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.

Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis.

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS. METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression. RESULTS: A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. INTERPRETATION: Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

The state of mental health among Ebola virus disease survivors through a cross-sectional study in Sierra Leone.

BACKGROUND: The West African Ebola virus disease (EVD) epidemic resulted in >28 000 disease cases and >11 000 fatalities. The unprecedented number of survivors from this epidemic has raised questions about the long-term mental health impacts of EVD survivorship and the capacity to meet these needs. OBJECTIVES: Assess the frequency and factors associated with mental health consequences of EVD survivorship in Sierra Leone. METHODS: A cross-sectional study of 595 EVD survivors and 403 close contacts (n=998) from Sierra Leone assessed via in-person survey between November 2021 and March 2022. The assessment included validated mental health screening tools (Patient Health Questionnaire-9, PTSD Checklist-5, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test-20) to indicate the presence/absence of disorder. The frequency of each disorder and factors associated with each disorder were assessed. FINDINGS: EVD-associated post-traumatic stress disorder (PTSD) was reported by 45.7% (n=257) of EVD survivors. Moreover, 3.9% (n=22) and 12.0% (n=67) of EVD survivors reported major depression (MD) and substance use, respectively; all mental health outcomes were higher than baseline rates in the region (PTSD: 6%-16%, MD: 1.1%, substance use: 2.2%). PTSD among EVD survivors was associated with acute EVD duration of ≥21 days (adjusted OR, AOR 2.24, 95% CI 1.16 to 4.43), 35-44 years of age (AOR 3.31, 95% CI 1.33 to 8.24; AOR 2.99, 95% CI 1.09 to 8.24) and residential mobility (AOR 4.16, 95% CI 2.35 to 7.35). CONCLUSIONS: Concerningly, the levels of mental health disorders among EVD survivors in Sierra Leone remained elevated 6-8 years after recovery. CLINICAL IMPLICATIONS: Results can be used to inform policy efforts and target resources to address mental health in EVD survivors.

Knowledge and perceptions of pharmacogenomics among pharmacists in Manitoba, Canada.

Objective: This work was designed to describe the knowledge and perceptions of pharmacogenomics (PGx) among pharmacists in the Canadian province of Manitoba. Methods: A 40-item, web-based survey was distributed to pharmacists in Manitoba. Results: Of 74 participants, one third had some education or training in PGx, and 12.2% had used PGx test results in their practice. Participants' self-rated knowledge of PGx testing and common PGx resources (e.g., Pharmacogenomics Knowledge Base, Clinical Pharmacogenetics Implementation Consortium) was low. Most pharmacists surveyed believe that PGx can improve medication efficacy (82.4%) or prevent adverse drug reactions (81.1%). Most (91%) desired more education on PGx. Conclusion: Manitoba pharmacists reported positive perceptions toward PGx. However, they are currently underprepared to implement PGx into practice.

Investigating the Prevalence of Comorbidity in Multiple Sclerosis Clinical Trial Populations.

BACKGROUND AND OBJECTIVES: Comorbidity is common in multiple sclerosis (MS) with the most prevalent conditions being depression, anxiety, hypertension, and hyperlipidemia. Limited information regarding the representation of comorbidity status is available from phase III clinical trials in MS leading to concern about the potential underrepresentation of individuals with comorbidity in clinical trials. The objective was to estimate the prevalence of comorbidities in MS clinical trial populations. METHODS: Individual-level data from multiple sponsors were requested for a 2-stage meta-analysis of phase III clinical trials of MS disease-modifying therapies. To ensure consistency of our approach across trials, we followed the Maelstrom retrospective harmonization guidelines. Chronic comorbidities at clinical trial enrollment recommended by the International Advisory Committee on Clinical Trials in MS were considered (depression, anxiety, hypertension, hyperlipidemia, migraine, diabetes, chronic lung disease). Additional comorbidities were also classified. Classification was based on medical history data. Individual comorbidities were summed and categorized as 0, 1, 2, or ≥3. We report the pooled prevalence (95% confidence interval [95% CI]) of comorbidity. The pooled prevalence and prevalence ratios across age, sex, race, disability level, and treatment were also reported. Heterogeneity was assessed using the I2 statistic. RESULTS: Seventeen trials involving 17,926 participants were included. Fourteen trials enrolled participants with relapsing MS (RMS) while 3 enrolled participants with progressive MS (PMS). The distributions of sex, age, and disability level were generally consistent within RMS and PMS trials. When pooled, almost half of trial participants (46.5%) had ≥1 comorbidity (1: 25.0%, 95% CI 23.0-27.0, I2 = 89.9; 2: 11.4% [9.3-14.0], I2 = 96.3; ≥3: 6.0% [4.2-8.4], I2 = 97.7). Depression (16.45% [12.96-20.88], I2 = 98.3) was the most prevalent comorbidity reported, followed by hypertension (10.16% [8.61-11.98], I2 = 93.2). Heterogeneity was high across trials. Older age and female participants were associated with increased number of comorbidities. Older individuals and male participants had a higher prevalence of hyperlipidemia, while older individuals and female participants had a higher prevalence of depression and anxiety. DISCUSSION: Individuals with comorbidities are included in clinical trials, although they may still be underrepresented compared with the general MS population. Given the comorbidity prevalence in the trial populations and studies suggesting an association of comorbidities with disease activity, comorbidity may influence outcomes in clinical trials.

Knowledge, perceptions, and attitudes toward pharmacogenomics among pharmacists and pharmacy students: A systematic review.

Background and Aims: Pharmacists have been recognized as one of the most qualified healthcare professionals in the clinical implementation of pharmacogenomics, yet its widespread implementation in clinical pharmacy practice has remained limited. The review aims to systematically investigate knowledge, perceptions, and attitudes toward pharmacogenomics among pharmacists and pharmacy students to inform the future delivery of pharmacogenomics education programs. Methods: PubMed, MEDLINE, Embase, Scopus, and the International Pharmaceutical Abstracts were searched up to May 17, 2022. Studies were selected if they included data on pharmacists' or pharmacy students' knowledge, perception, or attitude about pharmacogenomics and were published in a peer-reviewed, English-language journal with full-text availability. Any published study not deemed original research was excluded. All included studies were critically appraised using the Center for Evidence-Based Management's critical appraisal tools. The data were descriptively analyzed and presented based on pharmacists' and pharmacy students' knowledge/awareness, perception/attitudes toward pharmacogenomic (PGx), confidence in using or interpreting PGx testing results, and their desire to get further PGx education or their most preferred method of further education. Results: A combined total of 12,430 pharmacists and pharmacy students from 26 countries are represented in the 52 included studies. Despite overwhelmingly positive attitudes and perceptions toward pharmacogenomics among pharmacists and pharmacy students, an overall lack of adequate knowledge and confidence was found. The review also found a strong desire for further pharmacogenomics education among pharmacists and pharmacy students. Conclusion: Pharmacists and pharmacy students have positive perceptions and attitudes toward pharmacogenomics, which is hindered by a lack of knowledge and confidence. However, inadequate control for confounders, limited representativeness of the studied population or region, and small sample sizes diminish the generalizability of the review results. Knowledge and confidence could be improved through enhanced delivery of pharmacogenomic courses within the pharmacy curriculum and continuing education programs.

Sex differences evident in elevated anxiety symptoms in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.

Introduction: Immune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management. We evaluated whether the frequency and factors associated with comorbid elevated anxiety symptoms in those with an IMID differed by sex. Methods: Participants with an IMID (MS, IBD or RA) completed two anxiety measures (HADS, GAD-7). We used logistic regression to investigate whether sex differences exist in the presence of comorbid elevated anxiety symptoms or in the endorsement of individual anxiety items in those with an IMID. Results: Of 656 participants, females with an IMID were more likely to have elevated anxiety symptoms compared to males (adjusted odds ratio [aOR] 2.05; 95%CI: 1.2, 3.6). Younger age, higher depressive symptoms and income were also associated with elevated anxiety symptoms in IMID. Lower income in males with an IMID, but not females, was associated with elevated anxiety symptoms (aOR: 4.8; 95%CI: 1.5, 15.6). No other factors demonstrated a sex difference. Males had nearly twice the odds of endorsing restlessness on the GAD-7 (OR = 1.8, 95%CI: 1.07, 3.15) compared to females. Discussion: We found evidence for sex differences in the factors associated with experiencing elevated anxiety symptoms in those with an IMID. These findings could be helpful to sensitize clinicians to monitor for comorbid anxiety symptoms in males with an IMID.

