Sex-specific Subgroups Research Articles

Sex-specific association between anatomical variants of the circle of Willis and intracranial aneurysms in individuals with a familial predisposition.

First-degree relatives of aneurysmal subarachnoid hemorrhage patients face elevated risks for intracranial aneurysm development and aneurysmal subarachnoid hemorrhage, which both occur more often in women. Anatomical variants of the circle of Willis affect its hemodynamics and are associated with unruptured intracranial aneurysms. It is unknown if these findings apply to patients with a familial predisposition for these conditions, and if they are sex-specific. We therefore assessed if anatomical circle of Willis variants are associated with intracranial aneurysms identified at screening in individuals with a familial predisposition, and if these associations are sex-specific. Individuals with and without intracranial aneurysms, identified at MRA-TOF screening, were compared. Circle of Willis arterial diameters were measured to identify anatomical variants, categorized into six types for both the anterior and posterior parts. Logistic regression was used for comparison, adjusted for age, hypertension, and the cohorts the individuals were part of, and stratified for sex-specific subgroups. Of all 1,291 included individuals, 94 (7.3%) had aneurysms. A normal anterior variant was less common among individuals with aneurysms (OR 0.59, 95% CI 0.37-0.93). This effect was only observed in women (OR 0.45, 95% CI 0.25-0.80), and not in men (OR 1.39, 95% CI 0.57-3.35). The variant with anterior communicating artery hypoplasia or absence was more common in individuals with aneurysms (OR 1.61, 95% CI 1.03-2.54). This effect was observed in both women (OR 1.62, 95% CI 0.95-2.75) and men (OR 1.37, 95% CI 0.55-3.41). No differences were found for variants of the posterior part of the circle of Willis. Women with intracranial aneurysms identified at screening less frequently had a normal anterior part of the circle of Willis compared to those without aneurysms. Additionally, individuals with aneurysms more often had anterior communicating artery hypoplasia or absence, which association was not sex-specific. These anatomical variations may enhance the effectiveness of screening for intracranial aneurysms. ACA = anterior cerebral artery; Acom = anterior communicating artery; ADPKD = autosomal dominant polycystic kidney disease; aSAH = aneurysmal subarachnoid hemorrhage; CoW = circle of Willis; PCA = posterior cerebral artery; Pcom = posterior communicating artery; UIA = unruptured intracranial aneurysm; UMCU = University Medical Center Utrecht.

Prognostic importance of baseline and changes in serum uric acid for macro/microvascular and mortality outcomes in individuals with type 2 diabetes: The Rio de Janeiro type 2 diabetes cohort

AimsTo investigate the associations between baseline/changes in serum uric acid (sUA) and the risks for cardiovascular/microvascular outcomes and mortality in a type 2 diabetes cohort. MethodsBaseline sUA was measured in 685 individuals, and 463 had a second sUA measurement during follow-up; sUA was analyzed as a continuous variable and categorized into sex-specific tertile subgroups and low/high levels (>4.5 mg/dl women; >5.5 mg/dl men). The risks associated with baseline sUA and its changes were examined by Cox analyses for all outcomes. ResultsMedian follow up was 10.7 years, there were 173 major cardiovascular events (MACEs), 268 all-cause deaths, 127 microalbuminuria, 104 renal failure, 160 retinopathy and 178 peripheral neuropathy outcomes. Baseline sUA was predictor of all outcomes, except all-cause mortality and retinopathy. In tertile and high/low sUA analyses, the hazard ratios (HRs) varied from 1.6 (microalbuminuria development) to 2.4 (MACEs; cardiovascular mortality). There was interaction with sex for MACEs, an increased risk was observed in women (HR: 2.6), but not in men (HR: 1.2). Changes in sUA were associated with the renal failure (HR: 2.4). ConclusionsIn a prospective cohort, high baseline sUA was a predictor of cardiovascular, renal and peripheral neuropathy. However, sUA changes were only predictor of renal failure.

Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups.

