130 results found
Gimeno H, Brown R, Lin JP, et al., 2019, AUGMENTING FUNCTIONAL PERFORMANCE FOLLOWING DEEP BRAIN STIMULATION WITH A COGNITIVE APPROACH FOR INDIVIDUALS WITH HYPERKINETIC MOVEMENT DISORDERS, Publisher: SAGE PUBLICATIONS LTD, Pages: 52-53, ISSN: 0308-0226
Sayar Z, Czuprynska J, Patel JP, et al., 2019, What are the difficulties in conducting randomised controlled trials of thromboprophylaxis in myeloma patients and how can we address these? Lessons from apixaban versus LMWH or aspirin as thromboprophylaxis in newly diagnosed multiple myeloma (TiMM) feasibility clinical trial, Journal of Thrombosis and Thrombolysis, Vol: 48, Pages: 315-322, ISSN: 0929-5305
Routine thromboprophylaxis (TP) in newly-diagnosed multiple myeloma (NDMM) patients comprises either aspirin for standard risk patients or low molecular weight heparin for high risk patients. Studies using DOACs in cancer patients include few with myeloma. The aim of this feasibility clinical trial was to establish the foundations for creating a multicentre trial and identify any safety concerns with apixaban. Patient perspectives were sought. NDMM patients were stratified according to VTE risk and randomised to either standard TP or apixaban 2.5 mg BD and reviewed every 3 weeks throughout their chemotherapy. Two focus groups were carried out on 2 occasions at King’s College Hospital and Guy’s Hospital, London. Each lasted an hour, were recorded, transcribed and themes explored using NVivo 11. Ten patients were recruited, 2 considered high risk and received apixaban and 8 standard risk; 4 randomised to aspirin and 4 to apixaban. Five patients and 2 carers participated in the focus groups. There were no major bleeding or VTE events. Patients were not aware of the thrombotic risk associated with cancer. There is a lack of both written and verbal information on this topic. Myeloma patients were happy to be included in more than one trial simultaneously. Our study provides information on the difficulties facing physicians and patients on obtaining evidence of the safety of DOACs in the context of myeloma. Despite patients being happy to co-recruit into thromboprophylaxis trials along with chemotherapy trials this is not current practice.
Chen T, Li C, Qin R, et al., 2019, Comparison of clinical trial changes in primary outcome and reported intervention effect size between trial registration and publication., JAMA Network Open, Vol: 2, Pages: 1-12, ISSN: 2574-3805
Importance: Primary outcome change could threaten the validity of a clinical trial; however, evidence about the consequences on the reported intervention effect size is unclear. Objectives: To examine the status of randomized clinical trials whose primary outcome changed between trial registration and publication and to quantify the association of this change with the reported intervention effect size. Design, Setting, and Participants: In this cross-sectional study on the primary report of randomized clinical trials with clear prospectively registered primary outcomes, PubMed and Embase were searched for articles published between January 1, 2011, and December 31, 2015. The search was conducted in January 2016, identifying randomized clinical trials and the combination of keywords and text words related to registry. Main Outcomes and Measures: Based on the developed approach, trials were classified as having primary outcome change when there was a major discrepancy between the registered and published primary outcomes. Intervention effect was estimated or recalculated using the odds ratio (OR) for each comparison. Each component OR is structured so that an OR is less than 1 if the intervention group has a more favorable result than the control group. The ratio of ORs (ROR), which is the summary OR for trials with primary outcome change divided by those without, and its 95% CI were calculated, with a value less than 1 indicating a larger reported intervention effect size in trials with primary outcome change than those without. Results: Among 29 749 searched articles (28 810 MEDLINE and 939 Embase), 1488 articles were randomly selected for review. Of 389 trials with clear primary outcomes prospectively described in the registry (416 outcomes reported), 33.4% (130 of 389) of trials had at least 1 primary outcome change. Most (66 of 130) of the changes were either not reporting or omitting the primary outcome. In total, 338 trials (365 outcomes and 487 comparisons) we
Cornelius V, Johnston CL, 2019, The enhanced peri-operative care for high-risk patients trial: an independent discussion and commentary, British Journal of Anaesthesia, ISSN: 0007-0912
Gulati S, Dubois P, Carter B, et al., 2019, A Randomized Crossover Trial of Conventional vs Virtual Chromoendoscopy for Colitis Surveillance: Dysplasia Detection, Feasibility, and Patient Acceptability (CONVINCE), INFLAMMATORY BOWEL DISEASES, Vol: 25, Pages: 1096-1106, ISSN: 1078-0998
