The impact of COVID-19 public health measures on the utilization of antipsychotics in schizophrenia in Manitoba - A population-based study.

PURPOSE: During the COVID-19 pandemic, public health measures were implemented, yet it is unknown whether these measures affected medication access in those with schizophrenia (SCZ). This study aimed to assess whether the antipsychotic utilization in SCZ changed during the pandemic. METHODS: We used dispensed prescription drug data from the Canadian province of Manitoba in individuals with SCZ using linked administrative data from the Manitoba Population Research Data Repository. The quarterly incident and prevalent dispensation of antipsychotics at two periods were compared with the expected trend (April 1, 2015 to April 1, 2020 and 2021) using linear autoregression. We stratified the primary results by age and sex and examined multiple subgroups. RESULTS: There were 9045 individuals with SCZ in the first fiscal quarter of 2020. The prevalent use of the most common antipsychotics were: olanzapine (206.7/1000), risperidone (190.8/1000), quetiapine (174.4/1000), and clozapine (100.9/1000). The overall prevalent use of antipsychotics remained stable during the pandemic compared with the expected trend. A significant decrease in the incident use in April-June 2020 (estimate: -1.3, 95%CI:-2.2,-0.3) was noted compared with the expected. A significantly higher incidence of atypical antipsychotics (estimate: 1.4, 95%CI: 0.2,2.5) and risperidone separately (estimate: 1.8, 95%CI: 0.2,3.3) was noted in 2021 compared with expected. CONCLUSION: This study found a decline in the receipt of antipsychotics for people with SCZ during the initial implementation of COVID-19 public health measures, particularly on the overall incidence. Future work on investigating the impact of these trends on SCZ outcomes is needed to inform future pandemic-related policies.

Trend in Prescription Medication Utilization for Opioid Use Disorder and Alcohol Use Disorder From 2015 to 2021: A Population-wide Study in a Canadian Province.

OBJECTIVE: To examine the quarterly incidence and prevalence of medications for opioid use disorder (OUD) and alcohol use disorder (AUD) from 2015 to 2021. METHODS: A retrospective population-wide observational study in Manitoba, Canada, was conducted using administrative claims data from the Manitoba Centre for Health Policy to examine the incidence and prevalence of OUD (methadone, buprenorphine-naloxone, buprenorphine) or AUD medications (naltrexone, acamprosate, disulfiram) per 10,000 individuals in each quarter between January 1, 2015, and December 31, 2021. RESULTS: There were 1179 and 451 individuals who received at least one prescription for OUD and AUD, respectively, in the first quarter of 2020. The prevalence of OUD medications more than doubled from 6.3 to 14.3 per 10,000 from January 1, 2015, to December 31, 2021. Likewise, AUD medication prevalence increased almost 10-fold from 0.68 to 6.5 per 10,000 from January 1, 2015, to December 31, 2021, primarily due to naltrexone. The incidence of AUD prescription use increased 8.6-fold from 0.29 to 2.51 per 10,000 during the study period. In contrast, the incidence of opioid agonist therapy declined from 2.1 per 10,000 in the first quarter of 2015 to 0.53 per 10,000 the first quarter of 2016, primarily due to methadone. Whereas methadone incidence declined, buprenorphine-naloxone incidence increased almost 15-fold during the study period. CONCLUSION: An increase in both AUD medication prevalence and incidence in addition to an increase in buprenorphine-naloxone incidence was observed. These findings reflect an increase in the uptake of medications for treating AUD and OUD following changes to improve coverage and access to these medications.

Third generation antiseizure medications exposure during pregnancy and neonatal adverse birth outcomes: A systematic review.

Background: Third generation antiseizure medications (ASMs) are currently used for seizure control as well as several other indications, including pain management and psychiatric disorders. As a result, maternal exposure to third generation ASMs during pregnancy has become increasingly prevalent. The current systematic review aimed to summarize the published evidence on third generation ASMs and their effect on preterm birth, cesarean section (c-section) and fetal loss. Methods: The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, Cochrane Library and Scopus until September 2022. Results: We screened 2987 studies, and identified 32 studies or case reports for inclusion, however only one study utilized a control group. Narrative systematic evidence synthesis was conducted for brivaracetam, eslicarbazepine, fosphenytoin, lacosamide and perampanel. Conclusion: Due to the scarcity and quality of published studies, drawing clear-cut conclusions regarding third generation ASMs and the outcomes of interest is challenging. More comparative safety studies focusing on neonatal safety of third generation ASMs in pregnancy are essential.

Rates and determinants of breastfeeding initiation in women with and without epilepsy: A 25-year study.

PURPOSE: To examine the rates and determinants of breastfeeding initiation (BFI) amongst women with epilepsy (WWE) and women without epilepsy (WWoE) in Manitoba, Canada. METHODS: We conducted a retrospective cohort study using province-wide health databases from 1995 to 2019. Annual BFI rates for WWE and WWoE were examined. Multivariable logistic regression models were used to quantify the association between maternal and infant characteristics and BFI in both groups. RESULTS: During the study period, 1,331 pregnant WWE and 357,334 WWoE were examined. Among WWE, 70.9 % initiated breastfeeding compared to 81.8 % among WWoE. We observed a significant small increase in yearly trends of BFI in both WWE (ß=0.45, p = 0.008) and WWoE (ß=0.23, p < 0.001). In WWE, BFI was associated with caesarean delivery (aOR=0.72,95 % CI: 0.53-0.97), chronic pain (aOR=0.67,95 % Cl: 0.46-0.97), lower income (aOR=0.34,95 % Cl: 0.26-0.44), and gestational age (aOR= 1.09,95 % CI:1.01-1.18). In WWoE, BFI was associated with chronic pain (aOR=0.83,95 % Cl: 0.80-0.86), lower income (aOR=0.45, 95 %CI:0.44-0.46), mood and anxiety disorder (aOR=0.84,95 % CI:0.81-0.86), and gestational age (aOR=1.13,95 % Cl:1.12-1.14). The use of any ASM (aOR=0.66,95 % Cl:0.51-0.85), new generation (aOR=0.86,95 % Cl: 0.62-1.20), polytherapy (aOR=0.46,95 % Cl: 0.31-0.69) and gabapentin (aOR=0.49,95 % Cl: 0.17-1.24) reduced the likelihood of BFI among WWE. CONCLUSION: BFI was approximately 10 % lower in WWE compared to WWoE. Determinants such as low income, ASM use, and comorbidities were significant contributors to a reduced BFI in both groups. Targeted counselling for WWE on breastfeeding benefits is essential. Further research is needed to investigate breastfeeding continuation in WWE.

Genetic Prognostic Factors in Adult Diffuse Gliomas: A 10-Year Experience at a Single Institution.

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical variables and molecular profiles may have affected overall survival (OS) over the past ten years. A retrospective study was conducted at Sina Hospital in Tehran, Iran and examined patients with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GB patients and sociodemographic as well as clinical factors and molecular profiling based on IDH1, O-6-Methylguanine-DNA Methyltransferase (MGMT), TERTp, and epidermal growth factor receptor (EGFR) amplification (EGFR-amp) status. Kaplan-Meier and multivariate Cox regression models were used to assess patient survival. A total of 178 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 61.0%. Among the 127 patients with available IDH measurements, 100 (78.7%) exhibited mutated IDH1 (IDH1-mut) tumors. Of the 127 patients with assessed MGMT promoter methylation (MGMTp-met), 89 (70.1%) had MGMT methylated tumors. Mutant TERTp (TERTp-mut) was detected in 20 out of 127 cases (15.7%), while wildtype TERTp (wildtype TERTp-wt) was observed in 107 cases (84.3%). Analyses using multivariable models revealed that age at histological grade (p < 0.0001), adjuvant radiotherapy (p < 0.018), IDH1 status (p < 0.043), and TERT-p status (p < 0.014) were independently associated with OS. Our study demonstrates that patients with higher tumor histological grades who had received adjuvant radiotherapy exhibited IDH1-mut or presented with TERTp-wt experienced improved OS. Besides, an interesting finding showed an association between methylation of MGMTp and TERTp status with tumor location.

Risks of congenital malformations and neonatal intensive care unit admissions with gabapentin use in pregnancy: A cohort study and scoping review with meta-analysis.

BACKGROUND: The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety. OBJECTIVES: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence. METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results. RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99, 95% CI 1.70, 2.32). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%). CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.

Weight loss associated with semaglutide treatment among people with HIV.

