Use of multiple sclerosis disease-modifying therapies during pregnancy in France: Nationwide study between 2010 and 2021.

BACKGROUND: Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women. OBJECTIVE: To assess the use of MS disease-modifying therapies (DMTs) during pregnancy in France over the last decade, marked by an increasing DMTs availability. METHODS: All pregnancies ended from April 2010 to December 2021 in women with MS were identified based on the nationwide Mother-Child Register EPI-MERES, built from the French National Health Data System (Système National des Données de Santé (SNDS)). RESULTS: Of a total of 20,567 pregnancies in women with MS, 7587 were exposed to DMT. The number of DMT-exposed pregnancies markedly increased from 1079 in 2010-2012 to 2413 in 2019-2021 (+124%), especially those exposed to glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20. Among pregnancies of women on DMT 6 months before pregnancy, 78.0% underwent DMT discontinuation and 7.6% switched DMT, generally before (33.0% and 77.0%, respectively) or during the first trimester of pregnancy (58.3% and 17.8%, respectively). DMT discontinuation decreased from 84.0% in 2010-2012 to 72.4% in 2019-2021 and was less frequent among women aged ⩾35 years and those socioeconomically disadvantaged. CONCLUSION: Despite MS therapeutic management adaptations to pregnancy, exposure during pregnancy to treatments whose safety profile has not yet been clearly established has increased sharply over the last decade.

Patterns of initial and first-intensifying antidiabetic drug utilization among patients with type 2 diabetes mellitus in Scotland, 2010-2020: A retrospective population-based cohort study.

AIM: To evaluate the utilization and prescribing patterns of antidiabetic drugs (ADDs) for patients with type 2 diabetes mellitus (T2DM) at treatment initiation and first intensification. METHODS: A retrospective cohort study was performed using linked routinely collected data of patients with T2DM who received ADDs between January 2010 and December 2020 in Scotland. The prescribing patterns were quantified using frequency/percentages, absolute/relative change, and trend tests. RESULTS: Overall, 145 909 new ADD users were identified, with approximately 91% (N = 132 382) of patients receiving a single ADD at first treatment initiation. Metformin was the most often prescribed monotherapy (N = 118 737, 89.69%). A total of 50 731 patients (39.40%) who were started on metformin (N = 46 730/118 737, 39.36%) or sulphonylurea (SU; N = 4001/10 029, 39.89%) monotherapy had their treatment intensified with one or more additional ADD. Most initial-metformin (45 963/46 730; 98.36%) and initial-SU users (3894/4001; 97.33%) who added further drugs were intensified with single ADDs. SUs (22 197/45 963; 48.29%) were the most common first-intensifying monotherapy after initial metformin use, but these were replaced by sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2019 (SGLT2 inhibitors: 2039/6065, 33.62% vs. SUs: 1924/6065, 31.72%). Metformin was the most frequently added monotherapy to initial SU use (2924/3894, 75.09%). Although the majority of patients received a single ADD, the use of combination therapy significantly increased over time. Nevertheless, there was a significant increasing trend towards prescribing the newer ADD classes (SGLT2 inhibitors, dipeptidyl peptidase-4 inhibitors) as monotherapy or in combination compared with the older ones (SUs, insulin, thiazolidinediones) at both drug initiation and first intensification. CONCLUSIONS: An overall increasing trend in prescribing the newer ADD classes compared to older ADDs was observed. However, metformin remained the most commonly prescribed first-line ADD, while SGLT2 inhibitors replaced SUs as the most common add-on therapy to initial metformin use in 2019.

Screening of dermatology drugs for aberrant use-patterns: An application of epidemiologic estimates and measures of inequality in drug use.

AIMS: Dermatology treatments require adherence for safe and effective use. Real-world healthcare databases can reveal drug utilization patterns and uncover inappropriate or unexpected use. This study aimed to analyse dermatology drug utilization patterns using epidemiological and inequality measures, leveraging Danish nationwide registries. It also assessed the feasibility of this method for detecting aberrant drug use. METHODS: We formed a 2019 cohort of all patients treated for skin conditions through Danish healthcare registries. We calculated prevalence, incidence rates and treatment duration for dermatological drugs. Inequality in drug utilization was assessed using Lorenz curves, Gini coefficients and other measures. RESULTS: The study encompassed 1 021 255 patients using 94 dermatology drugs. Most usage aligned with 'expected clinical use', but we detected inequality, with some drugs having high Gini coefficients and disproportionate consumption by the top percentile of users. Notable findings included potential inappropriate antibiotic use, excessive topical corticosteroid use and unexpected drug use duration. CONCLUSIONS: In Denmark, dermatology drugs are used primarily as anticipated, with minimal unexpected patterns. Specific follow-up is required to draw conclusions about inappropriate use. This approach demonstrates broad applicability for screening aberrant drug utilization.

The effect of deprescribing interventions on mortality and health outcomes in older people: An updated systematic review and meta-analysis.

AIMS: Previous systematic reviews suggest that deprescribing may improve survival, particularly in frail older people. Evidence is rapidly accumulating, suggesting a need for an updated review of the literature. METHODS: We updated a 2016 systematic review and meta-analysis to include studies published from inception to 26 April 2024 from specified databases. Studies in which older people had at least one medication deprescribed were included and grouped by study designs and targeted medications. The risk of bias was assessed using the Cochrane tool and the Newcastle-Ottawa tool. Odds ratios (OR) or mean differences were calculated as the effect measures using either the Mantel-Haenszel or generic inverse-variance method with fixed- or random-effects meta-analyses. The primary outcome was mortality. Secondary outcomes were adverse drug withdrawal events, physical health, cognitive function, quality of life and effect on medication regimen. Subgroup analyses were performed based on age and intervention types. RESULTS: A total of 259 studies (reported in 286 papers) were included in this updated review. Deprescribing polypharmacy did not result in a significant reduction in mortality in both randomized (OR 0.96, 95% confidence interval [CI] 0.84-1.09) and non-randomized studies (OR 0.70, 95% CI 0.36-1.38). Further subgroup analyses of randomized studies on deprescribing polypharmacy demonstrated a significant reduction in mortality in the young old (aged 65-79) (OR 0.71, 95% CI 0.51-0.99) and when patient-specific interventions were applied (OR 0.79, 95% CI 0.63-0.99). CONCLUSIONS: Deprescribing can be achieved with potentially important benefits in terms of improved survival, particularly when patient-specific interventions are applied and initiated early in the young old.

Design and statistical analysis reporting among interrupted time series studies in drug utilization research: a cross-sectional survey.

INTRODUCTION: Interrupted time series (ITS) design is a commonly used method for evaluating large-scale interventions in clinical practice or public health. However, improperly using this method can lead to biased results. OBJECTIVE: To investigate design and statistical analysis characteristics of drug utilization studies using ITS design, and give recommendations for improvements. METHODS: A literature search was conducted based on PubMed from January 2021 to December 2021. We included original articles that used ITS design to investigate drug utilization without restriction on study population or outcome types. A structured, pilot-tested questionnaire was developed to extract information regarding study characteristics and details about design and statistical analysis. RESULTS: We included 153 eligible studies. Among those, 28.1% (43/153) clearly explained the rationale for using the ITS design and 13.7% (21/153) clarified the rationale of using the specified ITS model structure. One hundred and forty-nine studies used aggregated data to do ITS analysis, and 20.8% (31/149) clarified the rationale for the number of time points. The consideration of autocorrelation, non-stationary and seasonality was often lacking among those studies, and only 14 studies mentioned all of three methodological issues. Missing data was mentioned in 31 studies. Only 39.22% (60/153) reported the regression models, while 15 studies gave the incorrect interpretation of level change due to time parameterization. Time-varying participant characteristics were considered in 24 studies. In 97 studies containing hierarchical data, 23 studies clarified the heterogeneity among clusters and used statistical methods to address this issue. CONCLUSION: The quality of design and statistical analyses in ITS studies for drug utilization remains unsatisfactory. Three emerging methodological issues warranted particular attention, including incorrect interpretation of level change due to time parameterization, time-varying participant characteristics and hierarchical data analysis. We offered specific recommendations about the design, analysis and reporting of the ITS study.

Antibiotic De-Escalation Practices in the Intensive Care Unit: A Multicenter Observational Study.

BACKGROUND: There is little known about antibiotic de-escalation (ADE) practices in the intensive care unit (ICU). OBJECTIVE: The objective was to determine the proportion of patients who received ADE within 24 hours of actionable cultures and identify predictors of timely ADE. METHODS: Multicenter cohort study in ICUs of 15 hospitals in Australia and New Zealand. Adult patients were included if they were started on broad-spectrum antibiotics within 24 hours of ICU admission. The ADE was defined as switching from a broad-spectrum agent to a narrower-spectrum agent or antibiotic cessation. The primary outcome was ADE within 24 hours of an actionable culture, where ADE was possible. RESULTS: The 446 patients included in the study had a mean age of 63 ± 16 years, 60% were male, 32% were mechanically ventilated, and 19% were immunocompromised. Of these, 161 (36.1%) were not eligible for ADE and 37 (8.3%) for whom ADE within 24 hours of actionable culture could not be determined. In the remaining 248 patients, ADE occurred ≤24 hours in 60.5% (n = 150/248) after actionable cultures. In the multivariable logistic regression analysis, ADE was less likely to occur within 24 hours for patients with negative cultures (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.25-0.92, P = 0.03). CONCLUSION AND RELEVANCE: Timely ADE may not occur in 40% of patients in the ICU and is less likely to occur in patients with negative cultures. Timely ADE can be improved, and patients with negative cultures should be targeted as part of antimicrobial stewardship efforts.

Statin treatment for primary and secondary prevention in elderly patients-a cross-sectional study in Stockholm, Sweden.

BACKGROUND: Age is a major risk factor for atherosclerotic cardiovascular disease (CVD) and death, but there has been a debate about benefit-risk of statin treatment in the elderly with limited evidence on benefits for primary prevention, while there is strong evidence for its use in secondary prevention. AIM: The aim of this study was to provide an overview of statin utilization in primary and secondary prevention for patients 75-84 years and ≥ 85 years in the Swedish capital Region Stockholm in 2019. METHODS: This is a cross-sectional study based on the regional healthcare database VAL containing all diagnoses and dispensed prescription drugs for all 174,950 inhabitants ≥ 75 years old in the Stockholm Region. Prevalence and incidence were analyzed by sex, age, cardiovascular risk, substance, and the intensity of treatment. RESULTS: A total of 35% of all individuals above the age of 75 in the region were treated with statins in 2019. The overall incidence in this age group was 31 patients per 1000 inhabitants. Men, individuals 75-84 compared to ≥ 85 years of age, and those with higher cardiovascular risk were treated to a greater extent. Simvastatin was used primarily by prevalent users and atorvastatin by incident users. The majority was treated with moderate-intensity dosages and fewer women received high intensity treatment. CONCLUSIONS: Statins are widely prescribed in the elderly. Physicians seem to consider individual cardiovascular risk when deciding to initiate statin treatment for elderly patients, but here may still be some undertreatment among high-risk patients (especially women and elderly 85 + years) and some overtreatment among patients with low-risk for CVD.

COVID-19 and pregnancy: A European study on pre- and post-infection medication use.

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

Real-world drug utilization and treatment patterns in patients with tenosynovial giant cell tumors in the USA.

Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Objective: To characterize drug utilization and treatment patterns in TGCT patients. Methods: In a retrospective observational study using IQVIA's linked prescription and medical claims databases (2018-2021), TGCT patients were stratified by their earliest systemic therapy claim (pexidartinib [N = 82] or non-FDA-approved systemic therapy [N = 263]). Results: TGCT patients treated with pexidartinib versus non-FDA-approved systemic therapies were predominantly female (61 vs 50.6%) and their median age was 47 and 54 years, respectively. Pexidartinib-treated patients had the highest 12-month probability of remaining on treatment (54%); 34.1% of pexidartinib users had dose reduction after their first claim. Conclusion: This study provides new insights into the unmet need, utilization and treatment patterns of systemic therapies for the treatment of TGCT patients.

Treatment patterns in patients with tenosynovial giant cell tumors in the USAThis database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world. We researched adult TGCT patients from IQVIA's prescription and medical claims databases who started treatment with pexidartinib (N = 82) or other non-US FDA-approved systemic therapies (N = 263). The patients included in this analysis were mostly women (61.0 and 50.6%) and their median age was 47 and 54 years for pexidartinib and other non-FDA-approved systemic therapies, respectively. The patients treated with pexidartinib were most likely to remain on treatment (54.0%) at the end of the first year. Most patients (79.3%) started pexidartinib treatment at a total daily dose of 800 mg/day, as per the product label. Only 34.1% of patients had reduced medication dose during follow-up. Of note, this study found that TGCT patients were treated with other systemic therapies which remain unproven to be safe and effective in medical studies of TGCT. Given the unmet need, and with pexidartinib being the only approved systemic treatment in USA, there is an opportunity for the larger population of adult TGCT patients to benefit from its use. Further research is needed to identify barriers for access to pexidartinib and treatment of TGCT patients.

National surveillance using a clinical quality indicator for prolonged antipsychotic use among older Australians with dementia who access aged care services.

OBJECTIVES: Dementia guidelines recommend antipsychotics are only used for behavioral and psychological symptoms when non-drug interventions fail, and to regularly review use. Population-level clinical quality indicators (CQIs) for dementia care in permanent residential aged care (PRAC) typically monitor prevalence of antipsychotic use but not prolonged use. This study aimed to develop a CQI for antipsychotic use >90 days and examine trends, associated factors, and variation in CQI incidence; and examine duration of the first episode of use among individuals with dementia accessing home care packages (HCPs) or PRAC. METHODS: Retrospective cohort study, including older individuals with dementia who accessed HCPs (n = 50,257) or PRAC (n = 250,196). Trends in annual CQI incidence (2011-12 to 2015-16) and associated factors were determined using Poisson regression. Funnel plots examined geographical and facility variation. Time to antipsychotic discontinuation was estimated among new antipsychotic users accessing HCP (n = 2367) and PRAC (n = 15,597) using the cumulative incidence function. RESULTS: Between 2011-12 and 2015-16, antipsychotic use for >90 days decreased in HCP recipients from 10.7% (95% CI 10.2-11.1) to 10.1% (95% CI 9.6-10.5, adjusted incidence rate ratio (aIRR) 0.97 (95% CI 0.95-0.98)), and in PRAC residents from 24.5% (95% CI 24.2-24.7) to 21.8% (95% CI 21.5-22.0, aIRR 0.97 (95% CI 0.96-0.98)). Prior antipsychotic use (both cohorts) and being male and greater socioeconomic disadvantage (PRAC cohort) were associated with higher CQI incidence. Little geographical/facility variation was observed. Median treatment duration in HCP and PRAC was 334 (interquartile range [IQR] 108-958) and 555 (IQR 197-1239) days, respectively. CONCLUSIONS: While small decreases in antipsychotic use >90 days were observed between 2011-12 and 2015-16, findings suggest antipsychotic use among aged care recipients with dementia can be further minimized.

Use of molnupiravir: A Danish nationwide drug utilization study.

PURPOSE: To describe utilization patterns, characteristics of users and prescribers of the new oral antiviral medication, molnupiravir, indicated for mild-to-moderate COVID-19. METHODS: Using nationwide registries, we identified all Danish adults who filled a prescription for molnupiravir from December 16th, 2021, to August 31st, 2022. We described weekly incidence rates and patient characteristics over time, prescriber characteristics as well as time between molnupiravir initiation and a positive SARs-CoV-2 test. Patient characteristics were compared to matched, untreated SARS-CoV-2 positive reference groups. RESULTS: By August 31st, 2022, 5847 individuals had filled a prescription for molnupiravir. The incidence rate gradually increased to 16 weekly prescriptions per 1000 RT-PCR SARS-CoV-2 positives. Users of molnupiravir were most often men (55% vs. 45% women). The majority (81%) had a positive RT-PCR SARS-CoV-2 test and few (2.9%) redeemed molnupiravir outside the recommended window of 5 days from the positive test result. Compared to matched, untreated SARS-CoV-2 positive reference groups, users of molnupiravir had a median age of 74 years versus 49 years, a higher proportion resided in a nursing home (12% vs. 1.5%) and had a higher number of comorbidities (median of 3 vs. 0); most commonly hypertension (38%), chronic lung disease (35%), diabetes (20%) and mood disorders (20%). General practitioners were the primary prescribers of molnupiravir (91%). CONCLUSIONS: Molnupiravir was mainly prescribed by general practitioners to RT-PCR SARS-CoV-2 positive individuals who had a potentially increased risk of severe COVID-19. Though some off-label prescribing occurred, our study indicates a high level of adherence to contemporary guidelines.

