Estimation and prediction of avoidable health care costs of cardiovascular diseases and type 2 diabetes through adequate dairy food consumption: a systematic review and micro simulation modeling study

Background: Recent evidence from prospective cohort studies show a relationship between consumption of dairy foods and cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM). This association highlights the importance of dairy foods consumption in prevention of these diseases and also reduction of associated healthcare costs. The aim of this study was to estimate avoidable healthcare costs of CVD and T2D through adequate dairy foods consumption in Iran. Methods: This was a multistage modelling study. We conducted a systematic literature review in PubMed and EMBASE to identify any association between incidence of CVD and T2DM and dairy foods intake, and also associated relative risks. We obtained age- and sex-specific dairy foods consumption level and healthcare expenditures from national surveys and studies. Patient level simulation Markov models were constructed to predict the disease incidence, patient population size and associated healthcare costs for current and optimal dairy foods consumption at different time horizons (1, 5, 10 and 20 years). All parameters including costs and transition probabilities were defined as statistical distributions in the models, and all analyses were conducted by accounting for first and second order uncertainty. Results: The systematic review results indicated that dairy foods consumption was inversely associated with incidence of T2DM, coronary heart disease (CHD) and stroke. We estimated that the introduction of a diet containing 3 servings of dairy foods per day may produce a $0.43 saving in annual per capita healthcare costs in Iran in the first year due to saving in cost of CVD and T2DM treatment. The estimated savings in per capita healthcare costs were$8.42, $39.97 and$190.25 in 5, 10 and 20-years’ time, respectively. Corresponding total aggregated avoidable costs for the entire Iranian population within the study time horizons were $33.83,$661.31, $3,138.21 and$14,934.63 million, respectively. Conclusion: Our analysis demonstrated that increasing dairy foods consumption to recommended levels would be associated with reductions in healthcare costs. Further randomized trial studies are required to investigate the effect of dairy foods intake on cost of CVD and T2DM in the population

Burden of Drug and Alcohol Use Disorders in Iran: Findings from the Global Burden of Disease Study 2010

Background: Due to its specific socio-cultural and geographical situation, Iran has a major public health problem in terms of drug and alcohol use. The aim of this study is to report and critique the burden of drug and alcohol use disorders in Iran, and to compare these measurements with similar findings. Methods: This study used data for Iran for the years 1990, 2005, and 2010 derived from the Global Burden of Disease study conducted by the Institute for Health Metrics and Evaluation (IHME) in 2010. The burden of drug and alcohol use disorders was evaluated in terms of disability adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Results: All rates were reported per 100,000 individuals. Death rates attributed to drug and alcohol use disorders were 7.7 and 0.16 for men, and 0.62 and 0.02 for women, respectively. YLL rates regarding drug use disorders were 351.8 and 24.8 for men and women, while these figures were 5.8 and 1.0 for alcohol use disorders for men and women, respectively. YLD rates of drug use disorders were 452.6 for men and 202.1 for women, and 105.8 for men and 23.7 for women for alcohol use disorders. DALY rates attributed to drug use disorders were 804.5 for men and 227 for women, while these rates were 111.7 for men and 24.7 for women, related to alcohol use disorders. Conclusions: Similar to the cases in many other countries, the burden of both drug and alcohol use disorders is higher for men than women in Iran. Although prevention policies and programs for drug and alcohol use are required for both genders, the need for drug and alcohol use intervention seems more urgent for men in Iran

Landslide Risk Assessment by Using a New Combination Model Based on a Fuzzy Inference System Method

Landslides are one of the most dangerous phenomena that pose widespread damage to property and human lives. Over the recent decades, a large number of models have been developed for landslide risk assessment to prevent the natural hazards. These models provide a systematic approach to assess the risk value of a typical landslide. However, often models only utilize the numerical data to formulate a problem of landslide risk assessment and neglect the valuable information provided by experts’ opinion. This leads to an inherent uncertainty in the process of modelling. On the other hand, fuzzy inference systems are among the most powerful techniques in handling the inherent uncertainty. This paper develops a powerful model based on fuzzy inference system that uses both numerical data and subjective information to formulate the landslide risk more reliable and accurate. The results show that the proposed model is capable of assessing the landslide risk index. Likewise, the performance of the proposed model is better in comparison with that of the conventional techniques

Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking

Charcot-Marie-Tooth type 4 (CMT4) is an autosomal recessive severe form of neuropathy with genetic heterogeneity. CMT4B1 is caused by mutations in the myotubularin-related 2 (MTMR2) gene and as a member of the myotubularin family, the MTMR2 protein is crucial for the modulation of membrane trafficking. To enable future clinical trials, we performed a detailed review of the published cases with MTMR2 mutations and describe four novel cases identified through whole-exome sequencing (WES). The four unrelated families harbor novel homozygous mutations in MTMR2 (NM_016156, Family 1: c.1490dupC; p.Phe498IlefsTer2; Family 2: c.1479+1G>A; Family 3: c.1090C>T; p.Arg364Ter; Family 4: c.883C>T; p.Arg295Ter) and present with CMT4B1-related severe early-onset motor and sensory neuropathy, generalized muscle atrophy, facial and bulbar weakness, and pes cavus deformity. The clinical description of the new mutations reported here overlap with previously reported CMT4B1 phenotypes caused by mutations in the phosphatase domain of MTMR2, suggesting that nonsense MTMR2 mutations, which are predicted to result in loss or disruption of the phosphatase domain, are associated with a severe phenotype and loss of independent ambulation by the early twenties. Whereas the few reported missense mutations and also those truncating mutations occurring at the C-terminus after the phosphatase domain cause a rather mild phenotype and patients were still ambulatory above the age 30 years. Charcot-Marie-Tooth neuropathy and Centronuclear Myopathy causing mutations have been shown to occur in proteins involved in membrane remodeling and trafficking pathway mediated by phosphoinositides. Earlier studies have showing the rescue of MTM1 myopathy by MTMR2 overexpression, emphasize the importance of maintaining the phosphoinositides equilibrium and highlight a potential compensatory mechanism amongst members of this pathway. This proved that the regulation of expression of these proteins involved in the membrane remodeling pathway may compensate each other's loss- or gain-of-function mutations by restoring the phosphoinositides equilibrium. This provides a potential therapeutic strategy for neuromuscular diseases resulting from mutations in the membrane remodeling pathway

Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy.

Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability

National, sub-national, and risk-attributed burden of thyroid cancer in Iran from 1990 to 2019

An updated exploration of the burden of thyroid cancer across a country is always required for making correct decisions. The objective of this study is to present the thyroid cancer burden and attributed burden to the high Body Mass Index (BMI) in Iran at national and sub-national levels from 1990 to 2019. The data was obtained from the GBD 2019 study estimates. To explain the pattern of changes in incidence from 1990 to 2019, decomposition analysis was conducted. Besides, the attribution of high BMI in the thyroid cancer DALYs and deaths were obtained. The age-standardized incidence rate of thyroid cancer was 1.57 (95% UI: 1.33–1.86) in 1990 and increased 131% (53–191) until 2019. The age-standardized prevalence rate of thyroid cancer was 30.19 (18.75–34.55) in 2019 which increased 164% (77–246) from 11.44 (9.38–13.85) in 1990. In 2019, the death rate, and Disability-adjusted life years of thyroid cancer was 0.49 (0.36–0.53), and 13.16 (8.93–14.62), respectively. These numbers also increased since 1990. The DALYs and deaths attributable to high BMI was 1.91 (0.95–3.11) and 0.07 (0.04–0.11), respectively. The thyroid cancer burden and high BMI attributed burden has increased from 1990 to 2019 in Iran. This study and similar studies’ results can be used for accurate resource allocation for efficient management and all potential risks’ modification for thyroid cancer with a cost-conscious view

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Burden of tracheal, bronchus, and lung cancer in North Africa and Middle East countries, 1990 to 2019: Results from the GBD study 2019

ObjectiveTo provide estimates on the regional and national burden of tracheal, bronchus, and lung (TBL) cancer and its attributable risk factors from 1990 to 2019 in the North Africa and Middle East (NAME) region.Methods and materialsThe Global Burden of Disease (GBD) 2019 data were used. Disability-adjusted life years (DALYs), death, incidence, and prevalence rates were categorized by sex and age groups in the NAME region, in 21 countries, from 1990 to 2019. Decomposition analysis was performed to calculate the proportion of responsible factors in the emergence of new cases. Data are presented as point estimates with their 95% uncertainty intervals (UIs).ResultsIn the NAME region, TBL cancer caused 15,396 and 57,114 deaths in women and men, respectively, in 2019. The age-standardized incidence rate (ASIR) increased by 0.7% (95% UI -20.6 to 24.1) and reached 16.8 per 100,000 (14.9 to 19.0) in 2019. All the age-standardized indices had a decreasing trend in men and an increasing trend in women from 1990 to 2019. Turkey (34.9 per 100,000 [27.6 to 43.5]) and Sudan (8.0 per 100,000 [5.2 to 12.5]) had the highest and lowest age-standardized prevalence rates (ASPRs) in 2019, respectively. The highest and lowest absolute slopes of change in ASPR, from 1990 to 2019, were seen in Bahrain (-50.0% (-63.6 to -31.7)) and the United Arab Emirates (-1.2% (-34.1 to 53.8)), respectively. The number of deaths attributable to risk factors was 58,816 (51,709 to 67,323) in 2019 and increased by 136.5%. Decomposition analysis showed that population growth and age structure change positively contributed to new incident cases. More than 80% of DALYs could be decreased by controlling risk factors, particularly tobacco use.ConclusionThe incidence, prevalence, and DALY rates of TBL cancer increased, and the death rate remained unchanged from 1990 to 2019. All the indices and contribution of risk factors decreased in men but increased in women. Tobacco is still the leading risk factor. Early diagnosis and tobacco cessation policies should be improved