Search

The recent Typhoid Fever Surveillance in Africa Program demonstrated an overall adjusted incidence of typhoid fever 2–3 times higher than previous estimates in Africa. Recently, a single-dose typhoid conjugate vaccine that allows infants as young as 6 months old to be vaccinated was prequalified by the World Health Organization (WHO). This Vi-based conjugate vaccine demonstrated robust immunogenicity after 1 dose in infants and children 6 through 23 months of age in India with no safety signal, and is currently being tested for the first time on the African continent in Malawi. The WHO Strategic Advisory Group of Experts recommends studies to evaluate co-administering Vi-typhoid conjugate vaccine (Vi-TCV) with routine childhood vaccines in typhoid-endemic countries. The Burkina Faso immunization schedule includes yellow fever vaccine (YFV) at 9 months and meningococcal A conjugate vaccine (MCV-A) at 15 months, in addition to measles-rubella vaccine at both 9 and 15 months. Co-administration testing of Vi-TCV with these routine vaccinations will provide the data needed to support large-scale uptake of Vi-TCV in sub-Saharan Africa. A randomized, controlled, Phase II trial of Vi-TCV co-administration with the vaccinations routinely given at 9 and 15 months of age is planned in Burkina Faso. The overall aim is to assess the safety and immunogenicity of Vi-TCV when co-administered with YFV at 9 months of age and with MCV-A at 15 months of age. A total of 250 participants (100 infants aged 9–11 months and 150 children aged 15–23 months) will be enrolled. Clinical Trials Registration. NCT03614533. [ABSTRACT FROM AUTHOR]

Background We aimed to elucidate household and community-level shedding and transmission of trivalent oral polio vaccine (tOPV) in communities with inactivated polio vaccine (IPV) routine immunization after tOPV is administered during a national health week (NHW). Methods We conducted a 3-arm, randomized trial with data collected at baseline through 10 weeks post-NHW in households with at least 1 child <5 years old in 3 semi-rural communities in Orizaba, Mexico. Selected communities were geographically isolated but socio-demographically similar. Each community was assigned an oral polio vaccine (OPV) immunization rate: 10, 30, or 70% of participating households. From 2653 households in the 3 communities, ~150 households per community were selected, for 466 in total. Households were randomized as vaccinated or unvaccinated, with only 1 child under 5 in the vaccinated household receiving OPV during the February 2015 NHW. No other community members received OPV during this NHW. Stool samples were collected up to 10 weeks post-vaccination for all members of the 466 study households and were analyzed for the presence of OPV serotypes using a multiplex polymerase chain reaction assay. Results We will report on the factors associated with, and incidence and duration of, household and community shedding and transmission of OPV. The secondary outcomes will characterize temporal and geospatial OPV serotype shedding patterns. Conclusions The current global polio eradication plan relies on transitioning away from OPV to IPV. This study contributes to understanding patterns of OPV shedding and transmission dynamics in communities with primary IPV immunity, in order to optimize the reduction of OPV transmission. [ABSTRACT FROM AUTHOR]

Background Emollients are universally recommended for atopic dermatitis/eczema ('eczema'), to improve the skin barrier and reduce symptoms. However, our knowledge of the frequency and nature of adverse effects associated with their use is limited. Objectives We sought to determine how well adverse events are reported in randomized controlled trials (RCTs) of emollients for eczema. Methods MEDLINE was searched from inception (1946) to May 2022. Inclusion criteria were RCTs of moisturizers or emollients used as a leave-on treatment (as the intervention or control) in adults or children with eczema. Exclusion criteria were non-RCTs; patients with other diagnoses included; use of emollient as bath additives, soap substitutes or as preventative; and not published in English. References of eligible papers were reviewed for any additional, relevant research. Data were extracted into an Excel spreadsheet and analysed descriptively. An assessment of study quality was carried out using the Joanna Briggs Institute tool for RCTs. Results From 369 potential papers, 35 papers (reporting on 34 studies) were included. Most research was conducted in research centres or hospitals (unclear in 34%). In total, 89% reported collecting data on adverse events related to emollient treatment use but the methods used were poorly reported (40% unclear). Four papers used patient questionnaires/diaries. However, it was unclear how and what was collected as only two studies showed the questionnaires used. Conclusions Reporting of adverse events related to emollient use in trials of patients with eczema is poor and inconsistent. Agreement should be reached on how and what adverse events should be collected, to standardize reporting across studies. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence for effective obesity treatment programs that engage men. Purpose: This study evaluated the efficacy of two gender-tailored weight loss interventions for men, which required no face-to-face contact. Methods: This was a three-arm, randomized controlled trial: (1) Resources ( n = 54), gender-tailored weight loss materials (DVD, handbooks, pedometer, tape measure); (2) Online ( n = 53), Resources materials plus study website and e-feedback; and (3) Wait-list control ( n = 52). The interventions lasted 3 months and were grounded in Social Cognitive Theory. Results: At 6 months, significantly greater weight loss was observed for the Online (−4.7 kg; 95 % CI −6.1, −3.2) and Resources (−3.7 kg; 95 % CI −4.9, −2.5) groups compared to the control (−0.5 kg; 95 % CI −1.4, 0.4). Additionally, both intervention groups significantly improved body mass index, percent body fat, waist circumference, blood pressure, physical activity, quality of life, alcohol risk, and portion size, compared to controls. Conclusions: Men achieved significant weight loss after receiving novel, minimal-contact, gender-tailored programs, which were designed for widespread dissemination. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses risk of bias in the papers and letters reporting dermatological randomized controlled trials.

Objectives To assess the changes in compliance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized controlled trials (RCTs) in four orthodontic journals. To assess whether reporting of randomization, concealment, and blinding has improved. Methods Electronic hand searching was undertaken to identify orthodontic RCTs published in four orthodontic journals from January 2016 to June 2017 (T1) and from January 2019 to June 2020 (T2). The journals were the American Journal of Orthodontics and Dentofacial Orthopaedics (AJO-DO), Angle Orthodontist (AO), European Journal of Orthodontics (EJO), and Journal of Orthodontics (JO). Each item on the CONSORT checklist was scored as either reported, not reported, or not applicable for each paper reporting an RCT. Results The study included 69 papers reporting an RCT published in T1 and 64 RCTs published in T2. The median CONSORT score in T1 was 48.7% (interquartile range [IQR] 27.6%, 68.6%) and 67% in T2 (IQR 43.9%, 79.5%). This increase was statistically significant (P = 0.001) and largely attributable to improved reporting in AO (P = 0.016) and EJO (P = 0.023). Reporting did not change significantly in AJO-DO (P = 0.13) or in JO (P = 1.0). Reporting of random allocation sequence generation (OR 2.09; 95% CI 1.01, 4.29) and concealment of allocation (OR 2.27%, 95% CI 1.12, 4.57) were significantly higher in T2 compared with T1. Reporting of blinding did not change significantly. Conclusion Overall reporting of CONSORT items in reports of orthodontic RCTs published in the AJO-DO, AO, EJO, and JO, improved significantly from 2016–17 to 2019–20. This could be improved further by authors, journal referees, and editors adhering to the guidelines. [ABSTRACT FROM AUTHOR]

When properly implemented, Randomized Controlled Trials (RCT) achieve a high degree of internal validity. Yet, if an RCT is to inform policy, it is critical to establish external validity. This paper systematically reviews all RCTs conducted in developing countries and published in leading economic journals between 2009 and 2014 with respect to how they deal with external validity. Following Duflo, Glennerster and Kremer (2008), we scrutinize the following hazards to external validity: Hawthorne effects, general equilibrium effects, specific sample problems and special care in treatment provision. Based on a set of objective indicators, we find that the majority of published RCTs does not discuss these hazards and many do not provide the necessary information to assess potential problems. The paper calls for including external validity dimensions in a more systematic reporting on the results of RCTs. Thismay create incentives to avoid overgeneralizing findings and help policymakers to interpret results appropriately. [ABSTRACT FROM AUTHOR]

Purpose of the Study This mixed-methods study explored the feasibility and acceptability of using a tablet-based research consent process with adults aged ≥65 years. Design and Methods In the first phase, focus group participants reported on their perceptions of a tablet-based consent process. In the second phase, older adults were randomized to view either a tablet-based or paper-based consent for a mock clinical trial. Measurements included: time to complete, adverse/unexpected events, user-friendliness, immediate comprehension, and retention at a 1-week delay. Results Focus group participants (N = 15) expressed interest in the novel format, cautioning that peers would need comprehensive orientation to use the technology. In the randomized pilot (N = 20), retention was 100% and all participants completed the protocol without the occurrence of adverse/unexpected events. Although the participants took longer to complete the tablet-based consent than the paper-based version, user-friendliness, immediate comprehension, and retention of the tablet-based consent were similar to the paper-based consent. Discussion and Implications The findings suggest that a tablet-based consent process is feasible to implement with older adults and acceptable to this population, but we would underscore that efforts to optimize design of tablet-based consent forms for older adults are warranted. [ABSTRACT FROM AUTHOR]

Background Chronic pain (CP) remains the second commonest reason for being off work. Tertiary return to work (RTW) interventions aim to improve psychological and physical capacity amongst workers already off sick. Their effectiveness for workers with CP is unclear. Aims To explore which tertiary interventions effectively promote RTW for CP sufferers. Methods We searched eight databases for randomized controlled trials evaluating the effectiveness of tertiary RTW interventions for CP sufferers. We employed the Cochrane Risk of Bias (ROB) and methodological quality assessment tools for all included papers. We synthesized findings narratively. Meta-analysis was not possible due to heterogeneity of study characteristics. Results We included 16 papers pertaining to 13 trials. The types, delivery format and follow-up schedules of RTW interventions varied greatly. Most treatments were multidisciplinary, comprising psychological, physical and workplace elements. Five trials reported that tertiary interventions with multidisciplinary elements promoted RTW for workers with CP compared to controls. We gave a high ROB rating for one or more assessment criteria to three out of the five successful intervention trials. Two had medium- and low-risk elements across all categories. One compared different intensity multidisciplinary treatment and one comprised work-hardening with a job coach. Seven trials found treatment effects for secondary outcomes but no RTW improvement. Conclusions There is no conclusive evidence to support any specific tertiary RTW intervention for workers with CP, but multidisciplinary efforts should be considered. Workers' compensation is an important area for RTW policymakers to consider. [ABSTRACT FROM AUTHOR]

There exist a wide variety of statistical methods for clinical trials. Despite decades of clinical trial research, little is known about which methods are used in data analysis practice of the real world. This review describes the evidence of existing practices on survival data analysis and identifies potential opportunities to improve them. [ABSTRACT FROM AUTHOR]

This scoping review aims to identify and critically appraise published economic evaluations of self-help group (SHG) interventions in low- and middle-income countries (LMICs) that seek to improve health and potentially also non-health outcomes. Through a systematic search of MEDLINE ALL (Ovid), EMBASE Ovid, PsychINFO, EconLit (Ovid) and Global Index Medicus, we identified studies published between 2014 and 2020 that were based in LMICs, included at least a health outcome, estimated intervention costs and reported the methods used. We critically analysed whether the methods employed can meaningfully inform decisions by ministries of health and other sectors, including donors, regarding whether to fund such interventions, and prioritized the aspects of evaluations that support decision-making and cross-sectoral decision-making especially. Nine studies met our inclusion criteria. Randomized controlled trials were the most commonly used vehicle to collect data and to establish a causal effect across studies. While all studies clearly stated one or more perspectives justifying the costs and effects that are reported, few papers clearly laid out the decision context or the decision maker(s) informed by the study. The latter is required to inform which costs, effects and opportunity costs are relevant to the decision and should be included in the analysis. Costs were typically reported from the provider or health-care sector perspective although other perspectives were also employed. Four papers reported outcomes in terms of a generic measure of health. Contrary to expectation, no studies reported outcomes beyond health. Our findings suggest limitations in the extent to which published studies are able to inform decision makers around the value of implementing SHG interventions in their particular context. Funders can make better informed decisions when evidence is presented using a cross-sectoral framework. [ABSTRACT FROM AUTHOR]

Jager and Leek have tried to estimate a false-discovery rate (FDR) in abstracts of articles published in five medical journals during 2000–2010. Their approach is flawed in sampling, calculations, and conclusions. It uses a tiny portion of select papers in highly select journals. Randomized controlled trials and systematic reviews (designs with the lowest anticipated false-positive rates) are 52% of the analyzed papers, while these designs account for only 4% in PubMed in the same period. The FDR calculations consider the entire published literature as equivalent to a single genomic experiment where all performed analyses are reported without selection or distortion. However, the data used are the P-values reported in the abstracts of published papers; these P-values are a highly distorted, highly select sample. Besides selective reporting biases, all other biases, in particular confounding in observational studies, are also ignored, while these are often the main drivers for high false-positive rates in the biomedical literature. A reproducibility check of the raw data shows that much of the data Jager and Leek used are either wrong or make no sense: most of the usable data were missed by their script, 94% of the abstracts that reported ≥2 P-values had high correlation/overlap between reported outcomes, and only a minority of P-values corresponded to relevant primary outcomes. The Jager and Leek paper exemplifies the dreadful combination of using automated scripts with wrong methods and unreliable data. Sadly, this combination is common in the medical literature. [ABSTRACT FROM PUBLISHER]

The article offers information on the new section of the "British Journal of Dermatology" (BJD) entitled "Putting Papers into Practice." It states that the new section aimed to alert busy readers regarding the important papers from the broader dermatological and general medical literature which are significant to the clinical research or practice in dermatology. Moreover, it will discuss observational studies in dermatology, randomized controlled trials, and advancement in research reporting.