An observational post-authorization safety study (PASS) of naloxegol drug utilization in four European countries.

PURPOSE: Naloxegol has been shown to be an efficient alternative to treat opioid-induced constipation (OIC). This study aimed at describing the characteristics of naloxegol users and assessing patterns of naloxegol use and associated factors. METHODS: This drug utilization cohort study used observational registry data on patients newly prescribed naloxegol in four European countries. Patient characteristics and patterns of naloxegol use and associated factors were described. RESULTS: A total of 17 254 naloxegol users were identified across the countries. Their median age was 56-71 years, and each country had a majority of women (ranging 57.5%-62.9%). Multiple comorbidities, including cancer, were common. Natural opium alkaloids and osmotically acting laxatives (excluding saline) were the most frequently used opioids and laxatives. Overall prior use of opioids ranged from 91.9% to 99.6% and overall prior use of laxatives ranged from 69.9% to 92.4%. Up to 77.7% had prior use of medications with interaction potential, and up to 44.5% used them concurrently with naloxegol. Naloxegol was discontinued by 55.1%-90.9% of users, typically during the first 30 days. Approximately 10%-30% switched to or augmented the treatment with another constipation medication or restarted naloxegol after discontinuation. Augmentation with another constipation medication was relatively common, suggesting that naloxegol was used for multifactorial constipation. CONCLUSION: The present study reflects real-world clinical use of naloxegol, including in vulnerable patient groups. Some naloxegol users lacked laxative or regular opioid use within six months before index date or used naloxegol concomitantly with medications presenting an interaction potential.

Use of Hydrochlorothiazide in the United States Following Label Update About Skin Cancer Risk.

PURPOSE: On August 20, 2020, the United States (U.S.) Food and Drug Administration (FDA) issued a Drug Safety Communication (DSC) along with labeling updates to inform the public about a small increased risk of non-melanoma skin cancer (NMSC) associated with hydrochlorothiazide (HCTZ) use. This study aims to assess whether the DSC impacted HCTZ use in the U.S. METHODS: We conducted a trend analysis in the Sentinel Distributed Database using national healthcare administrative data from January 2017 to November 2022. We identified two cohorts each month: An overall cohort of all enrollees and a skin cancer cohort of those with a history of NMSC. For each cohort, we plotted the monthly proportion of patients receiving HCTZ-containing products among those receiving any thiazide diuretics. We performed interrupted time series analyses to quantify the impact of the DSC on these monthly proportions. Secondary analyses were conducted on the proportion of HCTZ users among patients receiving any antihypertensives. RESULTS: In the overall cohort, the DSC was only associated with a statistically significant but clinically negligible trend change of monthly HCTZ proportion within this cohort (0.018%; 95% CI, 0.012%-0.025%). Similar results were observed in the skin cancer cohort. The secondary analysis found no significant level change or trend change in the monthly proportion of HCTZ use among antihypertensive users. CONCLUSIONS: We did not observe significant changes in HCTZ use following the DSC about its NMSC risk, among the overall population and those with a history of NMSC. Our findings were in accordance with the DSC recommendation.

Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study.

BACKGROUND: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. SETTING: Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model. METHODS: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). RESULTS: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. CONCLUSIONS: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.

Opioid analgesics prescribing trends 2010-2019 in Slovenia: National database study.

