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

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

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

Liver transplantation: Intraoperative changes in coagulation factors in 100 first transplants

Six intraoperative blood samples were obtained at intervals from each of 100 individuals undergoing their first liver transplants. The patients fell into the following diagnostic categories: postnecrotic cirrhosis 28, primary biliary cirrhosis 20, sclerosing cholangitis 19, miscellaneous diseases 14, carcinoma/neoplasia 12 and fulminant hepatitis 7. Coagulation factor values in the initial (baseline) blood samples varied by patient diagnosis. In general, all factor levels were reduced except factor VIII:C, which was increased to almost twice normal. The slight intraoperative changes in factors II, VII, IX, X, XI and XII suggested that a steady‐state relationship existed between depletion (consumption/bleeding) and repletion (transfusion, transit from extra‐ to intravascular space), even in the anhepatic state. In contrast, there were rapid and very significant falls in factor VIII and fibrinogen and a less pronounced decrease in factor V, all reaching their nadirs in early to mid‐Stage III. The cause of these coagulation changes appears to be activation of the fibrinolytic system. Copyright © 1989 American Association for the Study of Liver Disease

Forecasting the type 2 diabetes mellitus epidemic and the role of key risk factors in Oman up to 2050: Mathematical modeling analyses.

AIMS/INTRODUCTION: To investigate and forecast type 2 diabetes mellitus epidemic, its related risk factors and cost in Oman by 2050. MATERIALS AND METHODS: An age-structured mathematical model was used to characterize type 2 diabetes mellitus epidemiology and trends in Oman between 1990 and 2050. The model was parametrized using current and quality data, including six nationally representative population-based epidemiological surveys for type 2 diabetes mellitus and its key risk factors. RESULTS: The projected type 2 diabetes mellitus prevalence increased from 15.2% in 2020 to 23.8% in 2050. The prevalence increased from 16.8 and 13.8% in 2020 among women and men to 26.3 and 21.4% in 2050, respectively. In 2020, 190,489 Omanis were living with type 2 diabetes mellitus compared with 570,227 in 2050. The incidence rate per 1,000 person-years changed from 8.3 in 2020 to 12.1 in 2050. Type 2 diabetes mellitus' share of Oman's national health expenditure grew by 36% between 2020 and 2050 (from 21.2 to 28.8%). Obesity explained 56.7% of type 2 diabetes mellitus cases in 2020 and 71.4% in 2050, physical inactivity explained 4.3% in 2020 and 2.7% in 2050, whereas smoking accounted for <1% of type 2 diabetes mellitus cases throughout 2020-2050. Sensitivity and uncertainty analyses affirmed these predictions. CONCLUSIONS: The type 2 diabetes mellitus epidemic in Oman is expected to increase significantly over the next three decades, consuming nearly one-third of the national health expenditure. The type 2 diabetes mellitus burden is heavily influenced by obesity. Interventions targeting this single risk factor should be a national priority to reduce and control the burden of type 2 diabetes mellitus in Oman

Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as “too esoteric”, the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and “fitness for purpose”, and avoid omission of vital knowledge

Global burden of human brucellosis : a systematic review of disease frequency

BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understand of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources

Impact of trends and gender disparity in obesity on future type 2 diabetes in Turkey: a mathematical modelling analysis.

BACKGROUND: Using a previously developed and validated mathematical model, we predicted future prevalence of type 2 diabetes mellitus (T2DM) and major modifiable risk factors (obesity, physical inactivity and smoking) stratified by age and sex in Turkey up to the year 2050. METHODS: Our deterministic compartmental model fitted nationally representative demographic and risk factor data simultaneously for Turkish adults (aged 20-79) between 1997 and 2017, then estimated future trends. Our novel approach explored the impact of future obesity trends on these projections, specifically modelling (1) a gradual fall in obesity in women after the year 2020 until it equalled the age-specific levels seen in men and (2) cessation of the rise in obesity after 2020. RESULTS: T2DM prevalence is projected to rise from an estimated 14.0% (95% uncertainty interval (UI) 12.8% to 16.0%) in 2020 to 18.4% (95% UI 16.9% to 20.9%) by 2050; 19.7% in women and 17.2% in men by 2050; reflecting high levels of obesity (39.7% for women and 22.0% for men in 2050). Overall, T2DM prevalence could be reduced by about 4% if obesity stopped rising after 2020 or by 12% (22% in women) if obesity prevalence among women could be lowered to equal that of men. The higher age-specific obesity prevalence among women resulted in 2 076 040 additional women developing T2DM by the year 2050. CONCLUSION: T2DM is common in Turkey and will remain so. Interventions and policies targeting the high burden of obesity (and low physical activity levels), particularly in women, could significantly impact future disease burdens

Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

BACKGROUND: In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. METHOD: Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. RESULTS: A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. CONCLUSION: Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000