Summary: Randomized trials (RTs) are used to learn about treatment effects. This paper studies identification of average treatment response (ATR) and average treatment effect (ATE) from RT data under various assumptions. The focus is the problem of external validity of the RT. RT data need not point identify the ATR or ATE because of selective participation in the RT. The paper reports partial‐identification and point‐identification results for the ATR and ATE based on RT data under a variety of assumptions. The results include assumptions sufficient to point identify the ATR or ATE from RT data. Under weaker assumptions, the ATR or ATE is partially identified. Further, attention is given to identification of the sign of the ATE and identification of whether participation in the RT is selective. Finally, identification from RT data is compared to identification from observational data. [ABSTRACT FROM AUTHOR]

Treatment switching in a randomized controlled trial occurs when a patient in one treatment arm switches to another arm during follow‐up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously bias the estimated treatment causal effect. In this paper, we aim to account for the potential impact of treatment switching in a reanalysis evaluating the treatment effect of nucleoside reverse transcriptase inhibitors (NRTIs) on a safety outcome (time to first severe or worse sign or symptom) in participants receiving a new antiretroviral regimen that either included or omitted NRTIs in the optimized treatment that includes or omits NRTIs trial. We propose an estimator of a treatment causal effect for a censored time to event outcome under a structural cumulative survival model that leverages randomization as an instrumental variable to account for selective treatment switching. We establish that the proposed estimator is uniformly consistent and asymptotically Gaussian, with a consistent variance estimator and confidence intervals given, whose finite‐sample performance is evaluated via extensive simulations. An R package 'ivsacim' implementing all proposed methods is freely available on R CRAN. Results indicate that adding NRTIs versus omitting NRTIs to a new optimized treatment regime may increase the risk for a safety outcome. [ABSTRACT FROM AUTHOR]

Estimation of empirical relationships is prone to bias. Economists have carefully studied sources of bias in structural and quasi-experimental approaches, but the randomized control trial (RCT) has only begun to receive such scrutiny. In this paper, we argue that several lessons from medicine, derived from analysis of thousands of RCTs establishing a clear link between certain practices and biased estimates, can be used to reduce the risk of bias in economics RCTs. We identify the subset of these lessons applicable to economics and use them to assess risk of bias in estimates from economics RCTs published between 2001 and 2011. In comparison to medical studies, we find most economics studies do not report important details on study design necessary to assess risk of bias. Many report practices that suggest risk of bias, though this does not necessarily mean bias resulted. We conclude with suggestions on how to remedy these issues. [ABSTRACT FROM AUTHOR]

Teaching epidemiological concepts in academic settings poses a challenge due to the intricate nature of the discipline as both a science and a practice. Whereas traditional classroom-based teaching methods are commonly employed, evidence suggests they may not be the most effective approach for fostering core competencies and skills required in real-life scientific work. In this article, we describe our process of transitioning from traditional classroom teaching of epidemiology towards practice-based coaching to convey epidemiological concepts to bachelor's and master's students in Biomedicine. We chose the framework of randomized controlled trials (RCT) since they offer a great opportunity to teach epidemiological concepts in a hands-on course. This practice-based course encompasses the entire life cycle of a study, allowing students to design and conduct a short-term experiment, analyse its data and prepare a scientific paper. We provide a comprehensive overview of the course structure, content, learning objectives and course evaluation, while also discussing the advantages and disadvantages of this innovative format. Our approach offers a promising alternative to classroom teaching by incorporating practical, hands-on experiences offering students a high level of independence and self-determination, as well as facilitation and coaching by faculty. It has the potential to be applied across diverse academic settings, providing students with valuable skills and competencies in epidemiology. [ABSTRACT FROM AUTHOR]

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P  = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P  = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P  = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this. [ABSTRACT FROM AUTHOR]

Objective To compare two ways of combining postal and electronic data collection for a maternity services user-experience survey. Design Cross-sectional survey. Setting Maternity services in Norway. Participants All women who gave birth at a university hospital in Norway between 1 June and 27 July 2010. Intervention Patients were randomized into the following groups (n= 752): Group A, who were posted questionnaires with both electronic and paper response options for both the initial and reminder postal requests; and Group B, who were posted questionnaires with an electronic response option for the initial request, and both electronic and paper response options for the reminder postal request. Main outcome measures Response rate, the amount of difference in background variables between respondents and non-respondents, main study results and estimated cost-effectiveness. Results The final response rate was significantly higher in Group A (51.9%) than Group B (41.1%). None of the background variables differed significantly between the respondents and non-respondents in Group A, while two variables differed significantly between the respondents and non-respondents in Group B. None of the 11 user-experience scales differed significantly between Groups A and B. The estimated costs per response for the forthcoming national survey was €11.7 for data collection Model A and €9.0 for Model B. Conclusions The model with electronic-only response option in the first request had lowest response rate. However, this model performed equal to the other model on non-response bias and better on estimated cost-effectiveness, and is the better of the two models in large-scale user experiences surveys with maternity services. [ABSTRACT FROM PUBLISHER]

The phenomenon of widespread genetic ancestry testing has raised questions about its social impact, particularly on issues of race. Some accounts suggest testing can promote bridging social capital – connections between racial groups. In this multi-method paper, we ask whether (1) taking genetic ancestry tests (GATs) and (2) receiving results of African, Asian, or Native American ancestry increases network racial diversity for White Americans. We use a randomized controlled trial of 802 White, non-Hispanic Americans, half of whom received GATs. Unexpected findings show that test-takers' network racial diversity decreases after testing. Using 58 follow-up interviews, we develop and test a possible theory, finding initial evidence that test-takers' network racial diversity declines because they reconsider their racial appraisals of others in their networks. [ABSTRACT FROM AUTHOR]

Background In the work and stress literature, surprisingly few studies of stress management interventions have evaluated effects on the perceived psychosocial work environment. Using data from a randomized controlled trial we investigated whether the perceived psychosocial work environment and overcommitment to work improved following a group-based, cognitive-behavioural stress management intervention. Aims We hypothesized that the participants would experience less job demand, overcommitment and effort-reward imbalance (ERI) as well as higher job control following the intervention. Methods Using a wait-list controlled design, 102 participants were randomized to either an intervention group or a wait-list control group. Outcome measures were assessed at baseline and follow-up after three, six and nine months, and analysed using mixed model univariate repeated measures analyses of variance. Results are presented as effect sizes using Cohen's d with confidence intervals (95% CI). Results Changes from 0 to 3 months for the intervention group were significantly superior to changes for the wait-list control group on all outcomes. The controlled effect size for job demands was d = 0.42 (0.01–0.84 95% CI), for job control d = 0.39 (0.06–0.71 95% CI), for effort-reward imbalance d = 0.61 (0.22–1.01 95% CI) and for overcommitment d = 0.44 (0.06–0.81 95% CI). Improvements were maintained at three months follow-up after the end of treatment. Conclusions The intervention improved the perceived psychosocial work environment and attitude to work with small-medium effect sizes. To our knowledge, this is the first paper from a randomized controlled trial of a stress-management intervention reporting on these important outcomes. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Impaired insight into one's illness is common in first episode psychosis (FEP), is associated with worse symptoms and functioning, and predicts a worse course of illness. Despite its importance, little research has examined the effects of early intervention services (EIS) on insight. Designs This paper evaluated the impact of EIS (NAVIGATE) on insight compared to usual community care (CC) in a large cluster randomized controlled trial. Assessments were conducted at baseline and every 6 months for 2 years. Results A multilevel regression model including all time points showed a significant time by treatment group interaction (P <.001), reflecting greater improvement in insight for NAVIGATE than CC participants. Impaired insight was related to less severe depression but worse other symptoms and functioning at baseline for the total sample. At 6 months, the same pattern was found within each group except insight was no longer associated with depression among NAVIGATE participants. Impaired insight was more strongly associated with worse interpersonal relationships at 6 months in NAVIGATE than in CC, and changes in insight from baseline to 6 months were more strongly correlated with changes in relationships in NAVIGATE than CC. Conclusions The NAVIGATE program improved insight significantly more than CC. Although greater awareness of illness has frequently been found to be associated with higher depression in schizophrenia, these findings suggest EIS programs can improve insight without worsening depression in FEP. The increased association between insight and social relationships in NAVIGATE suggests these 2 outcomes may synergistically interact to improve each other in treatment. [ABSTRACT FROM AUTHOR]

This paper explored training methods to improve the Theory of Mind levels of Chinese college students with hearing loss and investigated the transfer effect of training. Ninety Chinese college students with hearing loss were randomly divided into two groups: the ToM training group and the physical-conversation training group. The ToM training group received ToM training, and the physical-conversation training group as the control group received physical-conversation training. All the participants attended four separate 60-min lectures. The ToM Story Task and the False Belief Task were used to assess the training's effect, and the ToM animation task was adopted to investigate the transfer effect. Before training, the level of ToM of the two participant groups was similar. After training, the ToM level of Chinese college students with hearing loss who participated in ToM training was significantly higher than the students who underwent physical-conversation training. Moreover, the findings revealed that ToM training has long-term transfer effects. This study thus showed that ToM training can effectively improve the ToM level of Chinese college students with hearing loss. [ABSTRACT FROM AUTHOR]

Patients in Intensive Care Unit (ICU) often require sedatives which commonly include midazolam and the more recently developed α2-receptor agonist, dexmedetomidine. It was our aim to compare the sedative and clinical effectiveness of dexmedetomidine vs midazolam in adults admitted to ICU, using an objective appraisal of randomized control trials. Medline, Embase, SCOPUS, Web of Knowledge, Cinhal, the United States National Library of Medicine, and the Cochrane Database of Systematic Reviews were searched using keywords: 'dexmedetomidine', 'midazolam', and 'intensive care'. These were limited to human studies and adults (>18 yr old). Six randomized controlled trials were found and were critically appraised using a standardized appraisal method. Two papers described the time spent by each intervention group within a specified target sedation range and both found no statistically significant difference between midazolam and dexmedetomidine (P=0.18 and P=0.15). A third paper found no statistically significant difference in the length of time that patients were sedated within a target zone (P=0.445). Two additional pilot studies did not report P values as they were insufficiently statistically powered. A final paper found that, of the eight occasions measured, patients on dexmedetomidine were more often within the target sedation range than patients on midazolam. The sedative benefits of dexmedetomidine vs midazolam remain inconclusive. While some secondary outcomes showed clinical effectiveness of dexmedetomidine, more research is needed to validate the findings of these studies. [ABSTRACT FROM AUTHOR]

Background There is a growing interest in teledermatology in today's clinical practice, but the maturity of the evaluation research of this technology is still unclear. Objectives This systematic review describes the maturity of teledermatology evaluation research over time and explores what kind of teledermatology outcome measures have been evaluated. Methods Systematic review of literature found in Medline database (1966 up to April 2006). A telemedicine evaluation strategy consisting of four consecutive research phases (parallel to drug and diagnostics evaluation research) extended with a fifth postimplementation phase was used to classify all included studies by two independent reviewers. In addition, main characteristics (store-and-forward or real-time, study design, outcome measures) were registered. Results Three hundred and forty-five papers were systematically selected from Medline, and 244 papers were excluded. For two randomized controlled trials (RCTs), multiple papers in phase III were found. After correcting for this, 99 studies remained included (11 phase I, 72 phase II, two phase III, six phase IV, eight postimplementation phase). The number of phase II studies is the largest and still growing, while other phases are much less represented. Diagnostic accuracy was the most often used outcome measure and was found in phase I, II and IV. Store-and-forward teledermatology has been evaluated more since 2001, but most phase IV studies (RCTs, including cost aspects) are on real-time teledermatology. Conclusions Most teledermatology evaluation studies are classified as feasibility studies (phase II). The number of phase III and IV studies remains low through the years. Compared with other specialties in telemedicine (i.e. telesurgery, telepaediatrics), teledermatology seems to be a mature application. However, more evaluation studies with a focus on clinical outcomes such as preventable referrals or time to recovery are needed to prove that teledermatology indeed is a promising and cost-saving technology. [ABSTRACT FROM AUTHOR]

Background The aim of this study is to determine the feasibility of implementing and evaluating the World Health Organization Package of Essential Non-communicable Disease Interventions (WHO PEN) approach in primary healthcare in the Republic of Moldova. Methods According to our published a priori methods, 20 primary care clinics were randomized to 10 intervention and 10 control clinics. The intervention consisted of implementation of adapted WHO PEN guidelines and structured training for health workers; the control clinics continued with usual care. Data were gathered from paper-based patient records in July 2017 and August 2018 resulting in a total of 1174 and 995 patients in intervention and control clinics at baseline and 1329 and 1256 at follow-up. Pre-defined indicators describing assessment of risk factors and total cardiovascular risk, prescribing medications and treatment outcomes were calculated. Differences between baseline and follow-up as well as between intervention and control clinics were calculated using logistic and linear regression models and by assessing interaction effects. Results Improvements were seen in recording smoking status, activity to measure HbA1c among diabetes patients and achieving control in hypertension treatment. Improvement was also seen in identification of patients with hypertension or diabetes. Less improvement or even deterioration was seen in assessing total risk or prescribing statins for high-risk patients. Conclusions It is feasible to evaluate the quality and management of patients with non-communicable diseases in low-resource settings from routine data. Modest improvements in risk factor identification and management can be achieved in a relatively short period of time. [ABSTRACT FROM AUTHOR]

Enabling worker voice could improve worker retention and effort by providing workers the chance to improve their situation or an outlet to express discontent. We provide a test of this hypothesis via a randomised controlled trial in Indian garment factories. Just after what proved to be a disappointing wage hike, workers were chosen at random to participate in an anonymous survey in which they were asked for feedback on job conditions, supervisor performance and overall job satisfaction. Enabling voice in this manner reduced turnover and absenteeism after the hike, particularly for the most disappointed workers. [ABSTRACT FROM AUTHOR]

Local coalitions can advance public health initiative but have not been widely used or well-studied in low- and middle-income countries. This paper provides (i) an overview of an ongoing matched-pairs community-randomized controlled trial in 28 communities in Armenia and Georgia (N = 14/country) testing local coalitions to promote smoke-free policies/enforcement and (ii) characteristics of the communities involved. In July–August 2018, key informants (e.g. local public health center directors) were surveyed to compare their non-communicable disease (NCD) and tobacco-related activities across countries and across condition (intervention/control). More than half of the informants (50.0–57.1%) reported their communities had programs addressing hypertension, diabetes, cancer and human papilloma virus, with 85.7% involving community education and 32.1% patient education programs. Eleven communities (39.3%) addressed tobacco control, all of which were in Georgia. Of those, all included public/community education and the majority (72.7–81.8%) provided cessation counseling/classes, school/youth prevention programs, healthcare provider training or activities addressing smoke-free environments. Informants in Georgia versus Armenia perceived greater support for tobacco control from various sectors (e.g. government, community). No differences were found by condition assignment. This paper provides a foundation for presenting subsequent analyses of this ongoing trial. These analyses indicate wide variability regarding NCD-related activities and support across communities and countries. [ABSTRACT FROM AUTHOR]

Background The effectiveness of Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy is limited by inconsistent and incorrect use. This paper describes the development process for "Baby, Me, & NRT", a novel pregnancy-specific intervention aimed at enhancing adherence to NRT. Methods An integrated approach to intervention development was used, combining evidence, theory, stakeholders' feedback, and tailoring principles. The process involved six iterative steps: (1) synthesizing relevant published evidence and guidance, (2) collecting primary qualitative data on barriers and facilitators to NRT adherence along with potential intervention design features, (3) identifying relevant behavioral theories and mapping the evidence against these, (4) prioritizing behavioral determinants identified in steps 1 and 2, generating intervention objectives, and identifying behavior change techniques which target the prioritized determinants, (5) consulting with stakeholders on intervention components, key content and tailoring features, and (6) producing a prototype intervention along with implementation guidance. Results The prototype intervention comprises of a multi-component, 1-month cessation programme, which includes six enhanced behavioral support sessions delivered by a trained advisor, tailored text messages, a website, and an illustrated booklet. It promotes the uptake of high-dose and combination NRT, emphasizes the importance of adherence, addresses motivation to use NRT, proactively helps problem solve NRT use issues, and provides guidance on preventing and managing smoking lapses. Conclusion The development process generated an evidence- and theory-guided intervention, designed with stakeholder input, aimed at improving NRT effectiveness for smoking cessation in pregnancy. The prototype intervention has since been optimized and is being evaluated in a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Aims Heart failure nurse practitioners (HF NPs) are an emerging component of the heart failure (HF) specialist workforce but their impact in an inpatient setting is untested. The aim of this paper is to explore the impact of an inpatient HF NP service on 12- month all-cause rehospitalizations, emergency department (ED) presentations, and mortality in patients hospitalized with HF compared with usual hospital care. Methods and results Retrospective, two-group comparative design involving patients (n= 408) admitted via ED with acute HF to a metropolitan quaternary hospital between January 2013 and August 2017. Doubly robust estimation with augmented inverse probability weighting (DR-AIPW) was used to account for the non-random allocation of patients to usual hospital care or the HF NP service in addition to usual in-hospital care. Among 408 patients (186 usual care and 222 HF NP service) admitted with acute HF, the mean age was 76.5 [standard deviation (SD) 12.0] years and 56.4% (n=230) were male. After IPW adjustment, patients seen by the HF NP service had a lower risk of 12-month rehospitalization (61.3 vs. 78.3% usual care; difference -16.9%, 95% CI: -26.4%, -6.6%) and ED presentations (12.6 vs. 22.0%; difference -9.4%, 95% CI: -17.3%, -1.4%) with no difference in 6- or 12-month mortality. The HF NP service improved referrals to a home visiting programme that was available to HF patients (64.4 vs. 45.4%; difference 19%, 95% CI: 8.8%, 28.8%). Conclusion Additional support by an inpatient HF NP service has the potential to significantly reduce rehospitalizations and ED presentations over 12 months. Further evidence from a multicentre randomized control trial is warranted. [ABSTRACT FROM AUTHOR]

Background Fluoride varnish (FV) is an established technology for primary and secondary caries prevention. Objective The aim of this review was to evaluate the preventive effect of FV on development of white spot lesions (WSL) when regularly applied during orthodontic treatment with fixed appliances. Search methods We searched PubMed, Scopus and Google Scholar up to October 2022 using predetermined keywords. Selection criteria We included randomized controlled trials of a duration of minimum 12 months and at least quarterly FV applications. Data collection and analysis Based on abstracts, we retrieved full-text papers, extracted key outcome data, and assessed risk of bias. Primary outcome was prevalence of WSLs on subject level after debonding. We conducted a narrative synthesis and pooled comparable outcome data in a random effects model. Results We included seven studies covering 666 patients and assessed four publications with low or moderate risk of bias and three with high. The prevalence of WSLs at debonding varied between 12 and 55%. All studies presented results in favour for the FV intervention, one reached statistical significance on subject level. Five studies provided data for a meta-analysis. The pooled risk ratio was 0.64 [95% CI: 0.42, 0.98], indicating a statistically significant preventive effect. Certainty of evidence was graded as very low after reducing for risk of bias, inconsistency and imprecision. Limitations We pooled data on subject level and did not consider lesion severity on tooth level. Conclusions and implications Even if the certainty of evidence was very low, it was shown that FV can prevent development of WSL when regularly applied during orthodontic treatment. Larger investigations reporting a core outcome set are required to increase the certainty of evidence. Registration PROSPERO database (CRD42022370062). [ABSTRACT FROM AUTHOR]

This paper proposes an adaptive randomisation procedure for two-stage randomised controlled trials. The method uses data from a first-wave experiment in order to determine how to stratify in a second wave of the experiment, where the objective is to minimise the variance of an estimator for the average treatment effect. We consider selection from a class of stratified randomisation procedures which we call stratification trees: these are procedures whose strata can be represented as decision trees, with differing treatment assignment probabilities across strata. By using the first wave to estimate a stratification tree, we simultaneously select which covariates to use for stratification, how to stratify over these covariates, and the assignment probabilities within these strata. Our main result shows that using this randomisation procedure with an appropriate estimator results in an asymptotic variance which is minimal in the class of stratification trees. Moreover, our results are able to accommodate a large class of assignment mechanisms within strata, including stratified block randomisation. In a simulation study, we find that our method, paired with an appropriate cross-validation procedure, can improve on ad-hoc choices of stratification. We conclude by applying our method to the study in Karlan and Wood (2017, Journal of Behavioral and Experimental Economics , vol. 66, 1–8), where we estimate stratification trees using the first wave of their experiment. [ABSTRACT FROM AUTHOR]

Ulipristal acetate (UPA) is a medical treatment for uterine fibroids and was authorized for surgical pre-treatment in 2012 after the conduct of the PEARL I and II randomized controlled trials and for intermittent treatment after the observational PEARL III and IV trials. However, UPA came into disrepute due to its temporary suspension in 2017 and 2020 because of an apparent association with liver injury. This clinical opinion paper aims to review the process of marketing authorization and implementation of UPA, in order to provide all involved stakeholders with recommendations for the introduction of future drugs. Before marketing authorization, the European Medicines Agency (EMA) states that Phase III registration trials should evaluate relevant outcomes in a representative population, while comparing to gold-standard treatment. This review shows that the representativeness of the study populations in all PEARL trials was limited, surgical outcomes were not evaluated and intermittent treatment was assessed without comparative groups. Implementation into clinical practice was extensive, with 900 000 prescribed treatment cycles in 5 years in Europe and Canada combined. Extremely high costs are involved in developing and evaluating pre-marketing studies in new drugs, influencing trial design and relevance of chosen outcomes, thereby impeding clinical applicability. It is vitally important that the marketing implementation after authorization is regulated in such way that necessary evidence is generated before widespread prescription of a new drug. All stakeholders, from pharmaceutical companies to authorizing bodies, governmental funding bodies and medical professionals should be aware of their role and take responsibility for their part in this process. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) protocols are now widely practiced in major surgery, improving postsurgical outcomes. Uptake of these programmes have been slow in kidney transplantation due to challenges in evaluating their safety and efficacy in this high-risk cohort. To date, there are no unified guidance and protocols specific to ERAS in kidney transplantation surgery. This paper aims to summarise current evidence in the literature and develop ERAS protocol recommendations for kidney transplantation recipients. Methods: PubMed, Cochrane, Embase and Medline databases were screened for studies relevant to ERAS protocols in kidney transplantation, up to August 2021. A secondary search was repeated for each ERAS recommendation to explore the specific evidence base available for each section of the protocol. Randomised controlled trials, case-control and cohort studies were included. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used to evaluate the quality of evidence available and recommendations. Results: We identified six eligible studies with a total of 1225 participants. All studies found a reduction in length of hospital stay without affecting readmission rates. The evidence behind specific pre-operative, intra-operative and post-operative interventions included in current ERAS protocols are reviewed and discussed. Conclusion: Compared to other surgical specialties, the evidence base for ERAS in kidney transplantation remains lacking, with further room for research and development. However, significant improvements to patient outcomes are already possible with application of the currently available evidence. This has shown that ERAS in kidney transplantation surgery is safe and feasible, with improved postoperative outcomes. [ABSTRACT FROM AUTHOR]

This paper reviews the use of descriptive statistics to describe the participants included in a study. It discusses the practicalities of incorporating statistics in papers for publication in Age and Aging, concisely and in ways that are easy for readers to understand and interpret. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity.Methods: A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion.Results: Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies.Conclusions: This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin. [ABSTRACT FROM AUTHOR]

This paper presents results of an impact evaluation of Teen Council, a program that trains youth as peer educators. Teen Council is designed to help peer educators make healthy sexual and reproductive decisions, increase their confidence and abilities to educate their peers and inspire them to advocate for just sexual policies. The program's impact on these educators was evaluated using a randomized controlled trial. Over 5 years, interested high school students in seven states were randomly assigned to a study condition. An intent-to-treat framework using ordinary least square (OLS) regression was employed to measure program effects. Relative to control, Teen Council youth showed enhanced comfort with their own sexuality, greater comfort with and more frequent communication with parents about sexuality and more positive sexual health behaviors, including accessing reproductive health care and adopting more effective means of contraception. Teen Council youth also reported greater confidence in talking with peers about sexuality and more confidence in their civic engagement skills. [ABSTRACT FROM AUTHOR]

INTRODUCTION Adhesion formation is the most common complication following peritoneal surgery and the leading cause of small bowel obstruction, acquired infertility and inadvertent organ injury at reoperation. Using a ‘good surgical technique’ is advocated as a first step in preventing adhesions. However, the evidence for different surgical techniques to reduce adhesion formation needs confirmation. METHODS Pubmed, Embase and CENTRAL were searched to identify randomized controlled trials that investigated the effect of various aspects of surgical technique on adhesion-related outcomes. Clinical outcomes and incidence of adhesions were the primary endpoints. Identification of papers and data extraction were performed by two independent researchers. RESULTS There were 28 papers with 27 studies included for a systematic review. Of these, 17 studies were eligible for meta-analysis and 11 for qualitative assessment only. None of the techniques that were compared significantly reduced the incidence of adhesive small bowel obstruction. In a small low-quality trial, the pregnancy rate increased after subserous fixation of suture knots. However, the incidence of adhesions was lower after laparoscopic compared with open surgery [relative risk (RR) 0.14; 95% confidence interval (CI): 0.03–0.61] and when the peritoneum was not closed (RR 0.36; 95% CI: 0.21–0.63). CONCLUSIONS None of the specific techniques that were compared reduced the two main adhesion-related clinical outcomes, small bowel obstruction and infertility. The meta-analysis provides little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischaemia reduces the extent and severity of adhesions. [ABSTRACT FROM PUBLISHER]

Background Oral phenytoin was first introduced as an antiseizure medication in 1937. Over 60 years investigators have shown an interest in how topical phenytoin may be used to promote wound healing in a variety of chronic wounds. Objectives Systematically to identify, summarize and critically appraise the clinical evidence available on the effects of topical phenytoin on wound healing. Methods Systematic searches were carried out in PubMed (1963–2005), Medline (1966–2005) and Cinahl (1982–2005) for the years listed and in the Cochrane Library and the University of York NHS Centre for Reviews and Dissemination. The search terms used the following key words alone and in combination: phenytoin, wounds and injuries, wound healing, and wound care. Secondary hand searching was also carried out using relevant journal articles and reference lists, historical books, conference proceedings and theses in the area of wound healing. Papers were included if they described randomized controlled trials (RCTs) on humans and if the primary aim was wound closure, with a secondary aim of measuring wound healing over time. The methodological quality of the papers in this systematic review was assessed using the van Tulder method and in addition best-evidence synthesis was carried out. The magnitude of the effect of phenytoin therapy in the studies included in the systematic review was investigated in four of the 14 trials. Results Fourteen RCTs were included in the systematic review. Two papers were of high and 12 papers of low to moderate methodological quality. Most papers failed to describe randomization, treatment allocation and blinding techniques adequately. There was moderate evidence presented to support the use of phenytoin for the treatment of leg ulcers, leprosy wounds, chronic wounds and diabetic foot ulcers. There was a positive percentage treatment effect in favour of the phenytoin-treated group in one study investigating diabetic foot wounds and one study on chronic wounds. There was limited evidence for the use of phenytoin on burns and war wounds. Conclusions Overall it would appear that studies investigating the effect of topical phenytoin on wound healing are of moderate methodological quality, and these suggest that there may be a positive effect on wound healing in a variety of wounds. [ABSTRACT FROM AUTHOR]

Instrumental variables are widely used to deal with unmeasured confounding in observational studies and imperfect randomized controlled trials. In these studies, researchers often target the so-called local average treatment effect as it is identifiable under mild conditions. In this paper we consider estimation of the local average treatment effect under the binary instrumental variable model. We discuss the challenges of causal estimation with a binary outcome and show that, surprisingly, it can be more difficult than in the case with a continuous outcome. We propose novel modelling and estimation procedures that improve upon existing proposals in terms of model congeniality, interpretability, robustness and efficiency. Our approach is illustrated via simulation studies and a real data analysis. [ABSTRACT FROM AUTHOR]

Introduction: Smoking rates are alarmingly high among young people experiencing homelessness (YEH), yet there are no evidence-based cessation programs for this population. This paper presents results from a pilot evaluation of a text messaging-based smoking cessation treatment, as an adjunct to brief group cessation counseling, to improve abstinence rates among 18-25-year-old smokers experiencing homelessness. The goal of this study was to estimate effect sizes for a larger trial and it was not powered to detect group differences.Aims and Methods: YEH smokers who had a working cell phone with them at recruitment were randomized to receive a group counseling session, nicotine patches, and written material on quitting (n = 37) or a similar program that also included a 6-week automated text messaging intervention (TMI) to provide ongoing support for quitting (n = 40). Smoking outcomes were evaluated through a 90-day follow-up.Results: Seven-day point prevalence abstinence at 90-day follow-up was higher in the TMI condition than standard condition (17.50% vs. 8.11%, respectively; Cohen's h = .37); however, the 90-day continuous abstinence rate was not statistically different from zero in either condition. Reductions in the number of days smoked in the past 30 days from baseline to follow-up were greater in the TMI condition than the standard condition (-14.24 vs. -8.62, respectively; Cohen's d = .49).Conclusions: Adding a 6-week TMI support to a brief group counseling and pharmacotherapy protocol holds promise for smoking reduction and abstinence among YEH smokers. Results indicate that further development and evaluation of the TMI in this population is warranted.Trial Registration: ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585.Implications: This is the first study to evaluate the feasibility of using a text messaging-based intervention (TMI) for behavior change with 18-25 year olds experiencing homelessness, and more specifically, the first to test a TMI to provide ongoing support for smoking cessation. Small to medium effect sizes for the TMI are promising in terms of implementing a TMI using participants' own cell phones, as well as the efficacy of this approach as an adjunct to standard care (brief group counseling and pharmacotherapy) for smoking cessation among YEH. [ABSTRACT FROM AUTHOR]

Background Children's second-hand smoke (SHS) exposure in the home is highest in socio-economically disadvantaged areas. Personalized household air-quality measurements can promote changes in smoking that reduce SHS exposure. The 'First Steps 2 Smoke-free' (FS2SF) intervention is the first to trial this approach delivered as part of health professionals' routine work. This paper reports the findings of qualitative interviews with participants that explored their experiences of the intervention and why outcomes varied. Methods 120 women were recruited from the NHS First Steps Programme, which supports disadvantaged mothers. They received either personalized feedback on their home air quality and advice on reducing SHS or standard SHS advice. Qualitative interviews with 15 mothers were analyzed thematically using the Capability, Opportunity, Motivation, Behaviour (COM-B) model. Results The intervention increased women's capability to change home-smoking behaviour, through increasing awareness and salience of SHS risks to their children, and motivation to act. However, taking effective action was constrained by their limited social and environmental opportunities, including others' smoking in the home. Conclusions The FS2SF intervention was ineffective as it was unable to fully address the precarious, complex life circumstances that make creating a smoke-free home particularly difficult for women experiencing intersecting dimensions of disadvantage. [ABSTRACT FROM AUTHOR]

This paper characterizes the identified set for finite mixture models with one exclusion restriction on the data-generating process. It provides necessary and sufficient conditions on the observed data for point identification and for when the identified set has measure zero. The results are illustrated in a simulation study and with data from a randomized controlled trial on chemotherapy for colon cancer as well as with data from an observational study used to estimate returns to schooling. [ABSTRACT FROM AUTHOR]

Few studies address publication and outcome reporting biases of randomized controlled trials (RCTs) in psychiatry. The objective of this study was to determine publication and outcome reporting bias in RCTs funded by the Stanley Medical Research Institute (SMRI), a U.S. based, non-profit organization funding RCTs in schizophrenia and bipolar disorder. We identified all RCTs (n = 280) funded by SMRI between 2000 and 2011, and using non-public, final study reports and published manuscripts, we classified the results as positive or negative in terms of the drug compared to placebo. Design, outcome measures and statistical methods specified in the original protocol were compared to the published manuscript. Of 280 RCTs funded by SMRI between 2000 and 2011, at the time of this writing, three RCTs were ongoing and 39 were not performed. Among the 238 completed RCTs, 86 (36.1%) reported positive and 152 (63.9%) reported negative results: 86% (74/86) of those with positive findings were published in contrast to 53% (80/152) of those with negative findings (P <.001). In 70% of the manuscripts published, there were major discrepancies between the published manuscript and the original RCT protocol (change in the primary outcome measure or statistics, change in a number of patient groups, 25% or more reduction in sample size). We conclude that publication bias and outcome reporting bias is common in papers reporting RCTs in schizophrenia and bipolar disorder. These data have major implications regarding the validity of the reports of clinical trials published in the literature. [ABSTRACT FROM AUTHOR]

Background: A nudge corresponds to any procedure that influences choice architecture, without using persuasion or financial incentives. Nudges are effective in increasing vaccination with heterogeneous levels of acceptability.Objective: To evaluate the effectiveness and acceptability of a nudge promoting influenza vaccination for general practice trainees, also called residents.Methods: The hypothesis was that a reminder would be efficient and accepted and that prior exposure to a nudge increases its acceptability. Residents were randomly divided into three parallel experimental arms: a nudge group, a no-nudge group and a control group in order to evaluate the Hawthorne effect. The nudge consisted of providing a paper form for the free delivery of the vaccine and contacts for occupational health services.Results: The analysis included 161 residents. There was a strong consensus among the residents that it is very acceptable to nudge their peers and patients. Acceptability was better with residents exposed to the nudge and with residents included in step 1 (Hawthorne effect). The nudge did not increase vaccination coverage.Conclusion: The failure of this nudge highlights the importance of matching an intervention to the population's needs. The experimental approach is innovative in this context and deserves further attention.Clinicaltrials.gov Pre-registration: NCT03768596. [ABSTRACT FROM AUTHOR]

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials ( RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes ( PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 142 5 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in gametes from infertile couples and the possibility of an increased risk of imprinting defects and somatic epigenetic changes in ART conceived children, but the results have been heterogeneous. We performed a systematic review of existing studies to compare the incidence of imprinting disorders and levels of DNA methylation in key imprinted genes in children conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with those in children conceived spontaneously. METHODS A detailed search strategy was used to conduct electronic literature searches (spanning 1978 to 2013) on Medline, EMBASE, the Cochrane Library and Web of Science. Abstracts of relevant conference papers were identified. As randomized trials are not feasible in this context, we included observational (cohort and case–control) studies comparing outcomes in children conceived through ART with those conceived spontaneously, irrespective of the language of publication. The outcome measures were DNA methylation and the incidence of imprinting disorders. RESULTS A total of 351 publications were identified by the initial search. Of these, 26 were excluded as duplicates and 241 were excluded after reviewing the abstracts, then of those remaining 66 were excluded after review of the full text. A total of 18 papers were included in the review. Apart from one case–control study, all were cohort studies. There was a degree of clinical heterogeneity in terms of the study population, type of infertility treatment, and samples obtained from exposed and unexposed children. DNA methylation levels were either presented as categorical data (hypo-, hyper- or normally methylated DNA) or continuous data (i.e. percentage of methylated DNA). The combined odds ratio (95% confidence intervals) of any imprinting disorder in children conceived through ART was 3.67 (1.39, 9.74) in comparison with spontaneously conceived children. Meta-analysis of data from relevant studies revealed that the weighted mean difference (95% confidence intervals) in methylation percent between IVF/ICSI versus spontaneously conceived children were as follows: H19: −0.46(−1.41, 0.49), PEG1-MEST: 0.47 (−2.07, 3.01), GRB10: −0.05 (−0.43, 0.33), IGF2: −0.15 (−1.09, 0.79), SNRPN: −0.55 (−1.55, 0.46), KvDMR/KCNQ10T1: −0.16 (−0.34, 0.02) and PEG3: −0.24 (−1.72, 1.24). CONCLUSIONS There was an increase in imprinting disorders in children conceived though IVF and ICSI but insufficient evidence for an association between ART and methylation in other imprinted genes. Heterogeneity in the types of fertility treatment, the imprinted regions studied, the tissues used and the methods of measurement, reduce our ability to assess the full effect of ART on DNA methylation and imprinting. More controlled studies, using standardized methodologies, in larger, better clinically defined populations are needed. [ABSTRACT FROM AUTHOR]

Drawing on a Cochrane systematic review, this paper examines the relatively limited range of outcomes measured in published evaluations of antimicrobial stewardship interventions (ASIs) in hospitals. We describe a structured framework for considering the range of consequences that ASIs can have, in terms of their desirability and the extent to which they were expected when planning an ASI: expected, desirable consequences (intervention goals); expected, undesirable consequences (intervention trade-offs); unexpected, undesirable consequences (unpleasant surprises); and unexpected, desirable consequences (pleasant surprises). Of 49 randomized controlled trials identified by the Cochrane review, 28 (57%) pre-specified increased length of stay and/or mortality as potential trade-offs of ASI, with measurement intended to provide reassurance about safety. In actuality, some studies found unexpected decreases in length of stay (a pleasant surprise). In contrast, only 11 (10%) of 110 interrupted time series studies included any information about unintended consequences, with 10 examining unexpected, undesirable outcomes (unpleasant surprises) using case-control, qualitative or cohort designs. Overall, a large proportion of the ASIs reported in the literature only assess impact on their targeted process goals-antimicrobial prescribing-with limited examination of other potential outcomes, including microbial and clinical outcomes. Achieving a balanced accounting of the impact of an ASI requires careful consideration of expected undesirable effects (potential trade-offs) from the outset, and more consideration of unexpected effects after implementation (both pleasant and unpleasant surprises, although the latter will often be more important). The proposed framework supports the systematic consideration of all types of consequences of improvement before and after implementation. [ABSTRACT FROM AUTHOR]

Objective.: To demonstrate proof of concept for a smart phone‐empowered community health worker (CHW) model of care for breast health promotion, clinical breast examination (CBE), and patient navigation in rural Bangladesh. Methods.: This study was a randomized controlled trial; July 1 to October 31, 2012, 30 CHWs conducted door‐to‐door interviews of women aged 25 and older in Khulna Division. Only women who disclosed a breast symptom were offered CBE. Arm A: smart phone with applications to guide interview, report data, show motivational video, and offer appointment for women with an abnormal CBE. Arm B: smart phone/applications identical to Arm A plus CHW had training in “patient navigation” to address potential barriers to seeking care. Arm C: control arm (no smart phone; same interview recorded on paper). Outcomes are presented as the “adherence” (to advice regarding a clinic appointment) for women with an abnormal CBE. This study was approved by Women's College Hospital Research Ethics Board (Toronto, Ontario, Canada) and district government officials (Khulna, Bangladesh). Funded by Grand Challenges Canada. Results.: In 4 months, 22,337 women were interviewed; <1% declined participation, and 556 women had an abnormal CBE. Control group CHWs completed fewer interviews, had inferior data quality, and identified significantly fewer women with abnormal breast exams compared with CHWs in arms A and B. Arm B had the highest adherence. Conclusion.: CHWs guided by our smart phone applications were more efficient and effective in breast health promotion compared with the control group. CHW “navigators” were most effective in encouraging women with an abnormal breast examination to adhere to advice regarding clinic attendance. Community health workers (CHWs) used smart phones with and without patient navigation to promote breast health in rural Bangladesh and were compared with CHWs using paper‐and‐pencil methods only. Findings showed that CHWs who did not use the smart phone applications completed fewer interviews, had inferior data quality, and identified significantly fewer women with abnormal breast exams, indicating that smart phones can be used to promote breast health in rural areas. CHWs with smart phones and 1‐day training in patient navigation were more effective in encouraging women with abnormal breast exams to attend for proper care. [ABSTRACT FROM AUTHOR]