Epidemiological impact of targeted interventions for people with diabetes mellitus on tuberculosis transmission in India: Modelling based predictions.

INTRODUCTION: Diabetes mellitus (DM) is a leading driver of tuberculosis (TB) disease in TB-DM burdened countries. We aimed to assess the impact on TB disease of several intervention strategies targeting people with DM in India. METHODS: A previously validated TB-DM mathematical model was extended to include interventions targeting DM individuals. The model stratified the population by age, DM status, TB infection status and stage, TB disease form, treatment, recovery, and intervention status. RESULTS: By 2050, different TB vaccination strategies (coverage of 50 % and vaccine efficacies ranging between 50 %-60 %) reduced TB incidence and mortality rates by 4.5 %-20.8 % and 4.1 %-22.1 %, respectively, and averted 3.1 %-12.8 % of TB disease cases in the total population. Number of vaccinations needed to avert one TB case (effectiveness) was 14-105. Varying the coverage levels of latent TB treatment (coverage of 50 %-80 % and drug effectiveness of 90 %) reduced TB incidence and mortality rates by 7.1 %-11.3 % and 8.2 %-13.0 %, respectively, averting 4.2 %-6.7 % of TB cases, with effectiveness of 38-40. Different scenarios for dual and concurrent treatment of those with TB and DM, reduced TB incidence and mortality rates by 0.1 %-0.4 % and 1.3 %-4.8 %, respectively, averting 0.1 %-0.2 % of TB cases, with effectiveness of 28-107. Different scenarios for managing and controlling DM (regardless of TB status) reduced TB incidence and mortality rates by 4.5 %-16.5 % and 6.5 %-22.2 %, respectively, averting 2.9 %-10.8 % of TB cases, with effectiveness of 6-24. CONCLUSION: Gains can be attained by targeting DM individuals with interventions to reduce TB burden. Most strategies were effective with <50 intervention doses needed to avert one TB disease case, informing key updates of current treatment guidelines

Comparing primary prevention with secondary prevention to explain decreasing Coronary Heart Disease death rates in Ireland, 1985-2000.

BACKGROUND: To investigate whether primary prevention might be more favourable than secondary prevention (risk factor reduction in patients with coronary heart disease(CHD)). METHODS: The cell-based IMPACT CHD mortality model was used to integrate data for Ireland describing CHD patient numbers, uptake of specific treatments, trends in major cardiovascular risk factors, and the mortality benefits of these specific risk factor changes in CHD patients and in healthy people without recognised CHD. RESULTS: Between 1985 and 2000, approximately 2,530 fewer deaths were attributable to reductions in the three major risk factors in Ireland. Overall smoking prevalence declined by 14% between 1985 and 2000, resulting in about 685 fewer deaths (minimum estimate 330, maximum estimate 1,285) attributable to smoking cessation: about 275 in healthy people and 410 in known CHD patients. Population total cholesterol concentrations fell by 4.6%, resulting in approximately 1,300 (minimum estimate 1,115, maximum estimate 1,660) fewer deaths attributable to dietary changes(1,185 in healthy people and 115 in CHD patients) plus 305 fewer deaths attributable to statin treatment (45 in people without CHD and 260 in CHD patients). Mean population diastolic blood pressure fell by 7.2%, resulting in approximately 170 (minimum estimate 105, maximum estimate 300) fewer deaths attributable to secular falls in blood pressure (140 in healthy people and 30 in CHD patients), plus approximately 70 fewer deaths attributable to antihypertensive treatments in people without CHD. Of all the deaths attributable to risk factor falls, some 1,715 (68%) occurred in people without recognized CHD and 815(32%) in CHD patients. CONCLUSION: Compared with secondary prevention, primary prevention achieved a two-fold larger reduction in CHD deaths. Future national CHD policies should therefore prioritize nationwide interventions to promote healthy diets and reduce smoking

Impact of Smoking Reduction on Coronary Heart Disease Mortality Trends During 1981–2000 in England and Wales

OBJECTIVE: To explore how much of the coronary heart disease (CHD) mortality fall in England and Wales can be attributed to changes in smoking prevalence. METHODS: A previously validated cell-based IMPACT CHD mortality model was used to estimate the deaths prevented or postponed by changes in population smoking prevalence in England and Wales between 1981 and 2000. CHD mortality statistics and population trends in smoking were obtained from routine data sources. RESULTS: In England and Wales between 1981 and 2000, smoking prevalence in adults aged 25-84 decreased from 43% to 28% in men and from 35% to 24% in women. In men, most of the decrease occurred in those aged over 55. Smoking prevalence changed little in older women. An estimated 29,460 deaths were prevented or postponed (DPP) by this population reduction in smoking prevalence. Most of this benefit was seen in men (86% of the DPPs versus 14% in women). CONCLUSION: Large declines in smoking prevalence accounted for 29,460 fewer CHD deaths in England and Wales in 2000 compared with 1981. This emphasises the importance of a national strategy with comprehensive tobacco control programmes to further reduce smoking

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice.

Diabetes Mellitus increases the risk of developing Tuberculosis (TB) disease by about three times; it also doubles the risk of death during TB treatment and other poor TB treatment outcomes. Diabetes may increase the risk of latent infection with Mycobacterium tuberculosis (LTBI), but the magnitude of this effect is less clear. Whilst this syndemic has received considerable attention, most of the published research has focussed on screening for undiagnosed diabetes in TB patients or observational follow-up of TB treatment outcomes by diabetes status. There are thus substantial research and policy gaps, particularly with regard to prevention of TB disease in people with diabetes and management of patients with TB-diabetes, both during TB treatment and after successful completion of TB treatment, when they likely remain at high risk of TB recurrence, mortality from TB and cardiovascular disease. Potential strategies to prevent development of TB disease might include targeted vaccination programmes, screening for LTBI and preventive therapy among diabetes patients or, perhaps ideally, improved diabetes management and prevention. The cost-effectiveness of each of these, and in particular how each strategy might compare with targeted TB prevention among other population groups at higher risk of developing TB disease, is also unknown. Despite research gaps, clinicians urgently need practical management advice and more research evidence on the choice and dose of different anti-diabetes medication and effective medical therapies to reduce cardiovascular risks (statins, anti-hypertensives and aspirin). Substantial health system strengthening and integration may be needed to prevent these at risk patients being lost to care at the end of TB treatment

Analytical Exploration of Potential Pathways by which Diabetes Mellitus Impacts Tuberculosis Epidemiology.

We aimed to develop a conceptual framework of diabetes mellitus (DM) effects on tuberculosis (TB) natural history and treatment outcomes, and to assess the impact of these effects on TB-transmission dynamics. The model was calibrated using TB data for India. A conceptual framework was developed based on a literature review, and then translated into a mathematical model to assess the impact of the DM-on-TB effects. The impact was analyzed using TB-disease incidence hazard ratio (HR) and population attributable fraction (PAF) measures. Evidence was identified for 10 plausible DM-on-TB effects. Assuming a flat change of 300% (meaning an effect size of 3.0) for each DM-on-TB effect, the HR ranged between 1.0 (Effect 9-Recovery) and 2.7 (Effect 2-Fast progression); most effects did not have an impact on the HR. Meanwhile, TB-disease incidence attributed directly and indirectly to each effect ranged between -4.6% (Effect 7-TB mortality) and 34.5% (Effect 2-Fast progression). The second largest impact was for Effect 6-Disease infectiousness at 29.9%. In conclusion, DM can affect TB-transmission dynamics in multiple ways, most of which are poorly characterized and difficult to assess in epidemiologic studies. The indirect (e.g. onward transmission) impacts of some DM-on-TB effects are comparable in scale to the direct impacts. While the impact of several effects on the HR was limited, the impact on the PAF was substantial suggesting that DM could be impacting TB epidemiology to a larger extent than previously thought

Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009.

BACKGROUND: In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing. OBJECTIVE: To explain recent CHD trends in Tunisia between 1997 and 2009. METHODS: DATA SOURCES: Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys. ANALYSIS: Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity). RESULTS: CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (-0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75). CONCLUSIONS: Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and cholesterol, BMI and diabetes. Current prevention strategies are mainly focused on treatments but should become more comprehensive

Effect of subsidies on healthful consumption: a protocol for a systematic review update.

INTRODUCTION: The prevalence of diet-related non-communicable diseases (NCDs) are rapidly increasing in most parts of the world. In order to ameliorate the related public health burden, evidence-informed policies to improve diet need to be implemented. Financial subsidies that promote healthful consumption patterns have the potential to reduce NCD risk and may also reduce inequality if targeted at those of low socio-economic position. This protocol is for an updated systematic review of such evidence. METHODS AND ANALYSIS: A systematic search strategy will be used to identify publications on fiscal intervention studies indexed in Embase, CINAHL, Web of Science, EconLit and PubMed in between January 2013 to February 2019. Two reviewers will independently sift identified citations using prespecified inclusion and exclusion criteria to inform full-text review. The outcomes of interest are: consumption patterns (% change in targeted items and in overall dietary patterns), purchasing patterns (% change) or body mass index. Pretested data capture forms will be used for double data extraction. Any inconsistencies in citation sifting or data extraction will be resolved by a third investigator and study authors will be contacted if needed. Systematic searches will be supplemented by reference checking of key articles. Study quality will be assessed and a narrative summary of findings will be produced. Meta-analyses and exploration of heterogeneity will be completed if appropriate. ETHICS AND DISSEMINATION: The review aims to strengthen findings of the primary studies it incorporates. It will synthesise existing published aggregated patient data and only present further aggregate data. Given this, no concerns are held relating to confidentiality and informed consent due to re-use of patient data.If publications or data with ethical concerns are identified, they will be excluded from the review.Results of the systematic review will be published in full and authors will engage directly with research audiences and key stakeholders to share findings. PROSPERO REGISTRATION NUMBER: CRD42019125013

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state