Inverse Probability Research Articles

Evaluating the impact of brachytherapy duration on therapeutic outcomes in patients with cervical cancer

The total duration of radiotherapy for patients with cervical cancer should be limited to 56 days to optimize treatment outcomes. This study aimed to statistically evaluate the effects of extended radiotherapy duration on survival and complications in 649 patients with cervical cancer treated with brachytherapy at our institution from 2014 to 2019. All patients had undergone intensity-modulated external beam radiation therapy, with 525 receiving two-dimensional (2D) brachytherapy and 124 receiving three-dimensional (3D) brachytherapy. Using the inverse probability of treatment weighting (IPTW) and propensity score matching (PSM), clinical data regarding treatment duration, survival outcomes, and complications were analyzed. PSM revealed that overall survival (OS) did not significantly differ between patients receiving prolonged treatment (>56 days) and those receiving treatment for a standard duration (<56 days) (P > 0.05). However, among patients who had received 2D brachytherapy, prolonged treatment correlated with increased recurrence and metastasis risks (P < 0.001); this trend was not evident in patients receiving 3D brachytherapy (P = 0.287). Higher FIGO stages were associated with worse OS and higher progression risks, which persisted post-IPTW adjustment. Extended radiotherapy duration was linked to a higher incidence of rectal and bladder reactions, particularly in the 2D group. Consequently, strictly controlling radiotherapy duration for patients receiving 2D brachytherapy is essential to reduce recurrence and metastasis risks. Close monitoring of rectal and bladder reactions is also recommended.

Sodium zirconium cyclosilicate treatment and rates of emergency interventions for hyperkalaemia: a propensity-score weighted case-control study

Abstract Background Sodium zirconium cyclosilicate (SZC) reduces serum potassium in patients with chronic hyperkalaemia in clinical trials, but its role in the emergency treatment of hyperkalaemia is unproven. We hypothesised that SZC use for emergent hyperkalaemia would be associated with a reduction in rates of emergency interventions for hyperkalaemia. Methods This was a single centre, propensity-score weighted case-control study of patients admitted with hyperkalaemia to a specialist renal centre. We randomly selected 250 patients admitted between April 2021 and September 2022 (post-SZC era) with a potassium ≥ 5.5 mmol/L treated with at least one ≥ 10g dose of SZC (treatment group). We randomly selected a comparator group of 250 patients admitted between January 2018 and December 2019 (pre-SZC era) with a potassium ≥ 5.5 mmol/L (control group). Baseline demographic and clinical characteristics were recorded and used as covariates for propensity scoring (PS) and inverse probability treatment weighting (IPTW). Our primary outcome measure, rates of emergency haemodialysis, were tested using unadjusted models and multivariable logistic regression models on unweighted data in addition to unadjusted models on weighted data. We also reviewed rates of emergency temporary central venous access as a secondary outcome. Results 59% were male, the mean age was 67 (SD 14) years and 149 (30%) were receiving maintenance dialysis. IPTW achieved satisfactory balance of covariates between the treatment and control groups. In the treatment group, patients were 77% less likely to need emergency haemodialysis (OR 0.23; CI 0.17 to 0.31); this result was consistent following analysis of weighted and unweighted data. Similarly, patients treated with SZC were 73% less likely to require emergency temporary central venous access (OR 0.27; CI 0.20–0.36). Conclusion SZC was associated with signification reduction in rates of emergency haemodialysis and emergency temporary central venous access in patients admitted to a specialised renal centre with emergent hyperkalaemia.

Rapid reduction in fracture risk after the discontinuation of long-term oral glucocorticoid therapy: a retrospective cohort study using a nationwide health insurance claims database in Japan.