OBJECTIVE: There is limited real-world evidence about the effectiveness of semaglutide for weight loss among people with HIV (PWH). We aimed to investigate weight change in a US cohort of PWH who initiated semaglutide treatment. DESIGN: Observational study using the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: We identified adult PWH who initiated semaglutide between 2018 and 2022 and with at least two weight measurements. The primary outcome was within-person bodyweight change in kilograms at 1 year. The secondary outcome was within-person Hemoglobin A1c percentage (HbA1c) change. Both outcomes were estimated using multivariable linear mixed model. RESULTS: In total, 222 new users of semaglutide met inclusion criteria. Mean follow-up was 1.1 years. Approximately 75% of new semaglutide users were men, and at baseline, mean age was 53 years [standard deviation (SD): 10], average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (viral load < 50 copies/ml). In the adjusted mixed model analysis, treatment with semaglutide was associated with an average weight loss of 6.47 kg at 1 year (95% CI -7.67 to -5.18) and with a reduction in HbA1c of 1.07% at 1 year (95% CI -1.64 to -0.50) among the 157 PWH with a postindex HbA1c value. CONCLUSION: Semaglutide was associated with significant weight loss and HbA1c reduction among PWH, comparable to results of previous studies from the general population.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

ABSTRACT: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ). RESULTS: Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = -  2.18; 95% CI -  2.88 to -  1.49; I 2 =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = -  2.10; 95% CI -  3.09 to -  1.11; I2 = 71%; n = 8 studies) and zonisamide (MD = -  2.31; 95% CI -  3.35 to -  1.27; I2 = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results. CONCLUSIONS: Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.

Annual trends of hepatitis C virus infection in Manitoba between 1998 and 2018: A focus on special populations.

Background: Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality worldwide. Epidemiological data of HCV infection in the Canadian province of Manitoba are limited. Methods: A population-based retrospective study was conducted using data from the Manitoba Centre for Health Policy repository. Using the test results provided by the Cadham provincial laboratory, individuals in Manitoba with a diagnosis of HCV infection were identified. Annual prevalence and incidence rates (crude and standardized) were calculated for the overall population and stratified by sex, regional health authority (RHA), residence area, income quintile, and special population groups (children, older adults, and pregnant persons). Results: A total of 8,721 HCV cases were diagnosed between 1998 and 2018 in Manitoba. Overall crude HCV incidence and prevalence were estimated as 0.03% and 0.37% during the study period, respectively. No significant change was observed in the standardized HCV incidence rate (per 100,000) during the study period (54.3 in 1998 and 54.8 in 2018). However, the standardized HCV prevalence (per 100,000) increased from 52.5 (95% CI 39.2-68.7) in 1998 to 655.2 (95% CI 605.9-707.3) in 2018. An overall average incidence rate based on sex, RHA, region, income, and special population groups was observed to be higher in males (40.1), Winnipeg RHA (42.7), urban region (42.3), low-income quintiles (78.5), and pregnant persons (94.3), respectively. Conclusion: Although incidence rates of HCV infection in Manitoba appeared to have initially declined, rates showed an upward trend by the end of the study period while prevalence increased steadily.

Tobacco Smoking and Pack-Years Are Associated With Frailty Among People With HIV.

BACKGROUND: Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population. METHODS: We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count. RESULTS: The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration. CONCLUSIONS: Among PWH, smoking status and duration are associated with incident and worsening frailty.

