Ministry of Health

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

Next-Generation Gene Therapy Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by Verma ). Biffi et al. ( 1233158 , published online 11 July) and Aiuti et al. ( 1233151 ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional MLD or WAS genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional MLD or WAS genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety.

On January 30, 2020, the WHO declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic in order to emphasize the gravity of the situation and urge all countries to take action in detecting infection and preventing spread. Unfortunately, there is no medication that has been approved by the FDA, gone through controlled studies and demonstrated an effect on the virus for this global pandemic. Although there are cures for illnesses and developments made by leaps and bounds in our day, the strongest and most effective weapon that society has against this virus that is affecting not just health but also economics, politics, and social order, is the prevention of its spread. The main points in preventing the spread in society are hand hygiene, social distancing and quarantine. With increased testing capacity, detecting more COVID-19 positive patients in the community will also enable the reduction of secondary cases with stricter quarantine rules.

BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success. METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29,000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030. FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone. INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030. FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

Abstract Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3–6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

INTRODUCTION: Brucellosis is the most prevalent bacterial zoonosis worldwide. In this study, we aimed to compare our 1028 brucellosis cases with other big series in the literature in view of epidemiological, clinical, and laboratory findings and therapeutic features. METHODS: A total of 1028 brucellosis cases admitted to the Department of Infectious Diseases and Clinical Microbiology over a 10-year period were included in the study. A retrospective analysis was undertaken and patient files were reviewed for history, clinical and laboratory findings, and therapeutic features, as well as complications. RESULTS: Of the 1028 patients, 539 (52.4%) were female and 489 (47.6%) were male. The mean age of patients was 33.7+/-16.34 years and 69.6% of cases were aged 13-44 years. Four hundred and thirty-five cases (42.3%) had a history of raising livestock and 55.2% of the cases were found to have no occupational risk for brucellosis. Six hundred and fifty-four of the cases (63.6%) had a history of raw milk and dairy products consumption. The most frequently seen symptoms were arthralgia (73.7%) and fever (72.2%), while the most common clinical findings were fever (28.8%) and hepatomegaly (20.6%). The most frequent laboratory finding was a high C-reactive protein level (58.4%). The standard tube agglutination (STA) test+Coombs STA test was positive in 1016 cases (98.8%). Focal involvement was present in 371 (36.1%) cases. The most frequent involvement was osteoarticular involvement with 260 cases (25.3%). The overall relapse rate for patients with brucellosis was 4.7%. The highest relapse rate, 8.5%, was observed in the group of patients with osteoarticular involvement. Regimens including doxycycline and streptomycin with or without rifampin appeared more effective than other regimens in osteoarticular involvement. CONCLUSIONS: In humans, brucellosis may lead to serious morbidity, and it continues to be a major health problem in Turkey. There is no recommended treatment protocol for complicated brucellosis. Large multicenter studies are needed to determine the most appropriate treatment choices and durations in complicated brucellosis.

OBJECTIVES: To investigate for the first time the prevalence of diabetes and impaired glucose tolerance (IGT) nationwide in Turkey; to assess regional variations and relationships between glucose intolerance and lifestyle and physical risk factors. RESEARCH DESIGN AND METHODS: The Turkish Diabetes Epidemiology Study (TURDEP) is a cross-sectional, population-based survey that included 24,788 subjects (age > or =20 years, women 55%, response 85%). Glucose tolerance was classified according to World Health Organization recommendations on the basis of 2-h blood glucose values. RESULTS: Crude prevalence of diabetes was 7.2% (previously undiagnosed, 2.3%) and of IGT, 6.7% (age-standardized to world and European populations, 7.9 and 7.0%). Both were more frequent in women than men (P < 0.0001) and in those living in urban rather than rural communities (P < 0.001). Prevalence rates of hypertension and obesity were 29 and 22%, respectively. Both were more common among women than men (P < 0.0001). Prevalence of diabetes and IGT increased with rising BMI, waist-to-hip ratio (WHR), and waist girth (P < 0.0001). Multiple logistic regression analysis revealed that age, BMI, WHR, familial diabetes, and hypertension were independently associated with diabetes, age, BMI, WHR, familial diabetes, and hypertension with IGT (except for familial diabetes in women with IGT). Education was related to diabetes in men but was protective for diabetes and IGT in women. Socioeconomic status appeared to decrease the risk of IGT in men while it increased the risk in women. Smoking had a protective effect for IGT in both sexes. CONCLUSIONS: Diabetes and IGT are moderately common in Turkey by international standards. Associations with obesity and hypertension have been confirmed. Other lifestyle factors had a variable relationship with glucose tolerance.

OBJECTIVES: Several sets of criteria mainly for adults have been proposed for the diagnosis of FMF. The aim of the present study is to validate the most widely used diagnostic 'Tel Hashomer' criteria in children and to establish a new set of criteria for use in childhood. METHODS: The study group consisted of 170 recently diagnosed FMF patients who had mutations at both alleles. They were interviewed about the presence of 35 features and manifestations of FMF at the time of diagnosis. Controls were consecutive patients without FMF (n = 141) who had episodes of fever and clinical features mimicking that of FMF. The diagnostic performance of the candidate features was assessed by multiple logistic regression analysis. RESULTS: The sensitivity and specificity of Tel Hashomer criteria in our study group were 98.8 and 54.6%, respectively. The multiple logistic regression analysis showed that 5 (fever, abdominal pain, chest pain, arthritis and family history of FMF) of the 35 candidate criteria discriminate FMF from controls with a sensitivity and specificity of 88.8 and 92.2%, respectively. The presence of two or more of these five criteria diagnosed FMF with a sensitivity of 86.5% and a specificity of 93.6%. CONCLUSION: It was demonstrated that although the Tel Hashomer criteria were successful in diagnosing the FMF patients in childhood, its specificity was definitely low in children. The new set of criteria has a high sensitivity and specificity for the diagnosis of FMF and is practical to use on an everyday basis.

Introduction: Intravenous(IV) immunoglobulin(Ig) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Methods: Sepsis was induced by cecal ligation perforation(CLP) in rats. The animals were divided into five groups; sham, control, CLP + saline, CLP + immunoglobulin G IgG(250 mg/kg,iv), and CLP + immunoglobulins enriched with immunoglobulin M-IgGAM(250 mg/kg,iv). Blood and brain samples were taken in two sets of experiments after CLP to see the early(24 hrs) and late(10 days) effects of treatment. Total complement activity, complement 3(C3) and soluble complement C5b-9 levels were measured in sera of rats using ELISA-based methods. Cerebral complement content was analyzed by Western Blot. Immune cell infiltration and gliosis were examined by immunohistochemistry using cluster of differentiation 3, CD4, CD8, CD11b, CD19 and glial fibrillary acidic protein antibodies. Apoptotic neuronal death was investigated by TUNEL staining and Western Blot-based semi-quantitative evaluation of brain homogenates by bax and bcl-2 antibodies. Results: IV IgG and IgGAM administration significantly reduced systemic complement activity but increased serum C3 and soluble C5b-9 levels. Likewise, Western Blot data showed slightly increased C5b-9 expression and significantly reduced C1q expression in brain samples of IgGAM-treated but not IgG-treated septic rats especially in the first day of administration. No cerebral cellular infiltrates were observed in treated and non-treated septic rats. By contrast, IV IgG and IgGAM treatment induced considerable amelioration in glial cell proliferation which was increased in non-treated rats. IgG and IgGAM treated rats exhibited significantly reduced numbers of apoptotic neurons and cerebral expression levels of bax and bcl-2 as compared to nontreated rats. Conclusions: We suggest that IV IgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might be suppressing classical complement pathway by reducing C1q expression.

The objective was to evaluate the prevalence of dysmenorrhea and determine its effect on health-related quality of life (HRQoL) among a group of female university students. This cross-sectional study was conducted between 15 March and 15 April 2009 at Dumlupinar University, Kutahya, Health High School, Western Turkey. The study group included 623 female students. The severity of dysmenorrhea was determined with a 10-point visual analog scale. The Short Form-36 (SF-36) form was used to determinate HRQoL. Chi-square test, Student's t test, and logistic regression and variance analyses (ANOVA) were used for statistical analyses. The average age of the study group was 20.8 +/- 1.8 years (range 17-30). Prevalence of dysmenorrhea was found to be 72.7% and was significantly higher in coffee consumers, females with menstrual bleeding duration > or =7 days, and those who had a positive family history of dysmenorrhea when compared to the others (P < 0.05, for each one). By multivariate analysis, coffee consumption (OR 2.084), menstrual bleeding duration > or =7 days (OR 1.590), and positive family history of dysmenorrhea (OR 3.043) were important risk factors for dysmenorrhea. Except for social functioning, role-emotional, and mental health domains, the SF-36 points received from the other domains were higher in females with dysmenorrhea (for each one P < 0.05). With the exception of the scores received from physical functioning and role-emotional domains, the scores received from the other domains of the SF-36 scale showed a decrease with increasing severity of dysmenorrhea (P < 0.05, for each one). Dysmenorrhea is a common health problem, having negative effects on the HRQoL among university female students.

Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19’s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

BACKGROUND: To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. METHODS: We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses. RESULTS: 98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95% CI -1.66, -0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95% CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI -0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. CONCLUSIONS: AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness.

