DeepTraSynergy: drug combinations using multimodal deep learning with transformers.

MOTIVATION: Screening bioactive compounds in cancer cell lines receive more attention. Multidisciplinary drugs or drug combinations have a more effective role in treatments and selectively inhibit the growth of cancer cells. RESULTS: Hence, we propose a new deep learning-based approach for drug combination synergy prediction called DeepTraSynergy. Our proposed approach utilizes multimodal input including drug-target interaction, protein-protein interaction, and cell-target interaction to predict drug combination synergy. To learn the feature representation of drugs, we have utilized transformers. It is worth noting that our approach is a multitask approach that predicts three outputs including the drug-target interaction, its toxic effect, and drug combination synergy. In our approach, drug combination synergy is the main task and the two other ones are the auxiliary tasks that help the approach to learn a better model. In the proposed approach three loss functions are defined: synergy loss, toxic loss, and drug-protein interaction loss. The last two loss functions are designed as auxiliary losses to help learn a better solution. DeepTraSynergy outperforms the classic and state-of-the-art models in predicting synergistic drug combinations on the two latest drug combination datasets. The DeepTraSynergy algorithm achieves accuracy values of 0.7715 and 0.8052 (an improvement over other approaches) on the DrugCombDB and Oncology-Screen datasets, respectively. Also, we evaluate the contribution of each component of DeepTraSynergy to show its effectiveness in the proposed method. The introduction of the relation between proteins (PPI networks) and drug-protein interaction significantly improves the prediction of synergistic drug combinations. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/fatemeh-rafiei/DeepTraSynergy.

CFSSynergy: Combining Feature-Based and Similarity-Based Methods for Drug Synergy Prediction.

Drug synergy prediction plays a vital role in cancer treatment. Because experimental approaches are labor-intensive and expensive, computational-based approaches get more attention. There are two types of computational methods for drug synergy prediction: feature-based and similarity-based. In feature-based methods, the main focus is to extract more discriminative features from drug pairs and cell lines to pass to the task predictor. In similarity-based methods, the similarities among all drugs and cell lines are utilized as features and fed into the task predictor. In this work, a novel approach, called CFSSynergy, that combines these two viewpoints is proposed. First, a discriminative representation is extracted for paired drugs and cell lines as input. We have utilized transformer-based architecture for drugs. For cell lines, we have created a similarity matrix between proteins using the Node2Vec algorithm. Then, the new cell line representation is computed by multiplying the protein-protein similarity matrix and the initial cell line representation. Next, we compute the similarity between unique drugs and unique cells using the learned representation for paired drugs and cell lines. Then, we compute a new representation for paired drugs and cell lines based on the similarity-based features and the learned features. Finally, these features are fed to XGBoost as a task predictor. Two well-known data sets were used to evaluate the performance of our proposed method: DrugCombDB and OncologyScreen. The CFSSynergy approach consistently outperformed existing methods in comparative evaluations. This substantiates the efficacy of our approach in capturing complex synergistic interactions between drugs and cell lines, setting it apart from conventional similarity-based or feature-based methods.

Inequality in prevalence, awareness, treatment, and control of hypertension in Iran: the analysis of national households' data.

BACKGROUND: Providing an equitable Universal Health Coverage (UHC) is key for progressing towards the sustainable development goals in the health systems. To help policymakers make hypertension services more equitable with existing (limited) resources in Iran, we examined the inequality of the prevalence, awareness, treatment, and control (PATC) of hypertension as the four indicators of hypertension UHC in Iran.  METHODS: This research was a cross-sectional study of inequality of PATC of hypertension using a representative sample of Iranians aged ≥ 25 years from the Iran 2016 STEP wise approach to Surveillance study (STEPS). Outcome variables consisted of PATC of hypertension. Covariates were demographic (age, sex, and marital status) and living standard (area of residence, wealth status, education, and health insurance) indicators. We drew concentration curves (CC) and estimated concentration indices (C). We also conducted normalized Erreygers decomposition analysis for binary outcomes to identify covariates that explain the wealth-related inequality in the outcomes. Analysis was conducted in STATA 14.1. RESULTS: The normalized concentration index of hypertension prevalence and control was -0.066 (p < .001) and 0.082 (p < .001), respectively. The C of awareness and treatment showed nonsignificant difference between the richest and poorest. Inequality in the hypertension prevalence of females was significantly higher than males (C = -0.103 vs. male C = -0.023, p < .001). Our analyses explained 33% of variation in the C of hypertension prevalence and 99.7% of variation in the C of control. Education, wealth index, and complementary insurance explained most inequality in the prevalence. Area of residence, education, wealth status, and complementary insurance had the largest contribution to C of control by 30%, 28%, 26%, and 21%, respectively. CONCLUSIONS: This study showed a pro-rich inequality in the prevalence and control of hypertension in Iran. We call for expanding the coverage of complementary insurance to reduce inequality of hypertension prevalence and control as compared with other factors it can be manipulated in short run. We furthermore advocate for interventions to reduce the inequality of hypertension control between rural and urban areas.

