Difference In Proportion Of Participants Research Articles

A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1)

BackgroundV114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa–HBV–IPV/Hib and rotavirus RV1 vaccines. MethodsV114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes. Results1184 healthy infants 42–90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 μg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa–HBV–IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa–HBV–IPV/Hib and anti-rotavirus IgA geometric mean titers. ConclusionsAfter a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants.Trial registration: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31

Effects of a digital diabetes prevention program on cardiovascular risk among individuals with prediabetes

ObjectiveTo examine changes in cardiovascular disease (CVD) risk outcomes of overweight/obese adults with prediabetes. MethodsUsing data from a randomized control trial of digital diabetes prevention program (d‐DPP) with 599 participants. We applied the atherosclerotic CVD (ASCVD) risk calculator to predict 10-year CVD risk for d‐DPP and small education (comparison) groups. Between-group risk changes at 4 and 12 months were compared using a repeated measures linear mixed-effect model. We examined within-group differences in proportion of participants over time for specific CVD risk factors using generalized estimating equations. ResultsWe found no differences between baseline 10-year ASCVD risk. Relative to the comparison group, the d‐DPP group experienced greater reductions in predicted 10-year ASCVD risk at each follow-up visit and a significant group difference at 4 months (−0.96%; 95% confidence interval: −1.58%, −0.34%) (but not at 12 months). Additionally, we observed that the d‐DPP group experienced a decreased proportion of individuals with hyperlipidemia (18% and 16% from baseline to 4 and 12 months), high-risk total cholesterol (8% from baseline to 12 months), and being insufficiently active (26% and 22% from baseline to 4 and 12 months at follow-up time points. ConclusionsOur findings suggest that a digitally adapted DPP may promote the prevention of cardiometabolic disease among overweight/obese individuals with prediabetes. However, given the lack of maintenance of effect on ASCVD risk at 12 months, there may also be a need for additional interventions to sustain the effect detected at 4 months.

Efficacy and safety of house dust mite sublingual immunotherapy tablets in allergic rhinitis: A systematic review and meta-analysis

BackgroundHouse dust mite (HDM) sublingual immunotherapy (SLIT) tablets have been approved for the treatment of patients with allergic rhinitis (AR). However, the meta-analysis on the efficacy of HDM-SLIT tablets for HDM-induced AR patients remained limited. MethodsFive databases were searched including: PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CINAHL for randomized controlled trials (RCTs) that addressed the efficacy and safetyof HDM-SLIT tablets compared with placebo until January 2022. The primary outcome was a combined symptom and medication score (CSMS) after treatment. ResultsEight eligible RCTs were identified with a total of 3601 patients treated with HDM-SLIT tablets and 2783 patients who received a placebo. The CSMS was significantly lower in the HDM-SLIT tablet group compared with the placebo (standardized mean difference (SMD) −0.28 [95% CI: −0.32 to −0.23]). There was a significant reduction in rhinitis symptom scores, rhinitis medication scores, total combined conjunctivitis scores, and rhinoconjunctivitis quality of life questionnaire scores. The consistent efficacy compared to the placebo has been exhibited over the different kinds and doses of HDM tablets (6 SQ, 12 SQ, 300 IR, and 500 IR) and age groups (>5 years old, adolescents and adults) with low degrees of variability across the studies. There was no significant difference in proportions of participants who were injected with epinephrine between the treatment- and placebo groups. ConclusionsHDM-SLIT tablet is an effective treatment in reducing rhinitis symptoms and medication use in AR patients with favorable safety. They also improve quality of life and conjunctivitis symptoms.

A multi-center pediatric to adult care transition intervention program to improve clinic visit adherence and clinical outcomes among adolescents and emerging adults with type 1 diabetes mellitus [PATHWAY]: Protocol for a randomized controlled trial

ObjectiveThis multi-center randomized controlled trial aims to evaluate the effectiveness of a context-specific transition intervention program to improve clinic visit adherence and clinical outcomes among emerging adults with type 1 diabetes mellitus (T1DM) in Delhi, India. MethodsWe will recruit patients with T1DM of duration ≥1 year and age 15–19.5 years from the participating pediatric sites. After a baseline assessment and a “basic introductory session”, which apprises participants about the concept of transition, study participants (proposed sample size =156) will be randomly allocated into an intervention and control arm. Participants in the intervention arm will receive a structured transition program delivered over 15 months. On the other hand, control arm participants will continue to receive usual care from the pediatric site till the time of transfer to the adult site. The study assessments will be done at baseline, at the time of transfer, and at 1 and 2 years following the transfer. The primary outcome is the difference in clinic attendance rate between intervention and control arms at the end of 1 year post-transfer. The secondary outcomes include the difference in clinic attendance rate at the end of 2 years, the difference in proportion of participants with a minimum of 4 visits in the first follow-up year, and process indicators such as diabetes knowledge and self-management skills, diabetes treatment satisfaction, overall quality of life, diabetes-related distress, hospitalization for acute complications and screening for chronic diabetes complications, and HbA1c. ConclusionThis study will provide important new evidence about a potential strategy to improve clinical care among adolescents and emerging adults with T1DM in lower resource contexts during the vulnerable phase of transition from pediatric to adult healthcare.The trial is registered on the Clinical Trials Registry of India (http://ctri.nic.in) under the CTRI registration number CTRI/2020/10/028379.

Efficacy and safety of Efavirenz 400 mg-based regimens switching from 600 mg-based regimens in people living with HIV with virological suppression in China: a randomized, open-label, non-inferiority study

BackgroundEfavirenz (EFV) 400 mg has been recommended to replace EFV 600 mg. There are only 200 mg and 600 mg dosage forms of EFV in China. Whether switching from one-tablet EFV 600 mg to two-tablet EFV 200 mg would weaken adherence or further affect efficacy or safety is unknown. MethodsVirologically suppressed people living with HIV with a regimen composed of one-tablet tenofovir (TDF), one-tablet lamivudine (3TC), and one-tablet EFV (600 mg) were randomized to continue original regimen or switch to two-tablet EFV (200 mg). Self-reported adherence questionnaires, 12-Item Short-Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were used. Primary end point was the difference in proportions of participants with plasma HIV-RNA ≥ 50 copies/mL at week 48 with noninferiority margin of 4%. ResultsA total of 209 participants were randomized to the EFV 400 mg group and 211 to the EFV 600 mg. Primary end point result was −3.3% (95% CI −8.1–1.6). Further decrease of GGT (−3.1 vs. −0.3 U/L) and TC (−0.26 vs. 0.12 U/L) was observed in EFV 400 mg participants through 48 weeks. No significant changes in adherence, quality of life, and neuropsychologic condition were reported. ConclusionsEFV 400 mg was noninferior to EFV 600 mg and showed mild improvement of safety profile. Adherence was not weakened in patients taking EFV 400 mg. For patients taking EFV 600 mg with neuropsychologic symptoms, it would be better to switch to other drugs instead of EFV 400 mg.

Effect of a backboard on chest compression quality during in-hospital adult cardiopulmonary resuscitation: A randomised, single-blind, controlled trial using a manikin model

IntroductionChest compression quality during in-hospital resuscitation is often suboptimal on a soft surface. Scientific evidence regarding the effectiveness of a backboard is scarce. This single-blinded manikin study evaluated the effect of a backboard on compression depth, rate and chest recoil performed by nurses. Sex, BMI, age and clinical department were considered as potential predictors. MethodsUsing self-learning, nurses were retrained to achieve a minimal combined compression score at baseline. This combined score consisted of ≥70% compressions with depth 50–60 mm, ≥70% compressions with complete release (≤5mm) and a mean compression rate of 100–120 bpm. Subsequently, nurses were allocated to a backboard or control group and performed a two-minute cardiopulmonary resuscitation test. The main outcome measure was the difference in proportion of participants achieving a combined compression score of ≥70%. ResultsIn total 278 nurses were retrained, 158 nurses dropped out and 120 were allocated to the backboard (n = 61) or control group (n = 59). The proportion of participants achieving a combined compression score of ≥70% was not significantly different (p = 0.475) and suboptimal in both groups: backboard group 47.5% (backboard) versus 41.0% (control). Older age (≥51 years) was associated with a lower probability of achieving a combined compression score >70% [OR = 0.133; 95% confidence interval (CI), 0.037–0.479; p = 0.002]. ConclusionUsing a backboard did not significantly improve compression quality in our study. Important decay of compression skills was observed in both groups, highlighting the importance of frequent retraining, particularly in some age groups.

A phase 3 trial of safety, tolerability, and immunogenicity of V114, 15-valent pneumococcal conjugate vaccine, compared with 13-valent pneumococcal conjugate vaccine in adults 50 years of age and older (PNEU-AGE)

BackgroundPneumococcal conjugate vaccines (PCVs) have greatly reduced the incidence of pneumococcal disease, yet unmet medical need remains due to increased disease caused by non-vaccine serotypes (STs). V114 (VAXNEUVANCETM, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA) is a 15-valent PCV containing 13 serotypes in licensed PCV13 and 2 additional serotypes (22F, 33F) which significantly contribute to pneumococcal disease burden. This phase 3 trial compared safety, tolerability, and immunogenicity of V114 to PCV13 in adults ≥50 years of age. MethodsAdults were randomized 1:1 to receive a single dose of V114 or PCV13; randomization was stratified by age (50–64 years, 65–74 years, and ≥75 years). Adverse events (AEs) were collected following vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were measured prior to and 30 days after vaccination (Day 30). Primary objectives included assessing noninferiority of V114 to PCV13 for the 13 shared serotypes and superiority of V114 to PCV13 for the two unique serotypes. Superiority of V114 to PCV13 for shared serotype 3 was assessed as a secondary objective. ResultsOverall, 1,202 participants were vaccinated (V114 N = 602, PCV13 N = 600). The most commonly reported AEs across both groups were injection-site pain, fatigue, and myalgia. V114 met noninferiority criteria compared to PCV13 for the 13 shared serotypes (using a 2-fold non-inferiority margin for the ratio of OPA geometric mean titers [GMTs] [V114/PCV13] at Day 30) and met superiority for the 2 unique serotypes (using a 2-fold super-superiority margin for the ratio of OPA GMTs [V114/PCV13] at Day 30 and a 0.10 super-superiority margin for the difference in proportions of participants with ≥4-fold rise from prevaccination to Day 30). V114 met superiority criteria compared to PCV13 for serotype 3 (based on a super-superiority margin of 1.2 for the ratio of the OPA GMTs [V114/PCV13] and a superiority margin of 0 for the difference in proportions of participants with ≥4-fold rise). [NCT03950622, EudraCT#2018-004316-22, Japic-CTI#194845].

Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection

Azithromycin has been hypothesized to have activity against SARS-CoV-2. To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. ClinicalTrials.gov Identifier: NCT04332107.

"Easier said than done": A qualitative investigation of Black emerging adults coping with multilevel racism.

This qualitative investigation examined how Black emerging adults cope with their worst experiences of racism at multiple levels (individual, cultural, and institutional). A sample of 189 Black emerging adults (M age = 19.34, 68.3% female) from a predominantly White institution completed an online questionnaire with an open-ended question regarding their worst experience of racism and how they coped. Responses to these questions were coded using deductive coding schemes based on established theory-Jones' (1997) tripartite model of racism and Harrell's (2000) typology of coping. Results indicated that the majority of participants utilized active and inner-directed coping strategies in response to their worst experience. More participants responded to institutional-level racism with active rather than passive coping. There were no differences in proportions of participants who responded to individual- or cultural-level racism with active rather than passive coping. Similar proportions of participants also reported inner-directed versus outer-directed coping in response to individual-, cultural-, and institutional-level experiences. Implications for practice, policy, and programming to support the mental health of Black emerging adults are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Is violence ever right? Moral reasoning about violence among youngsters belonging to gangs and peacebuilding groups.

Objective: We investigate cultural group-level understandings of violence and their connections to individual moral reasoning about violence among disadvantaged young people belonging to gangs (n = 33) and peacebuilding (n = 30) groups. Methods: Drawing from in-depth interviews in two low-income neighborhoods in Colombia, we use thematic analysis to explore and compare group-level understandings of violence-entailing definitions of violence, causal attributions of violence, and strategies to handle violence in everyday life-by type of youth group. Next, we use a chi-square analysis to assess between-group differences in proportion of participants endorsing morality of violence according to eight potential moral violence triggers. Results: Youths from both types of groups define violence in similar terms with one key difference. Only gang members ascribe agency to the (i.e., gang and family) describing it as a social entity capable of harming and being harmed. This taken-for-granted cultural assumption frames gang members' justifications of violence as moral to defend one's group. Concurrently, a higher proportion of youths from violent groups support morality of violence to defend one's reputation (p = .001), honor (p <.001), and group (p = .001). Conclusions: Between-group differences in shared understandings of violence are consistent with differences in individual moral reasoning about violence across group type. The findings have implications for improving efficacy of violence prevention interventions, which rarely account for link between young people's shared understandings of violence and moral reasoning about its use.

Palliative radiotherapy after oesophageal cancer stenting (ROCS): a multicentre, open-label, phase 3 randomised controlled trial

SummaryBackgroundPatients with advanced oesophageal cancer have a median survival of 3–6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion.MethodsThis was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I–III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (>11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed.Findings220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40–1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4–27·7) with usual care and 18·9 weeks (14·7–25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78–1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3–not reached) with usual care versus 65·9 weeks (52·7–not reached) with EBRT (adjusted subhazard ratio 0·52 [95% CI 0·28–0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3–4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care.InterpretationPatients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions.FundingNational Institute for Health Research Health Technology Assessment Programme.

Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: a 1-year randomized clinical trial

The aim of this trial was to determine whether a toothpaste with microcrystalline hydroxyapatite is not inferior to a fluoride toothpaste in prevention of caries in children. This double-blinded randomized control trial compared two toothpastes regarding the occurrence of caries lesions using International Caries Detection and Assessment System (ICDAS) ≥ code 1 on the primary dentition within 336 days. The test group used a fluoride-free hydroxyapatite toothpaste three times daily while control group used a toothpaste with fluoride. 207 children were included in the intention-to-treat analysis; 177 of them finished the study per protocol. An increase in caries ICDAS ≥ code 1 per tooth was observed in 72.7% of the hydroxyapatite-group (n = 88), compared with 74.2% of the fluoride-group (n = 89). The exact one-sided upper 95% confidence limit for the difference in proportion of participants with ICDAS increase ≥ 1 (-1.4%) was 9.8%, which is below the non-inferiority margin of 20% demonstrating non-inferiority of hydroxyapatite compared to the fluoride control toothpaste. This RCT showed for the first time, that in children, the impact of the daily use of a toothpaste with microcrystalline hydroxyapatite on enamel caries progression in the primary dentition is not inferior to a fluoride control toothpaste (Clinical Trials NCT03553966).

A Randomised Clinical Trial of Azithromycin Versus Standard Care in Ambulatory COVID-19 – The ATOMIC2 Trial

Background: The antibacterial, anti-inflammatory and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-moderate disease are lacking. We assessed whether azithromycin is effective in reducing hospitalisation in patients with mild-moderate COVID-19. Methods: This open-label, randomised superiority clinical trial at 19 centres in the United Kingdom enrolled adults, ≥18 years, presenting to hospitals with clinically-diagnosed highly-probable or confirmed COVID-19 infection, with Findings: 298 participants were enrolled from 3 rd June 2020 to 29 th January 2021. The primary outcome was assessed in 292 participants. The primary endpoint was not significantly different between the azithromycin and control groups (Adjusted OR 0·91 [95% CI 0·43-1·92], p=0·80). Rates of respiratory failure, progression to pneumonia, all-cause mortality, and adverse events, including serious cardiovascular events, were not significantly different between groups. Interpretation: In patients with mild-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospitalisation or death. Our findings do not support the use of azithromycin in patients with mild-moderate COVID-19. Trial Registration: This trial was registered with ClinicalTrials.gov (NCT04381962) and EudraCT (2020-001740-26).Funding: NIHR Oxford BRC, University of Oxford and Pfizer Inc.Declaration of Interests: TSCH has received grants from Pfizer Inc., grants from University of Oxford, grants from the Wellcome Trust, grants from The Guardians of the Beit Fellowship, and grants from the NIHR Oxford Biomedical Research Centre during the conduct of the study; and personal fees from Astra Zeneca, personal fees from TEVA, personal fees from Peer Voice outside the submitted work. MJ has received grants from the University of Oxford and NIHR Oxford Biomedical Research Centre. DR has undertaken paid consultancy for GSK outside the submitted work. IDP reports personal fees from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, GlaxoSmithKline, Genentech, Regeneron, Teva, Chiesi, Sanofi, Circassia, Knopp, and grants from NIHR outside the submitted work. JU has received honoraria for preparation of educational materials and has served on an advisory board for Gilead Sciences and ViiV Healthcare outside of the submitted work. LC, RK, AW, JLC, VSB, JB, SJD, JM, PM, RG, TB, GJ, FC, DC, SE, DL and SM declare they have no competing interests.Ethics Approval Statement: The trial protocol was reviewed and approved by the UK Medicines and Healthcare products Regulatory Agency and an independent ethical committee (London – Brent Research Ethics Committee, Research Ethics Committee reference number 20/HRA/2105).

Rehabilitation following rotator cuff repair: A multi-centre pilot & feasibility randomised controlled trial (RaCeR)

Objective: To evaluate the feasibility of a multi-centre randomised controlled trial to compare the clinical and cost-effectiveness of early patient-directed rehabilitation versus standard rehabilitation following surgical repair of the rotator cuff of the shoulder. Design: Two-arm, multi-centre pilot and feasibility randomised controlled trial. Setting: Five National Health Service hospitals in England. Participants: Adults (n = 73) with non-traumatic rotator cuff tears scheduled for repair were recruited and randomly allocated remotely prior to surgery. Interventions: Early patient-directed rehabilitation (n = 37); advised to remove their sling as soon as able and move as symptoms allow. Standard rehabilitation (n = 36); sling immobilisation for four weeks. Measures: (1) Randomisation of 20% or more eligible patients. (2) Difference in time out of sling of 40% or more between groups. (3) Follow-up greater than 70%. Results: 73/185 (39%) potentially eligible patients were randomised. Twenty participants were withdrawn, 11 due to not receiving rotator cuff repair. The between-group difference in proportions of participants who exceeded the cut-off of 222.6 hours out of the sling was 50% (80% CI = 29%, 72%), with the early patient-directed rehabilitation group reporting greater time out of sling. 52/73 (71%) and 52/53 (98%) participants were followed-up at 12 weeks when withdrawals were included and excluded respectively. Eighteen full-thickness re-tears were reported (early patient-directed rehabilitation = 7, standard rehabilitation = 11). Five serious adverse events were reported. Conclusion: A main randomised controlled trial is feasible but would require allocation of participants following surgery to counter the issue of withdrawal due to not receiving surgery.

Radiotherapy after esophageal cancer stenting (ROCS): A pragmatic randomized controlled trial evaluating the role of palliative radiotherapy in maintaining swallow.

4569 Background: Most patients with oesophageal cancer (OC) present with incurable disease; 80% of new cases, and deaths, occur in low and middle income nations. Median survival for advanced disease is 3-5 months, a majority requiring intervention for dysphagia. Insertion of self expanding metal stents is the commonest way of palliating, but dysphagia may recur within three months owing to tumour progression. Evidence reviews have called for trials of combination treatment for OC dysphagia. The ROCS study (funding - UK NIHR programme) examined effectiveness of palliative radiotherapy, following stent, in maintaining swallow. It also examined impact on quality of life, bleeding events, and survival. Methods: A multicentre RCT with follow up monthly for a year. Patients referred for stent insertion as primary management of dysphagia related to incurable OC were recruited in secondary care, with all planned follow up at home. Patients were randomised 1:1 to stent insertion alone or stent insertion plus palliative radiotherapy at a dose of 20Gy in five fractions or 30Gy in ten fractions. Primary outcome was difference in proportions of participants with recurrent dysphagia at 12 weeks, defined as deterioration of 11 points or more in the dysphagia scale of the EORTC QLQ-OG25 questionnaire. Secondary outcomes included quality of life, bleeding risk, survival. Results: 220 patients were randomised Dec 2013-Aug 2018 at 23 UK sites. Addition of radiotherapy did not reduce the proportion of primary events at 12 weeks: 49% in control arm vs 45% in the intervention, adjusted OR 0.82 (95%CI 0.40-1.68; p = 0.587) and it was less cost effective. Sensitivity analyses did not alter the results. Dysphagia deterioration-free survival was similar in both arms: adjusted HR 0.92 (95%CI 0.68-1.26; p = 0.618). Median survival was 19.7 weeks in control arm and 18.9 weeks in the intervention. Those in the radiotherapy arm had significantly fewer bleeding events (18.6% compared to 10.3%), giving a number needed to treat of 12. Conclusions: Palliative external beam radiotherapy is widely accessible to patients with advanced cancer. ROCS is the largest trial assessing its role in combination with stenting for OC dysphagia, and is the first to prospectively assess impact on bleeding risk. It demonstrates no reduction in risk of dysphagia recurrence at 12 weeks, nor impact on survival. Reductions in bleeding events should be considered in the context of patient described trade offs of fatigue and burdens of attending hospital. Clinical trial information: NCT01915693 .

Effect of on-site behavioural modification intervention on lifestyle risk factors of hypertension among adult market traders in Abakaliki, Nigeria

ABSTRACT The rising prevalence of hypertension in developing countries has been attributed to changing lifestyle and exposure to modifiable risks. Interventions that particularly target high risk sub-population groups such as informal sector workers are underexplored. This study was undertaken to assess the effectiveness of on-site behavioural modification intervention on modifiable risk factors for hypertension among market traders in a metropolitan city. A non-randomized intervention study with control arm was conducted among market traders. A lifestyle/behavioural modification programme consisting of on-site health education on prevention, early detection and control of hypertension through increased physical activity, and dietary adjustment was adapted and implemented. Pre-tested structured questionnaire was used to collect data from 379 traders that were selected through systematic random sampling technique. Descriptive and inferential statistics were performed at 95% confidence interval. There was statistically significant difference in proportion of participants with adequate physical activity in intervention group compared to control group (p < 0.001). Among intervention group participants, there was a statistically significant increase in the proportion with adequate consumption of fruits and vegetables (p<0.001); significant decreases in the proportion with excessive alcohol consumption/binge drinking (p<0.001), and proportion with ≥2 risky behaviours for hypertension (p<0.001). Age and sex were predictors of ≥2 risky behaviours for hypertension. Lifestyle modification programme was effective in reducing risky behaviours that predispose traders to hypertension, and it should be promoted within large markets.

New Topical Treatment of Symptomatic Internal Haemorrhoids in a General Practice Setting

Introduction: Oral usage of flavonoid-based drugs can be successfully applied in the conservative treatment of internal haemorrhoids; however, its efficiency in a form of topical preparations has not been demonstrated yet. The aim of the present study was to determine the efficiency of ointment with propolis extract (containing minimally 115 mg/kg of flavonoid galangin) in relief and suppression of the symptomatic internal haemorrhoids grade 1 and 2 (bleeding, prolapse, pain, and itching).&#x0D; Methods: This prospective cohort epidemiological study that included 46 participants of both genders, mean age 53.6±14.3 years, was conducted in the general practice setting in Osijek, Croatia and lasted for three months. A specially designed questionnaire was used to collect demographic data and data concerning the haemorrhoid disease symptoms and to evaluate the intensity of the latter data according to the scale defined in the research protocol.&#x0D; Results: The study showed statistically significant improvements in the intensity of all the symptoms connected with the internal haemorrhoids grade 1 and 2 (p&lt;0.001) during the follow up period, as well as statistically significant differences in proportions of participants with and without of the each of the analysed symptoms before and after the therapy (p&lt;0.001). After three months of therapy with ointment containing propolis extract 82.7% patients (38/46) had none of the analysed symptoms.&#x0D; Conclusions: Ointment with propolis extract efficiently affected all the analysed symptoms of the haemorrhoid disease thus having a very significant place within the conservative treatment of haemorrhoids.

Cost-effectiveness and long-term follow-up of three forms of minimal-contact cognitive behaviour therapy for severe health anxiety: Results from a randomised controlled trial

Strategies to increase the availability of cognitive behaviour therapy (CBT) for severe health anxiety (SHA) are needed, and this study investigated the cost-effectiveness and long-term efficacy of three forms of minimal-contact CBT for SHA. We hypothesised that therapist-guided internet CBT (G-ICBT), unguided internet CBT (U-ICBT), and cognitive behavioural bibliotherapy (BIB-CBT) would all be more cost-effective than a waiting-list condition (WLC), as assessed over the main phase of the trial. We also hypothesised that improvements would remain stable up to one-year follow-up. Adults (N = 132) with principal SHA were randomised to 12 weeks of G-ICBT, U-ICBT, BIB-CBT, or WLC. The primary measure of cost-effectiveness was the incremental cost-effectiveness ratio, or the between-group difference in per capita costs divided by the between-group difference in proportion of participants in remission. The Health anxiety inventory (HAI) was the primary efficacy outcome. G-ICBT, U-ICBT, and BIB-CBT were more cost-effective than the WLC. Over the follow-up period, the G-ICBT and BIB-CBT groups made further improvements in health anxiety, whereas the U-ICBT group did not change. As expected, all three treatments were cost-effective with persistent long-term effects. CBT without therapist support appears to be a valuable alternative to G-ICBT for scaling up treatment for SHA.

Neurocognitive functions and psychological distress in young adults with cancer (YAC): A prospective, longitudinal study.

10064 Background: Non-CNS cancer and treatments are associated with neurocognitive sequelae in older adults; whether YAC (age 18-39 yrs) are protected from these effects is unknown. In YAC, cancer interferes with education and occupational attainment and is associated with psychological distress. This prospective, inception-cohort study characterizes neurocognitive functions and psychological distress in YAC. Methods: YAC completed a 2-hr battery of standardized neurocognitive tests and questionnaires 1.7 ± 1 months after diagnosis prior to chemotherapy (mean ± SD, T1) and 8.2 ± 1.2 (T2) and 14.2 ± 1.6 (T3) months later. Healthy YA with no cancer history (HYA) were tested at similar time points. Tests were scored using published norms, transformed to T-scores, and grouped into neurocognitive domains. Results: YAC (n = 108; lymphoma, breast, gyne, GI, GU, sarcoma) were grouped according to whether they required chemotherapy (n = 70) or not (n = 38), and compared to 63 HYA. At baseline, there were no group differences in neurocognitive performance, number of impaired tests, or neurocognitive complaints (Kruskal Wallis, all p-values &gt; .4). About 70% of each group completed assessments at T2 and T3. Mean performance improved over time (random effects models, all p-values &lt; .01), but there were no group differences or interactions between group and time. There were also no differences in proportions of participants in each group whose test scores improved ( &gt; 10 points) or declined ( &lt; 10 points) from T1 to T2 or T3. Adjusting for psychological distress, fatigue, or neurocognitive complaints did not change these results, despite higher symptoms of somatic distress, anxiety and fatigue in YAC compared to healthy YA over time (all p-values &lt; .03). Conclusions: Before chemotherapy and up to about 14 months later, YAC have elevated distress and fatigue, but do not demonstrate the cognitive decline reported in older cancer patients. Our findings are consistent with research suggesting that aging brains are more vulnerable to neurotoxic insult. Whether the effects of cancer treatment emerge later in YAC, placing them at risk for accelerated aging as reported in older patients, remains to be examined.