OBJECTIVE: Significant increases in global opioid use have been reported in recent decades. This study analyzed opioid utilization in outpatient care in Slovenia between 2010 and 2019. METHODS: This retrospective cross-sectional study performed a nationwide database analysis of all outpatient opioid analgesic prescriptions based on Slovenian health insurance claims data. Prevalence was defined as the number of recipients prescribed at least one opioid per 1000 inhabitants. Opioid consumption was presented as the total number of dispensed prescriptions per 1000 inhabitants and dispensed defined daily doses (DDD) per 1000 inhabitants for each year analyzed. RESULTS: The age-standardized prevalence of opioid recipients decreased by 21.5% during the study period. Total opioid consumption decreased both in the number of prescriptions (-9.2%) and DDD (-5.4%). Tramadol consumption decreased in terms of the number of prescriptions (-12.2%) and DDD (-2.7%), whereas prescriptions for strong opioids increased (10.2%) and DDDs decreased (-16.2%). The results suggest less intensive prescribing of strong opioids and more intensive prescribing for tramadol. The most frequently used strong opioids were fentanyl and oxycodone/naloxone. CONCLUSIONS: The prevalence of opioid recipients and opioid consumption is decreasing in Slovenia. Further research is needed to understand whether this finding reflects safe use or underuse of these important analgesics.

Use of medication in pregnancy on the rise: Study on 1.4 million Danish pregnancies from 1998 to 2018.

INTRODUCTION: Maternal demographics have evolved, and more women than ever enter pregnancy with preexisting comorbidity and with potentially complex medication exposure, including polypharmacy (concomitant intake of multiple medications). This study aims to describe the evolution of medication use in pregnancy in Denmark from 1998 to 2018 with special focus on polypharmacy, patterns of use, and underlying demographics. MATERIAL AND METHODS: A Danish nationwide historical registry study based on all clinically recognized pregnancies with a gestation ≥10 weeks between 1998 and 2018. Medication use was estimated by redemption of prescriptions during pregnancy. RESULTS: Among a total of 1 402 327 clinically recognized pregnancies, redemption of at least one prescription medication during pregnancy increased from 56.9% in 1998 to 63.3% in 2018, coinciding with an increased use of polypharmacy (from 24.8% in 1998 to 35.2% in 2018). The prevalence of pregnant women who used medications for chronic conditions increased more than the prevalence of women treated for occasional or short-time conditions. Redemption of one or multiple prescription medications during pregnancy was mostly seen among pregnant women ≥35 years of age. However, pregnant women <25 years old exhibited the largest increase in medication use during the study period. CONCLUSIONS: Medication use in general, and polypharmacy in particular, increased from 1998 to 2008, possibly as the result of an increased prevalence of pregnant women with chronic conditions requiring pharmacological treatment. Notably, a marked maternal age-based discrepancy in usage pattern was observed, highlighting the need for further research in this area. The rise in the prevalence of polypharmacy during pregnancy underscores the need for pharmacovigilance to monitor adverse effects. Future studies should investigate the patterns of polypharmacy and the accompanying maternal and fetal risks.

Ten-Year Trends in Lithium Prescribing in Alberta, Canada.

AIMS: Despite lithium's clinical efficacy, it is commonly thought that its use is declining. The objective of this study is to describe the new and prevalent lithium users as well as rates of discontinuation of lithium use over a 10-year period. METHODS: This study used provincial administrative health data from Alberta, Canada between January 1, 2009 and December 31, 2018. Lithium prescriptions were identified within the Pharmaceutical Information Network database. Total and subgroup specific frequencies of new and prevalent lithium use were determined over the 10-year study period. Lithium discontinuation was also estimated through survival analysis. RESULTS: Between the calendar years of 2009 and 2018, 580,873 lithium prescriptions were dispensed in Alberta to 14,008 patients. The total number of new and prevalent lithium users appears to be decreasing over the 10-year timeframe, although the decline may have stopped or reversed in the latter years of the study period. Prevalent use of lithium was lowest among individuals between the ages of 18-24 years while the highest number of prevalent users were in the 50-64 age group, particularly among females. New lithium use was lowest amongst those 65 years and older. More than 60% (8,636) of patients prescribed lithium, discontinued use during the study timeframe. Lithium users between ages of 18-24 years were at the highest risk of discontinuations. CONCLUSIONS: Rather than a general decline in prescribing, trends in lithium use are dependent on age and sex. Further, the period soon after lithium initiation appears to be a key time period in which many lithium trials are abandoned. Detailed studies using primary data collection are needed to confirm and further explore these findings. These population-based results not only confirm a decline in lithium use, but also suggest that this may have stopped or even reversed. Population-based data on discontinuation pinpoint the period soon after initiation as the time when trials are most often discontinued.

