Differences in schizophrenia treatments by race and ethnicity-analysis of electronic health records.

Racial disparities in prescriptions of anti-psychotics have been highlighted before. However, (i) the evidence on other medications, including anti-depressant or mood stabilizing medications is lacking, and (ii) the role of potentially confounding factors and (iii) specificity of such disparities to schizophrenia (SCZ), are still unknown. We used electronic health records (EHRs) from 224,212 adults to estimate the odds ratios of receiving a prescription for different nervous system medications among patients with SCZ of different race/ethnicity, and analogous linear models to investigate differences in prescribed medication doses. To verify specificity of the observed patterns to SCZ, we conducted analogous analyses in depression and bipolar disorder (BD) patients. We found that Black/African American (AA) and Hispanic patients with SCZ were more likely to be prescribed haloperidol (Black/AA: OR = 1.52 (1.33-1.74); Hispanic: OR = 1.32 (1.12-1.55)) or risperidone (Black/AA: OR = 1.27 (1.11-1.45); Hispanic: OR = 1.40 (1.19-1.64)), but less likely to be prescribed clozapine (Black/AA: OR = 0.40 (0.33-0.49); Hispanic: OR = 0.45 (0.35-0.58)), compared to white patients. There were no race/ethnicity-related differences in the prescribed medication doses. These patterns were not specific to SCZ: Asian, Hispanic and Black/AA patients with BD or depression were more likely to be prescribed anti-psychotics, but less likely to be prescribed antidepressants or mood-stabilizers. In conclusion, we found racial/ethnic disparities in the medications prescribed to patients with SCZ and other psychiatric conditions. We discuss the potential implications for the quality of care for patients of diverse races/ethnicities.

Migraine headache and other risk factors associated with glaucoma among the adult population living in Armenia: a case-control study.

PURPOSE: This study aimed to assess the association between migraine headache and glaucoma among the adult population living in Armenia. METHODS: This case-control study recruited 145 cases with glaucoma and 250 controls without glaucoma and other ocular disorders except refractive error from Optomed Canada Diagnostic Eye Center in Armenia. A structured questionnaire contained questions on socio-demographics, family history of glaucoma and stroke, ocular health, smoking, migraine, and obstructive sleep apnea. The Migraine Screening Questionnaire assessed possible migraine and the Berlin Questionnaire measured obstructive sleep apnea. RESULTS: The mean ages of cases and controls were 63.3 (SD = 12.3) and 39.5 (SD = 13.5), respectively. Females comprised 62.8% of cases and 69.1% of controls. A total of 17.8% of cases and 19.0% of controls had possible migraine. In the adjusted analysis older age (OR 1.17; 95% CI 1.12; 1.23), average/lower than average socio-economic status (OR 5.27; 95% CI 1.30; 21.3), and family history of glaucoma (OR 4.25; 95% CI 1.51; 11.9) were associated with high-tension glaucoma. CONCLUSION: Timely case detection of glaucoma among those with average/low socio-economic status and those with family history of glaucoma could prevent further progression of the disease. Further studies to explore the relationship between migraine headache and specific types of glaucoma may be worthwhile.

Associations between acute and chronic lifetime stressors and psychosis-risk symptoms in individuals with 22q11.2 copy number variants.

BACKGROUND: The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis. METHOD: One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS). RESULTS: The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05). CONCLUSION: Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.

Comorbidities in autism spectrum disorder and their etiologies.

Individuals with autism spectrum disorder (ASD), in addition to the core features of the disease, experience a higher burden of co-occurring medical conditions. This study sought to describe the frequency and distribution of comorbidit conditions in individuals with ASD, and systematically evaluate the possibility that pre- and postnatal exposures (e.g., preterm birth, hypoxia at birth, traumatic brain injury, and fetal alcohol syndrome) associated with ASD may also be linked with distinct comorbidities. We used the SPARK study database, launched by the Simons Foundation Autism Research Initiative (SFARI). Comorbidities considered in the study included neurological, cognitive, psychiatric, and physical conditions. The study sample consisted of 42,569 individuals with ASD and their 11,389 non-ASD siblings (full and half siblings). Majority (74%) of individuals with ASD had at least one comorbidity, and had a greater average number of comorbidities than their non-ASD siblings. Preterm birth and hypoxia at birth were the most common peri-natal exposures in the sample. In logistic regression models adjusted for covariates, these exposures were associated with several distinct comorbidities in ASD cases, including attention and behavior problems, psychiatric and neurological disorders, and growth conditions. A similar pattern of association was also observed in non-ASD siblings. Our findings underscore that individuals with ASD experience a greater burden of comorbidities, which could be partly attributable to the higher rates of perinatal exposures compared to their non-ASD siblings. Study findings, if replicated in other samples, can inform the etiology of comorbidity in ASD.