Diabetes mellitus risk prediction in the presence of class imbalance using flexible machine learning methods.

BACKGROUND: Early detection and prediction of type two diabetes mellitus incidence by baseline measurements could reduce associated complications in the future. The low incidence rate of diabetes in comparison with non-diabetes makes accurate prediction of minority diabetes class more challenging. METHODS: Deep neural network (DNN), extremely gradient boosting (XGBoost), and random forest (RF) performance is compared in predicting minority diabetes class in Tehran Lipid and Glucose Study (TLGS) cohort data. The impact of changing threshold, cost-sensitive learning, over and under-sampling strategies as solutions to class imbalance have been compared in improving algorithms performance. RESULTS: DNN with the highest accuracy in predicting diabetes, 54.8%, outperformed XGBoost and RF in terms of AUROC, g-mean, and f1-measure in original imbalanced data. Changing threshold based on the maximum of f1-measure improved performance in g-mean, and f1-measure in three algorithms. Repeated edited nearest neighbors (RENN) under-sampling in DNN and cost-sensitive learning in tree-based algorithms were the best solutions to tackle the imbalance issue. RENN increased ROC and Precision-Recall AUCs, g-mean and f1-measure from 0.857, 0.603, 0.713, 0.575 to 0.862, 0.608, 0.773, 0.583, respectively in DNN. Weighing improved g-mean and f1-measure from 0.667, 0.554 to 0.776, 0.588 in XGBoost, and from 0.659, 0.543 to 0.775, 0.566 in RF, respectively. Also, ROC and Precision-Recall AUCs in RF increased from 0.840, 0.578 to 0.846, 0.591, respectively. CONCLUSION: G-mean experienced the most increase by all imbalance solutions. Weighing and changing threshold as efficient strategies, in comparison with resampling methods are faster solutions to handle class imbalance. Among sampling strategies, under-sampling methods had better performance than others.

Trends in dental caries of deciduous teeth in Iran: a systematic analysis of the national and sub-national data from 1990 to 2017.

BACKGROUND: Dental caries is the most prevalent child affliction in the world and can be reduced through effective preventive interventions. To plan cost-effective interventions, clear and integrated data are needed. This study has been designed to overcome the lack of national trend in deciduous dental caries in Iran. OBJECTIVE: To estimate the dental caries trend in deciduous teeth in the Iranian population at different ages from 1990 to 2017. METHODS: From 1990 to 2017 a literature search about dmf and its components (decayed, missed, and filled tooth, abbreviated as dt, mt, and ft) as well as dental caries was done in the Iranian population in three English (PubMed, Web of Science, and Scopus) and three national databases (in Persian). All eligible national oral health surveys in these 28 years were included. National dmft data were categorised based on age (1-4, 5-9, and 10-14), sex, province and year. The final trends were estimated using an age-spatio-temporal hierarchical model. We used the bootstrap method in multilevel models to predict the uncertainty interval (UI) of the modelled results. Finally, the estimations of dmft, dt, mt, and ft with a 95% UI were reported from 1990 to 2017. RESULTS: Almost 22% of the Iranian deciduous teeth were involved with dental caries in 1990 [dmft = 4.37; (95% UI 2.23, 6.62)] which more than 83% of it was dt [3.64 (1.53, 5.88)] and less than 7% was ft [0.30 (0.06, 0.65)]. During 1990-2017, dmft increased by more than 15% [in 2017, dmft = 5.03 (2.82, 7.29)]. The highest increase was seen in dt which was more than 17% [in 2017, dt = 4.27 (1.96, 6.57)]. CONCLUSION: Increasing dental caries among Iranian children over 28 years shows that oral health policies in Iran need critical evaluation. We need cost-effective nationwide interventions (e.g., supervised tooth brushing and improving dietary habits) and training well-experienced intermediate manpower (e.g., dental hygienists) to reduce dental caries.

