countries in Asia. The specialties included were general surgery and its sub-specialties, orthopaedic surgery, gynaecological surgery and intensive care unit. This survey involved teaching institutions, general hospitals and private hospitals. To gauge if the respondents were from hospitals that would likely encounter VTE cases, the hospital's bed-strength, intensive care facility and sub-specialty services were recorded. Over a period of six months, questionnaires and feedbacks were collected and analyzed. One hundred and ninety-one responses were received from 8 countries throughout Asia. Fifty-six percent of these were from large hospitals (800 bedded or more) and 62% of these hospitals have large intensive care facility (20 or more beds). Only half of the respondents practice routine thromboprophylaxis in moderate and high risk surgeries. Thirty six percent of them practices selective thromboprophylaxis and only 3% do not believe in any thromboprophylaxis. A third prescribed thromboprophylaxis for 3 to 5 days; another third extended it until patient is mobile. About 48.6% of the respondents do not have VTE guidelines in their institutions. Majority of the respondents agreed that more evidence is needed in the form of multi-centre randomized controlled trials to influence their decision on thromboprophylaxis. Despite the availability of strong epidemiological data, randomized controlled trials and multicentre case-controlled studies, perioperative VTE prophylactic practices are still suboptimal in Asia.

The impact of DECISION+2 on patient intention to engage in shared decision making: secondary analysis of a multicentre clustered randomized trial.

PubMed

Couët, Nicolas; Labrecque, Michel; Robitaille, Hubert; Turcotte, Stéphane; Légaré, France

2015-12-01

Training health professionals in shared decision making (SDM) may influence their patients' intention to engage in SDM. To assess the impact of DECISION+2, a SDM training programme for family physicians about the use of antibiotics to treat acute respiratory infections (ARIs), on their patients' intention to engage in SDM in future consultations. Secondary analysis of a multicentre clustered randomized trial. Three hundred and fifty-nine patients consulting family physicians about an ARI in nine family practice teaching units (FPTUs). DECISION+2 (two-hour online tutorial, two-hour workshop, and decision support tools) was offered in the experimental group (five FPTUs, 162 physicians, 181 patients). Usual care was provided in the control group (four FPTUs, 108 physicians, 178 patients). Change in patients' intention scores (range -3 to +3) between pre- and post-consultation. The mean ± SD [median] scores of intention to engage in SDM were high in both study groups before consultation (DECISION+2 group: 1.4 ± 1.0 [1.7]; control group: 1.5 ± 1.1 [1.7]) and increased in both groups after consultation (DECISION+2 group: 2.1 ± 1.1 [2.7]; control group: 1.9 ± 1.2 [2.3]). Change of intention, classified as either increased, stable or decreased, was not statistically associated with the exposure to the DECISION+2 programme after adjusting for the cluster design (proportional odds ratio = 1.5; 95% confidence interval = 0.8-3.0). DECISION+2 had no significant impact on patients' intention to engage in SDM for choosing to use antibiotics or not to treat an ARI in future consultations. Patient-targeted interventions may be necessary to achieve this purpose. © 2014 John Wiley & Sons Ltd.

Maternal Psychological Distress in the First Two Years after Very Preterm Birth and Early Intervention

ERIC Educational Resources Information Center

Meijssen, Dominique; Wolf, Marie-Jeanne; Koldewijn, Karen; van Baar, Anneloes; Kok, Joke

2011-01-01

Preterm delivery may have a strong impact on mothers. In a multicentre randomised controlled trial, including very preterm infants (less than 32 weeks and/or less than 1500 g), the effect of the Infant Behavioral Assessment and Intervention Program (IBAIP) on maternal psychological distress at 6, 12 and 24 (corrected) months after preterm birth…

INTER-ACT: prevention of pregnancy complications through an e-health driven interpregnancy lifestyle intervention - study protocol of a multicentre randomised controlled trial.

PubMed

Bogaerts, Annick; Ameye, Lieveke; Bijlholt, Margriet; Amuli, Kelly; Heynickx, Dorine; Devlieger, Roland

2017-05-26

Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum. At week 6 postpartum, participants are randomised into the intervention or control arm of the study. The intervention focuses on weight, diet, physical activity and mental well-being, and comprises face-to-face coaching, in which behavioural change techniques are central, and use of a mobile application, which is Bluetooth-connected to a weighing scale and activity tracker. The intervention is rolled out postpartum (4 coaching sessions between week 6 and month 6) and in a new pregnancy (3 coaching sessions, one in each trimester of pregnancy); the mobile app is used throughout the two intervention phases. Data collection includes data from the medical record of the participants (pregnancy outcomes and medical history), anthropometric data (height, weight, waist- and hip circumferences, skinfold thickness and body composition by bio-electrical impedance analysis), data from the mobile app (physical activity and weight; intervention group only) and questionnaires (socio-demographics, breastfeeding, food intake, physical activity, lifestyle, psychosocial factors and process evaluation). Medical record data are collected at inclusion and at delivery of the subsequent pregnancy. All other data are collected at week 6 and month 6 postpartum and every subsequent 6 months until a new pregnancy, and in every trimester in the new pregnancy. Primary outcome is the composite endpoint score of pregnancy-induced hypertension, gestational diabetes mellitus, caesarean section, and large-for-gestational-age infant in the subsequent pregnancy. INTER-ACT is a unique randomised controlled lifestyle intervention trial in its implementation between pregnancies and during the subsequent pregnancy, with an e-health driven approach. ClinicalTrials.gov Identifier: NCT02989142 . Registered August 2016.

Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer.

PubMed

Braam, Katja I; van Dijk, Elisabeth M; Veening, Margreet A; Bierings, Marc B; Merks, Johannes H M; Grootenhuis, Martha A; Chinapaw, Mai J M; Sinnema, Gerben; Takken, Tim; Huisman, Jaap; Kaspers, Gertjan J L; van Dulmen-den Broeder, Eline

2010-11-11

Childhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective. This multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group. Childhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care. NTR1531 (The Netherlands National Trial Register).

Effect of personalised citizen assistance for social participation (APIC) on older adults’ health and social participation: study protocol for a pragmatic multicentre randomised controlled trial (RCT)

PubMed Central

Levasseur, Mélanie; Dubois, Marie-France; Filliatrault, Johanne; Vasiliadis, Helen-Maria; Lacasse-Bédard, Joanie; Tourigny, André; Levert, Marie-Josée; Gabaude, Catherine; Lefebvre, Hélène; Berger, Valérie; Eymard, Chantal

2018-01-01

Introduction The challenges of global ageing and the growing burden of chronic diseases require innovative interventions acting on health determinants like social participation. Many older adults do not have equitable opportunities to achieve full social participation, and interventions might underempower their personal and environmental resources and only reach a minority. To optimise current practices, the Accompagnement-citoyen Personnalisé d’Intégration Communautaire (APIC), an intervention demonstrated as being feasible and having positive impacts, needs further evaluation. Methods and analysis A pragmatic multicentre, prospective, two-armed, randomised controlled trial will evaluate: (1) the short-term and long-term effects of the APIC on older adults’ health, social participation, life satisfaction and healthcare services utilisation and (2) its cost-effectiveness. A total of 376 participants restricted in at least one instrumental activity of daily living and living in three large cities in the province of Quebec, Canada, will be randomly assigned to the experimental or control group using a centralised computer-generated random number sequence procedure. The experimental group will receive weekly 3-hour personalised stimulation sessions given by a trained volunteer over the first 12 months. Sessions will encourage empowerment, gradual mobilisation of personal and environmental resources and community integration. The control group will receive the publicly funded universal healthcare services available to all Quebecers. Over 2 years (baseline and 12, 18 and 24 months later), self-administered questionnaires will assess physical and mental health (primary outcome; version 2 of the 36-item Short-Form Health Survey, converted to SF-6D utility scores for quality-adjusted life years), social participation (Social Participation Scale) and life satisfaction (Life Satisfaction Index-Z). Healthcare services utilisation will be recorded and costs of each intervention calculated. Ethics and dissemination The Research Ethics Committee of the CIUSSS Estrie – CHUS has approved the study (MP-31-2018-2424). An informed consent form will be read and signed by all study participants. Findings will be published and presented at conferences. Trial registration number NCT03161860; Pre-results. PMID:29605819

Resolving controversies in hip fracture care: the need for large collaborative trials in hip fractures.

PubMed

Bhandari, Mohit; Sprague, Sheila; Schemitsch, Emil H

2009-07-01

Hip fractures are a significant cause of morbidity and mortality worldwide and the burden of disability associated with hip fractures globally vindicate the need for high-quality research to advance the care of patients with hip fractures. Historically, large, multi-centre randomized controlled trials have been rare in the orthopaedic trauma literature. Similar to other medical specialties, orthopaedic research is currently undergoing a paradigm shift from single centre initiatives to larger collaborative groups. This is evident with the establishment of several collaborative groups in Canada, in the United States, and in Europe, which has proven that multi-centre trials can be extremely successful in orthopaedic trauma research.Despite ever increasing literature on the topic of his fractures, the optimal treatment of hip fractures remains unknown and controversial. To resolve this controversy large multi-national collaborative randomized controlled trials are required. In 2005, the International Hip Fracture Research Collaborative was officially established following funding from the Canadian Institute of Health Research International Opportunity Program with the mandate of resolving controversies in hip fracture management. This manuscript will describe the need, the information, the organization, and the accomplishments to date of the International Hip Fracture Research Collaborative.

Determining Surgical Complications in the Overweight (DISCOVER): a multicentre observational cohort study to evaluate the role of obesity as a risk factor for postoperative complications in general surgery.

PubMed

Nepogodiev, Dmitri; Chapman, Stephen J; Glasbey, James; Kelly, Michael; Khatri, Chetan; Drake, Thomas M; Kong, Chia Yew; Mitchell, Harriet; Harrison, Ewen M; Fitzgerald, J Edward; Bhangu, Aneel

2015-07-20

Obesity is increasingly prevalent among patients undergoing surgery. Conflicting evidence exists regarding the impact of obesity on postoperative complications. This multicentre study aims to determine whether obesity is associated with increased postoperative complications following general surgery. This prospective, multicentre cohort study will be performed utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency, gastrointestinal, bariatric or hepatobiliary surgery will be included. Day case patients will be excluded. The primary end point will be the overall 30-day major complication rate (Clavien-Dindo grade III-V complications). Data will be collected to risk-adjust outcomes for potential confounding factors, such as preoperative cardiac risk. This study will be disseminated through structured medical student networks using established collaborative methodology. The study will be powered to detect a two-percentage point increase in the major postoperative complication rate in obese versus non-obese patients. Following appropriate assessment, an exemption from full ethics committee review has been received, and the study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through national and local research collaborative networks. 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.

Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial

PubMed Central

Armstrong, Matthew J; Barton, Darren; Gaunt, Piers; Hull, Diana; Guo, Kathy; Stocken, Deborah; Gough, Stephen C L; Tomlinson, Jeremy W; Brown, Rachel M; Hübscher, Stefan G; Newsome, Philip N

2013-01-01

Introduction Non-alcoholic steatohepatitis (NASH) is now the commonest cause of chronic liver disease. Despite this, there are no universally accepted pharmacological therapies for NASH. Liraglutide (Victoza), a human glucagon-like peptide-1 (GLP-1) analogue, has been shown to improve weight loss, glycaemic control and liver enzymes in type 2 diabetes. There is currently a lack of prospective-controlled studies investigating the efficacy of GLP-1 analogues in patients with NASH. Methods and analysis Liraglutide efficacy and action in NASH (LEAN) is a phase II, multicentre, double-blinded, placebo-controlled, randomised clinical trial designed to investigate whether a 48-week treatment with 1.8 mg liraglutide will result in improvements in liver histology in patients with NASH. Adult, overweight (body mass index ≥25 kg/m2) patients with biopsy-confirmed NASH were assessed for eligibility at five recruitment centres in the UK. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). Using A'Hern's single stage phase II methodology (significance level 0.05; power 0.90) and accounting for an estimated 20% withdrawal rate, a minimum of 25 patients were randomised to each treatment group. The primary outcome measure will be centrally assessed using an intention-to-treat analysis of the proportion of evaluable patients achieving an improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. Histological improvement will be defined as a combination of the disappearance of active NASH and no worsening in fibrosis. Ethics and dissemination The protocol was approved by the National Research Ethics Service (East Midlands—Northampton committee; 10/H0402/32) and the Medicines and Healthcare products Regulatory Agency. Recruitment into the LEAN started in August 2010 and ended in May 2013, with 52 patients randomised. The treatment follow-up of LEAN participants is currently ongoing and is due to finish in July 2014. The findings of this trial will be disseminated through peer-reviewed publications and international presentations. Trial registration clinicaltrials.gov NCT01237119. PMID:24189085

Effect of a new insulin treatment regimen on glycaemic control and quality of life of Muslim patients with type 2 diabetes mellitus during Ramadan fast - an open label, controlled, multicentre, cluster randomised study.

PubMed

Shehadeh, N; Maor, Y

2015-11-01

We performed a non-inferiority trial comparing insulin detemir (Levemir) and biphasic insulin (NovoMix70) to standard care during Ramadan fast in insulin treated type 2 diabetes mellitus (T2DM) patients. This was an open label, controlled, multicentre, cluster randomised non-inferiority study. Insulin treated T2DM patients from 12 randomly selected primary clinics received Levemir and NovoMix 70 (intervention, n = 127) or standard care according to the American Diabetes Association recommendations (control, n = 118). Insulin dose (intervention) was 60% of the usual, of this 40% was dosed as Levemir at sunrise and 60% as NovoMix 70 before dinner. Insulin was titrated according to daily 4 point self-measured blood glucose (4P-SMBG) levels. The primary outcome was the difference in mean daily 4P-SMBG during days 23-30 of treatment. Mean age was 60.1 (SD 8.9) and 59.4 (SD 10.1) years in the intervention and control respectively. Mean HbA1c was 8.38% (68 mmol/mol) (SD 0.96) and 8.45% (69 mmol/mol) (SD 1.08). Mean BMI was 32.99 (SD 7.05) and 33.08 (SD 7.24), respectively. The intervention was non-inferior to standard care as assessed by mean 4P-SMBG during days 23-30 of treatment [155 (SD 30.76) mg% and 159 (SD 33.24) mg% respectively, p = 0.269]. Adverse event rate was significantly lower in the intervention group [0.04 (SD 0.06) vs. 0.07 (SD 0.11), p = 0.010]. In particular, hypoglycaemia event rate was lower in the intervention group [0.00 (SD 0.01) vs. 0.01 (SD 0.03), p ≤ 0.001]. To conclude, treatment with Levemir and NovoMix 70 was non-inferior to standard care in this heterogeneous group of patients and was associated with less adverse events. © 2015 John Wiley & Sons Ltd.

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

PubMed Central

Döbrönte, Zoltán; Szepes, Zoltán; Izbéki, Ferenc; Gervain, Judit; Lakatos, László; Pécsi, Gyula; Ihász, Miklós; Lakner, Lilla; Toldy, Erzsébet; Czakó, László

2014-01-01

AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. METHODS: A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. RESULTS: Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. CONCLUSION: 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis. PMID:25110443

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

PubMed

Döbrönte, Zoltán; Szepes, Zoltán; Izbéki, Ferenc; Gervain, Judit; Lakatos, László; Pécsi, Gyula; Ihász, Miklós; Lakner, Lilla; Toldy, Erzsébet; Czakó, László

2014-08-07

To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study

PubMed Central

Vychytil, Andreas; Remón, César; Michel, Catherine; Williams, Paul; Rodríguez-Carmona, Ana; Marrón, Belén; Vonesh, Ed; van der Heyden, Synke; Filho, Jose C. Divino

2008-01-01

Background. Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. Methods. The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal™) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. Results. There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. Conclusion. Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates. PMID:18556747

A multi-centre randomised controlled trial of rehabilitation aimed at improving outdoor mobility for people after stroke: Study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person’s quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. Methods/design This is a multi-centre parallel group individually randomised, controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to four months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood information is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. Discussion This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012. Trial registration ISRCTN58683841 PMID:22721452

Innovative Telemonitoring Enhanced Care Programme for Chronic Heart Failure (ITEC-CHF) to improve guideline compliance and collaborative care: protocol of a multicentre randomised controlled trial

PubMed Central

Jayasena, Rajiv; Maiorana, Andrew; Dowling, Alison; Chen, Sheau Huey; Karunanithi, Mohan; Layland, Jamie; Edwards, Iain

2017-01-01

Introduction Chronic heart failure (CHF) is a life-threatening chronic disease characterised by periodic exacerbations and recurrent hospitalisations. In the management of CHF, patient compliance with evidence-based clinical guidelines is essential, but remains difficult practically. The objective of this study is to examine whether an Innovative Telemonitoring Enhanced Care Programme for CHF (ITEC-CHF) improves patients’ compliance, and associated health and economic outcomes. Methods and analysis An open multicentre randomised controlled trial has been designed. Patients will be recruited and randomised to receive either ITEC-CHF (n=150) or usual care CHF (n=150) for at least 6 months. ITEC-CHF combines usual care and an additional telemonitoring service including remote weight monitoring, structured telephone support and nurse-led collaborative care. The primary outcomes are the compliance rates with the best-practice guidelines for daily weight monitoring. The secondary outcomes include the compliance with other guideline recommendations (health maintenance, medication, diet and exercise), health (health-related quality of life, risk factors, functional capacity and psychological states) and economic outcomes related to the use of healthcare resources such as hospital readmissions and general practitioner/emergency department visits. Ethics and dissemination The clinical trial has been approved by Peninsula Health Human Research Ethics Committee (HREC Reference: HREC/14/PH/27), Royal Perth Hospital Human Research Ethics Committee (Reference: 15-081) and the Curtin University Human Research Ethics Committee (Reference: HR 181/2014). We will disseminate the final results to the public via conferences and journal publications. A final study report will also be provided to the ethics committees. Trial registration number Registered with Australian New Zealand Clinical Trial Registry (ACTRN12614000916640). PMID:28993389

Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial

PubMed Central

Chandrashekhar, B S; Anitha, M.; Ruparelia, Mukesh; Vaidya, Pradyumna; Aamir, Riyaz; Shah, Sunil; Thilak, S; Aurangabadkar, Sanjeev; Pal, Sandeep; Saraswat, Abir

2015-01-01

Background: Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. Aim: The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. Materials and Methods: This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. Results: A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. Conclusion: In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation. PMID:25738069

Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study

PubMed Central

Predel, H; Koll, R; Pabst, H; Dieter, R; Gallacchi, G; Giannetti, B; Bulitta, M; Heidecker, J; Mueller, E

2004-01-01

Objectives: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. Methods: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. Conclusions: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries. PMID:15155436

Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial.

PubMed

Dirkmann, Daniel; Groeben, Harald; Farhan, Hassan; Stahl, David L; Eikermann, Matthias

2015-01-01

This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy. 105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed. In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL(-1) (3.6/4.9) versus (3.2 g⋅dL(-1) (2.4/4.95), p=0.02). Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss. ClinicalTrials.gov Identifier: NCT00346268.

Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

PubMed

Ducloy-Bouthors, Anne-Sophie; Mignon, Alexandre; Huissoud, Cyril; Grouin, Jean-Marie; Mercier, Frédéric J

2016-08-01

Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients≥18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

PubMed

Roulaud, M; Durand-Zaleski, I; Ingrand, P; Serrie, A; Diallo, B; Peruzzi, P; Hieu, P D; Voirin, J; Raoul, S; Page, P; Fontaine, D; Lantéri-Minet, M; Blond, S; Buisset, N; Cuny, E; Cadenne, M; Caire, F; Ranoux, D; Mertens, P; Naous, H; Simon, E; Emery, E; Gadan, B; Regis, J; Sol, J-C; Béraud, G; Debiais, F; Durand, G; Guetarni Ging, F; Prévost, A; Brandet, C; Monlezun, O; Delmotte, A; d'Houtaud, S; Bataille, B; Rigoard, P

2015-03-01

Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Protocol for the specialist supervised individualised multifactorial treatment of new clinically diagnosed type 2 diabetes in general practice (IDA): a prospective controlled multicentre open-label intervention study

PubMed Central

Stidsen, Jacob Volmer; Nielsen, Jens Steen; Henriksen, Jan Erik; Friborg, Søren Gunnar; Olesen, Thomas Bastholm; Olsen, Michael Hecht; Beck-Nielsen, Henning

2017-01-01

Introduction We present the protocol for a multifactorial intervention study designed to test whether individualised treatment, based on pathophysiological phenotyping and individualised treatment goals, improves type 2 diabetes (T2D) outcomes. Methods and analysis We will conduct a prospective controlled multicentre open-label intervention study, drawing on the longitudinal cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2). New clinically diagnosed patients with T2D in the intervention group will be assigned to receive individualised treatment by their general practitioner. Intervention patients will be compared with a matched control cohort of DD2 patients receiving routine clinical care. Among intervention patients, we will first do pathophysiological phenotyping to classify patients into WHO-defined T2D or other specific types of diabetes (monogenic diabetes, secondary diabetes etc). Patients with WHO-defined T2D will then be further subcharacterised by their beta-cell function (BCF) and insulin sensitivity (IS), using the revised homeostatic assessment model, as having either insulinopaenic T2D (high IS and low BCF), classical T2D (low IS and low BCF) or hyperinsulinaemic T2D (low IS and high BCF). For each subtype, a specific treatment algorithm will target the primary pathophysiological defect. Similarly, antihypertensive treatment will be targeted at the specific underlying pathophysiology, characterised by impedance cardiography (relative importance of vascular resistance, intravascular volume and cardiac inotropy). All treatment goals will be based on individual patient assessment of expected positive versus adverse effects. Web-based and face-to-face individualised lifestyle intervention will also be implemented to empower patients to make a sustainable improvement in daily physical activity and to change to a low-carbohydrate diet. Ethics and dissemination The study will use well-known pharmacological agents according to their labels; patient safety is therefore considered high. Study results will be published in international peer-reviewed journals. Trial registration number NCT02015130; Pre-results. PMID:29229652

A personal history of the MASTER Trial and its link to the clinical trials network of the Australian and New Zealand College of Anaesthetists.

PubMed

Rigg, J R A

2016-07-01

The aim of this paper is to link the history of the Multicentre Australian Study of Epidural Anaesthesia in high risk surgery, the MASTER Trial, the first National Health and Medical Research Council (NHMRC) funded multicentre randomised clinical trial in Australia led by anaesthetist researchers, and the decision of The Australian and New Zealand College of Anaesthetists (ANZCA) to establish a clinical trials network, in 2003, to the success of contemporary researchers in Australia and New Zealand in anaesthesia and perioperative medicine.

The talent study: a multicentre randomized controlled trial assessing the impact of a 'tailored lifestyle self-management intervention' (talent) on weight reduction.

PubMed

Melchart, Dieter; Doerfler, Wolfgang; Eustachi, Axel; Wellenhofer-Li, Yanqing; Weidenhammer, Wolfgang

2015-01-01

Overweight is considered an important risk factor for diseases in the context of metabolic syndrome. Lifestyle modifications are the means of choice to reduce weight in persons with a Body Mass Index of 28 to 35. The study examines whether there are any differences between two intervention strategies regarding weight reduction in overweight persons. The study is a multicentre randomized controlled trial with observation duration of 12 months. Eight study centres are involved to include a minimal sample size of 150 participants. Randomization ratio is 2:1. Feasible persons are checked according to inclusion and exclusion criteria and after given informed consent are assigned randomly to one of two intervention programs: A) intervention group: comprehensive lifestyle modification program (Individual Health Management IHM) with 3 months reduction phase plus 9 months maintaining phase, B) control group: written information with advice for healthy food habits (Usual care UC). Participants of the IHM group have access to a web-based health portal and join 3 full-day and 10 two-hour training sessions during the first 3 months. During the remaining 9 months four refresh trainings will be performed. There are 3 different diet strategies (fasting, two-day diet, meal replacement) for free choice. Participants of the control group are provided with acknowledged rules for healthy food according to the German Nutrition Society (DGE). Examinations are conducted at baseline, after 3, 6, 9 and 12 months. They include body weight, waist circumference, blood pressure, laboratory findings and a bio-impedance analysis to measure body composition. Statistical analysis of the primary outcome 'change of body weight after 12 months' is based on ITT population including analysis of variance of the weight differences between month 0 and 12 with the factors 'group', 'baseline value' and 'study centre'. Secondary outcomes will be analyzed exploratively. The monitoring of the study will implement different measures to enhance compliance, avoid attrition and ensure data quality. Based on a blended learning concept and using web-based e-health tools the program promises to achieve sustainable effects in weight reduction. German Clinical Trials Register Freiburg (DRKS): DRKS00006736 (date registered 20/09/2014).

EBV+ HHV-8+ Multicentric Castleman Disease With Plasmablastic Aggregates in an HIV+ Man: An Evolving Clinicopathologic Entity.

PubMed

Shivane, Aditya; Pearce, Amy; Khatib, Nadia; Smith, Mark E F

2018-06-01

We report a case of EBV+ and HHV-8+ multicentric Castleman disease with plasmablastic aggregates in an HIV-positive individual. A 41-year-old man presented in early 2015 with fevers, sweats, weight loss, intractable itching, and on subsequent testing was found to be HIV positive. Investigations showed cervical lymphadenopathy and splenomegaly. He was treated for HIV and his symptoms resolved. His symptoms recurred in January 2016, and a provisional diagnosis of multicentric Castleman disease was entertained. The HHV-8 (human herpesvirus-8) and EBV (Epstein-Barr virus) viral load was elevated. A left supraclavicular lymph node core biopsy was performed, which showed features of multicentric Castleman disease with plasmablastic aggregates that are EBV (EBER) and HHV-8 positive. He responded well to rituximab treatment and remains well with no symptoms at recent follow-up.

Multi-Centrality Graph Spectral Decompositions and Their Application to Cyber Intrusion Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Pin-Yu; Choudhury, Sutanay; Hero, Alfred

Many modern datasets can be represented as graphs and hence spectral decompositions such as graph principal component analysis (PCA) can be useful. Distinct from previous graph decomposition approaches based on subspace projection of a single topological feature, e.g., the centered graph adjacency matrix (graph Laplacian), we propose spectral decomposition approaches to graph PCA and graph dictionary learning that integrate multiple features, including graph walk statistics, centrality measures and graph distances to reference nodes. In this paper we propose a new PCA method for single graph analysis, called multi-centrality graph PCA (MC-GPCA), and a new dictionary learning method for ensembles ofmore » graphs, called multi-centrality graph dictionary learning (MC-GDL), both based on spectral decomposition of multi-centrality matrices. As an application to cyber intrusion detection, MC-GPCA can be an effective indicator of anomalous connectivity pattern and MC-GDL can provide discriminative basis for attack classification.« less

Twelve-month short-term safety and visual-acuity results from a multicentre prospective study of epiretinal strontium-90 brachytherapy with bevacizumab for the treatment of subfoveal choroidal neovascularisation secondary to age-related macular degeneration.

PubMed

Avila, M P; Farah, M E; Santos, A; Duprat, J P; Woodward, B W; Nau, J

2009-03-01

This study evaluated the short-term safety and feasibility of epiretinal strontium-90 brachytherapy delivered concomitantly with intravitreal bevacizumab for the treatment of subfoveal CNV due to AMD for 12 months. A 3-year follow-up is planned. In this prospective, non-randomised, multicentre study, 34 treatment-naïve patients with predominantly classic, minimally classic and occult subfoveal CNV lesions received a single treatment with 24 Gy beta radiation (strontium-90) and two injections of the anti-VEGF antibody bevacizumab. Adverse events were observed. BCVA was measured using standard ETDRS vision charts. Twelve months after treatment, no radiation-associated adverse events were observed. In the intent-to-treat (ITT) population, 91% of patients lost <3 lines (15 ETDRS letters) of vision at 12 months, 68% improved or maintained their BCVA at 12 months, and 38% gained >/=3 lines. The mean change in BCVA observed at month 12 was a gain of 8.9 letters. The safety and efficacy of intraocular, epiretinal brachytherapy delivered concomitantly with anti-VEGF therapy for the treatment of subfoveal CNV secondary to AMD were promising in this small study population. Long-term safety will be assessed for 3 years. This regimen is being evaluated in a large, multicentre, phase III study.

Harmonization Process and Reliability Assessment of Anthropometric Measurements in the Elderly EXERNET Multi-Centre Study

PubMed Central

Gómez-Cabello, Alba; Vicente-Rodríguez, Germán; Albers, Ulrike; Mata, Esmeralda; Rodriguez-Marroyo, Jose A.; Olivares, Pedro R.; Gusi, Narcis; Villa, Gerardo; Aznar, Susana; Gonzalez-Gross, Marcela; Casajús, Jose A.; Ara, Ignacio

2012-01-01

Background The elderly EXERNET multi-centre study aims to collect normative anthropometric data for old functionally independent adults living in Spain. Purpose To describe the standardization process and reliability of the anthropometric measurements carried out in the pilot study and during the final workshop, examining both intra- and inter-rater errors for measurements. Materials and Methods A total of 98 elderly from five different regions participated in the intra-rater error assessment, and 10 different seniors living in the city of Toledo (Spain) participated in the inter-rater assessment. We examined both intra- and inter-rater errors for heights and circumferences. Results For height, intra-rater technical errors of measurement (TEMs) were smaller than 0.25 cm. For circumferences and knee height, TEMs were smaller than 1 cm, except for waist circumference in the city of Cáceres. Reliability for heights and circumferences was greater than 98% in all cases. Inter-rater TEMs were 0.61 cm for height, 0.75 cm for knee-height and ranged between 2.70 and 3.09 cm for the circumferences measured. Inter-rater reliabilities for anthropometric measurements were always higher than 90%. Conclusion The harmonization process, including the workshop and pilot study, guarantee the quality of the anthropometric measurements in the elderly EXERNET multi-centre study. High reliability and low TEM may be expected when assessing anthropometry in elderly population. PMID:22860013

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale, Multicentre Study

PubMed Central

Zheng, Lei; Yin, Yuepeng; Zou, Zhenzhen; Zhou, Feiguo; Zhou, Weiping; Shen, Feng; Gao, Chunfang

2016-01-01

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population. PMID:27070780

Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

PubMed

Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W

2016-12-01

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ 2 =0.41; p=0.813) or the 16-weeks complete medication period (χ 2 =0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Recruitment and retention of participants in randomised controlled trials: a review of trials funded and published by the United Kingdom Health Technology Assessment Programme

PubMed Central

Bonacho dos Anjos Henriques-Cadby, Inês; Bortolami, Oscar; Flight, Laura; Hind, Daniel; Knox, Christopher; Nadin, Ben; Rothwell, Joanne; Surtees, Michael; Julious, Steven A

2017-01-01

Background Substantial amounts of public funds are invested in health research worldwide. Publicly funded randomised controlled trials (RCTs) often recruit participants at a slower than anticipated rate. Many trials fail to reach their planned sample size within the envisaged trial timescale and trial funding envelope. Objectives To review the consent, recruitment and retention rates for single and multicentre randomised control trials funded and published by the UK's National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme. Data sources and study selection HTA reports of individually randomised single or multicentre RCTs published from the start of 2004 to the end of April 2016 were reviewed. Data extraction Information was extracted, relating to the trial characteristics, sample size, recruitment and retention by two independent reviewers. Main outcome measures Target sample size and whether it was achieved; recruitment rates (number of participants recruited per centre per month) and retention rates (randomised participants retained and assessed with valid primary outcome data). Results This review identified 151 individually RCTs from 787 NIHR HTA reports. The final recruitment target sample size was achieved in 56% (85/151) of the RCTs and more than 80% of the final target sample size was achieved for 79% of the RCTs (119/151). The median recruitment rate (participants per centre per month) was found to be 0.92 (IQR 0.43–2.79) and the median retention rate (proportion of participants with valid primary outcome data at follow-up) was estimated at 89% (IQR 79–97%). Conclusions There is considerable variation in the consent, recruitment and retention rates in publicly funded RCTs. Investigators should bear this in mind at the planning stage of their study and not be overly optimistic about their recruitment projections. PMID:28320800

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

PubMed

Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

2015-02-01

The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Cognitive and emotional factors affecting avoidable decision-making delay in acute myocardial infarction male adults.

PubMed

Vidotto, Giulio; Bertolotti, Giorgio; Zotti, AnnaMaria; Marchi, Stefano; Tavazzi, Luigi

2013-01-01

To study the potentially avoidable decision-making delay in acute myocardial infarction (AMI) adults male with different psychological characteristics a nationwide multicentre study was conducted in Italy by the 118 Coronary Care Units (CCUs). 929 AMI patients consecutively presented to the CCU in a conscious condition less than two hours, 2-6 hours, 6-12 hours, and more than 12 hours after symptom onset and completing the Disease Distress Questionnaire (DDQ) were enrolled in a multicentre case-control study. The DDQ collects information regarding the decision time to seek help, and includes a set of items assessing psychological factors and pain-related symptoms. The relationship between the perceived threat and the delay due to decision-making was evaluated by means of a multivariate model using LISREL 8 structural equation modelling. The delay significantly correlated with perceived threat, which was mainly related to somatic awareness. It was only slightly related to pain and was not associated with any of the other variables. Perceived threat was also related to psychological upset, fear and health worries, the first of which was considerably influenced by emotional instability. Somatic awareness is the main dimension affecting perceived threat, but subjective pain intensity affects the delay both directly and indirectly. The core of the model is the relationship between perceived threat and the delay due to decision-making. The importance of subjective pain intensity is well documented, but it is still not clear how subjective and objective pain interact.

Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients.

PubMed

Mäurer, M; Ortler, S; Baier, M; Meergans, M; Scherer, P; Hofmann, We; Tracik, F

2013-04-01

Cognitive decline has been recognised as a frequent symptom in multiple sclerosis (MS). Cholinesterase inhibitors (ChEIs) are employed for the treatment of Alzheimer's disease, but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits, particularly deficits of memory function. The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test (SRT) after 16 weeks of treatment. Efficacy and safety of rivastigmine were analysed in a 16-week, multicentre, double-blind, randomised, placebo-controlled study, followed by an optional one-year open-label treatment phase. Effects of rivastigmine and placebo were compared by an analysis of covariance. In total, 86 patients were enrolled. Patients who received rivastigmine (n = 43) showed a non-significant increase in total recall score (sum of all words immediately recalled over all six trials) over placebo (n = 38) after 16 weeks of treatment (p = 0.2576). Other outcome measures provided no evidence supporting benefits of rivastigmine. Treatment with rivastigmine was well tolerated. With the results of this study, the need for an effective therapy in cognitively impaired MS patients is still required. Thus, intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients.

Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.

PubMed

Nishimura, Junichi; Satoh, Taroh; Fukunaga, Mutsumi; Takemoto, Hiroyoshi; Nakata, Ken; Ide, Yoshihito; Fukuzaki, Takayuki; Kudo, Toshihiro; Miyake, Yasuhiro; Yasui, Masayoshi; Morita, Shunji; Sakai, Daisuke; Uemura, Mamoru; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ohno, Yuko; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Nezu, Riichiro; Doki, Yuichiro; Mori, Masaki

2015-07-01

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness of a cognitive behavioural therapy-based rehabilitation programme (Progressive Goal Attainment Program) for patients who are work-disabled due to back pain: study protocol for a multicentre randomised controlled trial

PubMed Central

2013-01-01

Background Psychologically informed rehabilitation programmes such as the Progressive Goal Attainment Program (PGAP) have the potential to address pain-related disability by targeting known psychological factors that inhibit rehabilitation progress. However, no randomised controlled trials of this intervention exist and it has not been evaluated in the Irish health service context. Our objective was to evaluate the clinical efficacy and cost-effectiveness of the PGAP in a multicentre randomised controlled trial with patients who are work-disabled due to back pain. Methods and design Adult patients (ages 18 years and older) with nonmalignant back pain who are work-disabled because of chronic pain and not involved in litigation in relation to their pain were invited to take part. Patients were those who show at least one elevated psychosocial risk factor (above the 50th percentile) on pain disability, fear-based activity avoidance, fatigue, depression or pain catastrophizing. Following screening, patients are randomised equally to the intervention or control condition within each of the seven trial locations. Patients allocated to the control condition receive usual medical care only. Patients allocated to the PGAP intervention condition attend a maximum of 10 weekly individual sessions of structured active rehabilitation in addition to usual care. Sessions are delivered by a clinical psychologist and focus on graded activity, goal-setting, pacing activity and cognitive-behavioural therapy techniques to address possible barriers to rehabilitation. The primary analysis will be based on the amount of change on the Roland Morris Disability Questionnaire posttreatment. We will also measure changes in work status, pain intensity, catastrophizing, depression, fear avoidance and fatigue. Outcome measures are collected at baseline, posttreatment and 12-month follow-up. Health-related resource use is also collected pre- and posttreatment and at 12-month follow-up to evaluate cost-effectiveness. Discussion This study will be the first randomized controlled trial of the PGAP in chronic pain patients and will provide important information about the clinical and cost effectiveness of the programme as well as its feasibility in the context of the Irish health service. Trial registration Current Controlled Trials: ISRCTN61650533 PMID:24021094

Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.

PubMed

Wullt, Marlene; Hagslätt, Marie-Louise Johansson; Odenholt, Inga

2003-01-01

A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.

Lack of genetic association between the phospholipase A2 gene and bipolar mood disorder in a European multicentre case-control study.

PubMed

Dikeos, Dimitris G; Papadimitriou, George N; Souery, Daniel; Del-Favero, Jurgen; Massat, Isabelle; Blackwood, Douglas; Cichon, Sven; Daskalopoulou, Eugenia; Ivezic, Sladjana; Kaneva, Radka; Karadima, Georgia; Lorenzi, Cristina; Milanova, Vihra; Muir, Walter; Nöthen, Markus; Oruc, Lilijana; Rietschel, Marcella; Serretti, Alessandro; Van Broeckhoven, Christine; Soldatos, Constantin R; Stefanis, Costas N; Mendlewicz, Julien

2006-08-01

The possible association between phospholipase A2 gene and bipolar mood disorder was examined in 557 bipolar patients and 725 controls (all personally interviewed), recruited from seven countries (Belgium, Bulgaria, Croatia, Germany, Greece, Italy, and UK). The frequencies of the eight alleles that were identified did not differ between patients and control individuals in the whole population, while the power to detect an association based on our sample was relatively high. Some differences were noted among the various ethnic groups, but no significant trends existed, suggesting that population stratification by country may not be responsible for a type II error. On the basis of these results, mutations of the phospholipase A2 gene, at least in the region close to the polymorphism examined between exons 1 and 2, are not involved in the pathogenesis of bipolar mood disorder.

A randomised controlled trial of six weeks of home enteral nutrition versus standard care after oesophagectomy or total gastrectomy for cancer: report on a pilot and feasibility study.

PubMed

Bowrey, David J; Baker, Melanie; Halliday, Vanessa; Thomas, Anne L; Pulikottil-Jacob, Ruth; Smith, Karen; Morris, Tom; Ring, Arne

2015-11-21

Poor nutrition in the first months after oesophago-gastric resection is a contributing factor to the reduced quality of life seen in these patients. The aim of this pilot and feasibility study was to ascertain the feasibility of conducting a multi-centre randomised controlled trial to evaluate routine home enteral nutrition in these patients. Patients undergoing oesophagectomy or total gastrectomy were randomised to either six weeks of home feeding through a jejunostomy (intervention), or treatment as usual (control). Intervention comprised overnight feeding, providing 50 % of energy and protein requirements, in addition to usual oral intake. Primary outcome measures were recruitment and retention rates at six weeks and six months. Nutritional intake, nutritional parameters, quality of life and healthcare costs were also collected. Interviews were conducted with a sample of participants, to ascertain patient and carer experiences. Fifty-four of 112 (48 %) eligible patients participated in the study over the 20 months. Study retention at six weeks was 41/54 patients (76 %) and at six months was 36/54 (67 %). At six weeks, participants in the control group had lost on average 3.9 kg more than participants in the intervention group (95 % confidence interval [CI] 1.6 to 6.2). These differences remained evident at three months (mean difference 2.5 kg, 95 % CI -0.5 to 5.6) and at six months (mean difference 2.5 kg, 95 % CI -1.2 to 6.1). The mean values observed in the intervention group for mid arm circumference, mid arm muscle circumference, triceps skin fold thickness and right hand grip strength were greater than for the control group at all post hospital discharge time points. The economic evaluation suggested that it was feasible to collect resource use and EQ-5D data for a full cost-effectiveness analysis. Thematic analysis of 15 interviews identified three main themes related to the intervention and the trial: 1) a positive experience, 2) the reasons for taking part, and 3) uncertainty of the study process. This study demonstrated that home enteral feeding by jejunostomy was feasible, safe and acceptable to patients and their carers. Whether home enteral feeding as 'usual practice' is a cost-effective therapy would require confirmation in an appropriately powered, multi-centre study. UK Clinical Research Network ID 12447 (main trial, first registered 30 May 2012); UK Clinical Research Network ID 13361 (qualitative substudy, first registered 30 May 2012); ClinicalTrials.gov NCT01870817 (first registered 28 May 2013).

Montelukast (Singulair) and Pregnancy

MedlinePlus

... 2009. Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes Eur J Clin Pharmacol. ... Conditions of Use Site By: Marketing and Advertising Design Group

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing

PubMed Central

2011-01-01

Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. Trial registration number Current Controlled Trials ISRCTN71327395 assigned 7th June 2010. PMID:21733166

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

PubMed

Dias, Katrin A; Coombes, Jeff S; Green, Daniel J; Gomersall, Sjaan R; Keating, Shelley E; Tjonna, Arnt Erik; Hollekim-Strand, Siri Marte; Hosseini, Mansoureh Sadat; Ro, Torstein Baade; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Ingul, Charlotte B

2016-04-04

The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. NCT01991106. 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/

Supplemental parenteral nutrition in critically ill patients: a study protocol for a phase II randomised controlled trial.

PubMed

Ridley, Emma J; Davies, Andrew R; Parke, Rachael; Bailey, Michael; McArthur, Colin; Gillanders, Lyn; Cooper, David J; McGuinness, Shay

2015-12-24

Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill. This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first). This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zealand. Trial outcomes will guide development of a subsequent larger randomised controlled trial. NCT01847534 (First registered 5 February 2013, last updated 14 October 2015).

Authorship issues in multi-centre clinical trials: the importance of making an authorship contract.

PubMed

Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian; Vinther, Siri

2015-02-01

Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them to qualify for authorship as defined by the International Committee of Medical Journal Editors. Therefore, rules for authorship in multi-centre trials are strongly recommended. We propose two contracts to prevent conflicts regarding authorship; both are freely available for use without pay but with reference to the original source.

Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

PubMed

Platz, T; Eickhof, C; van Kaick, S; Engel, U; Pinkowski, C; Kalok, S; Pause, M

2005-10-01

To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Single blind, multicentre randomized control trial. Three inpatient neurorehabilitation centres. Sixty-two anterior circulation ischaemic stroke patients. Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

Activity and participation, quality of life and user satisfaction outcomes of environmental control systems and smart home technology: a systematic review.

PubMed

Brandt, Ase; Samuelsson, Kersti; Töytäri, Outi; Salminen, Anna-Liisa

2011-01-01

To examine activity and participation, quality of life, and user satisfaction outcomes of environmental control systems (ECSs) and smart home technology (SHT) interventions for persons with impairments. A systematic review. Seventeen databases, three conference proceedings, and two journals were searched without language or study design restrictions covering the period January 1993 - June 2009. Reviewers selected studies, extracted data, and assessed the methodological quality independently. Of 1739 studies identified, five effect studies and six descriptive studies were included. One study was on SHT and the remainder on ECS; functionalities were overlapping. The studies varied in most aspects, and no synthesis could be drawn. However, ECS/SHT tended to increase study participants' independence, instrumental activities of daily living, socialising, and quality of life. Two studies showed high user satisfaction. The level of evidence was regarded as low, mainly due to small study sizes, lacking confounder control, and a majority of descriptive studies. Due to few and small studies and study diversity, it was not possible to determine whether ECS/SHT have positive outcomes for persons with impairment, even though the technologies seem to be promising. High quality outcomes studies such as randomised controlled trials, when feasible, and large longitudinal multi-centre studies are required.

An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial.

PubMed

Langston, Anne L; McCallum, Marilyn; Campbell, Marion K; Robertson, Clare; Ralston, Stuart H

2005-01-01

Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.

The electrical heart axis and ST events in fetal monitoring: A post-hoc analysis following a multicentre randomised controlled trial.

PubMed

Vullings, Rik; Verdurmen, Kim M J; Hulsenboom, Alexandra D J; Scheffer, Stephanie; de Lau, Hinke; Kwee, Anneke; Wijn, Pieter F F; Amer-Wåhlin, Isis; van Laar, Judith O E H; Oei, S Guid

2017-01-01

Reducing perinatal morbidity and mortality is one of the major challenges in modern health care. Analysing the ST segment of the fetal electrocardiogram was thought to be the breakthrough in fetal monitoring during labour. However, its implementation in clinical practice yields many false alarms and ST monitoring is highly dependent on cardiotocogram assessment, limiting its value for the prediction of fetal distress during labour. This study aims to evaluate the relation between physiological variations in the orientation of the fetal electrical heart axis and the occurrence of ST events. A post-hoc analysis was performed following a multicentre randomised controlled trial, including 1097 patients from two participating centres. All women were monitored with ST analysis during labour. Cases of fetal metabolic acidosis, poor signal quality, missing blood gas analysis, and congenital heart disease were excluded. The orientation of the fetal electrical heart axis affects the height of the initial T/QRS baseline, and therefore the incidence of ST events. We grouped tracings with the same initial baseline T/QRS value. We depicted the number of ST events as a function of the initial baseline T/QRS value with a linear regression model. A significant increment of ST events was observed with increasing height of the initial T/QRS baseline, irrespective of the fetal condition; correlation coefficient 0.63, p<0.001. The most frequent T/QRS baseline is 0.12. The orientation of the fetal electrical heart axis and accordingly the height of the initial T/QRS baseline should be taken into account in fetal monitoring with ST analysis.

Persistent occiput posterior: OUTcomes following digital rotation: a pilot randomised controlled trial.

PubMed

Graham, Kathryn; Phipps, Hala; Hyett, Jon A; Ludlow, Joanne P; Mackie, Adam; Marren, Anthony; De Vries, Bradley

2014-06-01

To determine the feasibility of a multicentre randomised controlled trial (RCT) to investigate whether digital rotation of the fetal head from occiput posterior (OP) position in the second stage of labour reduces the risk of operative delivery (defined as caesarean section (CS) or instrumental delivery). We conducted the study between December 2010 and December 2011 in a tertiary referral hospital in Australia. A transabdominal ultrasound was performed early in the second stage of labour on women with cephalic, singleton pregnancies to determine the fetal position. Those women with a fetus in the OP position were randomised to either a digital rotation or a sham procedure. In all other ways, participants received their usual intrapartum care. Data regarding demographics, mode of delivery, labour, post natal period and neonatal outcomes were collected. One thousand and four women were consented, 834 achieved full dilatation, and 30 were randomised. An additional portable ultrasound scan and a blinded 'sham' digital rotation were acceptable to women and staff. Operative delivery rates were 13/15 in the digital rotation (four CS and nine instrumental) and 12/15 in the sham (three CS and nine instrumental) groups, respectively. A large double-blinded multicentre RCT would be feasible and acceptable to women and staff. Strategies to improve recruitment such as consenting women with an effective epidural in active labour should be considered. This would be the first RCT to answer a clinically important question which could significantly affect the operative delivery rate in Australia and internationally. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Treatment of Advanced Glaucoma Study: a multicentre randomised controlled trial comparing primary medical treatment with primary trabeculectomy for people with newly diagnosed advanced glaucoma-study protocol.

PubMed

King, Anthony J; Fernie, Gordon; Azuara-Blanco, Augusto; Burr, Jennifer M; Garway-Heath, Ted; Sparrow, John M; Vale, Luke; Hudson, Jemma; MacLennan, Graeme; McDonald, Alison; Barton, Keith; Norrie, John

2017-10-26

Presentation with advanced glaucoma is the major risk factor for lifetime blindness. Effective intervention at diagnosis is expected to minimise risk of further visual loss in this group of patients. To compare clinical and cost-effectiveness of primary medical management compared with primary surgery for people presenting with advanced open-angle glaucoma (OAG). Design : A prospective, pragmatic multicentre randomised controlled trial (RCT). Twenty-seven UK hospital eye services. Four hundred and forty patients presenting with advanced OAG, according to the Hodapp-Parish-Anderson classification of visual field loss. Participants will be randomised to medical treatment or augmented trabeculectomy (1:1 allocation minimised by centre and presence of advanced disease in both eyes). The primary outcome is vision-related quality of life measured by the National Eye Institute-Visual Function Questionnaire-25 at 24 months. Secondary outcomes include generic EQ-5D-5L, Health Utility Index-3 and glaucoma-related health status (Glaucoma Utility Index), patient experience, visual field measured by mean deviation value, logarithm of the mean angle of resolution visual acuity, intraocular pressure, adverse events, standards for driving and eligibility for blind certification. Incremental cost per quality-adjusted life-year (QALY) based on EQ-5D-5L and glaucoma profile instrument will be estimated. The study will report the comparative effectiveness and cost-effectiveness of medical treatment against augmented trabeculectomy in patients presenting with advanced glaucoma in terms of patient-reported health and visual function, clinical outcomes and incremental cost per QALY at 2 years. Treatment of Advanced Glaucoma Study will be the first RCT reporting outcomes from the perspective of those with advanced glaucoma. ISRCTN56878850, 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.

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial.

PubMed

Neubert, Antje; Baarslag, Manuel Alberto; Dijk, Monique van; Rosmalen, Joost van; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

2017-06-21

Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2-18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; 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.

Cost effectiveness of interpersonal community psychiatric treatment for people with long-term severe non-psychotic mental disorders: protocol of a multi-centre randomized controlled trial.

PubMed

van Veen, Mark; Koekkoek, Bauke; Mulder, Niels; Postulart, Debby; Adang, Eddy; Teerenstra, Steven; Schoonhoven, Lisette; van Achterberg, Theo

2015-05-02

This study aims for health gain and cost reduction in the care for people with long-term non-psychotic psychiatric disorders. Present care for this population has a limited evidence base, is often open ended, little effective, and expensive. Recent epidemiological data shows that 43.5% of the Dutch are affected by mental illness during their life. About 80% of all patients receiving mental health services (MHS) have one or more non-psychotic disorders. Particularly for this group, long-term treatment and care is poorly developed. Care As Usual (CAU) currently is a form of low-structured treatment/care. Interpersonal Community Psychiatric Treatment (ICPT) is a structured treatment for people with long-term, non-psychotic disorders, developed together with patients, professionals, and experts. ICPT uses a number of evidence-based techniques and was positively evaluated in a controlled pilot study. Multi-centre cluster-randomized clinical trial: 36 professionals will be randomly allocated to either ICPT or CAU for an intervention period of 12 months, and a follow-up of 6 months. 180 Patients between 18-65 years of age will be included, who have been diagnosed with a non-psychotic psychiatric disorder (depressive, anxiety, personality or substance abuse disorder), have long-term (>2 years) or high care use (>1 outpatient contact per week or >2 crisis contacts per year or >1 inpatient admission per year), and who receive treatment in a specialized mental health care setting. The primary outcome variable is quality of life; secondary outcomes are costs, recovery, general mental health, therapeutic alliance, professional-perceived difficulty of patient, care needs and social contacts. No RCT, nor cost-effectiveness study, has been conducted on ICPT so far. The empirical base for current CAU is weak, if not absent. This study will fill this void, and generate data needed to improve daily mental health care. Netherlands Trial Register (NTR): 3988 . Registered 13th of May 2013.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective.

PubMed

Ezzat, Hanna; Ross, Sue; von Dadelszen, Peter; Morris, Tara; Liston, Robert; Magee, Laura A

2010-07-30

For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review.

The EuroNet paediatric hodgkin network - modern imaging data management for real time central review in multicentre trials.

PubMed

Kurch, L; Mauz-Körholz, C; Bertling, S; Wallinder, M; Kaminska, M; Marwede, D; Tchavdarova, L; Georgi, T W; Elsner, A; Barthel, A; Stoevesandt, D; Hasenclever, D; Sattler, B; Sabri, O; Körholz, D; Kluge, R

2013-11-01

Since 2007, children and adolescents with Hodgkin lymphomas are treated in the Europe-wide EuroNet-PHL trials. A real time central review process for stratification of the patients enhances quality control and efficient therapy management. This process includes reading of all cross-sectional-images. Since reference evaluation is time critical, a fast, easy to handle and safe data transfer is important. In addition, immediate and constant access to all the data has to be guaranteed in case of queries and for regulatory reasons. To meet the mentioned requirements the EuroNet Paediatric Hodgkin Data Network (funded by the European Union - Project Number: 2007108) was established between 2008 and 2011. A respective tailored data protection plan was formulated. The aim of this article is to describe the networks' mode of operation and the advantages for multi-centre trials that include centralized image review. © Georg Thieme Verlag KG Stuttgart · New York.

Strengthening Data Confidentiality and Integrity Protection in the Context of a Multi-Centric Information System Dedicated to Autism Spectrum Disorder.

PubMed

Ben Said, Mohamed; Robel, Laurence; Golse, Bernard; Jais, Jean Philippe

2017-01-01

Autism spectrum disorders (ASD) are complex neuro-developmental disorders affecting children in early age. Diagnosis relies on multidisciplinary investigations, in psychiatry, neurology, genetics, electrophysiology, neuro-imagery, audiology, and ophthalmology. To support clinicians, researchers, and public health decision makers, we developed an information system dedicated to ASD, called TEDIS. It was designed to manage systematic, exhaustive and continuous multi-centric patient data collection via secured internet connections. TEDIS will be deployed in nine ASD expert assessment centers in Ile-DeFrance district. We present security policy and infrastructure developed in context of TEDIS to protect patient privacy and clinical information. TEDIS security policy was organized around governance, ethical and organisational chart-agreement, patients consents, controlled user access, patients' privacy protection, constrained patients' data access. Security infrastructure was enriched by further technical solutions to reinforce ASD patients' privacy protection. Solutions were tested on local secured intranet environment and showed fluid functionality with consistent, transparent and safe encrypting-decrypting results.

Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction

PubMed Central

Nordlund, David; Klug, Gert; Heiberg, Einar; Koul, Sasha; Larsen, Terje H.; Hoffmann, Pavel; Metzler, Bernhard; Erlinge, David; Atar, Dan; Aletras, Anthony H.; Carlsson, Marcus; Engblom, Henrik; Arheden, Håkan

2016-01-01

Aims Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings. Methods and results A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1–8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r2 = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44). Conclusion In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials. PMID:27002140

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.

Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology.

PubMed

Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne; Albertsen, Birgitte K; Frisk, Tony; Tedgård, Ulf; Jónsson, Ólafur G; Pruunsild, Kaie; Gretenkort Andersson, Nadine; Winther Gunnes, Maria; Saulyte Trakymiene, Sonata; Frandsen, Thomas; Heyman, Mats; Ruud, Ellen; Helgestad, Jon

2015-02-01

We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%. Sixteen of the thromboses were related to asparaginase and 16 to steroids. Most CSVTs occurred in the consolidation phase. Nearly all were treated with low molecular weight heparin without bleeding complications. Mortality related to CSVT directly or indirectly was 10%, emphasizing the importance of this complication. © 2014 John Wiley & Sons Ltd.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings.

PubMed

Dickson, Sylvia; Logan, Janet; Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; McDonald, Alison M; McPherson, Gladys

2013-11-15

Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Current Controlled Trials ISRCTN35911035.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings

PubMed Central

2013-01-01

Background Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Methods Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Results Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Conclusions Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Trial registration Current Controlled Trials ISRCTN35911035 PMID:24228935

Efficacy and safety of acarbose chewable tablet in patients with type 2 diabetes: a multicentre, randomized, double-blinded, double-dummy positive controlled trial.

PubMed

Wu, Qian Lin; Liu, Yu Ping; Lu, Ju Ming; Wang, Chang Jiang; Yang, Tao; Dong, Ji Xiang; Li, Cheng Jiang; Ma, Jian Hua; Xue, Yao Ming; Sun, Rui Hua; Wei, Dong; Tian, Hao Ming

2012-08-01

To evaluate the effect and safety of HbA1c and glycemic control of acarbose chewable tablets in patients with type 2 diabetic. A multicentre, randomized, double-blinded, double-dummy, positive controlled clinical trial was conducted. Two hundred thirty-four Chinese patients with type 2 diabetic were enrolled in eight clinical centres, who were divided randomly into the acarbose chewable tablet group (experimental group, n = 116) and the acarbose treatment group (control group, n = 118). Two hundred seven patients (88.5%) took part in the 12-week trial. At the beginning and end of the clinical trial, HbA1c and blood glucose as well as safety indexes were measured. After the treatment, the level of finger two-hour postprandial blood glucose (PPBG) was decreased 4.15 mmol/L (26.82%) and 3.54 mmol/L (22.77%), respectively, in the experiment group and the control group. The levels of venous two-hour PPBG in the experiment group and the control group were decreased 4.04 mmol/L (25.38%) and 2.75 mmol/L (17.26%), respectively, with the means of HbA1c lowering 11.67% and 12.44%, respectively. Fasting blood glucose (FBG) also was reduced significantly in both groups. Patients in both groups showed obvious weight reduction (P < 0.0001). There were no significant differences in the incidence of adverse events between the two groups. In summary, acarbose chewable tablets have a definite curative effect in treating type 2 diabetic patients as HbA1c and blood glucose levels decreased significantly after the 12-week treatment. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Staff regard towards working with substance users: a European multi-centre study.

PubMed

Gilchrist, Gail; Moskalewicz, Jacek; Slezakova, Silvia; Okruhlica, Lubomir; Torrens, Marta; Vajd, Rajko; Baldacchino, Alex

2011-06-01

To compare regard for working with different patient groups (including substance users) among different professional groups in different health-care settings in eight European countries. A multi-centre, cross-sectional comparative study. Primary care, general psychiatry and specialist addiction services in Bulgaria, Greece, Italy, Poland, Scotland, Slovakia, Slovenia and Spain. A multi-disciplinary convenience sample of 866 professionals (physicians, psychiatrists, psychologists, nurses and social workers) from 253 services. The Medical Condition Regard Scale measured regard for working with different patient groups. Multi-factor between-subjects analysis of variance determined the factors associated with regard for each condition by country and all countries. Regard for working with alcohol (mean score alcohol: 45.35, 95% CI 44.76, 45.95) and drug users (mean score drugs: 43.67, 95% CI 42.98, 44.36) was consistently lower than for other patient groups (mean score diabetes: 50.19, 95% CI 49.71, 50.66; mean score depression: 51.34, 95% CI 50.89, 51.79) across all countries participating in the study, particularly among staff from primary care compared to general psychiatry or specialist addiction services (P<0.001). After controlling for sex of staff, profession and duration of time working in profession, treatment entry point and country remained the only statistically significant variables associated with regard for working with alcohol and drug users. Health professionals appear to ascribe lower status to working with substance users than helping other patient groups, particularly in primary care; the effect is larger in some countries than others. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; Findings from the New Zealand multicentre stillbirth case-control study

PubMed Central

Thompson, John M. D.; Cronin, Robin S.; Li, Minglan; Stacey, Tomasina; Stone, Peter R.; Lawton, Beverley A.; Ekeroma, Alec J.; Mitchell, Edwin A.

2017-01-01

Objective Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). Methods A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n = 164) were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n = 569) were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going-to-sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders. Results Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR) 3.67, 95% confidence interval (CI) 1.74 to 7.78) with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI) were: BMI (1.04, 1.01 to 1.08) per unit, maternal age ≥40 (2.88, 1.31 to 6.32), birthweight <10th customised centile (2.76, 1.59 to 4.80), and <6 hours sleep on the last night (1.81, 1.14 to 2.88). The risk associated with supine-going-to-sleep position was greater for term (aOR 10.26, 3.00 to 35.04) than preterm stillbirths (aOR 3.12, 0.97 to 10.05). Conclusions Supine going-to-sleep position is associated with a 3.7 fold increase in overall late stillbirth risk, independent of other common risk factors. A public health campaign encouraging women not to go-to-sleep supine in the third trimester has potential to reduce late stillbirth by approximately 9%. PMID:28609468

A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial.

PubMed

Watson, Angus J M; Bruhn, Hanne; MacLeod, Kathleen; McDonald, Alison; McPherson, Gladys; Kilonzo, Mary; Norrie, John; Loudon, Malcolm A; McCormack, Kirsty; Buckley, Brian; Brown, Steven; Curran, Finlay; Jayne, David; Rajagopal, Ramesh; Cook, Jonathan A

2014-11-11

Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions and, more importantly, patients can make informed choices. Current Controlled Trials ISRCTN80061723 (assigned 8 March 2010).

Efficacy and tolerability of pale sulfonated shale oil cream 4% in the treatment of mild to moderate atopic eczema in children: a multicentre, randomized vehicle-controlled trial.

PubMed

Korting, H C; Schöllmann, C; Cholcha, W; Wolff, L

2010-10-01

Reports on controlled trials on the efficacy and tolerability of sulfonated shale oils in atopic eczema are not available so far. The aim of this study was to investigate whether topically applied, specially prepared pale sulfonated shale oil (PSSO) cream is capable of improving symptoms/signs of mild to moderate atopic eczema in children more efficaciously than a corresponding vehicle cream. A total of 99 children suffering from mild to moderate atopic eczema were enrolled in this multicentre, randomized, vehicle-controlled study. Verum or vehicle cream was applied to the affected skin area three times a day over 4 weeks. As the primary outcome parameter served the reduction of the total score after 4 weeks of treatment, compared with the initial examination. Secondary outcome parameters were addressed as well. Tolerability was judged by investigators and patients/parents, and adverse events were documented. After 4 weeks of treatment, the total score declined from 13.4 ± 3.7 to 4.5 ± 7.4 score points in the verum group and from 13.0 ± 3.1 to 11.7 ± 8.6 score points in the vehicle group (P < 0.0001). The superiority of verum regarding total score was already apparent after a treatment period of 1 week (reduction by 5.6 ± 4.3 vs. 1.3 ± 5.9 score points; P < 0.0001). Tolerability was found superior at the end of the treatment in the verum when compared with the control group--both by investigators (P < 0.0001) and patients/parents (P = 0.0051). Pale sulfonated shale oil cream 4% is capable to treat mild to moderate atopic eczema in children more efficaciously than vehicle and is well tolerated. PSSO thus represents a valuable addition to our therapeutic armamentarium. PSSO should be considered in particular when valid alternatives for topical glucocorticoids are sought for. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol

PubMed Central

Marjanovic, Nicolas; Frasca, Denis; Asehnoune, Karim; Paugam, Catherine; Lasocki, Sigismond; Ichai, Carole; Lefrant, Jean-Yves; Leone, Marc; Dahyot-Fizelier, Claire; Pottecher, Julien; Falcon, Dominique; Veber, Benoit; Constantin, Jean-Michel; Seguin, Sabrina; Guénézan, Jérémy; Mimoz, Olivier

2017-01-01

Introduction Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. Methods and analysis This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. Ethics and dissemination This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. Trial registration Clinical Trials NCT02534974 PMID:28790042

Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.

PubMed

Marjanovic, Nicolas; Frasca, Denis; Asehnoune, Karim; Paugam, Catherine; Lasocki, Sigismond; Ichai, Carole; Lefrant, Jean-Yves; Leone, Marc; Dahyot-Fizelier, Claire; Pottecher, Julien; Falcon, Dominique; Veber, Benoit; Constantin, Jean-Michel; Seguin, Sabrina; Guénézan, Jérémy; Mimoz, Olivier

2017-08-07

Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. Clinical Trials NCT02534974. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effectiveness of a Hospital-Based Work Support Intervention for Female Cancer Patients – A Multi-Centre Randomised Controlled Trial

PubMed Central

Tamminga, Sietske J.; Verbeek, Jos H. A. M.; Bos, Monique M. E. M.; Fons, Guus; Kitzen, Jos J. E. M.; Plaisier, Peter W.; Frings-Dresen, Monique H. W.; de Boer, Angela G. E. M.

2013-01-01

Objective One key aspect of cancer survivorship is return-to-work. Unfortunately, many cancer survivors face problems upon their return-to-work. For that reason, we developed a hospital-based work support intervention aimed at enhancing return-to-work. We studied effectiveness of the intervention compared to usual care for female cancer patients in a multi-centre randomised controlled trial. Methods Breast and gynaecological cancer patients who were treated with curative intent and had paid work were randomised to the intervention group (n = 65) or control group (n = 68). The intervention involved patient education and support at the hospital and improvement of communication between treating and occupational physicians. In addition, we asked patient's occupational physician to organise a meeting with the patient and the supervisor to make a concrete gradual return-to-work plan. Outcomes at 12 months of follow-up included rate and time until return-to-work (full or partial), quality of life, work ability, work functioning, and lost productivity costs. Time until return-to-work was analyzed with Kaplan-Meier survival analysis. Results Return-to-work rates were 86% and 83% (p = 0.6) for the intervention group and control group when excluding 8 patients who died or with a life expectancy of months at follow-up. Median time from initial sick leave to partial return-to-work was 194 days (range 14–435) versus 192 days (range 82–465) (p = 0.90) with a hazard ratio of 1.03 (95% CI 0.64–1.6). Quality of life and work ability improved statistically over time but did not differ statistically between groups. Work functioning and costs did not differ statistically between groups. Conclusion The intervention was easily implemented into usual psycho-oncological care and showed high return-to-work rates. We failed to show any differences between groups on return-to-work outcomes and quality of life scores. Further research is needed to study which aspects of the intervention are useful and which elements need improvement. Trial Registration Nederlands Trial Register (NTR) 1658 PMID:23717406

Efficient, quality-assured data capture in operational research through innovative use of open-access technology

PubMed Central

Naik, B.; Guddemane, D. K.; Bhat, P.; Wilson, N.; Sreenivas, A. N.; Lauritsen, J. M.; Rieder, H. L.

2013-01-01

Ensuring quality of data during electronic data capture has been one of the most neglected components of operational research. Multicentre studies are also challenged with issues about logistics of travel, training, supervision, monitoring and troubleshooting support. Allocating resources to these issues can pose a significant bottleneck for operational research in resource-limited settings. In this article, we describe an innovative and efficient way of coordinating data capture in multicentre operational research using a combination of three open access technologies—EpiData for data capture, Dropbox for sharing files and TeamViewer for providing remote support. PMID:26392997

Gender and regional differences in perceived job stress across Europe.

PubMed

de Smet, P; Sans, S; Dramaix, M; Boulenguez, C; de Backer, G; Ferrario, M; Cesana, G; Houtman, I; Isacsson, S O; Kittel, F; Ostergren, P O; Peres, I; Pelfrene, E; Romon, M; Rosengren, A; Wilhelmsen, L; Kornitzer, M

2005-10-01

Over the last 20 years stress at work has been found to be predictive of several conditions such as coronary heart disease, high blood pressure and non-specific sick leave. The Karasek demand/control/strain concept has been the most widely used in prospective epidemiological studies. To describe distribution in Karasek's demand/control (DC) dimensions as well as prevalence of strain in samples from different parts of Europe grouped into three regions (South, Middle, Sweden), adjusting for occupation. To describe gender differences in Karasek's DC dimensions along with strain prevalence and assess the regional stability of those differences in different occupational groups. The Job stress, Absenteeism and Coronary heart disease in Europe (JACE) study, a Concerted Action (Biomed I) of the European Union, is a multicentre prospective cohort epidemiological study: 38,019 subjects at work aged 35-59 years were surveyed at baseline. Standardised techniques were used for occupation coding (International Standardised Classification of Occupations) and for the DC model (Karasek scale): five items for the psychological demand and nine items for the control or decision latitude dimensions, respectively. A total of 34,972 subjects had a complete data set. There were important regional differences in the Karasek scales and in prevalence of strain even after adjustment for occupational class. Mean demand and control were higher in the Swedish centres when compared to two centres in Milano and Barcelona (Southern region) and values observed in four centres (Ghent, Brussels, Lille and Hoofddorp) in Middle Europe were closer to those observed in the Southern cities than to those obtained in the Swedish cities. Clerks (ISCO 4) and, more specifically, office clerks (ISCO 41) exhibited the smallest regional variation. In a multivariate model, the factor 'region' explained a small fraction of total variance. In the two Southern centres as well as in the four Middle European centres, men perceived marginally less job-demand as compared to women whereas the reverse was observed in the two Swedish centres. Differences were larger for control: men appeared to perceive more control at work than did women. In a multivariate model, gender explained a small fraction whereas occupational level explained a large fraction of the variance. In this standardised multicentre European study Karasek's DC model showed large gender and occupational differences whereas geographic region explained a small fraction of the total DC variance, notwithstanding large differences in labour market and working conditions as pointed out by the European Commission as recently as 2000.

Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial.

PubMed

Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

2016-03-02

Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years.The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy may pave the way for personalised medicine approaches in treatment of diabetes complications. NCT02040441; 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/

Determinants and impact of suboptimal asthma control in Europe: The INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study.

PubMed

Braido, Fulvio; Brusselle, Guy; Guastalla, Daniele; Ingrassia, Eleonora; Nicolini, Gabriele; Price, David; Roche, Nicolas; Soriano, Joan B; Worth, Heinrich

2016-05-14

According to the Global Initiative of Asthma, the aim of asthma treatment is to gain and maintain control. In the INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study, we evaluated the level of asthma control and quality of life (QoL), as well as their determinants and impact in a population consulting specialist settings. LIAISON is a prospective, multicentre, observational study with a cross-sectional and a 12-month longitudinal phase. Adults with an asthma diagnosis since at least 6 months, receiving the same asthma treatment in the 4 weeks before enrolment were included. Asthma control was assessed with the 6-item Asthma Control Questionnaire (ACQ) and QoL with the MiniAsthma Quality of Life Questionnaire (MiniAQLQ). Overall, 8111 asthmatic patients were enrolled in 12 European countries. Asthma control was suboptimal in 56.5 % of patients and it was associated with poorer asthma-related QoL, higher risk of exacerbations and greater consumption of healthcare resources. Variables associated with suboptimal control were age, gender, obesity, smoking and comorbidities. Major determinants of poor asthma control were seasonal worsening and persisting exposure to allergens/irritants/triggers, followed by treatment-related issues. The cross-sectional phase results confirm that suboptimal control is frequent and has a high individual and economic impact. The clinicaltrials.gov identifier is NCT01567280 .

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

[Role of Institutional Review Boards for multi-centre studies in national health services research - a cross-sectional study of the effort to obtain secondary ethical approvals for the DACAPO study].

PubMed

Blecha, Sebastian; Thomann-Hackner, Kathrin; Brandstetter, Susanne; Dodoo-Schittko, Frank; Seboek, Philipp; Apfelbacher, Christian; Graf, Bernhard M; Bein, Thomas

2015-09-01

Health services research (HSR) is of fundamental importance for the continuous improvement of preventive, diagnostic or therapeutic measures. The conduct of multi-centre HSR studies requires that ethical approval by Institutional review boards (IRB's) is obtained. We documented the effort, the complexity and the man power necessary to obtain secondary ethical approval for a national HSR in Germany ("Surviving the Acute Respiratory Distress Syndrome" [DACAPO-study]). Having obtained a primary ethical approval by the IRB of Regensburg University, the time, correspondence, necessity for amendments, corrections, or additional costs by 34 IRB's for 64 participating study centers was documented. The complete obtainment was found to be time consuming and associated with a high workload and man power. A time span of seven month was needed to receive votes from all IRB's. The median time span was 25,5 days (25 %/75 % percentile 13 and 42 days, respectively). Requirements in terms of corrections or amendments were inhomogeneous and frequent changes were necessary. There were additional fees for secondary votes of 4328,40 €. Total costs for the study center Regensburg were 21.193,40 € (2,6 % of the grant volume). Obtaining all ethical approvals for a multi-centre observational HSR study in Germany is complex and time consuming. Various and inhomogeneous formalities may delay the plan and realization of HSR. A Homogenization and simplification of the procedure of ethics votes should be discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results.

PubMed

Hurtado-Chong, Anahí; Joeris, Alexander; Hess, Denise; Blauth, Michael

2017-07-12

A considerable number of clinical studies experience delays, which result in increased duration and costs. In multicentre studies, patient recruitment is among the leading causes of delays. Poor site selection can result in low recruitment and bad data quality. Site selection is therefore crucial for study quality and completion, but currently no specific guidelines are available. Selection of sites adequate to participate in a prospective multicentre cohort study was performed through an open call using a newly developed objective multistep approach. The method is based on use of a network, definition of objective criteria and a systematic screening process. Out of 266 interested sites, 24 were shortlisted and finally 12 sites were selected to participate in the study. The steps in the process included an open call through a network, use of selection questionnaires tailored to the study, evaluation of responses using objective criteria and scripted telephone interviews. At each step, the number of candidate sites was quickly reduced leaving only the most promising candidates. Recruitment and quality of data went according to expectations in spite of the contracting problems faced with some sites. The results of our first experience with a standardised and objective method of site selection are encouraging. The site selection method described here can serve as a guideline for other researchers performing multicentre studies. ClinicalTrials.gov: NCT02297581. © 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.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

PubMed

Falivene, S; Pezzulla, D; Di Franco, R; Giugliano, F M; Esposito, E; Scoglio, C; Amato, B; Borzillo, V; D'Aiuto, M; Muto, P

2017-02-01

Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

Comparison of a CHOP-LAsp-based protocol with and without maintenance for canine multicentric lymphoma.

PubMed

Lautscham, E M; Kessler, M; Ernst, T; Willimzig, L; Neiger, R

2017-03-25

The recommendation to treat canine lymphoma with a discontinuous protocol is based on small case numbers and mostly historic controls. This study compares duration of first remission (DFR) and overall survival time (ST) with a discontinuous protocol to the same protocol with maintenance phase. 408 dogs were treated with a CHOP-LAsp (C=cyclophosphamide; H=hydroxydaunorubicin; O=Oncovin; P=prednisolone; LAsp=l-asparaginase)-based 28-week induction protocol. In 75 dogs (cohort 1), this was followed by a maintenance phase consisting of vincristine, chlorambucil and actinomycin-D with a total treatment duration of two years. In the subsequent 333 dogs, therapy was discontinued after induction (cohort 2). Median DFR and ST in cohort 1 were 216 and 375 days and 184 and 304 days in cohort 2. 6-Month, 1-year and 2-year survival rates in cohort 1 were 73 per cent, 50 per cent, 24 per cent and 67 per cent, 39 per cent, 21 per cent in cohort 2. There was no significant difference between the two protocols (P=0.291 for ST, P=0.071 for DFR). On multivariate analysis, corticosteroid pretreatment (P=0.005), thrombocytopenia at diagnosis (P=0.019), stage (P=0.009), substage b at relapse (P<0.001), age (P=0.002) and incomplete or unstable remission necessitating intensification of therapy (P=0.004) were negatively correlated with ST in both groups. This study supports the use of a discontinuous protocol for canine multicentric lymphoma. British Veterinary Association.

Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study.

PubMed

Dargère, S; Parienti, J-J; Roupie, E; Gancel, P-E; Wiel, E; Smaiti, N; Loiez, C; Joly, L-M; Lemée, L; Pestel-Caron, M; du Cheyron, D; Verdon, R; Leclercq, R; Cattoir, V

2014-11-01

Detection of microorganisms by blood cultures (BCs) is essential in managing patients with bacteraemia. Rather than the number of punctures, the volume of blood drawn is considered paramount in efficient and reliable detection of microorganisms. We performed a 1-year prospective multicentre study in adult emergency departments of three French university hospitals comparing two methods for BCs: a unique blood culture (UBC) collecting a large volume of blood (40 mL) and the standard method of multiple blood cultures (MBC). The performances of both methods for bacterial contamination and efficient microbial detection were compared, each patient serving as his own control. Amongst the 2314 patients included, three hundred were positive for pathogens (n=245) or contaminants (n=55). Out of the 245 patients, 11 were positive for pathogens by UBC but negative by MBC and seven negative by UBC but positive by MBC (p 0.480). In the subgroup of 137 patients with only two BCs, UBC was superior to MBC (p 0.044). Seven and 17 patients had contaminated BCs by UBC and MBC only, respectively (p 0.062). Considering the sums of pathogens missed and contaminants, UBC significantly outperformed MBC (p 0.045). Considering the complete picture of cost savings, efficient detection of microorganisms and decrease in contaminations, UBC offers an interesting alternative to MBC. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Cinacalcet for hypercalcaemic secondary hyperparathyroidism after renal transplantation: a multicentre, retrospective, 3-year study.

PubMed

Torregrosa, Jose-Vicente; Morales, Enrique; Díaz, Juan Manuel; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel Ángel; Rodríguez Benot, Alberto; García, Minerva Rodríguez; Jiménez, Verónica López; Gutiérrez Dalmau, Alex; Jimeno, Luisa; Sáez, María José Pérez; Romero, Rafael; Gómez Alamillo, Carlos

2014-02-01

Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population. We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH) > 120 pg/mL) who initiated cinacalcet in the clinical practice. We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P < 0.0001). Median iPTH was reduced by 23.0% at 6 months (P = 0.0005) and mean phosphorus levels increased by 11.1% (P < 0.0001). The effects were maintained up to 3-years. No changes were observed in renal function or anticalcineurin drug levels. Only 4.1% of patients discontinued cinacalcet due to intolerance and 1.0% due to lack of efficacy. In renal transplant patients with hypercalcaemic SHPT, cinacalcet controlled serum calcium, iPTH and phosphorus levels up to 3 years. Tolerability was good. © 2013 Asian Pacific Society of Nephrology.

Homeopathy in chronic sinusitis: a prospective multi-centric observational study.

PubMed

Nayak, Chaturbhuja; Singh, Vikram; Singh, V P; Oberai, Praveen; Roja, Varanasi; Shitanshu, Shashi Shekhar; Sinha, M N; Deewan, Deepti; Lakhera, B C; Ramteke, Sunil; Kaushik, Subhash; Sarkar, Sarabjit; Mandal, N R; Mohanan, P G; Singh, J R; Biswas, Sabyasachi; Mathew, Georgekutty

2012-04-01

The primary objective was to ascertain the therapeutic usefulness of homeopathic medicine in the management of chronic sinusitis (CS). Multicentre observational study at Institutes and Units of the Central Council for Research in Homoeopathy, India. Symptoms were assessed using the chronic sinusitis assessment score (CSAS). 17 pre-defined homeopathic medicines were shortlisted for prescription on the basis of repertorisation for the pathological symptoms of CS. Regimes and adjustment of regimes in the event of a change of symptoms were pre-defined. The follow-up period was for 6 months. Statistical analysis was done using SPSS version 16. 628 patients suffering from CS confirmed on X-ray were enrolled from eight Institutes and Units of the Central Council for Research in Homoeopathy. All 550 patients with at least one follow-up assessment were analyzed. There was a statistically significant reduction in CSAS (P = 0.0001, Friedman test) after 3 and 6 months of treatment. Radiological appearances also improved. A total of 13 out of 17 pre-defined medicines were prescribed in 550 patients, Sil. (55.2% of 210), Calc. (62.5% of 98), Lyc. (69% of 55), Phos. (66.7% of 45) and Kali iod. (65% of 40) were found to be most useful having marked improvement. 4/17 medicines were never prescribed. No complications were observed during treatment. Homeopathic treatment may be effective for CS patients. Controlled trials are required for further validation. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

The Biosulin equivalence in standard therapy (BEST) study - a multicentre, open-label, non-randomised, interventional, observational study in subjects using Biosulin 30/70 for the treatment of insulin-dependent type 1 and type 2 diabetes mellitus.

PubMed

Segal, D; Tupy, D; Distiller, L

2013-04-02

The need for more cost-effective insulin therapy is critical in reducing the burden on patients and health systems. Biosimilar insulins have the potential to dramatically lower healthcare costs by delivering insulin with a similar anti-glycaemic effect and adverse reaction profile. The purpose of this study was to confirm equivalence in glycaemic outcomes and side-effect profiles between Biosulin 30/70 and other human premixed insulin preparations on the South African market in a clinical practice setting. Subjects in this interventional, observational, multicentre, open-label, prospective study were switched from their existing human premix insulin (Actraphane, Humulin 30/70 or Insuman) to the study insulin Biosulin 30/70. The primary endpoint was the change in HbA1c from baseline to 6 months. Seventy-seven adult patients with type 1(n=18) or type 2 (n=59) diabetes were enrolled. The baseline HbA1c in the overall cohort was 7.9%, 8.0% at 3 months (p=0.50) and 7.6% at 6 months (p=0.14).There was a small increase in the total daily dose of insulin used in both the type 1 and type 2 cohort, from 0.62 to 0.65 units/kg/day (p=0.0004). There was no significant difference in weight in the study subjects during the 6-month period on Biosulin 30/70 (p=0.67). Biosulin 30/70 achieved at least equivalent glycaemic control to existing human premix insulins, with no reported new or severe adverse events. Increased use of biosimilar insulins has the potential for significant cost savings.

A prospective multi-centric open clinical trial of homeopathy in diabetic distal symmetric polyneuropathy.

PubMed

Nayak, Chaturbhuja; Oberai, Praveen; Varanasi, Roja; Baig, Hafeezullah; Ch, Raveender; Reddy, G R C; Devi, Pratima; S, Bhubaneshwari; Singh, Vikram; Singh, V P; Singh, Hari; Shitanshu, Shashi Shekhar

2013-04-01

To evaluate homeopathic treatment in the management of diabetic distal symmetric polyneuropathy. A prospective multi-centric clinical observational study was carried out from October 2005 to September 2009 by Central Council for Research in Homeopathy (CCRH) (India) at its five institutes/units. Patients suffering from diabetes mellitus (DM) and presenting with symptoms of diabetic polyneuropathy (DPN) were screened, investigated and were enrolled in the study after fulfilling the inclusion and exclusion criteria. Patients were evaluated by the diabetic distal symmetric polyneuropathy symptom score (DDSPSS) developed by the Council. A total of 15 homeopathic medicines were identified after repertorizing the nosological symptoms and signs of the disease. The appropriate constitutional medicine was selected and prescribed in 30, 200 and 1 M potency on an individualized basis. Patients were followed up regularly for 12 months. Out of 336 patients (167 males and 169 females) enrolled in the study, 247 patients (123 males and 124 females) were analyzed. All patients who attended at least three follow-up appointments and baseline curve conduction studies were included in the analysis.). A statistically significant improvement in DDSPSS total score (p = 0.0001) was found at 12 months from baseline. Most objective measures did not show significant improvement. Lycopodium clavatum (n = 132), Phosphorus (n = 27) and Sulphur (n = 26) were the medicines most frequently prescribed. Adverse event of hypoglycaemia was observed in one patient only. This study suggests homeopathic medicines may be effective in managing the symptoms of DPN patients. Further studies should be controlled and include the quality of life (QOL) assessment. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

PubMed Central

2011-01-01

Objectives To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas. Patients and methods Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category). Results Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas. Conclusion The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs. Registration details ORPHA86301 PMID:21752287

Detection of Mycoplasma pneumoniae and Legionella pneumophila in Patients Having Community-Acquired Pneumonia: A Multicentric Study from New Delhi, India.

PubMed

Chaudhry, Rama; Valavane, Arvind; Sreenath, K; Choudhary, Mamta; Sagar, Tanu; Shende, Trupti; Varma-Basil, Mandira; Mohanty, Srujana; Kabra, S K; Dey, A B; Thakur, Bhaskar

2017-12-01

Atypical pathogens including Mycoplasma pneumoniae and Legionella pneumophila are increasingly recognized as important causes of community-acquired pneumonia (CAP). Mycoplasma pneumoniae accounts for 20-40% of all CAP and L. pneumophila is responsible for 3-15% of cases. The paucity of data from India in this regard prompted us to conduct this prospective multicentric analysis to detect the prevalence of M. pneumoniae and L. pneumophila in our geographical region. A total of 453 patients with symptoms of pneumonia and 90 controls with no history of lower respiratory tract infections were included in the study. A duplex polymerase chain reaction (PCR) targeting 543 bp region of P1 adhesin gene of M. pneumoniae and 375 bp region of macrophage infectivity potentiator (mip) gene of L. pneumophila was standardized for simultaneous detection of these atypical pathogens. Respiratory secretions, blood, and urine samples were collected from each patient and control and were subjected to duplex PCR, culture and serology for M. pneumoniae and L. pneumophila . Urine samples were subjected for detecting L. pneumophila antigen. Among the 453 patients investigated for M. pneumoniae , 52 (11.4%) were positive for IgM antibodies, 17 were positive by culture, and seven tested positive by PCR ( P1 gene). Similarly for L. pneumophila , 50 cases (11%) were serologically positive for IgM antibodies, one was positive by PCR ( mip gene) and urine antigen detection. A total of eight samples were positive by duplex PCR for M. pneumoniae P1 gene ( N = 7) and L. pneumophila mip gene ( N = 1). Of the 90 controls, two samples (2.2%) showed IgM positivity, and 15 (16.7%) showed IgG positivity for M. pneumoniae . For L. pneumophila , three samples (3.3%) tested positive for IgM, and 12 (13.3%) tested positive for IgG antibodies. The study findings indicate the presence of M. pneumoniae and L. pneumophila in our geographical region, and a combination of laboratory approaches including PCR, culture, and serology is required for effective detection of these agents.

Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.

PubMed

Weis, S; Hagel, S; Schmitz, R P H; Scherag, A; Brunkhorst, F M; Forstner, C; Löffler, B; Pletz, M W

2017-04-08

Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question. SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC. We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media. DRKS00010135. 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/.

At-risk phenotype of neurofibromatose-1 patients: a multicentre case-control study.

PubMed

Sbidian, Emilie; Bastuji-Garin, Sylvie; Valeyrie-Allanore, Laurence; Ferkal, Salah; Lefaucheur, Jean P; Drouet, Alain; Brugière, Pierre; Vialette, Cédric; Combemale, Patrick; Barbarot, Sébastien; Wolkenstein, Pierre

2011-07-13

To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas. Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category). Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas. The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.

Individualised cognitive functional therapy compared with a combined exercise and pain education class for patients with non-specific chronic low back pain: study protocol for a multicentre randomised controlled trial

PubMed Central

O'Keeffe, Mary; Purtill, Helen; Kennedy, Norelee; O'Sullivan, Peter; Dankaerts, Wim; Tighe, Aidan; Allworthy, Lars; Dolan, Louise; Bargary, Norma; O'Sullivan, Kieran

2015-01-01

Introduction Non-specific chronic low back pain (NSCLBP) is a very common and costly musculoskeletal disorder associated with a complex interplay of biopsychosocial factors. Cognitive functional therapy (CFT) represents a novel, patient-centred intervention which directly challenges pain-related behaviours in a cognitively integrated, functionally specific and graduated manner. CFT aims to target all biopsychosocial factors that are deemed to be barriers to recovery for an individual patient with NSCLBP. A recent randomised controlled trial (RCT) demonstrated the superiority of individualised CFT for NSCLBP compared to manual therapy combined with exercise. However, several previous RCTs have suggested that class-based interventions are as effective as individualised interventions. Therefore, it is important to examine whether an individualised intervention, such as CFT, demonstrates clinical effectiveness compared to a relatively cheaper exercise and education class. The current study will compare the clinical effectiveness of individualised CFT with a combined exercise and pain education class in people with NSCLBP. Methods and analysis This study is a multicentre RCT. 214 participants, aged 18–75 years, with NSCLBP for at least 6 months will be randomised to one of two interventions across three sites. The experimental group will receive individualised CFT and the length of the intervention will be varied in a pragmatic manner based on the clinical progression of participants. The control group will attend six classes which will be provided over a period of 6–8 weeks. Participants will be assessed preintervention, postintervention and after 6 and12 months. The primary outcomes will be functional disability and pain intensity. Non-specific predictors, moderators and mediators of outcome will also be analysed. Ethics and dissemination Ethical approval has been obtained from the Mayo General Hospital Research Ethics Committee (MGH-14-UL). Outcomes will be disseminated through publication according to the SPIRIT statement and will be presented at scientific conferences. Trial registration number (ClinicalTrials.gov NCT02145728). PMID:26033941

Multicentre validation of the bedside paediatric early warning system score: a severity of illness score to detect evolving critical illness in hospitalised children

PubMed Central

2011-01-01

Introduction The timely provision of critical care to hospitalised patients at risk for cardiopulmonary arrest is contingent upon identification and referral by frontline providers. Current approaches require improvement. In a single-centre study, we developed the Bedside Paediatric Early Warning System (Bedside PEWS) score to identify patients at risk. The objective of this study was to validate the Bedside PEWS score in a large patient population at multiple hospitals. Methods We performed an international, multicentre, case-control study of children admitted to hospital inpatient units with no limitations on care. Case patients had experienced a clinical deterioration event involving either an immediate call to a resuscitation team or urgent admission to a paediatric intensive care unit. Control patients had no events. The scores ranged from 0 to 26 and were assessed in the 24 hours prior to the clinical deterioration event. Score performance was assessed using the area under the receiver operating characteristic (AUCROC) curve by comparison with the retrospective rating of nurses and the temporal progression of scores in case patients. Results A total of 2,074 patients were evaluated at 4 participating hospitals. The median (interquartile range) maximum Bedside PEWS scores for the 12 hours ending 1 hour before the clinical deterioration event were 8 (5 to 12) in case patients and 2 (1 to 4) in control patients (P < 0.0001). The AUCROC curve (95% confidence interval) was 0.87 (0.85 to 0.89). In case patients, mean scores were 5.3 at 20 to 24 hours and 8.4 at 0 to 4 hours before the event (P < 0.0001). The AUCROC curve (95% CI) of the retrospective nurse ratings was 0.83 (0.81 to 0.86). This was significantly lower than that of the Bedside PEWS score (P < 0.0001). Conclusions The Bedside PEWS score identified children at risk for cardiopulmonary arrest. Scores were elevated and continued to increase in the 24 hours before the clinical deterioration event. Prospective clinical evaluation is needed to determine whether this score will improve the quality of care and patient outcomes. PMID:21812993

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.

PubMed

Meulenbroek, Olga; O'Dwyer, Sarah; de Jong, Daan; van Spijker, Gerrita; Kennelly, Sean; Cregg, Fiona; Olde Rikkert, Marcel; Abdullah, Laila; Wallin, Anders; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Daly, Leslie; Segurado, Ricardo; Borjesson-Hanson, Anne; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Molloy, William; Tsolaki, Magda; Howard, Robert; Adams, Jessica; Gaynor, Siobhan; Lawlor, Brian

2016-07-19

In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers. All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78. All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal. EUDRACT 2012-002764-27; 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/

Comparing meta-analysis and ecological-longitudinal analysis in time-series studies. A case study of the effects of air pollution on mortality in three Spanish cities.

PubMed

Saez, M; Figueiras, A; Ballester, F; Pérez-Hoyos, S; Ocaña, R; Tobías, A

2001-06-01

The objective of this paper is to introduce a different approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. The approach is illustrated by providing quantitative estimates of the short-term effects of air pollution on mortality in three Spanish cities, Barcelona, Valencia and Vigo, for the period 1992-1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were non-linear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 microg/m(3) and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 microg/m(3) of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant, especially those among air pollutants and meteorological variables. Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities.

WebBioBank: a new platform for integrating clinical forms and shared neurosignal analyses to support multi-centre studies in Parkinson's Disease.

PubMed

Rossi, Elena; Rosa, Manuela; Rossi, Lorenzo; Priori, Alberto; Marceglia, Sara

2014-12-01

The web-based systems available for multi-centre clinical trials do not combine clinical data collection (Electronic Health Records, EHRs) with signal processing storage and analysis tools. However, in pathophysiological research, the correlation between clinical data and signals is crucial for uncovering the underlying neurophysiological mechanisms. A specific example is the investigation of the mechanisms of action for Deep Brain Stimulation (DBS) used for Parkinson's Disease (PD); the neurosignals recorded from the DBS target structure and clinical data must be investigated. The aim of this study is the development and testing of a new system dedicated to a multi-centre study of Parkinson's Disease that integrates biosignal analysis tools and data collection in a shared and secure environment. We designed a web-based platform (WebBioBank) for managing the clinical data and biosignals of PD patients treated with DBS in different clinical research centres. Homogeneous data collection was ensured in the different centres (Operative Units, OUs). The anonymity of the data was preserved using unique identifiers associated with patients (ID BAC). The patients' personal details and their equivalent ID BACs were archived inside the corresponding OU and were not uploaded on the web-based platform; data sharing occurred using the ID BACs. The system allowed researchers to upload different signal processing functions (in a .dll extension) onto the web-based platform and to combine them to define dedicated algorithms. Four clinical research centres used WebBioBank for 1year. The clinical data from 58 patients treated using DBS were managed, and 186 biosignals were uploaded and classified into 4 categories based on the treatment (pharmacological and/or electrical). The user's satisfaction mean score exceeded the satisfaction threshold. WebBioBank enabled anonymous data sharing for a clinical study conducted at multiple centres and demonstrated the capabilities of the signal processing chain configuration as well as its effectiveness and efficiency for integrating the neurophysiological results with clinical data in multi-centre studies, which will allow the future collection of homogeneous data in large cohorts of patients. Copyright © 2014 Elsevier Inc. All rights reserved.

RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies

PubMed Central

Dahlberg, K; Odencrants, S; Hagberg, L

2016-01-01

Introduction Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. Methods and analysis This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery. The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A–C) at 1 and 2 weeks and (D) at 1 and 4 months. Trial registration number NCT02492191; Pre-results. PMID:26769788

RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies.

PubMed

Nilsson, U; Jaensson, M; Dahlberg, K; Odencrants, S; Grönlund, Å; Hagberg, L; Eriksson, M

2016-01-13

Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery.The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A-C) at 1 and 2 weeks and (D) at 1 and 4 months. NCT02492191; 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/

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

PubMed

Senin, U; Abate, G; Fieschi, C; Gori, G; Guala, A; Marini, G; Villardita, C; Parnetti, L

1991-12-01

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

PubMed Central

2012-01-01

Abstract Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid. Trial registration Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151. PMID:22369511

Development of a web-based register for the Dutch national study on biologicals in JIA: www.ABC-register.nl.

PubMed

Prince, F H M; Ferket, I S; Kamphuis, S; Armbrust, W; Ten Cate, R; Hoppenreijs, E P A H; Koopman-Keemink, Y; van Rossum, M A J; van Santen-Hoeufft, M; Twilt, M; van Suijlekom-Smit, L W A

2008-09-01

Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study. We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data. The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved. By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

International Collaboration Enhances Cancer Screening Efforts

Cancer.gov

CGH is working with the International Agency for Research on CancerExit Disclaimer (IARC) and the Pan American Health Organization (PAHO) on the ESTAMPA Study, a multi-centric study of cervical cancer screening and triage with HPV testing.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

PubMed Central

2010-01-01

Background For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. Methods The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Results Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. Conclusions For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review. PMID:20673343

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

PubMed

Omitola, Olufemi Gbenga; Soyele, Olujide Oladele; Sigbeku, Opeyemi; Okoh, Dickson; Akinshipo, Abdulwarith Olaitan; Butali, Azeez; Adeola, Henry Ademola

2017-01-01

Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 th and 7 th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

PubMed

Molenaar, Nina M; Brouwer, Marlies E; Bockting, Claudi L H; Bonsel, Gouke J; van der Veere, Christine N; Torij, Hanneke W; Hoogendijk, Witte J G; Duvekot, Johannes J; Burger, Huibert; Lambregtse-van den Berg, Mijke P

2016-03-18

Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy. Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease.

PubMed

Lawlor, Brian; Kennelly, Sean; O'Dwyer, Sarah; Cregg, Fiona; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Howard, Robert; Murphy, Caroline; Adams, Jessica; Daly, Leslie; Segurado, Ricardo; Gaynor, Siobhan; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Wallin, Anders; Borjesson, Anne; Molloy, William; Tsolaki, Magda; Olde Rikkert, Marcel

2014-10-09

This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. EUDRACT Reference Number: 2012-002764-27. 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.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

PubMed

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy and safety of a selective α1 -adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

PubMed

Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Jiménez-Jorge, Silvia; Horváth, Judit K; Donnell, Joan M O; Pitigoi, Daniela; Machado, Ausenda; Pozo, Francisco

2015-06-04

In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A person-centred and thriving-promoting intervention in nursing homes - study protocol for the U-Age nursing home multi-centre, non-equivalent controlled group before-after trial.

PubMed

Edvardsson, David; Sjögren, Karin; Lood, Qarin; Bergland, Ådel; Kirkevold, Marit; Sandman, Per-Olof

2017-01-17

The literature suggests that person-centred care can contribute to quality of life and wellbeing of nursing home residents, relatives and staff. However, there is sparse research evidence on how person-centred care can be operationalised and implemented in practice, and the extent to which it may promote wellbeing and satisfaction. Therefore, the U-Age nursing home study was initiated to deepen the understanding of how to integrate person-centred care into daily practice and to explore the effects and meanings of this. The study aims to evaluate effects and meanings of a person-centred and thriving-promoting intervention in nursing homes through a multi-centre, non-equivalent controlled group before-after trial design. Three nursing homes across three international sites have been allocated to a person-centred and thriving-promoting intervention group, and three nursing homes have been allocated to an inert control group. Staff at intervention sites will participate in a 12-month interactive educational programme that operationalises thriving-promoting and person-centred care three dimensions: 1) Doing a little extra, 2) Developing a caring environment, and 3) Assessing and meeting highly prioritised psychosocial needs. A pedagogical framework will guide the intervention. The primary study endpoints are; residents' thriving, relatives' satisfaction with care and staff job satisfaction. Secondary endpoints are; resident, relative and staff experiences of the caring environment, relatives' experience of visiting their relative and the nursing home, as well as staff stress of conscience and perceived person-centredness of care. Data on study endpoints will be collected pre-intervention, post-intervention, and at a six-month follow up. Interviews will be conducted with relatives and staff to explore experiences and meanings of the intervention. The study is expected to provide evidence that can inform further research, policy and practice development on if and how person-centred care may improve wellbeing, thriving and satisfaction for people who reside in, visit or work in nursing homes. The combination of quantitative and qualitative data will illuminate the operationalisation, effects and meaning of person-centred and thriving-promoting care. The trial was registered at ClinicalTrials.gov March 19, 2016, identifier NCT02714452 .

WHEDA study: Effectiveness of occupational therapy at home for older people with dementia and their caregivers - the design of a pragmatic randomised controlled trial evaluating a Dutch programme in seven German centres

PubMed Central

Voigt-Radloff, Sebastian; Graff, Maud; Leonhart, Rainer; Schornstein, Katrin; Vernooij-Dassen, Myrra; Olde-Rikkert, Marcel; Huell, Michael

2009-01-01

Background A recent Dutch mono-centre randomised controlled trial has shown that occupational therapy improves daily functioning in dementia. The aim of this present study is to compare the effects of the Dutch community occupational therapy programme with a community occupational therapy consultation on daily functioning in older people with mild or moderate dementia and their primary caregivers in a German multi-centre context. Methods/Design A multi-centre single blind randomised controlled trial design is being used in seven health care centres (neurological, psychiatric and for older people) in urban regions. Patients are 1:1 randomised to treatment or control group. Assessors are blind to group assignment and perform measurements on both groups at baseline, directly after intervention at 6 weeks and at 16, 26 and 52 weeks follow-up. A sample of 140 community dwelling older people (aged >65 years) with mild or moderate dementia and their primary caregivers is planned. The experimental intervention consists of an evidence-based community occupational therapy programme including 10 sessions occupational therapy at home. The control intervention consists of one community occupational therapy consultation based on information material of the Alzheimer Society. Providers of both interventions are occupational therapists experienced in treatment of cognitively impaired older people and trained in both programmes. 'Community' indicates that occupational therapy intervention occurs in the person's own home. The primary outcome is patients' daily functioning assessed with the performance scale of the Interview for Deterioration in Daily Living Activities in Dementia and video tapes of daily activities rated by external raters blind to group assignment using the Perceive, Recall, Plan and Perform System of Task Analysis. Secondary outcomes are patients' and caregivers' quality of life, mood and satisfaction with treatment; the caregiver's sense of competence, caregiver's diary (medication, resource utilisation, time of informal care); and the incidence of long-term institutionalisation. Process evaluation is performed by questionnaires and focus group discussion. Discussion The transfer from the Dutch mono-centre design to the pragmatic multi-site trial in a German context implicates several changes in design issues including differences in recruitment time, training of interventionists and active control group treatment. The study is registered under DRKS00000053 at the German register of clinical trials, which is connected to the International Clinical Trials Registry Platform. PMID:19799779

Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC) in women: a prospective cohort study in an urban urological ambulatory setting.

PubMed

Seitz, Michael; Stief, Christian; Waidelich, Raphaela

2017-10-16

Acute uncomplicated cystitis (AUC) is a common ailment in the urological setting. Guidelines for urinary tract infections are based on large-scale multi-centre, epidemiological and international studies. The objective of this observational study was to establish whether the results of a multi-centre study on the resistance profile of Escherichia coli (E. coli) in patients with AUC could be directly applied to an urological practice in a major European city or whether there are divergences in the resistance profile. An observational study was applied prospectively to 502 patients with AUC between January 2015 and January 2017). Personal data were anonymised. Exclusion criteria were the patient's age (<18) and treatment with an antibiotic in the week preceding examination. The average age was 32 (range 18-56). The most commonly detected bacteria was E. coli with 86%, followed by Enterococcus faecalis with 10% and Klebsiella pneumoniae with 4%. Resistance tests showed E. coli to be highly sensitive to fosfomycin (99.2%), nitrofurantoin (98.1%) and cefpodoxime (92.9%). E. coli exhibited resistance to ciprofloxacin (CIP) in 15.1%, to trimethoprim/sulfamethoxazole (TRS) in 25.2% and to amoxicillin/clavulanic acid (AMC) in 34% of cases. The comparison between data from this study and data from a multi-centre European (ECO-SENSI, ECO-SENSII and the 2014 update) showed relatively good sensitivity rates for fosfomycin and nitrofurantoin but significant differences in respect of resistance levels to TRS, CIP and AMC. AUC should therefore only be treated with TRS, CIP and AMC after a susceptibility test has been carried out.

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

PubMed

Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

2015-11-01

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Multicentre cluster randomised controlled trial evaluating implementation of a fire prevention Injury Prevention Briefing in children's centres: study protocol.