Somatic comorbidities of mental disorders in pregnancy.

BACKGROUND: Mental and physical health conditions are frequently comorbid. Despite the widespread physiological and behavioral changes during pregnancy, the pattern of comorbidities among women in pregnancy is not well studied. This study aimed to systematically examine the associations between mental and somatic disorders before and during pregnancy. METHOD: The study used data from mothers of a nationally representative birth cohort of children born in Israel (1997-2008). We compared the risk of all major somatic disorders (International Classification of Diseases, Ninth Revision) in pregnant women with and without a mental disorder. All analyses were adjusted for maternal age, child's birth year, family socioeconomic status, and the total number of maternal encounters with health services around pregnancy period. RESULTS: The analytical sample included 77,030 mother-child dyads, with 30,083 unique mothers. The mean age at child's birth was 29.8 years. Prevalence of diagnosis of mental disorder around pregnancy in our sample was 4.4%. Comorbidity between mental and somatic disorders was two times higher than the comorbidity between pairs of different somatic disorders. Of the 17 somatic disorder categories, seven were positively associated with mental health disorders. The highly prevalent comorbidities associated with mental disorders in pregnancy included e.g. musculoskeletal (OR = 1.30; 95% CI = 1.20-1.42) and digestive system diseases (OR = 1.23; 95% CI = 1.13-1.34). CONCLUSIONS: We observed that associations between maternal diagnoses and mental health stand out from the general pattern of comorbidity between nonmental health diseases. The study results confirm the need for screening for mental disorders during pregnancy and for potential comorbid conditions associated with mental disorders.

Predicting COVID-19 vaccination uptake in Armenia using the Health Belief Model: Results from a nationwide survey.

Health behavior theories have been effectively used for studying populations' awareness, attitudes, and beliefs related to COVID-19 preventative behaviors. The aim of this study was to explore the factors associated with the intention to get vaccinated against COVID-19 in the Armenian population using the Health Belief Model (HBM) as a framework. We applied stratified two-stage random sampling to conduct a telephone survey of 3,483 adults in 2021. The multi-domain survey instrument included questions on socio-demographic characteristics, COVID-19-related knowledge, COVID-19 susceptibility, severity and self-efficacy beliefs, sources of information on COVID-19, COVID-19 vaccination practice, and its benefits and barriers. We performed bivariate and hierarchical multivariate regression analysis with the entry of variables in blocks. In total, about 12% of the sample (n = 393) was vaccinated against COVID-19. Of 2,838 unvaccinated participants, about 53% (n = 1516) had an intention to get vaccinated. The final hierarchical logistic regression model containing socio-demographic characteristics, knowledge about COVID-19, and HBM constructs explained 43% of the variance in the intention to get vaccinated against COVID-19. Participants' age, employment status, average monthly expenditures, perceived threat, benefits, perceived barriers, self-efficacy, and cues to action were significant and independent predictors of the intention to get COVID-19 vaccination. This study confirmed the utility of the HBM in highlighting drivers of an important health-protective behavior in the context of pandemics. Health policy makers, communication specialists, and healthcare providers should particularly stress the effectiveness and safety of the vaccines in their efforts to increase vaccination rates and focus on unemployed and low-income population groups.

Reprint of: Advanced paternal age and risk of schizophrenia in offspring - Review of epidemiological findings and potential mechanisms.

A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.

The course, trajectories and predictors of depression 23 years after the 1988 Spitak earthquake in Armenia: A prospective cohort study.