Spatio-temporal analysis of misaligned burden of disease data using a geo-statistical approach.

Data used to estimate the burden of diseases (BOD) are usually sparse, noisy, and heterogeneous. These data are collected from surveys, registries, and systematic reviews that have different areal units, are conducted at different times, and are reported for different age groups. In this study, we developed a Bayesian geo-statistical model to combine aggregated sparse, noisy BOD data from different sources with misaligned areal units. Our model incorporates the correlation of space, time, and age to estimate health indicators for areas with no data or a small number of observations. The model also considers the heterogeneity of data sources and the measurement errors of input data in the final estimates and uncertainty intervals. We applied the model to combine data from nine different sources of body mass index in a national and sub-national BOD study. The cross-validation results confirmed a high out-of-sample predictive ability in sparse and noisy data. The proposed model can be used by other BOD studies especially at the sub-national level when the areal units are subject to misalignment.

Malaria intermittent preventive treatment in Nigeria: a qualitative study to explore barriers.

BACKGROUND: While the use of sulphadoxine pyrimethamine (SP) is effective in preventing malaria infection during pregnancy, there are challenges limiting its uptake in Nigeria. This study aimed at exploring the barriers to IPTp usage among pregnant women in Kano state - Nigeria. METHODS: This is a qualitative study. The purposive sampling strategy was used for identification and selection of 14 key informants for interviews. In addition, six focus group discussions (FGDs) were conducted with pregnant women (3 FGDs) and married men (3 FGDs). The conventional content analysis method was used to interpret meaning from the content of the data. MAXQDA 10 software was used for data management and analysis. RESULTS: Poor policy implementation, poor antenatal care attendance, inadequate access to intermittent preventive treatment at the community levels, lack of sustainable funding, and poor community engagement emerged as major barriers to IPTp use in Nigeria. CONCLUSION: While the political will to allocate sufficient financial resources could help improve service delivery and IPTp usage among pregnant women, community participation is critical to sustain the gains.

Introducing an efficient sampling method for national surveys with limited sample sizes: application to a national study to determine quality and cost of healthcare.

BACKGROUND: Sampling a small number of participants from an entire country is not straightforward. In this case, researchers reluctantly sample from a single setting or few settings, which limits the generalizability of findings. Therefore, there is a need to design efficient sampling method for small sample size surveys that can produce generalizable results at the country level. METHODS: Data comprised of twenty proxy variables to measure health services demands, structures, and outcomes of 413 districts of Iran. We used two data mining methods (hierarchical clustering method (HCM) and model-based clustering method (MCM)) to create homogenous groups of districts, i.e., strata based on these variables. We compared the internal and stability validity of the methods by statistical indices. An expert group checked the face validity of the methods, particularly regarding the total number of strata and the combination of districts in each stratum. The efficiency of selected method, which is measured by the inverse of variance, was compared with a simple random sampling (SRS) through simulation. The sampling design was tested in a national study in Iran, which aimed to evaluate the quality and costs of medical care for eight selected diseases by only recruiting 300 participants per disease at the country level. RESULTS: MCM and HCM divided the districts into eight and two clusters, respectively. The measures of internal and stability validity showed that clusters created by MCM were more separated, compact, and stable, thus forming our optimum strata. The probability of death from stroke, chronic obstructive pulmonary disease, and in-hospital mortality rate were the most important indicators that distinguished the eight strata. Based on the simulation results, MCM increased the efficiency of the sampling design up to 1.7 times compared to SRS. CONCLUSIONS: The use of data mining improved the efficiency of sampling up to 1.7 times greater than SRS and markedly reduced the number of strata to eight in the entire country. The proposed sampling design also identified key variables that could be used to classify districts in Iran for sampling from these target populations in the future studies.

Identifying associations between health services operational factors and health experience for patients with type 2 diabetes in Iran.