Surgery for nonarteritic anterior ischemic optic neuropathy.

Nonarteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden and painless loss of vision in the eye, accompanied by pallid swelling of the optic disc. Its etiology is unknown and no medical therapy has been proven effective in treating this condition. Optic nerve decompression surgery, a proposed treatment for NAION, involves making two or more slits or a window in the tissue surrounding the optic nerve, thereby allowing cerebrospinal fluid to escape, and theoretically reducing the pressure surrounding the optic nerve. The objective of this review was to assess the safety and efficacy of surgery compared with other treatment or no treatment in people with NAION. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2014), EMBASE (January 1980 to October 2014), PubMed (1948 to October 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 October 2014. All randomized trials of surgical treatment of NAION were eligible for inclusion in this review. From full-text copies of all reports from relevant trials, one author extracted data which were verified by another author. No data synthesis was required. The one included trial, in which 258 participants were randomized, was stopped early for futility. At the time of the 24-month report the follow-up rate was 95.3% for six months and 67.4% for 24 months (174 participants; 89 careful follow-up and 85 surgery). There was no evidence of a benefit of surgery on visual acuity. Measurements of visual acuity and visual fields were performed by a technician masked to the treatment received. At six months 32.0% of the surgery group had improved visual acuity by 3 or more lines compared with 42.6% of the careful follow-up group (unadjusted risk ratio (RR) 0.75, 95% confidence interval (CI) 0.54 to 1.04). At 24 months 29.4% of the surgery group had improved compared with 31.0% of the careful follow-up group (unadjusted RR 0.95, 95% CI 0.60 to 1.49). Participants who underwent surgery more often lost 3 or more lines of visual acuity in the study eye, although the increased risk was not statistically significant. At six months 18.9% in the surgery group had worsened visual acuity in the study eye compared with 14.8% in the careful follow-up group (RR 1.28; 95% CI 0.73 to 2.24). At 24 months 20.0% in the surgery group had worsened visual acuity in the study eye compared with 21.8% in the careful follow-up group (RR 0.92; 95% CI 0.51 to 1.64). Participants who received surgery experienced both intraoperative and postoperative adverse events, including central retinal artery occlusion during surgery and light perception vision at six months (one participant); and immediate loss of light perception following surgery and loss of vision that persisted to the 12-month visit (two participants). In the careful follow-up group, two participants had no light perception at the six-month follow-up visit; one of these had improved to light perception at 12 months. Pain was the most common adverse event in the surgery group (17% in surgery group versus 3% in the careful follow-up group at one week). Diplopia (double vision) was the next most common complication (8% in the surgery group versus 1% in the careful follow-up group at one week); at three months there was no statistically significant difference in proportion of participants with diplopia between the two groups. The only eligible trial provided no evidence of a beneficial effect of optic nerve decompression surgery for NAION. Future research should focus on increasing our understanding of the etiology and prognosis of NAION. New treatment options should be examined in the context of randomized clinical trials.