Use of antimicrobials in pediatric wards of five Brazilian hospitals.

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Impact of the COVID-19 pandemic on antidepressant consumption in the Central region of Portugal: interrupted time series.

PURPOSE: To evaluate the impact of the pandemic on the consumption of antidepressive agents in Central Portugal. METHODS: To estimate the causal effect of the pandemic an interrupted time series analysis was conducted. Data of antidepressant drugs monthly dispensed in community pharmacies between Jan-2010 and Dec-2021 were provided by the regional Health Administration. Anti-Parkinson dopaminergic agents and statins, theoretically not influenced by COVID-19 pandemics, were used as comparator series. The number of packages was converted into defined daily doses and presented as defined daily doses/1000 inhabitants/day. A Bayesian structural time-series model with CausalImpact on R/RStudio was used to predict the counterfactual. Analyses with different geographical granularity (9 sub-regions and 78 municipalities) were performed. RESULTS: When compared to counterfactual, regional consumption non-significantly increased after the pandemic declaration, with a relative effect of + 1.30% [95%CI -1.6%:4.2%]. When increasing the granularity, differences appeared between sub-region with significant increases in Baixo Mondego + 6.5% [1.4%:11.0%], Guarda + 4.4% [1.1%:7.7%] or Cova da Beira + 4.1% [0.17%:8.3%], but non-significant variation in the remaining 6 sub-regions. Differences are more obvious at municipality level, ranging from increases of + 37.00% [32.00%:42.00%] to decreases of -11.00% [-17.00%:-4.20%]. Relative impact positively correlated with percentage of elderly in the municipality (r = 0.301; p = 0.007), and negatively with population density (r=-0.243; p = 0.032). No other predicting variables were found. CONCLUSION: Antidepressant consumption suffered very slight variations at regional level after the COVID-19 pandemic declaration. Analysis with higher granularity allowed identifying municipalities with higher impact (increase or decrease). The absence of clear association patterns suggests other causal hypotheses of the differences.

Cluster B personality disorders and psychotropic medications: a focused analysis of trends and patterns across sex and age groups.

PURPOSE: This study investigated sex and age differences in patterns of psychotropic medication use before and after the initial diagnosis of Cluster B personality disorders (PDs) and analyzed trends over time. METHODS: Analyzing data from the Quebec Integrated Chronic Disease Surveillance System for individuals newly diagnosed with Cluster B PD (≥ 14 years) between 2002 and 2018 and under the provincial public drug plan, we calculated yearly and monthly proportions of individuals exposed to psychotropic medications during the year before and after their diagnosis by sex and age. Robust Poisson regression models assessed the association between sex and exposure to psychotropic medications after the diagnosis of Cluster B PD. RESULTS: Among 87,778 individuals with a first Cluster B PD diagnosis (mean age: 44.5 years; 57.5% women), the proportion of users increased post-diagnosis. Notably, after diagnosis, females were more likely to receive psychiatric medications (between 78.9% and 83.7% during the study period vs. 72.8% and 76.8%). Males were less likely than females to receive antidepressants (adjusted prevalence ratio (aPR): 0.83; 99% confidence interval (CI): 0.82-0.85) and anxiolytics (aPR: 0.86; 99%CI: 0.84-0.88), whereas they had higher exposure to antipsychotics (aPR: 1.04; 99%CI: 1.02-1.06) and ADHD medications (aPR: 1.14; 99%CI: 1.07-1.2). Age-specific trends showed increased ADHD medication use among younger patients (14-24 years), and anxiolytic use predominated in those aged ≥ 65 years. CONCLUSIONS: Psychotropic medication use was high among Cluster B PD patients, with differences in medication classes according to age and sex. The marked sex and age differences in psychotropic medication use among Cluster B PD patients underscore the need for a sex-sensitive and age-specific approach in psychiatric care.