Effective fall prevention exercise in residential aged care: an intervention component analysis from an updated systematic review.

OBJECTIVE: The effect of fall prevention exercise programmes in residential aged care (RAC) is uncertain. This paper reports on an intervention component analysis (ICA) of randomised controlled trials (RCTs), from an update of a Cochrane review, to develop a theory of features of successful fall prevention exercise in RAC. METHODS: Trial characteristics were extracted from RCTs testing exercise interventions in RAC identified from an update of a Cochrane review to December 2022 (n=32). Eligible trials included RCTs or cluster RCTs in RAC, focusing on participants aged 65 or older, assessing fall outcomes with stand-alone exercise interventions. ICA was conducted on trials with >30 participants per treatment arm compared with control (n=17). Two authors coded trialists' perceptions on intervention features that may have contributed to the observed effect on falls. Inductive thematic analysis was used to identify the key differences between the trials which might account for positive and negative outcomes. RESULTS: 32 RCTs involving 3960 residents including people with cognitive (57%) and mobility (41%) impairments were included. ICA on the 17 eligible RCTs informed the development of a theory that (1) effective fall prevention exercise delivers the right exercise by specifically targeting balance and strength, tailored to the individual and delivered simply at a moderate intensity and (2) successful implementation needs to be sufficiently resourced to deliver structured and supervised exercise at an adequate dose. CONCLUSIONS: This analysis suggests that delivering the right exercise, sufficiently resourced, is important for preventing falls in RAC. This clinical guidance requires confirmation in larger trials.

Critical features of multifactorial interventions for effective falls reduction in residential aged care: a systematic review, intervention component analysis and qualitative comparative analysis.

BACKGROUND: Multifactorial fall prevention trials providing interventions based on individual risk factors have variable success in aged care facilities. To determine configurations of trial features that reduce falls, intervention component analysis (ICA) and qualitative comparative analysis (QCA) were undertaken. METHODS: Randomised controlled trials (RCTs) from a Cochrane Collaboration review (Cameron, 2018) with meta-analysis data, plus trials identified in a systematic search update to December 2021 were included. Meta-analyses were updated. A theory developed through ICA of English publications of trialist's perspectives was assessed through QCA and a subgroup meta-analysis. RESULTS: Pooled effectiveness of multifactorial interventions indicated a falls rate ratio of 0.85 (95% confidence interval, CI, 0.65-1.10; I2 = 85%; 11 trials). All tested interventions targeted both environmental and personal risk factors by including assessment of environmental hazards, a medical or medication review and exercise intervention. ICA emphasised the importance of co-design involving facility staff and managers and tailored intervention delivery to resident's intrinsic factors for successful outcomes. QCA of facility engagement plus tailored delivery was consistent with greater reduction in falls, supported by high consistency (0.91) and coverage (0.85). An associated subgroup meta-analysis demonstrated strong falls reduction without heterogeneity (rate ratio 0.61, 95%CI 0.54-0.69, I2 = 0%; 7 trials). CONCLUSION: Multifactorial falls prevention interventions should engage aged care staff and managers to implement strategies which include tailored intervention delivery according to each resident's intrinsic factors. Such approaches are consistently associated with a successful reduction in falls, as demonstrated by QCA and subgroup meta-analyses. Co-design approaches may also enhance intervention success.

Educational interventions targeting pregnant women to optimise the use of caesarean section: What are the essential elements? A qualitative comparative analysis.

BACKGROUND: Caesarean section (CS) rates are increasing globally, posing risks to women and babies. To reduce CS, educational interventions targeting pregnant women have been implemented globally, however, their effectiveness is varied. To optimise benefits of these interventions, it is important to understand which intervention components influence success. In this study, we aimed to identify essential intervention components that lead to successful implementation of interventions focusing on pregnant women to optimise CS use. METHODS: We re-analysed existing systematic reviews that were used to develop and update WHO guidelines on non-clinical interventions to optimise CS. To identify if certain combinations of intervention components (e.g., how the intervention was delivered, and contextual characteristics) are associated with successful implementation, we conducted a Qualitative Comparative Analysis (QCA). We defined successful interventions as interventions that were able to reduce CS rates. We included 36 papers, comprising 17 CS intervention studies and an additional 19 sibling studies (e.g., secondary analyses, process evaluations) reporting on these interventions to identify intervention components. We conducted QCA in six stages: 1) Identifying conditions and calibrating the data; 2) Constructing truth tables, 3) Checking quality of truth tables; 4) Identifying parsimonious configurations through Boolean minimization; 5) Checking quality of the solution; 6) Interpretation of solutions. We used existing published qualitative evidence synthesis to develop potential theories driving intervention success. RESULTS: We found successful interventions were those that leveraged social or peer support through group-based intervention delivery, provided communication materials to women, encouraged emotional support by partner or family participation, and gave women opportunities to interact with health providers. Unsuccessful interventions were characterised by the absence of at least two of these components. CONCLUSION: We identified four key essential intervention components which can lead to successful interventions targeting women to reduce CS. These four components are 1) group-based delivery, 2) provision of IEC materials, 3) partner or family member involvement, and 4) opportunity for women to interact with health providers. Maternal health services and hospitals aiming to better prepare women for vaginal birth and reduce CS can consider including the identified components to optimise health and well-being benefits for the woman and baby.

