Search

Background:Delirium is a common neuropsychiatric syndrome associated with poor outcomes. Evidence supports a neuroinflammatory etiology, but the role of the inflammatory marker C-reactive protein (C-RP) remains unclear. We investigated the relationship between C-RP and delirium and its severity as well as interaction with medical diagnosis.Methods:From an existing database (710 patients over 70 years old admitted to a Medical Acute Admissions Unit) we analyzed data which included C-RP levels, delirium (using the Confusion Assessment Method), and other clinical and demographic factors. Primary diagnoses were grouped (cardiovascular, musculoskeletal, infection, metabolic, and other).Results:There was a strong association between elevated C-RP and delirium (t = 5.09; p < 0.001), independent of other potential risk factors for delirium (odds ratio (OR) = 1.32 (95% CI: 1.10–1.58) p = 0.003). There was no significant association between C-RP and delirium severity, and between C-RP and delirium in the populations with cardiovascular disease, infection upon admission, or from the metabolic group despite an OR of 2.24 (95% CI: 0.92–5.45). There was an association in the musculoskeletal group (OR 2.19 (95% CI: 1.19–4.02)).Conclusions: There is an association between elevated C-RP and delirium. This is strongest in patients admitted with musculoskeletal disease but not in others, implying that C-RP is involved in the genesis of delirium in musculoskeletal disease, but that other factors or processes may be more important in those with cardiovascular disease or infection. [ABSTRACT FROM PUBLISHER]

Purpose: To evaluate the effects of plasma treatment, a cleaning process for removal of organic contaminants from the knit-wire surface of tantalum Strecker stents, on biocompatibility and thrombogenicity.Methods: A treated or untreated stent was randomly implanted in both femoral arteries of 15 sheep studied for periods of 4 (group 1), 15 (group 2), or 42 (group 3) days. Patency, histological changes, and mechanical effects were compared by means of radiologic and pathologic controls.Results: Plasma treatment did not influence overall patency (93.3% vs 86.7%), maximal neointimal hyperplasia in groups 2 and 3 (801 +/- 123 vs 733 +/- 179 microns), or media thinning in any group (254 +/- 92 vs 285 +/- 72 microns), but modified the elastic properties of the stents by limiting (p = 0.01) shortening at implantation.Conclusion: Plasma treatment does not affect the biocompatibility and thrombogenicity of Strecker stents implanted in normal femoral arteries of sheep but modifies their elastic properties. Further studies are needed to account for this effect. [ABSTRACT FROM AUTHOR]

Based on a study of 20 patients operated on between the ages of 21 and 38 for congenital valvular aortic stenosis, the distinguishing features of congenital aortic valvular stenosis in adults are reviewed: valvular calcification (75%), valvular dome rarely present (10%), usually moderate cardiac disability (70%), diminished or inaudible second heart sound (50%), associated diastolic murmur (75%). electrocardiographic left ventricular hypertrophy (70%), and an infrequent protosystolic click (30%). Surgery is necessary for symptomatic patients. If patients are asymptomatic, surgery is decided after measuring the left ventricle-aortic pressure gradient by continuous Doppler wave study, or by cardiac catheterization. If surgery is not performed, a regular follow-up is necessary because stenosis can evolve. Valvular replacement by a mechanical valve is preferable. Even if the aortic valve is not calcified and a simple commissurotomy is technically possible, it is only a palliative method with unsatisfactory results and an annual mortality rate after surgery of 1%. [ABSTRACT FROM PUBLISHER]

Experiences of violence have been reported to be associated with lower levels of subjective wellbeing (SWB). However, little is known about this association in conflict settings and among forcibly displaced populations. In this study we exploit data from a representative sample of refugee teachers from Nyarugusu Refugee Camp collected as part of a larger study, to examine the association between demographic characteristics and SWB, and between experiences of violence and SWB. Three cross-sectional surveys of primary and secondary school teachers were conducted, collecting data on lifetime experience of violence (physical and sexual) and SWB (measured by life satisfaction and current happiness, on 1-5 Likert scales). Linear mixed models were used to estimate the associations between violence and SWB accounting for teacher and school clustering, unadjusted and adjusted for main factors associated with SWB. The 3 surveys included 1,666 responses completed by 885 teachers. Country of origin and number of meals consumed per day were strongly associated with SWB. Individuals who experienced physical violence reported on average, 0.13 lower life satisfaction scores (95% CI [-0.23, -0.02], p  = .016) compared to those who did not experience physical violence, while survivors of sexual violence reported on average, 0.24 lower happiness scores ([-0.43, -0.05], p  = .014) compared to those who did not experience sexual violence, after adjusting for confounders and clustering. We found an important negative association between past experience of violence and SWB in a refugee camp setting. These findings contribute to the evidence that violent experiences are likely to have a long-lasting impact on people's wellbeing. There is a need for improved mental health and psychosocial support in humanitarian settings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: School-based water, sanitation and hygiene (WASH) may improve the health and attendance of schoolchildren, particularly post-menarcheal girls, but existing evidence is mixed. We examined the impact of an urban school-based WASH programme (Project WISE) on child health and attendance., Methods: The WISE cluster-randomised trial, conducted in 60 public primary schools in Addis Ababa, Ethiopia over one academic year, enrolled 2-4 randomly selected classes per school (~ 100 pupils) from grades 2 to 8 (aged 7-16) in an 'open cohort'. Schools were assigned 1:1 by stratified randomisation to receive the intervention during the 2021/2022 or the 2022/2023 academic year (waitlist control). The intervention included improvements to drinking water storage, filtration and access, handwashing stations and behaviour change promotion. Planned sanitation improvements were not realised. At four unannounced classroom visits post-intervention (March-June 2022), enumerators recorded primary outcomes of roll-call absence, and pupil-reported respiratory illness and diarrhoea in the past 7 days among pupils present. Analysis was by intention-to-treat., Results: Of 83 eligible schools, 60 were randomly selected and assigned. In total, 6229 eligible pupils were enrolled (median per school 101.5; IQR 94-112), 5987 enrolled at study initiation (23rd November-22nd December 2021) and the remaining 242 during follow-up. Data were available on roll-call absence for 6166 pupils (99.0%), and pupil-reported illness for 6145 pupils (98.6%). We observed a 16% relative reduction in odds of pupil-reported respiratory illness in the past 7 days during follow-up in intervention vs. control schools (aOR 0.84; 95% CI 0.71-1.00; p = 0.046). There was no evidence of effect on pupil-reported diarrhoea in the past 7 days (aOR 1.15; 95% CI 0.84-1.59; p = 0.39) nor roll-call absence (aOR 1.07; 95% 0.83-1.38; p = 0.59). There was a small increase in menstrual care self-efficacy (aMD 3.32 on 0-100 scale; 95% CI 0.05-6.59), and no evidence of effects on other secondary outcomes., Conclusions: This large-scale intervention to improve school WASH conditions city-wide had a borderline impact on pupil-reported respiratory illness but no effect on diarrhoeal disease nor pupil absence. Future research should establish relationships between WASH-related illness, absence and other educational outcomes., Trial Registration: ClinicalTrials.gov, number NCT05024890., (© 2024. The Author(s).)

