Model-Robust Inference for Clinical Trials that Improve Precision by Stratified Randomization and Adjustment for Additional Baseline Variables

We focus on estimating the average treatment effect in clinical trials that involve stratified randomization, which is commonly used. It is important to understand the large sample properties of estimators that adjust for stratum variables (those used in the randomization procedure) and additional baseline variables, since this can lead to substantial gains in precision and power. Surprisingly, to the best of our knowledge, this is an open problem. It was only recently that a simpler problem was solved by Bugni et al. (2018) for the case with no additional baseline variables, continuous outcomes, the analysis of covariance (ANCOVA) estimator, and no missing data. We generalize their results in three directions. First, in addition to continuous outcomes, we handle binary and time-to-event outcomes; this broadens the applicability of the results. Second, we allow adjustment for an additional, preplanned set of baseline variables, which can improve precision. Third, we handle missing outcomes under the missing at random assumption. We prove that a wide class of estimators is asymptotically normally distributed under stratified randomization and has equal or smaller asymptotic variance than under simple randomization. For each estimator in this class, we give a consistent variance estimator. This is important in order to fully capitalize on the combined precision gains from stratified randomization and adjustment for additional baseline variables. The above results also hold for the biased-coin covariate-adaptive design. We demonstrate our results using completed trial data sets of treatments for substance use disorder, where adjustment for additional baseline variables brings substantial variance reduction

HIV, hepatitis C virus, and hepatitis B virus co-infections among injecting drug users in Tehran, Iran

SummaryObjectivesTo assess the prevalence of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and co-infections among injecting drug users (IDUs) in Tehran.MethodsA sample of 899 IDUs (861 male and 38 female) was recruited in Tehran from treatment and harm reduction facilities and from drug user hangouts in public areas in equal proportions. ELISA testing for HIV, HCV antibody (HCV-Ab), hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb) was carried out. Positive HIV tests were rechecked by Western blot.ResultsThe prevalence of HIV was 10.7%, HCV infection was 34.5%, and past or current HBV infection was 50.7%. Infection with all three viruses was seen in 6.5% (95% confidence interval 4.9–8.2) of participants. HIV/HCV, HIV/HBV, and HBV/HCV co-infections were seen in 8.7%, 7.8%, and 21.0% of participants, respectively. The rate of HCV infection among HIV-positive cases was significantly higher than in HIV-negative IDUs (80.6% vs. 28.7%, p<0.0001). There was no significant association between these infections and co-infections with gender and source of sampling.ConclusionIn general, co-infection with these three blood-borne viruses is common among IDUs. Since co-infection increases the morbidity and mortality of all infections, the observed level of co-infection in the high number of IDUs in Iran necessitates a serious comprehensive response

A Scientometric Study of Iranian Scientific Productions in the Field of ‎Substance Use and Addiction Research in the Years 2008 to 2012‎

Background: We aimed to evaluate the current status of scientific production in the field of substance use and addiction in Iran, to determine its trend and pattern during a 5 years period (2008-2012). Methods: Using relevant keywords, we searched three international databases (Web of Science, Medline, and Scopus) and two local databases (SID and Iranmedex) to locate the papers published in the field of addiction by Iranian researchers during 2008-2012. Findings: The results indicated a significant increase in the number of studies published in the field during the 5 years study period, with more than half of the papers published in the last 2 years. Results also indicated that over half (53.5%) of the papers were published in Persian-language Iranian Journals, but the rate of increase in the number of papers published in English was slightly higher than that of Persian ones. Opioid substances were found to be the topic of approximately 75% of the papers. Studies on key topics, including national surveys, evaluation of current programs, addiction in women and children, and so forth, were found to be highly lacking. Conclusion: Results suggested a significant growth in the scientific production of Iran in the field of substance use and addiction. However, considering the significance of substance use and dependence in the country, and compared to the scientific production of developed countries, the amount of research conducted in the field of addiction in Iran is still limited

Inclusion of gaming disorder in the diagnostic classifications and promotion of public health response

There are ongoing controversies regarding the upcoming ICD-11 concept of gaming disorder. Recently, Aarseth et al. have put this diagnostic entity into scrutiny. Although we, a group of Iranian researchers and clinicians, acknowledge some of Aarseth et al.’s concerns, believe that the inclusion of gaming disorder in the upcoming ICD-11 would facilitate necessary steps to raise public awareness, enhance development of proper diagnostic approaches and treatment interventions, and improve health and non-health policies

A Six-Year Follow-up of People Who Use Cannabis in Iran – A Case Series

Background: Frequent cannabis use is associated with adverse health-related outcomes. This study followed up individuals who used cannabis to assess their use and adverse event status. Methods: The eligible individuals, recruited in the Iranian Mental Health Survey (IranMHS), were contacted via telephone calls six years after the index interview. The frequency of cannabis use and the occurrence of selected adverse events were recorded. The baseline status was extracted from the index survey. If any individual was inaccessible, his/her vital status was assessed.  Findings: Of the 50 eligible individuals (all male), two had died. Moreover, from among 25 reached participants, 19 reported abstinence from cannabis in the past year, and 18 reported at least one adverse event in the past six years. Violence and imprisonment were the most common events reported.  Conclusion: Six years after the index interview, most of the participants abstained from cannabis. Besides, adverse events were common, emphasizing the need for further investigations on larger samples of cannabis users

Province-level Prevalence of Psychiatric Disorders: Application of Small-Area Methodology to the Iranian Mental Health Survey (IranMHS)

Objective: National surveys revealed a high prevalence of psychiatric disorders in Iran. Province-level estimates are needed to manage the resources and focus on preventive efforts more efficiently. The objective of this study was to provide province-level estimates of psychiatric disorders. Method: In this study, Iranian Mental Health Survey (IranMHS) data (n = 7886) was used to produce province-level prevalence estimates of any psychiatric disorders among 15-64 year old males and females. Psychiatric disorders were diagnosed based on structured diagnostic interview of the Persian version of Composite International Diagnostic Interview (CIDI, version, 2.1). The Hierarchical Bayesian (HB) random effect model was used to calculate the estimates. The mental health status of half of the participants was also measured using a 28-item general health questionnaire (GHQ). Results: A wide variation in the prevalence of psychiatric disorders was found among 31 provinces of Iran. The direct estimates ranged from 3.6% to 62.6%, while the HB estimates ranged from 12.6% to 36.5%. The provincial prevalence among men ranged from 11.9% to 34.5%, while it ranged from 18.4% to 38.8% among women. The Pearson correlation coefficient between HB estimates and GHQ scores was 0.73. Conclusion: The Bayesian small area estimation provides estimation with improved precision at local levels. Detecting high-priority communities with small-area approach could lead to a better distribution of limited facilities and more effective mental health interventions

Ambiguities in existing Iranian national policies addressing excessive gaming : Commentary on: Policy responses to problematic video game use: A systematic review of current measures and future possibilities (Király et al., 2018)

Considering the scarcity of available science and controversies around effective policies addressing gaming disorder and its health-related consequences, Király et al. have conducted a systematic review on current evidence regarding this issue. We, a group of researchers in this field, would like to express our perspective from Iran. With rapid growth of gaming, Iran seems to be facing some specific policy issues and challenges, which are going to be reviewed in this short commentary

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions