A time-series study of percutaneous closure of patent foramen ovale: premature adoption?

To evaluate the impact of National Institute for Health and Care Excellence (NICE) guidance in January 2005 and subsequent trial evidence on the adoption of percutaneous closure of patent foramen ovale (PCPFO).A retrospective time series study was conducted using the Inpatient Hospital Episode Statistics (HES) England. A total of 3801 patients, aged ≥18 and ≤60 years, who had PCPFO from 1 April 2006 to 31 March 2012 in England. Percentage change annualised (PCA) in PCPFO procedure rates between initial NICE guidance and publication of trial results was analysed.Between Quarter 2, 2006 and Quarter 4, 2009, 2163 PCPFO procedures were performed, with an increasing PCA of 48.4%. The procedure rate peaked before the presentation of equivocal results from the first randomised controlled trial (RCT) in late 2010, and declined between Quarter 4, 2009 and Quarter 4, 2011 (PCA=-15.3%). Of more than 2300 patients recruited to three RCTs, only 71 were recruited in English hospitals.PCPFO was rapidly adopted after the publication of initial NICE guidance despite the absence of RCT evidence of efficacy. Very few English patients participated in international RCTs of PCPFO, suggesting that NICE recommendations also failed to encourage the generation of RCT evidence

Reducing smoking in adolescents: cost-effectiveness results from the cluster randomized ASSIST (A Stop Smoking In Schools Trial)

Introduction: School-based smoking prevention programmes can be effective, but evidence on cost-effectiveness is lacking. We conducted a cost-effectiveness analysis of a school-based “peer-led” intervention.<p></p> Methods: We evaluated the ASSIST (A Stop Smoking In Schools Trial) programme in a cluster randomized controlled trial. The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke. Fifty-nine secondary schools in England and Wales were randomized to receive the ASSIST programme or usual smoking education. Ten thousand seven hundred and thirty students aged 12–13 years attended participating schools. Previous work has demonstrated that the ASSIST programme achieved a 2.1% (95% CI = 0%–4.2%) reduction in smoking prevalence. We evaluated the public sector cost, prevalence of weekly smoking, and cost per additional student not smoking at 24 months.<p></p> Results: The ASSIST programme cost of £32 (95% CI = £29.70–£33.80) per student. The incremental cost per student not smoking at 2 years was £1,500 (95% CI = £669–£9,947). Students in intervention schools were less likely to believe that they would be a smoker at age 16 years (odds ratio [OR] = 0.80; 95% CI = 0.66–0.96).<p></p> Conclusions: A peer-led intervention reduced smoking among adolescents at a modest cost. The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and/or earlier smoking cessation in adulthood. The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £38 million and could result in 20,400 fewer adolescent smokers.<p></p&gt

Effects of Tetracaine on Voltage-activated Calcium Sparks in Frog Intact Skeletal Muscle Fibers

The properties of Ca2+ sparks in frog intact skeletal muscle fibers depolarized with 13 mM [K+] Ringer's are well described by a computational model with a Ca2+ source flux of amplitude 2.5 pA (units of current) and duration 4.6 ms (18 °C; Model 2 of Baylor et al., 2002). This result, in combination with the values of single-channel Ca2+ current reported for ryanodine receptors (RyRs) in bilayers under physiological ion conditions, 0.5 pA (Kettlun et al., 2003) to 2 pA (Tinker et al., 1993), suggests that 1–5 RyR Ca2+ release channels open during a voltage-activated Ca2+ spark in an intact fiber. To distinguish between one and greater than one channel per spark, sparks were measured in 8 mM [K+] Ringer's in the absence and presence of tetracaine, an inhibitor of RyR channel openings in bilayers. The most prominent effect of 75–100 μM tetracaine was an approximately sixfold reduction in spark frequency. The remaining sparks showed significant reductions in the mean values of peak amplitude, decay time constant, full duration at half maximum (FDHM), full width at half maximum (FWHM), and mass, but not in the mean value of rise time. Spark properties in tetracaine were simulated with an updated spark model that differed in minor ways from our previous model. The simulations show that (a) the properties of sparks in tetracaine are those expected if tetracaine reduces the number of active RyR Ca2+ channels per spark, and (b) the single-channel Ca2+ current of an RyR channel is ≤1.2 pA under physiological conditions. The results support the conclusion that some normal voltage-activated sparks (i.e., in the absence of tetracaine) are produced by two or more active RyR Ca2+ channels. The question of how the activation of multiple RyRs is coordinated is discussed

Care leavers in early adulthood: How do they fare in Britain, Finland and Germany?

In this paper we examine the longer term outcomes of young people who experienced out of home care (OHC) as children, in Britain, Germany and Finland, countries characterised by different welfare regimes. While there is some evidence on immediate transitions after leaving care (up to age 21), there is less evidence on experiences around age 30, a phase of early adulthood. Drawing on existing longitudinal data for general population samples we focus on outcomes related to education, employment, family, health and receipt of welfare benefits for those who were ever in care and those who were not. We find evidence for continuing disadvantage regarding education and employment for those who were in care as children, but also indications of subjective wellbeing and commitment to family life – possibly a reflection of “normality” and efforts to “fit in” as parents. Surprisingly, despite variations in welfare system and differences in the scope and quality of available data, trends were similar in each of the countries, suggesting that none provide adequately for the needs of care experienced young adults. The findings point towards the need for a revised conceptualisation of the notion of “independence” which has to take into account the manifold and changing relationships between individuals and the state. Instead of a “cliff edge” approach there should be support for a more gradual shift from “dependence” to “independence” enabling those with care experience to develop their full potential. In interpreting the findings, limitations of the available data have to be acknowledged, pointing to the need for generating harmonised and longitudinal data on vulnerable subpopulations to enable effective monitoring of needs and provision

Depressive and subthreshold depressive symptomatology among older adults in a socioeconomically deprived area in Brazil

Depressive and subthreshold depressive symptomatology are common but often neglected in older adults. / Objective: This study aimed to assess rates of depressive and subthreshold depressive symptomatology, and the characteristics associated, among older adults living in a socioeconomically deprived area of Brazil. / Methods: This study is part of the PROACTIVE cluster randomised controlled trial. 3356 adults aged 60+ years and registered in 20 primary health clinics were screened for depressive symptomatology with the Patient Health Questionnaire-9 (PHQ-9). Depressive status was classified according to the total PHQ-9 score and the presence of core depressive symptoms (depressed mood and anhedonia) as follows: no depressive symptomatology (PHQ-9 score 0–4, or 5–9 but with no core depressive symptom); subthreshold depressive symptomatology (PHQ-9 score 5–9 and at least one core depressive symptom); and depressive symptomatology (PHQ-9 score ≥ 10). Sociodemographic information and self-reported chronic conditions were collected. Relative risk ratios and 95% CIs were obtained using a multinomial regression model. / Results: Depressive and subthreshold depressive symptomatology were present in 30% and 14% of the screened sample. Depressive symptomatology was associated with female gender, low socioeconomic conditions and presence of chronic conditions, whereas subthreshold depressive symptomatology was only associated with female gender and having hypertension. / Conclusions: Depressive and subthreshold depressive symptomatology is highly prevalent in this population registered with primary care clinics. Strategies managed by primary care non-mental health specialists can be a first step for improving this alarming and neglected situation among older adults

Methods for think-aloud interviews in health-related resource-use research:the PECUNIA RUM instrument

The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent’s perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap. Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A ‘before the interview’ (including translation, recruitment, training), Part B ‘during the interview’ (including setting, opening, completing the instrument, open-ended questions, closing), and part C ‘after the interview’ (including transcription and data analysis, trustworthiness). This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.</p

A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition. OBJECTIVES: To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. DATA SOURCES: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. REVIEW METHODS: We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ). RESULTS: We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. LIMITATIONS: The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. CONCLUSIONS: In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. STUDY REGISTRATION: The study is registered as PROSPERO CRD42012002441. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme