Real-World Experience of Adalimumab Biosimilar (ABP 501) Use in Patients with Inflammatory Bowel Disease in Europe.

INTRODUCTION: Approval of adalimumab biosimilar ABP 501 (Amgevita®) for inflammatory bowel disease (IBD) was based upon the principle of extrapolation. Real-world experience of ABP 501 utilization in IBD can provide useful information to healthcare providers and patients. METHODS: Data were drawn from the 2020-2021 Adelphi IBD Disease Specific Programme™ conducted in five major European countries. Participating gastroenterologists completed a point-in-time survey to provide patient medical record data, and patients voluntarily completed questionnaires to report health-related quality of life (HRQoL). Descriptive analyses were conducted for "ABP 501 initiators" (received ABP 501 as first advanced therapy) and "RP-ABP 501 switchers" (switched to ABP 501 from reference product [RP; Humira®] as first advanced therapy). RESULTS: This analysis included 239 ABP 501 initiators and 136 RP-ABP 501 switchers. At consultation, initiators had been on ABP 501 treatment for a median of 7.5 months and switchers had received ABP 501 for a median of 7.7 months following the switch from a median of 14.0 months treatment with RP. About 74% of initiators and 89% of switchers were reported by their treating physicians as being in clinical remission. Physicians and patients reported satisfaction with ABP 501 in the range of 92-99% across both groups. Patient self-assessment, including EuroQol visual analogue scale, Short IBD Questionnaire, and Work Productivity and Activity Impairment scores, suggested minimal impairment of HRQoL while on ABP 501. The most common reason for RP to ABP 501 switch was lower healthcare costs. CONCLUSION: Both patients with IBD and treating physicians reported high levels of satisfaction with ABP 501 among initiators and switchers.

ABP 501 (Amgevita^®) is the first approved biosimilar to adalimumab originator (Humira^®), referred to here as the reference product. A biosimilar is a biological product that is highly similar to its reference product in terms of safety, purity, and effectiveness. ABP 501 has been approved for the treatment of certain chronic inflammatory diseases. The approval of ABP 501 for inflammatory disease is based upon the principle of extrapolation, with no clinical trial being conducted in patients with inflammatory bowel disease. Therefore, in this current study, we evaluated the utilization experience of biosimilar ABP 501 in the real-world setting from both physicians' and patients' perspectives. We reported that patients with inflammatory bowel disease who initiated ABP 501 as the first advanced therapy as well as patients who continued therapy on ABP 501 after a switch from the adalimumab reference product both had a high level of satisfaction when using the biosimilar ABP 501. Treating physicians also reported that most of their patients were in clinical remission while on treatment with ABP 501, and patients themselves reported minimal impairment of health-related quality of life.

The potential impact of policies and structural interventions in reducing cardiovascular disease and mortality: a systematic review of simulation-based studies.

Background: The aim of the study was to investigate the potential effect of different structural interventions for preventing cardiovascular disease. Methods: Medline and EMBASE were searched for peer-reviewed simulation-based studies of structural interventions for prevention of cardiovascular disease. We performed a systematic narrative synthesis. Results: A total of 54 studies met the inclusion criteria. Diet, nutrition, tobacco and alcohol control and other programmes are among the policy simulation models explored. Food tax and subsidies, healthy food and lifestyles policies, palm oil tax, processed meat tax, reduction in ultra-processed foods, supplementary nutrition assistance programmes, stricter food policy and subsidised community-supported agriculture were among the diet and nutrition initiatives. Initiatives to reduce tobacco and alcohol use included a smoking ban, a national tobacco control initiative and a tax on alcohol. Others included the NHS Health Check, WHO 25 × 25 and air quality management policy. Future work and limitations: There is significant heterogeneity in simulation models, making comparisons of output data impossible. While policy interventions typically include a variety of strategies, none of the models considered possible interrelationships between multiple policies or potential interactions. Research that investigates dose-response interactions between numerous modifications as well as longer-term clinical outcomes can help us better understand the potential impact of policy-level interventions. Conclusions: The reviewed studies underscore the potential of structural interventions in addressing cardiovascular diseases. Notably, interventions in areas such as diet, tobacco, and alcohol control demonstrate a prospective decrease in cardiovascular incidents. However, to realize the full potential of such interventions, there is a pressing need for models that consider the interplay and cumulative impacts of multiple policies. Rigorous research into holistic and interconnected interventions will pave the way for more effective policy strategies in the future. Study registration: The study is registered as PROSPERO CRD42019154836. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/148/05.

This study aimed to explore the potential effects of various policy changes on the prevention of heart disease. By searching two large medical databases, we identified studies that employed computer models to estimate the impact of these policies on heart disease rates. In total, 54 studies matched our criteria. These studies considered a diverse range of policy interventions. Some delved into food and nutrition, investigating aspects like unhealthy food taxes, healthy food subsidies, stricter food regulations, and nutritional assistance programs. Others examined the impact of policies targeting tobacco and alcohol, encompassing smoking bans, nationwide tobacco control measures, and alcohol taxation. Further policies assessed included routine health checkups, global health goals, and measures to enhance air quality. One significant challenge lies in the varied approaches and models each study employed, making direct comparisons difficult. Furthermore, there's a gap in understanding how these policies might influence one another, as the studies did not consider potential interactions between them. While these policies show promise in the computer models, more comprehensive research is needed to fully appreciate their combined and long-term effects on heart health in real-world scenarios. As of now, we recognize the potential of these interventions, but further studies will determine their true impact on reducing heart disease rates.