PubMed

Deave, Toity; Towner, Elizabeth; McColl, Elaine; Reading, Richard; Sutton, Alex; Coupland, Carol; Cooper, Nicola; Stewart, Jane; Hayes, Mike; Pitchforth, Emma; Watson, Michael; Kendrick, Denise

2014-01-22

The UK has one of the highest fatality rates for deaths from fire-related injuries in children aged 0-14 years; these injuries have the steepest social gradient of all injuries in the UK. Children's centres provide children under five years old and their families with a range of services and information, including home safety, but their effectiveness in promoting injury prevention has yet to be evaluated. We developed a fire prevention intervention for use in children's centres comprising an Injury Prevention Briefing (IPB) which provides evidence on what works and best practice from those running injury prevention programmes, and a facilitation package to support implementation of the IPB. This protocol describes the design and methods of a trial evaluating the effectiveness and cost-effectiveness of the IPB and facilitation package in promoting fire prevention. Pragmatic, multicentre cluster randomised controlled trial, with a nested qualitative study, in four study centres in England. Children's centres in the most disadvantaged areas will be eligible to participate and will be randomised to one of three treatment arms comprising: IPB with facilitation package; IPB with no facilitation package; usual care (control). The primary outcome measure will be the proportion of families who have a fire escape plan at follow-up. Eleven children's centres per arm are required to detect an absolute difference in the percentage of families with a fire escape plan of 20% in either of the two intervention arms compared with the control arm, with 80% power and a 5% significance level (2-sided), an intraclass correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families per children's centre. Secondary outcomes include the assessment of the cost-effectiveness of the intervention, other fire safety behaviours and factors associated with degree of implementation of the IPB. This will be the first trial to develop and evaluate a fire prevention intervention for use in children's centres in the UK. Its findings will be generalisable to children's centres in the most disadvantaged areas of the UK and may also be generalisable to similar interventions to prevent other types of injury. http://NCT01452191 (date of registration: 13/10/2011).

Multicentre cluster randomised controlled trial evaluating implementation of a fire prevention Injury Prevention Briefing in children’s centres: study protocol

PubMed Central

2014-01-01

Background The UK has one of the highest fatality rates for deaths from fire-related injuries in children aged 0–14 years; these injuries have the steepest social gradient of all injuries in the UK. Children’s centres provide children under five years old and their families with a range of services and information, including home safety, but their effectiveness in promoting injury prevention has yet to be evaluated. We developed a fire prevention intervention for use in children’s centres comprising an Injury Prevention Briefing (IPB) which provides evidence on what works and best practice from those running injury prevention programmes, and a facilitation package to support implementation of the IPB. This protocol describes the design and methods of a trial evaluating the effectiveness and cost-effectiveness of the IPB and facilitation package in promoting fire prevention. Methods/Design Pragmatic, multicentre cluster randomised controlled trial, with a nested qualitative study, in four study centres in England. Children’s centres in the most disadvantaged areas will be eligible to participate and will be randomised to one of three treatment arms comprising: IPB with facilitation package; IPB with no facilitation package; usual care (control). The primary outcome measure will be the proportion of families who have a fire escape plan at follow-up. Eleven children’s centres per arm are required to detect an absolute difference in the percentage of families with a fire escape plan of 20% in either of the two intervention arms compared with the control arm, with 80% power and a 5% significance level (2-sided), an intraclass correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families per children’s centre. Secondary outcomes include the assessment of the cost-effectiveness of the intervention, other fire safety behaviours and factors associated with degree of implementation of the IPB. Discussion This will be the first trial to develop and evaluate a fire prevention intervention for use in children’s centres in the UK. Its findings will be generalisable to children’s centres in the most disadvantaged areas of the UK and may also be generalisable to similar interventions to prevent other types of injury. Trial registration http://NCT01452191 (date of registration: 13/10/2011). PMID:24450931

Effect of personalised citizen assistance for social participation (APIC) on older adults' health and social participation: study protocol for a pragmatic multicentre randomised controlled trial (RCT).

PubMed

Levasseur, Mélanie; Dubois, Marie-France; Filliatrault, Johanne; Vasiliadis, Helen-Maria; Lacasse-Bédard, Joanie; Tourigny, André; Levert, Marie-Josée; Gabaude, Catherine; Lefebvre, Hélène; Berger, Valérie; Eymard, Chantal

2018-03-31

The challenges of global ageing and the growing burden of chronic diseases require innovative interventions acting on health determinants like social participation. Many older adults do not have equitable opportunities to achieve full social participation, and interventions might underempower their personal and environmental resources and only reach a minority. To optimise current practices, the Accompagnement-citoyen Personnalisé d'Intégration Communautaire (APIC), an intervention demonstrated as being feasible and having positive impacts, needs further evaluation. A pragmatic multicentre, prospective, two-armed, randomised controlled trial will evaluate: (1) the short-term and long-term effects of the APIC on older adults' health, social participation, life satisfaction and healthcare services utilisation and (2) its cost-effectiveness. A total of 376 participants restricted in at least one instrumental activity of daily living and living in three large cities in the province of Quebec, Canada, will be randomly assigned to the experimental or control group using a centralised computer-generated random number sequence procedure. The experimental group will receive weekly 3-hour personalised stimulation sessions given by a trained volunteer over the first 12 months. Sessions will encourage empowerment, gradual mobilisation of personal and environmental resources and community integration. The control group will receive the publicly funded universal healthcare services available to all Quebecers. Over 2 years (baseline and 12, 18 and 24 months later), self-administered questionnaires will assess physical and mental health (primary outcome; version 2 of the 36-item Short-Form Health Survey, converted to SF-6D utility scores for quality-adjusted life years), social participation (Social Participation Scale) and life satisfaction (Life Satisfaction Index-Z). Healthcare services utilisation will be recorded and costs of each intervention calculated. The Research Ethics Committee of the CIUSSS Estrie - CHUS has approved the study (MP-31-2018-2424). An informed consent form will be read and signed by all study participants. Findings will be published and presented at conferences. NCT03161860; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571).

PubMed

Tabbers, Merit M; Chmielewska, Ania; Roseboom, Maaike G; Boudet, Claire; Perrin, Catherine; Szajewska, Hania; Benninga, Marc A

2009-03-18

Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30-50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week. It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3-16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing Bifidobacterium lactis DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5-10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as > or = 3 bowel movements per week and < or =1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency > or = 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated. This study is aimed to show that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation frequency < 3/week.

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571)

PubMed Central

Tabbers, Merit M; Chmielewska, Ania; Roseboom, Maaike G; Boudet, Claire; Perrin, Catherine; Szajewska, Hania; Benninga, Marc A

2009-01-01

Background Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week. Methods/design It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing Bifidobacterium lactis DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated. Conclusion This study is aimed to show that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation frequency < 3/week. PMID:19296845

The effect of pelvic physiotherapy on reduction of functional constipation in children: design of a multicentre randomised controlled trial.

PubMed

van Engelenburg-van Lonkhuyzen, Marieke L; Bols, Esther M J; Benninga, Marc A; Verwijs, Wim A; Bluijssen, Netty M W L; de Bie, Rob A

2013-08-02

Functional constipation is a common disorder worldwide and is found in all paediatric age groups. Functional constipation can be caused by delayed colonic transit or dysfunction of the pelvic floor muscles. Standard medical care in paediatric practice is often based on clinical experience and mainly consists of a behavioural approach and toilet training, along with the prescription of laxatives. Evidence to evaluate the effectiveness of pelvic physiotherapy for this complaint is lacking. A two-armed multicentre randomised controlled trial has been designed. We hypothesise that the combination of pelvic physiotherapy and standard medical care will be more effective than standard medical care alone for constipated children, aged 5 to 17 years. Children with functional constipation according to the Rome III will be included. Web-based baseline and follow-up measurements, scheduled at 3 and 6 months after inclusion, consist of the numeric rating scale in relation to the perceived severity of the problem, the Strength and Difficulties Questionnaire and subjective improvement post-intervention (global perceived effect). Examination of the pelvic floor muscle functions, including digital testing and biofeedback, will take place during baseline and follow-up measurements at the physiotherapist. The control group will only receive standard medical care, involving at least three contacts during five months, whereas the experimental group will receive standard medical care plus pelvic physiotherapy, with a maximum of six contacts. The physiotherapy intervention will include standard medical care, pelvic floor muscle training, attention to breathing, relaxation and awareness of body and posture. The study duration will be six months from randomisation, with a three-year recruitment period. The primary outcome is the absence of functional constipation according to the Rome III criteria. This section discusses the relevance of publishing the study design and the development of the presented physiotherapy protocol. It also addresses difficulties when interpreting the literature with regard to the effectiveness of biofeedback, potential confounding, and future research indications. To our knowledge, this article is the first to describe the design of a randomised controlled trial among children with constipation to assess the effect of pelvic physiotherapy as an add-on to standard medical care. Current Controlled Trials NL30551.068.09.

The effect of pelvic physiotherapy on reduction of functional constipation in children: design of a multicentre randomised controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common disorder worldwide and is found in all paediatric age groups. Functional constipation can be caused by delayed colonic transit or dysfunction of the pelvic floor muscles. Standard medical care in paediatric practice is often based on clinical experience and mainly consists of a behavioural approach and toilet training, along with the prescription of laxatives. Evidence to evaluate the effectiveness of pelvic physiotherapy for this complaint is lacking. Methods/design A two-armed multicentre randomised controlled trial has been designed. We hypothesise that the combination of pelvic physiotherapy and standard medical care will be more effective than standard medical care alone for constipated children, aged 5 to 17 years. Children with functional constipation according to the Rome III will be included. Web-based baseline and follow-up measurements, scheduled at 3 and 6 months after inclusion, consist of the numeric rating scale in relation to the perceived severity of the problem, the Strength and Difficulties Questionnaire and subjective improvement post-intervention (global perceived effect). Examination of the pelvic floor muscle functions, including digital testing and biofeedback, will take place during baseline and follow-up measurements at the physiotherapist. The control group will only receive standard medical care, involving at least three contacts during five months, whereas the experimental group will receive standard medical care plus pelvic physiotherapy, with a maximum of six contacts. The physiotherapy intervention will include standard medical care, pelvic floor muscle training, attention to breathing, relaxation and awareness of body and posture. The study duration will be six months from randomisation, with a three-year recruitment period. The primary outcome is the absence of functional constipation according to the Rome III criteria. Discussion This section discusses the relevance of publishing the study design and the development of the presented physiotherapy protocol. It also addresses difficulties when interpreting the literature with regard to the effectiveness of biofeedback, potential confounding, and future research indications. To our knowledge, this article is the first to describe the design of a randomised controlled trial among children with constipation to assess the effect of pelvic physiotherapy as an add-on to standard medical care. Trial registration Current Controlled Trials NL30551.068.09 PMID:23914827

Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

PubMed

Schellekens, M P J; van den Hurk, D G M; Prins, J B; Donders, A R T; Molema, J; Dekhuijzen, R; van der Drift, M A; Speckens, A E M

2017-12-01

Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own. Copyright © 2017 John Wiley & Sons, Ltd.

Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial.

PubMed

Vos-Vromans, D C W M; Smeets, R J E M; Huijnen, I P J; Köke, A J A; Hitters, W M G C; Rijnders, L J M; Pont, M; Winkens, B; Knottnerus, J A

2016-03-01

The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS). Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT. Four rehabilitation centres in the Netherlands. A total of 122 patients participated in the trial. Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation. A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was -3.02 [95% confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI -10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant. This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial. © 2015 The Association for the Publication of the Journal of Internal Medicine.

Effectiveness of a standardised exercise programme for recurrent neck and low back pain: a multicentre, randomised, two-arm, parallel group trial across 34 fitness clubs in Finland.

PubMed

Suni, Jaana H; Rinne, Marjo; Tokola, Kari; Mänttäri, Ari; Vasankari, Tommi

2017-01-01

Neck and low back pain (LBP) are common in office workers. Exercise trials to reduce neck and LBP conducted in sport sector are lacking. We investigated the effectiveness of the standardised Fustra20Neck&Back exercise program for reducing pain and increasing fitness in office workers with recurrent non-specific neck and/or LBP. Volunteers were recruited through newspaper and Facebook. The design is a multi-centre randomised, two-arm, parallel group trial across 34 fitness clubs in Finland. Eligibility was determined by structured telephone interview. Instructors were specially educated professionals. Neuromuscular exercise was individually guided twice weekly for 10 weeks. Webropol survey, and objective measurements of fitness, physical activity, and sedentary behavior were conducted at baseline, and at 3 and 12 months. Mean differences between study groups (Exercise vs Control) were analysed using a general linear mixed model according to the intention-to-treat principle. At least moderate intensity pain (≥40 mm) in both the neck and back was detected in 44% of participants at baseline. Exercise compliance was excellent: 92% participated 15-20 times out of 20 possible. Intensity and frequency of neck pain, and strain in neck/shoulders decreased significantly in the Exercise group compared with the Control group. No differences in LBP and strain were detected. Neck/shoulder and trunk flexibility improved, as did quality of life in terms of pain and physical functioning. The Fustra20Neck&Back exercise program was effective for reducing neck/shoulder pain and strain, but not LBP. Evidence-based exercise programs of sports clubs have potential to prevent persistent, disabling musculoskeletal problems.

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

PubMed

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

2009-09-19

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

A randomised controlled multicentre trial of women's and men's satisfaction with two models of antenatal education.

PubMed

Bergström, Malin; Kieler, Helle; Waldenström, Ulla

2011-12-01

To study women's and men's satisfaction with two models of antenatal education: natural childbirth preparation with psychoprophylaxis, and standard antenatal education including preparation for childbirth and parenthood but no psychoprophylaxis. Randomised controlled multicentre trial. 15 Antenatal clinics in Sweden between January 2006 and May 2007. 1087 Nulliparous women and 1064 of their partners. Both models had four two-hour sessions during pregnancy and one session post partum. The natural model was manual-based and focused on childbirth preparation, including psychoprophylaxis. In the standard care model, the group leader was free to choose her teaching approach, with an equal amount of time allocated to preparation for childbirth and for parenthood. Women's and men's evaluation of antenatal education at three months post partum. The proportion of women and men in each model that expressed satisfaction with the education were compared using χ(2) test. More women and men in the natural groups were satisfied with the education compared with the standard care groups: women 76% versus 68% (p = 0.03) and men 73% versus 65% (p = 0.03). The figures were similar for satisfaction with the childbirth preparation component: 78% and 62% in women (p < 0.001), and 79% and 67% in men (p < 0.001) in the natural and standard care groups, respectively. Fewer participants were satisfied with the parenthood preparation component, but the proportions were higher in the standard care groups: women 37% versus 32% (p < 0.001) and men 23% versus 20% (p < 0.001). A structured manual-based model of antenatal education which focuses on childbirth preparation with psychoprophylaxis may better meet expectant parents' expectations than standard antenatal education in Sweden. Copyright © 2010 Elsevier Ltd. All rights reserved.

A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis.

PubMed

Conaghan, Philip G; Dickson, John; Bolten, Wolfgang; Cevc, Gregor; Rother, Matthias

2013-07-01

To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS; A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12. A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg). IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.

COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol.

PubMed

Goldstein, Laura H; Mellers, John D C; Landau, Sabine; Stone, Jon; Carson, Alan; Medford, Nick; Reuber, Markus; Richardson, Mark; McCrone, Paul; Murray, Joanna; Chalder, Trudie

2015-06-27

The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse events. We will include a nested qualitative study to evaluate participants' views of the intervention and factors that acted as facilitators and barriers to participation. This study will be the first adequately powered evaluation of CBT for this patient group and offers the potential to provide an evidence base for treating this patient group. Current Controlled Trials ISRCTN05681227 ClinicalTrials.gov NCT02325544.

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study.

PubMed

Dalziel, Stuart R; Furyk, Jeremy; Bonisch, Megan; Oakley, Ed; Borland, Meredith; Neutze, Jocelyn; Donath, Susan; Sharpe, Cynthia; Harvey, Simon; Davidson, Andrew; Craig, Simon; Phillips, Natalie; George, Shane; Rao, Arjun; Cheng, Nicholas; Zhang, Michael; Sinn, Kam; Kochar, Amit; Brabyn, Christine; Babl, Franz E

2017-06-22

Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines. Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

Moxibustion for treating knee osteoarthritis: study protocol of a multicentre randomised controlled trial

PubMed Central

2013-01-01

Background The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity. However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety, cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual care. Methods/designs This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments. Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation and a qualitative study will be conducted as a mixed-methods approach. Discussion This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for treating knee osteoarthritis. Trial registration Trial registration number: KCT0000130 PMID:23497032

Effect of transcutaneous electrical stimulation treatment on lower urinary tract symptoms after class III radical hysterectomy in cervical cancer patients: study protocol for a multicentre, randomized controlled trial.

PubMed

Sun, Xiu-Li; Wang, Hai-Bo; Wang, Zhi-Qi; Cao, Ting-Ting; Yang, Xin; Han, Jing-Song; Wu, Yang-Feng; Reilly, Kathleen H; Wang, Jian-Liu

2017-06-15

Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients. The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5-7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50-100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect. To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life. The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015.

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

PubMed Central

Drummond, Colin; Deluca, Paolo; Coulton, Simon; Bland, Martin; Cassidy, Paul; Crawford, Mike; Dale, Veronica; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; McGovern, Ruth; Myles, Judy; Newbury-Birch, Dorothy; Oyefeso, Adenekan; Parrott, Steve; Patton, Robert; Perryman, Katherine; Phillips, Tom; Shepherd, Jonathan; Touquet, Robin; Kaner, Eileen

2014-01-01

Background Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. Methods and Findings Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n = 863) at six, and 67% (n = 810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. Conclusions SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions. Trial Registration Current Controlled Trials ISRCTN 93681536 PMID:24963731

Recruitment and retention of participants in randomised controlled trials: a review of trials funded and published by the United Kingdom Health Technology Assessment Programme.

PubMed

Walters, Stephen J; Bonacho Dos Anjos Henriques-Cadby, Inês; Bortolami, Oscar; Flight, Laura; Hind, Daniel; Jacques, Richard M; Knox, Christopher; Nadin, Ben; Rothwell, Joanne; Surtees, Michael; Julious, Steven A

2017-03-20

Substantial amounts of public funds are invested in health research worldwide. Publicly funded randomised controlled trials (RCTs) often recruit participants at a slower than anticipated rate. Many trials fail to reach their planned sample size within the envisaged trial timescale and trial funding envelope. To review the consent, recruitment and retention rates for single and multicentre randomised control trials funded and published by the UK's National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme. HTA reports of individually randomised single or multicentre RCTs published from the start of 2004 to the end of April 2016 were reviewed. Information was extracted, relating to the trial characteristics, sample size, recruitment and retention by two independent reviewers. Target sample size and whether it was achieved; recruitment rates (number of participants recruited per centre per month) and retention rates (randomised participants retained and assessed with valid primary outcome data). This review identified 151 individually RCTs from 787 NIHR HTA reports. The final recruitment target sample size was achieved in 56% (85/151) of the RCTs and more than 80% of the final target sample size was achieved for 79% of the RCTs (119/151). The median recruitment rate (participants per centre per month) was found to be 0.92 (IQR 0.43-2.79) and the median retention rate (proportion of participants with valid primary outcome data at follow-up) was estimated at 89% (IQR 79-97%). There is considerable variation in the consent, recruitment and retention rates in publicly funded RCTs. Investigators should bear this in mind at the planning stage of their study and not be overly optimistic about their recruitment projections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The role of socio-economic and clinical factors on HbA1c in children and adolescents with type 1 diabetes: an Italian multicentre survey.

PubMed

Gesuita, Rosaria; Skrami, Edlira; Bonfanti, Riccardo; Cipriano, Paola; Ferrito, Lucia; Frongia, Paola; Iafusco, Dario; Iannilli, Antonio; Lombardo, Fortunato; Mozzillo, Enza; Paleari, Renata; Rabbone, Ivana; Sabbion, Alberto; Salvatoni, Alessandro; Scaramuzza, Andrea; Schiaffini, Riccardo; Sulli, Nicoletta; Toni, Sonia; Carle, Flavia; Cherubini, Valentino

2017-05-01

To identify the role of the family's socio-economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes. In this cross-sectional, multicentre study, 768 subjects with type 1 diabetes under 18 years of age were consecutively recruited from January 2008 to February 2009. Target condition was considered for HbA 1c values <7.5% (<58 mmol/mol). A multiple correspondence analysis (MCA) was performed to analyze the association between the socio-economic and clinical characteristics of the participants. A logistic regression analysis was performed to identify factors associated with the subjects metabolic control. In both analyses, the family's socio-economic status was represented, measured by the Hollingshead Four-Factor Index of Social Status (SES) or by parental years of education. A total of 28.1% of subjects reached target HbA1c values. The MCA identified a strong association between at-target condition and several factors: high levels of SES or high levels of parental education, the use of the carbohydrate counting system, the use of insulin pumps, the use of the insulin delivery system over a short period of time, a normal body mass index. The logistic regression analysis showed that SES and the mother's years of education were significantly associated with the target condition [odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01-1.03, p = 0.029; OR: 1.05, 95% CI: 1.01-1.10, p = 0.027, respectively). Personal, clinical, and family characteristics were found to be associated with HbA 1c target. Their identification can be crucial in addressing strategies to optimize metabolic control and improve diabetes management. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Ghali, Jalal K; Orlandi, Cesare; Abraham, William T

2012-06-01

Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload. This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P < 0.001) and at Weeks 1, 2, and 4 (P < 0.01). Cardiovascular changes were generally similar in both groups, though orthopnoea and dyspnoea improved in the lixivaptan group vs. placebo. The TMT-B and MOS-6 showed no significant differences between groups. Lixivaptan was well tolerated-thirst and polyuria occurred more frequently vs. placebo. In outpatients with HF and volume overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated. NCT01055912.

Delays in receiving obstetric care and poor maternal outcomes: results from a national multicentre cross-sectional study

PubMed Central

2014-01-01

Background The vast majority of maternal deaths in low-and middle-income countries are preventable. Delay in obtaining access to appropriate health care is a fairly common problem which can be improved. The objective of this study was to explore the association between delay in providing obstetric health care and severe maternal morbidity/death. Methods This was a multicentre cross-sectional study, involving 27 referral obstetric facilities in all Brazilian regions between 2009 and 2010. All women admitted to the hospital with a pregnancy-related cause were screened, searching for potentially life-threatening conditions (PLTC), maternal death (MD) and maternal near-miss (MNM) cases, according to the WHO criteria. Data on delays were collected by medical chart review and interview with the medical staff. The prevalence of the three different types of delays was estimated according to the level of care and outcome of the complication. For factors associated with any delay, the PR and 95%CI controlled for cluster design were estimated. Results A total of 82,144 live births were screened, with 9,555 PLTC, MNM or MD cases prospectively identified. Overall, any type of delay was observed in 53.8% of cases; delay related to user factors was observed in 10.2%, 34.6% of delays were related to health service accessibility and 25.7% were related to quality of medical care. The occurrence of any delay was associated with increasing severity of maternal outcome: 52% in PLTC, 68.4% in MNM and 84.1% in MD. Conclusions Although this was not a population-based study and the results could not be generalized, there was a very clear and significant association between frequency of delay and severity of outcome, suggesting that timely and proper management are related to survival. PMID:24886330

Evolution of ischemic damage and behavioural deficit over 6 months after MCAo in the rat: Selecting the optimal outcomes and statistical power for multi-centre preclinical trials

PubMed Central

Churilov, Leonid; Sidon, T. Kate; Aleksoska, Elena; Cox, Susan F.; Macleod, Malcolm R.; Howells, David W.

2017-01-01

Key disparities between the timing and methods of assessment in animal stroke studies and clinical trial may be part of the reason for the failure to translate promising findings. This study investigates the development of ischemic damage after thread occlusion MCAo in the rat, using histological and behavioural outcomes. Using the adhesive removal test we investigate the longevity of behavioural deficit after ischemic stroke in rats, and examine the practicality of using such measures as the primary outcome for future studies. Ischemic stroke was induced in 132 Spontaneously Hypertensive Rats which were assessed for behavioural and histological deficits at 1, 3, 7, 14, 21, 28 days, 12 and 24 weeks (n>11 per timepoint). The basic behavioural score confirmed induction of stroke, with deficits specific to stroke animals. Within 7 days, these deficits resolved in 50% of animals. The adhesive removal test revealed contralateral neglect for up to 6 months following stroke. Sample size calculations to facilitate the use of this test as the primary experimental outcome resulted in cohort sizes much larger than are the norm for experimental studies. Histological damage progressed from a necrotic infarct to a hypercellular area that cleared to leave a fluid filled cavity. Whilst absolute volume of damage changed over time, when corrected for changes in hemispheric volume, an equivalent area of damage was lost at all timepoints. Using behavioural measures at chronic timepoints presents significant challenges to the basic science community in terms of the large number of animals required and the practicalities associated with this. Multicentre preclinical randomised controlled trials as advocated by the MultiPART consortium may be the only practical way to deal with this issue. PMID:28182727

Delays in receiving obstetric care and poor maternal outcomes: results from a national multicentre cross-sectional study.

PubMed

Pacagnella, Rodolfo C; Cecatti, José G; Parpinelli, Mary A; Sousa, Maria H; Haddad, Samira M; Costa, Maria L; Souza, João P; Pattinson, Robert C

2014-05-05

The vast majority of maternal deaths in low-and middle-income countries are preventable. Delay in obtaining access to appropriate health care is a fairly common problem which can be improved. The objective of this study was to explore the association between delay in providing obstetric health care and severe maternal morbidity/death. This was a multicentre cross-sectional study, involving 27 referral obstetric facilities in all Brazilian regions between 2009 and 2010. All women admitted to the hospital with a pregnancy-related cause were screened, searching for potentially life-threatening conditions (PLTC), maternal death (MD) and maternal near-miss (MNM) cases, according to the WHO criteria. Data on delays were collected by medical chart review and interview with the medical staff. The prevalence of the three different types of delays was estimated according to the level of care and outcome of the complication. For factors associated with any delay, the PR and 95%CI controlled for cluster design were estimated. A total of 82,144 live births were screened, with 9,555 PLTC, MNM or MD cases prospectively identified. Overall, any type of delay was observed in 53.8% of cases; delay related to user factors was observed in 10.2%, 34.6% of delays were related to health service accessibility and 25.7% were related to quality of medical care. The occurrence of any delay was associated with increasing severity of maternal outcome: 52% in PLTC, 68.4% in MNM and 84.1% in MD. Although this was not a population-based study and the results could not be generalized, there was a very clear and significant association between frequency of delay and severity of outcome, suggesting that timely and proper management are related to survival.

Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

Asymptomatic population reference values for three knee patient-reported outcomes measures: evaluation of an electronic data collection system and implications for future international, multi-centre cohort studies.

PubMed

McLean, James M; Brumby-Rendell, Oscar; Lisle, Ryan; Brazier, Jacob; Dunn, Kieran; Gill, Tiffany; Hill, Catherine L; Mandziak, Daniel; Leith, Jordan

2018-05-01

The aim was to assess whether the Knee Society Score, Oxford Knee Score (OKS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were comparable in asymptomatic, healthy, individuals of different age, gender and ethnicity, across two remote continents. The purpose of this study was to establish normal population values for these scores using an electronic data collection system. There is no difference in clinical knee scores in an asymptomatic population when comparing age, gender and ethnicity, across two remote continents. 312 Australian and 314 Canadian citizens, aged 18-94 years, with no active knee pain, injury or pathology in the ipsilateral knee corresponding to their dominant arm, were evaluated. A knee examination was performed and participants completed an electronically administered questionnaire covering the subjective components of the knee scores. The cohorts were age- and gender-matched. Chi-square tests, Fisher's exact test and Poisson regression models were used where appropriate, to investigate the association between knee scores, age, gender, ethnicity and nationality. There was a significant inverse relationship between age and all assessment tools. OKS recorded a significant difference between gender with females scoring on average 1% lower score. There was no significant difference between international cohorts when comparing all assessment tools. An electronic, multi-centre data collection system can be effectively utilized to assess remote international cohorts. Differences in gender, age, ethnicity and nationality should be taken into consideration when using knee scores to compare to pathological patient scores. This study has established an electronic, normal control group for future studies using the Knee society, Oxford, and KOOS knee scores. Diagnostic Level II.

Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study.

PubMed

Barthel, Henryk; Gertz, Hermann-Josef; Dresel, Stefan; Peters, Oliver; Bartenstein, Peter; Buerger, Katharina; Hiemeyer, Florian; Wittemer-Rump, Sabine M; Seibyl, John; Reininger, Cornelia; Sabri, Osama

2011-05-01

Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben (¹⁸F) is a promising ¹⁸F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben (¹⁸F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls. We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben (¹⁸F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18-26, clinical dementia rating [CDR]=0·5-2·0) and age-matched healthy controls (MMSE ≥ 28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90-110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282. 81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84-98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p < 0·0001) compared with the healthy controls, with the posterior cingulate being the best discriminator. Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85% and a specificity of 91%. Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores (r -0·27 to -0·33, p ≤ 0·021). APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans (65%vs 22% [p=0·027] in patients with Alzheimer's disease; 50%vs 16% [p = 0·074] in healthy controls). No safety concerns were noted. We provide verification of the efficacy, safety, and biological relevance of florbetaben (¹⁸F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. Bayer Schering Pharma AG. Copyright © 2011 Elsevier Ltd. All rights reserved.

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

PubMed

Newman, Samantha Kass; Jayanthan, Raj K; Mitchell, Grant W; Carreras Tartak, Jossie A; Croglio, Michael P; Suarez, Alexander; Liu, Amy Y; Razzo, Beatrice M; Oyeniran, Enny; Ruth, Jason R; Fajgenbaum, David C

2015-12-01

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Moral imperialism and multi-centric clinical trials in peripheral countries.

PubMed

Garrafa, Volnei; Lorenzo, Claudio

2008-10-01

Moral imperialism is expressed in attempts to impose moral standards from one particular culture, geopolitical region or culture onto other cultures, regions or countries. Examples of Direct Moral Imperialism can be seen in various recurrent events involving multi-centric clinical trials promoted by developed (central) countries in poor and developing (peripheral) countries, particularly projects related to the theory of double standards in research. After the WMA General Assembly refused to change the Helsinki Declaration - which would have given moral recognition to the above mentioned theory - the USA abandoned the declaration and began to promote regional seminars in peripheral countries with the aim of "training" researchers on ethical perspectives that reflect America's best interests. Individuals who received such training became transmitters of these central countries' ideas across the peripheral countries, representing a form of Indirect Moral Imperialism. The paper proposes the establishment of regulatory and social control systems for clinical trials implemented in peripheral countries, through the formulation of ethical norms that reflect the specific contexts of these countries, along with the drawing up and validation of their own national norms.

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

PubMed

Ranganath, Lakshminarayan R; Milan, Anna M; Hughes, Andrew T; Dutton, John J; Fitzgerald, Richard; Briggs, Michael C; Bygott, Helen; Psarelli, Eftychia E; Cox, Trevor F; Gallagher, James A; Jarvis, Jonathan C; van Kan, Christa; Hall, Anthony K; Laan, Dinny; Olsson, Birgitta; Szamosi, Johan; Rudebeck, Mattias; Kullenberg, Torbjörn; Cronlund, Arvid; Svensson, Lennart; Junestrand, Carin; Ayoob, Hana; Timmis, Oliver G; Sireau, Nicolas; Le Quan Sang, Kim-Hanh; Genovese, Federica; Braconi, Daniela; Santucci, Annalisa; Nemethova, Martina; Zatkova, Andrea; McCaffrey, Judith; Christensen, Peter; Ross, Gordon; Imrich, Richard; Rovensky, Jozef

2016-02-01

Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The effectiveness of telemedicine for paediatric retrieval consultations: rationale and study design for a pragmatic multicentre randomised controlled trial.

PubMed

Armfield, Nigel R; Coulthard, Mark G; Slater, Anthony; McEniery, Julie; Elcock, Mark; Ware, Robert S; Scuffham, Paul A; Bensink, Mark E; Smith, Anthony C

2014-11-11

In many health systems, specialist services for critically ill children are typically regionalised or centralised. Studies have shown that high-risk paediatric patients have improved survival when managed in specialist centres and that volume of cases is a predictor of care quality. In acute cases where distance and time impede access to specialist care, clinical advice may be provided remotely by telephone. Emergency retrieval services, attended by medical and nursing staff may be used to transport patients to specialist centres. Even with the best quality retrieval services, stabilisation of the patient and transport logistics may delay evacuation to definitive care. Several studies have examined the use of telemedicine for providing specialist consultations for critically ill children. However, no studies have yet formally examined the clinical effectiveness and economic implications of using telemedicine in the context of paediatric patient retrieval. The study is a pragmatic, multicentre randomised controlled trial running over 24 months which will compare the use of telemedicine with the use of the telephone for paediatric retrieval consultations between four referring hospitals and a tertiary paediatric intensive care unit. We aim to recruit 160 children for whom a specialist retrieval consultation is required. The primary outcome measure is stabilisation time (time spent on site at the referring hospital by the retrieval team) adjusted for initial risk. Secondary outcome measures are change in patient's physiological status (repeated measure, two time points) scored using the Children's Emergency Warning Tool; change in diagnosis (repeated measure taken at three time points); change in destination of retrieved patients at the tertiary hospital (general ward or paediatric intensive care unit); retrieval decision, and length of stay in the Paediatric Intensive Care Unit for retrieved patients. The trial has been approved by the Human Research Ethics Committees of Children's Health Services Queensland and The University of Queensland, Australia. Health services are adopting telemedicine, however formal evidence to support its use in paediatric acute care is limited. Generalisable evidence is required to inform clinical use and health system policy relating to the effectiveness and economic implications of the use in telemedicine in paediatric retrieval. Australian and New Zealand Clinical Trials Registry ACTRN12612000156886 .

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

PubMed

Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

2018-05-24

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Xyloglucan for the treatment of acute diarrhea: results of a randomized, controlled, open-label, parallel group, multicentre, national clinical trial.

