Simple steps to develop trial follow-up procedures.

BACKGROUND: Loss to follow-up in randomised controlled trials reduces statistical power and increases the potential for bias. Almost half of all trials fail to achieve their follow-up target. Statistical methods have been described for handling losses to follow-up and systematic reviews have identified interventions that increase follow-up. However, there is little guidance on how to develop practical follow-up procedures. This paper describes the development of follow-up procedures in a pilot randomised controlled trial of a sexual health intervention that required participants to provide and return questionnaires and chlamydia test samples in the post. We identified effective methods to increase follow-up from systematic reviews. We developed and tested prototype procedures to identify barriers to follow-up completion. We asked trial participants about their views on our follow-up procedures and revised the methods accordingly. RESULTS: We identified 17 strategies to increase follow-up and employed all but five. We found that some postal test kits do not fit through letterboxes and that that the test instructions were complicated. After identifying the appropriate sized test kit and simplifying the instructions, we obtained user opinions. Users wanted kits to be sent in coloured envelopes (so that they could identify them easily), with simple instructions and questionnaires and wanted to be notified before we sent the kits. We achieved 92 % (183/200) overall follow-up for the postal questionnaire at 1 month and 82 % (163/200) at 12 months. We achieved 86 % (171/200) overall follow-up for the postal chlamydia test at 3 months and 80 % (160/200) at 12 months. CONCLUSIONS: By using established methods to increase follow-up, testing prototype procedures and seeking user opinions, we achieved higher follow-up than previous sexual health trials. However, it is not possible to determine if the increase in response was due to our follow-up procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02304709 Date of registration: 27 March 2013

Erratum to: Simple steps to develop trial follow-up procedures.

Unfortunately, the original version of this article [1] contained an error. There were errors in the reference numbers in Additional file 1. This has now been corrected and Additional file 1 is included here with the correct reference numbers

Does repetitive task training improve functional activity after stroke? A Cochrane systematic review and meta-analysis.

Repetitive task training resulted in modest improvement across a range of lower limb outcome measures, but not upper limb outcome measures. Training may be sufficient to have a small impact on activities of daily living. Interventions involving elements of repetition and task training are diverse and difficult to classify: the results presented are specific to trials where both elements are clearly present in the intervention, without major confounding by other potential mechanisms of action

What do we want to get out of this?:a critical interpretive synthesis of the value of process evaluations, with a practical planning framework

BACKGROUND: Process evaluations aim to understand how complex interventions bring about outcomes by examining intervention mechanisms, implementation, and context. While much attention has been paid to the methodology of process evaluations in health research, the value of process evaluations has received less critical attention. We aimed to unpack how value is conceptualised in process evaluations by identifying and critically analysing 1) how process evaluations may create value and 2) what kind of value they may create. METHODS: We systematically searched for and identified published literature on process evaluation, including guidance, opinion pieces, primary research, reviews, and discussion of methodological and practical issues. We conducted a critical interpretive synthesis and developed a practical planning framework. RESULTS: We identified and included 147 literature items. From these we determined three ways in which process evaluations may create value or negative consequences: 1) through the socio-technical processes of ‘doing’ the process evaluation, 2) through the features/qualities of process evaluation knowledge, and 3) through using process evaluation knowledge. We identified 15 value themes. We also found that value varies according to the characteristics of individual process evaluations, and is subjective and context dependent. CONCLUSION: The concept of value in process evaluations is complex and multi-faceted. Stakeholders in different contexts may have very different expectations of process evaluations and the value that can and should be obtained from them. We propose a planning framework to support an open and transparent process to plan and create value from process evaluations and negotiate trade-offs. This will support the development of joint solutions and, ultimately, generate more value from process evaluations to all. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-022-01767-7

Minimum Incidence of Adult Invasive Pneumococcal Disease in Blantyre, Malawi an Urban African Setting: A Hospital Based Prospective Cohort Study

Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect impact of PCV13 introduction to the childhood immunisation program

Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

Texting Sexual Health Pilot - Interview Guide

A semi-structured topic guide used to discover participants’ views, experiences, and recommendations for improvements to behavioral intervention on sexual health. Questions cover tone and frequency of text messages, views regarding the message content, any concerns about others viewing texts, what (if anything) they had learned from text messages, sexual behavior since enrolment (such as condom use and partner notification), and suggested improvements to the intervention

Mouse Models to Understand Mutagenic Outcomes and Illegitimate Repair of DNA Damage

Maintenance of genome integrity is critical to prevent cell death or disease. Illegitimate repair of chromosomal DNA breaks can lead to mutations and genome rearrangements which are a well-known hallmark of multiple cancers and disorders. Endogenous causes of DNA double-strand breaks (DSBs) include reactive oxygen species (ROS) and replication errors while exogenous causes of DNA breaks include ionizing radiation, UV radiation, alkylating agents, and inhibitors of topoisomerase II (Top2). Recent evidence suggests that a growing list of environmental agents or toxins and natural dietary compounds also cause DNA breaks. Understanding the consequences of exposure to a broad spectrum of DSB-inducing agents has significant implications for understanding mutagenicity, genome stability and human health. This chapter will review in vivo mouse models designed to measure DNA damage and mutagenicity, and illegitimate repair of DNA DSBs caused by exposure to environmental agents

Isomorphic forces and their effects on gender gap in Australian project-based organisations

This paper demonstrates that strong isomorphic forces contribute to the ongoing female underrepresentation in project-based organisations in Australia. Through a qualitative study of career experiences of women project managers, the underlying structural barriers to their career progression in construction and property development organisations are examined. The barriers appear as unique to project-based organisations and include project work practices; lack of career paths for project managers and limited organisational commitment to gender diversity. The Australian project-based organisations must purposely foster their female project managers to overcome isomorphism and thereby bolster their productivity and stay competitive on a global scale now and into the future

Repetitive Task Training for Improving Functional Ability After Stroke: A major update of a Cochrane Review

Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation