Marginal Structural Models Research Articles

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

Unequal effects of adolescent health behaviors on adult cardiometabolic conditions: a cohort study

Abstract Background Health behaviors in adolescence could have a life-long effect on cardiometabolic health and differ by parental socioeconomic conditions. Adopting a life course perspective and a causal inference framework, we aimed to quantify the differential effect of adolescent unhealthy behaviors on adult cardiometabolic conditions by parental financial situation. Methods Using the National Longitudinal Study of Adolescent to Adult Health in the United States (n = 3,772), we estimated conditional causal effect by parental financial situation through inverse probability-weighted marginal structural models. Exposures were adolescent health behaviors (dietary habits, cigarette smoking, alcohol consumption and physical activity) and the effect modifier was parental financial situation (difficulty paying bills vs. no difficulty), both measured at ages 12-19 (1994-1995). Outcomes were cardiometabolic conditions (hypertension, stroke, cardiac failure, diabetes, chronic kidney disease), measured at ages 33 - 43 (2016-2018) using biomarkers and self-reports. Results There were 1,206 participants with cardiometabolic conditions after 20 years of follow-up. Alcohol consumption among adolescents with parental financial difficulty led to 325 more cardiometabolic cases (95% confidence interval: 2 - 647) compared to alcohol consumption by their peers without financial difficulty. This differential effect is driven more by cardiovascular conditions (hypertension, stroke, or cardiac failure) than by metabolic conditions (diabetes or chronic kidney disease). There were no differential effects of dietary habits, cigarette smoking and physical inactivity on the occurrence of adult cardiometabolic conditions. Conclusions Public health initiatives targeting alcohol consumption during adolescence could mitigate socioeconomic inequalities in adult cardiometabolic conditions. Key messages • Socioeconomically disadvantaged adolescents are more susceptible to the long-term detrimental health effects of alcohol consumption. • These susceptible groups may need targeted interventions to mitigate the cardiometabolic effect of alcohol consumption.

Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

BackgroundTwo-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.MethodsVirologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.ResultsA total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).ConclusionsAmong virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Association between atherosclerotic disease and cervical artery dissection in a population-based cohort of older people.

Many cases of cervical artery dissection are considered "spontaneous." Recent data suggest that while cervical artery dissection may proportionally explain more strokes in young patients, hospitalization for dissection increases with age, suggesting a potential role of acquired vascular disease. In this study, we hypothesized that traditional vascular risk factors and comorbidities are associated with cervical artery dissection. We performed a retrospective cohort study using administrative claims data from a 5% sample of Medicare beneficiaries. Exposures of interest included traditional vascular risk factors and comorbidities: coronary artery disease, hyperlipidemia, hypertension, diabetes mellitus, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, atrial fibrillation, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of cervical artery dissection. Marginal structural Cox models were used to characterize the association between the exposures and outcomes, adjusted for time-dependent confounding. Among 2,256,710 eligible Medicare beneficiaries, 730 (0.03%) developed cervical artery dissection. The following exposures were found to be significantly associated with the development of cervical artery dissection: hypertension (HR 1.84 [95% CI: 1.40-2.41]), alcohol use (HR 1.83 [1.52-2.21]), atrial fibrillation (HR 1.80 [1.53-2.11]), tobacco use (HR 1.80 [1.52-2.13]), coronary artery disease (HR 1.56 [1.33-1.82]), and valvular heart disease (HR 1.23 [1.05-1.45]). In a large cohort of older people, several traditional vascular risk factors and comorbidities were associated with subsequent cervical artery dissection. Further studies exploring the role of such factors in the development of cervical artery dissection are warranted.

Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period.

We assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes. We used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 - March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models. Among 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days. A third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.

The Real-World Effectiveness of Antifungals in People with Cystic Fibrosis and Aspergillus-Positive Cultures.

The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus positive cultures using the Cystic Fibrosis Foundation patient registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test if antifungal exposure was associated with forced expiratory volume in one second percent predicted (FEV1pp) and pulmonary exacerbation rate, while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). A total of 14,754 individuals with Aspergillus positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV1pp (adjusted estimate -0.96 percentage points, 95% CI -2.21,0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (IV) antibiotics (adjusted IRR=1.29, 95% CI 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA< antifungals were associated with 1.88 lower FEV1pp (95% CI -3.35, -0.41) and an increased rate of pulmonary exacerbations (adjusted IRR= 1.30, 95% CI 1.21,1.40). Whereas, in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV1pp. Antifungal therapy in PwCF and Aspergillus positive cultures was not associated with improvements in FEV>1pp. While antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections are warranted.

Risk of Venous Thromboembolism in Statin Users Compared to Fibrate Users in the United Kingdom Clinical Practice Research Datalink (UK CPRD) GOLD.

A substantial proportion of adults receive statins for treatment of hypercholesterolemia and cardiovascular risk, and statins have been found to improve outcomes in this patient population. However, studies have not consistently demonstrated the potential benefits of statins in preventing venous thromboembolism (VTE). Therefore, we conducted this study to investigate this association. We conducted a cohort analysis in a study sample comprised of 40-79-year-old patients with hyperlipidemia who received at least one fibrate or statin prescription between January 1995 and December 2018 in the United Kingdom Clinical Practice Research Datalink (CPRD) GOLD. We evaluated the association between statin use and incident unprovoked VTE, compared to fibrate use, an active comparator, using Kaplan-Meier (KM) analysis, Poisson regression (with and without propensity score matching), and inverse probability of treatment weights (IPTW) marginal structural models (MSM). In this cohort of 166,292 patients with hyperlipidemia, 0.81% (N=1,353) developed incident unprovoked VTE. In analyses using the KM method, patients who received statins had a slightly lower risk of VTE compared to those who received fibrates (Log rank test: p=0.0524). The adjusted incident rate ratio (95% CI) for VTE, calculated using Poisson regression, controlling for serum cholesterol and other baseline covariates, in patients prescribed statins compared to fibrates was 0.77 (0.45-1.33) in the full cohort, 0.74 (0.38-1.45) in the propensity score matched analysis, and 0.51 (95% conservative CI: 0.34-0.76) in the IPTW MSM analysis. While the magnitude of effect varied across the different analytic methods, there is consistent evidence for a protective effect of statin use on the occurrence of unprovoked VTE.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation

BackgroundAn association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with...

Effect of Early Levodopa Treatment on Mortality in People with Parkinson's Disease.

The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long-term effects of levodopa. The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries. Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as "early initiators" (initiating levodopa within 2 years of diagnosis) or "nonearly initiators." We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates. Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05). Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.

Did Religious Well-Being Benefits Converge or Diverge During the Early Stages of the COVID-19 Pandemic in Germany?

A large body of literature highlights the benefits of being religious in terms of subjective well-being. We examine changes to these so-called religious well-being benefits during the early stages of the COVID-19 pandemic in Germany and address the role of (formal and informal) social integration when explaining these changes. We empirically test two contrasting scenarios: The first scenario predicts a decrease in religious well-being benefits (convergence hypothesis), while the second scenario predicts an increase in religious well-being benefits (divergence hypothesis). We adopt a potential outcomes framework and apply marginal structural models and inverse probability of treatment weighting to nationally representative, longitudinal data including both pre- and during-pandemic periods. Thereby, we show that initial religious well-being benefits declined during the early stages of the COVID-19 pandemic in Germany. This decline was partly due to religious individuals’ perception of decreasing social integration. Our results challenge the widespread idea that religious individuals are better protected against crises.

The Effect of Long-Term Particulate Matter Exposure on Respiratory Mortality: Cohort Study in China.

Particulate matter (PM), which affects respiratory health, has been well documented; however, substantial evidence from large cohorts is still limited, particularly in highly polluted countries and for PM1. Our objective was to examine the potential causal links between long-term exposure to PMs (PM2.5, PM10, and more importantly, PM1) and respiratory mortality. A total of 580,757 participants from the Guangzhou area, China, were recruited from 2009 to 2015 and followed up through 2020. The annual average concentrations of PMs at a 1-km spatial resolution around the residential addresses were estimated using validated spatiotemporal models. The marginal structural Cox model was used to estimate the associations of PM exposure with respiratory mortality, accounting for time-varying PM exposure. Results were stratified by demographics and lifestyle behaviors factors. Among the participants, the mean age was 48.33 (SD 17.55) years, and 275,676 (47.47%) of them were men. During the follow-up period, 7260 deaths occurred due to respiratory diseases. The annual average concentrations of PM1, PM2.5, and PM10 showed a declining trend during the follow-up period. After adjusting for confounders, a 6.6% (95% CI 5.6%-7.6%), 4.2% (95% CI 3.6%-4.7%), and 4.0% (95% CI 3.6%-4.5%) increase in the risk of respiratory mortality was observed following each 1-μg/m3 increase in concentrations of PM1, PM2.5, and PM10, respectively. In addition, older participants, nonsmokers, participants with higher exercise frequency, and those exposed to a lower normalized difference vegetation index tended to be more susceptible to the effects of PMs. Furthermore, participants in the low-exposure group tended to be at a 7.6% and 2.7% greater risk of respiratory mortality following PM1 and PM10 exposure, respectively, compared to the entire cohort. This cohort study provides causal clues of the respiratory impact of long-term ambient PM exposure, indicating that PM reduction efforts may continuously benefit the population's respiratory health.

Immediate-Release versus Extended-Release Tacrolimus: Comparing Blood Pressure Control in Kidney Transplant Recipients – A Retrospective Cohort Study

Background: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis. Methods: This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER. Results: The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: −1.00, 2.57) or DBP (p = 0.797, 95% CI: −1.38, 1.06). Conclusion: Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study

Purpose Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005–2013. Methods Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA&lt;100% versus CAA = 100% (ref), 2) CAA&lt;80% versus CAA≥80% (ref) and 3) CAA&lt;80% versus 80%≤CAA&lt;100% versus CAA = 100%. Results Poor statin adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA&lt;100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Conclusions Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

Trajectories in mammographic breast screening participation in middle-age overweight and obese women: A retrospective cohort study using linked data

ObjectivesDespite the established benefits and availability of mammographic breast screening, participation rates remain suboptimal. Women with higher BMIs may not screen regularly, despite being at increased risk of postmenopausal breast cancer and worse outcomes. This study investigated the association between prospective changes in BMI and longitudinal adherence to mammographic screening among women with overweight or obesity. MethodsRetrospective cohort study of women (N = 2822) participating in the Australian Longitudinal Study on Women's Health with an average follow-up of 20 years, with screening participation enumerated via BreastScreen NSW, Australia clinical records over the period 1996–2016. Association between BMI and subsequent adherence to screening was investigated in a series of marginal structural models, incorporating a time variant/invariant socio-demographic, clinical, and health behaviour confounders. Models were also stratified by a proxy measure of socio-economic status (education). ResultsParticipants with overweight/obesity were less adherent to mammography screening, compared to healthy/underweight participants (OR=1.29, 95 % CI=1.07, 1.55). The association between overweight/obesity and non-adherence was higher among those who ever had private health insurance (OR=1.30, 95 % CI=1.05, 1.61) compared to those who never had private health insurance and among those with lower educational background (OR=1.38, 95 % CI=1.08, 1.75) compared to those with higher educational background. ConclusionsLong-term impacts on screening participation exist among women with higher BMI, who are less likely to participate in routinely organised breast screening. Women with a higher BMI should be a focus of efforts to improve breast screening participation, particularly given their increased risk of breast cancer and association of higher BMI with worse breast cancer outcomes among older women.

An Examination of Sleep as a Protective Factor for Depression and Anxiety in the Perinatal Period: Novel Causal Analyses in a Prospective Pregnancy Cohort.

Sleep problems are common in the perinatal period. But the effects of sleep health on long-term postpartum depression and anxiety are underexamined. Using marginal structural models, we estimated the effect of sustained restful sleep quality, or adequate sleep quantity, or both, on clinically significant depression and anxiety at 23- and 32-weeks gestation, and 8-weeks, 8-, and 21-months postpartum. Women (n = 9,211) in the Avon Longitudinal Study of Parents and Children cohort reported on sleep quality (difficulty falling asleep, and early morning awakening), sleep quantity (< or > 5 hours and perceived sleep adequacy), depression (Edinburgh Postnatal Depression Scale), and anxiety (Crown-Crisp Experiential Index). Analyses adjusted for fixed (maternal education, age, body mass index, parity, marital status, smoking) and time varying (alcohol use, psychosocial adversities, depression, anxiety or sleep problems at prior time periods) covariates. Descriptive analyses suggest that sleep alterations persist beyond the immediate postpartum period. Estimates of counterfactual prevalences of outcomes under restful sleep quality and adequate sleep suggest a reduction of the population burden of clinically significant depression between 2.4% - 5.9%, and anxiety by 3.4% - 8.0% for the time points assessed. Interventions for perinatal sleep problems may reduce clinically significant depression and anxiety.