There is a scarcity of long-term studies of depression after natural disasters. This prospective epidemiologic study evaluated the course of depression and factors associated with it among survivors 23-years post-earthquake. A geographically stratified subsample of 725 adults exposed to the Spitak earthquake was assessed for depression using DSM-III-R criteria in 1991 and 2012. Additionally, an adapted CES-D-16 scale was used to assess depressive symptoms in 2012. A fitted multi-nominal logistic regression model identified predictors of different trajectories of depression. For the whole group, the rate of clinical depression dropped from 51.5% in 1991 to 31.7% in 2012. Earthquake intensity and experiencing strong fear at baseline were strongly associated with chronic (depressed at both assessments, 18.1%) and recovered (depressed only in 1991, 33.5%) depression trajectories compared with the healthy group, with odds ratios (OR) over 4.0 and 3.0, respectively. Predictors distinguishing chronic depression included earthquake-related nuclear-family deaths (OR=3.79), chronic illnesses at baseline (OR=1.24), and social support (OR=0.91). Predictors of the late-onset trajectory (depressed only in 2012, 13.5% of the cohort) included post-earthquake trauma (OR=1.42), socioeconomic status (OR=0.45), and social support (OR=0.86). The factors associated with the different trajectories of depression provide guidance for planning more effective mental health interventions after disasters.

Comparison of Conditional and Marginal Models in Assessing a Child Nutrition Intervention in Armenia.

INTRODUCTION: Child malnutrition is a major issue in conflict zones. Evidence-based interventions and their thorough evaluation could help to eliminate malnutrition. We aimed to assess the causal effect of a community-based multidisciplinary nutrition program for children in a chronic conflict zone near the northeastern border of Armenia on two main outcomes: stunting and anemia. We further compared the interpretations and public health relevance of the obtained effect estimates. METHODS: In 2016, the study measured hemoglobin and anthropometric measures and collected data from the children's caregivers. We used propensity score matching analyses, inverse probability weighting, and overlap weighting methods to examine the average treatment effects among treated population (ATT), and among population with overlapping weights (ATO). RESULTS: The ATT for stunting among children who participated in the intervention program estimated by propensity score matching analyses (PSM-ATT) was (1.95; 95%CI 1.15-3.28). Nevertheless, children who took part in the program had a lower risk of anemia (0.28; 95%CI 0.19-0.42). The ATT, estimated by inverse probability weighting (IPTW-ATT), was slightly lower for stunting (1.82; 95%CI 1.16-2.86) while similar for anemia (0.33; 95%CI 0.23-0.46) compared to PSM-ATT. Compared to the IPTW-ATT and PSM-ATT the ATO was lower for stunting (1.75; 95%CI 1.14-2.68) and similar for anemia (0.31; 95%CI 0.22-0.43). DISCUSSION: Marginal models could be used in similar quasi-experimental settings to identify the causal effect of interventions in specific populations of interest. Nonetheless, these methods do not eliminate threats to internal validity. Thorough study design and accurate data collection are necessary to improve the efficiency of marginal models.

Visual impairment and associated risk factors in patients with diabetes mellitus in Tavush and Armavir provinces of Armenia.

BACKGROUND: Visual impairment (VI) and blindness remain serious public health problems among patients with diabetes. This study assessed the prevalence of VI and its associated risk factors in individuals with diabetes mellitus (DM) in Armenia. METHODS: This cross-sectional study recruited 1287 people with DM. All participants underwent comprehensive ophthalmic examination and responded to a structured questionnaire on sociodemographic and health characteristics, health-seeking behavior, and ocular health. The presence of eye diseases and VI was defined based on the International Classification of Diseases-11. Descriptive statistics and logistic regression were used to address the study objectives. RESULTS: The mean age of participants was 61.5 (SD = 9.6) ranging from 19.4 to 99.8 years. The mean duration of diabetes was 7.4 years. The majority of participants (70.5%) were women. The prevalence of VI and blindness was 12.1% and 0.9%, respectively. Overall, 22.4% of participants had diabetic retinopathy. In the adjusted analysis, advanced age (OR = 1.08; 95%CI: 1.06-1.11), higher education (OR = 0.37; 95%CI: 0.19-0.74), diabetes duration (OR = 1.05; 95%CI: 1.02-1.08), the presence of diabetic retinopathy (OR = 3.61; 95%CI: 2.38-5.46), age-related macular degeneration (OR = 1.88; 95%CI: 1.15-3.05), cataract (OR = 2.45; 95%CI: 1.66-3.63), and glaucoma (OR = 2.32; 95%CI: 1.25-4.30) were associated with VI. CONCLUSION: The findings highlight the importance and need for regular eye screening and diabetes prevention programs in the country. Continuous educational programs on diabetes self-management among patients with DM can reduce complications of diabetes including vision loss due to diabetes.

Advanced paternal age and risk of schizophrenia in offspring - Review of epidemiological findings and potential mechanisms.

A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.