CFTR Modulators: From Mechanism to Targeted Therapeutics.

People with cystic fibrosis (CF) suffer from a multi-organ disorder caused by loss-of-function variants in the gene encoding the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Tremendous progress has been made in both basic and clinical sciences over the past three decades since the identification of the CFTR gene. Over 90% of people with CF now have access to therapies targeting dysfunctional CFTR. This success was made possible by numerous studies in the field that incrementally paved the way for the development of small molecules known as CFTR modulators. The advent of CFTR modulators transformed this life-threatening illness into a treatable disease by directly binding to the CFTR protein and correcting defects induced by pathogenic variants. In this chapter, we trace the trajectory of structural and functional studies that brought CF therapies from bench to bedside, with an emphasis on mechanistic understanding of CFTR modulators.

Comparison of national surveillance systems for Lyme disease in humans in Europe and North America: a policy review.

BACKGROUND: Lyme disease incidence is increasing in Europe, the USA, and Canada. In 2010, a comparison of surveillance systems for Lyme disease (LD) in humans in 28 European countries showed that systems highly varied, making epidemiological comparisons difficult. Details by country were not published. In 2018, one of LD clinical manifestations, neuroborreliosis, was added under European Union (EU) surveillance to standardise definitions. In this study, we identified and compared, 10 years after the European inventory, the characteristics of national surveillance systems and policies for LD in humans, with additional countries. METHODS: Thirty-four European and North American countries were included. Information on national "traditional" systems (which compile data reported by clinicians and laboratories) and "public participatory" websites and mobile applications (which collect information directly from the public) were searched in MEDLINE, a systematic evidence map, and Google. An existing framework on LD surveillance was adapted to capture information on the administration level, indicators, reporting entities, coverage, and obligation to report. RESULTS: A surveillance system was found for 29 (85%) countries. Twenty-four had a traditional system alone, one had a public participatory system alone, and the remaining had both. Among countries with traditional systems, 23 (82%) administered them at the national level. Nineteen (68%) required mandatory reporting. Sixteen (57%) used both clinicians and laboratories as reporting entities. Eighteen (64%) employed case definitions, most of which considered both neuroborreliosis and erythema migrans (n = 14). Others monitored the number of positive laboratory tests and/or patient consultations. Public participatory systems were only implemented in countries employing either also sentinels or voluntary surveys, or no traditional system, suggesting their use as a complementary tool. Only 56% of EU countries had neuroborreliosis as an indicator. CONCLUSION: The situation remains similar to 2010 with persisting heterogeneity between systems, suggesting that countries prioritise different surveillance objectives for LD. Without a common indicator in Europe, it is difficult to get a clear epidemiological picture. We discuss four factors that potentially influence LD surveillance strategies: perceptions of severity, burden on resources, two-way communication, and the medical conflicts about LD. Addressing these with countries might help moving towards the adoption of common practices.

'Leading from the front' implementation increases the success of influenza vaccination drives among healthcare workers: a reanalysis of systematic review evidence using Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA).

