On thermodynamic and quantum fluctuations of cosmological constant

We discuss from the condensed-matter point of view the recent idea that the Poisson fluctuations of cosmological constant about zero could be a source of the observed dark energy. We argue that the thermodynamic fluctuations of Lambda are much bigger. Since the amplitude of fluctuations is proportional to V^{-1/2}, where V is the volume of the Universe, the present constraint on the cosmological constant provides the lower limit for V, which is much bigger than the volume within the cosmological horizon.Comment: 4 pages, version submitted to JETP Letter

Design, analysis and presentation of factorial randomised controlled trials

BackgroundThe evaluation of more than one intervention in the same randomised controlled trial can be achieved using a parallel group design. However this requires increased sample size and can be inefficient, especially if there is also interest in considering combinations of the interventions. An alternative may be a factorial trial, where for two interventions participants are allocated to receive neither intervention, one or the other, or both. Factorial trials require special considerations, however, particularly at the design and analysis stages.DiscussionUsing a 2 × 2 factorial trial as an example, we present a number of issues that should be considered when planning a factorial trial. The main design issue is that of sample size. Factorial trials are most often powered to detect the main effects of interventions, since adequate power to detect plausible interactions requires greatly increased sample sizes. The main analytical issues relate to the investigation of main effects and the interaction between the interventions in appropriate regression models. Presentation of results should reflect the analytical strategy with an emphasis on the principal research questions. We also give an example of how baseline and follow-up data should be presented. Lastly, we discuss the implications of the design, analytical and presentational issues covered.SummaryDifficulties in interpreting the results of factorial trials if an influential interaction is observed is the cost of the potential for efficient, simultaneous consideration of two or more interventions. Factorial trials can in principle be designed to have adequate power to detect realistic interactions, and in any case they are the only design that allows such effects to be investigated

Patients’ experience and satisfaction in primary care: secondary analysis using multilevel modelling

Objective To explore whether responses to questions in surveys of patients that purport to assess the performance of general practices or doctors reflect differences between practices, doctors, or the patients themselves

Should we adjudicate outcomes in stroke trials? A systematic review

BACKGROUND: Central adjudication of outcomes is common in randomized clinical trials in stroke. The rationale for adjudication is clear; centrally adjudicated outcomes should have less random and systematic errors than outcomes assessed locally by site investigators. However, adjudication brings added complexities to a clinical trial and can be costly. AIM: To assess the evidence for outcome adjudication in stroke trials. SUMMARY OF REVIEW: We identified 12 studies evaluating central adjudication in stroke trials. The majority of these were secondary analyses of trials, and the results of all of these would have remained unchanged had central adjudication not taken place, even for trials without sufficient blinding. The largest differences between site-assessed and adjudicator-assessed outcomes were between the most subjective outcomes, such as causality of serious adverse events. We found that the cost of adjudication could be upward of £100,000 for medium to large prevention trials. These findings suggest that the cost of central adjudication may outweigh the advantages it brings in many cases. However, through simulation, we found that only a small amount of bias is required in site investigators’ outcome assessments before adjudication becomes important. CONCLUSION: Central adjudication may not be necessary in stroke trials with blinded outcome assessment. However, for open-label studies, central adjudication may be more important

A cluster randomized clinical trial of a stepped care intervention for depression in primary care (STEPCARE)--study protocol.

BACKGROUND: Depression constitutes a significant public health burden and is associated is with high level of individual suffering. Insufficient human and material resources impede the provision of adequate care for persons with the condition in low- and middle-income countries. It is commonly recognized that, to bridge this treatment gap, it is essential to integrate the treatment of depression into primary health care system. METHODS/DESIGN: STEPCARE is a two-arm parallel cluster randomized controlled trial to compare a stepped-care intervention package for depression in primary health care with care as usual in Nigeria. Randomization was conducted at the level of the participating primary health care clinics, while interventions are delivered to consenting individual participants who screen positive on the 9-item patient health questionnaire (PHQ-9 score ≥ 11) and fulfil the DSM-IV criteria for major depression. Intervention delivered by trained primary health care workers (PHCW) supported by general physicians and psychiatrists as needed is in 3 steps determined by response to treatment. Each step consists of psychological interventions (including psychoeducation, activity scheduling, social network reactivation and problem solving treatment) offered to all participants and, depending on severity and response, medication. Primary outcome, assessed at 12 months following recruitment into the trial, is recovery from depression as shown by a PHQ-9 score of less than 6. Secondary outcomes include changes in disability, quality of life and service utilization assessed at 6 and 12 months. DISCUSSION: The stepped care model examines the effectiveness of an intervention package for depression in which the intensity of treatment is determined by the clinical need of the patients. This approach is designed to make the most efficient use of available resources. TRIAL REGISTRATION: ISRCTN46754188 (ISRTCN registry at isrtcn.com; registered 23 September 2013)

Inter-rater agreement in the scoring of abstracts submitted to a primary care research conference

BACKGROUND: Checklists for peer review aim to guide referees when assessing the quality of papers, but little evidence exists on the extent to which referees agree when evaluating the same paper. The aim of this study was to investigate agreement on dimensions of a checklist between two referees when evaluating abstracts submitted for a primary care conference. METHODS: Anonymised abstracts were scored using a structured assessment comprising seven categories. Between one (poor) and four (excellent) marks were awarded for each category, giving a maximum possible score of 28 marks. Every abstract was assessed independently by two referees and agreement measured using intraclass correlation coefficients. Mean total scores of abstracts accepted and rejected for the meeting were compared using an unpaired t test. RESULTS: Of 52 abstracts, agreement between reviewers was greater for three components relating to study design (adjusted intraclass correlation coefficients 0.40 to 0.45) compared to four components relating to more subjective elements such as the importance of the study and likelihood of provoking discussion (0.01 to 0.25). Mean score for accepted abstracts was significantly greater than those that were rejected (17.4 versus 14.6, 95% CI for difference 1.3 to 4.1, p = 0.0003). CONCLUSIONS: The findings suggest that inclusion of subjective components in a review checklist may result in greater disagreement between reviewers. However in terms of overall quality scores, abstracts accepted for the meeting were rated significantly higher than those that were rejected

Experiences of patients and healthcare professionals of NHS cardiovascular health checks: a qualitative study

Background NHS Health Checks are a national cardiovascular risk assessment and management programme in England and Wales. We examined the experiences of patients attending and healthcare professionals (HCPs) conducting NHS Health Checks. Methods Interviews were conducted with a purposive sample of 28 patients and 16 HCPs recruited from eight general practices across a range of socio-economic localities. Interviews were audio recorded, transcribed, anonymized and analysed thematically. Results Patients were motivated to attend an NHS Health Check because of health beliefs, the perceived value of the programme, a family history of cardiovascular and other diseases and expectations of receiving a general health assessment. Some patients reported benefits including reassurance and reinforcement of healthy lifestyles. Others experienced confusion and frustration about how results and advice were communicated, some having a poor understanding of the implications of their results. HCPs raised concerns about the skill set of some staff to competently communicate risk and lifestyle information. Conclusions To improve the satisfaction of patients attending and improve facilitation of lifestyle change, HCPs conducting the NHS Health Checks require sufficient training to equip them with appropriate skills and knowledge to deliver the service effectively

Associations between physical activity parenting practices and adolescent girls’ self-9 perceptions and physical activity intentions

Background: The present study investigated cross-sectional associations between maternal and paternal logistic and modelling physical activity support and the self-efficacy, self-esteem and physical activity intentions of 11-12 year old girls. Method: 210 girls reported perceptions of maternal and paternal logistic and modelling support and their self-efficacy, self-esteem and intention to be physically active. Data were analysed using multivariable regression models. Results: Maternal logistic support was positively associated with participants’ self-esteem, physical activity self-efficacy and intention to be active. Maternal modelling was positively associated with self-efficacy. Paternal modelling was positively associated with self-esteem and self-efficacy but there was no evidence that paternal logistic support was associated with the psychosocial variables. Conclusions: Activity-related parenting practices were associated with psychosocial correlates of physical activity among adolescent girls. Logistic support from mothers, rather than modelling support or paternal support may be a particularly important target when designing interventions aimed at preventing the age-related decline in physical activity among girls

Two-by-two factorial randomised study within a trial (SWAT) to evaluate strategies for follow-up in a randomised prevention trial

BackgroundFailure to collect outcome data in randomised trials can result in bias and loss of statistical power. Further evaluations of strategies to increase retention are required. We assessed the effectiveness of two strategies for retention in a randomised prevention trial using a two-by-two factorial randomised study within a trial (SWAT).MethodsParents of babies included in the host trial were randomised to (1) short message service (SMS) notification prior to sending questionnaires at 3, 6, 12 and 18 months versus no SMS notification and (2) a £10 voucher sent with the invitation letter for the primary follow-up visit at 24 months or given at the visit. The two co-primary outcomes were collection of host trial (1) questionnaire data at interim follow-up times and (2) primary outcome at 24 months during a home/clinic visit with a research nurse.ResultsBetween November 2014 and November 2016, 1394 participants were randomised: 350 to no SMS + voucher at visit, 345 to SMS + voucher at visit, 352 to no SMS + voucher before visit and 347 to SMS + voucher before visit. Overall questionnaire data was collected at interim follow-up times for 75% in both the group allocated to the prior SMS notification and the group allocated to no SMS notification (odds ratio (OR) SMS versus none 1.02, 95% CI 0.83 to 1.25). Host trial primary outcome data was collected at a visit for 557 (80%) allocated to the voucher before the visit in the invitation letter and for 566 (81%) whose parents were allocated to receive the voucher at the visit (OR before versus at visit 0.89, 95% CI 0.69 to 1.17).ConclusionThere was no evidence of a difference in retention according to SMS notification or voucher timing. Future synthesis of SWAT results is required to be able to detect small but important incremental effects of retention strategies

Depression symptom trajectories and associated risk factors among adolescents in Chile.

Adolescence is a key period for studying the development of depression, with studies in Europe and North America showing a pattern of elevated risk that begins in early adolescence and continues to increase as adolescents age. Few studies have examined the course of adolescent depression and associated risk factors in low and middle-income countries. This longitudinal cohort study examined depression symptom trajectories and risk factors in a sample of socio-economically disadvantaged adolescents in Chile (n = 2,508). Data were collected over an 18-month period as part of a clinical trial for secondary students aged 12 to 18 (median age 14). Clinical levels of depression were prevalent in this sample at baseline (35% for girls and 28% for boys); yet latent growth models of symptom trajectories revealed a pattern of decreasing symptoms over time. There was evidence of an anxiety-depression developmental pathway for girls, with elevated anxiety levels initially predicting poorer depression outcomes later on. Poor problem-solving skills were associated with initial depression levels but did not predict the course of depressive symptoms. Critically, the declining symptom trajectories raise important methodological issues regarding the effects of repeated assessment in longitudinal studies