SUPPORT Tools for evidence-informed health Policymaking (STP) 16: Using research evidence in balancing the pros and cons of policies

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners

Combined inhibition of Ref‐1 and STAT3 leads to synergistic tumour inhibition in multiple cancers using 3D and in vivo tumour co‐culture models

With a plethora of molecularly targeted agents under investigation in cancer, a clear need exists to understand which pathways can be targeted simultaneously with multiple agents to elicit a maximal killing effect on the tumour. Combination therapy provides the most promise in difficult to treat cancers such as pancreatic. Ref‐1 is a multifunctional protein with a role in redox signalling that activates transcription factors such as NF‐κB, AP‐1, HIF‐1α and STAT3. Formerly, we have demonstrated that dual targeting of Ref‐1 (redox factor‐1) and STAT3 is synergistic and decreases cell viability in pancreatic cancer cells. Data presented here extensively expands upon this work and provides further insights into the relationship of STAT3 and Ref‐1 in multiple cancer types. Using targeted small molecule inhibitors, Ref‐1 redox signalling was blocked along with STAT3 activation, and tumour growth evaluated in the presence and absence of the relevant tumour microenvironment. Our study utilized qPCR, cytotoxicity and in vivo analysis of tumour and cancer‐associated fibroblasts (CAF) response to determine the synergy of Ref‐1 and STAT3 inhibitors. Overall, pancreatic tumours grown in the presence of CAFs were sensitized to the combination of STAT3 and Ref‐1 inhibition in vivo. In vitro bladder and pancreatic cancer demonstrated the most synergistic responses. By disabling both of these important pathways, this combination therapy has the capacity to hinder crosstalk between the tumour and its microenvironment, leading to improved tumour response

Outcomes for Implementation Research: Conceptual Distinctions, Measurement Challenges, and Research Agenda

An unresolved issue in the field of implementation research is how to conceptualize and evaluate successful implementation. This paper advances the concept of “implementation outcomes” distinct from service system and clinical treatment outcomes. This paper proposes a heuristic, working “taxonomy” of eight conceptually distinct implementation outcomes—acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability—along with their nominal definitions. We propose a two-pronged agenda for research on implementation outcomes. Conceptualizing and measuring implementation outcomes will advance understanding of implementation processes, enhance efficiency in implementation research, and pave the way for studies of the comparative effectiveness of implementation strategies

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease

The association between prison cell spatial density and infectious and communicable disease: a systematic review

Background: In many countries public and political interest exists on the communicable disease effects of prison crowding, prompting standards on minimum floor area of sleeping accommodation per person. Yet the extent and reliability of the worldwide evidence on the association between prison cell spatial density and communicable diseases is uncertain.Method: We conducted a systematic review of the peer-reviewed and grey literature for articles that reported on the association between prison cell spatial density and communicable disease effects in prisoners. Included studies were assessed for quality. A draft report was peer-reviewed by an independent researcher. Some revisions were made in light of reviewer comments.Findings: 3,532 articles were identified and 6 were included. Studies were conducted in the US (1980s), Pakistan (2003) and Nigeria (2012, 2013). Communicable disease effects/outcomes included pneumococcal disease/acute pneumonia, mycobacterium tuberculosis, infectious skin conditions, and communicable disease reporting to the prison clinic. There was mostly consistent evidence that cell spatial density is associated with communicable diseases. The associations and statistical precision observed suggest a ‘slight’ communicable disease impact of cell spatial density on prisoners. However, it is possible that these associations are due to confounding, bias and/or chance. Conclusion: The evidence provides some support that communicable disease effects are associated with cell spatial density but care should be taken in the interpretation of the findings. Socio-cultural demographic and historical differences between study populations examined also restrict the generalisability of findings. Key words: Communicable diseases; Population health planning, demography, needs assessment; Justice and ethics Key messages:1. There is paucity of research examining the association between prison cell crowding (‘spatial density’) and communicable disease effects 2. The small amount of evidence that exists provides some support that communicable disease effects in prisoners are associated with prison cell spatial density3. Care should be taken in the interpretation of these findings, as associations may be due to confounding, bias and/or chance

Identifying significant contributors for smoking cessation among male prisoners in Australia: results from a randomised clinical trial

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: In Australia, an estimated 90% of those entering prison are current tobacco smokers and three-quarters of current prisoners are tobacco smokers. AIMS: To identify factors and their relative contributions to smoking cessation among male prisoners. METHODS: A total of 425 male tobacco smokers with a median age of 32 years in Australian prisons. The primary outcome was continuous abstinence at 3, 6 and 12 months. We measured various sociodemographic characteristics, drug use, psychological distress and the mental and physical health status of the participants. Multivariate logistic regression models and population attributable risks (PAR%) were used to identify the significant factors and their contributions to smoking cessation rates. RESULTS: The median age of participants was 32 years (IQR 25-41 years). High smoking cessation rates were collectively associated with not using drugs, lower psychological distress, good mental health scores and better physical health (PAR%: 93%, 98% and 88% at 3, 6 and 12 months). CONCLUSION: Our study suggests that not using drugs and being in good mental/physical health are the important contributors to continuous abstinence among prisoners. Thus, effective smoking cessation programmes require a multicomponent approach that includes addressing drug problems and mental health functioning. TRIAL REGISTRATION NUMBER: 12606000229572