Explore the vast range of titles available.

AbstractObjectiveTo determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse.DesignDouble blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis.Setting125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres.Participants237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome.InterventionsChildren were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more).Main outcome measuresThe primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat.ResultsNo significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval −0.005 to 0.037) and cost savings (difference −£1673 ($2160; €1930), 95% confidence interval −£3455 to £109).ConclusionsClinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life.Trial registrationISRCTN16645249; EudraCT 2010-022489-29.

Grapevine trunk diseases (GTDs) are a threat to grape production worldwide, with a diverse collection of fungal species implicated in disease onset. Due to the long-term and complex nature of GTDs, simultaneous detection of multiple microbial species can enhance understanding of disease development. We used DNA metabarcoding of ribosomal internal transcribed spacer 1 (ITS1) sequences, supported by specific PCR and microbial isolation, to establish the presence of trunk pathogens across 11 vineyards (11–26 years old) over three years in Marlborough, the largest wine producing region in New Zealand. Using a reference database of trunk pathogen sequences, species previously associated with GTD, such as Cadophora luteo-olivacea , Diplodia seriata, Diplodia mutila , Neofusicoccum australe, and Seimatosporium vitis , were identified as highly represented across the vineyard region. The well-known pathogens Phaeomoniella chlamydospora and Eutypa lata had especially high relative abundance across the dataset, with P. chlamydospora reads present between 22 and 84% (average 52%) across the vineyards. Screening of sequences against broader, publicly available databases revealed further fungal species within families and orders known to contain pathogens, many of which appeared to be endemic to New Zealand. The presence of several wood-rotting basidiomycetes (mostly Hymenochaetales) was detected for the first time in the Marlborough vineyard region, notably, the native Inonotus nothofagii which was present at 1–2% relative abundance in two vineyards.

Background The effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) is poorly understood. Our objectives were to compare QOL in IIH to the normal UK population; to investigate QOL changes with treatment of IIH, using a weight loss intervention, and to determine which clinical factors influence QOL. Methods This was a prospective cohort evaluation of QOL, using the 36-Item Short Form (SF-36) Health Survey questionnaire, before and after a therapeutic dietary intervention which resulted in significant reduction in body mass index (BMI), intracranial pressure (ICP), papilloedema, visual acuity, perimetric mean deviation (Humphrey 24–2) and headache (six-item headache impact test (HIT-6) and headache diary). Baseline QOL was compared to an age and gender matched population. The relationship between each clinical outcome and change in QOL was evaluated. Results At baseline, QOL was significantly lower in IIH compared to an age and gender matched population in most domains, p < 0.001. Therapeutic weight loss led to a significant improvement in 10 out of 11 QOL domains in conjunction with the previously published data demonstrating significant improvement in papilloedema, visual acuity, perimetry and headache (p < 0.001) and large effect size. Despite significant improvement in clinical measures only headache correlated significantly (p < 0.001) with improving QOL domains. Conclusions QOL in IIH patients is significantly reduced. It improved with weight loss alongside significant improvement in clinical measures and headache. However, headache was the only clinical outcome that correlated with enhanced QOL. Effective headache management is required to improve QOL in IIH.

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical disease frequently leading to permanent disabilities. The ulcers are treated with rifampicin and streptomycin, wound care and, if necessary surgical intervention. Professionals have exclusively shaped the research agenda concerning management and control, while patients' perspective on priorities and preferences have not explicitly been explored or addressed. To get insight into patient perception of the management and control of Buruli ulcer a mixed methods research design was applied with a questionnaire and focus group discussions among former BU patients. Data collection was obtained in collaboration with a local team of native speakers in Ghana. A questionnaire was completed by 60 former patients and four focus group discussions were conducted with eight participants per group. Former patients positively evaluated both the effectiveness of the treatment and the financial contribution received for the travel costs to the hospitals. Pain experienced during treatment procedures, in particular wound care and the streptomycin injections, and the side-effects of the treatment were negatively evaluated. Former patients considered the development of preventive measures and knowledge on the transmission as priorities. Additionally, former patients asked for improved accessibility of health services, counselling and economic support. These findings can be used to improve clinical management and to guide the international research agenda.

ObjectiveTo compare recovery after laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH).DesignA parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial.Setting10 NHS (National Health Service) hospitals within the UK.ParticipantsWomen undergoing hysterectomy for a benign gynaecological condition.InterventionsConsenting women of 18–55 years were randomised to LH or AH using a secure internet facility by a surgeon with self-declared expertise. Major complications were recorded by clinicians, and recovery was assessed by regular text messaging and postal questionnaires.Primary and secondary outcome measuresMajor surgical complications (Clavien-Dindo≥level 3) up to six completed weeks postsurgery, time to resumption of normal activities measured by the Patient-Reported Outcomes Measurement Information System Physical Function tool and quality of recovery at 24 hours (Quality of Recovery 15 score; 0–150).Results75 women were randomised before early curtailment of the trial; 32/39 (82%) and 30/36 (83%) women underwent LH and AH, respectively. Major complications occurred in 2/32 (6%) LH versus 4/30 (13%) AH groups. No difference in time to resumption of usual activities was found (median [IQR, n] 7.5 weeks (3.6–8.2, 25) LH vs 7.5 weeks (5.5–10.6, 26) AH groups or quality of recovery (mean [SD, n] 81.1 (13.4, 27) vs 72.3 (17.6, 22), respectively; adjusted mean difference 7.2, 95% CI −3.2 to 17.6).ConclusionsNo differences were found in complications or recovery between LH and AH. However, early cessation of the trial due to recruitment challenges limits clinical inferences. It is important that larger comparative trials are conducted now that LH, including robotics, is becoming adopted as standard practice.Trial registration numberISRCTN14566195, IRAS ID 287988.

Background Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder involving inattention, hyperactivity and impulsivity, which starts in childhood and frequently persists into adulthood. Stimulant and non-stimulant medication are the mainstay of treatment in adults. ADHD in adults is commonly comorbid in people with severe mental illness (SMI) such as bipolar disorder (bipolar) and psychosis. There is substantial uncertainty over the effectiveness of stimulant and non-stimulant medication in adult ADHD comorbid with SMI. There is also concern that they could trigger or worsen psychotic or manic symptoms. Whilst National Institute of Health and Care Evidence (NICE) ADHD guidelines indicate available evidence does not justify a deviation from their main recommendations of using stimulants first line, this is based on limited studies within this comorbid population. A randomised controlled trial (RCT) is needed to address this evidence gap. We present a protocol for a pragmatic, observer-blind, multi-centre, two-arm, RCT called SNAPPER that aims to investigate the clinical and cost-effectiveness of stimulant compared with non-stimulant medication for adults with ADHD and a history of SMI. Methods The recruitment target is 244 participants, aged 18 years or above, who have a history of SMI (either bipolar disorder or psychosis) with ADHD. Having provided informed consent for screening, participants will undergo validated diagnostic screening assessments to re-confirm the diagnosis of bipolar or psychosis and confirm an ADHD diagnosis. Those with confirmed diagnoses will provide informed consent for entry to the main trial and will then be randomised to receive either stimulant (lisdexamfetamine) or non-stimulant (atomoxetine) medication. The primary outcome measure is observer-rated ADHD symptom severity at 6 months. Secondary outcomes include ADHD symptom severity at 12 months, emergence of symptoms of bipolar or psychosis, health-related quality of life, occupational, daily functioning, substance misuse, cost-effectiveness, adherence, concomitant medication and process outcomes at 6 and 12 months. Discussion Given that untreated ADHD is associated with poor clinical outcomes, unemployment and criminal justice system involvement, clear evidence in this area is likely to improve recovery for individuals with ADHD and a history of SMI, reducing costs for the individual, the NHS and society. Trial registration ISRCTN79796233. Registered on 19/05/2022.  https://www.isrctn.com/ISRCTN79796233 .