Tirzepatide, a novel GIP and GLP1 agonist, has been extensively examined in clinical trials. However, specific data on its adverse drug events (ADEs) remain limited. This study aims to comprehensively assess real-world ADEs associated with tirzepatide by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. ADE reports from the FAERS database were retrieved for the second quarter of 2022 through the first quarter of 2024. Significant associations between ADEs and tirzepatide were evaluated using proportional disproportionality analyses, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS). A total of 37,827 ADE reports associated with tirzepatide were identified, with 100 significantly disproportionate preferred terms (PTs) recognized by all four algorithms. The top five PTs with the highest reporting rates were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. Additionally, unexpected signals such as starvation ketoacidosis were identified. The median time to onset for all ADEs was 23 days. Furthermore, sex-specific high-intensity signals were found, with males primarily experiencing gastrointestinal disorders and females experiencing general disorders and administration site conditions. This study provides valuable insights into the occurrence of ADEs following tirzepatide administration, potentially supporting clinical monitoring and risk identification efforts.

Development and Validation of Physical Disability Index and Mental Disability Index and Their Associations With Falls Among Older Adults.

To enhance the precision of measuring, analyzing, and forecasting care needs for older adults with physical and/or mental disabilities, we developed the Physical Disability Index (PDI) and Mental Disability Index (MDI). Furthermore, we evaluated the reliability and validity of the PDI and MDI. Additionally, we investigate their associations with falls to further indicate the predictive validity. A total of 11621 older adults (53.1% women; mean age = 83.2; SD = 10.8) from 23 provinces in China were investigated in 2017-2018 to assess the reliability and validity of the PDI and MDI among older adults aged 65 to 105. Among which, 6071 older adults with both baseline (2017-2018) and follow-up (2021) data were included in analyses to evaluate associations between the baseline health status determined by PDI and MDI and the number and severity of falls at baseline and follow-up. Cronbach's alpha was used to determine internal consistency. The convergent and divergent validity, known-group validity and concurrent validity were assessed. Multinomial logistic regression models were utilized to assess associations. We found satisfactory internal consistency (Cronbach's alpha ≥ 0.70) of the PDI and MDI in the total sample and sex-specific subgroups. Our results support the convergent and divergent validity, known-group validity, and concurrent validity of the PDI and MDI. We also found baseline physical disability and comorbid physical and mental disability are associated with a higher risk of baseline and follow-up falls. The PDI and MDI are reliable and valid instruments to assess physical and mental disability status among older adults, respectively.

Analysis of Inclisiran in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and Sex-specific Subgroups.

ABSTRACT Background our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. Methods We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). Results Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and Various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). Conclusion Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

: A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

The Association between Molecular Initiating Events and Drug-Induced Hiccups.

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous reports have revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using the FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups was extracted from the overall population and sex-specific subgroups were divided. In each data table, the predicted activity values of nuclear receptors and stress response pathways for each drug were calculated using the Toxicity Predictor, a machine-learning model. Transforming growth factor-beta and antioxidant response elements were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups. The use of an adverse event database and the machine-learning model, Toxicity Predictor, may be useful for generating hypotheses for other adverse effects with unknown mechanisms.

Helicobacter pylori infection prevalence declined among an urban health check-up population in Chengdu, China: a longitudinal analysis of multiple cross-sectional studies.

The efficacy of updated health policy in improving the generalization of Helicobacter pylori screening and eradication in southwest China was assessed in a longitudinal analysis of multiple cross-sectional studies from an institution. In the periods 2009-2010, 2013-2014, and 2019-2021, 8,365, 16,914, and 18,281 urban observations from health check-ups at West China Hospital were analyzed, respectively. The 14C-urea or 13C-urea breath test was consistently used for H. pylori detection. The protocol has been reported elsewhere (PROSPERO Registration number: CRD42019120764). The overall prevalence of H. pylori dramatically decreased from 53.1% to 30.7% over the past decade (OR = 0.39, 95% CI 0.37-0.41), with a similar decline in all sex-specific and age-specific subgroups. The age-specific prevalence consistently increased before 40 years of age and always peaked at 50-59 years. Longitudinal clearance increased along with aging, and prevalence dropped to 22.6%, 25.1%, and 23.6% in the 40-49, 50-59, and 60-69 years initial age groups, respectively. The generalization of H. pylori screening and eradication could greatly contribute to the control of H. pylori infection among urban health check-up populations and lower gastric cancer incidence.

Effect of moderate-intensity statin with ezetimibe combination vs. high-intensity statin therapy according to sex in patients with atherosclerosis

We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63–1.52] in women; HR 0.90 [0.71–1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001). LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes. There were no significant interactions between sex and treatment groups regarding the primary outcome, discontinuation, or dose reduction of study drugs, or the proportion of achievement of LDL cholesterol levels < 70 mg/dL. The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex.Trial registration: https://clinicaltrials.gov; Unique identifier: NCT03044665.