We evaluated a digital learning programme for non-specialists to develop knowledge-based competencies in a problem-solving intervention for adolescents to examine the overall impact of training on knowledge-based competencies among learners; and to compare the effects of two training conditions (self-guided digital training with or without coaching) in a nested parallel, two-arm, individually randomised controlled trial. Eligible participants were 18 or older; fluent in Hindi or English; able to access digital training; and had no prior experience of delivering structured psychotherapies. 277 participants were enrolled from 31 March 2022 to 19 June 2022 of which 230 (83%) completed the study. There was a significant increase in competency score from pre-training (Mean = 7.01, SD = 3.29) to post-training (Mean = 8.88, SD = 3.80), 6 weeks after the pre-training assessment. Knowledge competency scores showed larger increase among participants randomised to the coaching arm (AMD = 1.09, 95% CI 0.26-1.92, p  = 0.01) with an effect size ( d ) of 0.33 (95% CI 0.08-0.58). More participants completed training in the coaching arm ( n  = 96, 69.6%) compared to the self-guided training arm ( n  = 56, 40.3%). In conclusion, a coach-supported remote digital training intervention is associated with enhanced participation by learners and increased psychotherapeutic knowledge competencies., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2023.)

Background: The spread of COVID-19 has brought challenges to health, social and economic systems around the world. With little to no prior immunity in the global population, transmission has been driven primarily by human interaction. However, as with common respiratory illnesses such as influenza some authors have suggested COVID-19 may become seasonal as immunity grows. Despite this, the effects of meteorological conditions on the spread of COVID-19 are poorly understood. Previous studies have produced contrasting results, due in part to limited and inconsistent study designs., Methods: This study investigates the effects of meteorological conditions on COVID-19 infections in England using a Bayesian conditional auto-regressive spatio-temporal model. Our data consists of daily case counts from local authorities in England during the first lockdown from March-May 2020. During this period, legal restrictions limiting human interaction remained consistent, minimising the impact of changes in human interaction. We introduce a lag from weather conditions to daily cases to accommodate an incubation period and delays in obtaining test results. By modelling spatio-temporal random effects we account for the nature of a human transmissible virus, allowing the model to isolate meteorological effects., Results: Our analysis considers cases across England's 312 local authorities for a 55-day period. We find relative humidity is negatively associated with COVID-19 cases, with a 1% increase in relative humidity corresponding to a reduction in relative risk of 0.2% [95% highest posterior density (HPD): 0.1-0.3%]. However, we find no evidence for temperature, wind speed, precipitation or solar radiation being associated with COVID-19 spread. The inclusion of weekdays highlights systematic under reporting of cases on weekends with between 27.2-43.7% fewer cases reported on Saturdays and 26.3-44.8% fewer cases on Sundays respectively (based on 95% HPDs)., Conclusion: By applying a Bayesian conditional auto-regressive model to COVID-19 case data we capture the underlying spatio-temporal trends present in the data. This enables us to isolate the main meteorological effects and make robust claims about the association of weather variables to COVID-19 incidence. Overall, we find no strong association between meteorological factors and COVID-19 transmission., (© 2023. The Author(s).)

In this article, we introduce a new command, clan, that conducts a cluster-level analysis of cluster randomized trials. The command simplifies adjusting for individual- and cluster-level covariates and can also account for a stratified design. It can be used to analyze a continuous, binary, or rate outcome.

