QALY league table of Iran: a practical method for better resource allocation

Background: The limited health care resources cannot meet all the demands of the society. Thus, decision makers have to choose feasible interventions and reject the others. We aimed to collect and summarize the results of all cost utility analysis studies that were conducted in Iran and develop a Quality Adjusted Life Year (QALY) league table. Methods: A systematic mapping review was conducted to identify all cost utility analysis studies done in Iran and then map them in a table. PubMed, Embase, Cochrane library, Web of Science, as well as Iranian databases like Iran Medex, SID, Magiran, and Barakat Knowledge Network System were all searched for articles published from the inception of the databases to January 2020. Additionally, Cost per QALY or Incremental Cost Utility Ratio (ICUR) were collected from all studies. The Joanna Briggs checklist was used to assess quality appraisal. Results: In total, 51 cost-utility studies were included in the final analysis, out of which 14 studies were on cancer, six studies on coronary heart diseases. Two studies, each on hemophilia, multiple sclerosis and rheumatoid arthritis. The rest were on various other diseases. Markov model was the commonest one which has been applied to in 45 of the reviewed studies. Discount rates ranged from zero to 7.2. The cost per QALY ranged from 0.144 in radiography costs for patients with some orthopedic problems to 4,551,521 for immune tolerance induction (ITI) therapy in hemophilia patients. High heterogeneity was revealed; therefore, it would be biased to rank interventions based on reported cost per QALY or ICUR. Conclusions: However, it is instructive and informative to collect all economic evaluation studies and summarize them in a table. The information on the table would in turn be used to redirect resources for efficient allocation. in general, it was revealed that preventive programs are cost effective interventions from different perspectives in Iran. © 2021, The Author(s)

Prenatal maternal depressive symptoms are associated with smaller amygdalar volumes of four-year-old children

Prenatal maternal depressive symptoms are related to an increased offspring susceptibility to psychiatric disorders over the life course. Alterations in fetal brain development might partly mediate this association. The relation of prenatal depressive symptoms with child's amygdalar volumes is still underexplored, and this study aimed to address this gap. We explored the association of prenatal maternal depressive symptoms with amygdalar volumes in 28 4-year-old children (14 female). Amygdalar volumes were assessed using the volBrain pipeline and manual segmentation. Prenatal depressive symptoms were self-reported by mothers at gestational weeks 14, 24 and 34 (Edinburgh Postnatal Depression Scale). Sex differences were probed, and possible pre- and postnatal confounders, such as maternal general anxiety, were controlled for. We observed that elevated depressive symptoms of the early second trimester, after controlling for prenatal maternal general anxiety, were significantly related to smaller right amygdalar volumes in the whole sample. Higher depressive symptoms of the third trimester were associated with significantly smaller right amygdalar volumes in boys compared to girls. Altogether, our data suggest that offspring limbic brain development might be affected by maternal depressive symptoms in early pregnancy, and might also be more vulnerable to depressive symptoms in late pregnancy in boys compared to girls

Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men

Partial Support for an Interaction Between a Polygenic Risk Score for Major Depressive Disorder and Prenatal Maternal Depressive Symptoms on Infant Right Amygdalar Volumes

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother-infant dyads (44 female, 11-54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Ahmadi Acute toxicity test using сyanide on Daphnia magna by flow-through system

This study describes the acute toxicity of sodium cyanide on the crustacean Daphnia magna (Cladocera). A new flow-through system was innovated in which the microorganism continuously exposure to the toxicity of sodium cyanide during the test. We used twelve different concentration of sodium cyanide from low values (0 mg CN/L) to high values (1 mg CN /L) on bioassay test. D. magna were exposed to the concentrations for 24, 48, 72 and 96 h at 20 – 25°C. We controlled the three important parameters such as temperature, pH and DO to meet the standard requirements. The LC₅₀ values for 24, 48, 72 and 96 h (95% confidence limits in parentheses) were estimated statistically by the probit methods and were 0.171 (0.163 – 0.179), 0.12 (0.112 – 0.128), 0.07 (0.062 – 0.078) and 0.019 (0.011 – 0.027) mg/L respectively. Finally, we proposed two new values for SAR (safe application rate) and SAFE Coefficients

Evaluation of biological landfill leachate treatment incorporating struvite precipitation and powdered activated carbon addition

Direct application of aerobic biodegradation for leachate treatment is not feasible due to high concentrations of nitrogen and chemical oxygen demand. Several potential leachate treatment schemes incorporating struvite precipitation as pretreatment and two types of activated sludge processes (conventional activated sludge and batch decant reactor (intermittent cycle extended aeration system ICEAS process) with and without addition of powdered activated carbon (PAC) were evaluated in this study. The hydraulic retention times (HRT) of 6 h and 12 h were applied in the biological stages of each process. Treatment schemes incorporating PAC addition showed acceptable results. In the conventional activated sludge process, total chemical oxygen demand (TCOD), soluble chemical oxygen demand (SCOD), NH3, and P removal rates were 87, 84, 98.3, and 94%, respectively, with HRT of 6 h and 95.8, 95.1, 99.1, and 98.7% with HRT of 12 h. For the ICEAS process, removal rates were 89.3, 87.9, 98.2, and 94% with HRT of 6 h and 95.8, 95, 99.2, and 98.7% with HRT of 12 h. On the basis of these results, it can be concluded that struvite precipitation, followed by activated sludge process with PAC addition, can be a strong alternative leachate treatment, achieving the standards set for effluent discharges to receiving waters. © The Author(s), 2010

A variation in the infant oxytocin receptor gene modulates infant hippocampal volumes in association with sex and prenatal maternal anxiety

Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression.Peer reviewe