OBJECTIVE: To determine vaccine acceptance and hesitancy attitudes toward coronavirus disease 2019 (COVID-19) vaccines in pregnant women. METHODS: Three hundred pregnant women were surveyed face to face with 40 questions. Sociodemographic characteristics, vaccination history, perception of risk for the COVID-19 pandemic, the impact of the COVID-19 pandemic, and acceptance of and attitude toward future COVID-19 vaccination were prospectively evaluated. RESULTS: Among all participants, 111 (37%) stated their intent to receive the vaccine if it were recommended for pregnant women. Most common refusal reasons were lack of data about COVID-19 vaccine safety in pregnant populations and possibility of harm to the fetus. There was a weak positive correlation between COVID-19 vaccine acceptancy and number of school-age children. Pregnant women in the first trimester expressed higher acceptance of COVID-19 vaccination than those in the second and third trimesters. CONCLUSION: The present study reported low acceptance of COVID-19 vaccination in a sample of pregnant women. Concern about vaccine safety was the major reason for hesitancy. Identifying attitudes among priority groups will be useful for creating vaccination strategies that increase uptake during the current pandemic.

BACKGROUND: The World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was established more than 10 years ago to estimate prevalence and monitor changes in overweight and obesity in children aged 6-9 years. Since then, there have been five rounds of data collection in more than 40 countries involving more than half a million children. To date, no comparative studies with data on severe childhood obesity from European countries have been published. OBJECTIVES: The aim of this work was to present the prevalence of severe obesity in school-aged children from 21 countries participating in COSI. METHOD: The data are from cross-sectional studies in 21 European WHO member states that took part in the first three COSI rounds of data collection (2007/2008, 2009/2010, 2012/2013). School-aged children were measured using standardized instruments and methodology. Children were classified as severely obese using the definitions provided by WHO and the International Obesity Task Force (IOTF). Analyses overtime, by child's age and mother's educational level, were performed in a select group of countries. RESULTS: A total of 636,933 children were included in the analysis (323,648 boys and 313,285 girls). The prevalence of severe obesity varied greatly among countries, with higher values in Southern Europe. According to the WHO definition, severe obesity ranged from 1.0% in Swedish and Moldovan children (95% CI 0.7-1.3 and 0.7-1.5, respectively) to 5.5% (95% CI 4.9-6.1) in Maltese children. The prevalence was generally higher among boys compared to girls. The IOTF cut-offs lead to lower estimates, but confirm the differences among countries, and were more similar for both boys and girls. In many countries 1 in 4 obese children were severely obese. Applying the estimates of prevalence based on the WHO definition to the whole population of children aged 6-9 years in each country, around 398,000 children would be expected to be severely obese in the 21 European countries. The trend between 2007 and 2013 and the analysis by child's age did not show a clear pattern. Severe obesity was more common among children whose mother's educational level was lower. CONCLUSIONS: Severe obesity is a serious public health issue which affects a large number of children in Europe. Because of the impact on educational, health, social care, and economic systems, obesity needs to be addressed via a range of approaches from early prevention of overweight and obesity to treatment of those who need it.

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-alpha, TGF-beta1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-alpha) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-beta1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-beta1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a serious disease caused by the CCHF virus of the Bunyaviridae family. The disease has been reported in 30 countries in Africa, Asia, Eastern Europe, and the Middle East. It has been present in Turkey since 2002. In this study we present and discuss the epidemiological features, clinical and laboratory findings, treatment, and outcome of cases diagnosed with CCHF between 2002 and 2007 from the surveillance results of the Turkish Ministry of Health (MoH). METHODS: According to the surveillance system of the MoH, data for patients with clinical, laboratory, and epidemiological findings compatible with CCHF are recorded on case reporting forms. These forms are submitted to the General Directorate of Primary Health Care of the MoH by the city health directorates. All the surveillance data regarding CCHF were recorded on a database (SSPS 11.0) established in the Communicable Diseases Department of the MoH. RESULTS: According to the surveillance reports of the Turkish MoH, between 2002 and 2007, 1820 CCHF cases occurred (150 in 2002-2003, 249 in 2004, 266 in 2005, 438 in 2006, and 717 in 2007). The crude fatality rate was calculated to be 5% (92/1820). Two thirds of the CCHF cases were reported from five cities located in the Mid-Eastern Anatolia region; 69.4% of the cases were from rural areas. The male to female ratio was 1.13:1. Of all the reported cases, 68.9% had a history of tick-bite or tick contact and 84.1% were seen in the months of May, June, and July. Of 1820 CCHF cases, three (0.16%) were nosocomial infections. CONCLUSIONS: CCHF appears to be a seasonal problem in the Mid-Eastern Anatolia region of Turkey. The possible risk factors for transmission and the clinical and laboratory findings of patients with a diagnosis of CCHF were found to be similar to those reported in the literature. The mean fatality rate for Turkey is lower than the rate reported for other series from other parts of the world.

The Achilles tendon is the strongest and thickest tendon in the human body. It is also the commonest tendon to rupture. It begins near the middle of the calf and is the conjoint tendon of the gastrocnemius and soleus muscles. The relative contribution of the two muscles to the tendon varies. Spiralisation of the fibres of the tendon produces an area of concentrated stress and confers a mechanical advantage. The calcaneal insertion is specialised and designed to aid the dissipation of stress from the tendon to the calcaneum. The insertion is crescent shaped and has significant medial and lateral projections. The blood supply of the tendon is from the musculotendinous junction, vessels in surrounding connective tissue and the osteotendinous junction. The vascular territories can be classified simply in three, with the midsection supplied by the peroneal artery, and the proximal and distal sections supplied by the posterior tibial artery. This leaves a relatively hypovascular area in the mid-portion of the tendon where most problems occur. The Achilles tendon derives its innervation from the sural nerve with a smaller supply from the tibial nerve. Tenocytes produce type I collagen and form 90% of the cellular component of the normal tendon. Evidence suggests ruptured or pathological tendon produce more type III collagen, which may affect the tensile strength of the tendon. Direct measurements of forces reveal loading in the Achilles tendon as high as 9 KN during running, which is up to 12.5 times body weight.

BACKGROUND: There are no reliable data on antibiotic use in non-European Union (EU) southern and eastern European countries and newly independent states. We aimed to collect valid, representative, comparable data on systemic antimicrobial use in these non-EU countries of the WHO European region. METHODS: Validated 2011 total national wholesale antibiotic-use data of six southern and eastern European countries and regions and seven newly independent states were analysed in accordance with the WHO anatomical therapeutic chemical (ATC)/defined daily doses (DDD) method and expressed in DDD/1000 inhabitants per day (DID). FINDINGS: Total (outpatients and hospital care) antibiotic use ranged from 15·3 DID for Armenia to 42·3 DID for Turkey. Co-amoxiclav was mainly used in Georgia (42·9% of total antibiotic use) and Turkey (30·7%). Newly independent states used substantial quantities of ampicillin and amoxicillin (up to 55·9% of total antibiotic use in Azerbaijan). Montenegro and Serbia were the highest consumers of macrolides (15·8% and 19·5% of total antibiotic use, respectively), mainly azithromycin. Parenteral antibiotic treatment is common practice: 46·4% of total antibiotic use in Azerbaijan (mainly ampicillin; 5·3 DID) and 31·1% of total antibiotic use in Tajikistan (mainly ceftriaxone; 4·7 DID). INTERPRETATION: This study provides publicly available total antibiotic-use data for 13 non-EU countries and areas of the WHO European region. These data will raise awareness of inappropriate antibiotic use and stimulate policy makers to develop action plans. The established surveillance system provides a method to develop quality indicators of antibiotic use and to assess the effect of policy and regulatory actions. FUNDING: Netherlands Ministry of Health, Welfare, and Sport, and EU.

Our first COVID-19 case in Turkey was a 44-year-old male who referred to the hospital on March 9, 2020. The first related death occurred on March 17, 2020. Preparedness for the pandemic has been ongoing before the first case was detected. The National Pandemic Plan was published in 2006. The Pandemic Influenza National Preparedness Plan was available after being updated in light of experiences gained during the 2009 Influenza A pandemic. Accordingly, Pandemic Coordination Boards and Operation Centers have been established on the national and provincial levels. This was an adaptable plan to the Novel Coronavirus Disease (COVID-19). We formed teams to work on a 24/7 basis and established a Scientific Committee at the Public Health Emergency Operation Center within the General Directorate of Public Health. “COVID-19 Risk Assessment”, “COVID-19 Guideline” and “Case Report Form”, regulations of personal protective equipment along with need-based guidelines, treatment algorithms, brochures and related documents have been released. For the case-based follow-up, Public Health Management System (HSYS) is being used. PCR and rapid diagnostic kits are being used to analyze the samples at the central Microbiology Reference Laboratory and the authorized laboratories in several provinces. Various preventive measures were implemented including flight restrictions to certain countries, gradually expanded to suspending all flights and prohibiting the entry of foreign nationals, 14-day isolation and symptom monitoring for those that came from countries under risk. Persons with chronic diseases have been granted an administrative leave, on campus education at schools and activities of public rest and entertainment areas were temporarily suspended. The measures have been implemented for penitentiary institutions, dormitories, nursing homes, public transport and intercity buses, and also weekend curfews are implemented. In accordance with the pandemic plan, actions have been carried out with a multi-sectoral approach, and preventive measures have been implemented to cover the society as a whole.