The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model

Objective To model the long term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease

Self-sampling kits to increase HIV testing among black Africans in the UK: the HAUS mixed-methods study.

BACKGROUND: Timely diagnosis of human immunodeficiency virus (HIV) enables access to antiretroviral treatment, which reduces mortality, morbidity and further transmission in people living with HIV. In the UK, late diagnosis among black African people persists. Novel methods to enhance HIV testing in this population are needed. OBJECTIVES: To develop a self-sampling kit (SSK) intervention to increase HIV testing among black Africans, using existing community and health-care settings (stage 1) and to assess the feasibility for a Phase III evaluation (stage 2). DESIGN: A two-stage, mixed-methods design. Stage 1 involved a systematic literature review, focus groups and interviews with key stakeholders and black Africans. Data obtained provided the theoretical base for intervention development and operationalisation. Stage 2 was a prospective, non-randomised study of a provider-initiated, HIV SSK distribution intervention targeted at black Africans. The intervention was assessed for cost-effectiveness. A process evaluation explored feasibility, acceptability and fidelity. SETTING: Twelve general practices and three community settings in London. MAIN OUTCOME MEASURE: HIV SSK return rate. RESULTS: Stage 1 - the systematic review revealed support for HIV SSKs, but with scant evidence on their use and clinical effectiveness among black Africans. Although the qualitative findings supported SSK distribution in settings already used by black Africans, concerns were raised about the complexity of the SSK and the acceptability of targeting. These findings were used to develop a theoretically informed intervention. Stage 2 - of the 349 eligible people approached, 125 (35.8%) agreed to participate. Data from 119 were included in the analysis; 54.5% (65/119) of those who took a kit returned a sample; 83.1% of tests returned were HIV negative; and 16.9% were not processed, because of insufficient samples. Process evaluation showed the time pressures of the research process to be a significant barrier to feasibility. Other major barriers were difficulties with the SSK itself and ethnic targeting in general practice settings. The convenience and privacy associated with the SSK were described as beneficial aspects, and those who used the kit mostly found the intervention to be acceptable. Research governance delays prevented implementation in Glasgow. LIMITATIONS: Owing to the study failing to recruit adequate numbers (the intended sample was 1200 participants), we were unable to evaluate the clinical effectiveness of SSKs in increasing HIV testing in black African people. No samples were reactive, so we were unable to assess pathways to confirmatory testing and linkage to care. CONCLUSIONS: Our findings indicate that, although aspects of the intervention were acceptable, ethnic targeting and the SSK itself were problematic, and scale-up of the intervention to a Phase III trial was not feasible. The preliminary economic model suggests that, for the acceptance rate and test return seen in the trial, the SSK is potentially a cost-effective way to identify new infections of HIV. FUTURE WORK: Sexual and public health services are increasingly utilising self-sampling technologies. However, alternative, user-friendly SSKs that meet user and provider preferences and UK regulatory requirements are needed, and additional research is required to understand clinical effectiveness and cost-effectiveness for black African communities. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010698 and Integrated Research Application System project identification 184223. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the BHA for Equality in Health and Social Care

Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis

Importance  Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level.Objective  To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older.Data Sources  MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched.Study Selection  In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible.Data Extraction and Synthesis  The methodological quality of included studies was assessed using The Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model.Main Outcomes and Measures  Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration.Results  Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death.Conclusions and Relevance  Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.</p

Evaluating the clinical and cost effectiveness of a behaviour change intervention for lowering cardiovascular disease risk for people with severe mental illnesses in primary care (PRIMROSE study):study protocol for a cluster randomised controlled trial

BACKGROUND: People with severe mental illnesses die up to 20 years earlier than the general population, with cardiovascular disease being the leading cause of death. National guidelines recommend that the physical care of people with severe mental illnesses should be the responsibility of primary care; however, little is known about effective interventions to lower cardiovascular disease risk in this population and setting. Following extensive peer review, funding was secured from the United Kingdom National Institute for Health Research (NIHR) to deliver the proposed study. The aim of the trial is to test the effectiveness of a behavioural intervention to lower cardiovascular disease risk in people with severe mental illnesses in United Kingdom General Practices. METHODS/DESIGN: The study is a cluster randomised controlled trial in 70 GP practices for people with severe mental illnesses, aged 30 to 75 years old, with elevated cardiovascular disease risk factors. The trial will compare the effectiveness of a behavioural intervention designed to lower cardiovascular disease risk and delivered by a practice nurse or healthcare assistant, with standard care offered in General Practice. A total of 350 people will be recruited and followed up at 6 and 12 months. The primary outcome is total cholesterol level at the 12-month follow-up and secondary outcomes include blood pressure, body mass index, waist circumference, smoking status, quality of life, adherence to treatments and services and behavioural measures for diet, physical activity and alcohol use. An economic evaluation will be carried out to determine the cost effectiveness of the intervention compared with standard care. DISCUSSION: The results of this pragmatic trial will provide evidence on the clinical and cost effectiveness of the intervention on lowering total cholesterol and addressing multiple cardiovascular disease risk factors in people with severe mental illnesses in GP Practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13762819 . Date of Registration: 25 February 2013. Date and Version Number: 27 August 2014 Version 5