We investigated changes in fracture risk following discontinuation of long-term oral glucocorticoids (GCs) using Japan's nationwide health insurance claims database (NDBJ). We identified patients aged ≥ 50 years who initiated GC therapy in 2012-2019. Those receiving ≥ 5mg (prednisolone or equivalent, PSL)/day for ≥ 72days in the initial 90days of GC therapy were classified as the GC-exposure group, and those receiving < 5mg PSL/day for < 30days were classified as the reference group. Patients discontinuing GC after 90days of GC therapy were classified as the GC-discontinuation group; all others were classified as the GC-continuation group. We tracked the incidence rates of hip and clinical vertebral fractures for up to 990days, and assessed fracture risk after GC discontinuation by hazard ratios (HR) adjusted by inverse probability weighting using propensity scores for GC discontinuation. There was a total of 52,179 GC-discontinuation, 91,969 GC-continuation, and 43,138 reference group women, and 57,560, 93,736, and 33,696 men in the corresponding groups, respectively. According to adjusted HRs, incidence rates of fractures were significantly lower in the GC-discontinuation group than in the GC-continuation group in the initial 90days after GC discontinuation and remained significant for 360days, except for hip fracture in men. HRs for hip fractures remained significantly higher in the GC-discontinuation group compared to the reference group for 720days post-discontinuation. Fracture risk declines rapidly in the first year after GC discontinuation, but vigilance is necessary as the increased risk persists for two years post-discontinuation.

Higher dose antiviral therapy for herpes infections is associated with a risk of serious adverse events in older adults with chronic kidney disease.

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%.

Mammographic density and breast cancer risk among Black American women.

High mammographic density is a well-established risk factor for breast cancer; however, data from Black women are limited. It is largely unknown how mammographic density is associated with breast cancer subtypes among Black women. We examined the association between percent mammographic density (PMD) and breast cancer risk among participants in the Black Women's Health Study. Digital screening mammograms were available for 363 cases and 5541 non-cases. Cumulus software was used to assess PMD. We used inverse probability of sampling weights and Cox proportional hazards models, adjusted for age and body mass index, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and by age at mammography and estrogen receptor (ER) status of the breast tumors. Multivariable models included additional breast cancer risk factors. Tests of statistical significance were 2-sided. In simple models, women in the highest quartile of PMD had 53% increased odds of breast cancer compared to those in the lowest quartile (HR 1.53; 95% CI: 1.11, 2.11). HRs were 1.37 (95% CI: 0.83, 2.24) among women <55 years of age and 1.68 (95% CI: 1.10, 2.56) among women aged ≥55 years. HRs were 1.49 (95% CI: 1.02, 2.16) for ER+ cancer and 1.45 (95% CI: 0.73, 2.87) for ER- cancer. Associations were largely unchanged in multivariable models. In this study of U.S. Black women, higher PMD was associated with ER+ and ER- breast cancer risk. Findings from this study reinforce the importance of breast density as a risk factor for breast cancer in Black women.

Effect of facet joint resection on postoperative radiographic and clinical outcomes after microendoscopic laminectomy for single-level lumbar spinal stenosis

Facet joint destruction causes postoperative spinal instability, resulting in poor clinical outcomes after lumbar decompression surgery. However, the effect of facet joint destruction on radiographic and clinical outcomes after microendoscopic laminectomy (MEL) is unknown. Therefore, the current study aimed to examine the effect of facet joint resection on radiographic and clinical outcomes after single-level MEL surgery. This study included 116 patients with lumbar spinal canal stenosis (LSCS) who underwent single-level (L4/5) MEL surgery. Eligible patients were divided into the following groups: group P (facet joint preservation rate = 100%) (n = 70); group PR (50% ≤ the facet joint preservation rate < 100%) (n = 27); and group R (the facet joint preservation rate < 50%) (n = 19). The demographic characteristics of the patients, surgical data, pre- and 1-year postoperative radiographic measurements, and clinical outcomes were compared among the three groups. Moreover, pre- and postoperative radiographic and clinical outcomes were compared after adjusting the demographic characteristics of the patients and surgical data by the inverse probability weighting method with propensity scores. The three unweighted groups did not significantly differ in terms of demographic characteristics, surgical data, and pre- and postoperative radiographic and clinical outcomes. Even after adjusting for the demographic characteristics and surgical data, the pre- and postoperative radiographic and clinical outcomes were comparable among the three weighted groups. The extent of facet joint resection might have a minimal impact on radiographic and clinical outcomes at 1 year after single-level MEL surgery.