PubMed

Gnessi, Lucio; Bacarea, Vladimir; Marusteri, Marius; Piqué, Núria

2015-10-30

There is a strong rationale for the use of agents with film-forming protective properties, like xyloglucan, for the treatment of acute diarrhea. However, few data from clinical trials are available. A randomized, controlled, open-label, parallel group, multicentre, clinical trial was performed to evaluate the efficacy and safety of xyloglucan, in comparison with diosmectite and Saccharomyces in adult patients with acute diarrhea due to different causes. Patients were randomized to receive a 3-day treatment. Symptoms (stools type, nausea, vomiting, abdominal pain and flatulence) were assessed by a self-administered ad-hoc questionnaire 1, 3, 6, 12, 24, 48 and 72 h following the first dose administration. Adverse events were also recorded. A total of 150 patients (69.3 % women and 30.7 % men, mean age 47.3 ± 14.7 years) were included (n = 50 in each group). A faster onset of action was observed in the xyloglucan group compared with the diosmectite and S. bouliardii groups. At 6 h xyloglucan produced a statistically significant higher decrease in the mean number of type 6 and 7 stools compared with diosmectite (p = 0.031). Xyloglucan was the most efficient treatment in reducing the percentage of patients with nausea throughout the study period, particularly during the first hours (from 26 % at baseline to 4 % after 6 and 12 h). An important improvement of vomiting was observed in all three treatment groups. Xyloglucan was more effective than diosmectite and S. bouliardii in reducing abdominal pain, with a constant improvement observed throughout the study. The clinical evolution of flatulence followed similar patterns in the three groups, with continuous improvement of the symptom. All treatments were well tolerated, without reported adverse events. Xyloglucan is a fast, efficacious and safe option for the treatment of acute diarrhea. EudraCT number 2014-001814-24 (date: 2014-04-28) ISRCTN number: 90311828.

Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study.

PubMed

Ciani, Oriana; Arendsen, Erik; Romancik, Martin; Lunik, Richard; Costantini, Elisabetta; Di Biase, Manuel; Morgia, Giuseppe; Fragalà, Eugenia; Roman, Tomaskin; Bernat, Marian; Guazzoni, Giorgio; Tarricone, Rosanna; Lazzeri, Massimo

2016-03-31

To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). A European Union-based multicentre, retrospective nested case-control study. 276 adult women treated for RUTIs starting from 2009 to 2013. Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5. Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. NCT02016118. 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/

Multicentre experience with the BridgePoint devices to facilitate recanalisation of chronic total coronary occlusions through controlled subintimal re-entry.

PubMed

Werner, Gerald S; Schofer, Joachim; Sievert, Horst; Kugler, Chad; Reifart, Nicolaus J

2011-06-01

The major challenge for the interventional treatment of chronic total coronary occlusion (CTO) is a low primary success rate. A common problem is the passage of the recanalisation wire into a subintimal position. New devices, which were evaluated in the first multicentre study in CTOs resistant to a conventional wire approach, may help to facilitate a controlled re-entry into the true lumen. The aim of this study was to assess the safety and efficacy of this approach, with successful true lumen distal wire passage as the primary endpoint. Forty-two patients were enrolled in four centres with high expertise in PCI for CTOs. All CTOs were of at least three months duration, and were initially attempted with dedicated recanalisation wires. After failure to pass or creation of a subintimal dissection, the BridgePoint devices were applied, consisting of a ball-tipped catheter (CrossBoss) to pass the proximal occlusion cap, and a flat-shaped balloon catheter (Stingray catheter) to be inflated within the subintimal space to guide the re-entry into the true vessel lumen with a special wire (Stingray guidewire). The primary endpoint was met in 67% of all patients. A higher success rate seemed to be possible when all devices were used in sequenced beginning with the CrossBoss, and in the case of a subintimal passage, followed by the Stingray. True lumen re-entry failed because of the loss of distally contrast filling and thus loss of a target for re-entry, and by a failure to advance the Stingray balloon far enough distal and parallel to the distal lumen. There were no severe device related complications. In patients with complex CTOs referred to dedicated centres with high experience in CTOs, these results demonstrate the potential of a guided re-entry from a subintimal wire position by use of the BridgePoint devices.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

PubMed

Wahie, S; Meggitt, S J

2013-09-01

The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure. © 2013 British Association of Dermatologists.

Primaquine treatment and relapse in Plasmodium vivax malaria

PubMed Central

2016-01-01

The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once ‘neglected’ species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients’ G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe. PMID:27077309

Twelve-month results of a prospective, multicentre trial to assess the everolimus-eluting coronary stent system (PROMUS Element): the PLATINUM PLUS all-comers randomised trial.

PubMed

Fajadet, Jean; Neumann, Franz-Josef; Hildick-Smith, David; Petronio, Sonia; Zaman, Azfar; Spence, Mark; Wöhrle, Jochen; Elhadad, Simon; Roberts, David; Hovasse, Thomas; Valdés, Mariano; Silber, Sigmund

2017-01-20

The aim of the study was to compare the safety and efficacy of the platinum-chromium-based everolimus-eluting stent (EES) with a cobalt-chromium EES. We performed a prospective, multicentre, single-blind non-inferiority all-comers study randomising patients with stable or unstable coronary artery disease (2:1) to treatment with the platinum-chromium EES (n=1,952) or the control cobalt-chromium EES (n=1,028) in Europe (PLATINUM PLUS trial). The primary endpoint was target vessel failure (TVF) at 12 months, a composite of target vessel-related cardiac death, myocardial infarction (MI), and ischaemia-driven target vessel revascularisation (TVR). Among 2,980 patients, 33% presented with acute coronary syndromes, and 48% with multivessel disease. At 12 months, the intention-to-treat analysis determined that the platinum-chromium EES was non-inferior to the cobalt-chromium EES for the primary endpoint (86 [4.6%] patients vs. 32 [3.2%], absolute difference 1.4%, 95% confidence interval [CI]: -0.1-2.9; upper limit of the one-sided 95% CI: 2.57%; non-inferiority p=0.012; superiority analysis: hazard ratio [HR] 1.44, 95% CI: 0.96-2.16, p=0.08). In the per protocol analysis, however, the primary endpoint was significantly more common in the platinum-chromium EES (HR 1.64, 95% CI: 1.05-2.55, p=0.03). There were no significant differences in the rates of cardiac death (1.1% vs. 1.0%, p=0.78), MI (1.6% vs. 0.8%, p=0.09), or ischaemia-driven TLR (2.0% vs. 1.6%, p=0.49). The rates of ARC definite or probable stent thrombosis were comparable between platforms (0.8% vs. 0.5%, p=0.44). At one year, the platinum-chromium EES satisfied the pre-specified criteria for non-inferiority relative to the control cobalt-chromium EES in this all-comers trial.

Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study.

PubMed

Schaefer, Christof; Hannemann, Doreen; Meister, Reinhard; Eléfant, Elisabeth; Paulus, Wolfgang; Vial, Thierry; Reuvers, Minke; Robert-Gnansia, Elisabeth; Arnon, Judy; De Santis, Marco; Clementi, Maurizio; Rodriguez-Pinilla, Elvira; Dolivo, Alla; Merlob, Paul

2006-06-01

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Cost-Effectiveness Analysis of a Transparent Antimicrobial Dressing for Managing Central Venous and Arterial Catheters in Intensive Care Units

PubMed Central

Bernatchez, Stéphanie F.; Ruckly, Stéphane; Timsit, Jean-François

2015-01-01

Objective To model the cost-effectiveness impact of routine use of an antimicrobial chlorhexidine gluconate-containing securement dressing compared to non-antimicrobial transparent dressings for the protection of central vascular lines in intensive care unit patients. Design This study uses a novel health economic model to estimate the cost-effectiveness of using the chlorhexidine gluconate dressing versus transparent dressings in a French intensive care unit scenario. The 30-day time non-homogeneous markovian model comprises eight health states. The probabilities of events derive from a multicentre (12 French intensive care units) randomized controlled trial. 1,000 Monte Carlo simulations of 1,000 patients per dressing strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The outcome is the number of catheter-related bloodstream infections avoided. Costs of intensive care unit stay are based on a recent French multicentre study and the cost-effectiveness criterion is the cost per catheter-related bloodstream infections avoided. The incremental net monetary benefit per patient is also estimated. Patients 1000 patients per group simulated based on the source randomized controlled trial involving 1,879 adults expected to require intravascular catheterization for 48 hours. Intervention Chlorhexidine Gluconate-containing securement dressing compared to non-antimicrobial transparent dressings. Results The chlorhexidine gluconate dressing prevents 11.8 infections /1,000 patients (95% confidence interval: [3.85; 19.64]) with a number needed to treat of 85 patients. The mean cost difference per patient of €141 is not statistically significant (95% confidence interval: [€-975; €1,258]). The incremental cost-effectiveness ratio is of €12,046 per catheter-related bloodstream infection prevented, and the incremental net monetary benefit per patient is of €344.88. Conclusions According to the base case scenario, the chlorhexidine gluconate dressing is more cost-effective than the reference dressing. Trial Registration This model is based on the data from the RCT registered with www.clinicaltrials.gov (NCT01189682). PMID:26086783

Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial.

PubMed

Fang, Jianqiao; Chen, Lifang; Chen, Luni; Wang, Chao; Keeler, Crystal Lynn; Ma, Ruijie; Xu, Shouyu; Shen, Laihua; Bao, Yehua; Ji, Conghua

2014-12-04

Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture and Chinese herbal medicine. The assessment data will be collected at baseline, 4 and 8 weeks postrandomisation, and then at 12 weeks' follow-up. The primary outcome is measured by the Modified Barthel Index. The secondary outcomes are the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, the mini-mental state examination and Montreal Cognitive, Hamilton's Depression Scale and Self-Rating Depression Scale, and the incidence of adverse events. Ethical approval was obtained from ethics committees of three hospitals. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone, during follow-up calls inquiring on patient's post-study health status. Chinese Clinical Trial Register: ChiCTR-TRC-12001972, http://www.chictr.org/en/proj/show.aspx?proj=2561. 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.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

PubMed Central

McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

2017-01-01

Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

Physiotherapy and occupational therapy interventions for people with benign joint hypermobility syndrome: a systematic review of clinical trials.

PubMed

Smith, Toby O; Bacon, Holly; Jerman, Emma; Easton, Vicky; Armon, Kate; Poland, Fiona; Macgregor, Alex J

2014-01-01

This study assessed the literature to determine the efficacy and effectiveness of physiotherapy and occupational therapy interventions in the treatment of people with benign joint hypermobility syndrome (BJHS). Published literature databases including: AMED, CINAHL, MEDLINE, EMBASE, PubMed and the Cochrane Library, in addition to unpublished databases and trial registries were searched to October 2012. All clinical trials comparing the clinical outcomes of Occupational Therapy and Physiotherapy interventions compared to non-treatment or control intervention for people with BJHS were included. Of the 126 search results, 3 clinical studies satisfied the eligibility criteria. The data provides limited support for the use of wrist/hand splints for school children. While there is some support for exercise-based intervention, there is insufficient research to determine the optimal mode, frequency, dosage or type of exercise which should be delivered. The current evidence-base surrounding Occupational Therapy and Physiotherapy in the management of BJHS is limited in size and quality. There is insufficient research exploring the clinical outcomes of a number of interventions including sensory integration, positioning and posture management and education. Longer term, rigorous multi-centre randomised controlled trials are warranted to begin to assess the clinical and cost-effectiveness of interventions for children and adults with BJHS. Implications for Rehabilitation There is an evidence-base to support clinician's use of proprioceptive-based exercises in adults, and either tailored or generalised physiotherapy regimes for children with BJHS. Clinicians should be cautious when considering the prescription of hand/wrist splints for school age children with BJHS, based on the current research. Until further multi-centre trials are conducted assessing the clinical and cost-effectiveness of interventions for children and adult with BJHS, clinical decision-making should be based on theoretical rather than evidence-based grounds for this population.

Use of XenX™, the latest ureteric occlusion device with guide wire utility: results from a prospective multicentric comparative study.

PubMed

Sanguedolce, Francesco; Montanari, Emanuele; Alvarez-Maestro, Mario; Macchione, Nicola; Hruby, Stephan; Papatsoris, Athanasios; Kallidonis, Panagiotis; Villa, Luca; Honeck, Patrick; Traxer, Olivier; Greco, Francesco

2016-11-01

This is a prospective multicentric comparative study evaluating the performance of XenX-a new dual-purpose device for the prevention of stone fragments migration during ureteroscopic lithotripsy (URS). Between March 2014 and January 2015, 41 patients undertaking URS + XenX were matched with 41 patients undergoing standard URS. Patients included had unilateral ureteric stone(s) of 0.5-1.5 cm in maximum size. Demographics, complication rates and surgical outcomes were recorded for comparison. A Likert-like 5-grade scoring system was used for surgeons' evaluation of XenX properties. Cost analysis was performed by comparing weighted mean costs of the relevant procedures. Patients' characteristics between the two groups were comparable. Lasering time was longer for XenX group (13.59 vs. 5.17 min; p = 0.0001) whilst use of basket and need of JJ stent insertion was more frequent in control group (19.5 vs. 97.6 %; p = 0.0001 and 22 vs. 35 %; p = 0.001, respectively). Intra-operative SFR was significantly higher for XenX group (100 vs. 85.4 %; p = 0.0001), but not at 4-week follow-up, after ancillary procedures were needed in 17.1 % of the control group. Surgeons' evaluations for XenX were suboptimal for "Ease of Basketing" (2/5) and "Advancement of double J stent" (3/5). The use of XenX increased costs of procedures, but spared the costs associated to ancillary procedures and stent removals. XenX confirmed to be a safe and effective device especially for the treatment of upper ureteric tract stones; moreover, XenX may reduce the risk for the need of auxiliary procedures and for the insertion of a JJ stent.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)

PubMed Central

Williamson, Esther; Lait, Clare; Richmond, Helen; Betteley, Lauren; Lall, Ranjit; Petrou, Stavros; Rees, Sophie; Withers, Emma J; Lamb, Sarah E; Thompson, Alastair M

2018-01-01

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery. Methods This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions. Discussion The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation. Protocol version Version 2.1; dated 11 January 2017 Trial registration number ISRCTN35358984; Pre-results. PMID:29574439

Effectiveness of disease-specific cognitive–behavioural therapy on depression, anxiety, quality of life and the clinical course of disease in adolescents with inflammatory bowel disease: study protocol of a multicentre randomised controlled trial (HAPPY-IBD)

PubMed Central

van den Brink, Gertrude; Stapersma, Luuk; El Marroun, Hanan; Henrichs, Jens; Szigethy, Eva M; Utens, Elisabeth MWJ; Escher, Johanna C

2016-01-01

Introduction Adolescents with inflammatory bowel disease (IBD) show a higher prevalence of depression and anxiety, compared to youth with other chronic diseases. The inflammation-depression hypothesis might explain this association, and implies that treating depression can decrease intestinal inflammation and improve disease course. The present multicentre randomised controlled trial aims to test the effectiveness of an IBD-specific cognitive–behavioural therapy (CBT) protocol in reducing symptoms of subclinical depression and anxiety, while improving quality of life and disease course in adolescents with IBD. Methods and analysis Adolescents with IBD (10–20 years) from 7 hospitals undergo screening (online questionnaires) for symptoms of depression and anxiety. Those with elevated scores of depression (Child Depression Inventory (CDI) ≥13 or Beck Depression Inventory (BDI) II ≥14) and/or anxiety (Screen for Child Anxiety Related Disorders: boys ≥26, girls ≥30) receive a psychiatric interview. Patients meeting criteria for depressive/anxiety disorders are referred for psychotherapy outside the trial. Patients with elevated (subclinical) symptoms are randomly assigned to medical care-as-usual (CAU; n=50) or CAU plus IBD-specific CBT (n=50). Main outcomes: (1) reduction in depressive and/or anxiety symptoms after 3 months and (2) sustained remission for 12 months. Secondary outcomes: quality of life, psychosocial functioning, treatment adherence. In addition, we will assess inflammatory cytokines in peripheral blood mononuclear cells and whole blood RNA expression profiles. For analysis, multilevel linear models and generalised estimating equations will be used. Ethics and dissemination The Medical Ethics Committee of the Erasmus MC approved this study. If we prove that this CBT improves emotional well-being as well as disease course, implementation is recommended. Trial registration number NCT02265588. PMID:26966551

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs.

PubMed

Benchaoui, H A; Siedek, E M; De La Puente-Redondo, V A; Tilt, N; Rowan, T G; Clemence, R G

2007-09-29

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).

Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study.

PubMed

Papadimitriou, George N; Dikeos, Dimitris G; Souery, Daniel; Del-Favero, Jurgen; Massat, Isabelle; Avramopoulos, Dimitrios; Blairy, Sylvie; Cichon, Sven; Ivezic, Sladjana; Kaneva, Radka; Karadima, Georgia; Lilli, Roberta; Milanova, Vihra; Nöthen, Markus; Oruc, Lilijana; Rietschel, Marcella; Serretti, Alessandro; Van Broeckhoven, Christine; Stefanis, Costas N; Mendlewicz, Julien

2003-12-01

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.

High fat consumption in children with celiac disease.

PubMed

Ferrara, P; Cicala, M; Tiberi, E; Spadaccio, C; Marcella, L; Gatto, A; Calzolari, P; Castellucci, G

2009-01-01

The purpose of this study was to estimate the caloric intake and fat consumption in children with celiac disease (CD) following a gluten-free diet (GFD). This study enrolled 100 subjects, including 50 children with CD on a gluten-free diet and a control group of 50 healthy children. Statistical analysis to compare groups was performed using one-way ANOVA. A significant increase in fat consumption was observed in children with CD as compared to healthy children. The daily fat intake was 72.5 +/- 37.2 g per 100 g of food in the CD group and 52.9 +/- 35.4 g per 100 g of food in the control group (p < 0.008). A significant difference in fat intake was found between celiac and healthy females (10.21 +/- 3.15 g/100 g in the celiac group vs 7.46 +/- 2.91 g/100 g in the control group), p = 0.004. This study describes a significantly higher fat consumption in patients with CD on GFD as compared to controls. This increase was more pronounced in females and during the puberal age. Based on these interesting preliminary results we estimate that further investigations are necessary, such as a randomized multicentre study on the long-term effects of GFD with particular attention to the imbalance in daily fat intake.

External fixators in the treatment of midshaft clavicle non-unions: a systematic review.

PubMed

Barlow, Tim; Upadhyay, Piyush; Barlow, David

2014-02-01

Non- or mal-union of the clavicle is reported to occur in up to 15 % of conservatively treated fractures: the purpose of this systematic review is to examine the evidence for the use of external fixation in the treatment of clavicular non-union. We performed a search of MEDLINE and Embase, including all papers using external fixators for the treatment of clavicular non-union. Four papers satisfied our eligibility criteria: three case series and one case-control study. Level of evidence and quality assessment scoring were performed using published methods. Due to the heterogeneity of the study populations and interventions, no attempt at meta-analysis was made. External fixation in hypertrophic non-union of the clavicle, but not atrophic non-union, appears to be a reasonable treatment option. A pragmatic, multicentre, randomised controlled trial comparing external fixation and open reduction internal fixation in the treatment of hypertrophic non-union of the clavicle would be valuable.

Effect of family nursing therapeutic conversations on health-related quality of life, self-care and depression among outpatients with heart failure: A randomized multi-centre trial.

PubMed

Østergaard, Birte; Mahrer-Imhof, Romy; Wagner, Lis; Barington, Torben; Videbæk, Lars; Lauridsen, Jørgen

2018-03-07

To evaluate the short-term (3 months) effects of family nursing therapeutic conversations (FNTC) on health-related quality of life, self-care and depression in outpatients with Heart failure (HF). A randomised multi-centre trial was conducted in three Danish HF clinics. The control group (n = 167) received usual care, and the intervention group (n = 180) received FNTCs as supplement to usual care. Primary outcome was clinically significant changes (6 points) in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score between groups. Secondary outcomes were changes in self-care behaviour and depression scores. Data were assessed before first consultation and repeated after three months. No statistically significant difference was found in the change of KCCQ, self-care and depression scores between the groups. KCCQ scores of patients in the FNTC group changed clinically significant in seven domains, compared to one domain in the control group, with the highest improvement in self-efficacy, social limitation and symptom burden. FNTC was not superior to standard care of patients with HF regarding health-related quality of life, self-care and depression. Addressing the impact of the disease on the family, might improve self-efficacy, social limitation and symptom burden in patients with heart failure. Copyright © 2018 Elsevier B.V. All rights reserved.

A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

PubMed Central

Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

1999-01-01

BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial.

PubMed

Bolinder, Jan; Antuna, Ramiro; Geelhoed-Duijvestijn, Petronella; Kröger, Jens; Weitgasser, Raimund

2016-11-05

Tight control of blood glucose in type 1 diabetes delays onset of macrovascular and microvascular diabetic complications; however, glucose levels need to be closely monitored to prevent hypoglycaemia. We aimed to assess whether a factory-calibrated, sensor-based, flash glucose-monitoring system compared with self-monitored glucose testing reduced exposure to hypoglycaemia in patients with type 1 diabetes. In this multicentre, prospective, non-masked, randomised controlled trial, we enrolled adult patients with well controlled type 1 diabetes (HbA 1c ≤58 mmol/mol [7·5%]) from 23 European diabetes centres. After 2 weeks of all participants wearing the blinded sensor, those with readings for at least 50% of the period were randomly assigned (1:1) to flash sensor-based glucose monitoring (intervention group) or to self-monitoring of blood glucose with capillary strips (control group). Randomisation was done centrally using the biased-coin minimisation method dependent on study centre and type of insulin administration. Participants, investigators, and study staff were not masked to group allocation. The primary outcome was change in time in hypoglycaemia (<3·9 mmol/L [70 mg/dL]) between baseline and 6 months in the full analysis set (all participants randomised; excluding those who had a positive pregnancy test during the study). This trial was registered with ClinicalTrials.gov, number NCT02232698. Between Sept 4, 2014, and Feb 12, 2015, we enrolled 328 participants. After the screening and baseline phase, 120 participants were randomly assigned to the intervention group and 121 to the control group, with outcomes being evaluated in 119 and 120, respectively. Mean time in hypoglycaemia changed from 3·38 h/day at baseline to 2·03 h/day at 6 months (baseline adjusted mean change -1·39) in the intervention group, and from 3·44 h/day to 3·27 h/day in the control group (-0·14); with the between-group difference of -1·24 (SE 0·239; p<0·0001), equating to a 38% reduction in time in hypoglycaemia in the intervention group. No device-related hypoglycaemia or safety issues were reported. 13 adverse events were reported by ten participants related to the sensor-four of allergy events (one severe, three moderate); one itching (mild); one rash (mild); four insertion-site symptom (severe); two erythema (one severe, one mild); and one oedema (moderate). There were ten serious adverse events (five in each group) reported by nine participants; none were related to the device. Novel flash glucose testing reduced the time adults with well controlled type 1 diabetes spent in hypoglycaemia. Future studies are needed to assess the effectiveness of this technology in patients with less well controlled diabetes and in younger age groups. Abbott Diabetes Care. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reference values for voluntary and stimulated single-fibre EMG using concentric needle electrodes: a multicentre prospective study.

PubMed

Kokubun, Norito; Sonoo, Masahiro; Imai, Tomihiro; Arimura, Yumiko; Kuwabara, Satoshi; Komori, Tetsuo; Kobayashi, Masahito; Nagashima, Takahide; Hatanaka, Yuki; Tsuda, Emiko; Misawa, Sonoko; Abe, Tatsuya; Arimura, Kimiyoshi

2012-03-01

The aim of this study is to establish reference values for single-fibre electromyography (SFEMG) using concentric needles in a prospective, multicentre study. Voluntary or stimulated SFEMG at the extensor digitorum communis (EDC) or frontalis (FRO) muscles was conducted in 56-63 of a total of 69 normal subjects below the age of 60years at six Japanese institutes. The cut-off values for mean consecutive difference (MCD) of individual potentials were calculated using +2.5 SD or 95% prediction limit (one-tail) of the upper 10th percentile MCD value for individual subjects. The cut-off values for individual MCD (+2.5 SD) were 56.8μs for EDC-V (voluntary SFEMG for EDC), 58.8μs for EDC-S (stimulated SFEMG for EDC), 56.8μs for FRO-V (voluntary SFEMG for FRO) and 51.0μs for FRO-S (stimulated SFEMG for FRO). The false positive rates using these cut-off values were around 2%. The +2.5 SD and 95% prediction limit might be two optimal cut-off values, depending on the clinical question. The obtained reference values were larger than those reported previously using concentric needles, but might better coincide with conventional values. This is the first multicentre study reporting reference values for SFEMG using concentric needles. The way to determine cut-off values and the statistically correct definition of the percentile were discussed. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effectiveness of robot-assisted training added to conventional rehabilitation in patients with humeral fracture early after surgical treatment: protocol of a randomised, controlled, multicentre trial.

PubMed

Nerz, Corinna; Schwickert, Lars; Becker, Clemens; Studier-Fischer, Stefan; Müßig, Janina Anna; Augat, Peter

2017-12-06

The incidence of proximal humeral fractures increases with age. The functional recovery of the upper arm after such fractures is slow, and results are often disappointing. Treatment is associated with long immobilisation periods. Evidence-based exercise guidelines are missing. Loss of muscle mass as well as reduced range of motion and motor performance are common consequences. These losses could be partly counteracted by training interventions using robot-assisted arm support of the affected arm derived from neurorehabilitation. Thus, shorter immobilisation could be reached. Thus far, this approach has been tested in only a few small studies. The aim of the present study is to examine whether assistive robotic training augmenting conventional occupational and physical therapy can improve functional shoulder outcomes. Patients aged between 35 and 66 years with proximal humeral fracture and surgical treatment will be recruited at three different clinics in Germany and randomised into an intervention group and a control group. Participants will be assessed before randomisation and followed after completing an intervention period of 3 weeks and additionally after 3, 6 and 12 months. The baseline assessment will include cognition (Short Orientation-Memory-Concentration Test); level of pain in the affected arm; ability to work; gait speed (10-m walk); disability of the arm, shoulder and hand (Disabilities of the Arm, Shoulder and Hand Outcome Measure [DASH]); range of motion of the affected arm (goniometer measurement); visual acuity; and motor function of orthopaedic patients (Wolf Motor Function Test-Orthopaedic version [WMFT-O]). Clinical follow-up directly after the intervention will include assessment of disability of the arm, shoulder and hand (DASH) as well as range of motion and motor function (WMFT-O). The primary outcome parameter will be the DASH, and the secondary outcome parameter will be the WMFT-O. The long-term results will be assessed prospectively by postal follow-up. All patients will receive conventional occupational and physical therapy. The intervention group will receive additional robot-assisted training using the Armeo®Spring robot for 3 weeks. This study protocol describes a phase II, randomised, controlled, single-blind, multicentre intervention study. The results will guide and possibly improve methods of rehabilitation after proximal humeral fracture. Clinicaltrials.gov, NCT03100201 . Registered on 28 March 2017.

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study.

PubMed

Martín-Richard, Marta; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Angel; Quindós, Maria; Maisonobe, Pascal

2013-09-20

Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Hemostasis Committee of the "Société Française de Biologie Clinique".

PubMed

1992-05-15

The laboratory heterogeneity of the lupus anticoagulant (LA) was investigated in a multicentre study using a panel of 78 plasma samples diagnosed as containing a LA. Consecutive samples were collected by 12 participants using various screening tests, and sent to 7 laboratories which performed one or more clotting assays among the following: activated partial thromboplastin time (APTT), dilute Russell viper venom time, kaolin clotting time (KCT), dilute tissue thromboplastin time (dTTI) and a platelet neutralization test. For APTT and dTTI, 10 versions of these tests including standard and mixing procedures were carried out. They varied by reagents, phospholipid concentration or methodology. Cut-off times were determined for each test by comparing the results of the panel to those of a control population. When the data of all clotting assays were pooled, 70 of the 78 selected plasmas were considered to contain LA, 15 of them having a low-titer inhibitor. Sensitivity, defined as the proportion of positive results among LA-containing plasmas, varied from 62 to 100% and was positively related to responsiveness (defined as the mean ratio of clotting time to cut-off time). Laboratory heterogeneity of LA-containing plasma was illustrated by a star symbol plot analysis. Different populations of samples, with LA preferentially recognized by one assay (or group of assays) irrespective of the overall sensitivity of this assay, were identified. Multiple component analysis demonstrated the heterogeneity of low-titer inhibitors, which complicates their recognition in routine laboratory investigation.

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

PubMed Central

2013-01-01

Background Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. Methods This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Results Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Conclusion Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. Trial registration ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18. PMID:24053191

A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement

ClinicalTrials.gov

2016-08-03

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

Comparing meta-analysis and ecological-longitudinal analysis in time-series studies. A case study of the effects of air pollution on mortality in three Spanish cities

PubMed Central

Saez, M; Figueiras, A; Ballester, F; Perez-Hoyos, S; Ocana, R; Tobias, A

2001-01-01

STUDY OBJECTIVE—The objective of this paper is to introduce a different approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches.
DESIGN—The approach is illustrated by providing quantitative estimates of the short-term effects of air pollution on mortality in three Spanish cities, Barcelona, Valencia and Vigo, for the period 1992-1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were non-linear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models.
MAIN RESULTS—The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 µg/m3 and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 µg/m3 of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant, especially those among air pollutants and meteorological variables.
CONCLUSIONS—Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities.


Keywords: air pollution; mortality; longitudinal studies PMID:11351001

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy.

PubMed

Imms, Christine; Wallen, Margaret; Elliott, Catherine; Hoare, Brian; Randall, Melinda; Greaves, Susan; Adair, Brooke; Bradshaw, Elizabeth; Carter, Rob; Orsini, Francesca; Shih, Sophy T F; Reddihough, Dinah

2016-05-27

Upper limb orthoses are frequently prescribed for children with cerebral palsy (CP) who have muscle overactivity predominantly due to spasticity, with little evidence of long-term effectiveness. Clinical consensus is that orthoses help to preserve range of movement: nevertheless, they can be complex to construct, expensive, uncomfortable and require commitment from parents and children to wear. This protocol paper describes a randomised controlled trial to evaluate whether long-term use of rigid wrist/hand orthoses (WHO) in children with CP, combined with usual multidisciplinary care, can prevent or reduce musculoskeletal impairments, including muscle stiffness/tone and loss of movement range, compared to usual multidisciplinary care alone. This pragmatic, multicentre, assessor-blinded randomised controlled trial with economic analysis will recruit 194 children with CP, aged 5-15 years, who present with flexor muscle stiffness of the wrist and/or fingers/thumb (Modified Ashworth Scale score ≥1). Children, recruited from treatment centres in Victoria, New South Wales and Western Australia, will be randomised to groups (1:1 allocation) using concealed procedures. All children will receive care typically provided by their treating organisation. The treatment group will receive a custom-made serially adjustable rigid WHO, prescribed for 6 h nightly (or daily) to wear for 3 years. An application developed for mobile devices will monitor WHO wearing time and adverse events. The control group will not receive a WHO, and will cease wearing one if previously prescribed. Outcomes will be measured 6 monthly over a period of 3 years. The primary outcome is passive range of wrist extension, measured with fingers extended using a goniometer at 3 years. Secondary outcomes include muscle stiffness, spasticity, pain, grip strength and hand deformity. Activity, participation, quality of life, cost and cost-effectiveness will also be assessed. This study will provide evidence to inform clinicians, services, funding agencies and parents/carers of children with CP whether the provision of a rigid WHO to reduce upper limb impairment, in combination with usual multidisciplinary care, is worth the effort and costs. ANZ Clinical Trials Registry: U1111-1164-0572 .

Implementation of evidence-based weekend service recommendations for allied health managers: a cluster randomised controlled trial protocol.

PubMed

Sarkies, Mitchell N; White, Jennifer; Morris, Meg E; Taylor, Nicholas F; Williams, Cylie; O'Brien, Lisa; Martin, Jenny; Bardoel, Anne; Holland, Anne E; Carey, Leeanne; Skinner, Elizabeth H; Bowles, Kelly-Ann; Grant, Kellie; Philip, Kathleen; Haines, Terry P

2018-04-24

It is widely acknowledged that health policy and practice do not always reflect current research evidence. Whether knowledge transfer from research to practice is more successful when specific implementation approaches are used remains unclear. A model to assist engagement of allied health managers and clinicians with research implementation could involve disseminating evidence-based policy recommendations, along with the use of knowledge brokers. We developed such a model to aid decision-making for the provision of weekend allied health services. This protocol outlines the design and methods for a multi-centre cluster randomised controlled trial to evaluate the success of research implementation strategies to promote evidence-informed weekend allied health resource allocation decisions, especially in hospital managers. This multi-centre study will be a three-group parallel cluster randomised controlled trial. Allied health managers from Australian and New Zealand hospitals will be randomised to receive either (1) an evidence-based policy recommendation document to guide weekend allied health resource allocation decisions, (2) the same policy recommendation document with support from a knowledge broker to help implement weekend allied health policy recommendations, or (3) a usual practice control group. The primary outcome will be alignment of weekend allied health service provision with policy recommendations. This will be measured by the number of allied health service events (occasions of service) occurring on weekends as a proportion of total allied health service events for the relevant hospital wards at baseline and 12-month follow-up. Evidence-based policy recommendation documents communicate key research findings in an accessible format. This comparatively low-cost research implementation strategy could be combined with using a knowledge broker to work collaboratively with decision-makers to promote knowledge transfer. The results will assist managers to make decisions on resource allocation, based on evidence. More generally, the findings will inform the development of an allied health model for translating research into practice. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) ( ACTRN12618000029291 ). Universal Trial Number (UTN): U1111-1205-2621.

Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy.

PubMed

Probst, Pascal; Hüttner, Felix J; Klaiber, Ulla; Knebel, Phillip; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K

2015-11-06

Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.

PubMed

Reinisch, Walter; Panés, Julián; Khurana, Sunil; Toth, Gabor; Hua, Fei; Comer, Gail M; Hinz, Michelle; Page, Karen; O'Toole, Margot; Moorehead, Tara McDonnell; Zhu, Hua; Sun, YanHui; Cataldi, Fabio

2015-06-01

Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. ClinicalTrials.gov number NCT01284062. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The increases in potassium concentrations are greater with succinylcholine than with rocuronium-sugammadex in outpatient surgery: a randomized, multicentre trial.

PubMed

Sabo, Daniel; Jahr, Jonathan; Pavlin, Janet; Philip, Beverly; Shimode, Noriko; Rowe, Everton; Woo, Tiffany; Soto, Roy

2014-05-01

Succinylcholine provides rapid onset of neuromuscular blockade and short duration of action, but its administration may be associated with hyperkalemia. Rocuronium is not known to increase potassium concentration, has fast onset of activity, and can be rapidly reversed by sugammadex. This study evaluated changes in plasma potassium concentrations in patients randomized either to rocuronium followed by sugammadex reversal or to succinylcholine in ambulatory surgery. In this multicentre randomized active-controlled study, adult patients undergoing short surgical procedures in an outpatient setting received either rocuronium 0.6 mg·kg(-1) for intubation with sugammadex 4.0 mg·kg(-1) for reversal (n = 70) or succinylcholine 1.0 mg·kg(-1) with spontaneous recovery (n = 80). Blood potassium concentrations were assessed at baseline (before study drug administration) and at intervals up to 15 min after rocuronium, sugammadex, and succinylcholine. At the primary endpoint, five minutes post-administration, the changes in potassium concentrations from baseline were significantly smaller in patients treated with rocuronium than in those given succinylcholine [mean (SD): -0.06 (0.32) vs 0.30 (0.34) mmol·L(-1), respectively; P < 0.0001]. At baseline, potassium concentrations were similar in both groups, but they were greater at two, five, ten, and 15 min after succinylcholine than after rocuronium (P < 0.0001) for all time points. After sugammadex administration, there were no significant changes in mean potassium concentration from the pre-rocuronium baseline. No adverse effects related to hyperkalemia were observed. Succinylcholine was associated with a modest increase in potassium concentration; these changes were not seen after rocuronium or sugammadex ( NCT00751179).

Effectiveness of osteopathic manipulative treatment in neonatal intensive care units: protocol for a multicentre randomised clinical trial

PubMed Central

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; D'Incecco, Carmine; Fusilli, Paola; Perri, Paolo Francesco; Tubaldi, Lucia; Barlafante, Gina

2013-01-01

Introduction Neonatal care has been considered as one of the first priorities for improving quality of life in children. In 2010, 10% of babies were born prematurely influencing national healthcare policies, economic action plans and political decisions. The use of complementary medicine has been applied to the care of newborns. One previous study documented the positive effect of osteopathic manipulative treatment (OMT) in reducing newborns’ length of stay (LOS). Aim of this multicentre randomised controlled trial is to examine the association between OMT and LOS across three neonatal intensive care units (NICUs). Methods and analysis 690 preterm infants will be recruited from three secondary and tertiary NICUs from north and central Italy and allocated into two groups, using permuted-block randomisation. The two groups will receive standard medical care and OMT will be applied, twice a week, to the experimental group only. Outcome assessors will be blinded of study design and group allocation. The primary outcome is the mean difference in days between discharge and entry. Secondary outcomes are difference in daily weight gain, number of episodes of vomit, regurgitation, stooling, use of enema, time to full enteral feeding and NICU costs. Statistical analyses will take into account the intention-to-treat method. Missing data will be handled using last observation carried forward (LOCF) imputation technique. Ethics and dissemination Written informed consent will be obtained from parents or legal guardians at study enrolment. The trial has been approved by the ethical committee of Macerata hospital (n°22/int./CEI/27239) and it is under review by the other regional ethics committees. Results Dissemination of results from this trial will be through scientific medical journals and conferences. Trial registration This trial has been registered at http://www.clinicaltrials.org (identifier NCT01645137). PMID:23430598

Multicentric comparative assessment of the bio-evolution Toxoplasma gondii detection kit with eight laboratory-developed PCR assays for molecular diagnosis of congenital toxoplasmosis.

PubMed

Filisetti, Denis; Sterkers, Yvon; Brenier-Pinchart, Marie-Pierre; Cassaing, Sophie; Dalle, Frédéric; Delhaes, Laurence; Pelloux, Hervé; Touafek, Fériel; Varlet-Marie, Emmanuelle; Yera, Hélène; Candolfi, Ermano; Bastien, Patrick

2015-01-01

The detection of Toxoplasma gondii in amniotic fluid is an essential tool for the prenatal diagnosis of congenital toxoplasmosis and is currently essentially based on the use of PCR. Although some consensus is emerging, this molecular diagnosis suffers from a lack of standardization and an extreme diversity of laboratory-developed methods. Commercial kits for the detection of T. gondii by PCR were recently developed and offer certain advantages; however, they must be assessed in comparison with optimized reference PCR assays. The present multicentric study aimed to compare the performances of the Bio-Evolution T. gondii detection kit and laboratory-developed PCR assays set up in eight proficient centers in France. The study compared 157 amniotic fluid samples and found concordances of 99% and 100% using 76 T. gondii-infected samples and 81 uninfected samples, respectively. Moreover, taking into account the classification of the European Research Network on Congenital Toxoplasmosis, the overall diagnostic sensitivity of all assays was identical and calculated to be 86% (54/63); specificity was 100% for all assays. Finally, the relative quantification results were in good agreement between the kit and the laboratory-developed assays. The good performances of this commercial kit are probably in part linked to the use of a number of good practices: detection in multiplicate, amplification of the repetitive DNA target rep529, and the use of an internal control for the detection of PCR inhibitors. The only drawbacks noted at the time of the study were the absence of uracil-N-glycosylase and small defects in the reliability of the production of different reagents. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Multicentric Comparative Assessment of the Bio-Evolution Toxoplasma gondii Detection Kit with Eight Laboratory-Developed PCR Assays for Molecular Diagnosis of Congenital Toxoplasmosis

PubMed Central

Filisetti, Denis; Sterkers, Yvon; Brenier-Pinchart, Marie-Pierre; Cassaing, Sophie; Dalle, Frédéric; Delhaes, Laurence; Pelloux, Hervé; Touafek, Fériel; Varlet-Marie, Emmanuelle; Yera, Hélène; Candolfi, Ermano

2014-01-01

The detection of Toxoplasma gondii in amniotic fluid is an essential tool for the prenatal diagnosis of congenital toxoplasmosis and is currently essentially based on the use of PCR. Although some consensus is emerging, this molecular diagnosis suffers from a lack of standardization and an extreme diversity of laboratory-developed methods. Commercial kits for the detection of T. gondii by PCR were recently developed and offer certain advantages; however, they must be assessed in comparison with optimized reference PCR assays. The present multicentric study aimed to compare the performances of the Bio-Evolution T. gondii detection kit and laboratory-developed PCR assays set up in eight proficient centers in France. The study compared 157 amniotic fluid samples and found concordances of 99% and 100% using 76 T. gondii-infected samples and 81 uninfected samples, respectively. Moreover, taking into account the classification of the European Research Network on Congenital Toxoplasmosis, the overall diagnostic sensitivity of all assays was identical and calculated to be 86% (54/63); specificity was 100% for all assays. Finally, the relative quantification results were in good agreement between the kit and the laboratory-developed assays. The good performances of this commercial kit are probably in part linked to the use of a number of good practices: detection in multiplicate, amplification of the repetitive DNA target rep529, and the use of an internal control for the detection of PCR inhibitors. The only drawbacks noted at the time of the study were the absence of uracil-N-glycosylase and small defects in the reliability of the production of different reagents. PMID:25339393

Early prognostic value of an Algorithm based on spectral Variables of Ventricular fibrillAtion from the EKG of patients with suddEn cardiac death: A multicentre observational study (AWAKE).

PubMed

Palacios-Rubio, Julián; Marina-Breysse, Manuel; Quintanilla, Jorge G; Gil-Perdomo, José Miguel; Juárez-Fernández, Miriam; Garcia-Gonzalez, Inés; Rial-Bastón, Verónica; Corcobado, María Carmen; Espinosa, María Carmen; Ruiz, Francisco; Gómez-Mascaraque Pérez, Francisco; Bringas-Bollada, María; Lillo-Castellano, José María; Pérez-Castellano, Nicasio; Martínez-Sellés, Manuel; López de Sá, Esteban; Martín-Benítez, Juan Carlos; Perez-Villacastín, Julián; Filgueiras-Rama, David

2018-06-06

Ventricular fibrillation (VF)-related sudden cardiac death (SCD) is a leading cause of mortality and morbidity. Current biological and imaging parameters show significant limitations on predicting cerebral performance at hospital admission. The AWAKE study (NCT03248557) is a multicentre observational study to validate a model based on spectral ECG analysis to early predict cerebral performance and survival in resuscitated comatose survivors. Data from VF ECG tracings of patients resuscitated from SCD will be collected using an electronic Case Report Form. Patients can be either comatose (Glasgow Coma Scale - GCS - ≤8) survivors undergoing temperature control after return of spontaneous circulation (RoSC), or those who regain consciousness (GCS=15) after RoSC; all admitted to Intensive Cardiac Care Units in 4 major university hospitals. VF tracings prior to the first direct current shock will be digitized and analyzed to derive spectral data and feed a predictive model to estimate favorable neurological performance (FNP). The results of the model will be compared to the actual prognosis. The primary clinical outcome is FNP during hospitalization. Patients will be categorized into 4 subsets of neurological prognosis according to the risk score obtained from the predictive model. The secondary clinical outcomes are survival to hospital discharge, and FNP and survival after 6 months of follow-up. The model-derived categorisation will be also compared with clinical variables to assess model sensitivity, specificity, and accuracy. A model based on spectral analysis of VF tracings is a promising tool to obtain early prognostic data after SCD. Copyright © 2018 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Blunt Cardiac Injury in the Severely Injured – A Retrospective Multicentre Study

PubMed Central

Hanschen, Marc; Kanz, Karl-Georg; Kirchhoff, Chlodwig; Khalil, Philipe N.; Wierer, Matthias; van Griensven, Martijn; Laugwitz, Karl-Ludwig; Biberthaler, Peter; Lefering, Rolf; Huber-Wagner, Stefan

2015-01-01

Background Blunt cardiac injury is a rare trauma entity. Here, we sought to evaluate the relevance and prognostic significance of blunt cardiac injury in severely injured patients. Methods In a retrospective multicentre study, using data collected from 47,580 patients enrolled to TraumaRegister DGU (1993-2009), characteristics of trauma, prehospital / hospital trauma management, and outcome analysis were correlated to the severity of blunt cardiac injury. The severity of cardiac injury was assessed according to the abbreviated injury score (AIS score 1-6), the revised injury severity score (RISC) allowed comparison of expected outcome with injury severity-dependent outcome. N = 1.090 had blunt cardiac trauma (AIS 1-6) (2.3% of patients). Results Predictors of blunt cardiac injury could be identified. Sternal fractures indicate a high risk of the presence of blunt cardiac injury (AIS 0 [control]: 3.0%; AIS 1: 19.3%; AIS 2-6: 19.1%). The overall mortality rate was 13.9%, minor cardiac injury (AIS 1) and severe cardiac injury (AIS 2-6) are associated with higher rates. Severe blunt cardiac injury (AIS 4 and AIS 5-6) is associated with a higher mortality (OR 2.79 and 4.89, respectively) as compared to the predicted average mortality (OR 2.49) of the study collective. Conclusion Multiple injured patients with blunt cardiac trauma are at high risk to be underestimated. Careful evaluation of trauma patients is able to predict the presence of blunt cardiac injury. The severity of blunt cardiac injury needs to be stratified according to the AIS score, as the patients’ outcome is dependent on the severity of cardiac injury. PMID:26136126

Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

PubMed

Häussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhäufl, M; Müller, K-M; Huber, R-M; Pichlmeier, U; Bolliger, Ch T

2005-06-01

The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.

Cohort profile: the German ClinSurv HIV project--a multicentre open clinical cohort study supplementing national HIV surveillance.

PubMed

Bätzing-Feigenbaum, J; Kollan, C; Kühne, A; Matysiak-Klose, D; Gunsenheimer-Bartmeyer, B; Hamouda, O

2011-05-01

New forms of HIV/AIDS therapy require new surveillance instruments to meet shifting public health demands. The Clinical Surveillance of HIV Disease (ClinSurv HIV) project was established in 1999 as a collaboration between major HIV treatment centres in Germany and the Robert Koch Institute (RKI). The project contributes to national HIV surveillance and focuses on the changing epidemiology of HIV/AIDS after the introduction of new therapies in 1995. ClinSurv HIV is designed as an open multicentre observational cohort study of HIV-infected patients. Anonymized data on diagnoses, treatment and laboratory parameters are collected in a standardized format. Data are currently sampled biannually via 11 centres specializing in HIV diagnosis and care within the legal framework of the German Protection against Infection Act [Infektionsschutzgesetz (IfSG)]. A total of 14874 patients were enrolled in the study by 30 June 2009. Of these, 10221 patients (68.7%) were enrolled after 1 January 1999 and 6006 patients (40.4%) were known to have been diagnosed as positive for HIV before 1999. Evaluation indicators, such as the number of newly enrolled patients per half-year period, loss to follow-up, completeness of data per case, availability of data per possible clinical contact, and internal quality control parameters, show a very stable evolution in the cohort, which although open, can be observed. Comparison with the national HIV surveillance data suggests a high degree of representativeness according to major demographic variables. Bearing in mind the obvious strengths and weaknesses discussed, the German ClinSurv HIV cohort provides a broad range of research opportunities in the field of HIV/AIDS both within Germany and in international collaborative research.

Lifestyle correlates of self-reported sleep duration among Saudi adolescents: a multicentre school-based cross-sectional study.

PubMed

Al-Hazzaa, H M; Musaiger, A O; Abahussain, N A; Al-Sobayel, H I; Qahwaji, D M

2014-07-01

Lifestyle factors are important determinants of adequate sleep among adolescents. However, findings on sleep duration relative to lifestyle factors are conflicting. Therefore, this study examined the association of self-reported sleep duration with physical activity, sedentary behaviours and dietary habits among Saudi adolescents. A multicentre school-based cross-sectional study was conducted in three major cities in Saudi Arabia. The sample included 2868 secondary-school students (51.9% girls) aged 15-19 years, randomly selected using a multistage stratified cluster sampling technique. In addition to anthropometric measurements, sleep duration, physical activity, sedentary behaviours and dietary habits were assessed using self-reported questionnaire. Several lifestyle factors were associated with sleep duration in adolescents. While controlling for some potential confounders, the findings showed that high screen time [>5 h/day; adjusted odds ratio (aOR) = 1.505, 95% confidence interval (CI) = 1.180-1.920, P = 0.001] and low (aOR = 1.290, 95% CI = 1.064-1.566, P = 0.010) to medium (aOR = 1.316, 95% CI = 1.075-1.611, P = 0.008) physical activity levels were significantly related to daily sleep of 8 h or longer. Furthermore, having low intake of breakfast (<3 day/week compared with 5 days or more per week) decreased the odd of having adequate sleep duration by a factor of 0.795 (95% CI = 0.667-0.947, P < 0.010). Short sleep duration (<8 h/day) among Saudi adolescents 15-19 year olds was significantly associated with several lifestyle factors. Intervention programs aiming for improving sleeping habits among adolescents need to consider such potential association of lifestyle variables with sleep duration. © 2013 John Wiley & Sons Ltd.

Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial.

PubMed

Boriani, Giuseppe; Tukkie, Raymond; Manolis, Antonis S; Mont, Lluis; Pürerfellner, Helmut; Santini, Massimo; Inama, Giuseppe; Serra, Paolo; de Sousa, João; Botto, Giovanni Luca; Mangoni, Lorenza; Grammatico, Andrea; Padeletti, Luigi

2014-09-14

Atrial fibrillation (AF) is a common comorbidity in bradycardia patients. Advanced pacemakers feature atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), which minimizes unnecessary right ventricular pacing. We evaluated whether DDDRP and MVP might reduce mortality, morbidity, or progression to permanent AF when compared with standard dual-chamber pacing (Control DDDR). In a randomized, parallel, single-blind, multi-centre trial we enrolled 1300 patients with bradycardia and previous atrial tachyarrhythmias, in whom a DDDRP pacemaker had recently been implanted. History of permanent AF and third-degree atrioventricular block were exclusion criteria. After a 1-month run-in period, 1166 eligible patients, aged 74 ± 9 years, 50% females, were randomized to Control DDDR, DDDRP + MVP, or MVP. Analysis was intention-to-treat. The primary outcome, i.e. the 2-year incidence of a combined endpoint composed of death, cardiovascular hospitalizations, or permanent AF, occurred in 102/385 (26.5%) Control DDDR patients, in 76/383 (19.8%) DDDRP + MVP patients [hazard ratio (HR) = 0.74, 95% confidence interval 0.55-0.99, P = 0.04 vs. Control DDDR] and in 85/398 (21.4%) MVP patients (HR = 0.89, 95% confidence interval 0.77-1.03, P = 0.125 vs. Control DDDR). When compared with Control DDDR, DDDRP + MVP reduced the risk for AF longer than 1 day (HR = 0.66, 95% CI 0.52-0.85, P < 0.001), AF longer than 7 days (HR = 0.52, 95% CI 0.36-0.73, P < 0.001), and permanent AF (HR = 0.39, 95% CI 0.21-0.75, P = 0.004). In patients with bradycardia and atrial tachyarrhythmias, DDDRP + MVP is superior to standard dual-chamber pacing. The primary endpoint was significantly lowered through the reduction of the progression of atrial tachyarrhythmias to permanent AF. NCT00262119. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Long-term safety and efficacy of tofogliflozin as add-on to insulin in patients with type 2 diabetes: Results from a 52-week, multicentre, randomized, double-blind, open-label extension, Phase 4 study in Japan (J-STEP/INS).

PubMed

Terauchi, Yasuo; Tamura, Masahiro; Senda, Masayuki; Gunji, Ryoji; Kaku, Kohei

2018-05-01

To evaluate the long-term safety and efficacy of tofogliflozin as an add-on treatment to insulin over 52 weeks. This 52-week, multicentre, Phase 4 study consisted of a 16-week, randomized, double-blind, placebo-controlled phase and a 36-week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%-10.5%) receiving insulin monotherapy (basal-bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase-4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the 'tofo-tofo group' and patients who received placebo and tofogliflozin (36 weeks) were referred to as the 'pla-tofo group'. A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment-emergent adverse event (AE) (42.9% in the tofo-tofo group and 29.4% in the pla-tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo-tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla-tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo-tofo and pla-tofo groups were 8.53% (-0.76% ± 0.077) and 8.40% (-0.73% ± 0.102); 68.84 kg (-1.52 kg ± 0.207) and 72.24 kg (-2.13 kg ± 0.313), respectively. This study demonstrates the safety and efficacy of tofogliflozin as add-on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol.

PubMed

Fenlon, Deborah; Nuttall, Jacqueline; May, Carl; Raftery, James; Fields, Jo; Kirkpatrick, Emma; Abab, Julia; Ellis, Mary; Rose, Taylor; Khambhaita, Priya; Galanopoulou, Angeliki; Maishman, Tom; Haviland, Jo; Griffiths, Gareth; Turner, Lesley; Hunter, Myra

2018-05-08

Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer. This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed. There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice. ISRCTN 12824632 . Registered 25-01-2017.

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

PubMed

Abrate, Alberto; Lazzeri, Massimo; Lughezzani, Giovanni; Buffi, Nicolòmaria; Bini, Vittorio; Haese, Alexander; de la Taille, Alexandre; McNicholas, Thomas; Redorta, Joan Palou; Gadda, Giulio M; Lista, Giuliana; Kinzikeeva, Ella; Fossati, Nicola; Larcher, Alessandro; Dell'Oglio, Paolo; Mistretta, Francesco; Freschi, Massimo; Guazzoni, Giorgio

2015-04-01

To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer. © 2014 The Authors. BJU International © 2014 BJU International.

Randomised controlled trial of the sliding hip screw versus X-Bolt Dynamic Hip Plating System for the fixation of trochanteric fractures of the hip in adults: a protocol study for WHiTE 4 (WHiTE4).

PubMed

Griffin, Xavier L; Achten, Juul; Sones, William; Cook, Jonathan; Costa, Matthew L

2018-01-26

Sliding hip screw fixation is well established in the treatment of trochanteric fractures of the hip. The X-Bolt Dynamic Hip Plating System builds on the successful design features of the sliding hip screw but differs in the nature of the fixation in the femoral head. A randomised pilot study suggested that the X-bolt Dynamic Hip Plating System might provide similar health-related quality of life while reducing the risk of revision surgery when compared with the sliding hip screw. This is the protocol for a multicentre randomised trial of sliding hip screw versus X-Bolt Dynamic Hip Plating System for patients 60 years and over treated for a trochanteric fracture of the hip. Multicentre, multisurgeon, parallel, two-arm, randomised controlled trial. Patients aged 60 years and older with a trochanteric hip fracture are potentially eligible. Participants will be randomly allocated on a 1:1 basis to either sliding hip screw or X-Bolt Dynamic Hip Plating System. Otherwise, all care will be in accordance with National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in EuroQol-5D health-related quality of life at 4 months postrandomisation. Secondary outcomes include mortality, residential status, revision surgery and radiographic measures. The treatment effect will be estimated using a two-sided t-test adjusted for age, gender and cognitive impairment based on an intention-to-treat analysis. National Research Ethics Committee approved this study on 5 February 2016 (16/WM/0001). The study is sponsored by the University of Oxford and funded through an investigator initiated grant by X-Bolt Orthopaedics. A manuscript for a high-impact peer-reviewed journal will be prepared, and the results will be disseminated to patients through local mechanisms at participating centres. ISRCTN92825709. © 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.

Long‐term safety and efficacy of tofogliflozin as add‐on to insulin in patients with type 2 diabetes: Results from a 52‐week, multicentre, randomized, double‐blind, open‐label extension, Phase 4 study in Japan (J‐STEP/INS)

PubMed Central

Tamura, Masahiro; Senda, Masayuki; Gunji, Ryoji; Kaku, Kohei

2018-01-01

Aims To evaluate the long‐term safety and efficacy of tofogliflozin as an add‐on treatment to insulin over 52 weeks. Materials and methods This 52‐week, multicentre, Phase 4 study consisted of a 16‐week, randomized, double‐blind, placebo‐controlled phase and a 36‐week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%‐10.5%) receiving insulin monotherapy (basal‐bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase‐4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the ‘tofo‐tofo group’ and patients who received placebo and tofogliflozin (36 weeks) were referred to as the ‘pla‐tofo group’. Results A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment‐emergent adverse event (AE) (42.9% in the tofo‐tofo group and 29.4% in the pla‐tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo‐tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla‐tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo‐tofo and pla‐tofo groups were 8.53% (−0.76% ± 0.077) and 8.40% (−0.73% ± 0.102); 68.84 kg (−1.52 kg ± 0.207) and 72.24 kg (−2.13 kg ± 0.313), respectively. Conclusions This study demonstrates the safety and efficacy of tofogliflozin as add‐on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management. PMID:29316236

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. Trial registration number NCT02483351; Pre-results. PMID:27927658

Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial.

PubMed

Vigod, Simone; Dennis, Cindy-Lee; Daskalakis, Zafiris; Murphy, Kellie; Ray, Joel; Oberlander, Tim; Somerton, Sarah; Hussain-Shamsy, Neesha; Blumberger, Daniel

2014-09-18

Women with depression in pregnancy are faced with difficult treatment decisions. Untreated, antenatal depression has serious negative implications for mothers and children. While antidepressant drug treatment is likely to improve depressive symptoms, it crosses the placenta and may pose risks to the unborn child. Transcranial direct current stimulation is a focal brain stimulation treatment that improves depressive symptoms within 3 weeks of treatment by inducing changes to brain areas involved in depression, without impacting any other brain areas, and without inducing changes to heart rate, blood pressure or core body temperature. The localized nature of transcranial direct current stimulation makes it an ideal therapeutic approach for treating depression during pregnancy, although it has never previously been evaluated in this population. We describe a pilot randomized controlled trial of transcranial direct current stimulation among women with depression in pregnancy to assess the feasibility of a larger, multicentre efficacy study. Women over 18 years of age and between 14 and 32 weeks gestation can be enrolled in the study provided they meet diagnostic criteria for a major depressive episode of at least moderate severity and have been offered but refused antidepressant medication. Participants are randomized to receive active transcranial direct current stimulation or a sham condition that is administered in 15 30-minute treatments over three weeks. Women sit upright during treatment and receive obstetrical monitoring prior to, during and after each treatment session. Depressive symptoms, treatment acceptability, and pregnancy outcomes are assessed at baseline (prior to randomization), at the end of each treatment week, every four weeks post-treatment until delivery, and at 4 and 12 weeks postpartum. Transcranial direct current stimulation is a novel therapeutic option for treating depression during pregnancy. This protocol allows for assessment of the feasibility of, acceptability of and adherence with a clinical trial protocol to administer this treatment to pregnant women with moderate to severe depression. Results from this pilot study will guide the development of a larger multicentre trial to definitively test the efficacy and safety of transcranial direct current stimulation for pregnant women with depression. Clinical Trials Gov NCT02116127.

High-intensity interval training versus moderate-intensity steady-state training in UK cardiac rehabilitation programmes (HIIT or MISS UK): study protocol for a multicentre randomised controlled trial and economic evaluation.

PubMed

McGregor, Gordon; Nichols, Simon; Hamborg, Thomas; Bryning, Lucy; Tudor-Edwards, Rhiannon; Markland, David; Mercer, Jenny; Birkett, Stefan; Ennis, Stuart; Powell, Richard; Begg, Brian; Haykowsky, Mark J; Banerjee, Prithwish; Ingle, Lee; Shave, Rob; Backx, Karianne

2016-11-16

Current international guidelines for cardiac rehabilitation (CR) advocate moderate-intensity exercise training (MISS, moderate-intensity steady state). This recommendation predates significant advances in medical therapy for coronary heart disease (CHD) and may not be the most appropriate strategy for the 'modern' patient with CHD. High-intensity interval training (HIIT) appears to be a safe and effective alternative, resulting in greater improvements in peak oxygen uptake (VO 2 peak ). To date, HIIT trials have predominantly been proof-of-concept studies in the laboratory setting and conducted outside the UK. The purpose of this multicentre randomised controlled trial is to compare the effects of HIIT and MISS training in patients with CHD attending UK CR programmes. This pragmatic study will randomly allocate 510 patients with CHD to 8 weeks of twice weekly HIIT or MISS training at 3 centres in the UK. HIIT will consist of 10 high-intensity (85-90% peak power output (PPO)) and 10 low-intensity (20-25% PPO) intervals, each lasting 1 min. MISS training will follow usual care recommendations, adhering to currently accepted UK guidelines (ie, >20 min continuous exercise at 40-70% heart rate reserve). Outcome measures will be assessed at baseline, 8 weeks and 12 months. The primary outcome for the trial will be change in VO 2 peak as determined by maximal cardiopulmonary exercise testing. Secondary measures will assess physiological, psychosocial and economic outcomes. The study protocol V.1.0, dated 1 February 2016, was approved by the NHS Health Research Authority, East Midlands-Leicester South Research Ethics Committee (16/EM/0079). Recruitment will start in August 2016 and will be completed in June 2018. Results will be published in peer-reviewed journals, presented at national and international scientific meetings and are expected to inform future national guidelines for exercise training in UK CR. NCT02784873; 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/.

High-intensity interval training versus moderate-intensity steady-state training in UK cardiac rehabilitation programmes (HIIT or MISS UK): study protocol for a multicentre randomised controlled trial and economic evaluation

PubMed Central

McGregor, Gordon; Nichols, Simon; Hamborg, Thomas; Bryning, Lucy; Tudor-Edwards, Rhiannon; Markland, David; Mercer, Jenny; Birkett, Stefan; Ennis, Stuart; Powell, Richard; Begg, Brian; Haykowsky, Mark J; Banerjee, Prithwish; Ingle, Lee; Shave, Rob; Backx, Karianne

2016-01-01

Introduction Current international guidelines for cardiac rehabilitation (CR) advocate moderate-intensity exercise training (MISS, moderate-intensity steady state). This recommendation predates significant advances in medical therapy for coronary heart disease (CHD) and may not be the most appropriate strategy for the ‘modern’ patient with CHD. High-intensity interval training (HIIT) appears to be a safe and effective alternative, resulting in greater improvements in peak oxygen uptake (VO2 peak). To date, HIIT trials have predominantly been proof-of-concept studies in the laboratory setting and conducted outside the UK. The purpose of this multicentre randomised controlled trial is to compare the effects of HIIT and MISS training in patients with CHD attending UK CR programmes. Methods and analysis This pragmatic study will randomly allocate 510 patients with CHD to 8 weeks of twice weekly HIIT or MISS training at 3 centres in the UK. HIIT will consist of 10 high-intensity (85–90% peak power output (PPO)) and 10 low-intensity (20–25% PPO) intervals, each lasting 1 min. MISS training will follow usual care recommendations, adhering to currently accepted UK guidelines (ie, >20 min continuous exercise at 40–70% heart rate reserve). Outcome measures will be assessed at baseline, 8 weeks and 12 months. The primary outcome for the trial will be change in VO2 peak as determined by maximal cardiopulmonary exercise testing. Secondary measures will assess physiological, psychosocial and economic outcomes. Ethics and dissemination The study protocol V.1.0, dated 1 February 2016, was approved by the NHS Health Research Authority, East Midlands—Leicester South Research Ethics Committee (16/EM/0079). Recruitment will start in August 2016 and will be completed in June 2018. Results will be published in peer-reviewed journals, presented at national and international scientific meetings and are expected to inform future national guidelines for exercise training in UK CR. Trial registration number NCT02784873; pre-results. PMID:27852718

Protocol for a feasibility trial for improving breast feeding initiation and continuation: assets-based infant feeding help before and after birth (ABA)

PubMed Central

Jolly, Kate; Ingram, Jenny; Clarke, Joanne; Johnson, Debbie; Trickey, Heather; Thomson, Gill; Dombrowski, Stephan U; Sitch, Alice; Dykes, Fiona; Feltham, Max G; Darwent, Kirsty; MacArthur, Christine; Roberts, Tracy

2018-01-01

Introduction Breast feeding improves the health of mothers and infants; the UK has low rates, with marked socioeconomic inequalities. While trials of peer support services have been effective in some settings, UK trials have not improved breast feeding rates. Qualitative research suggests that many women are alienated by the focus on breast feeding. We propose a change from breast feeding-focused interactions to respecting a woman’s feeding choices, inclusion of behaviour change theory and an increased intensity of contacts in the 2 weeks after birth when many women cease to breast feed. This will take place alongside an assets-based approach that focuses on the positive capability of individuals, their social networks and communities. We propose a feasibility study for a multicentre randomised controlled trial of the Assets feeding help Before and After birth (ABA) infant feeding service versus usual care. Methods and analysis A two-arm, non-blinded randomised feasibility study will be conducted in two UK localities. Women expecting their first baby will be eligible, regardless of feeding intention. The ABA infant feeding intervention will apply a proactive, assets-based, woman-centred, non-judgemental approach, delivered antenatally and postnatally tailored through face-to-face contacts, telephone and SMS texts. Outcomes will test the feasibility of delivering the intervention with recommended intensity and duration to disadvantaged women; acceptability to women, feeding helpers and professionals; and feasibility of a future randomised controlled trial (RCT), detailing recruitment rates, willingness to be randomised, follow-up rates at 3 days, 8 weeks and 6 months, and level of outcome completion. Outcomes of the proposed full trial will also be collected. Mixed methods will include qualitative interviews with women/partners, feeding helpers and health service staff; feeding helper logs; and review of audio-recorded helper–women interactions to assess intervention fidelity. Ethics and dissemination Study results will inform the design of a larger multicentre RCT. The National Research Ethics Service Committee approved the study protocol. Trial registration number ISRCTN14760978; Pre-results. PMID:29362263

Protocol for a feasibility trial for improving breast feeding initiation and continuation: assets-based infant feeding help before and after birth (ABA).

PubMed

Jolly, Kate; Ingram, Jenny; Clarke, Joanne; Johnson, Debbie; Trickey, Heather; Thomson, Gill; Dombrowski, Stephan U; Sitch, Alice; Dykes, Fiona; Feltham, Max G; Darwent, Kirsty; MacArthur, Christine; Roberts, Tracy; Hoddinott, Pat

2018-01-23

Breast feeding improves the health of mothers and infants; the UK has low rates, with marked socioeconomic inequalities. While trials of peer support services have been effective in some settings, UK trials have not improved breast feeding rates. Qualitative research suggests that many women are alienated by the focus on breast feeding. We propose a change from breast feeding-focused interactions to respecting a woman's feeding choices, inclusion of behaviour change theory and an increased intensity of contacts in the 2 weeks after birth when many women cease to breast feed. This will take place alongside an assets-based approach that focuses on the positive capability of individuals, their social networks and communities.We propose a feasibility study for a multicentre randomised controlled trial of the Assets feeding help Before and After birth (ABA) infant feeding service versus usual care. A two-arm, non-blinded randomised feasibility study will be conducted in two UK localities. Women expecting their first baby will be eligible, regardless of feeding intention. The ABA infant feeding intervention will apply a proactive, assets-based, woman-centred, non-judgemental approach, delivered antenatally and postnatally tailored through face-to-face contacts, telephone and SMS texts. Outcomes will test the feasibility of delivering the intervention with recommended intensity and duration to disadvantaged women; acceptability to women, feeding helpers and professionals; and feasibility of a future randomised controlled trial (RCT), detailing recruitment rates, willingness to be randomised, follow-up rates at 3 days, 8 weeks and 6 months, and level of outcome completion. Outcomes of the proposed full trial will also be collected. Mixed methods will include qualitative interviews with women/partners, feeding helpers and health service staff; feeding helper logs; and review of audio-recorded helper-women interactions to assess intervention fidelity. Study results will inform the design of a larger multicentre RCT. The National Research Ethics Service Committee approved the study protocol. ISRCTN14760978; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A multi-centre, parallel group superiority trial of silk therapeutic clothing compared to standard care for the management of eczema in children (CLOTHES Trial): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor F; Haines, Rachel H; Cowdell, Fiona; Sach, Tracey H; Dean, Taraneh; Pollock, Ian; Burrows, Nigel P; Buckley, Hannah; Batchelor, Jonathan; Williams, Hywel C; Lawton, Sandra; Brown, Sara J; Bradshaw, Lucy E; Ahmed, Amina; Montgomery, Alan A; Mitchell, Eleanor J; Thomas, Kim S

2015-09-02

Eczema is a chronic, itchy skin condition that can have a large impact on the quality of life of patients and their families. People with eczema are often keen to try out non-pharmacological therapies like silk therapeutic garments that could reduce itching or the damage caused by scratching. However, the effectiveness and cost-effectiveness of these garments in the management of eczema has yet to be proven. The CLOTHES Trial will test the hypothesis that 'silk therapeutic garments plus standard eczema care' is superior to 'standard care alone' for children with moderate to severe eczema. Parallel group, observer-blind, pragmatic, multi-centre randomised controlled trial of 6 months' duration. Three hundred children aged 1 to 15 years with moderate to severe eczema will be randomised (1:1) to receive silk therapeutic garments plus standard eczema care, or standard eczema care alone. Primary outcome is eczema severity, as assessed by trained and blinded investigators at 2, 4 and 6 months (using the Eczema Area and Severity Index (EASI)). Secondary outcomes include: patient-reported eczema symptoms (collected weekly for 6 months to capture long-term control); global assessment of severity; quality of life of the child, family and main carer; use of standard eczema treatments (emollients, corticosteroids applied topically, calcineurin inhibitors applied topically and wet wraps); frequency of infections; and cost-effectiveness. The acceptability and durability of the clothing will also be assessed, as will adherence to wearing the garments. A nested qualitative study will assess the views of a subset of children wearing the garments and their parents, and those of healthcare providers and commissioners. Randomisation uses a computer-generated sequence of permuted blocks of randomly varying size, stratified by recruiting hospital and child's age (< 2 years; 2 to 5 years; > 5 years), and concealed using a secure web-based system. The sequence of treatment allocations will remain concealed until randomisation and data collection are complete. Recruitment is taking place from November 2013 to May 2015, and the trial will be completed in 2016. Full details of results will be published in the National Institute for Health Research Journal series. Current Controlled Trials ISRCTN77261365 (registered 11 November 2013).

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.

Compliance with clothing regulations and traffic flow in the operating room: a multi-centre study of staff discipline during surgical procedures.

PubMed

Loison, G; Troughton, R; Raymond, F; Lepelletier, D; Lucet, J-C; Avril, C; Birgand, G

2017-07-01

This multi-centre study assessed operating room (OR) staff compliance with clothing regulations and traffic flow during surgical procedures. Of 1615 surgical attires audited, 56% respected the eight clothing measures. Lack of compliance was mainly due to inappropriate wearing of jewellery (26%) and head coverage (25%). In 212 procedures observed, a median of five people [interquartile range (IQR) 4-6] were present at the time of incision. The median frequency of entries to/exits from the OR was 10.6/h (IQR 6-29) (range 0-93). Reasons for entries to/exits from the OR were mainly to obtain materials required in the OR (N=364, 44.5%). ORs with low compliance with clothing regulations tended to have higher traffic flows, although the difference was not significant (P=0.12). Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

[Antimicrobial susceptibility testing of anaerobic bacteria].

PubMed

García-Sánchez, José E; García-Sánchez, Enrique; García-García, María Inmaculada

2014-02-01

The anaerobic bacteria resistance to antibiotics is increasing, and even has appeared against the most active of those, like metronidazol and carbapenems. This fact forces to make and periodical sensibility tests -at least in the most aggressive and virulent species, in cases that they are isolated from life locations and in the absence of therapeutic response- to check the local sensibility and to establish suitable empiric therapies, all based on multicentric studies carried out in order to this or well to check the activity of new antibiotics. For the laboratory routine, the easiest sensibility method is the E-test/MIC evaluator. Another alternative is microdilution, that's only normalized for Bacteroides. There are preliminary facts that allow the use of disc diffusion method in some species of Bacteroides and Clostridium. For the temporal and multicentric studies, the procedure is dilution in agar plate, the reference method. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region.

PubMed

Nazir, H F; Al Lawati, T; Beshlawi, I; AlSharidah, S; Elshinawy, M; Alkasim, F; Khanani, M F; Tarawa, A; Al Subhi, T; Alrawas, A; Al Riyami, W; Al Kindi, S; Al Saadi, K; Al-Lamki, S; Wali, Y

2016-05-01

The optimum mode of delivery in a known carrier of a haemophilia A is still an issue of debate. This study was conducted to report a multicentre experience in Gulf Cooperation Council (GCC) on the incidence of intracranial haemorrhage (ICH) in newborns with severe haemophilia A delivered by different modalities. We have conducted a retrospective/prospective multicentre cohort study including a total of seven hospitals distributed in four GCC countries between 1998 and Jan 2015. A total of 163 patient with severe haemophilia A (factor VIII <1%) were enrolled in this study, age ranged between 2 weeks to 18 years. Most of the patients were born by spontaneous vaginal delivery (SVD) (131, 80.4%), whereas 26 patients (16%) were born by CS and only six patients were born by instrumental delivery (3.7%), five of them by vacuum and one was delivered using forceps. Five out of 163 patients developed ICH during the first 2 weeks of life (3.1%). Two of them were born by SVD (2/131; 1.5%) and two were born by instrumental delivery (2/6; 33.3%). Only one patient among those who were born by caesarean section developed ICH (1/26; 3.8%). Assisted vaginal delivery was associated with a significant risk of ICH, in comparison to SVD and CS (P = 0.0093). Normal vaginal delivery is still considered a safe journey through the birth canal for haemophilic newborns particularly in this area of the world. Larger prospective studies might be needed to define an evidence-based optimal mode of delivery for the haemophilia carrier expecting an affected child. © 2015 John Wiley & Sons Ltd.

ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study.

PubMed

Donat, Ester; Ramos, Jose M; Sánchez-Valverde, Félix; Moreno, Ana; Martinez, Maria-Jose; Leis, Rosaura; Peña-Quintana, Luis; Castillejo, Gemma; Fernández, Sonia; Garcia, Zuriñe; Ortigosa, Luis; Balmaseda, Elena; Marugán, José-Manuel; Eizaguirre, Francisco-Javier; Lorenzo, Helena; Barrio, Josefa; Ribes-Koninckx, Carmen

2016-02-01

A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study.

PubMed

Mackenzie, Isla S; Ford, Ian; Walker, Andrew; Hawkey, Chris; Begg, Alan; Avery, Anthony; Taggar, Jaspal; Wei, Li; Struthers, Allan D; MacDonald, Thomas M

2016-09-08

Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups. 32017426, 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/

The foundation of NCVD PCI Registry: the Malaysia's first multi-centre interventional cardiology project.

PubMed

Liew, H B; Rosli, M A; Wan Azman, W A; Robaayah, Z; Sim, K H

2008-09-01

The National Cardiovascular Database for Percutaneous Coronary Intervention (NCVD PCI) Registry is the first multicentre interventional cardiology project, involving the main cardiac centres in the country. The ultimate goal of NCVD PCI is to provide a contemporary appraisal of PCI in Malaysia. This article introduces the foundation, the aims, methodology, database collection and preliminary results of the first six-month database.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PubMed

Pio-Abreu, Andrea; Drager, Luciano F

2018-06-16

Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

PubMed

Marchewka, Artur; Kherif, Ferath; Krueger, Gunnar; Grabowska, Anna; Frackowiak, Richard; Draganski, Bogdan

2014-05-01

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS. Copyright © 2013 Wiley Periodicals, Inc.

Design and rationale of the ATHENA study--A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial.

PubMed

Sommerer, Claudia; Suwelack, Barbara; Dragun, Duska; Schenker, Peter; Hauser, Ingeborg A; Nashan, Björn; Thaiss, Friedrich

2016-02-17

Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3-8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3-8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact. Clinicaltrials.gov: NCT01843348, date of registration--18 April 2013; EUDRACT number: 2011-005238-21, date of registration--20 March 2012.

Oxidative Stress Induced in Nurses by Exposure to Preparation and Handling of Antineoplastic Drugs in Mexican Hospitals: A Multicentric Study

PubMed Central

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; SanJuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses. PMID:24719678

Oxidative stress induced in nurses by exposure to preparation and handling of antineoplastic drugs in Mexican hospitals: a multicentric study.

PubMed

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; Sanjuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses.

Clinical experience with biphasic insulin aspart in people with type 2 diabetes: Results from the Libya cohort of the A1chieve study.

PubMed

Hajjaji, Issam M; Sherif, Ibrahim; Elazrag, Aisha; Jaber, Suhair; Chakkarwar, Praful N; Eltabal, Salem

2013-11-01

The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled in biphasic insulin aspart sub group from Libya. A total of 179 patients were enrolled in the biphasic insulin aspart subgroup. All the patients were prior insulin users. At baseline glycaemic control was poor (mean HbA1c: 9.3%). After 24 weeks of treatment there was an improvement in HbA1c (-0.9%). Hypoglycaemic events reduced from 7.2 events/patient-year to 3.7 events/patient-year in 24 weeks. SADRs did not occur in any of the study patients. Starting or switching to biphasic insulin aspart was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

The safe and responsible disposal of unused controlled drugs.

PubMed

Ahmed, Iftikhar; Majeed, Amer

There are well-defined legal requirements for the safe storage, handling and disposal of controlled drugs (CDs): The Misuse of Drugs Act 1971, and Safer Management of Controlled Drugs (Department of Health, 2007). Clinical staff involved in the prescription and administration of CDs to patients are responsible and accountable for the appropriate disposal of these drugs because of the risk of substance abuse. A review of current practice, as followed by staff involved in the use and disposal of CDs, has been evaluated in a multi-centre audit. This audit showed that a wide variation in attitude towards disposal of CDs exists among medical and non-medical staff, and that the sample hospitals are falling short of meeting proposed standards.

Cognitive Profile of Children and Adolescents with Anorexia Nervosa

PubMed Central

Kjaersdam Telléus, Gry; Jepsen, Jens Richardt; Bentz, Mette; Christiansen, Eva; Jensen, Signe O W; Fagerlund, Birgitte; Thomsen, Per Hove

2015-01-01

Objective Few studies of cognitive functioning in children and adolescents with anorexia nervosa (AN) have been conducted. The aim of this study was to examine the neurocognitive and intelligence profile of this clinical group. Method The study was a matched case–control (N = 188), multi-centre study including children and adolescents with AN (N = 94) and healthy control participants (N = 94). Results The results suggest that Full Scale Intelligence Quotient (Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III) in this patient group is close to the normal population mean of 100. Individuals with AN exhibited significantly worse performance in nonverbal intelligence functions (i.e. Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III, Perceptual Organization Index) and in verbal memory (Test of Memory and Learning—Second Edition, Memory for Stories) and motor speed (Cambridge Neuropsychological Test Automated Battery, Simple and Choice Reaction Time) compared with healthy control participants. No significant difference in set-shifting ability (Cambridge Neuropsychological Test Automated Battery, Intra-Extra Dimensional Set Shift and Trail Making Test B) was found. Conclusions Inefficiency in nonverbal intelligence functions and in specific cognitive functions was found in this study of children and adolescents with AN. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd. PMID:25504443

Cognitive profile of children and adolescents with anorexia nervosa.

PubMed

Kjaersdam Telléus, Gry; Jepsen, Jens Richardt; Bentz, Mette; Christiansen, Eva; Jensen, Signe O W; Fagerlund, Birgitte; Thomsen, Per Hove

2015-01-01

Few studies of cognitive functioning in children and adolescents with anorexia nervosa (AN) have been conducted. The aim of this study was to examine the neurocognitive and intelligence profile of this clinical group. The study was a matched case-control (N = 188), multi-centre study including children and adolescents with AN (N = 94) and healthy control participants (N = 94). The results suggest that Full Scale Intelligence Quotient (Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III) in this patient group is close to the normal population mean of 100. Individuals with AN exhibited significantly worse performance in nonverbal intelligence functions (i.e. Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III, Perceptual Organization Index) and in verbal memory (Test of Memory and Learning-Second Edition, Memory for Stories) and motor speed (Cambridge Neuropsychological Test Automated Battery, Simple and Choice Reaction Time) compared with healthy control participants. No significant difference in set-shifting ability (Cambridge Neuropsychological Test Automated Battery, Intra-Extra Dimensional Set Shift and Trail Making Test B) was found. Inefficiency in nonverbal intelligence functions and in specific cognitive functions was found in this study of children and adolescents with AN. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

Multicentre studies of insecticide-treated durable wall lining in Africa and South-East Asia: entomological efficacy and household acceptability during one year of field use

PubMed Central

2012-01-01

Background Indoor residual spraying (IRS) is a primary method of malaria vector control, but its potential impact is constrained by several inherent limitations: spraying must be repeated when insecticide residues decay, householders can tire of the annual imposition and campaign costs are recurrent. Durable lining (DL) can be considered an advanced form of long-lasting IRS where insecticide is gradually released from an aesthetically attractive wall lining material to provide vector control for several years. A multicentre trial was carried out in Equatorial Guinea, Ghana, Mali, South Africa and Vietnam to assess the feasibility, durability, bioefficacy and household acceptability of DL, compared to conventional IRS or insecticide-treated curtains (LLITCs), in a variety of operational settings. Methods This study was conducted in 220 households in traditional rural villages over 12-15 months. In all sites, rolls of DL were cut to fit house dimensions and fixed to interior wall surfaces (usually with nails and caps) by trained teams. Acceptability was assessed using a standardized questionnaire covering such topics as installation, exposure reactions, entomology, indoor environment, aesthetics and durability. Bioefficacy of interventions was evaluated using WHO cone bioassay tests at regular intervals throughout the year. Results The deltamethrin DL demonstrated little to no decline in bioefficacy over 12-15 months, supported by minimal loss of insecticide content. By contrast, IRS displayed a significant decrease in bioactivity by 6 months and full loss after 12 months. The majority of participants in DL households perceived reductions in mosquito density (93%) and biting (82%), but no changes in indoor temperature (83%). Among those households that wanted to retain the DL, 73% cited protective reasons, 20% expressed a desire to keep theirs for decoration and 7% valued both qualities equally. In Equatorial Guinea, when offered a choice of vector control product at the end of the trial (DL, IRS or LLITCs), DL consistently emerged as the most popular intervention regardless of the earlier household allocation. Conclusions Just as long-lasting insecticidal nets overcame several of the technical and logistical constraints associated with conventionally treated nets and then went to scale, this study demonstrates the potential of DL to sustain user compliance and overcome the operational challenges associated with IRS. PMID:23107112

Adjuvant chemotherapy for rectal cancer: Is it needed?

PubMed Central

Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

2015-01-01

Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

Design of the Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial.

PubMed

Bradford, Andrew; Lees, Kennedy

2000-01-01

The Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial is a multicentre,randomised, placebo-controlled trial of magnesium sulphate (MgSO4) funded by the UK Medical Research Council. When complete, it will be the largest single neuroprotective study undertaken to date. Conscious patients presenting within 12 h of acute stroke with limb weakness are eligible. The primary outcome measure is combined death and disability as measured using the Barthel Index at 90-day follow up. By randomizing 2700 patients, the study will have 84% power to detect a 5.5% absolute reduction in the primary end-point. By April 2000, 86 centres were participating, with representation in Canada, USA, Europe, South America, Singapore and Australia. So far, 1206 patients have been randomised, of whom 37% were treated within 6 h. Overall 3-month mortality was 20% and the primary outcome event rate was 43%. The study is ongoing and centres worldwide are encouraged to participate.

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany.

PubMed

Seufert, R; Sedlacek, L; Kahl, B; Hogardt, M; Hamprecht, A; Haase, G; Gunzer, F; Haas, A; Grauling-Halama, S; MacKenzie, C R; Essig, A; Stehling, F; Sutharsan, S; Dittmer, S; Killengray, D; Schmidt, D; Eskandarian, N; Steinmann, E; Buer, J; Hagen, F; Meis, J F; Rath, P-M; Steinmann, J

2018-04-19

Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Münster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

PubMed

Hoare, Brian; Ditchfield, Michael; Thorley, Megan; Wallen, Margaret; Bracken, Jenny; Harvey, Adrienne; Elliott, Catherine; Novak, Iona; Crichton, Ali

2018-05-08

Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.

PubMed

Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

2015-12-01

A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf(®) (Organogenesis, Inc., Canton, MA), EpiFix(®) (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P-values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. © 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome.

PubMed

Roquilly, Antoine; Lasocki, Sigismond; Moyer, Jean Denis; Huet, Olivier; Perrigault, Pierre François; Dahyot-Fizelier, Claire; Seguin, Philippe; Sharshar, Tarek; Geeraerts, Thomas; Remerand, Francis; Feuillet, Fanny; Asehnoune, Karim

2017-09-24

Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI. The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR. The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery. Trial registration number is NCT03143751. © 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.

Protocol of a multi-centre randomised controlled trial of a web-based information intervention with nurse-delivered telephone support for haematological cancer patients and their support persons.

PubMed

Bryant, Jamie; Sanson-Fisher, Rob; Stevenson, William; Smits, Rochelle; Henskens, Frans; Wei, Andrew; Tzelepis, Flora; D'Este, Catherine; Paul, Christine; Carey, Mariko

2015-04-17

High rates of anxiety, depression and unmet needs are evident amongst haematological cancer patients undergoing treatment and their Support Persons. Psychosocial distress may be minimised by ensuring that patients are sufficiently involved in decision making, provided with tailored information and adequate preparation for potentially threatening procedures. To date, there are no published studies evaluating interventions designed to reduce psychosocial distress and unmet needs specifically in patients with haematological cancers and their Support Persons. This study will examine whether access to a web-based information tool and nurse-delivered telephone support reduces depression, anxiety and unmet information needs for haematological cancer patients and their Support Persons. A non-blinded, parallel-group, multi-centre randomised controlled trial will be conducted to compare the effectiveness of a web-based information tool and nurse-delivered telephone support with usual care. Participants will be recruited from the haematology inpatient wards of five hospitals in New South Wales, Australia. Patients diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, Burkitt's lymphoma, Lymphoblastic lymphoma (B or T cell), or Diffuse Large B-Cell lymphoma and their Support Persons will be eligible to participate. Patients and their Support Persons will be randomised as dyads. Participants allocated to the intervention will receive access to a tailored web-based tool that provides accurate, up-to-date and personalised information about: cancer and its causes; treatment options including treatment procedures information; complementary and alternative medicine; and available support. Patients and Support Persons will complete self-report measures of anxiety, depression and unmet needs at 2, 4, 8 and 12 weeks post-recruitment. Patient and Support Person outcomes will be assessed independently. This study will assess whether providing information and support using web-based and telephone support address the major psychosocial challenges faced by haematological patients and their Support Persons. The approach, if found to be effective, has potential to improve psychosocial outcomes for haematological and other cancer patients, reduce the complexity and burden of meeting patients' psychosocial needs for health care providers with high potential for translation into clinical practice. ACTRN12612000720819.

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years.

PubMed

Kon, Elizaveta; Filardo, Giuseppe; Brittberg, Mats; Busacca, Maurizio; Condello, Vincenzo; Engebretsen, Lars; Marlovits, Stefan; Niemeyer, Philipp; Platzer, Patrik; Posthumus, Michael; Verdonk, Peter; Verdonk, Renè; Victor, Jan; van der Merwe, Willem; Widuchowski, Wojciech; Zorzi, Claudio; Marcacci, Maurilio

2017-09-14

The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions. I.

Effects of person-centred care on health outcomes-A randomized controlled trial in patients with acute coronary syndrome.

PubMed

Pirhonen, Laura; Olofsson, Elisabeth Hansson; Fors, Andreas; Ekman, Inger; Bolin, Kristian

2017-02-01

To study the effects of person-centred care provided to patients with acute coronary syndrome, using four different health-related outcome measures. Also, to examine the performance of these outcomes when measuring person-centred care. The data used in this study consists of primary data from a multicentre randomized parallel group, controlled intervention study for patients with acute coronary syndrome at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention and control group consisted of 94 and 105 patients, respectively. The effect of the intervention on health-related outcomes was estimated, controlling for socio-economic and disease-related variables. Patients in the intervention group reported significantly higher general self-efficacy than those in the control group six months after intervention start-up. Moreover, the intervention group returned to work in a greater extent than controls; their physical activity level had increased more and they had a higher EQ-5D score, meaning higher health-related quality of life. These latter effects are not significant but are all pointing towards the beneficial effects of person-centred care. All the effects were estimated while controlling for important socio-economic and disease-related variables. The effectiveness of person-centred care varies between different outcomes considered. A statistically significant beneficial effect was found for one of the four outcome measures (self-efficacy). The other measures all captured beneficial, but not significant, effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Individualised pelvic floor muscle training in women with pelvic organ prolapse (POPPY): a multicentre randomised controlled trial.

PubMed

Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; Dickson, Sylvia; Barry, Sarah; Elders, Andrew; Frawley, Helena; Galea, Mary P; Logan, Janet; McDonald, Alison; McPherson, Gladys; Moore, Kate H; Norrie, John; Walker, Andrew; Wilson, Don

2014-03-01

Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapse are often advised to do pelvic floor muscle exercises, but evidence supporting the benefits of such exercises is scarce. We aimed to establish the effectiveness of one-to-one individualised pelvic floor muscle training for reducing prolapse symptoms. We did a parallel-group, multicentre, randomised controlled trial at 23 centres in the UK, one in New Zealand, and one in Australia, between June 22, 2007, and April 9, 2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III prolapse were randomly assigned (1:1), by remote computer allocation with minimsation, to receive an individualised programme of pelvic floor muscle training or a prolapse lifestyle advice leaflet and no muscle training (control group). Outcome assessors, and investigators who were gynaecologists at trial sites, were masked to group allocation; the statistician was masked until after data analysis. Our primary endpoint was participants' self-report of prolapse symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is registered, number ISRCTN35911035. 447 eligible patients were randomised to the intervention group (n=225) or the control group (n=222). 377 (84%) participants completed follow-up for questionnaires at 6 months and 295 (66%) for questionnaires at 12 months. Women in the intervention group reported fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic organ prolapse symptom score [POP-SS]) at 12 months than those in the control group (mean reduction in POP-SS from baseline 3.77 [SD 5.62] vs 2.09 [5.39]; adjusted difference 1.52, 95% CI 0.46-2.59; p=0.0053). Findings were robust to missing data. Eight adverse events (six vaginal symptoms, one case of back pain, and one case of abdominal pain) and one unexpected serious adverse event, all in women from the intervention group, were regarded as unrelated to the intervention or to participation in the study. One-to-one pelvic floor muscle training for prolapse is effective for improvement of prolapse symptoms. Long-term benefits should be investigated, as should the effects in specific subgroups. Chief Scientist Office of the Scottish Government Health and Social Care Directorates, New Zealand Lottery Board, and National Health and Medical Research Council (Australia). Copyright © 2014 Elsevier Ltd. All rights reserved.

A Randomised Multi-centre Study to Compare the Long-term Performance of the Future Hip to 3 Other Implants in Primary Total Hip Replacement

ClinicalTrials.gov

2016-10-06

Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis; Perthes Disease

A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement

ClinicalTrials.gov

2017-06-27

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence.

PubMed

Müller, Ueli C; Asherson, Philip; Banaschewski, Tobias; Buitelaar, Jan K; Ebstein, Richard P; Eisenberg, Jaques; Gill, Michael; Manor, Iris; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Sonuga-Barke, Edmund Js; Thompson, Margaret; Faraone, Stephen V; Steinhausen, Hans-Christoph

2011-04-07

The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures. Conners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures. Besides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores. When ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment.

PubMed

Bytzer, Peter; Morocutti, Anna; Kennerly, Peter; Ravic, Miroslav; Miller, Neil

2006-10-01

Gastro-oesophageal reflux disease (GORD) symptoms have a significant impact on patients' well-being. Onset of symptom relief is therefore an important consideration in GORD treatment. The primary objective was to compare the efficacy of rabeprazole (20 mg) and omeprazole (20 mg) regarding onset of heartburn control during the first 7 days of treatment in patients with erosive oesophagitis. Secondary objectives included maintenance of sustained heartburn control, control of other GORD symptoms (e.g. acid regurgitation, epigastric pain, dysphagia), effect on quality of life, patient satisfaction with treatment, and adverse events. In this multicentre, randomized, parallel-group, double-blind, comparative study, performed in Europe and Iceland, patients with endoscopically confirmed erosive oesophagitis were randomized to receive once-daily treatment with rabeprazole 20 mg (n=358) or omeprazole 20 mg (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale) twice daily by the patients on their diary cards. Median time to reach heartburn control was 1.5 days for both the rabeprazole and omeprazole groups (p<0.43). The results were similar between treatments for other study parameters. Both treatments were well tolerated. Unlike previous studies, no significant differences were found between treatments with rabeprazole (20 mg) and omeprazole (20 mg) in this study. Further studies are needed to evaluate the potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole, with respect to onset of symptom control in erosive GORD.

A randomised trial of high and low pressure level settings on an adjustable ventriculoperitoneal shunt valve for idiopathic normal pressure hydrocephalus: results of the Dutch evaluation programme Strata shunt (DEPSS) trial.

PubMed

Delwel, Ernst J; de Jong, Dirk A; Dammers, Ruben; Kurt, Erkan; van den Brink, Wimar; Dirven, Clemens M F

2013-07-01

In treating idiopathic normal pressure hydrocephalus (INPH) with a shunt there is always a risk of underdrainage or overdrainage. The hypothesis is tested whether patients treated using an adjustable valve preset at the highest opening pressure leads to comparable good clinical results with less subdural effusions than in a control group with an opening pressure preset at a low pressure level. A multicentre prospective randomised trial was performed on a total of 58 patients suspected of INPH. Thirty patients were assigned to (control) group 1 and received a Strata shunt (Medtronic, Goleta, USA) with the valve preset at a performance level (PL) of 1.0, while 28 patients were assigned to group 2 and received a Strata shunt with the valve preset at PL 2.5. In this group the PL was allowed to be lowered until improvement or radiological signs of overdrainage were met. Significantly more subdural effusions were observed in the improved patients of group 1. There was no statistically significant difference in improvement between both groups overall. On the basis of this multicentre prospective randomised trial it is to be recommended to treat patients with INPH with a shunt with an adjustable valve, preset at the highest opening pressure and lowered until clinical improvement or radiological signs of overdrainage occur although slower improvement and more shunt adjustments might be the consequence.

Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease.

PubMed

Hussain, Shazia T; Paul, Matthias; Plein, Sven; McCann, Gerry P; Shah, Ajay M; Marber, Michael S; Chiribiri, Amedeo; Morton, Geraint; Redwood, Simon; MacCarthy, Philip; Schuster, Andreas; Ishida, Masaki; Westwood, Mark A; Perera, Divaka; Nagel, Eike

2012-09-19

In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation. The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807. MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

Fixation using alternative implants for the treatment of hip fractures (FAITH): design and rationale for a multi-centre randomized trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures.

PubMed

2014-06-26

Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813).

Accelerated Titration of Oxytocin in Nulliparous Women with Labour Dystocia: Results of the ACTION Pilot Randomized Controlled Trial.

PubMed

Dy, Jessica; Rainey, Jenna; Walker, Mark C; Fraser, William; Smith, Graeme N; White, Ruth Rennicks; Waddell, Patti; Janoudi, Ghayath; Corsi, Daniel J; Wei, Shu Qin

2018-06-01

The primary objective was to determine the feasibility of a large RCT assessing the effectiveness of an accelerated oxytocin titration (AOT) protocol compared with a standard gradual oxytocin titration (GOT) in reducing the risk of CS in nulliparous women diagnosed with dystocia in the first stage of labour. The secondary objective was to obtain preliminary data on the safety and efficacy of the foregoing AOT protocol. This was a multicentre, double-masked, parallel-group pilot RCT. This study was conducted in three Canadian birthing centres. A total of 79 term nulliparous women carrying a singleton pregnancy in spontaneous labour, with a diagnosis of labour dystocia, were randomized to receive either GOT (initial dose 2 mU/min with increments of 2 mU/min) or AOT (initial dose 4 mU/min with increments of 4 mU/min), in a 1:1 ratio. An intention-to-treat analysis was applied. A total of 252 women were screened and approached, 137 (54.4%) consented, and 79 (31.3%) were randomized. Overall protocol adherence was 76 of 79 (96.2%). Of the women randomized, 10 (25.6%) allocated to GOT had a CS compared with six (15.0%) allocated to AOT (Fisher exact test P = 0.27). This pilot study demonstrated that a large, multicentre RCT is not only feasible, but also necessary to assess the effectiveness and safety of an AOT protocol for labour augmentation with regard to CS rate and indicators of maternal and perinatal morbidities. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Associations between community-based physiotherapy for musculoskeletal injury and health related quality of life (EQ-5D): a multi-centre retrospective analysis.

PubMed

Caplan, Nick; Robson, H; Robson, A; Barry, G; Wilkes, G

2017-10-25

Community-based musculoskeletal physiotherapy is used to improve function and health related quality of life (HRQoL). The purpose of this retrospective, multi-centre observational study was to determine the association between community-based physiotherapy management for musculoskeletal disorders and changes in HRQoL. Four thousand one hundred twelve patients' data were included in the study. Patients were included if they received a single period of treatment for a musculoskeletal injury or disorder. Patients were only included if they were being treated for a single morbidity. Patients received standard physiotherapy appropriate to their specific disorder, which could include health education/advice, exercise therapy, manual therapy, taping, soft tissue techniques, electrotherapy and/or acupuncture. Health related quality of life was assessed using the EQ-5D index. EQ-5D improved by 0.203 across all patients (d = 1.10). When grouped by anatomical site of symptom, the largest increases in EQ-5D was in foot pain (0.233; d = 1.29) and lumbar pain (0.231; d = 1.13). Improvements in EQ-5D greater than the minimum clinically important difference (MCID) were seen in 68.4% of all patients. The highest proportion of patients with positive responses to treatment were in ankle pain (74.2%) and thoracic pain (73.4%). The hand (40.5%), elbow (34.7%), and hip (33.9%) showed the greatest proportion of patients that did not respond to treatment. Community-based musculoskeletal physiotherapy is associated with improved health related quality of life. A randomised controlled trial is needed to determine any causal relationship between community-based physiotherapy and health related quality of life improvements.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

PubMed

Domènech, Eugeni; Panés, Julián; Hinojosa, Joaquín; Annese, Vito; Magro, Fernando; Sturniolo, Giacomo Carlo; Bossa, Fabrizio; Fernández, Francisco; González-Conde, Benito; García-Sánchez, Valle; Dignass, Axel; Herrera, José Manuel; Cabriada, José Luis; Guardiola, Jordi; Vecchi, Maurizio; Portela, Francisco; Ginard, Daniel

2018-05-25

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

SABRE: a multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis.

PubMed

Everard, Mark L; Hind, Daniel; Ugonna, Kelechi; Freeman, Jennifer; Bradburn, Mike; Cooper, Cindy L; Cross, Elizabeth; Maguire, Chin; Cantrill, Hannah; Alexander, John; McNamara, Paul S

2014-12-01

Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as 'fit' for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0-95, 95% CI: 0.75-1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76-1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation. This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings. NCT01469845. 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.

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.

PubMed

Lewis, S C; Warlow, C P; Bodenham, A R; Colam, B; Rothwell, P M; Torgerson, D; Dellagrammaticas, D; Horrocks, M; Liapis, C; Banning, A P; Gough, M; Gough, M J

2008-12-20

The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. The Health Foundation (UK) and European Society of Vascular Surgery.

Multicentric primary extramammary Paget disease: a Toker cell disorder?

PubMed

Hashemi, Pantea; Kao, Grace F; Konia, Thomas; Kauffman, Lisa C; Tam, Christine C; Sina, Bahram

2014-07-01

Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

PubMed

Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

2013-01-01

Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

The challenges of implementing a multi-centre audit of end-of-life care in care homes.

PubMed

Levy, Jean; Kinley, Julie; Conway, Frances

2016-11-02

This article aims to share the experience of a hospice in facilitating a multi-centre audit of end-of-life care in care homes, particularly noting the challenges and enablers of carrying out the audit. The audit was a retrospective multi-centre survey of bereaved relatives/next of kin of residents who died in the care home, using an anonymous, validated questionnaire: the Family Perception of Care Scale. Questionnaires were sent 3-months after bereavement. Returned questionnaires were analysed using SPSS and Excel. The care homes were in areas encompassing outer and inner city populations. The team identified eight challenges to the audit process, in particular, embedding procedures within the care homes, non-responses and developing action plans for improvement. Overall, the audit provided an indication of where improvements could be made and where care was already excellent, built confidence and increased expertise in the care-home staff.

Protocol for a multicentred randomised controlled trial investigating the use of personalised golimumab dosing tailored to inflammatory load in ulcerative colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis) led by the INITIAtive group (NCT 0268772)

PubMed Central

Sheridan, Juliette; Coe, Carol Ann; Doran, Peter; Egan, Laurence; Cullen, Garret; Kevans, David; Leyden, Jan; Galligan, Marie; O’Toole, Aoibhlinn; McCarthy, Jane; Doherty, Glen

2018-01-01

Introduction Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC. The design of GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis aims to address the impact of dose escalation of GLM immediately following induction and during the subsequent maintenance phase in response to suboptimal DL or persisting inflammatory burden as represented by raised faecal calprotectin (FCP). Aim The primary aim of the study is to ascertain if monitoring of FCP and DL of GLM to guide dose optimisation (during maintenance) improves rates of patient continuous clinical response and reduces disease activity in UC. Methods and analysis A randomised, multicentred two-arm trial studying the effect of dose optimisation of GLM based on FCP and DL versus treatment as per SMPC. Eligible patients will be randomised in a 1:1 ratio to 1 of 2 treatment groups and shall be treated over a period of 46 weeks. Ethics and dissemination The study protocol was approved by the Research Ethics committee of St. Vincent’s University Hospital. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial registration numbers EudraCT number: 2015-004724-62; Clinicaltrials.gov Identifier: NCT0268772; Pre-results. PMID:29379609

HOspitals and patients WoRking in Unity (HOW R U?): protocol for a prospective feasibility study of telephone peer support to improve older patients' quality of life after emergency department discharge.

PubMed

Lowthian, Judy A; Lennox, Alyse; Curtis, Andrea; Dale, Jeremy; Browning, Colette; Smit, De Villiers; Wilson, Gillian; O'Brien, Debra; Rosewarne, Cate; Boyd, Lee; Garner, Cath; Cameron, Peter

2016-12-02

Older people presenting to an emergency department (ED) have a higher likelihood of social isolation, loneliness and depression; which are all associated with negative health outcomes and increased health service use, including higher rates of ED attendance. The HOW R U? study aims to ascertain the feasibility and acceptability of a postdischarge telephone support programme for older ED patients following discharge. The intervention, which aims to improve quality of life, will be delivered by hospital-based volunteers. A multicentre prospective uncontrolled feasibility study will enrol 50 community-dwelling patients aged ≥70 years with symptoms of loneliness or depression who are discharged home within 72 hours from the ED or acute medical ward. Participants will receive weekly supportive telephone calls over a 3-month period from a volunteer-peer. Feasibility will be assessed in terms of recruitment, acceptability of the intervention to participants and level of retention in the programme. Changes in level of loneliness (UCLA-3 item Loneliness Scale), mood (Geriatric Depression Scale-5 item) and health-related quality of life (EQ-5D-5L and EQ-VAS) will also be measured postintervention (3 months). Research ethics and governance committee approval has been granted for this study by each participating centre (reference: 432/15 and 12-09-11-15). Study findings will inform the design and conduct of a future multicentre randomised controlled trial of a postdischarge volunteer-peer telephone support programme to improve social isolation, loneliness or depressive symptoms in older patients. Results will be disseminated through peer-reviewed journal publication, and conference and seminar presentation. ACTRN12615000715572, 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/.

Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study

PubMed Central

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-01-01

Background This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. Study design In this Phase III, multicentre, open-label study, women (aged 18–35 years) were randomised to EE/DRSP in the following regimens: flexibleMIB (24–120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexibleMIB regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexibleMIB, conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. Conclusions EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives. PMID:22454004

Emergence agitation during recovery from intracranial surgery under general anaesthesia: a protocol and statistical analysis plan for a prospective multicentre cohort study.

PubMed

Yan, Li-Mei; Chen, Han; Yu, Rong-Guo; Wang, Zhu-Heng; Zhou, Guan-Hua; Wang, Yong-Jin; Zhang, Xia; Xu, Ming; Chen, Lu; Zhou, Jian-Xin

2015-04-21

Emergence agitation after intracranial surgery is an important clinical issue during anaesthesia recovery. The aim of this multicentre cohort study is to investigate the incidence of emergence agitation, identify the risk factors and determine clinical outcomes in adult patients after intracranial surgery under general anaesthesia. Additionally, we will deliberately clarify the relationship between postoperative pneumocephalus and agitation. The present study is a prospective multicentre cohort study. Five intensive care units (ICUs) in China will participate in the study. Consecutive adult patients admitted to the ICUs after intracranial surgery will be enrolled. Sedation-Agitation Scale (SAS) or Richmond Agitation-Sedation Scale (RASS) will be used to evaluate the patients 12 h after the enrolment. Agitation is defined as an SAS score of 5-7, or an RASS score of +2 to +4. According to the maximal SAS and RASS score, patients will be divided into two cohorts: the agitation group and the non-agitation group. Factors potentially related to emergence agitation will be collected at study entry, during anaesthesia and operation, during postoperative care. Univariate analyses between the agitation and the non-agitation groups will be performed. The stepwise backward logistic regression will be carried out to identify the independent predictors of agitation. Patients will be followed up for 72 h after the operation. Accidental self-extubation of the endotracheal tube and removal of other catheters will be documented. The use of sedatives and analgesics will be collected. Ethics approval has been obtained from each of five participating hospitals. Study findings will be disseminated through peer-reviewed publications and conference presentations. NCT02318199. 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.

Effects of combined exercise training and electromyostimulation treatments in chronic heart failure: A prospective multicentre study.

PubMed

Iliou, Marie C; Vergès-Patois, Bénédicte; Pavy, Bruno; Charles-Nelson, Anais; Monpère, Catherine; Richard, Rudy; Verdier, Jean C

2017-08-01

Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure. It is a valuable method for the improvement of exercise tolerance. Some studies reported a similar improvement with quadricipital electrical myostimulation, but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospective multicentre study. Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and/or muscular strength in cardiac heart failure patients. Methods Ninety-one patients were included (mean age: 58 ± 9 years; New York Heart Association II/III: 52/48%, left ventricular ejection fraction: 30 ± 7%) in a prospective French study. The patients were randomised into two groups: 41 patients in exercise training and 50 in exercise training + electrical myostimulation. All patients underwent 20 exercise training sessions. In addition, in the exercise training + electrical myostimulation group, patients underwent 20 low frequency (10 Hz) quadricipital electrical myostimulation sessions. Each patient underwent a cardiopulmonary exercise test, a six-minute walk test, a muscular function evaluation and a quality of life questionnaire, before and at the end of the study. Results A significant improvement of exercise capacity (Δ peak oxygen uptake+15% in exercise training group and +14% in exercise training + electrical myostimulation group) and of quality of life was observed in both groups without statistically significant differences between the two groups. Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group. Conclusions This prospective multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients.

Influence of quality of care and individual patient characteristics on quality of life and return to work in survivors of the acute respiratory distress syndrome: protocol for a prospective, observational, multi-centre patient cohort study (DACAPO).

PubMed

Brandstetter, Susanne; Dodoo-Schittko, Frank; Blecha, Sebastian; Sebök, Philipp; Thomann-Hackner, Kathrin; Quintel, Michael; Weber-Carstens, Steffen; Bein, Thomas; Apfelbacher, Christian

2015-12-17

Health-related quality of life (HRQoL) and return to work are important outcomes in critical care medicine, reaching beyond mortality. Little is known on factors predictive of HRQoL and return to work in critical illness, including the acute respiratory distress syndrome (ARDS), and no evidence exists on the role of quality of care (QoC) for outcomes in survivors of ARDS. It is the aim of the DACAPO study ("Surviving ARDS: the influence of QoC and individual patient characteristics on quality of life") to investigate the role of QoC and individual patient characteristics on quality of life and return to work. A prospective, observational, multi-centre patient cohort study will be performed in Germany, using hospitals from the "ARDS Network Germany" as the main recruiting centres. It is envisaged to recruit 2400 patients into the DACAPO study and to analyse a study population of 1500 survivors. They will be followed up until 12 months after discharge from hospital. QoC will be assessed as process quality, structural quality and volume at the institutional level. The main outcomes (HRQoL and return to work) will be assessed by self-report questionnaires. Further data collection includes general medical and ARDS-related characteristics of patients as well as sociodemographic and psycho-social parameters. Multilevel hierarchical modelling will be performed to analyse the effects of QoC and individual patient characteristics on outcomes, taking the cluster structure of the data into account. By obtaining comprehensive data at patient and hospital level using a prospective multi-centre design, the DACAPO-study is the first study investigating the influence of QoC on individual outcomes of ARDS survivors.

Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link?

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-07-01

Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P < 0.01), compared with vincristine (n = 9) or doxorubicin (n = 5). Therefore, the therapeutic outcome of traditional CHOP-based chemotherapy might be improved by replacing cyclophosphamide with other cytotoxic drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive Modifiability of Children with Developmental Disabilities: A Multicentre Study Using Feuerstein's Instrumental Enrichment-Basic Program

ERIC Educational Resources Information Center

Kozulin, A.; Lebeer, J.; Madella-Noja, A.; Gonzalez, F.; Jeffrey, I.; Rosenthal, N.; Koslowsky, M.

2010-01-01

The study aimed at exploring the effectiveness of cognitive intervention with the new "Instrumental Enrichment Basic" program (IE-basic), based on Feuerstein's theory of structural cognitive modifiability that contends that a child's cognitive functioning can be significantly modified through mediated learning intervention. The IE-basic…

Development and validation of a paediatric long-bone fracture classification. A prospective multicentre study in 13 European paediatric trauma centres

PubMed Central

2011-01-01

Background The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Methods Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. Results The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of κ = 0.71 with no significant difference between experienced and less experienced raters. Conclusions In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future. PMID:21548939

Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system.

PubMed

Curvers, W L; Singh, R; Song, L-M Wong-Kee; Wolfsen, H C; Ragunath, K; Wang, K; Wallace, M B; Fockens, P; Bergman, J J G H M

2008-02-01

To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett's oesophagus. Prospective multi-centre study. Tertiary referral centres. 84 Patients with Barrett's oesophagus. The Barrett's oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett's oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.

One-year multicentre outcomes of transapical aortic valve implantation using the SAPIEN XT™ valve: the PREVAIL transapical study.

PubMed

Walther, Thomas; Thielmann, Matthias; Kempfert, Joerg; Schroefel, Holger; Wimmer-Greinecker, Gerhard; Treede, Hendrik; Wahlers, Thorsten; Wendler, Olaf

2013-05-01

The study aimed to evaluate 1-year outcomes of the multicentre PREVAIL transapical (TA) study of TA-aortic valve implantation (AVI) in high-risk patients. From September 2009 to August 2010, a total of 150 patients, aged 81.6 ± 5.8 years, 40.7% female, were included at 12 European TA-AVI experienced sites. Patients received 23 (n = 36), 26 (n = 57) and 29 mm (n = 57) second-generation SAPIEN XT™ (Edwards Lifesciences, Irvine, CA, USA) valves. The mean logistic EuroSCORE was 24.3 ± 7.0, and mean Society Thoracic Surgeons score was 7.5 ± 4.4%. Survival was 91.3% at 30 days and 77.9% at 1 year. Subgroup analysis revealed survivals of 91.7/88.9, 86.0/70.2, 96.55/91.2% for patients receiving 23-, 26- and 29-mm valves at 30 days and at 1 year, respectively. Transthoracic echocardiography revealed preserved left ventricular ejection fraction and low gradients. Aortic incompetence was none in 41/48, trace 30/36, mild 22/12 and moderate in 7/4% at discharge and 1 year. Walking distance increased from 221 (postimplant) to 284 m (at 1 year, P = 0.0004). Three patients required reoperation due to increasing aortic incompetence during follow-up. Causes of mortality at 1 year were cardiac (n = 7), stroke (n = 1) and others (n = 5). The European PREVAIL multicentre trial demonstrates good functionality and good outcomes for TA-AVI using the second-generation SAPIEN XT prosthesis and the ASCENDRA-II delivery system. The 29-mm SAPIEN XT valve was successfully introduced and showed excellent results.

Dose escalation study to evaluate safety, tolerability and efficacy of intravenous etoposide phosphate administration in 27 dogs with multicentric lymphoma

PubMed Central

Hordeaux, Juliette; Bouchaert, Emmanuel; Gomes, Bruno

2017-01-01

Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies. This work was part of a comparative oncology project assessing a new, clinical-stage topoisomerase II inhibitor and comparing it with etoposide in dogs with spontaneous lymphoma with the objective to translate findings from dogs to humans. Etoposide is a topoisomerase II inhibitor widely used in various humans’ solid and hematopoietic cancer, but little data is available concerning its potential antitumor efficacy in dogs. Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous etoposide phosphate in dogs with multicentric lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric lymphoma were enrolled and treated with three cycles of etoposide phosphate IV injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no hypersensitivity reaction were reported at this dose level. Beyond the characterization of etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human lymphomas. PMID:28505195

Keeping children safe at home: protocol for three matched case–control studies of modifiable risk factors for falls

PubMed Central

Kendrick, Denise; Stewart, Jane; Clacy, Rose; Coffey, Frank; Cooper, Nicola; Coupland, Carol; Hayes, Mike; McColl, Elaine; Reading, Richard; Sutton, Alex; M L Towner, Elizabeth; Craig Watson, Michael

2012-01-01

Background Childhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children. Objectives To estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity. Design Three multicentre case–control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0–4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences. Main outcome measures Falls on stairs, on one level and from furniture. Discussion As the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children. PMID:22628151

Multicenter external validation of two malignancy risk prediction models in patients undergoing 18F-FDG-PET for solitary pulmonary nodule evaluation.

PubMed

Perandini, Simone; Soardi, G A; Larici, A R; Del Ciello, A; Rizzardi, G; Solazzo, A; Mancino, L; Zeraj, F; Bernhart, M; Signorini, M; Motton, M; Montemezzi, S

2017-05-01

To achieve multicentre external validation of the Herder and Bayesian Inference Malignancy Calculator (BIMC) models. Two hundred and fifty-nine solitary pulmonary nodules (SPNs) collected from four major hospitals which underwent 18-FDG-PET characterization were included in this multicentre retrospective study. The Herder model was tested on all available lesions (group A). A subgroup of 180 SPNs (group B) was used to provide unbiased comparison between the Herder and BIMC models. Receiver operating characteristic (ROC) area under the curve (AUC) analysis was performed to assess diagnostic accuracy. Decision analysis was performed by adopting the risk threshold stated in British Thoracic Society (BTS) guidelines. Unbiased comparison performed In Group B showed a ROC AUC for the Herder model of 0.807 (95 % CI 0.742-0.862) and for the BIMC model of 0.822 (95 % CI 0.758-0.875). Both the Herder and the BIMC models were proven to accurately predict the risk of malignancy when tested on a large multicentre external case series. The BIMC model seems advantageous on the basis of a more favourable decision analysis. • The Herder model showed a ROC AUC of 0.807 on 180 SPNs. • The BIMC model showed a ROC AUC of 0.822 on 180 SPNs. • Decision analysis is more favourable to the BIMC model.

Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy

PubMed Central

Lähteenmäki, Pekka; Haukkamaa, Maija; Puolakka, Jukka; Riikonen, Ulla; Sainio, Susanna; Suvisaari, Janne; Nilsson, Carl Gustaf

1998-01-01

Objectives: To assess whether the levonorgestrel intrauterine system could provide a conservative alternative to hysterectomy in the treatment of excessive uterine bleeding. Design: Open randomised multicentre study with two parallel groups: a levonorgestrel intrauterine system group and a control group. Setting: Gynaecology departments of three hospitals in Finland. Subjects: Fifty six women aged 33-49 years scheduled to undergo hysterectomy for treatment of excessive uterine bleeding. Interventions: Women were randomised either to continue with their current medical treatment or to have a levonorgestrel intrauterine system inserted. Main outcome measure: Proportion of women cancelling their decision to undergo hysterectomy. Results: At 6 months, 64.3% (95% confidence interval 44.1 to 81.4%) of the women in the levonorgestrel intrauterine system group and 14.3% (4.0 to 32.7%) in the control group had cancelled their decision to undergo hysterectomy (P<0.001). Conclusions: The use of the levonorgestrel intrauterine system is a good conservative alternative to hysterectomy in the treatment of menorrhagia and should be considered before hysterectomy or other invasive treatments. PMID:9552948

Pregnancy outcomes after maternal varenicline use; analysis of surveillance data collected by the European Network of Teratology Information Services.

PubMed

Richardson, J L; Stephens, S; Yates, L M; Diav-Citrin, O; Arnon, J; Beghin, D; Kayser, A; Kennedy, D; Cupitt, D; Te Winkel, B; Peltonen, M; Kaplan, Y C; Thomas, S H L

2017-01-01

Varenicline is a smoking cessation aid for which limited data exist concerning safety during human pregnancy. This multicentre prospective observational comparative cohort study was undertaken using surveillance data collected by the European Network of Teratology Information Services. The study sample consisted of 89 varenicline exposed pregnancies and two matched comparator groups; 267 non-teratogen exposed (NTE) controls and 78 exposed to nicotine replacement therapy or bupropion (NRT/B) for smoking cessation. For all exposed pregnancies, varenicline use only occurred in the first trimester, with a considerable proportion discontinuing use in the very early stages of pregnancy. The major congenital malformation rate (n=2/89, 2.25%) was in keeping with the expected background rate (2-4%), and was not significantly increased for first trimester varenicline-exposed infants in comparison with non-exposed controls (vs. NTE: OR 2.02, 95%CI 0.166 to 17.9, vs. OR 0.874, 95%CI 0.0620 to 12.3). However, the small sample size produced very imprecise risk estimates. Copyright © 2016 Elsevier Inc. All rights reserved.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

PubMed

Gelardi, M; De Luca, C; Taliente, S; Fiorella, M L; Quaranta, N; Russo, C; Ciofalo, A; Macchi, A; Mancini, M; Rosso, P; Seccia, V; Guagnini, F; Ciprandi, G

2017-01-01

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD).

PubMed

Czigany, Zoltan; Schöning, Wenzel; Ulmer, Tom Florian; Bednarsch, Jan; Amygdalos, Iakovos; Cramer, Thorsten; Rogiers, Xavier; Popescu, Irinel; Botea, Florin; Froněk, Jiří; Kroy, Daniela; Koch, Alexander; Tacke, Frank; Trautwein, Christian; Tolba, Rene H; Hein, Marc; Koek, Ger H; Dejong, Cornelis H C; Neumann, Ulf Peter; Lurje, Georg

2017-10-10

Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT. HOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia-reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT. The study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018. NCT03124641. © 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.

Securing All intraVenous devices Effectively in hospitalised patients--the SAVE trial: study protocol for a multicentre randomised controlled trial.

PubMed

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-09-23

Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. 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.

Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial

PubMed Central

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-01-01

Introduction Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. Methods and analysis A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethics and dissemination Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. PMID:26399574

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

PubMed

Harji, Deena; Marshall, Helen; Gordon, Katie; Crow, Hannah; Hiley, Victoria; Burke, Dermot; Griffiths, Ben; Moriarty, Catherine; Twiddy, Maureen; O'Dwyer, John L; Verjee, Azmina; Brown, Julia; Sagar, Peter

2018-02-22

Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The results from the trial will be presented at national and international colorectal conferences and will be submitted for publication to peer-reviewed journals. ISRCTN15681041; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Telemonitoring based service redesign for the management of uncontrolled hypertension: multicentre randomised controlled trial

PubMed Central

Hanley, Janet; Wild, Sarah; Pagliari, Claudia; Paterson, Mary; Lewis, Steff; Sheikh, Aziz; Krishan, Ashma; Stoddart, Andrew; Padfield, Paul

2013-01-01

Objective To determine if an intervention consisting of telemonitoring and supervision by usual primary care clinicians of home self measured blood pressure and optional patient decision support leads to clinically important reductions in daytime systolic and diastolic ambulatory blood pressure in patients with uncontrolled blood pressure. Design Multicentre randomised controlled trial. Setting 20 primary care practices in south east Scotland. Participants 401 people aged 29-95 years with uncontrolled blood pressure (mean daytime ambulatory measurement ≥135/85 mm Hg but ≤210/135 mm Hg). Intervention Self measurement and transmission of blood pressure readings to a secure website for review by the attending nurse or doctor and participant, with optional automated patient decision support by text or email for six months. Main outcome measures Blinded assessment of mean daytime systolic ambulatory blood pressure six months after randomisation. Results 200 participants were randomised to the intervention and 201 to usual care; primary outcome data were available for 90% of participants (182 and 177, respectively). The mean difference in daytime systolic ambulatory blood pressure adjusted for baseline and minimisation factors between intervention and usual care was 4.3 mm Hg (95% confidence interval 2.0 to 6.5; P=0.0002) and for daytime diastolic ambulatory blood pressure was 2.3 mm Hg (0.9 to 3.6; P=0.001), with higher values in the usual care group. The intervention was associated with a mean increase of one general practitioner (95% confidence interval 0.5 to 1.6; P=0.0002) and 0.6 (0.1 to 1.0; P=0.01) practice nurse consultations during the course of the study. Conclusions Supported self monitoring by telemonitoring is an effective method for achieving clinically important reductions in blood pressure in patients with uncontrolled hypertension in primary care settings. However, it was associated with increase in use of National Health Service resources. Further research is required to determine if the reduction in blood pressure is maintained in the longer term and if the intervention is cost effective. Trial registration Current Controlled Trials ISRCTN72614272. PMID:23709583

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

PubMed

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, 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/.

Traumeel vs. diclofenac for reducing pain and improving ankle mobility after acute ankle sprain: a multicentre, randomised, blinded, controlled and non-inferiority trial.

PubMed

González de Vega, C; Speed, C; Wolfarth, B; González, J

2013-10-01

Acute ankle sprains are common and activity limiting injuries, and topical diclofenac gel has proven efficacy in alleviating pain and restoring function. This trial aimed to compare a topical natural agent, Traumeel with topical diclofenac gel (1%) in the management of acute ankle sprain. This prospective, multicentre, randomised, blinded, active-control and non-inferiority study involved 449 physically active adults sustaining unilateral grade 1 or 2 ankle sprain within the past 24 h. Participants were randomised to receive 2 g of Traumeel ointment (T-O) (n = 152) or Traumeel gel (T-G) (n = 150) or diclofenac gel (D-G) (n = 147), administered topically to the ankle three times a day for 14 days, with 6-weeks follow up. Day 7 median percentage reductions in Visual Analogue Scale pain score were 60.6%, 71.1% and 68.9% for the T-O, T-G and D-G groups, respectively. Total pain relief was reported by 12 (8.5%), 7 (5.0%) and 8 (5.9%) participants in each group, respectively. Median improvements in Foot and Ankle Ability Measure Activities of Daily Living subscale score were 26.2, 26.2 and 25.0 points for T-O, T-G and D-G groups, respectively. Mann-Whitney effect sizes and lower bound confidence intervals demonstrated non-inferiority of Traumeel vs. diclofenac for reducing pain and functional improvement. At 6 weeks, participants reported total pain relief and normal functioning. Adverse events (n = 43) were reported by 31/447 participants (6.9%). Treatments were equally well tolerated. T-O and T-G decreased pain and improved joint function to the same extent as D-G in acute ankle sprain, and were well tolerated. © 2013 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

PubMed Central

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-01-01

Introduction Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. Trial registration number ACTRN12614000418673, Pre-results. PMID:27932335

The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre randomised controlled trial: baseline patient characteristics.

PubMed

Konstantakopoulou, Evgenia; Gazzard, Gus; Vickerstaff, Victoria; Jiang, Yuzhen; Nathwani, Neil; Hunter, Rachael; Ambler, Gareth; Bunce, Catey

2018-05-01

The laser in glaucoma and ocular hypertension (LiGHT) trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open angle glaucoma (POAG) or ocular hypertension (OHT). LiGHT is a prospective unmasked, multicentre, pragmatic, randomised controlled trial (RCT). 718 previously untreated patients with POAG or OHT were recruited at 6 UK centres between 2012 and 2014. Patients were randomised to initial SLT followed by medical therapy or medical therapy without laser. Participants will be monitored for 3 years, according to routine clinical practice. The primary outcome is EQ-5D-5L. Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index (GUI), Glaucoma Symptom Scale, Glaucoma Quality of Life (GQL), pathway effectiveness, visual function, safety and concordance. A total of 555 patients had POAG and 163 OHT; 518 patients had both eyes eligible. The mean age for patients with POAG was 64 years and for OHT 58 years. 70% of all participants were white. Median IOP for OHT eyes was 26 mm Hg and 23 mm Hg for POAG eyes. Median baseline visual field mean deviation was -0.81 dB for OHT eyes and -2.82 dB for POAG eyes. There was no difference between patients with POAG and patients with OHT on the EQ-5D-5DL; the difference between OHT and POAG on the GUI was -0.02 and 1.23 on the GQL. The LiGHT trial is the first RCT to compare the two treatment options in a real-world setting. The baseline characteristics of the LiGHT cohort compare well with other landmark glaucoma studies. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Influence of de qi on the immediate analgesic effect of SP6 acupuncture in patients with primary dysmenorrhoea and cold and dampness stagnation: a multicentre randomised controlled trial.

PubMed

Zhao, Min-Yi; Zhang, Peng; Li, Jing; Wang, Lin-Peng; Zhou, Wei; Wang, Yan-Xia; She, Yan-Fen; Ma, Liang-Xiao; Wang, Pei; Hu, Ni-Juan; Lin, Chi; Hu, Shang-Qin; Wu, Gui-Wen; Wang, Ya-Feng; Sun, Jun-Jun; Jiang, Si-Zhu; Zhu, Jiang

2017-10-01

The aim of this multicentre randomised controlled trial was to investigate the contribution of de qi to the immediate analgesic effect of acupuncture in patients with primary dysmenorrhoea and the specific traditional Chinese medicine diagnosis cold and dampness stagnation . Eighty-eight patients with primary dysmenorrhoea and cold and dampness stagnation were randomly assigned to de qi (n=43) or no de qi (n=45) groups and underwent 30 min of SP6 acupuncture. The de qi group received deep needling at SP6 with manipulation using thick needles; the no de qi group received shallow needling with no manipulation using thin needles. In both groups the pain scores and actual de qi sensation were evaluated using a visual analogue scale for pain (VAS-P) and the acupuncture de qi clinical assessment scale (ADCAS), respectively. Both groups showed reductions in VAS-P, with no signficant differences between groups. ADCAS scores showed 43/43 and 25/45 patients in de qi and no de qi groups, respectively, actually experienced de qi sensation. Independent of original group allocation, VAS-P reductions associated with actual de qi (n=68) were greater than those without (28.4±18.19 mm vs 14.6±12.28 mm, p=0.008). This study showed no significant difference in VAS-P scores in patients with primary dysmenorrhoea and cold and dampness stagnation immediately after SP6 acupuncture designed to induce or avoid de qi sensation. Both treatments significantly reduced VAS-P relative to baseline. Irrespective of group allocation, patients experiencing actual de qi sensation demonstrated larger reductions in pain score relative to those without, suggesting greater analgesic effects. Chinese Clinical Trial Registry (ChiCTR-TRC-13003086); 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.

A 6-month randomized controlled trial to test the efficacy of a lifestyle intervention for weight gain management in schizophrenia

PubMed Central

2013-01-01

Background Patients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease, lifestyle and the use of medications, which are related to weight gain. Methods A multicentric, randomized, controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program (LWP). The program consists of a one-hour weekly session to discuss topics like dietary choices, lifestyle, physical activity and self-esteem with patients and their relatives. Patients were randomized into two groups: standard care (SC) and standard care plus intervention (LWP). Primary outcome was defined as the weight and body mass index (BMI). Results 160 patients participated in the study (81 in the intervention group and 79 in the SC group). On an intent to treat analysis, after three months the patients in the intervention group presented a decrease of 0.48 kg (CI 95% -0.65 to 1.13) while the standard care group showed an increase of 0.48 kg (CI 95% 0.13 to 0.83; p=0.055). At six-month follow-up, there was a significant weight decrease of −1.15 kg, (CI 95% -2.11 to 0.19) in the intervention group compared to a weight increase in the standard care group (+0.5 kg, CI 95% -0.42–1.42, p=0.017). Conclusion In conclusion, this was a multicentric randomized clinical trial with a lifestyle intervention for individuals with schizophrenia, where the intervention group maintained weight and presented a tendency to decrease weight after 6 months. It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight. Clinicaltrials.gov identifier NCT01368406 PMID:23418863

Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA‐033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial

PubMed Central

Rother, Matthias; Lavins, Bernard J; Kneer, Werner; Lehnhardt, Klaus; Seidel, Egbert J; Mazgareanu, Stefan

2007-01-01

Objective To compare epicutaneous ketoprofen in Transfersome (ultra‐deformable vesicles, IDEA‐033) versus oral celecoxib and placebo for relief of signs and symptoms in knee osteoarthritis. Methods This was a multicentre, randomised, double‐blind, controlled trial; 397 patients with knee osteoarthritis participated and 324 completed the trial. They were randomly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (n = 138), 100 mg oral celecoxib plus placebo gel (n = 132), or both placebo formulations (n = 127) twice daily for 6 weeks. Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale, physical function subscale and patient global assessment (PGA) of response. Results The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 (95% confidence interval −22.1 to −14.3), 20.3 (−24.3 to −16.2) and 9.9 (−13.9 to −5.8) in the IDEA‐033, celecoxib and placebo groups, respectively, and the physical function subscale score by 14.6 (−18.1 to −11.0), 16.6 (−20.2 to −13.0) and 10.2 (−13.8 to −6.6), respectively. The mean PGA of response scores were 1.8 (1.6 to 2.1), 1.7 (1.5 to 1.9) and 1.3 (1.1 to 1.5), respectively. The differences in change between IDEA‐033 and placebo were statistically significant for pain subscale (p<0.01) and PGA of response (p<0.01). Gastrointestinal adverse events for IDEA‐033 were similar to placebo. Conclusion IDEA‐033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. PMID:17363401

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH).

PubMed

Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc

2018-06-22

Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

PubMed

Palacio, M; Cobo, T; Antolín, E; Ramirez, M; Cabrera, F; Mozo de Rosales, F; Bartha, J L; Juan, M; Martí, A; Oros, D; Rodríguez, À; Scazzocchio, E; Olivares, J M; Varea, S; Ríos, J; Gratacós, E

2016-11-01

To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. Multicentre, randomised, double-blind, placebo-controlled trial. Twelve tertiary care centres in Spain. A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. Maintenance progesterone in 258 women after arrested PTL showed no benefit. © 2016 Royal College of Obstetricians and Gynaecologists.

Effects of remote monitoring on clinical outcomes and use of healthcare resources in heart failure patients with biventricular defibrillators: results of the MORE-CARE multicentre randomized controlled trial.

PubMed

Boriani, Giuseppe; Da Costa, Antoine; Quesada, Aurelio; Ricci, Renato Pietro; Favale, Stefano; Boscolo, Gabriele; Clementy, Nicolas; Amori, Valentina; Mangoni di S Stefano, Lorenza; Burri, Haran

2017-03-01

The aim of this study was to evaluate the clinical efficacy and safety of remote monitoring in patients with heart failure implanted with a biventricular defibrillator (CRT-D) with advanced diagnostics. The MORE-CARE trial is an international, prospective, multicentre, randomized controlled trial. Within 8 weeks of de novo implant of a CRT-D, patients were randomized to undergo remote checks alternating with in-office follow-ups (Remote arm) or in-office follow-ups alone (Standard arm). The primary endpoint was a composite of death and cardiovascular (CV) and device-related hospitalization. Use of healthcare resources was also evaluated. A total of 865 eligible patients (mean age 66 ± 10 years) were included in the final analysis (437 in the Remote arm and 428 in the Standard arm) and followed for a median of 24 (interquartile range = 15-26) months. No significant difference was found in the primary endpoint between the Remote and Standard arms [hazard ratio 1.02, 95% confidence interval (CI) 0.80-1.30, P = 0.89] or in the individual components of the primary endpoint (P > 0.05). For the composite endpoint of healthcare resource utilization (i.e. 2-year rates of CV hospitalizations, CV emergency department admissions, and CV in-office follow-ups), a significant 38% reduction was found in the Remote vs. Standard arm (incidence rate ratio 0.62, 95% CI 0.58-0.66, P < 0.001) mainly driven by a reduction of in-office visits. In heart failure patients implanted with a CRT-D, remote monitoring did not reduce mortality or risk of CV or device-related hospitalization. Use of healthcare resources was significantly reduced as a result of a marked reduction of in-office visits without compromising patient safety. NCT00885677. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Large multi-centre pilot randomized controlled trial testing a low-cost, tailored, self-help smoking cessation text message intervention for pregnant smokers (MiQuit).

PubMed

Naughton, Felix; Cooper, Sue; Foster, Katharine; Emery, Joanne; Leonardi-Bee, Jo; Sutton, Stephen; Jones, Matthew; Ussher, Michael; Whitemore, Rachel; Leighton, Matthew; Montgomery, Alan; Parrott, Steve; Coleman, Tim

2017-07-01

To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service (SMS) text message and key parameters needed to plan a definitive trial. Multi-centre, parallel-group, single-blinded, individual randomized controlled trial. Sixteen antenatal clinics in England. Four hundred and seven participants were randomized to the intervention (n = 203) or usual care (n = 204). Eligible women were < 25 weeks gestation, smoked at least one daily cigarette (> 5 pre-pregnancy), were able to receive and understand English SMS texts and were not already using text-based cessation support. All participants received a smoking cessation leaflet; intervention participants also received a 12-week programme of individually tailored, automated, interactive, self-help smoking cessation text messages (MiQuit). Seven smoking outcomes, including validated continuous abstinence from 4 weeks post-randomization until 36 weeks gestation, design parameters for a future trial and cost-per-quitter. Using the validated, continuous abstinence outcome, 5.4% (11 of 203) of MiQuit participants were abstinent versus 2.0% (four of 204) of usual care participants [odds ratio (OR) = 2.7, 95% confidence interval (CI) = 0.93-9.35]. The Bayes factor for this outcome was 2.23. Completeness of follow-up at 36 weeks gestation was similar in both groups; provision of self-report smoking data was 64% (MiQuit) and 65% (usual care) and abstinence validation rates were 56% (MiQuit) and 61% (usual care). The incremental cost-per-quitter was £133.53 (95% CI = -£395.78 to 843.62). There was some evidence, although not conclusive, that a text-messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

PubMed

Eastwood, Glenn M; Schneider, Antoine G; Suzuki, Satoshi; Peck, Leah; Young, Helen; Tanaka, Aiko; Mårtensson, Johan; Warrillow, Stephen; McGuinness, Shay; Parke, Rachael; Gilder, Eileen; Mccarthy, Lianne; Galt, Pauline; Taori, Gopal; Eliott, Suzanne; Lamac, Tammy; Bailey, Michael; Harley, Nerina; Barge, Deborah; Hodgson, Carol L; Morganti-Kossmann, Maria Cristina; Pébay, Alice; Conquest, Alison; Archer, John S; Bernard, Stephen; Stub, Dion; Hart, Graeme K; Bellomo, Rinaldo

2016-07-01

In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment. Copyright © 2016. Published by Elsevier Ireland Ltd.

HairMax LaserComb laser phototherapy device in the treatment of male androgenetic alopecia: A randomized, double-blind, sham device-controlled, multicentre trial.

PubMed

Leavitt, Matt; Charles, Glenn; Heyman, Eugene; Michaels, David

2009-01-01

The use of low levels of visible or near infrared light for reducing pain, inflammation and oedema, promoting healing of wounds, deeper tissue and nerves, and preventing tissue damage has been known for almost 40 years since the invention of lasers. The HairMax LaserComb is a hand-held Class 3R lower level laser therapy device that contains a single laser module that emulates 9 beams at a wavelength of 655 nm (+/-5%). The device uses a technique of parting the user's hair by combs that are attached to the device. This improves delivery of distributed laser light to the scalp. The combs are designed so that each of the teeth on the combs aligns with a laser beam. By aligning the teeth with the laser beams, the hair can be parted and the laser energy delivered to the scalp of the user without obstruction by the individual hairs on the scalp. The primary aim of the study was to assess the safety and effectiveness of the HairMax LaserComb laser phototherapy device in the promotion of hair growth and in the cessation of hair loss in males diagnosed with androgenetic alopecia (AGA). This double-blind, sham device-controlled, multicentre, 26-week trial randomized male patients with Norwood-Hamilton classes IIa-V AGA to treatment with the HairMax LaserComb or the sham device (2 : 1). The sham device used in the study was identical to the active device except that the laser light was replaced by a non-active incandescent light source. Of the 110 patients who completed the study, subjects in the HairMax LaserComb treatment group exhibited a significantly greater increase in mean terminal hair density than subjects in the sham device group (p < 0.0001). Consistent with this evidence for primary effectiveness, significant improvements in overall hair regrowth were demonstrated in terms of patients' subjective assessment (p < 0.015) at 26 weeks over baseline. The HairMax LaserComb was well tolerated with no serious adverse events reported and no statistical difference in adverse effects between the study groups. The results of this study suggest that the HairMax LaserComb is an effective, well tolerated and safe laser phototherapy device for the treatment of AGA in males.

The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

PubMed

Garcia, Esther; Robert, Marta; Peris, Francesc; Nakamura, Hiroshi; Sato, Noriko; Terazawa, Yoshikatsu

2009-01-01

Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%). Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.