BACKGROUND: Seasonal influenza vaccination of healthcare workers (HCW) is widely recommended to protect staff and patients. A previous systematic review examined interventions to encourage uptake finding that hard mandates, such as loss of employment for non-vaccination, were more effective than soft mandates, such as signing a declination form, or other interventions such as incentives. Despite these overarching patterns the authors of the review concluded that 'substantial heterogeneity' remained requiring further analysis. This paper reanalyses the evidence using Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) to examine whether the strategies used to implement interventions explain the residual heterogeneity. METHODS: We used ICA to extract implementation features and trialists' reflections on what underpinned the success of the intervention they evaluated. The ICA findings then informed and structured two QCA analyses to systematically examine associations between implementation features and intervention outcomes. Analysis 1 examined hard mandate studies. Analysis 2 examined soft mandates and other interventions. RESULTS: In Analysis 1 ICA revealed the significance of 'leading from the front' rather than 'top-down' implementation of hard mandates. Four key features underpinned this: providing education prior to implementation; two-way engagement so HCW can voice concerns prior to implementation; previous use of other strategies so that institutions 'don't-go-in-cold' with hard-mandates; and support from institutional leadership. QCA revealed that either of two configurations were associated with greater success of hard mandates. The first involves two-way engagement, leadership support and a 'don't-go-in-cold' approach. The second involves leadership support, education and a 'don't-go-in-cold' approach. Reapplying the 'leading from the front' theory in Analysis 2 revealed similar patterns. CONCLUSIONS: Regardless of intervention type a 'leading from the front' approach to implementation will likely enhance intervention success. While the results pertain to flu vaccination among HCWs, the components identified here may be relevant to public health campaigns regarding COVID-19 vaccination.

Interventions targeting healthcare providers to optimise use of caesarean section: a qualitative comparative analysis to identify important intervention features.

BACKGROUND: Rapid increases in caesarean section (CS) rates have been observed globally; however, CS rates exceeding 15% at a population-level have limited benefits for women and babies. Many interventions targeting healthcare providers have been developed to optimise use of CS, typically aiming to improve and monitor clinical decision-making. However, interventions are often complex, and effectiveness is varied. Understanding intervention and implementation features that likely lead to optimised CS use is important to optimise benefits. The aim of this study was to identify important components that lead to successful interventions to optimise CS, focusing on interventions targeting healthcare providers.  METHODS: We used Qualitative Comparative Analysis (QCA) to identify if certain combination of important intervention features (e.g. type of intervention, contextual characteristics, and how the intervention was delivered) are associated with a successful intervention as reflected in a reduction of CS. We included 21 intervention studies targeting healthcare providers to reduce CS, comprising of 34 papers reporting on these interventions. To develop potential theories driving intervention success, we used existing published qualitative evidence syntheses on healthcare providers' perspectives and experiences of interventions targeted at them to reduce CS. RESULTS: We identified five important components that trigger successful interventions targeting healthcare providers: 1) training to improve providers' knowledge and skills, 2) active dissemination of CS indications, 3) actionable recommendations, 4) multidisciplinary collaboration, and 5) providers' willingness to change. Importantly, when one or more of these components are absent, dictated nature of intervention, where providers are enforced to adhere to the intervention, is needed to prompt successful interventions. Unsuccessful interventions were characterised by the absence of these components. CONCLUSION: We identified five important intervention components and combinations of intervention components which can lead to successful interventions targeting healthcare providers to optimise CS use. Health facility managers, researchers, and policy-makers aiming to improve providers' clinical decision making and reduce CS may consider including the identified components to optimise benefits.

A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor.

An Australian estuarine isolate of Penicillium sp. MST-MF667 yielded 3 tetrapeptides named the bilaids with an unusual alternating LDLD chirality. Given their resemblance to known short peptide opioid agonists, we elucidated that they were weak (Ki low micromolar) µ-opioid agonists, which led to the design of bilorphin, a potent and selective µ-opioid receptor (MOPr) agonist (Ki 1.1 nM). In sharp contrast to all-natural product opioid peptides that efficaciously recruit ß-arrestin, bilorphin is G protein biased, weakly phosphorylating the MOPr and marginally recruiting ß-arrestin, with no receptor internalization. Importantly, bilorphin exhibits a similar G protein bias to oliceridine, a small nonpeptide with improved overdose safety. Molecular dynamics simulations of bilorphin and the strongly arrestin-biased endomorphin-2 with the MOPr indicate distinct receptor interactions and receptor conformations that could underlie their large differences in bias. Whereas bilorphin is systemically inactive, a glycosylated analog, bilactorphin, is orally active with similar in vivo potency to morphine. Bilorphin is both a unique molecular tool that enhances understanding of MOPr biased signaling and a promising lead in the development of next generation analgesics.

Children's informed signified and voluntary consent to heart surgery: Professionals' practical perspectives.

BACKGROUND: The law and literature about children's consent generally assume that patients aged under-18 cannot consent until around 12 years, and cannot refuse recommended surgery. Children deemed pre-competent do not have automatic rights to information or to protection from unwanted interventions. However, the observed practitioners tend to inform young children s, respect their consent or refusal, and help them to "want" to have the surgery. Refusal of heart transplantation by 6-year-olds is accepted. RESEARCH QUESTION: What are possible reasons to explain the differences between theories and practices about the ages when children begin to be informed about elective heart surgery, and when their consent or refusal begins to be respected? RESEARCH DESIGN, PARTICIPANTS AND CONTEXT: Research methods included reviews of related healthcare, law and ethics literature; observations and conversations with staff and families in two London hospitals; audio-recorded semi-structured interviews with a purposive sample of 45 healthcare professionals and related experts; interviews and a survey with parents and children aged 6- to 15-years having elective surgery (not reported in this paper); meetings with an interdisciplinary advisory group; thematic analysis of qualitative data and co-authorship of papers with participants. ETHICAL CONSIDERATIONS: Approval was granted by four research ethics committees/authorities. All interviewees gave their informed written consent. FINDINGS: Interviewees explained their views and experiences about children's ages of competence to understand and consent or refuse, analysed by their differing emphases on informed, signified or voluntary consent. DISCUSSION: Differing views about children's competence to understand and consent are associated with emphases on consent as an intellectual, practical and/or emotional process. Conclusion: Greater respect for children's practical signified, emotional voluntary and intellectual informed consent can increase respectful understanding of children's consent. Nurses play a vital part in children's practitioner-patient relationships and physical care and therefore in all three elements of consent.

Factors that impact on recruitment to randomised trials in health care: a qualitative evidence synthesis.

BACKGROUND: Randomised trials (also referred to as 'randomised controlled trials' or 'trials') are the optimal way to minimise bias in evaluating the effects of competing treatments, therapies and innovations in health care. It is important to achieve the required sample size for a trial, otherwise trialists may not be able to draw conclusive results leading to research waste and raising ethical questions about trial participation. The reasons why potential participants may accept or decline participation are multifaceted. Yet, the evidence of effectiveness of interventions to improve recruitment to trials is not substantial and fails to recognise these individual decision-making processes. It is important to synthesise the experiences and perceptions of those invited to participate in randomised trials to better inform recruitment strategies. OBJECTIVES: To explore potential trial participants' views and experiences of the recruitment process for participation. The specific objectives are to describe potential participants' perceptions and experiences of accepting or declining to participate in trials, to explore barriers and facilitators to trial participation, and to explore to what extent barriers and facilitators identified are addressed by strategies to improve recruitment evaluated in previous reviews of the effects of interventions including a Cochrane Methodology Review. SEARCH METHODS: We searched the Cochrane Library, Medline, Embase, CINAHL, Epistemonikos, LILACS, PsycINFO, ORRCA, and grey literature sources. We ran the most recent set of searches for which the results were incorporated into the review in July 2017. SELECTION CRITERIA: We included qualitative and mixed-methods studies (with an identifiable qualitative component) that explored potential trial participants' experiences and perceptions of being invited to participate in a trial. We excluded studies that focused only on recruiters' perspectives, and trials solely involving children under 18 years, or adults who were assessed as having impaired mental capacity. DATA COLLECTION AND ANALYSIS: Five review authors independently assessed the titles, abstracts and full texts identified by the search. We used the CART (completeness, accuracy, relevance, timeliness) criteria to exclude studies that had limited focus on the phenomenon of interest. We used QSR NVivo to extract and manage the data. We assessed methodological limitations using the Critical Skills Appraisal Programme (CASP) tool. We used thematic synthesis to analyse and synthesise the evidence. This provided analytical themes and a conceptual model. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. Our findings were integrated with two previous intervention effectiveness reviews by juxtaposing the quantitative and qualitative findings in a matrix. MAIN RESULTS: We included 29 studies (published in 30 papers) in our synthesis. Twenty-two key findings were produced under three broad themes (with six subthemes) to capture the experience of being invited to participate in a trial and making the decision whether to participate. Most of these findings had moderate to high confidence. We identified factors from the trial itself that influenced participation. These included how trial information was communicated, and elements of the trial such as the time commitment that might be considered burdensome. The second theme related to personal factors such as how other people can influence the individual's decision; and how a personal understanding of potential harms and benefits could impact on the decision. Finally, the potential benefits of participation were found to be key to the decision to participate, namely personal benefits such as access to new treatments, but also the chance to make a difference and help others. The conceptual model we developed presents the decision-making process as a gauge and the factors that influence whether the person will, or will not, take part. AUTHORS' CONCLUSIONS: This qualitative evidence synthesis has provided comprehensive insight into the complexity of factors that influence a person's decision whether to participate in a trial. We developed key questions that trialists can ask when developing their recruitment strategy. In addition, our conceptual model emphasises the need for participant-centred approaches to recruitment. We demonstrated moderate to high level confidence in our findings, which in some way can be attributed to the large volume of highly relevant studies in this field. We recommend that these insights be used to direct or influence or underpin future recruitment strategies that are developed in a participant-driven way that ultimately improves trial conduct and reduces research waste.

Interventions to support people exposed to adverse childhood experiences: systematic review of systematic reviews.

BACKGROUND: Adverse Childhood Experiences (ACEs) such as abuse, neglect or household adversity may have a range of serious negative impacts. There is a need to understand what interventions are effective to improve outcomes for people who have experienced ACEs. METHODS: Systematic review of systematic reviews. We searched 18 database sources from 2007 to 2018 for systematic reviews of effectiveness data on people who experienced ACEs aged 3-18, on any intervention and any outcome except incidence of ACEs. We included reviews with a summary quality score (AMSTAR) of 5.5 or above. RESULTS: Twenty-five reviews were included. Most reviews focus on psychological interventions and mental health outcomes. The strongest evidence is for cognitive-behavioural therapy for people exposed to abuse. For other interventions - including psychological therapies, parent training, and broader support interventions - the findings overall are inconclusive, although there are some positive results. CONCLUSIONS: There are significant gaps in the evidence on interventions for ACEs. Most approaches focus on mitigating individual psychological harms, and do not address the social pathways which may mediate the negative impacts of ACEs. Many negative impacts of ACEs (e.g. on health behaviours, social relationships and life circumstances) have also not been widely addressed by intervention studies.

Service needs of young people affected by adverse childhood experiences (ACEs): A systematic review of UK qualitative evidence.

BACKGROUND: Adverse Childhood Experiences (ACEs) such as, physical and sexual abuse, neglect, or living in a household with domestic violence or substance misuse, can have negative impacts on mental and physical health across the lifecourse. A deeper understanding of the kinds of services that people affected by ACEs feel they need to overcome these negative impacts is required. REVIEW QUESTION: How do people affected by ACEs between the ages of 3 to 18 experience support and services in the UK? What are their needs relating to services and support? METHODS: Systematic review of qualitative evidence. We harvested relevant studies from existing systematic reviews of qualitative evidence located through a search of 18 databases. Included studies needed to be published in or after 2008, conducted in the UK, and report the views of people exposed to ACEs relating to their service needs. We included studies with participants who were affected by ACEs between 3 and 18 years old with no restriction on the age at which they accessed services. RESULTS: We identified 71 reviews from which we harvested 238 references on title and abstract screening. Following full text screening and quality and relevance appraisal we included 20 studies. Each of the included studies focussed on a specific ACE population. Almost half focused on young people who were fostered, looked-after or leaving care. No studies focussed on parental incarceration or divorce. Young people value emotional and practical support. Service providers were most valued for displaying empathy, being non-judgemental, and being active listeners. Supportive relationships, especially with adults, are a key factor in feeling understood. CONCLUSIONS: People affected by ACEs describe the importance of stability and continuity in the support they receive. These factors are important for allowing necessary time to overcome obstacles and build up trust. Research often frames response to ACE in terms of short term individual psychological outcomes but these findings highlight the importance of focussing on wider social factors to encourage meaningful engagement with services.

Heterodox and Orthodox Discourses in the Case of Lyme Disease: A Synthesis of Arguments.

In this article, we examine the arguments made by authors of published academic articles concerning the debates surrounding chronic Lyme disease (CLD). CLD is an example of a contested condition and shares problems of legitimacy with other medically unexplained conditions such as chronic fatigue syndrome. We use a critical discourse analysis (CDA) approach to understand the arguments of the authors to establish the legitimacy, or not, of a CLD diagnosis. This enabled us to make sense of the nature of the stalemate between patient groups and advocates of the medical establishment, as performed by authors of academic articles. In this article, we bring together the arguments to explain the polemical debate and to support accounts that avoid the impasse to give us greater insight into the experience of chronic illness.