Polygenic risk scores of lithium response and treatment resistance in major depressive disorder.

Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.

Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers.

OBJECTIVE: Major depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder's symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive. The aim of this study was to investigate the genetic characterization of MDD heterogeneity. METHODS: Using Swedish patient register data on 1.5 million individuals, the authors identified 46,255 individuals with specialist-diagnosed MDD. Eighteen subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis. A sibling-based design and classic quantitative genetic models were applied to estimate heritability of MDD subgroups and genetic correlations between subgroups. RESULTS: Estimates of heritability ranged from 30.5% to 58.3% across subgroups. The disabled and youth-onset subgroups showed significantly higher heritability (55.1%-58.3%) than the overall MDD sample (45.3%, 95% CI=43.0-47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity showed significantly lower estimates (30.5%-34.4%). Estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90. Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data. CONCLUSIONS: The findings of differential heritability and partially distinct genetic components in subgroups provide important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.

Assessment of differential item functioning of the PHQ-9, HADS-D and PROMIS-depression scales in persons with and without multiple sclerosis.

OBJECTIVE: We tested for the presence of differential item functioning (DIF) in commonly used measures of depressive symptoms, in people with multiple sclerosis (MS) versus people with a psychiatric disorder without MS. METHODS: Participants included individuals with MS, or with a lifetime history of a depressive or anxiety disorder (Dep/Anx) but no immune-mediated inflammatory disease. Participants completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), and the Patient Reported Outcome Measurement Information System (PROMIS)-Depression. We assessed unidimensionality of the measures using factor analysis. We evaluated DIF using logistic regression, with and without adjustment for age, gender and body mass index (BMI). RESULTS: We included 555 participants (MS: 252, Dep/Anx: 303). Factor analysis showed that each depression symptom measure had acceptable evidence of unidimensionality. In unadjusted analyses comparing the MS versus Dep/Anx groups we identified multiple items with evidence of DIF, but few items showed DIF effects that were large enough to be clinically meaningful. We observed non-uniform DIF for one PHQ-9 item, and three HADS-D items. We also observed DIF with respect to gender (one HADS-D item), and BMI (one PHQ-9 item). For the MS versus Dep/Anx groups, we no longer observed DIF post-adjustment for age, gender and BMI. On unadjusted and adjusted analyses, we did not observe DIF for any PROMIS-D item. CONCLUSION: Our findings suggest that DIF exists for the PHQ-9 and HADS-D with respect to gender and BMI in clinical samples that include people with MS whereas DIF was not observed for the PROMIS-Depression scale.

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.

Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers.

Background: Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries. Methods: This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable. Findings: MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations. Interpretation: The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies. Funding: Swedish Research Council (Vetenskapsrådet, award D0886501 to PFS), US National Institutes of Mental HealthR01 MH123724 (to PFS), European Union's Horizon 2020 Research and Innovation Program (847776 and 964874, to OA) and European Research Council grant (grant agreement ID 101042183, to YL).