BACKGROUND: Facing limited health resources, healthcare providers need to rely on health service delivery models that produce the best clinical outcomes and patient experience. We aimed to contribute to developing a patient experience-based type 2 diabetes service delivery model by identifying operational structures and processes of care that were associated with clinical outcome, health experience, and service experience. METHODS: We conducted a cross-sectional survey of type 2 diabetes patients between January 2019 to February 2020. Having adjusted for demand variables, we examined relationships between independent variables (behaviours, services/processes, and structures) and three categories of dependent variables; clinical outcomes (HbA1c and fasting blood glucose), health experience (EuroQol quality of life (EQ-5D), evaluation of quality of life (visual analgene scale of EQ-5D), and satisfaction with overall health status), and service experience (evaluation of diabetes services in comparison with worst and best imaginable diabetes services and satisfaction with diabetes services). We analysed data using multivariate linear regression models using Stata software. RESULTS: After adjusting for demand variables; structures, diabetes-specific health behaviours, and processes explained up to 22, 12, and 9% of the variance in the outcomes, respectively. Based on significant associations between the diabetes service operations and outcomes, the components of an experience-based service delivery model included the structural elements (continuity of care, redistribution of task to low-cost resources, and improved access to provider), behaviours (improved patient awareness and adherence), and process elements (reduced variation in service utilization, increased responsiveness, caring, comprehensiveness of care, and shared decision-making). CONCLUSIONS: Based on the extent of explained variance and identified significant variables, health services operational factors that determine patient-reported outcomes for patients with type 2 diabetes in Iran were identified, which focus on improving continuity of care and access to providers at the first place, improving adherence to care at the second, and various operational process variables at the third place.

Evaluation of Hippocampal Function in Temporal Lobe Epilepsy: Spatial Bayesian Variable Selection and Grouping the Regression Coefficient in Multilevel Functional Magnetic Resonance Imaging Data Analysis.

Background: A pre-surgical evaluation of cognitive functions in patients with mesial temporal lobe epilepsy (mTLE) is critical. The limitations of the usual brain analysis model were resolved by the spatial Bayesian variable selection (SBVS) method. An Ising and Dirichlet Process (Ising-DP) model considers SBVS and the grouping of a large number of voxels. The present study aimed to identify brain areas involved in episodic memory in patients with right mTLE and controls via the Ising-DP model. The model was extended to include between-subject factors (BSFs), and the results were compared with other classical methods. Methods: The present cross-sectional study was conducted on 15 patients with right mTLE and 20 controls in Tehran, Iran, in 2018. During functional magnetic resonance imaging, the subjects were tested with the face-encoding memory task, followed by a recognition memory test. The participants demographic factors such as age, sex, marital status, area of residence, and years of schooling were considered to comprise BSFs. The independent t test, the chi-square test, and the correlation test were conducted using the SPSS software (version 20.0). The image processing was carried out using SPM (version 12.0) and MATLAB (version R2014a). Results: The Ising-DP model appropriately (R2=0.642) detected activated hippocampal areas. The model adjusted for BSFs indicated a better fit by the significant effect of age (P((γ]>0.91), sex (P[γ]>0.87), and years of schooling (P[γ]>0.89). The heat maps exhibited decreased activation in the right hippocampal region in the patients compared with the controls (P<0.0001). Right hippocampal activity had a significant positive correlation with the recognition memory test in the mTLE group (r=0.665) and the control group (r=0.593). Conclusion: The Ising-DP model was sufficiently sensitive to detect activated areas in our patients with right mTLE during the face-encoding memory task. Since the model adjusted for BSFs improved sensitivity, we recommend the use of more detailed BSFs such as seizure history in future research.

Efficient production of a lentiviral system for displaying Crimean-Congo hemorrhagic fever virus glycoproteins reveals a broad range of cellular susceptibility and neutralization ability.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with a mortality rate of up to 50% in humans. To avoid safety concerns associated with the use of live virus in virus neutralization assays and to detect human serum neutralizing antibodies, we prepared lentiviral particles containing the CCHF glycoprotein (lenti-CCHFV-GP). Incorporation of the GP into the lentiviral particle was confirmed by electron microscopy and Western blotting. Lenti-CCHFV-GP was found to be able to infect a wide range of cell lines, including BHK-21, HeLa, HepG2, and AsPC-1 cells. In addition, lenti-CCHFV-GP was successfully used as an alternative to CCHFV for the detection of neutralizing antibodies. Sera collected from CCHF survivors neutralized lenti-CCHFV-GP particles in a dose-dependent manner. Our results suggest that the lenti-CCHFV-GP pseudovirus can be used as a safe tool for neutralization assays in low-containment laboratories.

Socioeconomic inequality in intermittent preventive treatment using Sulphadoxine pyrimethamine among pregnant women in Nigeria.