Lifestyle weight management programmes for children: A systematic review using Qualitative Comparative Analysis to identify critical pathways to effectiveness.

This study aimed to identify critical features of successful lifestyle weight management interventions for overweight children (0-11years). Eleven qualitative UK-based studies examining children's, parents' and providers' perspectives and experiences of programmes were synthesised to identify components felt to be critical. Studies for this views synthesis were identified from existing reviews and an update of one review's search, which was run in December 2015. The identified components were then explored in a synthesis of intervention evaluations (five 'most effective' and 15 'least effective') conducted in western Europe, North America, Australia or New Zealand. The intervention evaluations were identified from existing reviews and an update of one review's search, which was run in March 2016. This evaluation synthesis was carried out using Qualitative Comparative Analysis. Three important mechanisms were present in all the most effective interventions but absent in all the least effective: 1/ showing families how to change: a) providing child physical activity sessions, b) delivering practical behaviour change strategy sessions, c) providing calorie intake advice; 2/ ensuring all the family are on board: a) delivering discussion/education sessions for both children and parents, b) delivering child-friendly sessions, c) aiming to change behaviours across the whole family; 3/ enabling social support for both parents and children by delivering both child group sessions and parent group sessions. To conclude, programmes should ensure the whole family is on board the programme, that parents and children can receive social support and are not just told what to change, but shown how.

The importance of service-users' perspectives: A systematic review of qualitative evidence reveals overlooked critical features of weight management programmes.

BACKGROUND: Extensive research effort shows that weight management programmes (WMPs) targeting both diet and exercise are broadly effective. However, the critical features of WMPs remain unclear. OBJECTIVE: To develop a deeper understanding of WMPs critical features, we undertook a systematic review of qualitative evidence. We sought to understand from a service-user perspective how programmes are experienced, and may be effective, on the ground. SEARCH STRATEGY: We identified qualitative studies from existing reviews and updated the searches of one review. INCLUSION CRITERIA: We included UK studies capturing the views of adult WMP users. DATA EXTRACTION AND SYNTHESIS: Thematic analysis was used inductively to code and synthesize the evidence. MAIN RESULTS: Service users were emphatic that supportive relationships, with service providers or WMP peers, are the most critical aspect of WMPs. Supportive relationships were described as providing an extrinsic motivator or "hook" which helped to overcome barriers such as scepticism about dietary advice or a lack confidence to engage in physical activity. DISCUSSION AND CONCLUSIONS: The evidence revealed that service-users' understandings of the critical features of WMPs differ from the focus of health promotion guidance or descriptions of evaluated programmes which largely emphasize educational or goal setting aspects of WMPs. Existing programme guidance may not therefore fully address the needs of service users. The study illustrates that the perspectives of service users can reveal unanticipated intervention mechanisms or underemphasized critical features and underscores the value of a holistic understanding about "what happens" in complex psychosocial interventions such as WMPs.

Weight management programmes: Re-analysis of a systematic review to identify pathways to effectiveness.

BACKGROUND: Previous systematic reviews of weight management programmes (WMPs) have not been able to account for heterogeneity of effectiveness within programmes using top-down behavioural change taxonomies. This could be due to overlapping causal pathways to effectiveness (or lack of effectiveness) in these complex interventions. Qualitative comparative analysis (QCA) can help identify these overlapping pathways. METHODS: Using trials of adult WMPs with dietary and physical activity components identified from a previous systematic review, we selected the 10 most and 10 least effective interventions by amount of weight loss at 12 months compared to minimal treatment. Using intervention components suggested by synthesis of studies of programme user views, we labelled interventions as to the presence of these components and, using qualitative comparative analysis, developed pathways of component combinations that created the conditions sufficient for interventions to be most effective and least effective. RESULTS: Informed by the synthesis of views studies, we constructed 3 truth tables relating to quality of the user-provider relationship; perceived high need for guidance from providers; and quality of the relationship between peers in weight management programmes. We found effective interventions were characterized by opportunities to develop supportive relationships with providers or peers, directive provider-led goal setting and components perceived to foster self-regulation. CONCLUSIONS: Although QCA is an inductive method, this innovative approach has enabled the identification of potentially critical aspects of WMPs, such as the nature of relationships within them, which were previously not considered to be as important as more concrete content such as dietary focus.

Seasonal influenza vaccination of healthcare workers: systematic review of qualitative evidence.