Socioeconomic Macro-Level Determinants of Hypertension: Ecological Analysis of 138 Low- and Middle-Income Countries.

AIM: To assess the relative importance of major socioeconomic determinants of population health on the burden of hypertension in Low-and-Middle-Income Countries (LMICs). METHODS: Country-level data from 138 countries based on World Development Indicators 2020 were used for correlation and linear regression analyses of eight socioeconomic predictors of hypertension: current health expenditure, domestic general government health expenditure per capita, GDP per capita, adult literacy rate, unemployment rate, urban population, multidimensional poverty index, and total population. RESULTS: The median prevalence of age-standardised hypertension was 25.8% across the 138 countries, ranging from 13.7% in Peru to 33.4% in Niger. For every 10% increase in the unemployment rate, the prevalence of hypertension increased by 2.70%. For every 10% increase in the percentage of people living in urban areas, hypertension was reduced by 0.63%. CONCLUSIONS: The findings revealed that countries with high GDP, more investment in health and an improved multidimensional poverty index have a lower prevalence of hypertension.

Determining optimal strategies for primary prevention of cardiovascular disease: systematic review of cost-effectiveness analyses in the United Kingdom.

BACKGROUND: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. The aim of the study was to guide researchers and commissioners of cardiovascular disease preventative services towards possible cost-effective interventions by reviewing published economic analyses of interventions for the primary prevention of cardiovascular disease, conducted for or within the UK NHS. METHODS: In January 2021, electronic searches of MEDLINE and Embase were carried out to find economic evaluations of cardiovascular disease preventative services. We included fully published economic evaluations (including economic models) conducted alongside randomised controlled trials of any form of intervention that was aimed at the primary prevention of cardiovascular disease, including, but not limited to, drugs, diet, physical activity and public health. Full systematic review methods were used with predetermined inclusion/exclusion criteria, data extraction and formal quality appraisal [using the Consolidated Health Economic Evaluation Reporting Standards checklist and the framework for the quality assessment of decision analytic modelling by Philips et al. (Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, et al. Review of guidelines for good practice in decision-analytic modelling in health technology assessment. Health Technol Assess 2004;8(36)]. RESULTS: Of 4351 non-duplicate citations, eight articles met the review's inclusion criteria. The eight articles focused on health promotion (n = 3), lipid-lowering medicine (n = 4) and blood pressure-lowering medication (n = 1). The majority of the populations in each study had at least one risk factor for cardiovascular disease or were at high risk of cardiovascular disease. For the primary prevention of cardiovascular disease, all strategies were cost-effective at a threshold of £25,000 per quality-adjusted life-year, except increasing motivational interviewing in addition to other behaviour change strategies. Where the cost per quality-adjusted life-year gained was reported, interventions varied from dominant (i.e. less expensive and more effective than the comparator intervention) to £55,000 per quality-adjusted life-year gained. FUTURE WORK AND LIMITATIONS: We found few health economic analyses of interventions for primary cardiovascular disease prevention conducted within the last decade. Future economic assessments should be undertaken and presented in accordance with best practices so that future reviews may make clear recommendations to improve health policy. CONCLUSIONS: It is difficult to establish direct comparisons or draw firm conclusions because of the uncertainty and heterogeneity among studies. However, interventions conducted for or within the UK NHS were likely to be cost-effective in people at increased risk of cardiovascular disease when compared with usual care or no intervention. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in Health Technology Assessment. See the NIHR Journals Library website for further project information.

Increasing comprehensiveness and reducing workload in a systematic review of complex interventions using automated machine learning.

BACKGROUND: As part of our ongoing systematic review of complex interventions for the primary prevention of cardiovascular diseases, we have developed and evaluated automated machine-learning classifiers for title and abstract screening. The aim was to develop a high-performing algorithm comparable to human screening. METHODS: We followed a three-phase process to develop and test an automated machine learning-based classifier for screening potential studies on interventions for primary prevention of cardiovascular disease. We labelled a total of 16,611 articles during the first phase of the project. In the second phase, we used the labelled articles to develop a machine learning-based classifier. After that, we examined the performance of the classifiers in correctly labelling the papers. We evaluated the performance of the five deep-learning models [i.e. parallel convolutional neural network ( CNN ), stacked CNN , parallel-stacked CNN , recurrent neural network ( RNN ) and CNN-RNN]. The models were evaluated using recall, precision and work saved over sampling at no less than 95% recall. RESULTS: We labelled a total of 16,611 articles, of which 676 (4.0%) were tagged as 'relevant' and 15,935 (96%) were tagged as 'irrelevant'. The recall ranged from 51.9% to 96.6%. The precision ranged from 64.6% to 99.1%. The work saved over sampling ranged from 8.9% to as high as 92.1%. The best-performing model was parallel CNN , yielding a 96.4% recall, as well as 99.1% precision, and a potential workload reduction of 89.9%. FUTURE WORK AND LIMITATIONS: We used words from the title and the abstract only. More work needs to be done to look into possible changes in performance, such as adding features such as full document text. The approach might also not be able to be used for other complex systematic reviews on different topics. CONCLUSION: Our study shows that machine learning has the potential to significantly aid the labour-intensive screening of abstracts in systematic reviews of complex interventions. Future research should concentrate on enhancing the classifier system and determining how it can be integrated into the systematic review workflow. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in Health Technology Assessment. See the NIHR Journals Library website for further project information.

Association between gender-based violence and hypertension among women in the Kyrgyzstan Republic.

BACKGROUND: Gender-based violence (GBV) is a significant global public health problem and the most prominent human rights violation severely impacting women's health and wellbeing. Therefore, the aim of this study is to evaluate the association between gender-based violence and hypertension in Kyrgyzstan Republic. METHODS: This study was conducted using population-based data of women from the 2018 Kyrgyzstan Demographic and Health Survey. The odds ratio was calculated to measure the association between GBV and hypertension, and p-values < 0.005 was considered statistically significant. RESULT: We included data of 4793 participants, and 621 (13%) of them had hypertension. Participants exposed to GBV were 24% more likely to have hypertension than unexposed participants (OR = 1.24, 95% CI: 1.03-1.48). Of all women with hypertension, 206 (33.0%) were exposed to GBV. Participants with secondary education or higher exposed to GBV were 24% more likely to be hypertensive than GBV unexposed women with the same education levels OR = 1.24, 95% CI: 1.04-1.49). Unemployed participants exposed to GBV were 45% more likely to develop hypertension than their unexposed counterparts (OR = 1.45, 95%CI: 1.15-1.81). Rural residents exposed to GBV were also 29% more likely to have hypertension than those unexposed to GBV (OR = 1.29, 95% CI: 1.04-1.59). The odds of hypertension among those exposed to GBV increase with age. CONCLUSION: The study revealed that GBV is a significant factor of having hypertension among Kyrgyz women.

One Hundred Years of Hypertension Research: Topic Modeling Study.

BACKGROUND: Due to scientific and technical advancements in the field, published hypertension research has developed substantially during the last decade. Given the amount of scientific material published in this field, identifying the relevant information is difficult. We used topic modeling, which is a strong approach for extracting useful information from enormous amounts of unstructured text. OBJECTIVE: This study aims to use a machine learning algorithm to uncover hidden topics and subtopics from 100 years of peer-reviewed hypertension publications and identify temporal trends. METHODS: The titles and abstracts of hypertension papers indexed in PubMed were examined. We used the latent Dirichlet allocation model to select 20 primary subjects and then ran a trend analysis to see how popular they were over time. RESULTS: We gathered 581,750 hypertension-related research articles from 1900 to 2018 and divided them into 20 topics. These topics were broadly categorized as preclinical, epidemiology, complications, and therapy studies. Topic 2 (evidence review) and topic 19 (major cardiovascular events) are the key (hot topics). Most of the cardiopulmonary disease subtopics show little variation over time, and only make a small contribution in terms of proportions. The majority of the articles (414,206/581,750; 71.2%) had a negative valency, followed by positive (119, 841/581,750; 20.6%) and neutral valency (47,704/581,750; 8.2%). Between 1980 and 2000, negative sentiment articles fell somewhat, while positive and neutral sentiment articles climbed substantially. CONCLUSIONS: The number of publications has been increasing exponentially over the period. Most of the uncovered topics can be grouped into four categories (ie, preclinical, epidemiology, complications, and treatment-related studies).

Household Air Pollution and High Blood Pressure: A Secondary Analysis of the 2016 Albania Demographic Health and Survey Dataset.

Background: Hypertension is a significant public health problem in low- and middle-income countries (LMICs). This study aimed to examine the association between household air pollution (HAP) and blood pressure using data from the 2016 Albania Demographic Health and Survey (DHS). Methods: We computed the odds ratio (OR) for the prevalence of hypertension between respondents exposed to clean fuels (e.g., electricity, liquid petroleum gas, natural gas, and biogas) and respondents exposed to polluting fuel (e.g., kerosene, coal/lignite, charcoal, wood, straw/shrubs/grass, and animal dung). Result: The results show that participants exposed to household polluting fuels in Albania were 17% more likely to develop hypertension than those not exposed to household air pollution (OR = 1.17, 95% CI 1.10 to 1.24). Subgroup analysis revealed that the odds of hypertension were more significant among women (OR = 1.22, 95% CI 1.13 to 1.31), rural residents (OR = 1.12, 95% CI 1.04 to 1.22), and participants aged >24 years (OR = 1.35, 95% CI 1.12 to 1.62) who were exposed to household polluting fuels compared to their counterparts who were not exposed. In summary, the results of the study show significant associations between household air pollution and hypertension risk overall, especially among women, rural dwellers, and people aged >24 years in Albania. Conclusion: In this study, an association between household air pollution and the risk of hypertension was found, particularly among low-income households, those with no education, women, and those who live in rural areas.

Factors associated with attendance at screening for breast cancer: a systematic review and meta-analysis.

