Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

Increasing understanding of the relationship between geographic access and gendered decision-making power for treatment-seeking for febrile children in the Chikwawa district of Malawi

Background: This study used qualitative methods to investigate the relationship between geographic access and gendered intra-household hierarchies and how these influence treatment-seeking decision-making for childhood fever within the Chikwawa district of Malawi. Previous cross-sectional survey findings in the district indicated that distance from facility and associated costs are important determinants of health facility attendance in the district. This paper uses qualitative data to add depth of understanding to these findings by exploring the relationship between distance from services, anticipated costs and cultural norms of intra-household decision-making, and to identify potential intervention opportunities to reduce challenges experienced by those in remote locations. Qualitative data collection included 12 focus group discussions and 22 critical incident interviews conducted in the local language, with primary caregivers of children who had recently experienced a febrile episode. Results: Low geographic accessibility to facilities inhibited care-seeking, sometimes by extending the ‘assessment period’ for a child’s illness episode, and led to delays in seeking formal treatment, particularly when the illness occurred at night. Although carers attempted to avoid incurring costs, cash was often needed for transport and food. Whilst in all communities fathers were normatively responsible for treatment costs, mothers generally had greater access to and control over resources and autonomy in decision-making in the matrilineal and matrilocal communities in the central part of the district, which were also closer to formal facilities. Conclusions: This study illustrates the complex interplay between geographic access and gender dynamics in shaping decisions on whether and when formal treatment is sought for febrile children in Chikwawa District. Geographic marginality and cultural norms intersect in remote areas both to increase the logistical and anticipated financial barriers to utilising services and to reduce caretakers’ autonomy to act quickly once they recognize the need for formal care. Health education campaigns should be based within communities, engaging all involved in treatment-seeking decision-making, including men and grandmothers, and should aim to promote the ability of junior women to influence the treatment-seeking process. Both mothers’ financial autonomy and fathers financial contributions are important to enable timely access to effective healthcare for children with malaria

High Efficiency Colloidal Quantum Dot Infrared Light Emitting Diodes via Engineering at the Supra-Nanocrystalline Level

Colloidal quantum dot (CQD) light-emitting diodes (LEDs) deliver a compelling performance in the visible, yet infrared CQD LEDs underperform their visible-emitting counterparts, largely due to their low photoluminescence quantum efficiency. Here we employ a ternary blend of CQD thin film that comprises a binary host matrix that serves to electronically passivate as well as to cater for an efficient and balanced carrier supply to the emitting quantum dot species. In doing so, we report infrared PbS CQD LEDs with an external quantum efficiency of ~7.9% and a power conversion efficiency of ~9.3%, thanks to their very low density of trap states, on the order of 1014 cm−3, and very high photoluminescence quantum efficiency in electrically conductive quantum dot solids of more than 60%. When these blend devices operate as solar cells they deliver an open circuit voltage that approaches their radiative limit thanks to the synergistic effect of the reduced trap-state density and the density of state modification in the nanocomposite.Peer ReviewedPostprint (author's final draft

Applying GRADE-CERQual to Interpretive Review Findings: Reflections From a Cochrane meta-ethnography on Childhood Vaccination Acceptance

GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) was developed to support the use of evidence from qualitative reviews within policy- and decision-making. To date, the approach has been applied predominantly to aggregative synthesis methodologies and descriptive review findings. GRADE-CERQual guidance recommends the approach be tested on more diverse review methodologies and outputs to support its evolution. This paper contributes to this evolution by reflecting on our experiences of applying GRADE-CERQual to findings that emerged from a recent Cochrane meta-ethnography on childhood vaccination. Specifically, we describe the similarities and differences, challenges and dilemmas we experienced applying the approach to more interpretive versus more descriptive review findings. We found that we were able to apply the core criteria and principles of GRADE-CERQual in ways that were congruent with the methodologies and epistemologies of a meta-ethnography and its findings. We also found that the practical application processes were similar across review finding types. The main differences related to the level of demand placed on the evidence and the level of complexity involved with the decisions. Compared to more descriptive findings, more interpretive findings required evidence that was richer, thicker, more contextually situated and methodologically stronger for us to have the same level of confidence in them. Making the assessments for these findings also involved more complicated forms of judgement. We provide practical examples to illustrate these complexities and how we approached them, which others applying GRADE-CERQual to more interpretive review findings could draw upon. We also highlight areas requiring further discussion, in the hope that this will offer a platform for engagement and the potential future refinement of the approach. Ultimately, this could enhance the usability of GRADE-CERQual for a larger range of qualitative review findings and in turn expand the kinds of knowledges that count within decision-making

Applying GRADE-CERQual to qualitative evidence synthesis findings: Introduction to the series

This is the final version. Available from BMC via the DOI in this record. Additional materials are available on the GRADE-CERQual website (www.cerqual.org)The GRADE-CERQual ('Confidence in the Evidence from Reviews of Qualitative research') approach provides guidance for assessing how much confidence to place in findings from systematic reviews of qualitative research (or qualitative evidence syntheses). The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. Confidence in the evidence from qualitative evidence syntheses is an assessment of the extent to which a review finding is a reasonable representation of the phenomenon of interest. CERQual provides a systematic and transparent framework for assessing confidence in individual review findings, based on consideration of four components: (1) methodological limitations, (2) coherence, (3) adequacy of data, and (4) relevance. A fifth component, dissemination (or publication) bias, may also be important and is being explored. As with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach for effectiveness evidence, CERQual suggests summarising evidence in succinct, transparent, and informative Summary of Qualitative Findings tables. These tables are designed to communicate the review findings and the CERQual assessment of confidence in each finding. This article is the first of a seven-part series providing guidance on how to apply the CERQual approach. In this paper, we describe the rationale and conceptual basis for CERQual, the aims of the approach, how the approach was developed, and its main components. We also outline the purpose and structure of this series and discuss the growing role for qualitative evidence in decision-making. Papers 3, 4, 5, 6, and 7 in this series discuss each CERQual component, including the rationale for including the component in the approach, how the component is conceptualised, and how it should be assessed. Paper 2 discusses how to make an overall assessment of confidence in a review finding and how to create a Summary of Qualitative Findings table. The series is intended primarily for those undertaking qualitative evidence syntheses or using their findings in decision-making processes but is also relevant to guideline development agencies, primary qualitative researchers, and implementation scientists and practitioners.WHONorad (Norwegian Agency for Development Cooperation)Research Council of NorwayCochrane Methods Innovation FundSouth African Medical Research Counci

Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 4: How to assess coherence

This is the final version. Available from BMC via the DOI in this record. Additional materials are available on the GRADE-CERQual website (www.cerqual.org)Background: The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE working group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) relevance, (3) coherence and (4) adequacy of data. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual's coherence component. Methods: We developed the coherence component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual coherence component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. Results: When applying CERQual, we define coherence as how clear and cogent the fit is between the data from the primary studies and a review finding that synthesises that data. In this paper, we describe the coherence component and its rationale and offer guidance on how to assess coherence in the context of a review finding as part of the CERQual approach. This guidance outlines the information required to assess coherence, the steps that need to be taken to assess coherence and examples of coherence assessments. Conclusions: This paper provides guidance for review authors and others on undertaking an assessment of coherence in the context of the CERQual approach. We suggest that threats to coherence may arise when the data supporting a review finding are contradictory, ambiguous or incomplete or where competing theories exist that could be used to synthesise the data. We expect the CERQual approach, and its individual components, to develop further as our experiences with the practical implementation of the approach increase.WHONorad (Norwegian Agency for Development Cooperation)Research Council of NorwayCochrane methods Innovation FundSouth African Medical Research Counci

Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 3: How to assess methodological limitations

This is the final version. Available from BMC via the DOI in this record. Additional materials are available on the GRADE-CERQual website (www.cerqual.org)Background: The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual's methodological limitations component. Methods: We developed the methodological limitations component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual methodological limitations component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. Results: When applying CERQual, we define methodological limitations as the extent to which there are concerns about the design or conduct of the primary studies that contributed evidence to an individual review finding. In this paper, we describe the methodological limitations component and its rationale and offer guidance on how to assess methodological limitations of a review finding as part of the CERQual approach. This guidance outlines the information required to assess methodological limitations component, the steps that need to be taken to assess methodological limitations of data contributing to a review finding and examples of methodological limitation assessments. Conclusions: This paper provides guidance for review authors and others on undertaking an assessment of methodological limitations in the context of the CERQual approach. More work is needed to determine which criteria critical appraisal tools should include when assessing methodological limitations. We currently recommend that whichever tool is used, review authors provide a transparent description of their assessments of methodological limitations in a review finding. We expect the CERQual approach and its individual components to develop further as our experiences with the practical implementation of the approach increase.WHONorad (Norwegian Agency for Development Cooperation)Research Council of NorwayCochrane Methods Innovation FundSouth African Medical Research Counci

Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 2: How to make an overall CERQual assessment of confidence and create a Summary of Qualitative Findings table

This is the final version. Available from BMC via the DOI in this record. Additional materials are available on the GRADE-CERQual website (www.cerqual.org)Background: The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on making an overall assessment of confidence in a review finding and creating a CERQual Evidence Profile and a CERQual Summary of Qualitative Findings table. Methods: We developed this guidance by examining the methods used by other GRADE approaches, gathering feedback from relevant research communities and developing consensus through project group meetings. We then piloted the guidance on several qualitative evidence syntheses before agreeing on the approach. Results: Confidence in the evidence is an assessment of the extent to which a review finding is a reasonable representation of the phenomenon of interest. Creating a summary of each review finding and deciding whether or not CERQual should be used are important steps prior to assessing confidence. Confidence should be assessed for each review finding individually, based on the judgements made for each of the four CERQual components. Four levels are used to describe the overall assessment of confidence: high, moderate, low or very low. The overall CERQual assessment for each review finding should be explained in a CERQual Evidence Profile and Summary of Qualitative Findings table. Conclusions: Structuring and summarising review findings, assessing confidence in those findings using CERQual and creating a CERQual Evidence Profile and Summary of Qualitative Findings table should be essential components of undertaking qualitative evidence syntheses. This paper describes the end point of a CERQual assessment and should be read in conjunction with the other papers in the series that provide information on assessing individual CERQual components.WHONorad (Norwegian Agency for Development Cooperation)Research Council of NorwayCochrane Methods Innovation FundSouth African Medical Research Counci

Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 6: How to assess relevance of the data

This is the final version. Available from BMC via the DOI in this record. Additional materials are available on the GRADE-CERQual website (www.cerqual.org)Background: The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual's relevance component. Methods: We developed the relevance component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual relevance component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. Results: When applying CERQual, we define relevance as the extent to which the body of data from the primary studies supporting a review finding is applicable to the context (perspective or population, phenomenon of interest, setting) specified in the review question. In this paper, we describe the relevance component and its rationale and offer guidance on how to assess relevance in the context of a review finding. This guidance outlines the information required to assess relevance, the steps that need to be taken to assess relevance and examples of relevance assessments. Conclusions: This paper provides guidance for review authors and others on undertaking an assessment of relevance in the context of the CERQual approach. Assessing the relevance component requires consideration of potentially important contextual factors at an early stage in the review process. We expect the CERQual approach, and its individual components, to develop further as our experiences with the practical implementation of the approach increase.WHONorad (Norwegian Agency for Development Cooperation)Research Council of NorwayCochrane Methods Innovation FundSouth African Medical Research Counci

Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 7: Understanding the potential impacts of dissemination bias

This is the final version. Available from BMC via the DOI in this record. Additional materials are available on the GRADE-CERQual website (www.cerqual.org).Background: The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on a probable fifth component, dissemination bias. Given its exploratory nature, we are not yet able to provide guidance on applying this potential component of the CERQual approach. Instead, we focus on how dissemination bias might be conceptualised in the context of qualitative research and the potential impact dissemination bias might have on an overall assessment of confidence in a review finding. We also set out a proposed research agenda in this area. Methods: We developed this paper by gathering feedback from relevant research communities, searching MEDLINE and Web of Science to identify and characterise the existing literature discussing or assessing dissemination bias in qualitative research and its wider implications, developing consensus through project group meetings, and conducting an online survey of the extent, awareness and perceptions of dissemination bias in qualitative research. Results: We have defined dissemination bias in qualitative research as a systematic distortion of the phenomenon of interest due to selective dissemination of studies or individual study findings. Dissemination bias is important for qualitative evidence syntheses as the selective dissemination of qualitative studies and/or study findings may distort our understanding of the phenomena that these syntheses aim to explore and thereby undermine our confidence in these findings. Dissemination bias has been extensively examined in the context of randomised controlled trials and systematic reviews of such studies. The effects of potential dissemination bias are formally considered, as publication bias, within the GRADE approach. However, the issue has received almost no attention in the context of qualitative research. Because of very limited understanding of dissemination bias and its potential impact on review findings in the context of qualitative evidence syntheses, this component is currently not included in the GRADE-CERQual approach. Conclusions: Further research is needed to establish the extent and impacts of dissemination bias in qualitative research and the extent to which dissemination bias needs to be taken into account when we assess how much confidence we have in findings from qualitative evidence syntheses.WHONorad (Norwegian Agency for Development Cooperation)Research Council of NorwayCochrane Methods Innovation FundSouth African Medical Research Counci