Factors that impact on recruitment to randomised trials in health care: a qualitative evidence synthesis

BACKGROUND: Randomised trials (also referred to as 'randomised controlled trials' or 'trials') are the optimal way to minimise bias in evaluating the effects of competing treatments, therapies and innovations in health care. It is important to achieve the required sample size for a trial, otherwise trialists may not be able to draw conclusive results leading to research waste and raising ethical questions about trial participation. The reasons why potential participants may accept or decline participation are multifaceted. Yet, the evidence of effectiveness of interventions to improve recruitment to trials is not substantial and fails to recognise these individual decision-making processes. It is important to synthesise the experiences and perceptions of those invited to participate in randomised trials to better inform recruitment strategies. OBJECTIVES: To explore potential trial participants' views and experiences of the recruitment process for participation. The specific objectives are to describe potential participants' perceptions and experiences of accepting or declining to participate in trials, to explore barriers and facilitators to trial participation, and to explore to what extent barriers and facilitators identified are addressed by strategies to improve recruitment evaluated in previous reviews of the effects of interventions including a Cochrane Methodology Review. SEARCH METHODS: We searched the Cochrane Library, Medline, Embase, CINAHL, Epistemonikos, LILACS, PsycINFO, ORRCA, and grey literature sources. We ran the most recent set of searches for which the results were incorporated into the review in July 2017. SELECTION CRITERIA: We included qualitative and mixed-methods studies (with an identifiable qualitative component) that explored potential trial participants' experiences and perceptions of being invited to participate in a trial. We excluded studies that focused only on recruiters' perspectives, and trials solely involving children under 18 years, or adults who were assessed as having impaired mental capacity. DATA COLLECTION AND ANALYSIS: Five review authors independently assessed the titles, abstracts and full texts identified by the search. We used the CART (completeness, accuracy, relevance, timeliness) criteria to exclude studies that had limited focus on the phenomenon of interest. We used QSR NVivo to extract and manage the data. We assessed methodological limitations using the Critical Skills Appraisal Programme (CASP) tool. We used thematic synthesis to analyse and synthesise the evidence. This provided analytical themes and a conceptual model. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. Our findings were integrated with two previous intervention effectiveness reviews by juxtaposing the quantitative and qualitative findings in a matrix. MAIN RESULTS: We included 29 studies (published in 30 papers) in our synthesis. Twenty-two key findings were produced under three broad themes (with six subthemes) to capture the experience of being invited to participate in a trial and making the decision whether to participate. Most of these findings had moderate to high confidence. We identified factors from the trial itself that influenced participation. These included how trial information was communicated, and elements of the trial such as the time commitment that might be considered burdensome. The second theme related to personal factors such as how other people can influence the individual's decision; and how a personal understanding of potential harms and benefits could impact on the decision. Finally, the potential benefits of participation were found to be key to the decision to participate, namely personal benefits such as access to new treatments, but also the chance to make a difference and help others. The conceptual model we developed presents the decision-making process as a gauge and the factors that influence whether the person will, or will not, take part. AUTHORS' CONCLUSIONS: This qualitative evidence synthesis has provided comprehensive insight into the complexity of factors that influence a person's decision whether to participate in a trial. We developed key questions that trialists can ask when developing their recruitment strategy. In addition, our conceptual model emphasises the need for participant-centred approaches to recruitment. We demonstrated moderate to high level confidence in our findings, which in some way can be attributed to the large volume of highly relevant studies in this field. We recommend that these insights be used to direct or influence or underpin future recruitment strategies that are developed in a participant-driven way that ultimately improves trial conduct and reduces research waste

The Cost-Effectiveness of Reclassification Sampling for Prevalence Estimation

Typically, a two-phase (double) sampling strategy is employed when classifications are subject to error and there is a gold standard (perfect) classifier available. Two-phase sampling involves classifying the entire sample with an imperfect classifier, and a subset of the sample with the gold-standard.In this paper we consider an alternative strategy termed reclassification sampling, which involves classifying individuals using the imperfect classifier more than one time. Estimates of sensitivity, specificity and prevalence are provided for reclassification sampling, when either one or two binary classifications of each individual using the imperfect classifier are available. Robustness of estimates and design decisions to model assumptions are considered. Software is provided to compute estimates and provide advice on the optimal sampling strategy.Reclassification sampling is shown to be cost-effective (lower standard error of estimates for the same cost) for estimating prevalence as compared to two-phase sampling in many practical situations

Late-stage diagnosis of HIV infection in Brazilian children: evidence from two national cohort studies

This study analyzed data from two consecutive retrospective cohort samples (1983 to 1998 and 1999 to 2002) of Brazilian children with AIDS (N = 1,758) through mother-to-child-transmission. Late-stage diagnosis (CDC category C) was investigated in relation to the following variables: year of birth, year of HIV diagnosis, and time periods related to changes in government treatment guidelines. Late-stage diagnosis occurred in 731 (41.6%) of cases and was more prevalent in infants under 12 months of age. The rate of late-stage diagnosis decreased from 48% to 36% between the two periods studied. We also observed a reduction in the proportion of late-stage diagnoses and the time lapse between HIV diagnosis and ART initiation. A significant association was found between timely diagnosis and having been born in recent years (OR = 0.62; p = 0.009) and year of HIV diagnosis (OR = 0.72; p = 0.002/OR = 0.62; p < 0.001). Infants under the age of 12 months were more likely to be diagnosed at a late stage than older children (OR = 1.70; p = 0.004). Despite advances, there is a need to improve the effectiveness of policies and programs focused on improving early diagnosis and management of HIV/AIDS

Depression and anxiety symptoms post-stroke/TIA:prevalence and associations in cross-sectional data from a regional stroke registry

BACKGROUND: Mood disorders are commonly seen in those with cerebrovascular disease. Literature to-date has tended to focus on depression and on patients with stroke, with relatively little known about post-stroke anxiety or mood disorder in those with transient ischaemic attack (TIA). We aimed to describe prevalence of depression and anxiety symptoms in stroke and TIA cohorts and to explore association with clinical and socio-demographic factors. METHODS: We used a city wide primary care stroke registry (Glasgow Local Enhanced Service for Stroke - LES). All community dwelling stroke-survivors were included. We described cross-sectional prevalence of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Data on clinical and demographic details was collected and univariable and multivariable analyses performed to describe associations with HADS scores. We examined those with a diagnosis of 'stroke' and 'TIA' as separate cohorts. RESULTS: From 13,283 potentially eligible stroke patients in the registry, we had full HADS data on 4,079. Of the 3,584 potentially eligible TIA patients, we had full HADS data on 1,247 patients. Across the stroke cohort, 1181 (29%) had HADS anxiety scores suggestive of probable or possible anxiety; 993 (24%) for depression. For TIA patients, 361 (29%) had anxiety and 254 (21%) had depression. Independent predictors of both depression and anxiety symptoms were female sex, younger age and higher socioeconomic deprivation score (all p < 0.001). CONCLUSION: Using HADS, we found a high prevalence of anxiety and depression symptoms in a community-based cohort of patients with cerebrovascular disease

Outcome of HIV-exposed uninfected children undergoing surgery

<p>Abstract</p> <p>Background</p> <p>HIV-exposed uninfected (HIVe) children are a rapidly growing population that may be at an increased risk of illness compared to HIV-unexposed children (HIVn). The aim of this study was to investigate the morbidity and mortality of HIVe compared to both HIVn and HIV-infected (HIVi) children after a general surgical procedure.</p> <p>Methods</p> <p>A prospective study of children less than 60 months of age undergoing general surgery at a paediatric referral hospital from July 2004 to July 2008 inclusive. Children underwent age-definitive HIV testing and were followed up post operatively for the development of complications, length of stay and mortality.</p> <p>Results</p> <p>Three hundred and eighty children were enrolled; 4 died and 11 were lost to follow up prior to HIV testing, thus 365 children were included. Of these, 38(10.4%) were HIVe, 245(67.1%) were HIVn and 82(22.5%) were HIVi children.</p> <p>The overall mortality was low, with 2(5.2%) deaths in the HIVe group, 0 in the HIVn group and 6(7.3%) in the HIVi group (p = 0.0003). HIVe had a longer stay than HIVn children (3 (2-7) vs. 2 (1-4) days p = 0.02). There was no significant difference in length of stay between the HIVe and HIVi groups. HIVe children had a higher rate of complications compared to HIVn children, (9 (23.7%) vs. 14(5.7%) (RR 3.8(2.1-7) p < 0.0001) but a similar rate of complications compared to HIVi children 34 (41.5%) (RR = 0.6 (0.3-1.1) p = 0.06).</p> <p>Conclusion</p> <p>HIVe children have a higher risk of developing complications and mortality after surgery compared to HIVn children. However, the risk of complications is lower than that of HIVi children.</p

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Improving spatial prioritisation for remote marine regions: optimising biodiversity conservation and sustainable development trade-offs

Creating large conservation zones in remote areas, with less intense stakeholder overlap and limited environmental information, requires periodic review to ensure zonation mitigates primary threats and fill gaps in representation, while achieving conservation targets. Follow-up reviews can utilise improved methods and data, potentially identifying new planning options yielding a desirable balance between stakeholder interests. This research explored a marine zoning system in north-west Australia–abiodiverse area with poorly documented biota. Although remote, it is economically significant (i.e. petroleum extraction and fishing). Stakeholder engagement was used to source the best available biodiversity and socio-economic data and advanced spatial analyses produced 765 high resolution data layers, including 674 species distributions representing 119 families. Gap analysis revealed the current proposed zoning system as inadequate, with 98.2% of species below the Convention on Biological Diversity 10% representation targets. A systematic conservation planning algorithm Maxan provided zoning options to meet representation targets while balancing this with industry interests. Resulting scenarios revealed that conservation targets could be met with minimal impacts on petroleum and fishing industries, with estimated losses of 4.9% and 7.2% respectively. The approach addressed important knowledge gaps and provided a powerful and transparent method to reconcile industry interests with marine conservation

Seasonal influenza vaccination of healthcare workers : Systematic review of qualitative evidence

Background Most countries recommend that healthcare workers (HCWs) are vaccinated seasonally against influenza in order to protect themselves and patients. However, in many cases coverage remains low. A range of strategies have been implemented to increase uptake. Qualitative evidence can help in understanding the context of interventions, including why interventions may fail to achieve the desired effect. This study aimed to synthesise evidence on HCWs’ perceptions and experiences of vaccination for seasonal influenza. Methods Systematic review of qualitative evidence. We searched MEDLINE, EMBASE and CINAHL and included English-language studies which reported substantive qualitative data on the vaccination of HCWs for seasonal influenza. Findings were synthesised thematically. Results Twenty-five studies were included in the review. HCWs may be motivated to accept vaccination to protect themselves and their patients against infection. However, a range of beliefs may act as barriers to vaccine uptake, including concerns about side-effects, scepticism about vaccine effectiveness, and the belief that influenza is not a serious illness. HCWs value their autonomy and professional responsibility in making decisions about vaccination. The implementation of interventions to promote vaccination uptake may face barriers both from HCWs’ personal beliefs and from the relationships between management and employees within the targeted organisations. Conclusions HCWs’ vaccination behaviour needs to be understood in the context of HCWs’ relationships with each other, with management and with patients. Interventions to promote vaccination should take into account both the individual beliefs of targeted HCWs and the organisational context within which they are implemented

Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

Contains fulltext : 86695.pdf (publisher's version ) (Open Access)Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives This study aims to establish a dose–response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI). Methods The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n=72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL. Results Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (rs=-0.33, p=0.022) and SO (rs=-0.38, p=0.004), whereas clock TOA was correlated with SO shift (r=-0.35, p=0.006) and not with DLMO shift. Conclusions No dose–response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05–0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime.13 p

Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death

Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective