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.

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.

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.

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.

Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis.

AIMS: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). METHODS: We conducted multicentre matched cohort studies with secondary meta-analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all-cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta-analyses. RESULTS: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint. CONCLUSION: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran.

The impact of COVID-19 first wave national lockdowns on perinatal outcomes: a rapid review and meta-analysis.

BACKGROUND: Since the emergence of COVID-19, preventative public health measures, including lockdown strategies, were declared in most countries to control viral transmission. Recent studies and anecdotes have reported changes in the prevalence of perinatal outcomes during national COVID-19lockdowns.The objective of this rapid review was to evaluate the impact of COVID-19 lockdowns on the incidence of low birth weight (LBW), preterm birth (PTB), and stillbirth. METHODS: Two reviewers searched EMBASE, CORD-19, LitCovid (PubMed), WHO Global research on corona virus disease (COVID-19), and MedRxiv for studies published in English from the first reports on COVID-19 until 17 July 2021. Perinatal outcomes of interest included LBW (< 2500 g), PTB (< 37 weeks), and stillbirth. RESULTS: Of the 1967 screened articles, 17 publications met the inclusion criteria (14 cohort studies, 1 case control and 2 cross-sectional studies). Studies included data from Denmark, UK, Ireland, Nepal, Italy, Israel, Botswana, Australia, China, Netherlands, Saudi Arabia, Austria, Zimbabwe, India, and Spain. The total sample size ranged from 3399 to 1,599,547 pregnant women. Thirteen studies examined PTB with conflicting results, reporting both an increase and a decrease in PTB incidence, with odds ratios [95% CI] ranging from 0.09 [0.01, 0.40] to 1.93 [0.76, 4.79]. Three studies found a decrease in LBW rates during lockdowns, one of which was statistically significant, with a rate ratio of 3.77 [1.21, 11.75]. Ten studies examined stillbirth rates, including four studies reporting a statistically significant increase in stillbirth rates, with adjusted relative risk ranging from 1.46 [1.13, 1.89] to 3.9 [1.83, 12.0]. Fourteen studies contained data that could be combined in a meta-analysis comparing perinatal outcomes before and during lockdown. We found that lockdown measures were associated with a significant risk of stillbirth with RR = 1.33 [95% CI 1.04, 1.69] when compared to before lockdown period. However, lockdown measures were not associated with a significant risk of PTB, LBW and VLBW compared to prepandemic periods. CONCLUSIONS: This review provides clues about the severity of the indirect influence of COVID-19 lockdown implementation; however, the criteria that lead to unexpected changes in LBW, PTB, and stillbirth remains unclear. Large studies showed conflicting results, reporting both increases and decreases in selected perinatal outcomes. Pooled results show a significant association between lockdown measures and stillbirth rates, but not low birth weight rates. Further studies examining the differences in other countries' lockdowns and sociodemographic groups from low to middle-income countries are needed. Exploration of perinatal outcomes during COVID-19 lockdown poses an opportunity to learn from and make changes to promote the reduction of the leading causes of childhood mortality worldwide.

The impact of life stresses on physical activity participation during adolescence: A 5-year longitudinal study.

Life stresses (LS) could affect levels of physical activity (PA) during adolescence, however research is limited. As different types of PA may have different determinants, the effects of LS on participation in moderate-to-vigorous PA (MVPA) and on organized and unorganized PA (OPA, UPA) were examined in a sample of 937 students (10-11 years-old) followed up over five years. Questionnaires were administered three times per year as part of the Monitoring Activities for Teenagers to Comprehend their Habits (MATCH) study. A total of 16 survey cycles were available for this analysis. At each survey cycle, participants reported exposure to nineteen LS, number of days per week attaining at least 60 min of MVPA, and participation in OPA and in UPA. LS were classified as personal or extrinsic life events, or personal or extrinsic life circumstances. Relationships among the four LS categories and PA outcomes were assessed using gender stratified mixed effects models. Personal circumstances attenuated the increase in MVPA in late childhood, and accentuated the decrease in MVPA in early adolescence (p < 0.001). In contrast, experiencing more extrinsic events attenuated the decrease in the number of reported UPA (p < 0.05). Among girls, experiencing more personal events attenuated the decrease in the number of UPA and OPA by 4.8% and 5.1% respectively. Among boys, experiencing more extrinsic circumstances attenuated the decrease in the number of UPA by 3.4%. The effect of LS on PA differed by gender and by type of PA, highlighting the need for careful tailoring of interventions.