Adherence to Psychotropic Medication Before and During COVID-19: A Population-Wide Retrospective Observational Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and associated public health measures have shifted the way people access health care. We aimed to study the effects of the COVID-19 pandemic on psychotropic medication adherence. METHODS: A retrospective cohort study using administrative data from the Manitoba Centre for Health Policy Manitoba Population Research Data Repository was conducted. Outpatients who received at least 1 prescription for an antidepressant, antipsychotic, anxiolytic/sedative-hypnotic, cannabinoid, lithium, or stimulants from 2015 to 2020 in Manitoba, Canada, were included. Adherence was measured using the proportion of individuals with a mean possession ratio of ≥0.8 over each quarter. Each quarter of 2020 after COVID-19-related health measures were implemented was compared with the expected trend using autoregression models for time series data plus indicator variables. Odds ratio of drug discontinuation among those previously adherent in 2020 was compared with each respective quarter of 2019. RESULTS: There were 1,394,885 individuals in the study population in the first quarter of 2020 (mean [SD] age, 38.9 [23.4] years; 50.3% female), with 36.1% having a psychiatric diagnosis in the preceding 5 years. Compared with the expected trend, increases in the proportions of individuals adherent to antidepressants and stimulants were observed in the fourth quarter (October-December) of 2020 (both P < 0.001). Increases in the proportions of individuals with anxiolytic and cannabinoid adherence were observed in the third quarter (July-September) of 2020 (both P < 0.05), whereas a decrease was seen with stimulants in the same quarter ( P < 0.0001). No significant changes were observed for antipsychotics. All drug classes except lithium had decreases in drug discontinuation in previously adherent patients during the pandemic compared with 2019. CONCLUSIONS: Improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted was observed. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic.

Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study.

BACKGROUND: The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. OBJECTIVE: To determine whether HCTZ is associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors and calcium channel blockers. METHODS: Two new-user, active comparator cohorts were assembled using 6 Canadian databases. Site-specific hazard ratios (HRs) with 95% CIs were estimated using standardized morbidity ratio weighted Cox proportional hazard models and pooled using random-effects meta-analysis. RESULTS: HCTZ was not associated with an overall increased risk of keratinocyte carcinoma compared with angiotensin-converting enzyme inhibitors or calcium channel blockers, although increased risks were observed with longer durations (≥10 years; HR: 1.12; 95% CI: 1.03-1.21) and higher cumulative doses (≥100,000 mg; HR: 1.49; 95% CI: 1.27-1.76). For melanoma, there was no association with angiotensin-converting enzyme inhibitors, but a 32% increased risk with calcium channel blockers (crude incidence rates: 64.2 vs 58.4 per 100,000 person-years; HR: 1.32; 95% CI: 1.19-1.46; estimated number needed to harm at 5 years of follow-up: 1627 patients), with increased risks with longer durations and cumulative doses. LIMITATIONS: Residual confounding due to the observational design. CONCLUSIONS: Increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ.

Prescription trends of antiseizure medications before and during the COVID-19 pandemic.

Introduction: Given the lack of evidence on how the COVID-19 pandemic impacted antiseizure medication (ASM) use, we examined the trends of ASMs before and during COVID-19. Methods: We conducted a population-based study using provincial-level health databases from Manitoba, Canada, between 1 June 2016 and 1 March 2021. We used interrupted time series autoregressive models to examine changes in the prevalence and incidence of ASM prescription rates associated with COVID-19 public health restrictions. Results: Among prevalent users, the COVID-19 pandemic led to a significant increase in new-generation ASMs with a percentage change of 0.09% (p = 0.03) and a significant decrease in incidence use of all ASMs with a percentage change of -4.35% (p = 0.04). Significant trend changes were observed in the prevalent use of new-generation ASMs (p = 0.04) and incidence use of all (p = 0.04) and new-generation ASMs (p = 0.02). Gabapentin and clonazepam prescriptions contributed 37% of prevalent and 54% of incident use. Conclusion: With the introduction of public health measures during COVID-19, small but significant changes in the incident and prevalent use of ASM prescriptions were observed. Further studies are needed to examine whether barriers to medication access were associated with potential deterioration in seizure control among patients. Conference presentation: The results from this study have been presented as an oral presentation at the 38th ICPE, International Society of Pharmacoepidemiology (ISPE) annual conference in Copenhagen.

Antiseizure medication use during pregnancy and neonatal growth outcomes: A systematic review and meta-analysis.

AIMS: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy. METHODS: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW. CONCLUSIONS: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV.

OBJECTIVE: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making. DESIGN: We followed PWH for up to 2 years to identify short-term predictors of becoming frail. METHODS: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots. RESULTS: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff. CONCLUSIONS: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics.

Sex, Gender, and the Regulation of Prescription Drugs: Omissions and Opportunities.

