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

Peer reviewedPublisher PD

Individualised pelvic floor muscle training in women with pelvic organ prolapse: a multicentre randomised controlled trial

<br>Background: Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapsed are often advised to do pelvic floor muscle exercises, but supporting evidence is limited. Our aim was to establish if one-to-one individualised pelvic floor muscle training (PFMT) is effective in reducing prolapse symptoms.</br> <br>Methods: A parallel‐group multicentre randomised controlled trial (ISRCTN35911035) in female outpatients with newly-diagnosed, symptomatic stage I, II or III prolapse, comparing five PFMT appointments over 16 weeks (n=225) versus a lifestyle advice leaflet (n=222). Treatment allocation was by remote computer allocation using minimisation. Our primary endpoint was participants’ self-report of prolapsed symptoms at 12 months. Group assignment was masked from outcome assessors. We compared outcomes between trial groups in an intention-to-treat analysis. The cost of PFMT and savings on subsequent treatments were calculated to estimate cost-effectiveness.</br> <br>Findings: Compared to the control group, the intervention group reported fewer prolapse symptoms at 12 months (mean difference between groups in change score 1.52, 95% CI [0.46, 2.59], p=0.0053); reported their prolapse to be “better” more often (57.2% versus 44.7%, difference 12.6%, 95% CI [1.1%, 24.1%], p=0.0336); and had an increased but non-significant odds of having less severe stage of prolapse at their 6-month clinical examination, (OR 1.47, 95% CI [0.97, 2.27], p=0.07). The control group had a greater uptake of other prolapse treatment (49.6% versus 24.1%, difference 25.5%, 95% CI [14.5%, 36.0%], p <0.0001). Findings were robust to missing data. The net cost of the 25 intervention was £131.61 per woman and the cost per one-point reduction in the symptom score was £86.59, 95% CI [£50.81, £286.11]. </br&gt

Comparison of a dietary record using reported portion size versus standard portion size for assessing nutrient intake

Objective: Because the percentage of missing portion sizes was large in the Aerobics Center Longitudinal Study (ACLS), careful consideration of the accuracy of standard portion sizes was necessary. The purpose of the present study was to investigate the consequences of using standard portion size instead of reported portion sizes on subjects\u27 nutrient intake. Methods: In 2307 men and 411 women, nutrient intake calculated from a 3-day dietary record using reported portion sizes was compared with nutrient intake calculated from the same record in which standard portion sizes were substituted for reported portion sizes. Results: The standard portion sizes provided significantly lower estimates (≥ 20%) of energy and nutrient intakes than the reported portion sizes. Spearman correlation coefficients obtained by the two methods were high, ranging from 0.67 to 0.93. Furthermore, the agreement between both methods was fairly good. Thus, in the ACLS the use of standard portion sizes rather than reported portion sizes did not appear to be suitable to assess the absolute intake at the group level, but appeared to lead to a good ranking of individuals according to nutrient intake. These results were confirmed by the Continuing Survey of Food Intake by Individuals (CSFII), in which the assessment of the portion size was optimal. When the standard portion sizes were adjusted using the correction factor, the ability of the standard portion sizes to assess the absolute nutrient intake at the group level was considerably improved. Conclusions: This study suggests that the adjusted standard portion sizes may be able to replace missing portion sizes in the ACLS database

Effectiveness and cost-effectiveness of basic versus biofeedback-mediated intensive pelvic floor muscle training for female stress or mixed urinary incontinence: protocol for the OPAL randomised trial

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordIntroduction Accidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence. Methods and analysis This multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score. Ethics and dissemination Approval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review. Trial registration number ISRCTN57746448; Pre-results.National Institute for Health Research (NIHR

Reducing recurrent stroke: Methodology of the motivational interviewing in stroke (MIST) randomized clinical trial

Rationale Recurrent stroke is prevalent in both developed and developing countries, contributing significantly to disability and death. Recurrent stroke rates can be reduced by adequate risk factor management. However, adherence to prescribed medications and lifestyle changes recommended by physicians at discharge after stroke is poor, leading to a large number of preventable recurrent strokes. Using behavior change methods such as Motivational Interviewing early after stroke occurrence has the potential to prevent recurrent stroke. Aims and/or hypothesis The overall aim of the study is to determine the effectiveness of motivational interviewing in improving adherence to medication and lifestyle changes recommended by treating physicians at and after hospital discharge in stroke patients 12 months poststroke to reduce risk factors for recurrent stroke. Design Recruitment of 430 first-ever stroke participants will occur in the Auckland and Waikato regions. Randomization will be to intervention or usual care groups. Participants randomized to intervention will receive four motivational interviews and five follow-up assessments over 12 months. Nonintervention participants will be assessed at the same time points. Study outcomes Primary outcome measures are changes in systolic blood pressure and low-density lipoprotein levels 12 months poststroke. Secondary outcomes include self-reported adherence and barriers to prescribed medications, new cardiovascular events (including stroke), changes in quality of life, and mood. Discussion The results of the motivational interviewing in stroke trial will add to our understanding of whether motivational interviewing may be potentially beneficial in the management of stroke and other diseases where similar lifestyle factors or medication adherence are relevant

Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat.

The myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal neoplastic disorders. Driver mutations in JAK2, CALR, and MPL genes have been identified in the majority of cases. Alongside these, an increasing number of genes are repeatedly identified as mutated in MPN. These, including ASXL1, TET2, DMNT3A, and EZH2, have key roles in epigenetic regulation. Dysregulation of epigenetic processes is therefore a key feature of MPN. Vorinostat is a pan histone deacetylase inhibitor (HDACi) that has been investigated in MPN. DNA methylation (DNAm) is a well-defined epigenetic mechanism of transcription modification. It is known to be affected by ageing, lifestyle, and disease. Epigenetic ageing signatures have been previously described allowing calculation of a methylation age (MA). In this study we examined the effect of vorinostat on MA in MPN cell lines and in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET) treated with vorinostat as part of a clinical trial. An older MA was observed in patients with a higher JAK2 V617F allele burden and those with a longer duration of disease. PV patients had a MA older than that predicted whilst MA was younger than predicted in ET. Treatment with vorinostat resulted in a younger MA in PV patients and older MA in ET patients, in both cases a trend towards the normal chronological age. When MA change was compared against response, nonresponse was associated with a younger than predicted MA in ET patients and a higher than predicted MA in PV patients. The link between MA and JAK2 mutant allele burden implies that allele burden has a role not only in clinical phenotype and disease evolution in MPN patients, but also in the overall methylation landscape of the mutated cells

Persistent problems 1 year after mild traumatic brain injury: a longitudinal population study in New Zealand

Background: Mild traumatic brain injury (mTBI) is a common problem in general practice settings, yet previous research does not take into account those who do not attend hospital after injury. This is important as there is evidence that effects may be far from mild. Aim To determine whether people sustain any persistent effects 1 year after mTBI, and to identify the predictors of health outcomes. Design and setting: A community-based, longitudinal population study of an mTBI incidence cohort (n = 341) from a mixed urban and rural region (Hamilton and Waikato Districts) of the North Island of New Zealand (NZ). Method: Adults (>16 years) completed assessments of cognitive functioning, global functioning, postconcussion symptoms, mood, and quality of life over the year after injury. Results: Nearly half of participants (47.9%) reported experiencing four or more post-concussion symptoms 1 year post-injury. Additionally, 10.9% of participants revealed very low cognitive functioning. Levels of anxiety, depression, or reduced quality of life were comparable with the general population. Having at least one comorbidity, history of brain injury, living alone, non-white ethnic group, alcohol and medication use, and being female were significant predictors of poorer outcomes at 12 months. Conclusion: Although some people make a spontaneous recovery after mTBI, nearly half continue to experience persistent symptoms linked to their injury. Monitoring of recovery from mTBI may be needed and interventions provided for those experiencing persistent difficulties. Demographic factors and medical history should be taken into account in treatment planning

A longitudinal study of well-being, confidence and competence in junior doctors and the impact of emergency medicine placements.

OBJECTIVES: To measure levels of, and change in junior doctor well-being, confidence and self-reported competence over their second postgraduate training year and the impact of emergency department (ED) placements on these outcomes. DESIGN: A longitudinal study using an online survey administered at four time points (2010-2011). SETTING: 28 Acute Hospital Trusts, drawn from nine participating Postgraduate Deaneries in England. PARTICIPANTS: Junior doctors who had a placement in an ED as part of their second postgraduate training year. MAIN OUTCOME MEASURES: Levels of anxiety, depression, motivation, job satisfaction, confidence and self-reported competence, collected at four time points spread over the period of the doctor's second training year (F2). RESULTS: 217 junior doctors were recruited to the study. Over the year there was a significant increase in their overall job satisfaction, confidence and self-reported competence. Junior doctors also reported significantly increased levels of motivation and anxiety, and significantly decreased levels of extrinsic job satisfaction when working in ED compared with other specialties. There were also significant increases in both junior doctor confidence and self-reported competence after their placement in ED relative to other specialties. CONCLUSIONS: While elements of junior doctor well-being worsened in their ED placement compared with their time spent in other specialties, the increased levels of anxiety and reduced extrinsic job satisfaction were within the normal range for other healthcare workers. These deficits were also balanced by greater improvements in motivation, confidence in managing common acute clinical conditions and perceived competence in performing acute procedures compared with benefits offered by placements in other specialties