Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders

The influence of contextual factors on healthcare quality improvement initiatives:what works, for whom and in what setting? Protocol for a realist review

Background  Context shapes the effectiveness of knowledge implementation and influences health improvement. Successful healthcare quality improvement (QI) initiatives frequently fail to transfer to different settings, with local contextual factors often cited as the cause. Understanding and overcoming contextual barriers is therefore crucial to implementing effective improvement; yet context is still poorly understood. There is a paucity of information on the mechanisms underlyinghowandwhyQI projects succeed or fail in given settings. A realist review of empirical studies of healthcare QI initiatives will be undertaken to examine the influence and impact of contextual factors on quality improvement in healthcare settings and explore whether QI initiatives can work in all contexts.  Methods  The review will explore which contextual factors are important, and how, why, when and for whom they are important, within varied settings. The dynamic nature of context and change over time will be explored by examining which aspects of context impact at key points in the improvement trajectory. The review will also consider the influence of context on improvement outcomes (provider- and patient-level), spread and sustainability. The review process will follow five iterative steps: (1) clarify scope, (2) search for evidence, (3) appraise primary studies and extract data, (4) synthesise evidence and draw conclusions and (5) disseminate findings. The reviewers will consult with experts and stakeholders in the early stages to focus the review and develop a programme theory consisting of explanatory ‘context–mechanism–outcome’ configurations. Searches for primary evidence will be conducted iteratively. Data will be extracted and tested against the programme theory. A review advisory group will oversee the review process. Review findings will follow RAMESES guidelines and will be disseminated via a report, presentations and peer-reviewed publications.  Discussion  The review will update and consolidate evidence on the contextual conditions for effective improvement and distil new knowledge to inform the design and development of context-sensitive QI initiatives. This review ties in with the study of improvement programmes as vehicles of change and the development of an evidence base around healthcare improvement by addressing whether QI initiatives can work in all contexts.  Systematic review registration  PROSPERO CRD4201706213

Policymakers\u27 experience of a capacity-building intervention designed to increase their use of research: A realist process evaluation

Background: An intervention’s success depends on how participants interact with it in local settings. Process evaluation examines these interactions, indicating why an intervention was or was not effective, and how it (and similar interventions) can be improved for better contextual fit. This is particularly important for innovative trials like Supporting Policy In health with Research: an Intervention Trial (SPIRIT), where causal mechanisms are poorly understood. SPIRIT was testing a multi-component intervention designed to increase the capacity of health policymakers to use research. Methods: Our mixed-methods process evaluation sought to explain variation in observed process effects across the six agencies that participated in SPIRIT. Data collection included observations of intervention workshops (n = 59), purposively sampled interviews (n = 76) and participant feedback forms (n = 553). Using a realist approach, data was coded for context-mechanism-process effect configurations (retroductive analysis) by two authors. Results: Intervention workshops were very well received. There was greater variation of views regarding other aspects of SPIRIT such as data collection, communication and the intervention’s overall value. We identified nine inter-related mechanisms that were crucial for engaging participants in these policy settings: (1) Accepting the premise (agreeing with the study’s assumptions); (2) Self-determination (participative choice); (3) The Value Proposition (seeing potential gain); (4) ‘Getting good stuff’ (identifying useful ideas, resources or connections); (5) Self-efficacy (believing ‘we can do this!’); (6) Respect (feeling that SPIRIT understands and values one’s work); (7) Confidence (believing in the study’s integrity and validity); (8) Persuasive leadership (authentic and compelling advocacy from leaders); and (9) Strategic insider facilitation (local translation and mediation). These findings were used to develop tentative explanatory propositions and to revise the programme theory. Conclusion: This paper describes how SPIRIT functioned in six policy agencies, including why strategies that worked well in one site were less effective in others. Findings indicate a complex interaction between participants’ perception of the intervention, shifting contextual factors, and the form that the intervention took in each site. Our propositions provide transferable lessons about contextualised areas of strength and weakness that may be useful in the development and implementation of similar studies

A realist approach to eliciting the initial programme theory of the antiretroviral treatment adherence club intervention in the Western Cape Province, South Africa

BACKGROUND: The successful initiation of people living with HIV/AIDS on antiretroviral therapy (ART) in South Africa has engendered challenges of poor retention in care and suboptimal adherence to medication. The adherence club intervention was implemented in the Metropolitan area of the Western Cape Province to address these challenges. The adherence club programme has shown potential to relieve clinic congestion, improve retention in care and enhance treatment adherence in the context of rapidly growing HIV patient populations being initiated on ART. Nevertheless, how and why the adherence club intervention works is not clearly understood. We aimed to elicit an initial programme theory as the first phase of the realist evaluation of the adherence club intervention in the Western Cape Province. METHODS: The realist evaluation approach guided the elicitation study. First, information was obtained from an exploratory qualitative study of programme designers’ and managers’ assumptions of the intervention. Second, a document review of the design, rollout, implementation and outcome of the adherence clubs followed. Third, a systematic review of available studies on group-based ART adherence support models in Sub-Saharan Africa was done, and finally, a scoping review of social, cognitive and behavioural theories that have been applied to explain adherence to ART. We used the realist evaluation heuristic tool (Intervention-context-actors-mechanism-outcome) to synthesise information from the sources into a configurational map. The configurational mapping, alignment of a specific combination of attributes, was based on the generative causality logic – retroduction. RESULTS: We identified two alternative theories: The first theory supposes that patients become encouraged, empowered and motivated, through the adherence club intervention to remain in care and adhere to the treatment. The second theory suggests that stable patients on ART are being nudged through club rules and regulations to remain in care and adhere to the treatment with the goal to decongest the primary health care facilities. CONCLUSION: The initial programme theory describes how (dynamics) and why (theories) the adherence club intervention is expected to work. By testing theories in “real intervention cases” using the realist evaluation approach, the theories can be modified, refuted and/or reconstructed to elicit a refined theory of how and why the adherence club intervention works

Stress responses in alfalfa (Medicago sativa L.) XIX. Transcriptional activation of oxidative pentose phosphate pathway genes at the onset of the isoflavonoid phytoalexin response

Article on stress responses in alfalfa (Medicago sativa L.) XIX and transcriptional activation of oxidative pentose phosphate pathway genes at the onset of the isoflavonoid phytoalexin response