OBJECTIVE: Attendance at population-based breast cancer (mammographic) screening varies. This comprehensive systematic review and meta-analysis assesses all identified patient-level factors associated with routine population breast screening attendance. DESIGN: CINAHL, Cochrane Library, Embase, Medline, OVID, PsycINFO and Web of Science were searched for studies of any design, published January 1987-June 2019, and reporting attendance in relation to at least one patient-level factor. DATA SYNTHESIS: Independent reviewers performed screening, data extraction and quality appraisal. OR and 95% CIs were calculated for attendance for each factor and random-effects meta-analysis was undertaken where possible. RESULTS: Of 19 776 studies, 335 were assessed at full text and 66 studies (n=22 150 922) were included. Risk of bias was generally low. In meta-analysis, increased attendance was associated with higher socioeconomic status (SES) (n=11 studies; OR 1.45, 95% CI: 1.20 to 1.75); higher income (n=5 studies; OR 1.96, 95% CI: 1.68 to 2.29); home ownership (n=3 studies; OR 2.16, 95% CI: 2.08 to 2.23); being non-immigrant (n=7 studies; OR 2.23, 95% CI: 2.00 to 2.48); being married/cohabiting (n=7 studies; OR 1.86, 95% CI: 1.58 to 2.19) and medium (vs low) level of education (n=6 studies; OR 1.24, 95% CI: 1.09 to 1.41). Women with previous false-positive results were less likely to reattend (n=6 studies; OR 0.77, 95% CI: 0.68 to 0.88). There were no differences by age group or by rural versus urban residence. CONCLUSIONS: Attendance was lower in women with lower SES, those who were immigrants, non-homeowners and those with previous false-positive results. Variations in service delivery, screening programmes and study populations may influence findings. Our findings are of univariable associations. Underlying causes of lower uptake such as practical, physical, psychological or financial barriers should be investigated. TRIAL REGISTRATION NUMBER: CRD42016051597.

Influence of contextual socioeconomic position on hypertension risk in low- and middle-income countries: disentangling context from composition.

BACKGROUND: Hypertension has emerged as the single most significant modifiable risk factor for cardiovascular disease and death worldwide. Resource-limited settings are currently experiencing the epidemiological transition from infectious diseases to chronic non-communicable diseases, primarily due to modifications in diet and lifestyle behaviour. The objective of this study was to examine the influence of individual-, community- and country-level factors associated with hypertension in low- and middle-income countries (LMICs). METHODS: Multivariable multi-level logistic regression analysis was applied using 12 Demographic and Health Survey (DHS) datasets collected between 2011 and 2018 in LMICs. We included 888,925 respondents (Level 1) nested within 33,883 neighbourhoods (Level 2) from 12 LMICs (Level 3). RESULTS: The prevalence of hypertension ranged from 10.3% in the Kyrgyz Republic to 52.2% in Haiti. After adjusting for the individual-, neighbourhood- and country-level factors, we found respondents living in the least deprived areas were 14% more likely to have hypertension than those from the most deprived areas (OR = 1.14, 95% CI 1.10 to 1.17). We observed a significant variation in the odds of hypertension across the countries and the neighbourhoods. Approximately 26.3 and 47.6% of the variance in the odds of hypertension could be attributed to country- and neighbourhood-level factors, respectively. We also observed that respondents moving to a different neighbourhood or country with a higher risk of hypertension had an increased chance of developing hypertension, the median increase in their odds of hypertension was 2.83-fold (95% CI 2.62 to 3.07) and 4.04- fold (95% CI 3.98 to 4.08), respectively. CONCLUSIONS: This study revealed that individual compositional and contextual measures of socioeconomic status were independently associated with the risk of developing hypertension. Therefore, prevention strategies should be implemented at the individual level and the socioeconomic and contextual levels to reduce the burden of hypertension.

Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials.

The coronavirus disease 19 (COVID-19) pandemic has caused significant morbidity and mortality worldwide and an effective treatment is needed. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro antiviral activity against SARS-CoV-2 which causes the disease, but the evidence from in vivo studies so far has been inconclusive. OBJECTIVE: To evaluate the efficacy and safety of CQ and HCQ in the treatment of COVID-19. DATA SOURCES: We systematically searched the PubMed, Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Scopus, Joanna Briggs Institute Database, ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR) for all articles published between 01 January 2020 to 15 September 2020 on CQ/HCQ and COVID-19 using a predefined search protocol; without any language restrictions. A search of grey literature repositories (New York Academy of Medicine Grey Literature and Open Grey), and pre-publication server deposits (medRxIV and bioRxIV) was also performed. STUDY SELECTION: Randomized clinical trials (RCT) which compared CQ/HCQ to standard supportive therapy in treating COVID-19 were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted from original publications by four independent reviewers. Risk of bias was assessed using the Cochrane Collaboration's assessment tool. Data were meta-analyzed using a random-effect models. Results are reported according to PRISMA guidelines. Main Outcome(s) and Measure(s): The primary prespecified efficacy outcome was all-cause mortality. The primary safety outcome was any adverse effect attributed to use of CQ/HCQ. RESULTS: Eight RCTs were included and pooled in the mortality meta-analysis (6,592 unique participants; mean age = 59.4 years; 42% women). CQ/HCQ did not show any mortality benefit when compared to standard supportive therapy (Pooled Relative Risk [RR] 1.07; 95% CI = 0.97-1.18; I2 statistic = 0.00%). Sensitivity and sub-group analyses showed similar findings. Any adverse event was significantly higher in patients randomized to CQ/HCQ (RR = 2.51; 95% CI = 1.53-4.12; n = 1,818 patients), but the risk of developing severe adverse event was not statistically significant (RR = 0.99, 95% CI = 0.53-1.86; n = 6,456 patients). CONCLUSIONS AND RELEVANCE: Evidence from currently published RCTs do not demonstrate any added benefit for the use of CQ or HCQ in the treatment of COVID-19 patients.

Rapid antigen detection and molecular tests for group A streptococcal infections for acute sore throat: systematic reviews and economic evaluation.

BACKGROUND: Sore throat is a common condition caused by an infection of the airway. Most cases are of a viral nature; however, a number of these infections may be caused by the group A Streptococcus bacterium. Most viral and bacterial sore throat infections resolve spontaneously within a few weeks. Point-of-care testing in primary care has been recognised as an emerging technology for aiding targeted antibiotic prescribing for sore throat in cases that do not spontaneously resolve. OBJECTIVE: Systematically review the evidence for 21 point-of-care tests for detecting group A Streptococcus bacteria and develop a de novo economic model to compare the cost-effectiveness of point-of-care tests alongside clinical scoring tools with the cost-effectiveness of clinical scoring tools alone for patients managed in primary care and hospital settings. DATA SOURCES: Multiple electronic databases were searched from inception to March 2019. The following databases were searched in November and December 2018 and searches were updated in March 2019: MEDLINE [via OvidSP (Health First, Rockledge, FL, USA)], MEDLINE In-Process & Other Non-Indexed Citations (via OvidSP), MEDLINE Epub Ahead of Print (via OvidSP), MEDLINE Daily Update (via OvidSP), EMBASE (via OvidSP), Cochrane Database of Systematic Reviews [via Wiley Online Library (John Wiley & Sons, Inc., Hoboken, NJ, USA)], Cochrane Central Register of Controlled Trials (CENTRAL) (via Wiley Online Library), Database of Abstracts of Reviews of Effects (DARE) (via Centre for Reviews and Dissemination), Health Technology Assessment database (via the Centre for Reviews and Dissemination), Science Citation Index and Conference Proceedings [via the Web of Science™ (Clarivate Analytics, Philadelphia, PA, USA)] and the PROSPERO International Prospective Register of Systematic Reviews (via the Centre for Reviews and Dissemination). REVIEW METHODS: Eligible studies included those of people aged ≥ 5 years presenting with sore throat symptoms, studies comparing point-of-care testing with antibiotic-prescribing decisions, studies of test accuracy and studies of cost-effectiveness. Quality assessment of eligible studies was undertaken. Meta-analysis of sensitivity and specificity was carried out for tests with sufficient data. A decision tree model estimated costs and quality-adjusted life-years from an NHS and Personal Social Services perspective. RESULTS: The searches identified 38 studies of clinical effectiveness and three studies of cost-effectiveness. Twenty-six full-text articles and abstracts reported on the test accuracy of point-of-care tests and/or clinical scores with biological culture as a reference standard. In the population of interest (patients with Centor/McIsaac scores of ≥ 3 points or FeverPAIN scores of ≥ 4 points), point estimates were 0.829 to 0.946 for sensitivity and 0.849 to 0.991 for specificity. There was considerable heterogeneity, even for studies using the same point-of-care test, suggesting that is unlikely that any single study will have accurately captured a test's true performance. There is some randomised controlled trial evidence to suggest that the use of rapid antigen detection tests may help to reduce antibiotic-prescribing rates. Sensitivity and specificity estimates for each test in each age group and care setting combination were obtained using meta-analyses where appropriate. Any apparent differences in test accuracy may not be attributable to the tests, and may have been caused by known differences in the studies, latent characteristics or chance. Fourteen of the 21 tests reviewed were included in the economic modelling, and these tests were not cost-effective within the current National Institute for Health and Care Excellence's cost-effectiveness thresholds. Uncertainties in the cost-effectiveness estimates included model parameter inputs and assumptions that increase the cost of testing, and the penalty for antibiotic overprescriptions. LIMITATIONS: No information was identified for the elderly population or pharmacy setting. It was not possible to identify which test is the most accurate owing to the paucity of evidence. CONCLUSIONS: The systematic review and the cost-effectiveness models identified uncertainties around the adoption of point-of-care tests in primary and secondary care settings. Although sensitivity and specificity estimates are promising, we have little information to establish the most accurate point-of-care test. Further research is needed to understand the test accuracy of point-of-care tests in the proposed NHS pathway and in comparable settings and patient groups. STUDY REGISTRATION: The protocol of the review is registered as PROSPERO CRD42018118653. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 31. See the NIHR Journals Library website for further project information.

Sore throat is a common condition caused by an infection of the airway. Most cases are viral; however, a small number may be caused by the group A Streptococcus bacterium. Most viral and bacterial sore throat infections resolve spontaneously within a few weeks; however, some may be more serious and require antibiotics. Currently, National Institute for Health and Care Excellence guidance recommends the use of clinical scoring tools to identify patients for whom antibiotic treatment is appropriate. Ideally, a throat swab culture should be obtained to identify the organism causing the infection in cases in which diagnosis is uncertain. However, this takes time, causing potential delays in administering the correct treatment. Point-of-care tests can be administered at or near the site of the patient; therefore, they are much faster. Our review considered evidence for the test accuracy and cost-effectiveness of 21 point-of-care tests for detecting group A Streptococcus bacteria. We built an economic model, predicting costs and benefits for adults and children in a primary care or hospital setting. The findings will support the National Institute for Health and Care Excellence to make recommendations about the use of these point-of-care tests for detecting group A Streptococcus bacteria in the NHS in England and Wales. The clinical effectiveness review found 38 relevant studies; of these, 26 reported on the accuracy of point-of-care tests. These studies found wide variation in the accuracy of the tests. The quality of the evidence was weak and there was little information on some of the 21 tests. As the studies were all so different, it was not possible to identify which test is the most accurate. The economic model found considerable uncertainty about how costs and benefits would change if point-of-care tests were introduced in different care settings. Further research is needed to see whether or not point-of-care testing provides value for money.

Determining optimal strategies for primary prevention of cardiovascular disease: systematic review, cost-effectiveness review and network meta-analysis protocol.

BACKGROUND: Despite recent improvements in the burden of cardiovascular disease (CVD) in the UK, deaths from CVD are relatively high compared with other high-income countries. An estimated 7 million people in the UK are living with CVD, and the healthcare cost is approximately £11 billion annually. In more than 90% of cases, the risk of a first heart attack is thought to be related to modifiable risk factors including smoking, poor diet, lipidemia, high blood pressure, inactivity, obesity and excess alcohol consumption. The aim of the study is to synthesise evidence for the comparative effectiveness and cost-effectiveness of different interventions for the primary prevention of CVD. METHODS: We will systematically search databases (for example, MEDLINE (Ovid), Embase (Ovid), Cochrane Library) and the reference lists of previous systematic reviews for randomised controlled trials that assess the effectiveness and cost-effectiveness of any form of intervention aimed at adult populations for the primary prevention of CVD, including but not limited to lipid lowering medications, blood pressure lowering medications, antiplatelet agents, nutritional supplements, dietary interventions, health promotion programmes, physical activity interventions or structural and policy interventions. Interventions may or may not be targeted at high-risk groups. Publications from any year will be considered for inclusion. The primary outcome will be all cause mortality. Secondary outcomes will be cardiovascular diseases related mortality, major cardiovascular events, coronary heart disease, incremental costs per quality-adjusted life years gained. If data permits, we will use network meta-analysis to compare and rank effectiveness of different interventions, and test effect modification of intervention effectiveness using subgroup analyses and meta-regression analyses. DISCUSSION: The results will be important for policymakers when making decisions between multiple possible alternative strategies to prevent CVD. Compared to results from existing multiple separate pairwise meta-analyses, this overarching synthesis of all relevant work will enhance decision-making. The findings will be crucial to inform evidence-based priorities and guidelines for policies and planning prevention strategies of CVD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019123940.

Correction to: Venetoclax for Treating Chronic Lymphocytic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

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Comparison of mHealth and Face-to-Face Interventions for Smoking Cessation Among People Living With HIV: Meta-Analysis.

BACKGROUND: The prevalence of smoking among people living with HIV (PLHIV) is higher than that reported in the general population, and it is a significant risk factor for noncommunicable diseases in this group. Mobile phone interventions to promote healthier behaviors (mobile health, mHealth) have the potential to reach a large number of people at a low cost. It has been hypothesized that mHealth interventions may not be as effective as face-to-face strategies in achieving smoking cessation, but there is no systematic evidence to support this, especially among PLHIV. OBJECTIVE: This study aimed to compare two modes of intervention delivery (mHealth vs face-to-face) for smoking cessation among PLHIV. METHODS: Literature on randomized controlled trials (RCTs) investigating effects of mHealth or face-to-face intervention strategies on short-term (4 weeks to <6 months) and long-term (≥6 months) smoking abstinence among PLHIV was sought. We systematically reviewed relevant RCTs and conducted pairwise meta-analyses to estimate relative treatment effects of mHealth and face-to-face interventions using standard care as comparison. Given the absence of head-to-head trials comparing mHealth with face-to-face interventions, we performed adjusted indirect comparison meta-analyses to compare these interventions. RESULTS: A total of 10 studies involving 1772 PLHIV met the inclusion criteria. The average age of the study population was 45 years, and women comprised about 37%. In the short term, mHealth-delivered interventions were significantly more efficacious in increasing smoking cessation than no intervention control (risk ratio, RR, 2.81, 95% CI 1.44-5.49; n=726) and face-to-face interventions (RR 2.31, 95% CI 1.13-4.72; n=726). In the short term, face-to-face interventions were no more effective than no intervention in increasing smoking cessation (RR 1.22, 95% CI 0.94-1.58; n=1144). In terms of achieving long-term results among PLHIV, there was no significant difference in the rates of smoking cessation between those who received mHealth-delivered interventions, face-to-face interventions, or no intervention. Trial sequential analysis showed that only 15.16% (726/1304) and 5.56% (632/11,364) of the required information sizes were accrued to accept or reject a 25% relative risk reduction for short- and long-term smoking cessation treatment effects. In addition, sequential monitoring boundaries were not crossed, indicating that the cumulative evidence may be unreliable and inconclusive. CONCLUSIONS: Compared with face-to-face interventions, mHealth-delivered interventions can better increase smoking cessation rate in the short term. The evidence that mHealth increases smoking cessation rate in the short term is encouraging but not sufficient to allow a definitive conclusion presently. Future research should focus on strategies for sustaining smoking cessation treatment effects among PLHIV in the long term.

Statin use and all-cause mortality in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: It is unknown whether statin use among people living with HIV results in a reduction in all-cause mortality. We aimed to evaluate the effect of statin use on all-cause mortality among people living with HIV. METHODS: We conducted comprehensive literature searches of Medline, Embase, CINAHL, the Cochrane Library, and cross-references up to April 2018. We included randomised, quasi-randomised trials and prospective cohort studies that examined the association between statin use and cardio-protective and mortality outcomes among people living with HIV. Two reviewers independently abstracted the data. Hazard ratios (HRs) were pooled using empirical Bayesian random-effect meta-analysis. A number of sensitivity analyses were conducted. RESULTS: We included seven studies with a total of 35,708 participants. The percentage of participants on statins across the studies ranged from 8 to 35%. Where reported, the percentage of participants with hypertension ranged from 14 to 35% and 7 to 10% had been diagnosed with diabetes mellitus. Statin use was associated with a 33% reduction in all-cause mortality (pooled HR = 0.67, 95% Credible Interval 0.39 to 0.96). The probability that statin use conferred a moderate mortality benefit (i.e. decreased risk of mortality of at least 25%, HR ≤ 0.75) was 71.5%. Down-weighting and excluding the lower quality studies resulted in a more conservative estimate of the pooled HR. CONCLUSION: Statin use appears to confer moderate mortality benefits in people living with HIV.

Venetoclax for Treating Chronic Lymphocytic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Venetoclax is licensed to treat relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL). As part of the Single Technology Appraisal (STA) ID944, the National Institute for Health and Care Excellence (NICE) invited AbbVie, the manufacturer, to submit evidence on the use of venetoclax, within its licensed indication. The Evidence Review Group (ERG), Warwick Evidence, was asked to provide an independent and critical review of the submitted evidence. Evidence came from three single-arm trials in CLL patients with or without 17p deletion [del(17p])/TP53 chromosomal abnormalities. The anticipated licensed indication specified that venetoclax-eligible del(17p)/TP53 patients should have not responded to, or be deemed unsuitable for, B-cell receptor inhibitor (BCRi) therapy, and that non-del(17p)/TP53 patients should have not responded to both chemoimmunotherapy and BCRi therapy. The three trials were heterogeneous in terms of both del(17p)/TP53 status and previous exposure to BCRi therapy. The M13-982 study investigated 158 R/R CLL patients with the 17p deletion, but only a small number had received previous BCRi therapy; the M12-175 study investigated 67 patients with CLL or small lymphocytic lymphoma, some with the 17p deletion, but very few previously treated with BCRi therapy; and the M14-032 study included 105 patients previously treated with BCRi therapy (either idelalisib or ibrutinib), some of whom had unknown mutation status. The ERG concluded that the study populations did not directly conform to those specified in the licensed indication or in the NICE scope. Outcomes reported included overall response rate (ORR), duration of response, progression-free survival (PFS) and overall survival (OS); adverse events were reported for the pooled population of all three studies, as well as separately for each study. The median PFS was 41.4 and 27.2 months among patients in the M12-175 and M13-982 trials, respectively, whereas the median PFS was not reached in the M14-032 trial. Some results were designated academic in confidence and cannot be reported here. The submission provided a de novo partitioned survival cost-effectiveness model with three health states: pre-progression, post-progression and dead. Transition probabilities between health states were estimated using Weibull models for PFS and OS. The ERG judged the model structure to be appropriate. Venetoclax was compared with best supportive care (BSC) in patients with or without del(17p)/TP53 mutation status, and with palliative care (PC). To populate the del(17p)/TP53 venetoclax arm, the submission pooled del(17p)/TP53 patients from all three studies and fitted Weibull models for PFS and OS. PFS and OS models for non-del(17p)/TP53 venetoclax patients were obtained by applying hazard ratios (HRs) to the del(17p)/TP53 OS and PFS models, derived using Cox's regression analysis comparing del(17p)/TP53 and non-del(17p)/TP53 patients pooled from the M14-032 and M12-175 studies. The ERG expressed reservations about the company's pooling procedure, but acknowledged its expedience given the small evidence base. For the BSC comparator arm, the submission used the rituximab + placebo arm from a randomised controlled trial comparing idelalisib + rituximab versus placebo + rituximab ('study 116'). Weibull regression data for OS and PFS were taken from the idelalisib STA (ID764) submitted by Gilead to NICE. The ERG considered the use of the study 116 rituximab arm to be inconsistent with the licensed indication for venetoclax because these patients had neither not responded to nor were inappropriate for BCRi therapy, being eligible to be randomised to idelalisib. Another difficulty was the requirement for a technical correction in survival analysis because of considerable switching from rituximab to idelalisib. The ERG considered that post-progression survival of patients from the idelalisib arm of study 116 provided a more appropriate representation of BSC since these patients had not responded to BCRi therapy, consistent with venetoclax's licensed indication. For PC, the company submission used data from the UK CLL Forum. The company's base-case analysis indicated that venetoclax was clinically effective, but the resulting incremental cost-effectiveness ratios (ICERs) for del(17p)/TP53 (£39,940/quality-adjusted life-year [QALY] gained) and non-del(17p)/TP53 (£47,370/QALY gained) patients were well above the NICE threshold of £20,000-30,000/QALY. The ERG identified two errors in the implementation of the company's parametric models-one related to the implementation of HRs, and the other to the derivation of the Weibull shape parameters obtained from the Gilead idelalisib submission. The ERG made plausible adjustments to the company's base-case and corrected errors, resulting in a reduced estimate of the cost effectiveness of venetoclax in non-del(17p)/TP53 and del(17p)/TP53 indications; in the ERG's preferred base case, using post-progression survival of patients in the idelalisib arm of study 116 as the BSC comparator, deterministic ICERs were higher than the company's base-case for both indications: £57,476/QALY gained for del(17p)/TP53 and £77,779/QALY gained for non-del(17p)/TP53. The NICE Appraisal Committee's preliminary recommendation was that venetoclax used within its licensed indication should not be recommended for use in the National Health Service (NHS). In response to the preliminary recommendation, the company submitted new analyses; however, at a subsequent appraisal committee meeting, the original recommendation was upheld and the committee concluded there were large uncertainties around the clinical effectiveness of venetoclax and BSC, and that under the committee's preferred assumptions, the ICERs were higher than those generally considered cost effective, even when end-of-life criteria were taken into account. The company submitted further evidence, and the final guidance recommended venetoclax for use with the Cancer Drugs Fund for the two populations in this technology appraisal.