EmpaTeach was the first intervention to address teacher violence to be tested in a humanitarian setting and the first to focus on reducing impulsive use of violence, but a cluster randomised trial found no evidence that the intervention was effective in reducing physical and emotional violence from teachers. We aimed to understand why. We conducted a quantitative process evaluation to describe the intervention implementation process (what was implemented and how); examine teachers' adoption of positive teaching practices (was the content of the intervention taken up by participants), and test mechanisms of impact underlying the program theory (how the intervention was supposed to produce change). Despite participation in the intervention activities and adoption of intervention-recommended strategies (classroom management and positive disciplinary methods), we show that teachers who used more positive discipline did not appear to use less violence; and teachers in intervention schools did not experience gains in intermediate outcomes such as empathy, growth mindset, self-efficacy or social support. Our findings suggest that the intervention did not work due to the failure of some key hypothesised mechanisms, rather than because of implementation challenges., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fabbri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Psychosocial interventions delivered by nonspecialists can be effective at reducing common adolescent mental health problems in low-resource settings. However, there is a lack of evidence on resource-efficient methods for building capacity to deliver these interventions., Objective: The objective of this study is to evaluate the effects of a digital training (DT) course, delivered in a self-guided format or with coaching, on nonspecialists' competency to deliver a problem-solving intervention intended for adolescents with common mental health problems in India., Methods: We will conduct a pre-post study with a nested parallel, 2-arm, individually randomized controlled trial. The study aims to recruit 262 participants, randomized 1:1 to receive either a self-guided DT course or a DT course with weekly individualized coaching provided remotely by telephone. In both arms, the DT will be accessed over 4 to 6 weeks. Participants will be nonspecialists (ie, without prior practice-based training in psychological therapies) recruited from among university students and affiliates of nongovernmental organizations in Delhi and Mumbai, India., Results: Outcomes will be assessed at baseline and 6 weeks post randomization using a knowledge-based competency measure that incorporates a multiple-choice quiz format. The primary hypothesis is that self-guided DT will lead to increased competency scores among novices with no prior experience of delivering psychotherapies. The secondary hypothesis is that digital training with coaching will have an incremental effect on competency scores compared with DT alone. The first participant was enrolled on April 4, 2022., Conclusions: The study will address an evidence gap on the effectiveness of training methods for nonspecialist providers of adolescent mental health interventions in low-resource settings. The findings from this study will be used to support wider efforts to scale up evidence-based mental health interventions for young people., Trial Registration: ClinicalTrials.gov NCT05290142; https://clinicaltrials.gov/ct2/show/NCT05290142., International Registered Report Identifier (irrid): DERR1-10.2196/41981., (©Sonal Mathur, Helen A Weiss, Melissa Neuman, Andy P Field, Baptiste Leurent, Tejaswi Shetty, James E J, Pooja Nair, Rhea Mathews, Kanika Malik, Daniel Michelson, Vikram Patel. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.06.2023.)

Background: 'POD Adventures' is a gamified problem-solving intervention delivered via smartphone app, and supported by non-specialist counsellors for a target population of secondary school students in India during the COVID-19 pandemic., Aims: To evaluate the feasibility and acceptability of undertaking a randomised controlled trial of POD Adventures when delivered online with telephone support from counsellors., Method: We conducted a parallel, two-arm, individually randomised pilot-controlled trial with 11 secondary schools in Goa, India. Participants received either the POD Adventures intervention delivered over 4 weeks or usual care comprising information about local mental health services and national helplines. Outcomes were assessed at two timepoints: baseline and 6 weeks post-randomisation., Results: Seventy-nine classroom sensitisation sessions reaching a total of 1575 students were conducted. Ninety-two self-initiated study referrals (5.8%) were received, but only 11 participants enrolled in the study. No intervention arm participants completed the intervention. Outcomes at 6 weeks were not available for intervention arm participants ( n = 5), and only four control arm participants completed outcomes. No qualitative interviews or participant satisfaction measures were completed because participants could not be reached by the study team., Conclusions: Despite modifications to address barriers arising from COVID-19 restrictions, online delivery was not feasible in the study context. Low recruitment and missing feasibility and acceptability data make it difficult to draw conclusions about intervention engagement and indicative clinical outcomes. Prior findings showing high uptake, adherence and engagement with POD Adventures when delivered in a school-based context suggest that an online study and delivery posed the biggest barriers to study participation and engagement.

Forcibly displaced children are at increased risk of violence and mental health disorders. In refugee contexts, schools are generally perceived as protective environments where children can build a sense of belonging and recover from trauma. Evidence shows that positive school climates can support student skills development and socio-emotional wellbeing and protect them against a host of adverse outcomes. However, schools are also places where children may experience violence, from both teachers and peers. Prevalence estimates of violence against children in humanitarian settings are scarce and evidence on the relationship between school climate and student outcomes in these contexts is non-existent. The aim of the study is to estimate the prevalence of school-based violence against children and to explore the association between perceptions of school climate and students' experiences and use of violence and their depression symptoms. We relied on data from a cross-sectional survey of students and teachers in all primary and secondary schools in Nyarugusu Refugee Camp in Tanzania, conducted as part of a cluster randomised controlled trial, to compute prevalence estimates and used mixed logistic regression analysis to assess the association between school climate and students' outcomes. We found that students in Nyarugusu experienced high levels of violence from both peers and teachers in both primary and secondary schools in the camp, with little difference between boys and girls. Nearly one in ten students screened positive for symptoms of depression. We found that opportunities for students and teachers to be involved in decision-making were associated with higher odds of violent discipline and teachers' self-efficacy was a significant protective factor against student depression symptoms. However, generally, school-level perceptions of school climate were not associated with student outcomes after adjusting for potential confounders. Our findings suggest that interventions to prevent and respond to teacher and peer violence in schools and to support students' mental health are urgently needed. Our results challenge the assumption that education environments are inherently protective for children and call for further investigation of norms around violence among students and teachers to better understand the role of school climate in refugee settings., (© 2022. The Author(s).)

Trial-based cost-effectiveness analyses (CEAs) are an important source of evidence in the assessment of health interventions. In these studies, cost and effectiveness outcomes are commonly measured at multiple time points, but some observations may be missing. Restricting the analysis to the participants with complete data can lead to biased and inefficient estimates. Methods, such as multiple imputation, have been recommended as they make better use of the data available and are valid under less restrictive Missing At Random (MAR) assumption. Linear mixed effects models (LMMs) offer a simple alternative to handle missing data under MAR without requiring imputations, and have not been very well explored in the CEA context. In this manuscript, we aim to familiarize readers with LMMs and demonstrate their implementation in CEA. We illustrate the approach on a randomized trial of antidepressants, and provide the implementation code in R and Stata. We hope that the more familiar statistical framework associated with LMMs, compared to other missing data approaches, will encourage their implementation and move practitioners away from inadequate methods., (© 2022 The Authors. Health Economics published by John Wiley & Sons Ltd.)

There are few treatments shown to slow disability progression in progressive multiple sclerosis (PMS). One challenge has been efficiently testing the pipeline of candidate therapies from preclinical studies in clinical trials. Multi-arm multistage (MAMS) platform trials may accelerate evaluation of new therapies compared to traditional sequential clinical trials. We describe a MAMS design in PMS focusing on selection of interim and final outcome measures, sample size, and statistical considerations. The UK MS Society Expert Consortium for Progression in MS Clinical Trials reviewed recent phase II and III PMS trials to inform interim and final outcome selection and design measures. Simulations were performed to evaluate trial operating characteristics under different treatment effect, recruitment rate, and sample size assumptions. People with MS formed a patient and public involvement group and contributed to the trial design, ensuring it would meet the needs of the MS community. The proposed design evaluates 3 experimental arms compared to a common standard of care arm in 2 stages. Stage 1 (interim) outcome will be whole brain atrophy on MRI at 18 months, assessed for 123 participants per arm. Treatments with sufficient evidence for slowing brain atrophy will continue to the second stage. The stage 2 (final) outcome will be time to 6-month confirmed disability progression, based on a composite clinical score comprising the Expanded Disability Status Scale, Timed 25-Foot Walk test, and 9-Hole Peg Test. To detect a hazard ratio of 0.75 for this primary final outcome with 90% power, 600 participants per arm are required. Assuming one treatment progresses to stage 2, the trial will recruit ≈1,900 participants and last ≈6 years. This is approximately two-thirds the size and half the time of separate 2-arm phase II and III trials. The proposed MAMS trial design will substantially reduce duration and sample size compared to traditional clinical trials, accelerating discovery of effective treatments for PMS. The design was well-received by people with multiple sclerosis. The practical and statistical principles of MAMS trial design may be applicable to other neurodegenerative conditions to facilitate efficient testing of new therapies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background and Objectives: Studies suggest that individual student-reported connection to school is associated with better mental health. However, there is less evidence for associations between schools' overall school climate and the mental health of their students. This may reflect limitations in which mental health outcomes have been examined. We conducted a large longitudinal study in schools, hypothesising that we would find associations at both the student and school levels between student-reported positive school climate, and reduced student conduct and emotional problems and improved mental wellbeing., Methods: We tracked students in 20 English secondary schools from near the end of the first year of secondary school (age 11/12) over 3 years using reliable measures of school climate and mental health., Results: We found associations between student-level reports of positive school climate at baseline, and reduced conduct and emotional problems and better mental wellbeing at 3-year follow-up adjusting for various potential confounders. We also found some evidence of adjusted associations between baseline school-level measures of overall positive climate and better student mental health at follow-up. However, these student- and school-level associations reduced considerably when also adjusting for baseline mental health., Conclusions: Our findings suggest that there are associations between school climate and student mental health at both the student and school level but these associations are complex and not necessarily causal., Competing Interests: The authors have no competing interests relevant to this article to disclose., (© 2021 The Authors.)

Background: School-based violence prevention interventions offer enormous potential to reduce children's experience of violence perpetrated by teachers, but few have been rigorously evaluated globally and, to the best of our knowledge, none in humanitarian settings. We tested whether the EmpaTeach intervention could reduce physical violence from teachers to students in Nyarugusu Refugee Camp, Tanzania., Methods and Findings: We conducted a 2-arm cluster-randomised controlled trial with parallel assignment. A complete sample of all 27 primary and secondary schools in Nyarugusu Refugee Camp were approached and agreed to participate in the study. Eligible students and teachers participated in cross-sectional baseline, midline, and endline surveys in November/December 2018, May/June 2019, and January/February 2020, respectively. Fourteen schools were randomly assigned to receive a violence prevention intervention targeted at teachers implemented in January-March 2019; 13 formed a wait-list control group. The EmpaTeach intervention used empathy-building exercises and group work to equip teachers with self-regulation, alternative discipline techniques, and classroom management strategies. Allocation was not concealed due to the nature of the intervention. The primary outcome was students' self-reported experience of physical violence from teachers, assessed at midline using a modified version of the ISPCAN Child Abuse Screening Tool-Child Institutional. Secondary outcomes included student reports of emotional violence, depressive symptoms, and school attendance. Analyses were by intention to treat, using generalised estimating equations adjusted for stratification factors. No schools left the study. In total, 1,493 of the 1,866 (80%) randomly sampled students approached for participation took part in the baseline survey; at baseline 54.1% of students reported past-week physical violence from school staff. In total, 1,619 of 1,978 students (81.9%) took part in the midline survey, and 1,617 of 2,032 students (79.6%) participated at endline. Prevalence of past-week violence at midline was not statistically different in intervention (408 of 839 students, 48.6%) and control schools (412 of 777 students, 53.0%; risk ratio = 0.91, 95% CI 0.80 to 1.02, p = 0.106). No effect was detected on secondary outcomes. A camp-wide educational policy change during intervention implementation resulted in 14.7% of teachers in the intervention arm receiving a compressed version of the intervention, but exploratory analyses showed no difference in our primary outcome by school-level adherence to the intervention. Main study limitations included the small number of schools in the camp, which limited statistical power to detect small differences between intervention and control groups. We also did not assess the test-retest reliability of our outcome measures, and interviewers were unmasked to intervention allocation., Conclusions: There was no evidence that the EmpaTeach intervention effectively reduced physical violence from teachers towards primary or secondary school students in Nyarugusu Refugee Camp. Further research is needed to develop and test interventions to prevent teacher violence in humanitarian settings., Trial Registration: clinicaltrials.gov (NCT03745573)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: the EmpaTeach intervention was developed by KR at the International Rescue Committee and MK, GTE, and ADF at the Behavioral Insights Team. They have provided input into study design but final decisions on study design and procedures were taken by KD.

Background: Although the most effective methods of contraception are available in Bolivia, unmet need for contraception among women aged 15 to 19 years is estimated to be 38% (2008), and the adolescent fertility rate is 71 per 1000 women (2016). Mobile phones are a popular mode to deliver health behavior support. We developed a contraceptive behavioral intervention for young Bolivian women delivered by mobile phone and guided by behavioral science. The intervention consists of short instant messages sent through an app over 4 months., Objective: This trial aimed to evaluate the effect of the intervention on young Bolivian women's use of and attitudes toward the effective contraceptive methods available in Bolivia., Methods: This was a parallel group, individually randomized superiority trial with a 1:1 allocation ratio. Women were eligible if they were aged 16 to 24 years, owned a personal Android mobile phone, lived in La Paz or El Alto, reported an unmet need for contraception, and could read Spanish. The target sample size was 1310 participants. Participants allocated to the intervention had access to an app with standard family planning information and intervention messages. Participants allocated to the control group had access to the same app and control messages. Coprimary outcomes were use of effective contraception and acceptability of at least one method of effective contraception at 4 months. Secondary outcomes were use of effective contraception during the study, acceptability of the individual methods, service uptake, unintended pregnancy, and abortion. Process outcomes included knowledge, perceived norms, personal agency, and intention. Outcomes were analyzed using logistic and linear regression. We also asked participants about physical violence., Results: A total of 640 participants were enrolled, and 67.0% (429) of them contributed follow-up data for the coprimary outcome, the use of effective contraception. There was no evidence that use differed between the groups (33% control vs 37% intervention; adjusted odds ratio [OR] 1.19, 95% CI 0.80 to 1.77; P=.40). There was a borderline significant effect regarding acceptability (63% control vs 72% intervention; adjusted OR 1.49, 95% CI 0.98 to 2.28; P=.06). There were no statistically significant differences in any of the secondary or process outcomes. The intervention dose received was low. In the control group, 2.8% (6/207) reported experiencing physical violence compared with 1.9% (4/202) in the intervention group (Fisher exact test P=.75)., Conclusions: This trial was unable to provide definitive conclusions regarding the effect of the intervention on use and acceptability of effective contraception because of under recruitment. Although we cannot strongly recommend implementation, the results suggest that it would be safe and may increase the acceptability of effective contraception if the intervention messages were offered alongside the download of the app., Trial Registration: ClinicalTrials.gov NCT02905526; https://clinicaltrials.gov/ct2/show/NCT02905526., (©Ona L McCarthy, Carolina Aliaga, Maria Eugenia Torrico Palacios, Jhonny López Gallardo, Silvia Huaynoca, Baptiste Leurent, Phil Edwards, Melissa Palmer, Irrfan Ahamed, Caroline Free. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.06.2020.)