Sarcopenia as an important determinant for adverse outcomes in patients with pyogenic liver abscess.

Low muscle mass/sarcopenia has been associated with poor prognosis in many diseases, but its clinical significance in pyogenic liver abscess (PLA) remains unclear. The purpose of this study is to investigate the relationship between muscle mass and prognosis of patients with PLA. A total of 154 adult patients with PLA hospitalized at Tongji Hospital (Wuhan, Hubei, China) between October 2011 and June 2021 were included in this retrospective analysis. Muscle-fat related indicators were measured by computed tomography (CT) images at the third lumbar vertebra (L3) level. The data of patients between the sarcopenia group and non-sarcopenia group were compared. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed. The skeletal muscle index (SMI) was independently associated with adverse outcomes (95% CI [0.649-0.954], P=0.015) of PLA in multivariate logistic regression analysis. This conclusion held true in sex-specific subgroup analysis. ROC analysis indicated that SMI may predict adverse outcomes in both male (area under the ROC curve [AUC], 0.718; cut-off, 52.59; P<0.001) and female (AUC, 0.714; cut-off, 38.39; P=0.017) patient populations. Sarcopenia serves as an independent risk factor for poor prognosis in PLA and patients with sarcopenia may be more prone to adverse outcomes.

Associations of brachial-ankle pulse wave velocity with left atrial stiffness and left atrial phasic function in inpatients with hypertension.

Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and an increase in arterial stiffness. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension. A total of 305 hypertensive inpatients enrolled and were divided into two groups based on baPWV [Group I, baPWV ≤ 1515 (cm/s), n = 153; Group II, baPWV > 1515 (cm/s), n = 152]. Two-dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e' to LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. LASI was significantly higher in Group II [0.35(0.26, 0.52)] compared with Group I [0.26(0.20, 0.36)] (P < 0.001). After adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio, and LVGLS), baPWV remained significantly correlated with LASI (P < 0.05). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.663 (95% CI: 0.607-0.716, P < 0.001). In conclusion, BaPWV was independently associated with LA stiffness in hypertensive inpatients. BaPWV also exhibited a certain predictive value for LA stiffness in these inpatients. Measuring arterial stiffness can provide clinicians clues for early cardiac target organ damage (TOD) in addition to vascular TOD.

Accounting for Nonhealth and Future Costs in Cost-Effectiveness Analysis: Distributional Impacts of a US Cancer Prevention Strategy.

To provide up-to-date and comprehensive US data tables to estimate future net resource use, including nonlabor market production, and examine distributional impacts of including nonhealth and future costs in cost-effectiveness results. Using a published US cancer prevention simulation model, the paper evaluated the lifetime cost effectiveness of implementing a 10% excise tax on processed meats across age- and sex-specific population subgroups. The model examined multiple scenarios accounting for cancer-related healthcare expenditure (HCE) only, cancer-related and unrelated background HCE, adding productivity benefits (i.e., patient time, cancer-related productivity loss, and background labor and nonlabor market production), and with nonhealth consumption costs, adjusted for household economies of scale. Additional analyses include using population-average versus age-sex-specific estimates for quantifying production and consumption value, as well as comparing direct model estimation versus postcorrections with Meltzer's approximation for incorporating future resource use. Accounting for nonhealth and future costs impacted cost-effectiveness results across population subgroups, often leading to changes in "cost-saving" determination. Including nonlabor market production had a noticeable impact on estimating future resource use and reduced the bias toward undervaluing productivity among females and older populations. The use of age-sex-specific estimates resulted in less favorable cost-effectiveness results compared with population-average estimates. Meltzer's approximation provided reasonable corrections among the middle-aged population for re-engineering cost-effectiveness ratios from a healthcare sector to a societal perspective. With updated US data tables, this paper can help researchers conduct a comprehensive value assessment to reflect net resource use (health and nonhealth resource use minus production value) from a societal perspective.

S-03-2: ASSOCIATIONS OF BRACHIAL-ANKLE PULSE WAVE VELOCITY WITH LEFT ATRIAL STIFFNESS AND LEFT ATRIAL PHASIC FUNCTION IN HYPERTENSION

Aims: Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and arterial stiffness increased. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension. Methods: A total of 309 hypertensive patients enrolled and were divided into two groups based on baPWV [Group I, baPWV&lt; 1517 (cm/s), n = 151; Group II, baPWV&gt; 1517 (cm/s), n = 158]. Two dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e’ to LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. Age, sex, and BMI were adjusted (Model 1), systolic blood pressure, Diabetes, HbA1c, LDL-C and eGFR were added (Model 2), then ACEIs/ARBs/ARNI treatment was added (Model 3), and last LVMI, LVEF, E/A ratio and LVGLS were added (Model 4). Results: LAS-S and LAS-E were significantly lower in Group II compared with Group I (P &lt; 0.05 for both). LASI was significantly higher in Group II [0.36(0.25, 0.53)] compared with Group I [0.26(0.20, 0.36)] (P &lt; 0.001). In multiple linear regression analysis, baPWV was associated with LASI, LAS-S, and LAS-E in Mode l, Model 2 and Model 3. However, after adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio and LVGLS), baPWV only remained significantly correlated with LASI in Model 4 (P = 0.002) for all patients and in both subgroups (Table). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.666 (95% CI: 0.605–0.726, P &lt; 0.001). Furthermore, baPWV also had predictive values for LASI in age-specific and sex-specific subgroups, however, there were no significant differences between both sexes, or between younger (&lt;50 years old) and older patients (&gt;50 years old) (DeLong test: P &gt; 0.05 for both). Conclusion: BaPWV was independently associated with LA stiffness, for all patients as well as in age-specific and sex-specific subgroups. BaPWV also had the predictive value for LA stiffness in hypertension. BaPWV maybe a convenient and useful screening tool for early detection of cardiac functional remodeling and interactions between cardiovascular abnormalities in hypertension.

CHA2DS2-VASc score for in-hospital recurrence risk stratification in patients with myocardial infarction.

Using the CHA2DS2-VASc score to recognize the risk of stroke in patients with atrial fibrillation has been well-established. However, few studies have assessed whether the CHA2DS2-VASc score has a similar predictive value in recurrence after myocardial infarction (MI). We conducted a retrospective observational cohort study of adult inpatients with MI. The CHA2DS2-VASc and modified CHA2DS2-VASc (MCHA2DS2-VASc) scores of all patients were calculated. The associations of both scores with recurrent MI were analyzed. A total of 6,700 patients with MI (60.0 ± 11.1 years, 77.2% men) were enrolled, and 759 (11.3%) presented a definite recurrence during hospitalization. After multivariable adjustment by logistic regression in patients with MI, the CHA2DS2-VASc and MCHA2DS2-VASc scores were independently associated with recurrence. The MCHA2DS2-VASc score showed a better predictive value for risk of recurrence than that of CHA2DS2-VASc in overall [area under the receiver operating characteristic curve (AUC) 0.757 vs. 0.676] or male patients (AUC 0.759 vs. 0.708). MCHA2DS2-VASc was superior to CHA2DS2-VASc for identifying "truly high-risk" patients with MI, regardless of overall patients or sex-specific subgroups. The two scores had a similar focus on the identification of "low-risk" patients in overall or women, but not in men. The CHA2DS2-VASc and MCHA2DS2-VASc scores for predicting recurrence are validated in patients with MI. However, MCHA2DS2-VASc could be more helpful to secondary prevention than CHA2DS2-VASc after MI, especially in men. The superiority of MCHA2DS2-VASc compared with CHA2DS2-VASc in women is just more discriminatory for "truly high-risk" patients.

Long-term weight loss and metabolic benefit from Roux-en-Y gastric bypass in patients with superobesity.

Although Roux-en-Y gastric bypass (RYGB) is widely performed worldwide, its efficacy in patients with a body mass index (BMI) greater than 50 kg/m2 remains controversial. The aim of the present paper was to assess long-term (10 years or more) weight loss and metabolic results of RYGB in patients with superobesity (SO; BMI > 50 kg/m2), compared with patients with morbid obesity (MO; BMI 35-50 kg/m2). This study involved retrospective analysis of a prospectively followed cohort of adult patients operated on for a primary RYGB between 1999 and 2008. Long-term weight loss and metabolic parameters were compared between SO and MO patients, with a sex-specific subgroup analysis in SO patients. Multiple logistic regression assessed independent predictors of poor long-term weight loss. Among the 957 included patients, 193 (20.2 per cent) were SO (mean BMI 55.3 kg/m2versus 43.3 kg/m2 in MO). Upon 10-year follow-up, which was complete in 86.3 per cent of patients, BMI remained higher in SO patients (mean 39.1 kg/m2versus 30.8 kg/m2, P < 0.001) although total bodyweight loss (per cent TBWL) was similar (28.3 per cent versus 28.8 per cent, P = 0.644). Male SO patients had a trend to higher 10-year per cent TBWL, while initial BMI greater than 50 kg/m2 and low 5-year per cent TBWL were independent predictors of long-term TBWL less than 20 per cent. Diabetes remission was observed in 39 per cent SO and 40.9 per cent MO patients (P = 0.335) at 10 years, and all patients had a significant lipid profile improvement. Substantial improvement in co-morbidities was observed in all patients 10 years after RYGB. Total weight loss was similar in SO and MO patients, leaving SO patients with higher BMI. Suboptimal TBWL 5 years after surgery in SO, especially female patients, may warrant prompt reassessment to improve long-term outcomes.

Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients

BackgroundIn view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset.MethodsWe identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves’ disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression.ResultsA total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670–1.114; CoronaVac: IRR 0.707, 95% CI 0.549–0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716–1.159; CoronaVac: IRR 0.778, 95% CI 0.618–0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744–1.023; CoronaVac: IRR 0.830, 95% CI 0.713–0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838–1.199; CoronaVac: IRR 0.963, 95% CI 0.807–1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770–1.227; CoronaVac: IRR 0.879, 95%CI 0.693–1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833–1.246; CoronaVac: IRR 0.768, 95% CI 0.613–0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899–1.201; CoronaVac: IRR 0.911, 95% CI 0.786–1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794–1.102; CoronaVac: IRR 0.945, 95% CI 0.799–1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines.ConclusionsOur population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.

Comparative risk of dementia among patients with atrial fibrillation treated with catheter ablation versus anti-arrhythmic drugs

Atrial fibrillation (AF) is associated with an increased risk of dementia. Emerging evidence suggests AF suppression is associated with reduced risk of dementia, but the optimal strategy to achieve this is unknown. We sought to compare the risk of dementia in patients with AF who underwent catheter ablation (CA) versus anti-arrhythmic drug (AAD) treatment. METHODS AND RESULTS: Using the 2000 to 2021 Optum Clinformatics database, patients with AF who underwent CA versus AAD treatment (≥1 prescription fill for ≥2 different AADs) were identified and propensity score matched overall and within sex subgroups. A cause-specific hazard model was performed to assess dementia overall and in sex-specific subgroups. After matching, there were 19,088 patients per group. CA was associated with a 41% lower risk of dementia compared with AAD alone (1.9% vs 3.3%; hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.52-0.67, log-rank P < .0001). When examined by sex, dementia risk reduction associated with CA versus AAD use alone was observed among both males (HR 0.55, 95% CI 0.46-0.66) and females (HR 0.60, 95% CI 0.50-0.72). Though not studied as a primary outcome, patients treated with CA were also observed to have 49% lower associated risk of mortality compared with AAD only (HR 0.51 95% CI 0.46-0.55, P < .0001). CONCLUSIONS: Among patients treated for AF, CA was associated with significantly lower risk of dementia and death compared with AADs only. These reductions in risk associated with CA versus AAD were seen in both males and females.

Muscle fat infiltration but not muscle cross-sectional area is independently associated with bone mineral density at the lumbar spine.