BACKGROUND: Intermittent preventive treatment using Sulphadoxine pyrimethamine (IPTp-SP) for malaria prevention is recommended for all pregnant women in malaria endemic areas. However, there is limited evidence on the level of socioeconomic inequality in IPTp-SP use among pregnant women in Nigeria. Thus, this study aimed to determine the level of socioeconomic inequality in IPTp-SP use among pregnant women in Nigeria and to decompose it into its contributing factors. METHODS: A secondary data analysis of Nigerian demographic and health survey of 2018 was conducted. A sample of 21,621 pregnant women aged between 15 and 49 years and had live birth in the previous 2 years before the survey were included in this analysis. The study participants were recruited based on a stratified two-stage cluster sampling method. Socioeconomic inequality was decomposed into its contributing factors by concentration index. RESULT: Totally 63.6% of pregnant women took at least one dose of IPTp-SP prophylaxis. Among IPTp-SP users, 35.1% took one dose, 38.6% took two doses and 26.2% took three doses and more. Based on both concentration index of 0.180 (p-value = < 0.001, 95% CI: 0.176 to 0.183) and Erreyger's normalization concentration index 0.280 (p-value = < 0.001, 95% CI: 0.251 to 0.309), the IPTp-SP utilization was pro-rich. The largest contributors to the inequality in IPTp-SP uptake were wealth index (47.81%) and educational status (28.66%). CONCLUSION: Our findings showed that IPTp-SP use was pro-rich in Nigeria. Wealth index and educational status were the factors that significantly contributed to the inequality. The disparities could be reduced through free IPTp service expansion by targeting pregnant women from low socioeconomic status.

Insight into blood pressure targets for universal coverage of hypertension services in Iran: the 2017 ACC/AHA versus JNC 8 hypertension guidelines.

BACKGROUND: We compared the prevalence, awareness, treatment, and control of hypertension in Iran based on two hypertension guidelines; the 2017 ACC/AHA -with an aggressive blood pressure target of 130/80 mmHg- and the commonly used JNC8 guideline cut-off of 140/90 mmHg. We shed light on the implications of the 2017 ACC/AHA for population subgroups and high-risk individuals who were eligible for non-pharmacologic and pharmacologic therapies. METHODS: Data was obtained from the Iran national STEPS 2016 study. Participants included 27,738 adults aged ≥25 years as a representative sample of Iranians. Regression models of survey design were used to examine the determinants of prevalence, awareness, treatment, and control of hypertension. RESULTS: The prevalence of hypertension based on JNC8 was 29.9% (95% CI: 29.2-30.6), which soared to 53.7% (52.9-54.4) based on the 2017 ACC/AHA. The percentage of awareness, treatment, and control were 59.2% (58.0-60.3), 80.2% (78.9-81.4), and 39.1% (37.4-40.7) based on JNC8, which dropped to 37.1% (36.2-38.0), 71.3% (69.9-72.7), and 19.6% (18.3-21.0), respectively, by applying the 2017 ACC/AHA. Based on the new guideline, adults aged 25-34 years had the largest increase in prevalence (from 7.3 to 30.7%). They also had the lowest awareness and treatment rate, contrary to the highest control rate (36.5%) between age groups. Compared with JNC8, based on the 2017 ACC/AHA, 24, 15, 17, and 11% more individuals with dyslipidaemia, high triglycerides, diabetes, and cardiovascular disease events, respectively, fell into the hypertensive category. Yet, based on the 2017 ACC/AHA, 68.2% of individuals falling into the hypertensive category were eligible for receiving pharmacologic therapy (versus 95.7% in JNC8). LDL cholesterol< 130 mg/dL, sufficient physical activity (Metabolic Equivalents≥600/week), and Body Mass Index were found to change blood pressure by - 3.56(- 4.38, - 2.74), - 2.04(- 2.58, - 1.50), and 0.48(0.42, 0.53) mmHg, respectively. CONCLUSIONS: Switching from JNC8 to 2017 ACC/AHA sharply increased the prevalence and drastically decreased the awareness, treatment, and control in Iran. Based on the 2017 ACC/AHA, more young adults and those with chronic comorbidities fell into the hypertensive category; these individuals might benefit from earlier interventions such as lifestyle modifications. The low control rate among individuals receiving treatment warrants a critical review of hypertension services.

Association between place of delivery for pregnant mothers and neonatal mortality: a systematic review and meta-analysis.

BACKGROUND: Neonatal mortality is a major health problem mainly in the developing countries and its reduction was remain stagnant during the era of Millennium Development Goal. Current global health policies emphasize institutional deliveries as a pathway to achieving reductions in neonatal mortality in developing countries. There are inconsistent conclusions of evidence about this fact, mainly in developing countries. Therefore, this study was conducted to assess the association between health facility delivery and neonatal mortality. METHODS: We systematically searched EMBASE, PubMed, ISI Web of Science and Scopus through 18 March 2018 and then updated on 14 February 2019. I2 test statistic was used to assess heterogeneity. Publication bias was checked using a funnel plot and meta-bias test. Random-effects model was used to determine the pooled effect size. RESULTS: Nineteen articles were included in the meta-analysis. The pooled odds ratios (ORs) indicated that health facility delivery was significantly associated with the odds of neonatal mortality (OR = 0.48; 95% CI: 0.38, 0.58). This significant inverse association was consistently found regardless of study design, geographical region and quality of the study. There is evidence of publication bias with high heterogeneity between studies (I2 = 84.5%). CONCLUSION: The odds of neonatal mortality were much likely lower among those delivered at a health facility than those delivery at home. Therefore, encouraging delivery in a health facility and minimizing any barrier to health facility are important. Further longitudinal studies based on larger, more representative samples are therefore needed to further assess the underlying relationships.

Sex Differences in 28-Day Mortality of Ischemic Stroke in Iran and Its Associated Factors: A Prospective Cohort Study.

INTRODUCTION: The mortality and morbidity rates of stroke in men and women have been reported differently and its effective factors have been discussed. The purpose of this study was to investigate sex differences in 28-day mortality of ischemic stroke and its associated factors. MATERIALS AND METHODS: This is a prospective cohort study conducted from June 2018 to September 2019 in patients with ischemic stroke referred to Firoozgar, Shariati and Sina hospitals in Tehran. Demographic data, risk factors, disease history, drug use, severity of stroke, and patient functional status were recorded in the hospital. The patients' functional status and severity of stroke were measured using the Modified Ranking Scale (MRS) and the National Institutes of Health Stroke Scale (NIHSS). After 28 days, the patients' survival status was monitored. Logistic regression was used to analyze the data. RESULTS: In this study, 703 patients were enrolled; of them, 260 (37.00%) were female and 443 (63.00%) were male. After 28 days, 21 female cases (8.17%) and 26 male (6.08%) ones died (P = 0.299). Functional status (OR = 4.65; 95%CI: 2.09 to 10.38), diastolic blood pressure (OR = 0.91; 95%CI: 0.85 to 0.96), warfarin use (OR = 0.15; 95%CI: 0.04 to 0.55), and hemoglobin (OR = 1.17; 95%CI: 1.02 to 1.35) were associated with 28-day mortality. Poor functional status in men had a greater association with 28-day mortality than women (OR 4.65 vs. 1.64). High diastolic blood pressure had a negative association with the 28-day mortality of cases and this association is more in women than in men (OR 0.88 vs. 0.91). High hemoglobin is a risk factor in men and a protective factor in 28-day mortality in women (OR 1.73 vs. 0.73). Smoking also had a greater association with 28-day mortality in women than men (OR 2.67 vs. 1.2). DISCUSSION: Twenty eight-day mortality was more in women than in men, but this difference was not significant. Women were older, had more severe stroke and poorer functional status than men. Variables including functional status, diastolic blood pressure, hemoglobin level, and smoking had interaction with sex, and their association with 28-day mortality rate was different between men and women. Sex differences should be considered, so that we can better manage stroke patients.

Effect of maternal mental health during pregnancy on infant growth at six months of age in Suburban communities in South of Iran.

Background: Due to the controversial effects of mental health disorders during pregnancy on infant health, the present study aimed to evaluate the effect of gestational depression, stress, and anxiety on the growth of offspring at six months of age in disadvantaged communities in South of Iran. Methods: The sample comprised of 470 pregnant women (response rate=98%) who are participated in the Bandar Abbas Pregnancy Cohort study. Maternal mental health was measured by the DASS-21 questionnaire during pregnancy. Data on infant growth was collected based on infant`s growth chart at six months of age. The relative risk of suboptimal infant growth was calculated by Modified Poisson regression models at 5% significant level. Results: The prevalence of depression, anxiety, and stress was 19.0%, 26.1% and 6.5%, respectively. At six months of age, the mean (SD) of infant`s weight (gram), height (cm) and head circumference (cm) were 7287.30 (1019.85), 63.23 (5.62) and 41.39 (2.70), respectively. Compared to normal mothers, the risk of suboptimal weight at six months of age significantly increased by 71% in mothers who were classified as having depression (Adjusted RR: 1.71, 95% CI: 1.07, 2.09). The presence of anxiety significantly increased the risk of suboptimal height at six months of age by 43% (ARR: 1.43, 95% CI: 1.07, 1.92). There were no statistically significant effects of either depression anxiety or stress on the suboptimal head circumference at six months of age. Conclusion: Our results showed that mental health disorders of pregnant women might adversely influence the weight and height growth of offspring within the first six months of age. Screening protocols to early diagnose of mental health disorders during pregnancy, and to strict follow up of diagnosed cases postpartum are proposed.

