Identifying a framework for hope in order to establish the Importance of generalised hopes for individuals who have suffered a stroke

Hope and hopelessness are important psychological constructs that physiotherapists should consider when working with patients who have experienced a stroke. The view of hope in rehabilitation is often focused around the concept of goals and how hope works within this framework. However, the current paper proposes a broader framework for hope and the importance of a more generalised view of understanding why a certain hope exists or is identified by a patient. A narrative review using an a priori thematic analysis was undertaken to consider how more generalised hopes are expressed by individuals who have suffered a stroke. An electronic search of 4 databases from inception until April 2014 was undertaken. Qualitative articles were included if they considered the concept of hope for patients who had suffered a stroke. The results identified three themes which included (1) consideration of the patient’s identity/identities, (2) meaningful activities, experiences, and interactions, and (3) the experience of suffering and need for relief. An awareness of patients’ generalised hopes should be a priority for HCPs. Detailed implications for HCPs are identified within the discussion

Survival time and differences between dementia with Lewy bodies and Alzheimer's disease following diagnosis: A meta-analysis of longitudinal studies.

OBJECTIVE: To synthesize the evidence across longitudinal studies comparing survival in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: We conducted a systematic review and meta-analysis of studies comparing survival in clinically diagnosed DLB to AD. Longitudinal cohort studies were identified through a systematic search of major electronic databases from inception to May 2018. A random effects meta-analysis was performed to calculate survival time and relative risk of death. RESULTS: Overall, 11 studies were identified including 22,952 patients with dementia: 2029 with DLB (mean diagnosis age 76.3; 47% female) compared with 20,923 with AD (mean diagnosis age 77.2; 65.1% female). Average survival time in DLB from diagnosis was 4.11 years (SD ± 4.10) and in AD 5.66 (SD ± 5.32) years, equating to a 1.60 (95% CI: -2.44 to -0.77) years shorter survival in DLB (p < 0.01). Relative risk of death was increased by 1.35 (95%CI: 1.17-1.55) in DLB compared to AD (p < 0.01). Differences in survival were not explained by follow-up time, age at diagnosis, gender, or cognitive score. CONCLUSIONS: There is consistent evidence for higher and earlier mortality in DLB compared to AD. This is important for all stakeholders and underlines the importance of expanding research into DLB.NIH

Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain : the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial

Peer reviewe

WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial - adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic.

BACKGROUND: As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology. METHODS: The trial (internal pilot) paused in March 2020, re-opened in July 2020, and is currently recruiting in 37 UK NHS consultant-led maternity units. We evaluated pandemic adaptations made to WILL processes and surveyed sites for their views of these changes (20 sites, videoconference). RESULTS: Despite 88% of sites favouring an electronic investigator site file (ISF), information technology requirements and clinical trial unit (CTU) operating procedures mandated the ongoing use of paper ISFs; site start-up delays resulted from restricted access to the CTU. Site initiation visits (SIVs) were conducted remotely; 50% of sites preferred remote SIVs and 44% felt that it was trial-dependent, while few preferred SIVs in-person as standard procedure. The Central team felt remote SIVs provided scheduling and attendance flexibility (for sites and trial staff), the option of recording discussions for missing or future staff, improved efficiency by having multiple sites attend, and time and cost savings; the negative impact on rapport-building and interaction was partially mitigated over time with more familiarity with technology and new ways-of-working. Two methods of remote consent were developed and used by 30/37 sites and for 54/156 recruits. Most (86%) sites using remote consenting felt it improved recruitment. For remote data monitoring (5 sites), advantages were primarily for the monitor (e.g. flexibility, no time constraints, reduced cost), and disadvantages primarily for the sites (e.g. document and access preparation, attendance at a follow-up meeting), but 81% of sites desired having the option of remote monitoring post-pandemic. CONCLUSIONS: COVID adaptations to WILL trial processes improved the flexibility of trial delivery, for Central and site staff, and participants. Flexibility to use these strategies should be retained post-pandemic. TRIAL REGISTRATION: ISRCTN77258279. Registered on 05 December 2018

Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding (UCON) : a randomised controlled phase III trial

Acknowledgments This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership (grant 12/206/52). Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care. We thank our Collaborative Group (listed in the Supplementary Material) for their contribution to recruitment, randomisation and collection of data, and to our Trial Steering and Data Monitoring Committees (members listed in Supplementary Material).Peer reviewedPublisher PD

Effectiveness and cost-effectiveness of Assets-based feeding help Before and After birth (ABA-feed) for improving breastfeeding initiation and continuation: protocol for a multicentre randomised controlled trial (Version 3.0)

Introduction: Breastfeeding has health benefits for infants and mothers, yet the UK has low rates with marked social inequalities. The Assets-based feeding help Before and After birth (ABA) feasibility study demonstrated the acceptability of a proactive, assets-based, woman-centred peer support intervention, inclusive of all feeding types, to mothers, peer supporters and maternity services. The ABA-feed study aims to assess the clinical and cost-effectiveness of the ABA-feed intervention compared with usual care in first-time mothers in a full trial. Methods and analysis: A multicentre randomised controlled trial with economic evaluation to explore clinical and cost-effectiveness, and embedded process evaluation to explore differences in implementation between sites. We aim to recruit 2730 primiparous women, regardless of feeding intention. Women will be recruited at 17 sites from antenatal clinics and various remote methods including social media and invitations from midwives and health visitors. Women will be randomised at a ratio of 1.43:1 to receive either ABA-feed intervention or usual care. A train the trainer model will be used to train local Infant Feeding Coordinators to train existing peer supporters to become ‘infant feeding helpers’ in the ABA-feed intervention. Infant feeding outcomes will be collected at 3 days, and 8, 16 and 24 weeks postbirth. The primary outcome will be any breastfeeding at 8 weeks postbirth. Secondary outcomes will include breastfeeding initiation, any and exclusive breastfeeding, formula feeding practices, anxiety, social support and healthcare utilisation. All analyses will be based on the intention-to-treat principle. Ethics and dissemination: The study protocol has been approved by the East of Scotland Research Ethics Committee. Trial results will be available through open-access publication in a peer-reviewed journal and presented at relevant meetings and conferences. Trial registration number: ISRCTN17395671

Gabapentin for chronic pelvic pain in women (GaPP2):a multicentre, randomised, double-blind, placebo-controlled trial

BackgroundChronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.MethodsWe performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.FindingsParticipants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.InterpretationThis study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.FundingNational Institute for Health Research

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert

BACKGROUND: Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower in achieving cervical ripening but have a lower risk of adverse effects. OBJECTIVE: This study aimed to compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with those of dinoprostone. STUDY DESIGN: This was an open-label superiority randomized controlled trial in 4 English hospitals. Eligible participants were women ≥16 years of age undergoing induction of labor for a singleton pregnancy at ≥37 weeks’ gestation with vertex presentation and intact membranes. The women were randomly assigned to receive either Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, body mass index, and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by the Bishop score. The primary outcome was failure to achieve vaginal delivery (ieor a cesarean delivery being performed). The secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. RESULTS: Between December 19, 2017 and January 26, 2021, 674 women were randomized (337 to Dilapan-S, and 337 to dinoprostone). The trial did not reach its planned sample size of 860 participants because of restrictions on research during the COVID-19 pandemic. The primary outcome was missing for 2 women in the dinoprostone group. Failure to achieve vaginal delivery (or a cesarean delivery being performed) occurred in 126 women (37.4%) allocated to Dilapan-S and in 115 (34.3%) women allocated to dinoprostone (adjusted risk difference, 0.02; 95% confidence interval, −0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. CONCLUSION: Women undergoing induction of labor with Dilapan-S have similar rates of cesarean delivery and maternal and neonatal adverse events compared with dinoprostone