The regulation of prescription drugs is an important health, safety, and equity issue. However, regulatory processes do not always consider evidence on sex, gender, and factors such as age and race, omissions that advocates have highlighted for several decades. Assessing the impact of sex-related factors is critical to ensuring drug safety and efficacy for females and males, and for informing clinical product monographs and consumer information. Gender-related factors affect prescribing, access to drugs, needs and desires for specific prescribed therapies. This article draws on a policy-research partnership project that examined the lifecycle management of prescription drugs in Canada using a sex and gender-based analysis plus (SGBA+) lens. In the same time period, Health Canada created a Scientific Advisory Committee on Health Products for Women, in part to examine drug regulation. We report on grey literature and selected regulatory documents to illustrate the extent to which sex and gender-based analysis plus (SGBA+) is utilized in regulation and policy. We identify omissions in the management of prescription drugs, and name opportunities for improvements by integrating SGBA+ into drug sponsor applications, clinical trials development, and pharmacovigilance. We report on recent efforts to incorporate sex disaggregated data and recommend ways that the management of prescription drugs can benefit from more integration of sex, gender, and equity.

Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study.

BACKGROUND: Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES). METHODS: Using the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models. RESULTS: We examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (ß2)=1.37; p=0.0247) and stillbirths (immediate increase (ß2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (ß2)=3.17; p=0.0057) and 27.19% (immediate increase (ß2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (ß3) =-0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047). CONCLUSION: While the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.

Vaporized Nicotine (E-Cigarette) and Tobacco Smoking Among People With HIV: Use Patterns and Associations With Depression and Panic Symptoms.

BACKGROUND: Vaporized nicotine (VN) use is increasing among people with HIV (PWH). We examined demographics, patterns of use, depression, and panic symptoms associated with VN and combustible cigarette (CC) use among PWH. METHODS: We analyzed VN use among PWH in care at 7 US sites. PWH completed a set of patient-reported outcomes, including substance use and mental health. We categorized VN use as never vs. ever with the frequency of use (days/month) and CC use as never, former, or current. We used relative risk regression to associate VN and CC use, depression, and panic symptoms. Linear regression estimated each relationship with VN frequency. Models were adjusted for demographics. RESULTS: Among 7431 PWH, 812 (11%) reported ever-using VN, and 264 (4%) reported daily use. Half (51%) of VN users concurrently used CC. VN users were more likely than those without use to be younger, to be White, and to report ever-using CC. PWH reporting former CC use reported ≥8.5 more days per month of VN use compared with never CC use [95% confidence interval (95% CI): 5.5 to 11.5 days/month] or current CC use (95% CI: 6.6 to 10.5 days/month). Depression (relative risk: 1.20 [95% CI: 1.02 to 1.42]) and panic disorder (1.71 [95% CI: 1.43 to 2.05]) were more common among PWH ever-using VN. Depression was common among PWH using VN (27%) and CC (22%), as was panic disorder (21% for VN and 16% for CC). CONCLUSION: Our study elucidated demographic associations with VN use among PWH, revealed the overlap of VN and CC use, and associations with depression/panic symptoms, suggesting roles of VN in self-medication and CC substitution, warranting further longitudinal/qualitative research.

Sex differences among users of NSAIDs and opioids during COVID-19 Pandemic.

BACKGROUND: Sex-based inequalities in healthcare have been exposed and amplified during the COVID-19 pandemic. However, few studies have reported sex differences in medication utilization and no studies have examined sex differences in prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids utilization. AIM: To compare the utilization patterns of prescribed NSAIDs and opioids between males and females in Manitoba, Canada during the COVID-19 pandemic. METHOD: A cohort of incident and prevalent users of prescribed NSAIDs and opioids was created. Interrupted times series analysis using autoregressive models were used to evaluate the quarterly change in the prevalent and incident users before and after COVID-19 restrictions were applied (first quarter of 2020). RESULTS: COVID-19 restrictions were associated with a significant decrease in the utilization of prescribed NSAIDs and opioids in all users, followed by a revert to the pre-pandemic trends. Among female prevalent and incident NSAIDs users, there was a significant change in trend after COVID-19 restrictions were introduced (ß3 = 0.087 and 0.078, P = 0.023 and 0.028, respectively). However, there was non-significant change in trend among male prevalent and incident NSAIDs and opioids users during the pandemic. CONCLUSION: In this study, a significant sharp decline in the use of prescribed NSAIDs and opioids was shown in both sexes at the onset of the pandemic. However, a significant upward trend is observed in female NSAIDs users as restrictions began to be lifted.