BACKGROUND: Most countries recommend that healthcare workers (HCWs) are vaccinated seasonally against influenza in order to protect themselves and patients. However, in many cases coverage remains low. A range of strategies have been implemented to increase uptake. Qualitative evidence can help in understanding the context of interventions, including why interventions may fail to achieve the desired effect. This study aimed to synthesise evidence on HCWs' perceptions and experiences of vaccination for seasonal influenza. METHODS: Systematic review of qualitative evidence. We searched MEDLINE, EMBASE and CINAHL and included English-language studies which reported substantive qualitative data on the vaccination of HCWs for seasonal influenza. Findings were synthesised thematically. RESULTS: Twenty-five studies were included in the review. HCWs may be motivated to accept vaccination to protect themselves and their patients against infection. However, a range of beliefs may act as barriers to vaccine uptake, including concerns about side-effects, scepticism about vaccine effectiveness, and the belief that influenza is not a serious illness. HCWs value their autonomy and professional responsibility in making decisions about vaccination. The implementation of interventions to promote vaccination uptake may face barriers both from HCWs' personal beliefs and from the relationships between management and employees within the targeted organisations. CONCLUSIONS: HCWs' vaccination behaviour needs to be understood in the context of HCWs' relationships with each other, with management and with patients. Interventions to promote vaccination should take into account both the individual beliefs of targeted HCWs and the organisational context within which they are implemented.

Communicating cardiovascular risk: Systematic review of qualitative evidence.

INTRODUCTION: Cardiovascular risk prediction models are widely used to help individuals understand risk and make decisions. METHODS: Systematic review of qualitative evidence. We searched MEDLINE, Embase, PsycINFO and CINAHL. We included English-language qualitative studies on the communication of cardiovascular risk. We assessed study quality using Hawker et al.'s tool and synthesised data thematically. RESULTS: Thirty-seven studies were included. Many patients think that risk scores are of limited practical value. Other sources of information feed into informal estimates of risk, which may lead patients to reject the results of clinical risk assessment when the two conflict. Clinicians identify a number of barriers to risk communication, including patients' limited understanding of risk and excessive anxiety. They use a range of strategies for adapting risk communication. Both clinicians and individuals express specific preferences for risk communication formats. DISCUSSION: Ways of communicating risk that provide some comparison or reference point seem more promising. The broader context of communication around risk may be more important than the risk scoring instrument. Risk communication interventions, in practice, may be more about appeals to emotion than a rationalistic model of decision-making.

The anomalous pharmacology of fentanyl.

Fentanyl is a key therapeutic, used in anaesthesia and pain management. It is also increasingly used illicitly and is responsible for a large and growing number of opioid overdose deaths, especially in North America. A number of factors have been suggested to contribute to fentanyl's lethality, including rapid onset of action, in vivo potency, ligand bias, induction of muscle rigidity and reduced sensitivity to reversal by naloxone. Some of these factors can be considered to represent 'anomalous' pharmacological properties of fentanyl when compared with prototypical opioid agonists such as morphine. In this review, we examine the nature of fentanyl's 'anomalous' properties, to determine whether there is really a pharmacological basis to support the existence of such properties, and also discuss whether such properties are likely to contribute to overdose deaths involving fentanyls. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Children's understanding and consent to heart surgery: Multidisciplinary teamwork and moral experiences.

Mainstream law and ethics literature on consent to children's surgery contrasts with moral experiences of children and adults observed in two heart surgery centres. Research interviews were conducted with 45 practitioners and related experts, and with 16 families of children aged 6 to 15, admitted for non-urgent surgery, as well as an online survey. Thematic data analysis was informed by critical realism and childhood studies.Impersonal adult-centric mainstream literature assumes young children cannot consent. It is based on dichotomies: adult/child, competent/incompetent, respect or protect children, inform or distract them, use time swiftly or flexibly, verbal/non-verbal communication, respect or control children and reason/emotion.Through their moral experiences, adults and children resolve these seeming dichotomies. Through understanding young children's reasoning and emotions about complex distressing decisions related to heart surgery, adults share knowledge, control, trust and respect with them. They see children's consent or refusal before non-urgent surgery as a shared personal moral experience within the child's life course, beyond mere legal compliance. Adults help children to understand and 'want' the surgery that offers things they value: better health or to 'be more like their friends'. If children are not convinced, sometimes surgery is postponed or occasionally cancelled.