Comparative Efficacy and Safety of Moxifloxacin and Levofloxacin in a Short Standardised Rifampicin Resistant TB Regimen: A STREAM 2 Secondary Analysis.

(1) Background: The World Health Organisation (WHO) categorises moxifloxacin and levofloxacin as Group A drugs, which should be prioritised in the treatment of rifampicin-resistant tuberculosis. We compare their relative efficacy and safety using data from the STREAM trial; (2) Methods: Marginal structural models were used to balance differences in the baseline characteristics of participants receiving the STREAM control regimen containing either moxifloxacin or levofloxacin as this was not a randomised comparison. The difference in proportions between regimens was estimated for favourable outcome, any grade 3/4 adverse event, QTcF increase to ≥500 ms, QTcF increase from baseline by at least 60 ms, and any grade 3/4 adverse event excluding QT events, using weighted analyses; (3) Results: In efficacy analyses (n = 123), the weighted risk difference (moxifloxacin-levofloxacin, wRD) for a favourable outcome was -0.045 (-0.213, 0.123), p = 0.60. Similarly, estimates from the safety analyses (n = 127) showed no evidence of a difference between the fluoroquinolones, other than a suggestion of fewer QTcF increases from baseline on levofloxacin (wRD 0.160 (-0.026, 0.346), p = 0.091); (4) Conclusions: In this small dataset, we found no statistically significant difference in key efficacy or safety outcomes between the moxifloxacin- and levofloxacin-containing regimens; there was a suggestion that QTcF increases from baseline were fewer on levofloxacin.

Association between fat-soluble vitamins and metabolic syndromes in US adults: a cross-section study from NHANES database

BackgroundPrevious studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It’s necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years.MethodsWe conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003–2006 and 2017–2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose–response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components.ResultsThe presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose–response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels.ConclusionFindings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds.

Optimizing physician-encounter frequency for type 2 diabetes patients in primary care based on cardiovascular risk assessment: A target trial emulation study.

To investigate whether the physician-encounter interval for patients with type 2 diabetes (T2D) can be optimized from 2-3 to 4-6 months among those with a calculated 10-year cardiovascular disease (CVD) risk score of less than 20% without compromising their long-term outcomes. Using territory-wide public electronic medical records in Hong Kong, we emulated a target trial to compare the effectiveness of the physician-encounter intervals of 4-6 versus 2-3 months for T2D patients without prior CVDs and with a predicted risk for CVDs of less than 20% (i.e. those patients not in the high-risk category). Propensity score matching was used to emulate the randomization of participants at baseline, where 42 154 matched individuals were included for analysis. The marginal structural model was applied to estimate the hazard ratio (HR) for CVD incidence and all-cause mortality, the incidence rate ratio of secondary and tertiary care utilization, as well as the between-group differences in HbA1c, blood pressure and cholesterol levels. During a follow-up period of up to 12 (average: 5.1) years, there was no significantly increased risk of CVD in patients with physician-encounter intervals of 4-6 months compared with those patients with physician-encounter intervals of 2-3 months (HR [95% confidence interval {CI}]: 1.01 [0.90, 1.14]; standardized 10-year risk difference [95% CI]: -0.1% [-0.7%, 0.6%]), nor for all-cause mortality (HR: 1.00 [0.84, 1.20]; standardized 10-year risk difference: -0.1% [-0.5%, 0.3%]). Additionally, there was no observable difference in the utilization of secondary and tertiary care or key clinical parameters between these two follow-up frequencies. For T2D patients with a calculated 10-year CVD risk of less than 20%, the interval of regular physician encounters can be optimized from 2-3 to 4-6 months without compromising patients' long-term outcomes and saving substantial service resources in primary care.