Polygenicity of Comorbid Depression in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Depression is common in multiple sclerosis (MS) and is associated with faster disability progression. The etiology of comorbid depression in MS remains poorly understood. Identification of individuals with a high risk of depression, through polygenic scores (PGS), may facilitate earlier identification. Previous genetic studies of depression considered depression as a primary disorder, not a comorbidity, and thus, findings may not generalize to MS. Body mass index (BMI) is a risk factor of both MS and depression, and its association may highlight differences in depression in MS. To improve the understanding of comorbid depression in MS, we will investigate PGS in people with MS, with the hypothesis that a higher depression PGS is associated with increased odds for comorbid depression in MS. METHODS: Samples from 3 sources (Canada, UK Biobank, and the United States) were used. Individuals were grouped into cases (MS/comorbid depression) and compared with 3 control groups: MS/no depression, depression/no immune disease, and healthy persons. We used 3 depression definitions: lifetime clinical diagnoses, self-reported diagnoses, and depressive symptoms. The PGS were tested in association with depression using regression. RESULTS: A total of 106,682 individuals of European genetic ancestry were used: Canada (n = 370; 213 with MS), UK Biobank (n = 105,734; 1,390 with MS), and the United States (n = 578 with MS). Meta-analyses revealed individuals with MS and depression had a higher depression PGS compared with both individuals with MS without depression (odds ratio range per SD 1.29-1.38, p < 0.05) and healthy controls (odds ratio range per SD 1.49-1.53, p < 0.025), regardless of the definition applied and when sex stratified. The BMI PGS was associated with depressive symptoms (p ≤ 0.001). The depression PGS did not differ between depression occurring as a comorbid condition with MS or as the primary condition (odds ratio range per SD 1.03-1.13, all p > 0.05). DISCUSSION: A higher depression genetic burden was associated with approximately 30%-40% increased odds of depression in European genetic ancestry participants with MS compared with those without depression and was no different compared with those with depression and no comorbid immune disease. This study paves the way for further investigations into the possible use of PGS for assessing psychiatric disorder risk in MS and its application to non-European genetic ancestries.

Etiology, effects and management of comorbidities in multiple sclerosis: recent advances.

Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens. Comorbidities exert effects throughout the disease course, from symptom onset through diagnosis to the end of life. At the individual level, comorbidity is associated with higher relapse rates, greater physical and cognitive impairments, lower health-related quality of life, and increased mortality. At the level of the health system and society, comorbidity is associated with increased health care utilization, costs and work impairment. A nascent literature suggests that MS affects outcomes from comorbidities. Comorbidity management needs to be integrated into MS care, and this would be facilitated by determining optimal models of care.

Investigating genetic overlap between antidepressant and lithium response and treatment resistance in major depressive disorder.

Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) within ~ 4 500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores of antidepressant and lithium response for individuals with MDD, and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1 778 ECT-treated MDD cases, nearly all (94%) used antidepressants before first ECT, and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We found that TRD cases tend to have lower genetic load of antidepressant response than non-TRD, although the difference was not significant; furthermore, TRD cases had significantly higher genetic load of lithium response (OR = 1.10-1.12 under different definitions). The results support evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.

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.

Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. METHODS: We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10-8) from a large GWAS including 485,762 individuals with circulating 25(OH)D levels measured. We included clinical and imaging outcomes: Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), radiologic activity, and optical coherence tomography-derived ganglion cell inner plexiform layer (GCIPL) thickness. A subset (n = 935) had measured circulating 25(OH)D levels. We fitted multivariable models based on the outcome of interest and pooled results across studies using random effects meta-analysis. Sensitivity analyses included a modified p value threshold for inclusion in the PGS (5 × 10-5) and applying Mendelian randomization (MR) rather than using PGS. RESULTS: Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; p = 4.33e-06; R2 = 2.24%). In analyses with outcomes, we did not observe an association between 25(OH)D-PGS and relapse rate (per 1SD increase in 25[OH]D-PGS: 0.98; 95% CI: 0.87-1.10), EDSS worsening (per 1SD: 1.05; 95% CI: 0.87-1.28), change in T25FW (per 1SD: 0.07%; 95% CI: -0.34 to 0.49), or change in 9HPT (per 1SD: 0.09%; 95% CI: -0.15 to 0.33). 25(OH)D-PGS was not associated with new lesion accrual, lesion volume or other imaging-based outcomes (whole brain, gray, white matter volume loss or GCIPL thinning). The results were similarly null in analyses using other p value thresholds or those applying MR. DISCUSSION: Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.

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.

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.

Association Between Polygenic Risk Scores and Outcome of ECT.

OBJECTIVE: Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode. METHODS: Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series. RESULTS: Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission. CONCLUSIONS: Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.