The revised JBI critical appraisal tool for the assessment of risk of bias for cohort studies.

Cohort studies are a robust analytical observational study design that explore the difference between two different cohorts on an outcome, differentiated by their exposure status. Despite being observational in nature, they are often included in systematic reviews of effectiveness, particularly when randomized controlled trials are limited or not feasible. Like all studies included in a systematic review, cohort studies must undergo a critical appraisal process to assess the extent to which a study has considered potential bias in its design, conduct, or analysis. Critical appraisal tools facilitate this evaluation. This paper introduces the revised critical appraisal tool for cohort studies, completed by the JBI Effectiveness Methodology Group (EMG), who are currently revising the suite of JBI critical appraisal tools for quantitative study designs. The revised tool responds to updates in methodological guidance from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group and reporting guidance from PRISMA 2020, providing a robust framework for evaluating risk of bias in a cohort study. Transparent and rigorous assessment using this tool will assist reviewers in understanding the validity and relevance of the results and conclusions drawn from a systematic review that includes cohort studies. This may contribute to better evidence-based decision-making in health care. This paper discusses the key changes made to the tool, justifications for these changes, and provides practical guidance on how this tool should be interpreted and applied by systematic reviewers.

A rapid literature review of the effect of alcohol marketing on people with, or at increased risk of, an alcohol problem.

AIMS: To explore the effect or potential effect of alcohol marketing in people with an alcohol use disorder, in recovery from an alcohol use disorder, and hazardous and harmful drinkers. METHODS: Relevant literature was identified by searching Medline (OVID), EMBASE (OVID), and PsycINFO (OVID) and relevant websites. Both quantitative and qualitative studies were eligible for inclusion. A narrative approach was used to synthesize the findings. RESULTS: The review included 10 studies. Two quantitative and three qualitative studies focused on participants recovering from an alcohol use disorder and five quantitative studies on those with hazardous or harmful consumption levels of alcohol. The effect of alcohol advertising on alcohol use was only assessed in one study, a small experimental study of young adult heavy drinkers, which found no significant association. Studies looking at other outcomes found that people with or at risk of alcohol problems were likely to notice alcohol advertisements and find them appealing, and that advertisements may have an effect on positive alcohol-related emotions and cognitions. Among people in recovery from an alcohol use disorder, findings suggested that there could be an effect on craving, and that alcohol marketing may be perceived to trigger a desire to drink. CONCLUSIONS: Alcohol marketing is likely to have an effect on alcohol consumption in people with, or at increased risk of, an alcohol problem. Studies have also found that alcohol marketing is perceived to act as a trigger by people in recovery from alcohol problems. SUMMARY: A rapid review explored the effect of alcohol marketing in people with an alcohol use disorder, in recovery from an alcohol use disorder, and hazardous and harmful drinkers. The findings of the 10 included studies suggest that an effect of alcohol marketing in these populations is likely.

Digitalising Specialist Smoking Cessation Support in Pregnancy: Views of Pregnant Smokers.

INTRODUCTION: Unsupported attempts to quit smoking during pregnancy have a low success rate. Chances of quitting successfully are higher with an interpersonal treatment programme but there is low uptake of this in the United Kingdom (UK). Delivering a pregnancy-specific treatment programme digitally may provide an alternative treatment route. This study explored pregnant smokers' perceptions of barriers and facilitators to using digital cessation support, along with identifying modes of delivery and engagement enhancers. METHODS: Semi-structured interviews were carried out with an ethnically and socioeconomically diverse sample of 25 participants with recent experience of attempting to quit smoking in pregnancy, aged 20 - 40, from the UK. An inductive thematic analysis approach was used. RESULTS: Digital smoking cessation support, particularly a smartphone app, for pregnancy was felt to overcome many barriers to engaging with interpersonal support, being viewed as more convenient and non-judgemental, providing better consistency of advice, and enhancing privacy and autonomy. However, some participants felt that removing access to a human could undermine a digital support package and reduce engagement. Popular engagement enhancers included self-monitoring (e.g. digital recording of smoking; smartphone-linked carbon monoxide monitoring), online communities, and remote access to nicotine substitution options. Digital support was viewed as having potential as a stand-alone intervention or working in conjunction with standard interpersonal treatment. CONCLUSIONS: The findings support the investigation of a digital support package as both a stand-alone and adjunct to standard interpersonal cessation support in pregnancy to increase the proportion of pregnant smokers who make a supported quit attempt. IMPLICATIONS: In many countries like the UK, there are few smoking cessation options routinely available that provide effective support for smoking cessation in pregnancy. To maximise impact, health services need an effective range of strategies to engage with and support quit attempts made by all pregnant smokers, particularly as interpersonal support options are not often well engaged with. Development of a pregnancy-specific digital support package for smoking cessation in pregnancy may represent a means to help address this gap.

Health net-outcome objectives and approaches for spatial planning and development: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to review the body of knowledge on net gain and no net loss (net-outcome) objectives and approaches applicable to health in spatial planning and development policies and practice. INTRODUCTION: There is an established body of academic and gray literature addressing environmental net-outcome objectives, such as biodiversity net gain, in spatial planning policies and practice. A "health net gain" objective has recently been proposed as a driver for health protection and the realization of health. Such an objective and approach are yet to be scoped and defined. INCLUSION CRITERIA: This review will consider sources in the scientific and gray literature that describe health net-outcome objectives that can be implemented in spatial planning and development policies and practice. Source contexts will not be limited to specific countries, geographical areas, or settings. All types of evidence will be considered. METHODS: This review will follow the JBI methodology for scoping reviews. Databases to be searched include PsycINFO (APA), Embase, HMIC Health Management Information Consortium, MEDLINE (Ovid), Scopus, and selected databases from the ProQuest Social Science Premium Collection. Sources of gray literature to be searched include ProQuest Dissertations and Theses, TRIP Pro, and BASE. No language or date restrictions will be applied. Two independent reviewers will retrieve and review full-text studies and extract data. The results will be presented in tabular or diagrammatic format with a narrative summary. REVIEW REGISTRATION: Open Science Framework https://osf.io/4dbcm.

Psychological interventions for mood and cognition after stroke and transient ischaemic attack: A protocol for an umbrella review.

Background: People who have had a stroke or a Transient Ischaemic Attack (TIA) can experience psychological and/or cognitive difficulties. The body of research for psychological and neuropsychological interventions after stroke is growing, however, published systematic reviews vary in scope and methodology, with different types and severity of strokes included, and at times, diverse conclusions drawn about the effectiveness of the interventions evaluated. In this umbrella review, we aim to systematically summarise the existing systematic reviews evaluating psychological interventions for mood and cognition post-stroke/TIA. Methods: We will conduct this umbrella review according to the JBI Manual for Evidence Synthesis. The following databases will be searched from inception: Cochrane Database of Systematic Reviews, Database of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Epistemonikos. Systematic reviews with or without meta-analysis published until the search date will be included. Reviews including psychological interventions addressing mood and/or cognition outcomes for any stroke type or severity will be screened for eligibility. A narrative synthesis, including content analysis, will be used. Each stage of the review will be processed by two independent reviewers and a third reviewer will be considered to resolve disagreements. The methodological quality of the included reviews will be assessed using AMSTAR 2. Discussion: Existing systematic reviews provide varied evidence on the effectiveness of psychological interventions post-stroke/TIA. This umbrella review aims to summarise knowledge and evidence on different types of psychological and neuropsychological interventions targeting mood and cognition. Findings will highlight important knowledge gaps and help prioritise future research questions. Systematic Review Registration: This protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 15, 2022; PROSPERO CRD42022375947.

What are the strengths and limitations to utilising creative methods in public and patient involvement in health and social care research? A qualitative systematic review.

BACKGROUND: There is increasing interest in using patient and public involvement (PPI) in research to improve the quality of healthcare. Ordinarily, traditional methods have been used such as interviews or focus groups. However, these methods tend to engage a similar demographic of people. Thus, creative methods are being developed to involve patients for whom traditional methods are inaccessible or non-engaging. OBJECTIVE: To determine the strengths and limitations to using creative PPI methods in health and social care research. METHOD: Electronic searches were conducted over five databases on 14th April 2023 (Web of Science, PubMed, ASSIA, CINAHL, Cochrane Library). Studies that involved traditional, non-creative PPI methods were excluded. Creative PPI methods were used to engage with people as research advisors, rather than study participants. Only primary data published in English from 2009 were accepted. Title, abstract and full text screening was undertaken by two independent reviewers before inductive thematic analysis was used to generate themes. RESULTS: Twelve papers met the inclusion criteria. The creative methods used included songs, poems, drawings, photograph elicitation, drama performance, visualisations, social media, photography, prototype development, cultural animation, card sorting and persona development. Analysis identified four limitations and five strengths to the creative approaches. Limitations included the time and resource intensive nature of creative PPI, the lack of generalisation to wider populations and ethical issues. External factors, such as the lack of infrastructure to support creative PPI, also affected their implementation. Strengths included the disruption of power hierarchies and the creation of a safe space for people to express mundane or "taboo" topics. Creative methods are also engaging, inclusive of people who struggle to participate in traditional PPI and can also be cost and time efficient. CONCLUSION: 'Creative PPI' is an umbrella term encapsulating many different methods of engagement and there are strengths and limitations to each. The choice of which should be determined by the aims and requirements of the research, as well as the characteristics of the PPI group and practical limitations. Creative PPI can be advantageous over more traditional methods, however a hybrid approach could be considered to reap the benefits of both. Creative PPI methods are not widely used; however, this could change over time as PPI becomes embedded even more into research.

It is important that patients and public are included in the research process from initial brainstorming, through design to delivery. This is known as public and patient involvement (PPI). Their input means that research closely aligns with their wants and needs. Traditionally to get this input, interviews and group discussions are held, but this can exclude people who find these activities non-engaging or inaccessible, for example those with language challenges, learning disabilities or memory issues. Creative methods of PPI can overcome this. This is a broad term describing different (non-traditional) ways of engaging patients and public in research, such as through the use or art, animation or performance. This review investigated the reasons why creative approaches to PPI could be difficult (limitations) or helpful (strengths) in health and social care research. After searching 5 online databases, 12 studies were included in the review. PPI groups included adults, children and people with language and memory impairments. Creative methods included songs, poems, drawings, the use of photos and drama, visualisations, Facebook, creating prototypes, personas and card sorting. Limitations included the time, cost and effort associated with creative methods, the lack of application to other populations, ethical issues and buy-in from the wider research community. Strengths included the feeling of equality between academics and the public, creation of a safe space for people to express themselves, inclusivity, and that creative PPI can be cost and time efficient. Overall, this review suggests that creative PPI is worthwhile, however each method has its own strengths and limitations and the choice of which will depend on the research project, PPI group characteristics and other practical limitations, such as time and financial constraints.

Bisphosphonate alternative regimens for the prevention of osteoporotic fragility fractures: BLAST-OFF, a mixed-methods study.

Background: Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives: 1. Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. 2. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. 3. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods: The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: • Stage 1A - we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. • Stage 1B - we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. • Stage 2 - we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates. Results: Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting. Conclusions: Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs. Future work: Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting. Limitations: Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates. Trial registration: This trial is registered as ISRCTN10491361. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in Health Technology Assessment; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.

Bisphosphonates are drug treatments commonly used to treat osteoporosis. Alendronate is the most used and is taken by mouth, weekly at a specific time of the week, which can be challenging. Less than one in four people continue this treatment beyond 2 years. Alternative bisphosphonates are available, which vary in frequency and how they are administered. The most acceptable and best value-for-money regimen is unclear. Our aim was to determine how effective alternative bisphosphonates are compared to alendronate at preventing fractures and whether reduction in fracture risk was achieved at a reasonable financial cost, but acceptable to patients. The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: a review of the published evidence on patients' and doctors' views, experiences and preferences regarding different bisphosphonate treatment regimens, followed by interviews with patients and healthcare professionals. Stage 1B: an update of an existing study on how effective bisphosphonates are in preventing fragility fractures caused by osteoporosis and whether they are good value for money. Stage 2: identification of questions that need to be answered about the effectiveness and acceptability of bisphosphonate treatments. Taking bisphosphonate medication often involves quite a lot of effort by patients, particularly when taking alendronate tablets. A yearly infusion of zoledronate treatment was more acceptable, easier to engage with and the most effective treatment compared to alendronate. However, the cost of administering zoledronate in hospital made alendronate better value for money. Bisphosphonates are effective in reducing the risk of fracture, but 'continuing with treatment', particularly alendronate tablets, remains a challenge. A yearly infusion of zoledronate offers an acceptable and effective treatment, but further research is needed to support patients and healthcare professionals in making decisions about the various treatments, benefits and cost savings of administering zoledronate outside of hospital and in the community.

The impact of conflict on infectious disease: a systematic literature review.

BACKGROUND: Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which infectious diseases emerge within conflict situations and to outline appropriate infectious disease preparedness and response strategies. METHODS: A systematic review was performed representing published evidence from January 2000 to October 2023. Ovid Medline and Embase were utilised to obtain literature on infectious diseases in any conflict settings. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis). No geographical restrictions were imposed. FINDINGS: Our review identified 51 studies covering AIDS, Hepatitis B, Tuberculosis, Cholera, Coronavirus 2, Ebola, Poliomyelitis, Malaria, Leishmaniasis, Measles, Diphtheria, Dengue and Acute Bacterial Meningitis within conflict settings in Europe, Middle East, Asia, and Africa since October 2023. Key factors contributing to disease emergence and transmission in conflict situations included population displacement, destruction of vital infrastructure, reduction in functioning healthcare systems and healthcare personnel, disruption of disease control programmes (including reduced surveillance, diagnostic delays, and interrupted vaccinations), reduced access by healthcare providers to populations within areas of active conflict, increased population vulnerability due to limited access to healthcare services, and disruptions in the supply chain of safe water, food, and medication. To mitigate these infectious disease risks reported preparedness and response strategies included both disease-specific intervention strategies as well as broader concepts such as the education of conflict-affected populations through infectious disease awareness programmes, investing in and enabling health care in locations with displaced populations, intensifying immunisation campaigns, and ensuring political commitment and intersectoral collaborations between governments and international organisations. CONCLUSION: Conflict plays a direct and indirect role in the transmission and propagation of infectious diseases. The findings from this review can assist decision-makers in the development of evidence-based preparedness and response strategies for the timely and effective containment of infectious disease outbreaks in conflict zones and amongst conflict-driven displaced populations. FUNDING: European Centre for Disease Prevention and Control under specific contract No. 22 ECD.13,154 within Framework contract ECDC/2019/001 Lot 1B.

Experts' views on translating NHS support to stop smoking in pregnancy into a comprehensive digital intervention.

Many pregnant smokers need support to quit successfully. In the United Kingdom, trained smoking cessation advisors deliver structured behavioural counselling alongside access to free nicotine replacement therapy (NRT); known as the 'Standard Treatment Programme' (STP). Pregnant smokers who access STP support are more likely to quit, but uptake is low. A digital intervention could be offered as an adjunct or alternative to existing STP support to increase cessation rates. However, there are few pregnancy-specific digital options routinely available and, among those that are, there is limited evidence of their effectiveness. This study investigated experts' views on the feasibility of translating the STP into a comprehensive digital intervention. Virtual group and individual interviews were undertaken with 37 experts (11 focus groups, 3 interviews) with a real-time voting activity in the focus groups to prompt discussion. Framework Analysis was applied to the data to examine themes and patterns. Experts were supportive of a digital translation of the STP and considered most behavioural counselling content to be transferable. However, replicating human-to-human accountability, empathy and the ability to go 'off-script' was thought more challenging. Suggestions for how this might be achieved included tailoring and personalisation, use of artificial intelligence tools, peer support and the option to escalate contact to a human advisor. Experts had mixed views on the role that exhaled breath carbon monoxide monitoring might have in a digital cessation intervention for pregnancy. Electronic provision of free NRT, and potentially e-cigarettes, without interpersonal support was generally well received. However, experts had concerns about it exacerbating low NRT adherence, governance issues (e.g. being accountable for the suitability of recommended products), and people's ability to misrepresent their eligibility. The STP was considered largely transferable to a digital intervention and potentially helpful for cessation in pregnancy, so merits further development and evaluation.

The Effectiveness of Text Support for Stopping Smoking in Pregnancy (MiQuit): Multi-Trial Pooled Analysis Investigating Effect Moderators and Mechanisms of Action.

INTRODUCTION: Digital cessation support appeals to pregnant smokers. In two pooled RCTs, MiQuit, a pregnancy-specific tailored text messaging intervention, did not show effectiveness for validated prolonged abstinence. However, secondary outcomes and potential moderators and mediators have not been investigated. We aimed to determine, using pooled RCT data: (1) MiQuit effectiveness on a range of smoking outcomes; (2) whether baseline tobacco dependence or quit motivation moderate effectiveness; (3) whether hypothesized mechanisms of action (quitting determination, self-efficacy, baby harm beliefs, lapse prevention strategies) mediate effectiveness. METHODS: Pooled data analysis from two procedurally identical RCTs comparing MiQuit (N = 704) to usual care (N = 705). Participants were smokers, <25 weeks pregnant, recruited from 40 English antenatal clinics. Outcomes included self-reported 7-day abstinence at 4 weeks post-baseline and late pregnancy, and prolonged abstinence. Late pregnancy outcomes were also biochemically validated. We used hierarchical regression and structural equation modeling. RESULTS: MiQuit increased self-reported, 7-day abstinence at 4 weeks (OR = 1.73 [95% CI 1.10-2.74]) and was borderline significant at late pregnancy (OR = 1.34 [0.99-1.82]) but not for prolonged or validated outcomes. Effectiveness was not moderated by baseline dependence (heaviness of smoking "low" vs. "moderate-high") or motivation (planning to quit ≤30 days [high] vs. >30 days [low]), but effects on self-reported outcomes were larger for the high motivation sub-group. MiQuit had a small effect on mean lapse prevention strategies (MiQuit 8.6 [SE 0.17], UC 8.1 [SE 0.17]; P = .030) but not other mechanisms. CONCLUSIONS: MiQuit increased short-term but not prolonged or validated abstinence and may be most effective for those motivated to quit sooner. IMPLICATIONS: Digital cessation support appeals to pregnant smokers. MiQuit, a tailored, theory-guided text messaging program for quitting smoking in pregnancy, has not shown effectiveness for validated prolonged abstinence in two previous RCTs but its impact on other smoking outcomes and potential mechanisms of action are unknown. When pooling trial data, MiQuit increased self-reported short-term abstinence, including making a quit attempt and abstinence at 4-week follow-up, but not late pregnancy, sustained, or validated abstinence. MiQuit appeared effective at late pregnancy for participants with high quitting motivation, but its mechanisms of action remain uncertain. Additional support components are likely required to enhance effectiveness.

Common tool structures and approaches to risk of bias assessment: implications for systematic reviewers.

There are numerous tools available to assess the risk of bias in individual studies in a systematic review. These tools have different structures, including scales and checklists, which may or may not separate their items by domains. There are also various approaches and guides for the process, scoring, and interpretation of risk of bias assessments, such as value judgments, quality scores, and relative ranks. The objective of this commentary, which is part of the JBI Series on Risk of Bias, is to discuss some of the distinctions among different tool structures and approaches to risk of bias assessment and the implications of these approaches for systematic reviewers.

The revised JBI critical appraisal tool for the assessment of risk of bias for quasi-experimental studies.

Systematic reviews of effectiveness offer a rigorous synthesis of the best evidence available regarding the effects of interventions or treatments. Randomized controlled trials are considered the optimal study design for evaluating the effectiveness of interventions and are the ideal study design for inclusion in a systematic review of effectiveness. In the absence of randomized controlled trials, quasi-experimental studies may be relied on to provide information on treatment or intervention effectiveness. However, such studies are subject to unique considerations regarding their internal validity and, consequently, the assessment of the risk of bias of these studies needs to consider these features of design and conduct. The JBI Effectiveness Methodology Group has recently commenced updating the suite of JBI critical appraisal tools for quantitative study designs to align with the latest advancements in risk of bias assessment. This paper presents the revised critical appraisal tool for risk of bias assessment of quasi-experimental studies; offers practical guidance for its use; provides examples for interpreting the results of risk of bias assessment; and discusses major changes from the previous version, along with the justifications for those changes.

Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.

Background: Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. Objectives: The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers. Design and methods: This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals. Result: Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable. Limitations: Systematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants. Conclusions: Based on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families. Future work: Establish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives. Study registration: This study is registered as PROSPERO CRD42018117445 and CRD42019125775. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 16. See the NIHR Journals Library website for further project information.

Familial hypercholesterolaemia is an inherited condition that causes raised cholesterol levels from birth and increases risk of heart disease if left untreated. After someone in a family is found to have familial hypercholesterolaemia (called an index case), their close relatives need to be contacted and checked to see if they have familial hypercholesterolaemia, using genetic or cholesterol testing. This is called 'cascade testing'. We planned to find the most cost-effective and acceptable way to do this. The relatives could be contacted for testing by the index case (indirect approach), by a health-care professional (direct approach) or by a combination of both approaches. We found, based on looking at hospital records, that more relatives were tested if health-care professionals directly contacted relatives. In previous studies, slightly more relatives were tested for familial hypercholesterolaemia with a combination approach. Interviews with patients also suggested that the direct approach was the most effective, but the most acceptable and successful approach depends on family relationships: using one approach for some families and using both for other families. Furthermore, by looking at the health-care records of large numbers of patients, we confirmed that people with a recorded diagnosis of familial hypercholesterolaemia in general practice records have a much higher risk of heart disease than the general population, and this was especially so for those with previous heart disease and/or raised cholesterols levels when diagnosed. However, one-quarter of new patients with familial hypercholesterolaemia recorded in their records were not treated within 2 years, with less than one-third reaching recommended cholesterol levels. We used what we had learned to help us estimate the most cost-effective way to do cascade testing. This showed that if the health service directly contact all relatives simultaneously for further assessment, rather than the current approach whereby close (first-degree) relatives are contacted first, this was cost-effective and good value for money.

Cost of the COVID-19 pandemic versus the cost-effectiveness of mitigation strategies in EU/UK/OECD: a systematic review.