Ojji DB, Mayosi B, Francis V, et al., 2019, Comparison of dual therapies for lowering blood pressure in black Africans, New England Journal of Medicine, ISSN: 0028-4793
BACKGROUND: The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS: In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS: The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, -3.14 mm Hg; 95% confidence interval [CI], -5.90 to -0.38; P = 0.03; and -3.00 mm Hg; 95% CI, -5.8 to -0.20; P = 0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was -0.14 mm Hg (95% CI, -2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS: Thes
Gimeno H, Brown RG, Lin J-P, et al., 2019, Cognitive approach to rehabilitation in children with hyperkinetic movement disorders post-DBS, NEUROLOGY, Vol: 92, Pages: E1212-E1224, ISSN: 0028-3878
Phillips R, Hazell L, Sauzet O, et al., Analysis and reporting of adverse events in randomised controlled trials: a review, BMJ Open, ISSN: 2044-6055
ObjectiveTo ascertain contemporaryapproaches to the collection, reporting and analysis of adverse events (AEs)inrandomised controlled trials(RCTs)with a primary efficacy outcome.DesignA reviewof clinical trials of drug interventions from four high impactmedical journals.Data sourcesElectronic contents table of the BMJ, the Journal of the American Medical Association, the Lancet,andthe New England Journal of Medicine were searchedfor reports of original RCTs published between September 2015 and September 2016.MethodsA pre-piloted checklist was used and single data extraction was performed by three reviewers with independent check of a randomly sampled subset to verify quality. We extracted data on collection methods, assessment of severity and causality, reporting criteria, analysis methods and presentation of AE data.ResultsWe identified 184 eligible reports (BMJ n=3; JAMA n=38, Lancet n=62; and NEJM n=81).Sixty-two percent reported some form of spontaneous AE collection but only 29% included details of specific prompts used to ascertain AE data. Numbers that withdrew from the trial were well reported (80%), however only 35% of these reported whether withdrawals were due toAEs.Results presented and analysis performed was predominantly on ‘patients with at least 1event’ with 84% of studies ignoring repeated events. Despite a lack of power to undertake formal hypothesis testing, 47% performed such tests for binary outcomes. ConclusionsThis review highlighted that the collection, reporting and analysis of AE data in clinical trials is inconsistent and RCTs as a source of safety data are underutilised. Areas to improve include reducing information loss when analysing at patient level and inappropriate practice of underpowered multiple hypothesis testing. Implementation of standard reporting practices could enable a more accurate synthesis of safety data and development of guidance for statistical methodology to assesscausality ofAEs could facilitate better s
Hemming K, Carroll K, Thompson J, et al., 2019, Quality of stepped-wedge trial reporting can be reliably assessed using an updated CONSORT: crowd-sourcing systematic review, Journal of Clinical Epidemiology, Vol: 107, Pages: 77-88, ISSN: 0895-4356
The Consolidated Standards Of Reporting Trials (CONSORT) extension for the stepped-wedge cluster randomised trial (SW-CRT) is a recently published reporting guideline for SW-CRTs. We assess the quality of reporting of a recent sample of SW-CRTs according to the 26 items in the new guideline using a novel crowd sourcing methodology conducted independently and in duplicate, with random assignment, by 50 reviewers. We assessed reliability of the quality assessments, proposing this as a novel way to assess robustness of items in reporting guidelines.Several items were well reported. Some items were very poorly reported, including several items that have unique requirements for the SW-CRT, such as the rationale for use of the design, description of the design, identification and recruitment of participants within clusters, and concealment of cluster allocation (not reported in more than 50% of the reports). Agreement across items was moderate (median percentage agreement was 76% [IQR 64 to 86]). Agreement was low for several items including the description of the trial design and why trial ended or stopped for example.When reporting SW-CRTs authors should pay particular attention to ensure clear reporting on the exact format of the design with justification, as well as how clusters and individuals were identified for inclusion in the study, and whether this was done before or after randomisation of the clusters, which are crucial for risk of bias assessments. Some items, including why the trial ended might either not be relevant to SW-CRTs, or might be unclearly described in the statement.
Wheeler GM, Mander AP, Bedding A, et al., 2019, How to design a dose-finding study using the continual reassessment method, BMC Medical Research Methodology, Vol: 19, ISSN: 1471-2288
IntroductionThe continual reassessment method (CRM) is a model-based design for phase I trials, which aims to find the maximum tolerated dose (MTD) of a new therapy. The CRM has been shown to be more accurate in targeting the MTD than traditional rule-based approaches such as the 3 + 3 design, which is used in most phase I trials. Furthermore, the CRM has been shown to assign more trial participants at or close to the MTD than the 3 + 3 design. However, the CRM’s uptake in clinical research has been incredibly slow, putting trial participants, drug development and patients at risk. Barriers to increasing the use of the CRM have been identified, most notably a lack of knowledge amongst clinicians and statisticians on how to apply new designs in practice. No recent tutorial, guidelines, or recommendations for clinicians on conducting dose-finding studies using the CRM are available. Furthermore, practical resources to support clinicians considering the CRM for their trials are scarce.MethodsTo help overcome these barriers, we present a structured framework for designing a dose-finding study using the CRM. We give recommendations for key design parameters and advise on conducting pre-trial simulation work to tailor the design to a specific trial. We provide practical tools to support clinicians and statisticians, including software recommendations, and template text and tables that can be edited and inserted into a trial protocol. We also give guidance on how to conduct and report dose-finding studies using the CRM.ResultsAn initial set of design recommendations are provided to kick-start the design process. To complement these and the additional resources, we describe two published dose-finding trials that used the CRM. We discuss their designs, how they were conducted and analysed, and compare them to what would have happened under a 3 + 3 design.ConclusionsThe framework and resources we provide are aimed at clinicians
Mehta S, Cro S, Coomber B, et al., 2019, A randomised controlled feasibility trial to evaluate local heat preconditioning on wound healing after reconstructive breast surgery: the preHEAT trial, Pilot and Feasibility Studies, Vol: 5, ISSN: 2055-5784
ObjectivepreHEAT was a randomised controlled feasibility trial to determine how best to measure skin necrosis in breast reconstruction to inform the design of a larger multicentre trial.BackgroundMastectomy skin flap necrosis (MSFN) is a serious complication resulting in prolonged wound healing. Local heat preconditioning of the MSF before surgery has been shown to reduce skin necrosis in immediate breast reconstruction patients (IBR).MethodpreHEAT was a single-centre, randomised control two-arm single-blind parallel arm feasibility trial of local heat preconditioning in breast cancer patients undergoing SSM and NSM at Guy’s and St Thomas’ Hospital, London, UK. All patients undergoing IBR above the age of 18 were included. Intervention patients heated breast skin to 43 °C in three, 30-min cycles interrupted by spontaneous cooling using hot water bottles. The primary aim was to compare measurement of skin necrosis using binary ‘yes/no’ assessment, the SKIN score, and wound area.ResultsOne hundred forty-one patients were randomised over a 2-year period (71 heated group, 70 controls). There was near perfect agreement between assessors using the “yes/no” measurement of necrosis. The proportion of patients experiencing necrosis in controls was 35% (n = 23/66) in the heated 26% (n = 18/68]). In the control group, 17% (n = 4/23) patients experiencing necrosis required surgical intervention for necrosis compared to 11% (n = 2/18) in the heated group.ConclusionThe binary outcome of MSFN “yes/no” is a suitable and reliable primary outcome measure of necrosis and was superior to the SKIN Score or necrosis area. The trial study design is feasible for a larger definitive trial.
Selby A, Munro A, Grimshaw KE, et al., 2018, Prevalence estimates and risk factors for early childhood wheeze across Europe: the EuroPrevall birth cohort, Thorax, Vol: 73, Pages: 1049-1061, ISSN: 1468-3296
BACKGROUND: Preschool wheeze is an important problem worldwide. No comparative population-based studies covering different countries have previously been undertaken. OBJECTIVE: To assess the prevalence of early childhood wheeze across Europe and evaluate risk factors focusing on food allergy, breast feeding and smoke exposure. METHODS: Infants from nine countries were recruited into the EuroPrevall birth cohort. At 12 and 24 months, data on wheeze, allergic signs/symptoms, feeding, smoke exposure, infections and day care attendance were collected using questionnaires. Poisson regression was used to assess risk factors for wheeze. RESULTS: 12 049 infants were recruited. Data from the second year of life were available in 8805 (73.1%). The prevalence of wheeze in the second year of life ranged from <2% in Lodz (Poland) and Vilnius (Lithuania) to 13.1% (95% CI 10.7% to 15.5%) in Southampton (UK) and 17.2% (95% CI 15.0% 19.5%) in Reykjavik (Iceland). In multivariable analysis, frequent lower respiratory tract infections in the first and second years of life (incidence rate ratio (IRR) 1.9 (95% CI 1.3 to 2.6) and 2.5 (95% CI 1.9 to3.4), respectively), postnatal maternal smoking (IRR 1.6, 95% CI 1.1 to 2.4), day care attendance (IRR 1.6, 95% CI 1.1 to 2.5) and male gender (IRR 1.3, 95% CI 1.0 to 1.7) were associated with wheeze. The strength of their association with wheeze differed between countries. Food allergy and breast feeding were not independently associated with wheeze. CONCLUSION: The prevalence of early childhood wheeze varied considerably across Europe. Lower respiratory tract infections, day care attendance, postnatal smoke exposure and male gender are important risk factors. Further research is needed to identify additional modifiable risk factors that may differ between countries.
Cro S, Smith C, Wilson R, et al., 2018, Treatment of pustular psoriasis with anakinra: a statistical analysis plan for stage 1 of an adaptive two-staged randomised placebo-controlled trial, Trials, Vol: 19, ISSN: 1745-6215
BackgroundPalmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin disease. It is known to affect quality of life at a level comparable to that from major medical and psychiatric illness, yet current treatment options are remarkably limited. Recent evidence however suggests that interleukin-1 (IL-1) blockade with anakinra will deliver therapeutic benefit in PPP.MethodsAnakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) is a two-staged, adaptive, double-blind, randomised placebo-controlled trial which aims to test the hypothesis that IL-1 blockade with anakinra will deliver therapeutic benefit in PPP. During stage 1 a total of 24 patients will be randomised (1:1) to receive either placebo or anakinra. The two candidate primary outcomes are fresh pustule count (across palms and soles) and the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score, recorded at baseline and at weeks 1, 4 and 8. Analysis at the end of stage 1 will compare treatment arms to ensure sufficient efficacy and safety in order to progress to stage 2. The primary outcome for stage 2 will also be identified following an assessment of the reliability and discriminative ability of fresh pustule count and PPPASI. The trial is powered to detect efficacy and will recruit an additional 40 patients in stage 2 (n = 64 in total). Analysis will follow the intention-to-treat principle and analyse patients as randomised.DiscussionThis manuscript describes the important features of the small population trial design for APRICOT and the pre-specified statistical analysis plan for stage 1. The statistical analysis plan has been developed prior to data extraction and in compliance with international guidelines. It will increase the transparency of the data analysis for the APRICOT trial. The findings of the trial will help to clarify the role of anakinra in the treatment of PPP.
Cornelius V, Wilson R, Cro S, et al., 2018, A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial, Trials, Vol: 19, ISSN: 1745-6215
BackgroundPalmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis.Methods/designWe will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2.DiscussionWe have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatm
Cornelius V, McDermott L, Forster A, et al., 2018, Automated recruitment and randomisation for an efficient randomised controlled trial in primary care, Trials, Vol: 19, ISSN: 1745-6215
Background/aimsUse of electronic health records and information technology to deliver more efficient clinical trials is attracting the attention of research funders and researchers. We report on methodological issues and data quality for a comparison of ‘automated’ and manual (or ‘in-practice’) methods for recruitment and randomisation in a large randomised controlled trial, with individual patient allocation in primary care.MethodsWe conducted a three-arm randomised controlled trial in primary care to evaluate interventions to improve the uptake of invited NHS health checks for cardiovascular risk assessment. Eligible participants were identified using a borough-wide health check management information system. An in-practice recruitment and randomisation method used at 12 general practices required the research team to complete monthly visits to each general practice. For the fully automated method, employed for six general practices, randomisation of eligible participants was performed automatically and remotely using a bespoke algorithm embedded in the health check management information system.ResultsThere were 8588 and 4093 participants recruited for the manual and automated methods, respectively. The in-practice method was ready for implementation 3 months sooner than the automated method and the in-practice method allowed for full control and documentation of the randomisation procedure. However the in-practice approach was labour intensive and the requirement for participant records to be stored locally resulted in the loss of data for 10 practice months. No records for participants allocated using the automated method were lost. A fixed-effects meta-analysis showed that effect estimates for the primary outcome were consistent for the two allocation methods.ConclusionsThis trial demonstrated the feasibility of automated recruitment and randomisation methods into a randomised controlled trial performed in primary care. Future research