Socioeconomic status and diabetes technology use in youth with type 1 diabetes: a comparison of two funding models

BackgroundTechnology use, including continuous glucose monitoring (CGM) and insulin pump therapy, is associated with improved outcomes in youth with type 1 diabetes (T1D). In 2017 CGM was universally funded for youth with T1D in Australia. In contrast, pump access is primarily accessed through private health insurance, self-funding or philanthropy. The study aim was to investigate the use of diabetes technology across different socioeconomic groups in Australian youth with T1D, in the setting of two contrasting funding models.MethodsA cross-sectional evaluation of 4957 youth with T1D aged &lt;18 years in the national registry was performed to determine technology use. The Index of Relative Socio-Economic Disadvantage (IRSD) derived from Australian census data is an area-based measure of socioeconomic status (SES). Lower quintiles represent greater disadvantage. IRSD based on most recent postcode of residence was used as a marker of SES. A multivariable generalised linear model adjusting for age, diabetes duration, sex, remoteness classification, and location within Australia was used to determine the association between SES and device use.ResultsCGM use was lower in IRSD quintile 1 in comparison to quintiles 2 to 5 (p&lt;0.001) where uptake across the quintiles was similar. A higher percentage of pump use was observed in the least disadvantaged IRSD quintiles. Compared to the most disadvantaged quintile 1, pump use progressively increased by 16% (95% CI: 4% to 31%) in quintile 2, 19% (6% to 33%) in quintile 3, 35% (21% to 50%) in quintile 4 and 51% (36% to 67%) in the least disadvantaged quintile 5.ConclusionIn this large national dataset, use of diabetes technologies was found to differ across socioeconomic groups. For nationally subsidised CGM, use was similar across socioeconomic groups with the exception of the most disadvantaged quintile, an important finding requiring further investigation into barriers to CGM use within a nationally subsidised model. User pays funding models for pump therapy result in lower use with socioeconomic disadvantage, highlighting inequities in this funding approach. For the full benefits of diabetes technology to be realised, equitable access to pump therapy needs to be a health policy priority

Epidemiological modelling of cardiovascular disease in those with metabolic syndrome

Metabolic syndrome, a clustering of cardiometabolic risk factors, significantly increases the risk of developing both cardiovascular disease (CVD) and T2DM. The exact pathogenesis remains unknown, however it is hypothesised that when metabolic susceptibility is present in individuals who are overweight or obese, the development of multiple cardiometabolic risk factors (metabolic syndrome) ensues. Metabolic syndrome is estimated to affect approximately 20-30% of the Western world, with rates expected to rise as a result of an ageing and increasingly obese population, in turn increasing CVD and diabetes. With the potential health and economic burden those with metabolic syndrome pose for society, considerable efforts are being focused on determining the most effective and cost-effective prevention strategies. While data from clinical trials provides the highest level of evidence regarding the efficacy of prevention strategies, their results alone are insufficient to critically inform clinical practice and health policy. Epidemiological modelling is a relatively new discipline that translates the results of clinical trials to estimate the potential benefits and costs. This thesis comprises a series of epidemiological models, developed to assess the effectiveness and cost-effectiveness of a variety of primary preventive strategies for CVD in those with metabolic syndrome. First-line therapy guidelines for the treatment of metabolic syndrome pertain to lifestyle changes; the uptake of physical activity to recommended guidelines (and reduction of total time spent in sedentary pursuits), as well as dietary changes. Analysis of the uptake of physical activity to recommended guidelines or the reduction of TV-viewing time in those with metabolic syndrome demonstrated that both behavioural changes were effective in the prevention of cardiovascular deaths. With regard to potential dietary changes, the consumption of dark chocolate in those classified as metabolic syndrome exhibited effective and potentially cost-effective results. Analysis of a therapeutic treatment option, a multi-component drug (polypill), demonstrated the polypill was an effective means of reducing CVD. Cost-effectiveness analyses, however, illustrated that the proposed cost of the polypill would not produce a cost-effective outcome. Other work contained in this thesis pertains to the development of epidemiological models. To determine the benefits and costs of a prevention strategy, models rely not only on efficacy data of the prevention strategy sourced from clinical trials, but also require the prediction of expected event rates. Risk prediction algorithms specific for use in a metabolic syndrome population are lacking, thus works as part of this thesis included validation of the most appropriate risk prediction tool. Analyses demonstrated the Framingham risk prediction algorithm published in 1991 was the most appropriate tool for risk prediction of cardiovascular events in those classified as metabolic syndrome. This was superior to other published Framingham risk prediction algorithms, as well as algorithms specific for those with diagnosed diabetes (United Kingdom Prospective Diabetes Study (UKPDS)). The findings of this doctorate project are based on extrapolation of the best-available current evidence. The results offer utility for health policy and practice. Considering the increasing burden of disease, and limited health care resources, epidemiological modelling will increasingly be required