Maternal health around pregnancy and autism risk: a diagnosis-wide, population-based study.

BACKGROUND: Many studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagnoses around pregnancy and ASD risk in offspring. METHODS: This exploratory case-cohort study included children born in Israel from 1997 to 2008, and followed up until 2015. We used information on all ICD-9 codes received by their mothers during pregnancy and the preceding year. ASD risk associated with each of those conditions was calculated using Cox proportional hazards regression, adjusted for the confounders (birth year, maternal age, socioeconomic status and number of ICD-9 diagnoses during the exposure period). RESULTS: The analytic sample consisted of 80 187 individuals (1132 cases, 79 055 controls), with 822 unique ICD-9 codes recorded in their mothers. After extensive quality control, 22 maternal diagnoses were nominally significantly associated with offspring ASD, with 16 of those surviving subsequent filtering steps (permutation testing, multiple testing correction, multiple regression). Among those, we recorded an increased risk of ASD associated with metabolic [e.g. hypertension; HR = 2.74 (1.92-3.90), p = 2.43 × 10-8], genitourinary [e.g. non-inflammatory disorders of cervix; HR = 1.88 (1.38-2.57), p = 7.06 × 10-5] and psychiatric [depressive disorder; HR = 2.11 (1.32-3.35), p = 1.70 × 10-3] diagnoses. Meanwhile, mothers of children with ASD were less likely to attend prenatal care appointment [HR = 0.62 (0.54-0.71), p = 1.80 × 10-11]. CONCLUSIONS: Sixteen maternal diagnoses were associated with ASD in the offspring, after rigorous filtering of potential false-positive associations. Replication in other cohorts and further research to understand the mechanisms underlying the observed associations with ASD are warranted.

Trans-nasal high-flow dehumidified air in acute migraine headaches: A randomized controlled trial.

BACKGROUND: Intranasal high flow of dehumidified (dry) air results in evaporative cooling of nasal passages. In this randomized clinical trial, we investigated the effect of dry gas induced nasal cooling on migraine headaches. METHODS: In this single-blind study, acute migraineurs were randomized to either nasal high-flow dry oxygen, dry air, humidified oxygen or humidified air (control) at 15 L/min for 15 min. All gases were delivered at 37°C. Severity of headache and other migraine associated symptoms (International Classification for Headache Disorders, 3rd edition criteria) were recorded before and after therapy. The primary endpoint was change in pain scores, while changes in nausea, photosensitivity and sound sensitivity scores served as secondary endpoints. A linear regression model was employed to estimate the impact of individual treatment components and their individual interactions. RESULTS: Fifty-one patients (48 ± 15 years of age, 82% women) were enrolled. When compared to the control arm (humidified air), all therapeutic arms showed a significantly greater reduction in pain scores (primary endpoint) at 2 h of therapy with dry oxygen (-1.6 [95% CI -2.3, -0.9]), dry air (-1.7 [95% CI -2.6, -0.7)]), and humidified oxygen (-2.3 [95% CI -3.5, -1.1]). A significantly greater reduction in 2-h photosensitivity scores was also noted in all therapeutic arms (-1.8 [95% CI -3.2, -0.4], dry oxygen; -1.7 [95% CI -2.9, -0.4], dry air; (-2.1 [95% CI -3.6, -0.6], humidified oxygen) as compared to controls. The presence of oxygen and dryness were independently associated with significant reductions in pain and photosensitivity scores. No adverse events were reported. CONCLUSION: Trans-nasal high-flow dry gas therapy may have a role in reducing migraine associated pain.Clinical Trial registration: NCT04129567.

Noninvasive biomarkers for prediction and diagnosis of heart transplantation rejection.

For most patients with end-stage heart failure, heart transplantation is the treatment of choice. Allograft rejection is one of the major post-transplantation complications affecting graft outcome and survival. Recent advancements in science and technology offer an opportunity to integrate genomic and other omics-based biomarkers into clinical practice, facilitating noninvasive evaluation of allograft for diagnostic and prognostic purposes. Omics, including gene expression profiling (GEP) of blood immune cell components and donor-derived cell-free DNA (dd-cfDNA) are of special interest to researchers. Several studies have investigated levels of dd-cfDNA and miroRNAs in blood as potential markers for early detection of allograft rejection. One of the achievements in the field of transcriptomics is AlloMap, GEP of peripheral blood mononuclear cells (PBMC), which can identify 11 differentially expressed genes and help with detection of moderate and severe acute cellular rejection in stable heart transplant recipients. In recent years, the utilization of GEP of PBMC for identifying differentially expressed genes to diagnose acute antibody-mediated rejection and cardiac allograft vasculopathy has yielded promising results. Advancements in the field of metabolomics and proteomics as well as their potential implications have been further discussed in this paper.

