Cathrine Axfors

Purpose: Medication use during pregnancy has increased worldwide. The aim was to investigate patterns of prescription medication use during pregnancy and postpartum in Sweden 2007–2022. Methods: We conducted a population‐based drug utilization study with linked data from the Swedish Medical Birth and Prescribed Drug Registers. From 90 days before pregnancy to 90 days after delivery, all dispensed prescriptions for each full‐level ATC code were identified. The proportion of women, by year and age, with ≥ 1 dispensed medication was calculated, as well as the number of different medications and dispensed prescriptions of structural teratogens and specific medication groups. Results: Overall, 1 065 593 (60.5%) women were dispensed ≥ 1 medication during pregnancy and 900 536 (51.1%) within 3 months postpartum. The proportion of women with ≥ 1 dispensed prescription in the postpartum period was stable but increased during pregnancy from 57.1% in 2007 to 67.5% in 2022, with the largest increase in women ≥ 40 years. The proportion using ≥ 5 different medications increased, while the proportion with a recognized or suspected structural teratogen in the first trimester remained low (< 1%). There was a notable decrease in the use of antibiotics and prescribed analgesics, and an increase in antiemetics, psychotropics, acetylsalicylic acid, anticoagulants, antihypertensives, and antidiabetics. Conclusion: Medication use during pregnancy in Sweden increased from 2007 to 2022, particularly among women ≥ 40 years, while postpartum use remained stable. Shifts in the use of specific medication groups highlight evolving maternal characteristics and clinical practice, as well as the importance of continuous surveillance and investigation of medication safety.

Background and Objective: Multiple stakeholders need to locate results of registered clinical trials but frequently struggle to find them. Summary results of clinical trials are often not published in trial registries, and publications containing trial results are often not explicitly linked to their respective trial registrations. Finding these results is important to researchers, systematic reviewers, research funders, regulators, clinical practitioners, and patients. Methods: We developed TrialScout, a computer program that uses a large language model to match clinical trials registered on ClinicalTrials.gov with corresponding result publications indexed in PubMed. TrialScout’s performance was evaluated through comparison to human-coded matches from previous studies of results reporting rates. Subsequently, TrialScout was applied to a random sample of 9,600 completed or terminated trials. Results: TrialScout had a sensitivity of 92.5% and a specificity of 81.2% compared to human coders. Manual review of 200 cases where TrialScout disagreed with human researchers showed that a majority (123/200, 61.5%, 95% CI, 54.4–68.3%) of disagreements were due to human errors. When used on 9,600 sampled trials in ClinicalTrials.gov , TrialScout found result publications for 6,110 (63.6%) of trials. Conclusions: TrialScout reliably located results of completed clinical trials. The tool offers benefits in terms of speed and efficiency. Estimating TrialScout’s accuracy is limited by the lack of a true gold standard. TrialScout can accelerate the process of locating trial results in the scientific literature and can assist in monitoring trial reporting practices. What is new: TrialScout matches published results to clinical trial registrations TrialScout uses a large language model to compare publications to registrations Accuracy rivals searching by human researchers Most disagreements between TrialScout and humans were due to human error TrialScout found published results for 63.6% of 9,600 trials from clinicaltrials.gov

Background: Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS). Methods: Randomized trials assessing approved DMTs in PwMS with results for at least one outcome referred to as “quality of life” were searched in PubMed and ClinicalTrials.gov. Results: We identified 38 trials published between 1999 and 2023 with a median of 531 participants (interquartile range (IQR) 202 to 941; total 23,225). The evaluated DMTs were mostly interferon-beta (n = 10; 26%), fingolimod (n = 7; 18%), natalizumab (n = 5; 13%), and glatiramer acetate (n = 4; 11%). The 38 trials used 18 different QoL instruments, with up to 11 QoL subscale measures per trial (median 2; IQR 1–3). QoL was never the single primary outcome. We identified quantitative QoL results in 24 trials (63%), and narrative statements in 15 trials (39%). In 16 trials (42%), at least one of the multiple QoL results was statistically significant. The effect sizes of the significant quantitative QoL results were large (median Cohen’s d 1.02; IQR 0.3–1.7; median Hedges’ g 1.01; IQR 0.3–1.69) and ranged between d 0.14 and 2.91. Conclusions: Certain DMTs have the potential to positively impact QoL of PwMS, and the assessment and reporting of QoL is suboptimal with a multitude of diverse instruments being used. There is an urgent need that design and reporting of clinical trials reflect the critical importance of QoL for PwMS.