Epidemiological modelling of cardiovascular disease in those with metabolic syndrome

Metabolic syndrome, a clustering of cardiometabolic risk factors, significantly increases the risk of developing both cardiovascular disease (CVD) and T2DM. The exact pathogenesis remains unknown, however it is hypothesised that when metabolic susceptibility is present in individuals who are overweight or obese, the development of multiple cardiometabolic risk factors (metabolic syndrome) ensues. Metabolic syndrome is estimated to affect approximately 20-30% of the Western world, with rates expected to rise as a result of an ageing and increasingly obese population, in turn increasing CVD and diabetes. With the potential health and economic burden those with metabolic syndrome pose for society, considerable efforts are being focused on determining the most effective and cost-effective prevention strategies. While data from clinical trials provides the highest level of evidence regarding the efficacy of prevention strategies, their results alone are insufficient to critically inform clinical practice and health policy. Epidemiological modelling is a relatively new discipline that translates the results of clinical trials to estimate the potential benefits and costs. This thesis comprises a series of epidemiological models, developed to assess the effectiveness and cost-effectiveness of a variety of primary preventive strategies for CVD in those with metabolic syndrome. First-line therapy guidelines for the treatment of metabolic syndrome pertain to lifestyle changes; the uptake of physical activity to recommended guidelines (and reduction of total time spent in sedentary pursuits), as well as dietary changes. Analysis of the uptake of physical activity to recommended guidelines or the reduction of TV-viewing time in those with metabolic syndrome demonstrated that both behavioural changes were effective in the prevention of cardiovascular deaths. With regard to potential dietary changes, the consumption of dark chocolate in those classified as metabolic syndrome exhibited effective and potentially cost-effective results. Analysis of a therapeutic treatment option, a multi-component drug (polypill), demonstrated the polypill was an effective means of reducing CVD. Cost-effectiveness analyses, however, illustrated that the proposed cost of the polypill would not produce a cost-effective outcome. Other work contained in this thesis pertains to the development of epidemiological models. To determine the benefits and costs of a prevention strategy, models rely not only on efficacy data of the prevention strategy sourced from clinical trials, but also require the prediction of expected event rates. Risk prediction algorithms specific for use in a metabolic syndrome population are lacking, thus works as part of this thesis included validation of the most appropriate risk prediction tool. Analyses demonstrated the Framingham risk prediction algorithm published in 1991 was the most appropriate tool for risk prediction of cardiovascular events in those classified as metabolic syndrome. This was superior to other published Framingham risk prediction algorithms, as well as algorithms specific for those with diagnosed diabetes (United Kingdom Prospective Diabetes Study (UKPDS)). The findings of this doctorate project are based on extrapolation of the best-available current evidence. The results offer utility for health policy and practice. Considering the increasing burden of disease, and limited health care resources, epidemiological modelling will increasingly be required

Productivity burden of hypertension in Japan

In the present study, we aimed to estimate the impact of hypertension in the working-age Japanese population. We developed life table models to estimate total deaths, years of life lived, and productivity-adjusted life years lived (a newly developed metric for quantifying the burden of acute and chronic health conditions on work productivity) among Japanese individuals with hypertension aged 20–64 years, with simulated follow-up until age 65 years. Data inputs were drawn from local population statistics and published sources. Gross domestic product per person employed, a measure of labor productivity, was used to assign an economic value to each productivity-adjusted life year lived. Outcomes and costs were discounted by 2% annually. In 2017, 26.3 million Japanese individuals aged 20–64 years (37.5%) had hypertension. Of these people, 23.7% were treated and had controlled blood pressure, 23.2% were treated but had uncontrolled blood pressure, and 53.1% were untreated. During the simulated follow-up until age 65 years, 335,342 deaths (28.0% of total deaths), 1.6 million years of life (0.8% of total), 3.1 million productivity-adjusted life years (1.9% of total), and US$242.9 billion or 28.3 trillion Japanese yen of gross domestic product were lost to hypertension. Our findings highlight the considerable economic burden of hypertension in Japan, as well as the importance of effective strategies for hypertension prevention and management, which are likely to deliver a significant return on investment