Frozen conflict in the midst of a global pandemic: potential impact on mental health in Armenian border communities.

Armenia has been in a conflict with its neighbor, Azerbaijan, since 1988. Civilians in Tavush Province are regularly affected by ceasefire violations along the armed border with recent escalations further threatening the population's safety. In the midst of the COVID-19 pandemic, concerns regarding the mental health of border village residents in Armenia are prevalent. We present context-related factors of psychiatric illness, the prevalence of mental health disorders, and the state of mental health services in Armenia. We recommend directing greater attention towards the mental health status of civilians residing in conflict zones during the ongoing COVID-19 pandemic.

Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999-2015.

OBJECTIVE: It is unclear whether relatively low glycated haemoglobin (HbA1c) levels are beneficial or harmful for the long-term health outcomes among people without diabetes. We aimed to investigate the association between low HbA1c levels and mortality among the US general population. METHODS: This study includes a nationally representative sample of 39 453 US adults from the National Health and Nutrition Examination Surveys 1999-2014, linked to mortality data through 2015. We employed the parametric g-formula with pooled logistic regression models and the ensemble machine learning algorithms to estimate the time-varying risk of all-cause and cardiovascular mortality by HbA1c categories (low, 4.0 to <5.0%; mid-level, 5.0 to <5.7%; prediabetes, 5.7 to <6.5%; and diabetes, ≥6.5% or taking antidiabetic medication), adjusting for 72 potential confounders including demographic characteristics, lifestyle, biomarkers, comorbidities and medications. RESULTS: Over a median follow-up of 7.5 years, 5118 (13%) all-cause deaths, and 1116 (3%) cardiovascular deaths were observed. Logistic regression models and machine learning algorithms showed nearly identical predictive performance of death and risk estimates. Compared with mid-level HbA1c, low HbA1c was associated with a 30% (95% CI, 16 to 48) and a 12% (95% CI, 3 to 22) increased risk of all-cause mortality at 5 years and 10 years of follow-up, respectively. We found no evidence that low HbA1c levels were associated with cardiovascular mortality risk. The diabetes group, but not the prediabetes group, also showed an increased risk of all-cause mortality. CONCLUSIONS: Using the US national database and adjusting for an extensive set of potential confounders with flexible modelling, we found that adults with low HbA1c were at increased risk of all-cause mortality. Further evaluation and careful monitoring of low HbA1c levels need to be considered.

How Effective Is Iron Supplementation During Pregnancy and Childhood in Reducing Anemia Among 6-59 Months Old Children in India?

Objectives: The study sought to identify whether iron and folic acid supplementation of pregnant women and preschool children is associated with child's anemia status and the predictors of anemia among children in India. Design: Secondary data analysis was performed using the National Family Health Survey 4 data. Multivariable logistic regression was used to identify the adjusted associations between child's anemia status and iron supplementation, both during pregnancy and childhood. Also, a model of significant predictors of anemia among children was fitted. Setting: India. Participants: Youngest children (6-59 months) in families. Results: The adjusted association between supplementation during pregnancy and child's anemia status was significant (p = 0.010), whereas the adjusted association between supplementation during childhood and child's anemia status was insignificant (p = 0.16). The variables independently associated with anemia status of the child included younger age (95% CI 2.67-2.86), child's recent diarrhea (95% CI 1.02-1.14), low birth weight (95% CI 1.17-1.27), current underweight (95% CI 1.14-1.28), diet diversity score (95% CI 0.96-0.98), higher birth order (95% CI 1.01-1.05), mother's current anemia (95% CI 1.68-1.81), months of breastfeeding (95% CI 0.99-1.00), no/primary education (95% CI 1.23-1.35), family's low wealth index (95% CI 1.11-1.23), and backward caste (95% CI 1.04-1.14). Conclusions: The National Iron Plus Initiative strategy of child's iron supplementation should be evaluated to identify the reasons of its ineffectiveness in anemia reduction. In addition, vulnerable groups of children, i.e., children from poor and less educated families and those with low birth weight, higher birth order, and poor nutritional status, should be targeted first with anemia reduction interventions.