Antithyroid drug use during pregnancy and the risk of birth defects in offspring:systematic review and meta-analysis of observational studies with methodological considerations

Aims Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies. Methods Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random-effects generic inverse variance method and absolute risk calculated. Results Seven cohort studies and 1 case–control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08–1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06–1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16–1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02–1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism. Conclusions When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism

Health conditions in adults with HIV compared with the general population:A population-based cross-sectional analysis

BACKGROUND: Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status. METHODS: We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015. We examined 47 health condition groups and 304 physical and mental health conditions by HIV status, after adjustment for age, sex, social deprivation status using logistic regression. FINDINGS: There were 964 patients with HIV (61.7% male; 92.8% aged <65 years) and 941,113 non-HIV patients (49.4% male; 75.2% aged <65 years). Condition groups with the greatest prevalence in HIV that were also highly prevalent in adults without HIV included: lipid disorder (41.4% vs 40.2%), and hypertension (19.1% vs 24.6%). Following adjustment, 18 (37.5%) condition groups were more likely in adults with HIV and ten (20.8%) were less likely. Individual conditions that were less likely in adults with HIV included: atrial fibrillation (odds ratio [OR] 0.37 [95% CI 0.20–0.64]) and hypertension (OR_0.78 [0.65–0.94]); rheumatoid arthritis (OR 0.27 [0.05–0.84]); asthma (OR_0.65 (0.53–0.80]); and certain eye diseases such as macular degeneration (OR_0.30 [0.09–0.70]). Meanwhile individual conditions that were more likely included: liver fibrosis, sclerosis, and cirrhosis (OR_3.23 [1.85–5.20]); pulmonary embolism (OR_2.06 [1.15–3.36]); male infertility (OR_2.23 [1.50–3.16]) and female infertility (OR_2.01 [1.34–2.88]); bipolar disorder (OR_2.93 [1.52–5.05]) and depression (OR_1.49 [1.28–1.71]); cervical malignancy (OR_4.64 [1.15–12.15]); and infections. INTERPRETATION: Comorbidity is common in adults with HIV, with physical and mental health conditions spanning a wide spectrum. HIV management should consider multidisciplinary care models to provide optimal patient care. FUNDING: The project was funded by the Bart’s Charity; DRM was funded by a Wellcome Trust Clinical Research Career Development Fellowship; DRM and DMM received funding from the HDR-UK Precision therapeutics programme

Intolerance to angiotensin converting enzyme inhibitors in asthma and the general population:a UK population-based cohort study

BACKGROUND: Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). Angiotensin converting enzyme inhibitor intolerance may be mediated by bradykinin, potentially affecting airway hyperresponsiveness. OBJECTIVE: To assess the risk for switching to ARBs in asthma. METHODS: We conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population was compared. Adjusted hazard ratios (HRs) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type. RESULTS: Of 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR = 1.16; 95% confidence interval [CI], 1.14-1.18; P ≤ .001) and highest in those at BTS step 3 or greater (HR = 1.35, 95% CI, 1.32-1.39; and HR = 1.18, 95% CI, 1.15-1.22, P ≤ .001 for patients aged ≥60 and <60 years, respectively). Hazard was highest with enalapril (HR = 1.25, 95% CI, 1.18-1.34, P ≤ .001; HR = 1.44, 95% CI, 1.32-1.58, P ≤ .001 for BTS step 3 or greater asthma). No increased hazard was observed in chronic obstructive pulmonary disease or those younger than age 60 years at BTS step 1/2. The number needed to treat varied by age, sex, and body mass index (BMI), ranging between 21 and 4, and was lowest in older women with a BMI of 25 or greater. CONCLUSIONS: People with active asthma are more likely to switch to ARBs after commencing ACEI therapy. The number needed to treat varies by age, sex, BMI, and BTS step. Angiotensin-II receptor blocker could potentially be considered first-line in people with asthma and in those with high-risk characteristics