Missing data are a common issue in cost-effectiveness analysis (CEA) alongside randomised trials and are often addressed assuming the data are 'missing at random'. However, this assumption is often questionable, and sensitivity analyses are required to assess the implications of departures from missing at random. Reference-based multiple imputation provides an attractive approach for conducting such sensitivity analyses, because missing data assumptions are framed in an intuitive way by making reference to other trial arms. For example, a plausible not at random mechanism in a placebo-controlled trial would be to assume that participants in the experimental arm who dropped out stop taking their treatment and have similar outcomes to those in the placebo arm. Drawing on the increasing use of this approach in other areas, this paper aims to extend and illustrate the reference-based multiple imputation approach in CEA. It introduces the principles of reference-based imputation and proposes an extension to the CEA context. The method is illustrated in the CEA of the CoBalT trial evaluating cognitive behavioural therapy for treatment-resistant depression. Stata code is provided. We find that reference-based multiple imputation provides a relevant and accessible framework for assessing the robustness of CEA conclusions to different missing data assumptions., (© 2019 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Background: Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the course of the day. It is commonly experienced during inpatient admission in the terminal phase of illness. It can cause symptoms such as agitation and hallucinations and is distressing for terminally ill people, their families and staff. Delirium may arise from any number of causes and treatment should aim to address these causes. When this is not possible, or treatment is unsuccessful, drug therapy to manage the symptoms may become necessary. This is the second update of the review first published in 2004., Objectives: To evaluate the effectiveness and safety of drug therapies to manage delirium symptoms in terminally ill adults., Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO from inception to July 2019, reference lists of retrieved papers, and online trial registries., Selection Criteria: We included randomised controlled trials of drug therapies in any dose by any route, compared to another drug therapy, a non-pharmacological approach, placebo, standard care or wait-list control, for the management of delirium symptoms in terminally ill adults (18 years or older)., Data Collection and Analysis: We independently screened citations, extracted data and assessed risk of bias. Primary outcomes were delirium symptoms; agitation score; adverse events. Secondary outcomes were: use of rescue medication; cognitive status; survival. We applied the GRADE approach to assess the overall quality of the evidence for each outcome and we include eight 'Summary of findings' tables., Main Results: We included four studies (three new to this update), with 399 participants. Most participants had advanced cancer or advanced AIDS, and mild- to moderate-severity delirium. Meta-analysis was not possible because no two studies examined the same comparison. Each study was at high risk of bias for at least one criterion. Most evidence was low to very low quality, downgraded due to very serious study limitations, imprecision or because there were so few data. Most studies reported delirium symptoms; two reported agitation scores; three reported adverse events with data on extrapyramidal effects; and none reported serious adverse events. 1. Haloperidol versus placebo There may be little to no difference between placebo and haloperidol in delirium symptoms within 24 hours (mean difference (MD) 0.34, 95% confidence interval (CI) -0.07 to 0.75; 133 participants). Haloperidol may slightly worsen delirium symptoms compared with placebo at 48 hours (MD 0.49, 95% CI 0.10 to 0.88; 123 participants with mild- to moderate-severity delirium). Haloperidol may reduce agitation slightly compared with placebo between 24 and 48 hours (MD -0.14, 95% -0.28 to -0.00; 123 participants with mild- to moderate-severity delirium). Haloperidol probably increases extrapyramidal adverse effects compared with placebo (MD 0.79, 95% CI 0.17 to 1.41; 123 participants with mild- to moderate-severity delirium). 2. Haloperidol versus risperidone There may be little to no difference in delirium symptoms with haloperidol compared with risperidone within 24 hours (MD -0.42, 95% CI -0.90 to 0.06; 126 participants) or 48 hours (MD -0.36, 95% CI -0.92 to 0.20; 106 participants with mild- to moderate-severity delirium). Agitation scores and adverse events were not reported for this comparison. 3. Haloperidol versus olanzapine We are uncertain whether haloperidol reduces delirium symptoms compared with olanzapine within 24 hours (MD 2.36, 95% CI -0.75 to 5.47; 28 participants) or 48 hours (MD 1.90, 95% CI -1.50 to 5.30, 24 participants). Agitation scores and adverse events were not reported for this comparison. 4. Risperidone versus placebo Risperidone may slightly worsen delirium symptoms compared with placebo within 24 hours (MD 0.76, 95% CI 0.30 to 1.22; 129 participants); and at 48 hours (MD 0.85, 95% CI 0.32 to 1.38; 111 participants with mild- to moderate-severity delirium). There may be little to no difference in agitation with risperidone compared with placebo between 24 and 48 hours (MD -0.05, 95% CI -0.19 to 0.09; 111 participants with mild- to moderate-severity delirium). Risperidone may increase extrapyramidal adverse effects compared with placebo (MD 0.73 95% CI 0.09 to 1.37; 111 participants with mild- to moderate-severity delirium). 5. Lorazepam plus haloperidol versus placebo plus haloperidol We are uncertain whether lorazepam plus haloperidol compared with placebo plus haloperidol improves delirium symptoms within 24 hours (MD 2.10, 95% CI -1.00 to 5.20; 50 participants with moderate to severe delirium), reduces agitation within 24 hours (MD 1.90, 95% CI 0.90 to 2.80; 52 participants), or increases adverse events (RR 0.70, 95% CI -0.19 to 2.63; 31 participants with moderate to severe delirium). 6. Haloperidol versus chlorpromazine We are uncertain whether haloperidol reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 0.37, 95% CI -4.58 to 5.32; 24 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with chlorpromazine (MD 0.46, 95% CI -4.22 to 5.14; 24 participants). 7. Haloperidol versus lorazepam We are uncertain whether haloperidol reduces delirium symptoms compared with lorazepam at 48 hours (MD -4.88, 95% CI -9.70 to 0.06; 17 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with lorazepam (MD -6.66, 95% CI -14.85 to 1.53; 17 participants). 8. Lorazepam versus chlorpromazine We are uncertain whether lorazepam reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 5.25, 95% CI 0.38 to 10.12; 19 participants), or increases adverse events (MD 7.12, 95% CI 1.08 to 15.32; 18 participants). Agitation scores were not reported., Secondary Outcomes: use of rescue medication, cognitive impairment, survival There were insufficient data to draw conclusions or assess GRADE., Authors' Conclusions: We found no high-quality evidence to support or refute the use of drug therapy for delirium symptoms in terminally ill adults. We found low-quality evidence that risperidone or haloperidol may slightly worsen delirium symptoms of mild to moderate severity for terminally ill people compared with placebo. We found moderate- to low-quality evidence that haloperidol and risperidone may slightly increase extrapyramidal adverse events for people with mild- to moderate-severity delirium. Given the small number of studies and participants on which current evidence is based, further research is essential., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Research has shown that mobile phone contraceptive behavioral interventions can increase knowledge and use of contraception, but other studies have failed to demonstrate a beneficial effect. The objective of this trial was to estimate the effect of a contraceptive behavioral intervention delivered by mobile phone text message on young Palestinian women's attitudes towards effective contraception., Methods: We conducted a randomized controlled trial among women aged 18-24 years living in the West Bank, who were not using an effective method of contraception. The intervention group received zero to three messages per day (113 messages for female-not married and 120 messages for female-married) for 120 days. The control group received 16 messages over 120 days about trial participation. The primary outcome was acceptability of at least one method of effective contraception at 4 months. Secondary outcomes were use of effective contraception at 4 months and any use during the study, acceptability of individual methods, service uptake, unintended pregnancy and abortion. Process outcomes included knowledge, perceived norms, personal agency and intention. All outcomes were self-reported. We analyzed the outcomes using logistic and linear regression., Results: A total of 578 participants were enrolled and 464 (80%) completed follow up at 4 months. Intervention group participants were more likely to find at least one method of effective contraception acceptable (31% in the intervention group versus 17% in the control group, adjusted OR 2.34, 95% CI 1.48-3.68, p < 0.001). They had a higher mean knowledge score, were more likely to find the intrauterine device, injection, implant and patch acceptable, to agree that their friends would use an effective method and to intend to use an effective method, compared to participants in the control group. While in the direction of intervention benefit, there were no differences between the groups in the use of effective contraception at 4 months and any use during the study, pill acceptability, service uptake, unintended pregnancy and induced abortion., Conclusions: The intervention can improve attitudes, knowledge-perceived norms and intention to use effective contraception among young women in Palestine. Research is needed to evaluate the efficacy of the intervention for contraceptive behavioral outcomes in Palestine., Trial Registration: ClinicalTrials.gov, NCT02905461 . Registered on 14 September 2016. World Health Organization Trial Registration Data Set: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02905461.