Although sarcopenia and osteoporosis are inter-related conditions that are common with advancing age, few studies have explored relationships between muscle quality and bone mineral density (BMD). We investigated age- and sex-specific paraspinal muscle fat infiltration (MFI), muscle cross-sectional area (CSA), and spine volumetric BMD (vBMD) in healthy Chinese adults. 605 healthy adults aged 20-59 years (340 women, mean age 39.2 years; 265 men, mean age 38.8 years) had axial T2WI MRI imaging of the lumbar spine and CSA (cm2) and MFI (%) were measured in the psoas and multifidus and erector spinae (MF-ES) muscles (L3-L4). MFI measurements were calibrated against a region of interest in an adjacent area of subcutaneous pure fat. L2-L4 vBMD was measured by quantitative CT. Age- and sex-specific subgroups were compared using the Mann-Whitney test. Multiple regression was used to test independent associations of MFI and CSA with vBMD. Females had lower CSA and higher MFI than males in both the psoas and MF-ES muscles (p < 0.001). In females and males, MF-ES MFI increased with age (p < 0.001) and in females age-related increases were observed for the psoas muscles (p < 0.05). Greater fat infiltration of the MS-ES muscle unit was associated with lower vBMD in both sexes (p < 0.001) but not with CSA. Following adjustment for demographic variables and CSA, MS-ES MFI remained predictive of vBMD (β = -0.408 to -0.157, p < 0.001). We have demonstrated that, independent of CSA and demographic variables, MFI of the MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes. This is the first study to demonstrate that, independent of muscle size and demographic variables, MFI of the paraspinal MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes.

Sex-specific effect of serum urate levels on coronary heart disease and myocardial infarction prevention: A Mendelian randomization study

Background and aimsObservational studies have examined serum urate levels in relation to coronary heart disease (CHD) and myocardial infarction (MI). Whether these associations are causal remains controversial, due to confounding factors and reverse causality. We aim to investigate the causality of these associations using Mendelian randomization method. Methods and resultsInstrumental variables were obtained from the largest genome-wide association studies of serum urate (457,690 individuals) to date. Summary statistics were from CARDIoGRAMplusC4D consortium (60,801 CHD cases; 43,676 MI cases), FinnGen (21,012 CHD cases; 12,801 MI cases), UK Biobank (10,157 CHD cases; 7018 MI cases), and Biobank Japan (29,319 CHD cases). Inverse-variance weighted method was applied as the main results. Other statistical methods and reverse MR analysis were conducted in the supplementary analyses. Elevated genetically determined serum urate levels were associated with increased risks of CHD and MI. The association pattern remained for the datasets in FinnGen, the combined results of three independent data sources (CHD: odds ratio (OR), 1.10; 95%CI, 1.06–1.15; p = 4.2 × 10−6; MI: OR, 1.12; 95%CI, 1.07–1.18; p = 2.7 × 10−6), and East Asian population. Interestingly, sex-specific subgroup analyses revealed that these associations kept in men only, but not among women in individuals of European ancestry. No consistent evidence was found for the causal effect of CHD or MI on serum urate levels. ConclusionWe provide consistent evidence for the causal effect of genetically predicted serum urate levels on CHD and MI, but not the reverse effect. Urate-lowering therapy may be of cardiovascular benefit in the prevention of CHD and MI, especially for men.

Are We Able to Determine Differences in Outcomes Between Male and Female Servicemembers Undergoing Hip Arthroscopy? A Systematic Review.

Background:Female servicemembers sustain higher rates of lower extremity injuries as compared with their male counterparts. This can include intra-articular pathology in the hip. Female patients are considered to have worse outcomes after hip arthroscopy for femoroacetabular impingement and for hip labral repair.Purpose:To (1) compare published rates of hip arthroscopy between male and female military servicemembers and (2) determine if there are any sex-based differences in outcomes after hip arthroscopy in the military.Study Design:Systematic review; Level of evidence, 3.Methods:We reviewed the literature published from January 1, 2000, through December 31, 2020, to identify studies in which hip arthroscopy was performed in military personnel. Clinical trials and cohort studies were included. The proportion of women within each cohort was identified, and results of any between-sex analyses were reported.Results:Identified were 11 studies that met established criteria. Studies included 2481 patients, 970 (39.1%) of whom were women. Surgery occurred between January 1998 and March 2018. Despite women accounting for approximately 15% of the active-duty military force, they represented 39.1% (range, 25.7%-57.6%) of patients undergoing hip arthroscopy. In most cases, there were no differences in self-reported outcomes (pain, disability, and physical function), return to duty, or medical disability status based on sex.Conclusion:Women account for approximately 15% of the military, but they made up 40% of patients undergoing hip arthroscopy. Outcomes were not different between the sexes; however, definitive conclusions were limited by the heterogeneity of outcomes, missing data, lack of sex-specific subgroup analyses, and zero studies with sex differences as the primary outcome. A proper understanding of sex-specific outcomes after hip arthroscopy will require a paradigm shift in the design and reporting of trials in the military health system.