Allopurinol, Febuxostat, and Nonuse of Xanthine Oxidoreductase Inhibitor Treatment in Patients Receiving Hemodialysis: A Longitudinal Analysis

Rationale & ObjectiveAllopurinol and febuxostat, which are xanthine oxidoreductase inhibitors, have been widely used as uric acid-lowering medications. However, evidence regarding their cardiovascular effects in hemodialysis is insufficient. This study compared the effects of allopurinol and febuxostat on mortality and cardiovascular outcomes in patients receiving hemodialysis. Study DesignRetrospective observational cohort study. Setting & ParticipantsData of 6,791 patients who had no history of topiroxostat usage and underwent maintenance hemodialysis between March 2016 and March 2019 at Yokohama Daiichi Hospital, Zenjinkai, and its affiliated dialysis clinics in Japan’s Kanagawa and Tokyo metropolitan areas were collected. ExposureAllopurinol, febuxostat, and non-treatment. OutcomesAll-cause mortality, cardiovascular disease (CVD) events, heart failure (HF), acute myocardial infarction (AMI), and stroke. Analytical ApproachFor the main analyses, marginal structural Cox proportional hazards models were used to estimate hazard ratios (HRs) adjusted for time-varying confounding and selection bias due to censoring. ResultsAllopurinol and febuxostat showed significantly better survival than non-treatment for all-cause mortality (HR: 0.40, 95% confidence interval [CI]: 0.30–0.54; HR: 0.49, 95% CI: 0.38–0.63, respectively), without significant difference between allopurinol and febuxostat. Allopurinol showed significantly better survival than non-treatment, whereas febuxostat did not for CVD events (HR: 0.89, 95% CI: 0.84–0.95; HR: 1.01, 95% CI: 0.96–1.07, respectively), HF (HR: 0.71, 95% CI: 0.56–0.90; HR: 1.03, 95% CI: 0.87–1.21, respectively), and AMI (HR: 0.48, 95% CI: 0.25–0.91; HR: 0.76, 95% CI: 0.49–1.19, respectively). No comparisons showed significant results for stroke. LimitationsThe ratio of renal or intestinal excretion of uric acid and uremic toxins could not be elucidated, and we could not investigate gene polymorphism because of the large number of cases. ConclusionsAllopurinol and febuxostat improved survival for all-cause mortality. Allopurinol, and not febuxostat, reduced the risk of CVD events, HF, and AMI.

Effects of aircraft noise exposure on self-reported health through aircraft noise annoyance: Causal mediation analysis in the DEBATS longitudinal study in France.

Previous studies reported an association between transportation noise and self-reported health status (SRHS). They also suggested a mediating role of noise annoyance using conventional statistical methods. These methods are subject to bias in longitudinal studies with time-dependent exposure, mediator and confounding factors. This study aims to investigate the mediating role of aircraft noise annoyance in the effect of aircraft noise on SRHS using a causal inference approach to address time-dependent variables issues. We used data from 881 participants in all three visits in the DEBATS longitudinal study conducted around three French airports. Participants over 18 years of age reported their self-perceived health status, aircraft noise annoyance, and noise sensitivity by completing a questionnaire at three visits in 2013, 2015 and 2017. Noise maps were used to estimate aircraft noise levels outside their homes. Marginal structural models with inverse probability weighting were used to estimate the total effect of aircraft noise levels on SRHS and its decomposition into direct and indirect effect through aircraft noise annoyance. This study showed a deleterious effect of aircraft noise on SRHS. The odds ratio (OR) corresponding to the total effect and comparing the highest aircraft noise category (≥60 dBA) to the reference category (<50 dBA) was significant (ORpoor/fair_SHRS = 1.25 (95%CI: 1.06 to 2.08)). It also showed no direct effect of aircraft noise levels on SRHS, but an indirect effect through annoyance. This indirect effect increased as aircraft noise levels increased, with a statistically significant OR when comparing the highest noise category (≥60 dBA) to the lowest (<50 dBA) (ORpoor/fair_SHRS = 1.16 (95%CI: 1.03 to 1.52)). Nearly 66% of aircraft noise's effect on SRHS was mediated by aircraft noise annoyance. This study supports the deleterious causal effect of aircraft noise on SRHS. The results highlight the important mediating role of aircraft noise annoyance in the causal pathway from exposure to aircraft noise to poor/fair SRHS.