Objective: Ten Top Tips (10TT) is a primary care-led behavioural intervention which aims to help adults reduce and manage their weight by following 10 weight loss tips. The intervention promotes habit formation to encourage long-term behavioural changes. The aim of this study was to estimate the cost-effectiveness of 10TT in general practice from the perspective of the UK National Health Service., Design: An economic evaluation was conducted alongside an individually randomised controlled trial., Setting: 14 general practitioner practices in England., Participants: All patients were aged ≥18 years, with body mass index ≥30 kg/m 2 . A total of 537 patients were recruited; 270 received the usual care offered by their practices and 267 received the 10TT intervention., Outcomes Measures: Health service use and quality-adjusted life years (QALYs) were measured over 2 years. Analysis was conducted in terms of incremental net monetary benefits (NMBs), using non-parametric bootstrapping and multiple imputation., Results: Over a 2-year time horizon, the mean costs and QALYs per patient in the 10TT group were £1889 (95% CI £1522 to £2566) and 1.51 (95% CI 1.44 to 1.58). The mean costs and QALYs for usual care were £1925 (95% CI £1599 to £2251) and 1.51 (95% CI 1.45 to 1.57), respectively. This generated a mean cost difference of -£36 (95% CI -£512 to £441) and a mean QALY difference of 0.001 (95% CI -0.080 to 0.082). The incremental NMB for 10TT versus usual care was £49 (95% CI -£1709 to £1800) at a maximum willingness to pay for a QALY of £20 000. 10TT had a 52% probability of being cost-effective at this threshold., Conclusions: Costs and QALYs for 10TT were not significantly different from usual care and therefore 10TT is as cost-effective as usual care. There was no evidence to recommend nor advice against offering 10TT to obese patients in general practices based on cost-effectiveness considerations., Trial Registration Number: ISRCTN16347068; Post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Cost-effectiveness analyses (CEA) of randomised controlled trials are a key source of information for health care decision makers. Missing data are, however, a common issue that can seriously undermine their validity. A major concern is that the chance of data being missing may be directly linked to the unobserved value itself [missing not at random (MNAR)]. For example, patients with poorer health may be less likely to complete quality-of-life questionnaires. However, the extent to which this occurs cannot be ascertained from the data at hand. Guidelines recommend conducting sensitivity analyses to assess the robustness of conclusions to plausible MNAR assumptions, but this is rarely done in practice, possibly because of a lack of practical guidance. This tutorial aims to address this by presenting an accessible framework and practical guidance for conducting sensitivity analysis for MNAR data in trial-based CEA. We review some of the methods for conducting sensitivity analysis, but focus on one particularly accessible approach, where the data are multiply-imputed and then modified to reflect plausible MNAR scenarios. We illustrate the implementation of this approach on a weight-loss trial, providing the software code. We then explore further issues around its use in practice.

After publication of the original article [1], it came to the authors' attention that there is a typo in the Results section.

Background: Unintended pregnancy is associated with poorer health outcomes for women and their families. In Tajikistan, around 26% of married 15-24 year old women have an unmet need for contraception. There is some evidence that interventions delivered by mobile phone can affect contraceptive-related behaviour and knowledge. We developed an intervention delivered by mobile phone app instant messaging to improve acceptability of effective contraceptive methods among young people in Tajikistan., Methods: This was a randomized controlled trial among Tajik people aged 16-24. Participants allocated to the intervention arm had access to an app plus intervention messages. Participants allocated to the control arm had access to the app plus control messages. The primary outcome was acceptability of at least one method of effective contraception at 4 months. Secondary outcomes were use of effective contraception at 4 months and during the study, acceptability of individual methods, service uptake, unintended pregnancy and induced abortion. Process outcomes were knowledge, perceived norms, personal agency and intention. Outcomes were analysed using logistic and linear regression. We conducted a pre-specified subgroup analysis and a post-hoc analysis of change in acceptability from baseline to follow-up., Results: Five hundred and seventy-three participants were enrolled. Intervention content was included on the app, causing contamination. Four hundred and seventy-two (82%) completed follow-up for the primary outcome. There was no evidence of a difference in acceptability of effective contraception between the groups (66% in the intervention arm vs 64% in the control arm, adjusted OR 1.21, 95% CI .80-1.83, p = 0.36). There were no differences in the secondary or process outcomes between groups. There was some evidence that the effect of the intervention was greater among women compared to men (interaction test p = 0.03). There was an increase in acceptability of effective contraception from baseline to follow-up (2% to 65%, p < 0.001)., Conclusions: The whole intervention delivered by instant messaging provided no additional benefit over a portion of the intervention delivered by app pages. The important increase in contraceptive acceptability from baseline to follow-up suggests that the intervention content included on the app may influence attitudes. Further research is needed to establish the effect of the intervention on attitudes towards and use of effective contraception among married/sexually active young people., Trial Registration: Clinicaltrial.gov NCT02905513 . Date of registration: 14 September 2016.