A spatio-temporal analysis of influenza-like illness in Iran from 2011 to 2016.

Background: Investigating the spatial aspects of the disease can help decision-makers and researchers better understand the pattern of the disease, and is also very important in the implementation of the disease control programs. Given the vast area of Iran, as well as the diverse geographical and climate conditions of the country, using the geographical information system (GIS) is a suitable method for the study of influenza. In this study, we provide a clear picture of the distribution of the influenza-like illness (ILI) in Iranian provinces through the years from 2011 to 2016 by applying a spatio-temporal analysis, using geographic information system (GIS). Disease rates by location and year are estimated, and then hot spots and cold spots are distinguished. Methods: This study was conducted using the ILI incidence rate data recorded in the Iranian Influenza Surveillance System from August 2011 to August 2016. The Choropleth map method and the various equal interval and natural break classifications were used. The local Getis-Ord Gi* method was then used to identify the hot spots and regions where, for some reason, the distribution of the disease had significantly clustered spatially. Statistical analyses were done using the ArcGIS 10.2 software. Results: This study indicates that the highest ILI rate belongs to the period from August 2014 to August 2015 with a rate of 180.26 (95%CI: 177.65 to 182.9) per 100,000 people. The results show that the highest 5-year mean of ILI rate belongs to Zanjan, Markazi, Lorestan, Ilam, North Khorasan, and South Khorasan provinces. Also, results from the local Getis-Ord Gi* method show that ILI has formed a hot spot between the years 2011 and 2013 on the eastern borders of Iran and afterward during the years 2014 to 2016 in the western regions of the country. Conclusion: Given the importance of influenza and its huge economic burden on the society, identifying the hot spot regions can help better manage the disease. This study indicates the distribution of the disease has formed a hot spot in the western regions of the country.

Prevalence of and Risk Factors for Genito-Pelvic Pain/Penetration Disorder: A Population-Based Study of Iranian Women.

INTRODUCTION: To date, few studies have investigated the prevalence of sexual pain in the context of the new diagnostic concept of genito-pelvic pain/penetration disorder (GPPPD). AIM: To evaluate the prevalence of GPPPD and its associated factors. METHODS: This was a population-based, cross-sectional study of 590 healthy married women age 18-70 years conducted between May and October 2017 in Tehran, Iran. MAIN OUTCOME MEASURES: Research tools included demographic characteristics checklist, factors affecting GPPPD, sexual distress and self-reporting of pain during intercourse, 2 standard questionnaires on depression (Patient Health Questionnaire 9) and Binik's guideline for the diagnosis of GPPPD. RESULTS: 196 women (33%) reported pain or fear in answer to self-report questions. Administration of Binik's guideline yielded a GPPPD prevalence of 16% (n = 94 women); however, this number decreased to 62 women (10.5%) when sexual distress was taken into account; thus, the final prevalence of GPPPD was considered to be 10.5%. However, if the threshold in Binik's guideline was lowered to also include those reporting "somewhat" pain in addition to the group reporting "moderate" and "quite a bit or always," then the prevalence of GPPPD increased to 25.8%. The results of backward logistic regression identified a strong aversion to looking at or touching the genitalia (odd ratio [OR] = 4.3), low sexual satisfaction (OR = 3.1), and severe depression (OR = 6.6) as independent risk factors for a diagnosis of GPPPD and secure financial status (OR = 0.3) and a high level of marital satisfaction (OR = 0.2) as protective factors against a diagnosis of GPPPD. CLINICAL IMPLICATIONS: Reliable diagnosis of GPPPD is crucial. Application of validated tools may mitigate the overestimation of GPPPD prevalence. Simultaneously, clinicians' judgment is essential in assessing a reasonable threshold and preventing underestimation that leads to the exclusion of women suffering from pain. STRENGTHS & LIMITATIONS: The present study is one of the few evaluating the prevalence of GPPPD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) definition and Binik's guideline. The study also aims to point out some new perspectives on merging the 2 concepts of vaginismus and dyspareunia. Study limitations include the evaluation of factors affecting GPPPD based on self-reporting and possible recall bias. CONCLUSION: Further research is needed to determine the appropriate threshold for a diagnosis of GPPPD. We suggest that a woman with mild to moderate pain or fear of vaginal penetration is under sexual distress and cannot be neglected. In addition, problems may arise following the DSM-5 merging of the 2 disorders of vaginismus and dyspareunia, owing to the significant prevalence and distress of lifelong vaginismus in some cultures. Alizadeh A, Farnam F, Raisi F, et al. Prevalence of and Risk Factors for Genito-Pelvic Pain/Penetration Disorder: A Population-Based Study of Iranian Women.J Sex Med 2019;16:1068-1077.