Objective: Investigate associations between pre-pregnancy participation and performance in a demanding cross-country ski race (proxy for exercise volume and fitness) and perinatal outcomes. Pre-registered protocol: osf.io/aywg2.Design: Prospective cohort study.Setting: Based on entire overlap between the Vasaloppet registry and the population-based Swedish Pregnancy Register.Sample: All female Vasaloppet participants 1991-2017 with subsequent singleton delivery (skiers), and age- and county-matched non-skiers.Methods: We calculated odds ratios (ORs) for non-skiers versus skiers (model 1) and, among skiers, by performance (model 2), in Bayesian logistic regressions adjusted for socio-demographics, lifestyle factors, and comorbidities. We repeated calculations adjusting for early pregnancy body mass index (potential mediator) and explored robustness (selection/exposure settings; multiple comparisons correction).Main outcome measures: Twenty-nine important perinatal outcomes, predefined based on existing expert consensus.Results: Non-skiers (n = 194 384) versus skiers (n = 15 377) (and slower versus faster performance, not shown) consistently had higher odds of gestational diabetes mellitus (GDM) (OR 1.70, 95% highest density interval: 1.40-2.09), excessive gestational weight gain (GWG) (1.28, 1.22-1.38), psychiatric morbidity (1.60, 1.49-1.72), any caesarean section (CS) (1.34, 1.28-1.40), elective CS (1.39, 1.29-1.49), and large-for-gestational-age babies (> 90th percentile, 1.11, 1.04-1.18); lower odds of inadequate GWG (0.83, 0.79-0.88); and no associations with fetal/neonatal complications (e.g. preterm birth [1.09, 0.98-1.20], small for gestational age [SGA] [1.23, 1.05-1.45]). Adjustment for body mass index attenuated associations with excessive (1.20, 1.14-1.30) and inadequate GWG (0.87, 0.83-0.92) and large for gestational age (1.07, 1.00-1.13).Conclusion: Non-skiers compared with skiers, and slower versus faster performance, consistently displayed higher odds of GDM, excessive GWG, psychiatric morbidity, CS and large-for-gestational-age babies; and lower odds of inadequate GWG, after adjustment for socio-demographic and lifestyle factors and comorbidities. There were no associations with fetal/neonatal complications.

This article includes Author Insights, a video abstract available at: https://vimeo.com/785911255

Background COVID-19 exhibits a steep age gradient of infection fatality rate. There has been debate about whether extra protection of elderly and other vulnerable individuals (precision shielding) is feasible, and, if so, to what extent. Methods We used systematically retrieved data from national seroprevalence studies conducted in the pre-vaccination era. Studies were identified through SeroTracker and PubMed searches (last update May 17, 2022). Studies were eligible if they targeted representative general populations without high risk of bias. Seroprevalence estimates were noted for children, non-elderly adults, and elderly adults, using cut-offs of 20, and 60 years (or as close to these ages, if they were not available). Results Thirty-eight national seroprevalence studies from 36 different countries were included in the analysis. 26/38 also included pediatric populations. 25/38 studies were from high-income countries. The median ratio of seroprevalence in the elderly versus non-elderly adults (or non-elderly in general, if pediatric and adult population data were not offered separately) was 0.90-0.95 in different analyses with large variability across studies. In 5 studies (all of them in high-income countries), there was significant protection of the elderly with ratio Conclusion Precision shielding of elderly community-dwelling populations before the availability of vaccines was feasible in some high-income countries, but most countries failed to achieve any substantial focused protection of this age group. summary 38 COVID-19 nationally representative seroprevalence studies conducted before vaccination campaigns were systematically identified. Median seroprevalence ratio in elderly versus non-elderly adults was 0.90-0.95, indicating no generally achieved precision shielding of elderly. In 5 studies, substantial protection (ratio <0.40) was observed.