Objectives: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period., Methods: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification., Results: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10 5 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/10 5 (+126%; P<0.001) and for UC, from 1.6 to 4.1/10 5 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC., Conclusions: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Background: Unintended pregnancy is associated with numerous poorer health outcomes for both women and their children. Fulfilling unmet need for contraception is essential in avoiding unintended pregnancies, yet millions of women in low- and middle-income countries continue to face obstacles in realizing their fertility desires. In Bolivia, family planning progress has improved in recent decades but lags behind other countries in the region. Unmet need for contraception among women aged 15 to 19 years is estimated to be 38%, with the adolescent fertility rate at 70 per 1000 women. Mobile phones are an established and popular mode in which to deliver health behavior support. The London School of Hygiene & Tropical Medicine and the Centro de Investigación, Educación y Servicios in Bolivia have partnered to develop and evaluate a contraceptive behavioral intervention for Bolivian young women delivered by mobile phone. The intervention was developed guided by behavioral science and consists of short instant messages sent through an app over 4 months., Objective: The objective of this study is to evaluate the effect of the intervention on young women's use of and attitudes toward the most effective contraceptive methods., Methods: We will allocate 1310 women aged 16 to 24 years with an unmet need for contraception in a 1:1 ratio to receive the intervention messages or the control messages about trial participation. The messages are sent through the Tú decides app, which contains standard family planning information. Coprimary outcomes are use and acceptability of at least one effective contraceptive method, both measured at 4 months., Results: Recruitment commenced on March 1, 2017 and was completed on July 29, 2017. We estimate that the follow-up period will end in January 2018., Conclusions: This trial will evaluate the effect of the intervention on young women's use of and attitudes toward the (nonpermanent) effective contraception methods available in Bolivia., Trial Registration: ClinicalTrials.gov NCT02905526; https://clinicaltrials.gov/ct2/show/NCT02905526 (Archived by WebCite at http://www.webcitation.org/6vT0yIFfN)., (©Ona L McCarthy, Veronica Osorio Calderon, Shelly Makleff, Silvia Huaynoca, Baptiste Leurent, Phil Edwards, Jhonny Lopez Gallardo, Caroline Free. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.12.2017.)

Background: Unintended pregnancy can negatively impact women's lives and is associated with poorer health outcomes for women and children. Many women, particularly in low- and middle-income countries, continue to face obstacles in avoiding unintended pregnancy. In the State of Palestine, a survey conducted in 2006 estimated that 38% of pregnancies are unintended. In 2014, unmet need for contraception was highest among young women aged 20-24 years, at 15%. Mobile phones are increasingly being used to deliver health support. Once developed, interventions delivered by mobile phone are often cheaper to deliver than face-to-face support. The London School of Hygiene and Tropical Medicine and the Palestinian Family Planning and Protection Association have partnered to develop and evaluate a contraceptive behavioural intervention for young women in Palestine delivered by mobile phone. The intervention was developed guided by behavioural science and consists of short, mobile phone text messages that contain information about contraception and behaviour change methods delivered over 4 months., Methods: We will evaluate the intervention by conducting a randomised controlled trial. Five hundred and seventy women aged 18-24 years, who do not report using an effective method of contraception, will be allocated with a 1:1 ratio to receive the intervention text messages or control text messages about trial participation. The primary outcome is self-reported acceptability of at least one method of effective contraception at 4 months. Secondary outcomes include the use of effective contraception, acceptability of individual methods, discontinuation, service uptake, unintended pregnancy and abortion. Process outcomes include knowledge, perceived norms, personal agency and intervention dose received. Outcomes at 4 months will be compared between arms using logistic regression., Discussion: This trial will determine the effect of the intervention on young women's attitudes towards the most effective methods of contraception. If the intervention is found to be effective, the intervention will be implemented widely across Palestine. The results could also be used to design a larger trial to establish its effect on unintended pregnancy., Trial Registration: ClinicalTrials.gov, ID: NCT02905461 . Registered on 14 September 2016.

Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.

Introduction: Women in lower income countries experience unintended pregnancies at a higher rate compared with women in higher income countries. Unintended pregnancy is associated with numerous poorer health outcomes for both women and their children. In Tajikistan, an estimated 26% of married individuals aged 15-24 years have an unmet need for contraception. The strong cultural value placed on childbearing and oppositional attitudes towards contraception are major barriers to contraceptive uptake in the country.Mobile phone ownership is widespread in Tajikistan. The option of receiving reproductive health support on your personal phone may be an appealing alternative to attending a clinic, particularly for young people. The London School of Hygiene & Tropical Medicine and the Tajik Family Planning Association have partnered to develop and evaluate a contraceptive behavioural intervention delivered by mobile phone. The intervention was developed in 2015-2016 guided by behavioural science. It consists of short instant messages sent through an app over 4 months, contains information about contraception and behaviour change methods., Methods and Analysis: This randomised controlled trial is designed to evaluate the effect of the intervention on self-reported acceptability of effective contraception at 4 months. 570 men and women aged 16-24 years will be allocated with a ratio of 1:1 to receive the intervention messages or the control messages about trial participation. The messages will be sent through the Tajik Family Planning Association's 'healthy lifestyles' app, which contains basic information about contraception., Ethics and Dissemination: The trial was granted ethical approval by the London School of Hygiene & Tropical Medicine Interventions Research Ethics Committee on 16 May 2016 and by the Tajik National Scientific and Research Centre on Paediatrics and Child Surgery on 15 April 2016. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated to study stakeholders., Trial Registration Number: Clinicaltrial.gov NCT02905513., Date of Registration: 14 September 2016. WHO TRIAL REGISTRATION DATASET: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02905513., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)