Health State Utilities for Patient's Current Health from Bipolar Type I Disorder.

BACKGROUND: Bipolar Type I Disorder (BID) is a disabling mental disorder among young adults that places enormous psychological, social, and economic burdens on patients, their families, and health care systems and decreases quality of life (QOL). Few studies have investigated the quality-adjusted life-years (QALY), health state preferences, and utilities in patients with BID. AIM OF STUDY: The aim of this study was to elicit health state utilities for current health among a sample of individuals with BID irrespective of their clinical conditions at the time of evaluation. METHODS: One hundred individuals with BID were consecutively enrolled in this cross-sectional study. Preferences were elicited from patients with visual analogous scale (VAS) and time trade-off (TTO). To assess quality of life, the Farsi version of the World Health Organization's QOL Instrument-Short Version (WHOQOL-BREF) was used. In addition, health state was assessed with the Short Form-36 (SF-36) health survey, and then a specially- derived reduced version of the SF-36 (the `SF-6D') was calculated as an alternative to existing preference-based measures of health for conducting economic evaluation of various interventions. Moreover, several clinical measures were administered to participants. RESULTS: The mean (S.D.) VAS, TTO, and SF-6D utility scores were 0.59 (0.21), 0.44 (0.33), and 0.61 (0.11), respectively. There were significant associations of most selected clinical characteristics with VAS and TTO scores. Additionally, there were strong correlations between all domains of WHOQOL-BREF and VAS scores as well as moderate to strong correlations with TTO scores. Furthermore, there were strong correlations between all scales of SF-36 scores and VAS scores as well as moderate to strong correlations between the scales of SF-36 scores and TTO scores. DISCUSSION: The current study showed that even unstable patients could evaluate their own health states. Furthermore, the present study showed substantial decrements in health-related life preferences among persons with BID. Additionally, the patients with most recent depressive or mixed episodes reported lower VAS scores than those with most recent manic episodes. LIMITATIONS: This study was performed on a group of patients with BID in a referral psychiatric center. This sample can potentially make a selection bias. Furthermore, this study was cross-sectional. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Generally, clinical features could explain more than half of the variances in VAS utility scores. Among all clinical features, severity of symptoms and duration of disease were among the main factors significantly associated with the utility decreases. IMPLICATION FOR HEALTH POLICIES: The present study data provide health state preferences useful for cost-utility and outcome-modeling studies as well as health policy and decision-making. Also, the evaluations were partially affected by severity of symptoms. Therefore, utilities obtained in this study can be utilized to develop QALY and provide utility values that can be used in economic models for cost-utility studies. IMPLICATIONS FOR FURTHER RESEARCH: The comparison of the utility in a group of patients in different mood episodes and in their controlled periods and calculating the proportion of each episode to total duration of disease and to the patient's life span in future investigations may add crucial information to the present knowledge. The evaluation of biological and non-biological therapies by measuring utility and health value as health output indicators is strongly suggested.

Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank.

The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation of potential observational and genetic protein-cancer risk associations. We investigated associations of 1463 plasma proteins with incidence of 19 cancers and 9 cancer subsites in UK Biobank participants (average 12 years follow-up). Emerging protein-cancer associations were further explored using two genetic approaches, cis-pQTL and exome-wide protein genetic scores (exGS). We identify 618 protein-cancer associations, of which 107 persist for cases diagnosed more than seven years after blood draw, 29 of 618 were associated in genetic analyses, and four had support from long time-to-diagnosis ( > 7 years) and both cis-pQTL and exGS analyses: CD74 and TNFRSF1B with NHL, ADAM8 with leukemia, and SFTPA2 with lung cancer. We present multiple blood protein-cancer risk associations, including many detectable more than seven years before cancer diagnosis and that had concordant evidence from genetic analyses, suggesting a possible role in cancer development.