First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study.

BACKGROUND: Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage. METHODS: We carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995-2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications. RESULTS: ASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20). CONCLUSION: We found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability.

Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

Primary and revision reverse total shoulder arthroplasty using a patient-matched glenoid implant for severe glenoid bone deficiency.

BACKGROUND: Severe glenoid bone loss in the setting of both primary and revision reverse total shoulder arthroplasty (rTSA) continues to remain a significant challenge. The purpose of this study was to report on radiographic and clinical outcomes of primary and revision rTSA using a patient-matched, 3-dimensionally printed metal glenoid implant to address severe glenoid bone deficiency. This is a follow-up study to previously reported preliminary results. METHODS: A retrospective review was performed on 62 patients with severe glenoid bone deficiency who underwent either primary or revision rTSA using the Comprehensive Vault Reconstruction System (VRS) (Zimmer Biomet) at a single institution. Preoperative and postoperative values for the Disabilities of the Arm, Shoulder and Hand (DASH), Constant, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Simple Shoulder Test (SST), Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) pain scores as well as active range of motion (ROM) were collected and compared using the Wilcoxon signed rank test with the level of statistical significance set at P < .05. The percentage of patients achieving minimal clinically important difference (MCID) and substantial clinical benefit (SCB) was also calculated. RESULTS: Fifty-five of 62 shoulders (88.7%) were able to be contacted at a minimum of 2 years postoperatively, with 47 of 62 (75.8%) having complete clinical and radiographic follow-up with a mean age of 67.5 years (range, 48-85 years) and follow-up of 39.2 months (range, 25-56 months). There were 19 primary and 28 revision rTSAs. Significant improvements were seen in mean active forward flexion (63.1° ± 30.3° to 116.8° ± 35°), abduction (48.1° ± 16.1 to 76.2° ± 13.4°) (P < .001), external rotation (16° ± 23.7° to 32.1° ± 24.5°) (P < .005), DASH (59.9 ± 17.7 to 35.7 ± 24.3), Constant (23.4 ± 13.1 to 53.1 ± 17.4), ASES (27.8 ± 16.2 to 69.1 ± 25.2), SST (3.3 ± 2.5 to 7.6 ± 3.5), SANE (28.9 ± 18.3 to 66.7 ± 21.2), and VAS pain (7.1 ± 2.4 to 1.8 ± 2.6) scores (P < .001). MCID and SCB was achieved in a majority of patients postoperatively. The overall complication rate was 29.1%, with only 1 baseplate failure. CONCLUSION: This study demonstrates promising evidence that the VRS implant can be used as a viable option to achieve clinically important improvement in a majority of patients treated for severe glenoid bone deficiency with rTSA in both the primary and revision setting.

Retrograde headless compression screw fixation of olecranon stress fractures in throwing athletes: a novel technique.

Background: An olecranon stress fracture (OSF) is a rare injury most commonly seen in high-level overhead throwing athletes with no clear consensus on surgical treatment. The most common surgical treatment described in the literature is cannulated screw fixation but there have been high rates of reported hardware irritation and need for subsequent hardware removal. Hypothesis/Purpose: This study describes a novel surgical technique in the treatment of OSFs in high-level throwing athletes using retrograde headless compression screws. We hypothesized that patients would have excellent outcomes and decreased rates of hardware irritation postoperatively. Methods: A retrospective review of competitive-level throwing athletes who sustained OSFs that were treated operatively using a novel technique using retrograde cannulated headless compression screws to avoid disruption of the triceps tendon. Postoperative outcome measures obtained included the Disabilities of the Arm, Shoulder and Hand score, Mayo Elbow Performance Score, Simple Elbow Test score, Single Assessment Numerical Evaluation score, Visual Analog Scale, arch of motion, and time to return to sport as well as level returned to. Radiographs were obtained routinely at 2-week, 6-week, 12-week, 6-month, 1-year, and 2-year follow-up. Results: Five of 5 patients who met inclusion criteria were available for final follow-up. Mean age at time of surgery was 20 years (range 17-24). Mean follow-up was 17 months (range 4-33). All patients were baseball players, 4 of which were pitchers and 1 position player. All patients were able to return to sport at the same level or higher at a mean of 5.8 months (range 3-8). Postoperatively, mean arch of motion was 138°, Visual Analog Scale score was 0, Single Assessment Numerical Evaluation score was 90, Disabilities of the Arm, Shoulder and Hand score was 2.0, Mayo Elbow Performance Score was 100, and Simple Elbow Test score was 12. There was no incidence of hardware removal. Conclusion: This study presents a novel surgical technique in the treatment of OSFs in high-level throwing athletes. The results presented demonstrate that this technique is safe and effective for getting athletes back to play quickly without any complications of hardware irritation which has previously shown to be a significant problem in prior literature.

Maternal intrahepatic cholestasis of pregnancy and neurodevelopmental conditions in offspring: A population-based cohort study of 2 million Swedish children.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions. METHODS AND FINDINGS: In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term (≥37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures. CONCLUSIONS: In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment.

Trends and patterns of antiseizure medication prescribing during pregnancy between 1995 and 2018 in the United Kingdom: A cohort study.

OBJECTIVE: To examine antiseizure medication (ASM) prescription during pregnancy. DESIGN: Population-based drug utilisation study. SETTING: UK primary and secondary care data, 1995-2018, from the Clinical Practice Research Datalink GOLD version. POPULATION OR SAMPLE: 752 112 completed pregnancies among women registered for a minimum of 12 months with an 'up to standard' general practice prior to the estimated start of pregnancy and for the duration of their pregnancy. METHODS: We described ASM prescription across the study period, overall and by ASM indication, examined patterns of prescription during pregnancy including continuous prescription and discontinuation, and used logistic regression to investigate factors associated with those ASM prescription patterns. MAIN OUTCOME MEASURES: Prescription of ASMs during pregnancy and discontinuation of ASMs before and during pregnancy. RESULTS: ASM prescription during pregnancy increased from 0.6% of pregnancies in 1995 to 1.6% in 2018, driven largely by an increase in women with indications other than epilepsy. Epilepsy was an indication for 62.5% of pregnancies with an ASM prescription and non-epilepsy indications were present for 66.6%. Continuous prescription of ASMs during pregnancy was more common in women with epilepsy (64.3%) than in women with other indications (25.3%). Switching ASMs was infrequent (0.8% of ASM users). Factors associated with discontinuation included age ≥35, higher social deprivation, more frequent contact with the GP and being prescribed antidepressants or antipsychotics. CONCLUSIONS: ASM prescription during pregnancy increased between 1995 and 2018 in the UK. Patterns of prescription around the pregnancy period vary by indication and are associated with several maternal characteristics.

Genetic testing in the evaluation of recipient candidates and living kidney donors.

PURPOSE OF REVIEW: The aim of this study is to provide an overview of the role of genetic testing in the evaluation of kidney transplant candidates and living donors who may be at risk for heritable kidney disease. We focus our discussion on monogenic diseases, excluding renal diseases that have complex polygenic influences. Adoption of new technologies such as next-generation sequencing (NGS) with comprehensive gene panels has greatly enabled access to genetic testing recently; yet transplant professionals rarely receive adequate training in clinical genetics. In addition to a broad discussion of genetic testing, we hope to illustrate the thought processes and resources used in clinical genetic evaluation of recipient candidates and donors. RECENT FINDINGS: Targeted renal genetic panels, whole exome and genome sequencing have greatly expanded our ability to test for pathogenic variants. Testing methods, analytic tools and the subsequent interpretation by the testing laboratory and treating physician impacts patient management and clinicians may lack the resources to practice in this new era of genomic medicine. SUMMARY: The expansion of genomics into transplant medicine can provide improved diagnosis in transplant candidates and potentially disease prediction in living donors. Transplant professionals need to be familiar with emerging trends, promises and limitations of NGS-based testing.

Psychotropic Medication Use in Children and Youth with Autism Enrolled in Medicaid.

Children with autism frequently present with complex mental health diagnoses and psychotropic medications are often a component of comprehensive biopsychosocial treatment plans for these conditions. The purpose of this study is to provide rates and patterns of psychotropic medication use, and predictors thereof, in children and youth with autism enrolled in Medicaid across the US. This study examined national Medicaid claims from 2008 to 2016 of all children and youth with autism ages 0-21 years enrolled in Medicaid. Psychotropic medication use was examined across several child and youth characteristics, including age, co-occurring mental health conditions, sex, and race and ethnicity. About half of children and youth with autism enrolled in Medicaid had at least one psychotropic prescription in a year, a number that decreased slightly across the study period due to decreases in the prescription of antipsychotics. As new medications for autism or co-occurring conditions are developed and deployed, and as the understanding of the characteristics of the population of children with autism evolves, studying rates of medication usage helps to understand utilization patterns and differences in access to quality care.