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.

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.

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.

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.

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.

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.

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.

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.

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.

Trends of COVID-19 incidence in Manitoba and public health measures: March 2020 to February 2022.

OBJECTIVES: The increasing spread of severe acute respiratory syndrome coronavirus-2 has prompted Canada to take unprecedented measures. The objective of this study was to examine the impact of the implemented public health measures on the incidence of COVID-19 in Manitoba. RESULTS: Using the COVID-19 dataset, we examined the temporal trends of daily reported COVID-19 cases and the coinciding public health measures implemented from March 12, 2020 to February 28, 2022. We calculated the 7-day moving average and crude COVID-19 infection rate/100,000 Manitobans. Due to the restrictions applied, the infection rate decreased from 2.4 (April 1) to 0.07 infections (May 1, 2020). Between May 4 and July 17, 2020, the reported cases stabilized, and some restrictions were lifted. However, in November, the cases peaked with infection rate of 29. Additional restrictions were implemented, and the rate dropped to 3.6 infections on March 31, 2021. As of August 2021, 62.8% of eligible Manitobans received two vaccine doses. The infection rate increased to 128.3 infections on December 31, 2021 and mitigation measures were implemented. This study describes how physical distancing in conjunction with other containment measures can reduce the COVID-19 burden. Future studies into the extent of the implementation of the restrictions are necessary.

Drug utilization patterns before and during COVID-19 pandemic in Manitoba, Canada: A population-based study.

BACKGROUND: The COVID-19 pandemic has led the Canadian provincial governments to take unprecedented measures, including restrictions to healthcare services and pharmacists. Limited evidence exists on changes in prescription trends in Canada during the pandemic period. OBJECTIVES: To examine the trend of prescription medications' utilization before and during COVID-19, among incident and prevalent users in the general population. We examined 18 major classes of medications. METHODS: We used the administrative health databases from the province of Manitoba, Canada, to conduct a province-wide cross-sectional study. Incident and prevalent use was compared between two time periods; pre-COVID-19: July 2016-March 2020 and during COVID-19: April 2020-March 2021. Interrupted time series analysis using autoregressive models was used to quantify the change in level and slope in quarterly medication use among incident and prevalent users. RESULTS: The quarterly study population ranged from 1,353,485 to 1,411,630 Manitobans. The most common comorbidities were asthma (26.67%), hypertension (20.64%), and diabetes (8.31%). On average, the pandemic restrictions resulted in a 45.55% and 12.17% relative decline in the aggregated utilization of all drugs among both incident and prevalent users, respectively. Subclass analysis showed a 46.83%, 23.05%, and 30.98% relative drop among incident users of antibiotics, cardiovascular drugs and opioids use, respectively. We observed a significant slope increase during COVID-19 among the quarterly cardiovascular, antidiabetics, alpha-1 blockers, and statins incident users compared to the pre-COVID-19 period. We noted a significant decrease in level among NSAIDs, opioids, and antibiotic prevalent users, however, no significant changes in slope were observed. CONCLUSION: Our findings show a significant impact of COVID-19 measures on prescription trends in the general population. The observed decline among several medication classes was temporary. Further research is needed to monitor prescription trends and better understand if those changes were associated with increased health services and worsened outcomes.

Efficacy and safety of perampanel in epilepsy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures. METHODS: This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs. RESULTS: From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I2 15% and RR 2.79, 95% CI 1.58 to 4.93, I2 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes. CONCLUSION: This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.

Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis.

OBJECTIVES: Alternative dosing strategies for ß-lactams - the most common antibiotics used to treat critically ill patients with respiratory tract infections - have been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal ß-lactams improves mortality and clinical efficacy. METHODS: Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (≥3h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated. RESULTS: Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD -0.10; 95% CI -0.15 to -0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed. CONCLUSIONS: Extended infusions of ß-lactams were associated with reduced mortality rates but not with clinical success.