Background Antiretroviral therapy (ART) has transformed HIV into a manageable health condition with normal life expectancy. However, people with HIV continue to have poorer mental health compared to background populations, which may be linked to stigma, lack of social support, or socioeconomic challenges. Personalised care aims to improve the outcomes of people with long-term health conditions and the National Health Service (NHS) Long Term Plan looks to implement this (including access to health coaching and social prescribing). The SPHERE trial aims to assess whether a health and well-being coaching and social prescribing intervention improves patient-reported health and well-being among people living with HIV who have psychosocial needs. Methods SPHERE will be conducted across seven HIV outpatient clinics in England and is a pragmatic, two-arm, parallel group randomised controlled trial (RCT) embedding a routine assessment of psychosocial needs in HIV care. Eligibility criteria are people living with HIV aged 18 or older, available for the duration of study follow-up and scoring 16 or more on an assessment of psychosocial need: “Positive-Outcomes-11” (PO-11), covering physical, psychological, social and socioeconomic aspects of health and well-being. The RCT requires 568 participants who will be individually randomised in a 1:1 ratio to either a health and well-being coaching and social prescribing intervention or usual care. The intervention consists of up to eight coaching sessions that will be delivered by health professionals (e.g. HIV nurses) who have received specialist training to become health and well-being coaches. The trial will also include an internal pilot phase, process evaluation (to evaluate intervention feasibility, acceptability and mechanisms of action), economic evaluation (to assess the cost-effectiveness of the intervention and impact on NHS resource use) and parallel observational study (to assess subsequent development of psychosocial needs among those not initially eligible for the trial). The primary outcome is defined as achieving a reduction in PO-11 score of at least 40% from baseline to 6 months post-randomisation. Secondary outcomes include symptoms of depression and anxiety, social support, self-stigma, coping self-efficacy, resilience, lifestyle factors and health-related quality of life. Discussion The SPHERE trial will evaluate the effectiveness and cost-effectiveness of implementing psychosocial health and well-being coaching in a secondary HIV care setting. If effective, this model of personalised care could be transferable to other long-term health conditions. Trial registration International Standard Randomised Controlled Trials Number (ISRCTN) Registry: ISRCTN47187932 [registered 12 July 2024].

IntroductionMyocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection. The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial will assess whether remote ischaemic preconditioning, applied to both lower limbs immediately prior to surgery, reduces myocardial injury in cyanotic and acyanotic young children.Methods and analysisThe BRICC trial is a two-centre, double-blind, randomised controlled trial recruiting up to 120 young children (age 3 months to 3 years) undergoing primary repair of tetralogy of Fallot or surgical closure of an isolated ventricular septal defect. Participants will be randomised in a 1:1 ratio to either bilateral remote ischaemic preconditioning (3×5 min cycles) or sham immediately prior to surgery, with follow-up until discharge from hospital or 30 days, whichever is sooner. The primary outcome is reduction in area under the time-concentration curve for high-sensitivity (hs) troponin-T release in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include peak hs-troponin-T, vasoactive inotrope score, arterial lactate and central venous oxygen saturations in the first 12 hours, and lengths of stay in the paediatric intensive care unit and the hospital.Ethics and disseminationThe trial was approved by the West Midlands-Solihull National Health Service Research Ethics Committee (16/WM/0309) on 5 August 2016. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a local charity.Trial registration numberISRCTN12923441.

IntroductionBreastfeeding 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 analysisA 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 disseminationThe 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 numberISRCTN17395671.

There is uncertainty about the advantages and disadvantages of laparoscopic hysterectomy compared with abdominal hysterectomy, particularly the relative rate of complications of the two procedures. While uptake of laparoscopic hysterectomy has been slow, the situation is changing with greater familiarity, better training, better equipment and increased proficiency in the technique. Thus, a large, robust, multicentre randomised controlled trial (RCT) is needed to compare contemporary laparoscopic hysterectomy with abdominal hysterectomy to determine the safest and most cost-effective technique. A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation. A within trial-based economic evaluation will explore the cost-effectiveness of laparoscopic hysterectomy compared with open abdominal hysterectomy. We will aim to recruit 3250 women requiring a hysterectomy for a benign gynaecological condition and who were suitable for either laparoscopic or open techniques. The primary outcome is major complications up to six completed weeks postsurgery and the key secondary outcome is time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation is to be cost per QALY at 12 months' postsurgery. A secondary analysis is to be undertaken to generate costs per major surgical complication avoided and costs per return to normal activities. The study was approved by the West Midlands-Edgbaston Research Ethics Committee, 18 February 2021 (Ethics ref: 21/WM/0019). REC approval for the protocol version 2.0 dated 2 February 2021 was issued on 18 February 2021.We will present the findings in national and international conferences. We will also aim to publish the findings in high impact peer-reviewed journals. We will disseminate the completed paper to the Department of Health, the Scientific Advisory Committees of the RCOG, the Royal College of Nurses (RCN) and the BSGE. ISRCTN14566195.