The Impact of Different Case Ascertainment Definitions on the Prevalence of Major Congenital Malformations and their Association with Asthma During Pregnancy.

Objectives To compare the prevalence of major malformations using different case ascertainment definitions and to evaluate their impact on maternal asthma-major malformations association. Methods A cohort of pregnancies with and without asthma between 1990 and 2010 was formed. We used two classification methods: the Two step Congenital Malformation Classification (TCMC) and the Canadian Congenital Anomalies Surveillance System (CCASS). Within each method, three case definitions were compared: (1) ≥1 diagnosis in the hospital database; (2) ≥1 diagnosis in the hospital database or ≥2 in the medical claims; and (3) ≥1 diagnosis in the hospital database or ≥1 in the medical claims. We calculated the prevalence of major malformations and adjusted odds ratios (aORs) for maternal asthma association. Results Of 467,946 pregnancies, 12.3 % were with active asthma. The prevalence estimates were: TCMC 5.10-7.08 % and CCASS 7.03-10.57 %. Asthma-major malformations association was weaker with the CCASS (aOR 1.14-1.20) versus TCMC (aOR 1.22-1.26). Discussion The case ascertainment definitions with ≥1 hospitalization are likely to be the most reliable in similar administrative databases. The case ascertainment definition had a considerable impact on the prevalence of major malformations, but hardly influenced the aORs. Future studies should formally assess the validity of the case ascertainment definitions and allow generalizability to other maternal exposures.

Systematic procedure for the classification of proven and potential teratogens for use in research.

BACKGROUND: Although there is strong evidence that some medications are teratogenic, the current lists of teratogens to be used in research are outdated. The objective of this study was to develop an updatable and systematic procedure to the classification of medications proven and potentially teratogenic in the first trimester of pregnancy, for use in research. METHODS: We developed a two-step procedure for teratogen classification. Step 1 includes classifying the medications from Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk (9th ed.) into two provisional lists: (1) teratogenic medications, and (2) potentially teratogenic medications. We also searched other references to add other medications. In Step 2, the Teratology Information System (TERIS) database was searched, and the medication was classified as teratogenic or potentially teratogenic according to a newly developed scheme. Expert consensus was used if a medication was not recorded in TERIS. RESULTS: A total of 114 medications were identified in Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk, with 57 medications in each provisional list. Seventy-eight medications were identified in other sources. A total of 135 medications were included in Step 2; the TERIS scheme classified 23 medications, and 112 medications required expert opinion. The two experts agreed on 78.6% of the medications (kappa = 0.63). We identified 91 teratogenic and 81 potentially teratogenic medications. CONCLUSION: Using reliable references, we established a systematic procedure to the classification of medications with evidence of or potential teratogenic risk. These exhaustive lists will be useful in teratology research and related fields.

Risk of congenital malformations for asthmatic pregnant women using a long-acting ß2-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy.

BACKGROUND: Current recommendations for managing persistent asthma during pregnancy when low-dose inhaled corticosteroids (ICSs) are insufficient include adding a long-acting ß2-agonist (LABA) or increasing the ICS dose. However, there are no data to help clinicians evaluate the safest regimen during pregnancy. OBJECTIVE: We sought to compare the risk of major congenital malformations in asthmatic women exposed to a LABA plus ICS combination and those exposed to ICS monotherapy at higher doses during the first trimester. METHODS: A cohort of asthmatic pregnant women exposed to ICSs during the first trimester who delivered between January 1990 and March 2009 was established. The primary outcome was major malformation recorded at birth or during the first year of life. Two subcohorts were established as follows: (1) users of a LABA plus low-dose ICS combination or users of a medium-dose ICS and (2) users of a LABA plus medium-dose ICS combination or users of a high-dose ICS. Generalized estimating equations were used to compare the risk of major malformations between the groups. RESULTS: In one subcohort there were 643 women who used a LABA plus low-dose ICS and 305 who used a medium-dose ICS; the other subcohort included 198 users of a LABA plus medium-dose ICS and 156 users of a high-dose ICS. The prevalence of major malformations was 6.9% and 7.2%, respectively. The adjusted odds ratio for major malformations was 1.1 (95% CI, 0.6-1.9) when a LABA plus low-dose ICS was used compared with a medium-dose ICS and 1.2 (95% CI, 0.5-2.7) when a LABA plus medium-dose ICS was used compared with a high-dose ICS. CONCLUSION: The risk of major malformations was similar with a LABA plus ICS combination and ICS monotherapy at higher doses, suggesting that both therapeutic options can be considered during pregnancy.

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.

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.

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.

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.

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.

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.

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.

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.

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.