Gimeno H, Polatajko HJ, Cornelius V, et al., 2018, Protocol for N-of-I trials proof of concept for rehabilitation of childhood-onset dystonia: Study I, CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE, Vol: 85, Pages: 242-254, ISSN: 0008-4174
Gimeno H, Polatajko HJ, Cornelius V, et al., 2018, Protocol for N-of-I trials with replications across therapists for childhood-onset dystonia rehabilitation: Study 2, CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE, Vol: 85, Pages: 255-260, ISSN: 0008-4174
Gulati S, Dubois P, Carter B, et al., 2018, CONVENTIONAL VERSUS VIRTUAL CHROMOENDOSCOPY FOR COLITIS SURVEILLANCE: DYSPLASIA DETECTION, FEASIBILITY AND PATIENT ACCEPTABILITY (CONVINCE), Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A27-A27, ISSN: 0017-5749
McDermott L, Cornelius VR, Wright AJ, et al., 2018, Enhanced invitations using the question-behavior effect and financial incentives to promote health check uptake in primary care, Annals of Behavioral Medicine, Vol: 31, Pages: 594-605, ISSN: 0883-6612
BackgroundUptake of health checks for cardiovascular risk assessment in primary care in England is lower than anticipated. The question-behavior effect (QBE) may offer a simple, scalable intervention to increase health check uptake.PurposeThe present study aimed to evaluate the effectiveness of enhanced invitation methods employing the QBE, with or without a financial incentive to return the questionnaire, at increasing uptake of health checks.MethodsWe conducted a three-arm randomized trial including all patients at 18 general practices in two London boroughs, who were invited for health checks from July 2013 to December 2014. Participants were randomized to three trial arms: (i) Standard health check invitation letter only; (ii) QBE questionnaire followed by standard invitation letter; or (iii) QBE questionnaire with offer of a financial incentive to return the questionnaire, followed by standard invitation letter. In intention to treat analysis, the primary outcome of completion of health check within 6 months of invitation, was evaluated using a p value of .0167 for significance.Results12,459 participants were randomized. Health check uptake was evaluated for 12,052 (97%) with outcome data collected. Health check uptake within 6 months of invitation was: standard invitation, 590 / 4,095 (14.41%); QBE questionnaire, 630 / 3,988 (15.80%); QBE questionnaire and financial incentive, 629 / 3,969 (15.85%). Difference following QBE questionnaire, 1.43% (95% confidence interval −0.12 to 2.97%, p = .070); following QBE questionnaire and financial incentive, 1.52% (−0.03 to 3.07%, p = .054).ConclusionsUptake of health checks following a standard invitation was low and not significantly increased through enhanced invitation methods using the QBE.
Sayar Z, Abrams ST, Alsabani M, et al., 2018, Neutrophil Extracellular Traps (NETs) formation in Patients newly diagnosed with Myeloma: Findings from the Thromboprophylaxis in Multiple Myeloma (TiMM) Study, 58th Annual Scientific Meeting of the British-Society-for-Haematology, Publisher: WILEY, Pages: 140-141, ISSN: 0007-1048
Sayar Z, Czuprynska J, Patel JP, et al., 2018, Patient Perspectives of Thromboprophylaxis in Multiple Myeloma: Results from the Thromboprophylaxis in Multiple Myeloma (TiMM) study, 9th International Conference on Thrombosis and Hemostasis Issues in Cancer (ICTHIC), Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: S189-S190, ISSN: 0049-3848
Harris J, Armes J, Ream E, et al., 2018, Lesson learnt in developing predictive risk models in psychosocial-oncology: from evidence to implementation, Publisher: WILEY, Pages: 14-14, ISSN: 1057-9249
Harris J, Cornelius V, Purssell E, et al., 2018, A systematic review to identify risk factors for anxiety after treatment for non-metastatic breast cancer and evaluate multivariate model development, Publisher: WILEY, Pages: 13-13, ISSN: 1057-9249
Sin J, Henderson C, Spain D, et al., 2018, eHealth interventions for family carers of people with long term illness: a promising approach?, Clinical Psychology Review, Vol: 60, Pages: 109-125, ISSN: 0272-7358
Family carers of people who have long term illness often experience physical and mental health morbidities, and burden. While there is good evidence to suggest that carers benefit from psychosocial interventions, these have primarily been delivered via face-to-face individual or group-formats. eHealth interventions offer a novel, accessible and self-paced approach to care delivery. Whether these are effective for carers' wellbeing has been little explored. This paper reports the first comprehensive systematic review in this area. A total of 78 studies, describing 62 discrete interventions, were identified. Interventions commonly aimed to promote carers' knowledge, self-efficacy, caregiving appraisal, and reduce global health morbidities. Interventions were offered to carers of people with a wide range of long term illness; dementia has been the most researched area, as reported in 40% of studies. Clinical and methodological heterogeneity in interventions precluded meta-analyses, and so data were analysed narratively. The most popular approach has comprised psychoeducational interventions delivered via an enriched online environment with supplementary modes of communication, such as network support with professionals and peers. Overall, carers appreciate the flexibility and self-paced nature of eHealth interventions, with high rates of satisfaction and acceptability. More studies using robust designs are needed to extend the evidence base.
Cro SM, Mehta S, Farhadi J, et al., 2018, Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery; study protocol and statistical analysis plan for the PREHEAT trial, Pilot and Feasibility Studies, Vol: 4, ISSN: 2055-5784
BackgroundEssential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition.MethodsPREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT.DiscussionThis article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the dat
Forster AS, Cornelius V, Rockliffe L, et al., 2017, A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination., British Journal of Cancer, Vol: 117, Pages: 1121-1127, ISSN: 0007-0920
BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com.
Howlin RP, Cathie K, Hall-Stoodley L, et al., 2017, Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis, MOLECULAR THERAPY, Vol: 25, Pages: 2104-2116, ISSN: 1525-0016
Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.
Craythorne E, Damato E, Pavel M, et al., 2017, Prospective study comparing the use of ex vivo fluorescence confocal microscopy and traditional frozen-section pathology in Mohs micrographic surgery of basal cell carcinoma, 97th Annual Meeting of the British-Association-of-Dermatologists, Publisher: WILEY, Pages: 109-109, ISSN: 0007-0963
Bourne S, DeVos R, North M, et al., 2017, Online versus face-to-face pulmonary rehabilitation for patients with chronic obstructive pulmonary disease: randomised controlled trial., BMJ Open, Vol: 7, ISSN: 2044-6055
OBJECTIVE: To obtain evidence whether the online pulmonary rehabilitation(PR) programme 'my-PR' is non-inferior to a conventional face-to-face PR in improving physical performance and symptom scores in patients with COPD. DESIGN: A two-arm parallel single-blind, randomised controlled trial. SETTING: The online arm carried out pulmonary rehabilitation in their own homes and the face to face arm in a local rehabilitation facility. PARTICIPANTS: 90 patients with a diagnosis of chronic obstructive pulmonary disease (COPD), modified Medical Research Council score of 2 or greater referred for pulmonary rehabilitation (PR), randomised in a 2:1 ratio to online (n=64) or face-to-face PR (n=26). Participants unable to use an internet-enabled device at home were excluded. MAIN OUTCOME MEASURES: Coprimary outcomes were 6 min walk distance test and the COPD assessment test (CAT) score at completion of the programme. INTERVENTIONS: A 6-week PR programme organised either as group sessions in a local rehabilitation facility, or online PR via log in and access to 'myPR'. RESULTS: The adjusted mean difference for the 6 min walk test (6MWT) between groups for the intention-to-treat (ITT) population was 23.8 m with the lower 95% CI well above the non-inferiority threshold of -40.5 m at -4.5 m with an upper 95% CI of +52.2 m. This result was consistent in the per-protocol (PP) population with a mean adjusted difference of 15 m (-13.7 to 43.8). The CAT score difference in the ITT was -1.0 in favour of the online intervention with the upper 95% CI well below the non-inferiority threshold of 1.8 at 0.86 and the lower 95% CI of -2.9. The PP analysis was consistent with the ITT. CONCLUSION: PR is an evidenced-based and guideline-mandated intervention for patients with COPD with functional limitation. A 6-week programme of online-supported PR was non-inferior to a conventional model delivered in face-to-face sessions in terms of effects on 6MWT distance, and
Love SB, Brown S, Weir CJ, et al., 2017, Embracing model-based designs for dose-finding trials, British Journal of Cancer, Vol: 117, Pages: 332-339, ISSN: 1532-1827
Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM).Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation.Results: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome.Conclusions: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.
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