OBJECTIVES: The economic burden of COVID-19 pandemic is substantial, with both direct and indirect costs playing a significant role. DESIGN: A systematic literature review was conducted to estimate the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions. All cost data were adjusted to the 2021 Euro, and interventions compared with null. DATA SOURCES: Ovid MEDLINE and EMBASE were searched from January 2020 through 22 April 2021. ELIGIBILITY CRITERIA: Studies regarding COVID-19 outbreak or public health preparedness measures or interventions with outcome measures related to the direct and indirect costs for disease and preparedness and/or response in countries of the European Union (EU), the European Economic Area (EEA), the UK and the Organisation for Economic Co-operation and Development (OECD) of all relevant epidemiological designs which estimate cost within the selected time frame were considered eligible. DATA EXTRACTION AND SYNTHESIS: Studies were searched, screened and coded independently by two reviewers with high measure of inter-rater agreement. Data were extracted to a predefined data extraction sheet. The risk of bias was assessed using the Consensus on Health Economic Criteria checklist. RESULTS: We included data from 41 economic studies. Ten studies evaluated the cost of the COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness and response measures. Overall, the economic burden of the COVID-19 pandemic was found to be substantial. Community screening, bed provision policies, investing in personal-protective-equipment and vaccination strategies were cost-effective. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented. CONCLUSIONS: COVID-19 pandemic is associated with substantial short-term and long-term economic costs to healthcare systems, payers and societies, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.

Clinicians' views of prescribing oral and intravenous bisphosphonates for osteoporosis: a qualitative study.

BACKGROUND: Bisphosphonate medications, including alendronate, ibandronate and risedronate administered orally and zoledronate, administered intravenously, are commonly prescribed for the treatment of osteoporosis based on evidence that, correctly taken, bisphosphonates can improve bone strength and lead to a reduction in the risk of fragility fractures. However, it is currently unclear how decisions to select between bisphosphonate regimens, including intravenous regimen, are made in practice and how clinicians support patients with different treatments. METHODS: This was an interpretivist qualitative study. 23 semi-structured telephone interviews were conducted with a sample of general practitioners (GPs), secondary care clinicians, specialist experts as well as those providing and leading novel treatments including participants from a community intravenous (IV) zoledronate service. Data analysis was undertaken through a process of iterative categorisation. RESULTS: The results report clinicians varying experiences of making treatment choices, as well as wider aspects of osteoporosis care. Secondary care and specialist clinicians conveyed some confidence in making treatment choices including on selecting IV treatment. This was aided by access to diagnostic testing and medication expertise. In contrast GPs reported a number of challenges in prescribing bisphosphonate medications for osteoporosis and uncertainty about treatment choice. Results also highlight how administering IV zoledronate was seen as an opportunity to engage in broader care practices. CONCLUSION: Approaches to making treatment decisions and supporting patients when prescribing bisphosphonates for osteoporosis vary in practice. This study points to the need to co-ordinate osteoporosis treatment and care across different care providers.

Social determinants of health and vaccine uptake during the first wave of the COVID-19 pandemic: A systematic review.

Social determinants of health significantly impact population health status. The aim of this systematic review was to examine which social vulnerability factors or determinants of health at the individual or county level affected vaccine uptake within the first phase of the vaccination program. We performed a systematic review of peer-reviewed literature published from January 2020 until September 2021 in Medline and Embase (Bagaria et al., 2022) and complemented the review with an assessment of pre-print literature within the same period. We restricted our criteria to studies performed in the EU/UK/EEA/US that report vaccine uptake in the general population as the primary outcome and included various social determinants of health as explanatory variables. This review provides evidence of significant associations between the early phases of vaccination uptake for SARS-CoV-2 and multiple socioeconomic factors including income, poverty, deprivation, race/ethnicity, education and health insurance. The identified associations should be taken into account to increase vaccine uptake in socially vulnerable groups, and to reduce disparities in uptake, in particular within the context of public health preparedness for future pandemics. While further corroboration is needed to explore the generalizability of these findings across the European setting, these results confirm the need to consider vulnerable groups and social determinants of health in the planning and roll-out of SARS-CoV-2 vaccination programs and within the context of future respiratory pandemics.