Features of cardiovascular disease in low-income and middle-income countries in adults and children living with HIV.

PURPOSE OF REVIEW: The current article addresses crucial issues in identifying risk of cardiovascular disease (CVD) in people living with HIV in low-income and middle-income countries (LMICs). These issues are in need of urgent attention to advance our knowledge and inform actions to mitigate CVD in this population. We address CVDs in adults living with HIV as well as the unique aspects pertaining to children living with HIV (CLHIV), a group sorely under-represented in this field. RECENT FINDINGS: CVDs affecting adults such as hypertension, dyslipidemia, coronary artery disease, and heart failure, in addition to myocardial dysfunction, vascular diseases, and autoimmune phenomena are also being reported in CLHIV. In addition to the background disparity in prevalence of traditional CVD risk factors, it is also likely that differential access to antiretroviral treatment, the younger age of the HIV-infected population, and types of antiretroviral treatment commonly used in LMICs contribute to the observed differences. SUMMARY: Overall, the state of evidence for CVD in LMICs is limited and at times contradictory. We summarize the evidence with suggestions for high priorities for further scientific investigation. Now is the crucial time to intervene in modifying CVD risk in LMICs.

Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV-infected patients? A meta-analysis.

The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes. We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV-infected patients naïve and exposed to ART. Mean difference in FPG concentrations and odds ratios of diabetes and metabolic syndrome were pooled using random-effects meta-analyses. Data on 20 178 participants from 41 observational studies were included in the meta-analyses. Mean FPG concentrations (Pooled mean difference: 4.66 mg/dL; 95% confidence interval [CI], 2.52 to 6.80; 24 studies) and the odds of diabetes (Pooled odds ratios: 3.85; 95% CI, 2.93 to 5.07; 10 studies) and metabolic syndrome (Pooled odds ratios: 1.45; 95% CI, 1.03 to 2.03; 18 studies) were significantly higher among ART-exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥18 months (Pooled mean difference: 4.97 mg/dL; 95% CI, 3.10 to 6.84; 14 studies), but not in studies with mean ART duration <18 months (Pooled mean difference: 4.40 mg/dL, 95% CI, -0.59 to 9.38; 7 studies). ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross-sectional studies in the meta-analysis, the association between ART and diabetes cannot be interpreted as cause and effect.

Adherence to antiretroviral therapy among HIV-infected prisoners: a systematic review and meta-analysis.

Data on antiretroviral therapy (ART) adherence among prison inmates are limited and not previously synthesized in a systematic manner. The objective of this study was to provide accurate and up-to-date ART adherence estimates among prison inmates. We searched electronic databases for all studies reporting adherence as a primary or secondary outcome among prison inmates. A random-effects model was used to pool adherence rates; sensitivity, heterogeneity and publication bias were assessed. Eleven studies involving 2895 HIV-infected prison inmates were included. The studies were carried out between 1992 and 2011 and reported between 1998 and 2013. A pooled analysis of all studies indicated a pooled estimate of 54.6% (95% confidence interval 48.1-60.9%) of prison inmates had adequate (≥95%) ART adherence. The adherence estimates were significantly higher among cross-studies and studies that used self-reported measures. In summary, our findings indicate that optimal adherence remains a challenge among prison inmates. It is crucial to monitor ART adherence and develop appropriate interventions to improve adherence among these population.