Remnant cholesterol elevates hyperuricemia risk in the middle aged and elderly Chinese: a longitudinal study.

Evidence regarding the relationship between remnant cholesterol (RC) and hyperuricemia is limited. The purpose of this study is to investigate the association between RC and hyperuricemia in the middle aged and elderly Chinese. Information was extracted from the China Health and Retirement Longitudinal Study (CHARLS) survey 2011 and survey 2015. Four logistic regression models were established. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to balance the baseline. Next, sensitivity analyses and restricted cubic spline (RCS) analysis were conducted to further explore the association. Cross-lagged panel model (CLPM) and mediation analysis were used to deduce the causal relationship between RC and hyperuricemia. This study contained 6,447 participants. A positive association between high RC and hyperuricemia was found in the full adjusted model (OR:1.80, P < 0.001). Similar results were also seen after PSM (OR:1.86, P < 0.001), IPTW (OR:1.80, P < 0.001) and sensitive analysis in non-overweight subgroups (OR:1.77, P < 0.001). Though non-linear relationship was not observed, CLPM exhibited that high level of RC can directly cause increase of blood uric acid (standardized β = 0.005, P < 0.001). Moreover, mediation analysis suggested that the positive association can be mediated by hypertension (β = 0.024; p = 0.004), CRP (β = 0.050; p < 0.001) and WBC (β = 0.024; p = 0.010). High level of RC is an independent risk factor for hyperuricemia, which can be mediated by inflammation and hypertension.

Impact of physical activity levels on the association between air pollution exposures and glycemic indicators in older individuals

BackgroundAir pollution may exacerbate diabetes-related indicators; however, the longitudinal associations between air pollutant concentrations and glycemic markers remain unclear. In this prospective cohort study, we examined the longitudinal associations between air pollution and glycemic indicators among older individuals with normoglycemia at baseline and determined whether these associations differed according to changes in physical activity levels.MethodsOverall, 1,856 participants (mean age, 70.9 years) underwent baseline and 4-year follow-up surveys. We used linear mixed-effect models to examine the associations between previous 1-year exposures to air pollutants and glycemic indicators. We further investigated associations between previous 5-year exposures to air pollutants and glycemic indicators after the inverse probability of treatment weighting (IPTW). We explored effect modifications by the level of physical activity maintenance and changes in metabolic equivalent of task (METs) for physical activity.ResultsLevels of particulate matter with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm, and nitrogen dioxide (NO2) were significantly associated with increased fasting blood glucose, Hemoglobin A1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) values. After IPTW, the associations remained significant for PM10 and NO2. The positive associations of NO2 with insulin and HOMA-IR remained significant in the maintained inactive group, but not in the maintained moderate-to-vigorous active group. The positive associations of PM10 or NO2 with insulin and HOMA-IR remained significant in the group with increased METs, but not in those with decreased METs. In the post-hoc analysis of non-linear relationships between an increase in METs and glycemic indicators, insulin and HOMA-IR remarkably increased in the higher PM10 and NO2 exposure group from the point of 12,000 and 13,500 METs-min/week increase, respectively.ConclusionsWe demonstrated longitudinal associations between air pollution exposures and increased insulin resistance in older individuals. Maintaining moderate-to-vigorous physical activity may mitigate the adverse effects of air pollution on insulin resistance. In older individuals dwelling in highly polluted areas, an increase of less than 12,000 METs-min/week may be beneficial for insulin resistance.

Disparities in receipt of 1-st line CDK4/6 inhibitors with endocrine therapy for treatment of hormone receptor positive, HER2 negative metastatic breast cancer in the real-world setting

ObjectiveThis study used real-world observational data to compare profiles of patients receiving different first-line treatment for hormone receptor positive (ER+), HER2 negative, metastatic breast cancer (MBC): CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) versus ET alone.MethodFrom a nationwide electronic health record-derived Flatiron Health de-identified database including 280 US cancer clinics, we identified patients with hormone receptor positive, HER2 negative, metastatic breast cancer receiving 1st -line therapy with ET alone or CDK4/6i plus ET between February 2015 and November 2021. Patient sociodemographic status, MBC treatment regimen and outcomes were the focus of this analysis. Patient characteristics were compared using t-tests and chi-square tests. Logistic regression analysis was performed to examine the association of patient characteristics with the likelihood of receiving 1st -line CDK4/6i plus ET vs. ET alone. Kaplan-Meier method and Cox proportional hazards were used to test the impact of 1st -line treatment regimen on real-world progression-free survival (PFS) and overall survival (OS). Baseline characteristics were balanced using inverse probability weighting (IPW).ResultsThe study population included 3,917 patients receiving CDK4/6i plus ET (n = 2170) and ET alone (n = 1747) for their MBC. Compared to patients receiving ET alone, those receiving CDK4/6i plus ET were younger (mean age 66.8 vs. 68.6, p < 0.001), more likely to present with de novo MBC (p < 0.001), had better performance status (50.2% vs. 40.5% patients with ECOG value 0, p = 0.001) and lower number of comorbidities (29.7% vs. 26.6% ≥ 1 comorbidity, p < 0.001). Logistic regression revealed increased odds of CDK4/6i plus ET in individuals aged 50–64 (OR: 3.42, 95% CI [2.41, 4.86]) and 65–74 (OR: 3.18, 95% CI [1.68, 6.02]) versus those aged 18–49 years of age. Black individuals had lower odds of CDK4/6i plus ET (OR: 0.76, 95% CI [0.58, 1.00]) compared to White individuals. Other characteristics associated with lower odds of CDK4/6i plus ET included patients with stage III disease (OR: 0.69, 95% CI [0.52, 0.92]), lower performance status (OR: 0.50, 95% CI [0.40, 0.62]), and Medicare insurance (OR: 0.73, 95% CI [0.30, 1.78]) compared to those with commercial and Medicaid insurance. After IPW adjustment, use of CDK4/6i plus ET as 1st -line treatment was associated with significantly longer median PFS compared to ET alone (27 vs. 17 months; hazard ratio [HR] = 0.61, p < 0.001). Median OS was 52 months in the CDK4/6i plus ET group and was 42 months with ET alone (HR = 0.74, p < 0.001).ConclusionIn this real-world database, disparities in receiving 1st -line CDK4/6 inhibitors were seen by age, diagnosis stage, baseline performance status, comorbidity, and insurance status. In adjusted analysis, the use of 1st -line CDK4/6i plus ET yielded better PFS and OS rates than ET alone. Further efforts are essential to enhance equitable use of and access to this crucial drug class.

Higher fraction of inspired oxygen during anesthesia increase the risk of postoperative pulmonary complications in patients undergoing non-cardiothoracic surgery: a retrospective cohort study

ObjectiveThe ideal intra-operative inspired oxygen concentration remains controversial. We aimed to investigate the association between the intraoperative fraction of inspired oxygen (FiO2) and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing non-cardiothoracic surgery.MethodsThis was a retrospective cohort study of elderly patients who underwent non-cardiothoracic surgery between April 2020 and January 2022. According to intraoperative FiO2, patients were divided into low (≤60%) and high (&amp;gt;60%) FiO2 groups. The primary outcome was the incidence of a composite of pulmonary complications (PPCs) within the first seven postoperative days. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were conducted to adjust for baseline characteristic differences between the two groups. Multivariate logistic regression analysis was used to calculate the odds ratios (OR) for FiO2 and PPCs.ResultsAmong the 3,515 included patients with a median age of 70 years (interquartile range: 68–74), 492 (14%) experienced PPCs within the first 7 postoperative days. Elevated FiO2 was associated with an increased risk of PPCs in all the logistic regression models. The OR of the FiO2 &amp;gt; 60% group was 1.252 (95%CI, 1.015–1.551, P = 0.038) in the univariate analysis. In the multivariate logistic regression models, the ORs of the FiO2 &amp;gt; 60% group were 1.259 (Model 2), 1.314 (Model 3), and 1.32 (model 4). A balanced covariate distribution between the two groups was created using PSM or IPTW. The correlation between elevated FiO2 and an increased risk of PPCs remained statistically significant with PSM analysis (OR, 1.393; 95% CI, 1.077–1.804; P = 0.012) and IPTW analysis (OR, 1.266; 95% CI, 1.086–1.476; P = 0.003).ConclusionHigh intraoperative FiO2 (&amp;gt;60%) was associated with the postoperative occurrence of pulmonary complications, independent of predefined risk factors, in elderly non-cardiothoracic surgery patients. High intraoperative FiO2 should be applied cautiously in surgical patients vulnerable to PPCs.

Impact of Perioperative Pulmonary Artery Catheter Use on Clinical Outcomes Following Cardiac Surgery: A Nationwide Cohort Study

BackgroundEvidence on the effectiveness of pulmonary artery catheters (PACs) in cardiac surgery is scarce. Research QuestionDoes perioperative PAC use decrease on 1-year all-cause mortality in patients undergoing cardiac surgery? Study Design and MethodsThis nationwide, population-based cohort study included all adult patients who underwent cardiac surgery in Korea between January 2011 and December 2020 using a Korean health insurance claim database. We compared the primary outcome, the risk of 1-year all-cause mortality, between patients with and without perioperative use of PACs (PAC and no-PAC groups, respectively) using logistic regression analysis after stabilized inverse probability of treatment weighting. A subgroup analysis was performed to determine whether the association varied according to the type of cardiac surgery and institutional case volume. ResultsA total of 61,405 patients were analyzed. The PAC group had a significantly lower risk of 1-year all-cause mortality than that in the no-PAC group (adjusted odds ratio [OR], 0.81; 95% confidence interval [CI], 0.76–0.86). In the subgroup analysis, both the type of cardiac surgery and institutional case volume were identified as significant modifiers (all P for interaction<0.001). Specifically, the PAC group had a significantly lower risk of 1-year all-cause mortality following isolated off-pump coronary artery bypass grafting (adjusted OR, 0.54; 95% CI, 0.48–0.61) compared to the no-PAC group. PAC use was associated with a significant reduction in the risk of 1-year all-cause mortality in the lowest-case volume centers (<100 cases/year; OR, 0.70; 95% CI, 0.65–0.76). InterpretationPerioperative use of PACs was associated with a significant reduction in the risk of postoperative 1-year all-cause mortality. This association was predominantly driven by patients who underwent off-pump coronary artery bypass grafting and those who underwent cardiac surgery in less experienced centers.

Chronic thyrotoxic myopathy development is associated with thyroid hormone sensitivity index, predicted by lower-limb fatigue and the squat-up test

Thyroid hormones (THs) may affect chronic thyrotoxic myopathy (CTM). The relationship between TH sensitivity and CTM is inconsistent. We aimed to investigate the associations between TH sensitivity and the risk of CTM and to screen potential CTMs with strength and function tests. A total of 162 Chinese patients (36.58% men) with Graves’ disease were enrolled and divided into CTM and non-CTM groups. TH and sensitivity indices were measured. Muscle power and function were assessed by grip, upper-limb fatigue (ULFT), lower-limb fatigue (LLFT), and squat-up (SUT) tests, and walking pace. Association between sensitivity to TH indices and the risk of developing CTM was assessed via multivariate logistic regression. The diagnostic effectiveness of muscle power and function for predicting CTM was evaluated via receiver operating characteristic (ROC) curves. Thyroid feedback quantile-based index FT3 (TFQIFT3) and the parametric TFQIFT3 (PTFQIFT3), TFQIFT4, and PTFQIFT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQIFT3 and PTFQIFT3, TFQIFT4 and PTFQIFT4, the odds ratios for CTM were 1.67 (95% CI = 1.17–2.48) ,1.64 (95% CI = 1.51–2.93), 1.60 (95%CI = 1.12–2.32), 1.58 (95%CI = 1.11–2.30), respectively. LLFT and SUT best predicted male/female CTM, respectively (AUC = 0.89/0.85). In Graves’ disease patients, TH sensitivity is associated with CTM development, which can be predicted by SUT and LLFT results.

Impact of Thrombocytopenia on Bleeding and Thrombotic Outcomes in Adults with Cancer-associated Splanchnic Vein Thrombosis

Malignancy is a risk factor for splanchnic vein thrombosis (SpVT). Data on the natural history of cancer-associated SpVT are limited. This was a single-center retrospective cohort study of 581 adult patients with cancer and SpVT. We aimed to characterize the impact of thrombocytopenia on major bleeding and progression or recurrence of SpVT within one year of initial cancer-associated SpVT diagnosis. Baseline thrombocytopenia (platelet < 100,000/uL within 15 days of SpVT diagnosis) was present in 39.5% of patients. A total of 39.2% of patients received therapeutic anticoagulation within two weeks of SpVT diagnosis. The cumulative once-year incidence of major bleeding was 10.7% (95% CI: 8.2–13.2), and for SpVT recurrence/progression was 16.2% (95% CI: 13.2–19.2). In multivariable regression analysis, therapeutic anticoagulation was associated with increased major bleeding (aRR: 1.74, 95% CI: 1.08-2.81) and decreased progression/recurrence of SpVT (aRR: 0.55, 95% CI: 0.35-0.86). Baseline thrombocytopenia was not independently associated with either major bleeding (aRR: 0.76, 95% CI: 0.43-1.34) or progression/recurrence of SpVT (aRR: 1.14, 95% CI: 0.73–1.78). A secondary analysis using inverse probability of treatment weighting with propensity scores for baseline thrombocytopenia corroborated that patients with thrombocytopenia did not have increased bleeding risk (aHR: 0.81, 95% CI: 0.48–1.39). Multivariable analysis treating platelets as a time varying covariate also did not reveal an association with major bleeding (aHR: 0.89, 95% CI: 0.55–1.45). Bleeding and thrombosis progression were frequent in patients with cancer-associated SpVT. Anticoagulation was associated with increased major bleeding and decreased thrombotic progression; thrombocytopenia did not impact outcomes.

Palbociclib plus aromatase inhibitors in patients with metastatic breast cancer and cardiovascular diseases: real-world effectiveness.

Patients with cardiovascular disease (CVD) comorbidities are often excluded from participating in breast cancer clinical trials. Consequently, data to inform treatment decisions for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and CVD are limited. We compared the effectiveness of first-line palbociclib plus an aromatase inhibitor (AI) vs an AI alone and evaluated palbociclib treatment patterns in patients with HR+/HER2- mBC and CVD in routine clinical practice. Data from the Flatiron Health Analytic Database were captured for patients with HR+/HER2- mBC and CVD who initiated first-line treatment with palbociclib plus an AI or an AI alone between February 2015 and March 2020 (data cutoff: September 30, 2020). Overall survival (OS), real-world progression-free survival (PFS), and treatment patterns were evaluated. Of the 469 patients with identifiable CVD, 160 received palbociclib plus an AI, and 309 received an AI alone. After stabilized inverse probability treatment weighting, both median OS (40.7 vs 26.5 months; hazard ratio [HR], 0.732 [95% CI, 0.537-0.997]; P = .048) and median real-world PFS (20.0 vs 12.5 months; HR, 0.679 [95% CI, 0.512-0.900]; P = .007) were significantly prolonged in patients treated with palbociclib plus an AI vs an AI alone. Among patients with a documented palbociclib starting dose, 78.5% started palbociclib at 125mg/day, and 38.6% experienced dose adjustment. In this real-world analysis, first-line palbociclib plus an AI was associated with improved effectiveness compared with an AI alone in patients with HR+/HER2- mBC and CVD. NCT05361655 (ClinicalTrials.gov).

Impact of letrozole co-treatment in an antagonist protocol for IVF/ICSI: a retrospective study

ObjectiveThe present study aimed to investigate the impact of combined use of letrozole in an antagonist protocol during IVF on live birth outcomes and to assess the safety of letrozole in terms of maternal and neonatal complications.MethodsThis retrospective cohort study included women undergoing IVF/ICSI and fresh embryo transfer (ET) treatment with and without letrozole co-treatment from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). The primary outcome was the live birth rate, while the incidences of maternal and neonatal complications were secondary outcomes. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the analyzed outcomes. Sensitivity analysis was performed using a propensity score-based patient-matching (PSM) model, an inverse probability weighting (IPW) model, logistic regression models with women undergoing their first IVF-ET cycle, and subgroup analysis.ResultsOf the 4780 women enrolled in the study, 3887 underwent an antagonist protocol for ovarian stimulation, while 893 received letrozole co-treatment. In this cohort, letrozole co-treatment demonstrated comparable live birth rates to the use of antagonist protocol alone (logistic regression: aOR, 0.88; 95% CI, 0.71–1.08; PSM: aOR, 0.97; 95% CI, 0.77–1.22; IPW: aOR, 0.88; 95% CI, 0.71–1.10). Notably, individuals with a body mass index (BMI) exceeding 24 and those with high ovarian response experienced higher live birth rates under the letrozole co-treatment regimen (BMI ≥ 24: aOR, 1.85; 95% CI, 1.14-3.00; high response: aOR, 1.60; 95% CI, 1.02–2.50). Letrozole co-treatment was also associated with decreased risks of gestational diabetes (aOR, 0.34; 95% CI, 0.15–0.69) and small for gestational age (SGA) fetuses (aOR, 0.42; 95% CI, 0.22–0.75) in fresh ET cycles. These finding were robust in both PSM and IPW models.ConclusionsOur findings suggested that letrozole co-treatment in antagonist protocol for IVF/ICSI was associated with a comparable live birth rate following fresh ET. Further prospective randomized studies are needed to verify our results.

Inotropes and mortality in patients with cardiogenic shock: an instrumental variable analysis from the SWEDEHEART registry.

The use of inotropic agents in treating cardiogenic shock (CS) remains controversial. This study investigates the effect of inotropes on 30-day mortality in CS patients using data from the SWEDEHEART registry (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies). Data were sourced from the national SWEDEHEART registry for all CS patients in Sweden from 2000 to 2022. The primary endpoint was 30-day all-cause mortality. We employed multilevel Cox proportional-hazards regression with instrumental variable and inverse probability weighting propensity score to adjust for confounders. The treatment-preference instrument was the quintile of preference for inotrope use at the treating hospital. A total of 16 214 patients (60.5% men, 39.5% women) were included; 23.5% had diabetes, 10.2% had a previous myocardial infarction (MI), and 13.8% had previous heart failure (HF). The median age was 70 years (IQR; 19), with 66.4% over 70. Acute coronary syndrome (ACS) caused CS in 82.9%. Inotropes were administered to 43.8% of patients, while 56.2% did not receive them. There were 7 875 (48.1%) deaths. Patients treated with inotropes were, on average, two years younger and more likely to have ACS, while those not treated had more previous MI and were less likely to undergo PCI. The number of CS cases decreased by 12% per year (Ptrend<0.001), and inotrope use increased by 5% per year (Ptrend<0.001). Unadjusted mortality in CS rose by 2% per calendar year (Ptrend<0.001). Inotropes were associated with higher mortality (adjusted HR 1.72; 95% CI 1.26-2.35; P=0.001), with significant interactions between inotrope treatment, age, and diagnosis (Pinteraction<0.001 and Pinteraction=0.018). In this observational study, inotropes were linked to higher mortality in CS patients, particularly those younger than 70. While CS cases decreased, inotrope use and mortality increased in Sweden.

Remdesivir Effectiveness in Reducing the Risk of 30-day Readmission in Vulnerable Patients Hospitalized for COVID-19: A Retrospective US Cohort Study Using Propensity Scores.

Reducing hospital readmission offer potential benefits for patients, providers, payers, and policymakers to improve quality of healthcare, reduce cost, and improve patient experience. We investigated effectiveness of remdesivir in reducing 30-day COVID-19-related readmission during the Omicron era, including older adults and those with underlying immunocompromising conditions. This retrospective study utilized the US PINC AI Healthcare Database to identify adult patients discharged alive from an index COVID-19 hospitalization between December 01, 2021 and February 29, 2024. Odds of 30-day COVID-19-related readmission to the same hospital were compared between patients who received remdesivir vs those not, after balancing characteristics of two groups using inverse probability of treatment weighting (IPTW). Analyses were stratified by maximum supplemental oxygen requirement during index hospitalization. Of 326,033 patients hospitalized for COVID-19 during study period, 210,586 patients met the eligibility criteria. Of these, 109,551 (52%) patients were treated with remdesivir. After IPTW, lower odds of 30-day COVID-19-related readmission were observed in patients who received remdesivir vs those who did not, in the overall population (3.3% vs 4.2%, respectively; odds ratio [95% confidence interval]: 0.78 [0.75-0.80]), elderly population (3.7% vs 4.7%, respectively; 0.78 [0.75-0.81]), and those with underlying immunocompromising conditions (5.3% vs 6.2%, respectively; 0.86 [0.80-0.92]). These results were consistent irrespective of supplemental oxygen requirements. Treating patients hospitalized for COVID-19 with remdesivir was associated with a significantly lower likelihood of 30-day COVID-19-related readmission across all patients discharged alive from the initial COVID-19 hospitalization, including older adults and those with underlying immunocompromising conditions.

Experience-based transition to robotic surgery in an experienced program in minimally invasive hepatobiliary surgery.

The adoption of robotic techniques in liver surgery introduces significant challenges for their safe integration within hepatobiliary surgery units. This study is designed to investigate the complexities associated with establishing a robotic surgery program. Data on robotic hepatobiliary surgeries were prospectively collected from October 2021 to October 2023. Historical cohorts from the institutional experiences for comparison were hand-assisted (HALS) and purely laparoscopic procedures (PLS). Inverse probability of treatment weighting and propensity score matching were employed to compare outcomes between PLS and robotic resections. The learning curve for robotic surgeries was evaluated by the cumulative sum method. In this study, 454 patients were enrolled (113 robotic surgeries, 157 HALS, and 184 PLS). The posterosuperior segments resections were significantly higher in the robotic group (47.8%) compared to PLS (31.5%) and HALS (35.7%). There were no conversions in the robotic group, in PLS 2.7% and HALS 3.8%. The degree of difficulty according to the median of the IWATE score and IMM score was significantly higher in the robot group (p < 0.001 and p = 0.008, respectively). No significant differences in short-term outcomes were observed between robotic procedures and PLS in a matched subset of patients. Operative efficiency and blood loss improved significantly after the 75th robotic surgery patient, with high-difficulty cases (IWATE ≥ 10) incorporated from the beginning. This study suggests that robotic liver surgery in units with prior experience in minimally invasive liver surgery offers benefits, such as a lower conversion rate and a higher rate of successful difficult resections.

Assessing the role of dietary acid load in the development of hypertensive disorders during pregnancy: uncovering the association through prospective cohort analysis

BackgroundHypertensive disorders of pregnancy (HDPs) are common complications encountered in pregnancy that affect between 5% and 15% of pregnancies worldwide. Some studies have associated adherence to a diet with a high acid load with an increased risk of HDPs. This study investigates the association between Dietary Acid Load (DAL) and the incidence of preeclampsia, chronic hypertension (HTN), and gestational hypertension (GHTN).MethodsPregnant women aged 18 to 45 in the first trimester of pregnancy were selected and followed up until delivery. Diet was evaluated using a 168-question semi-quantitative food frequency questionnaire (FFQ). After calculating the DAL score, the inverse probability weight of the propensity scores, estimated from augmented generalized models, was used to obtain a causal risk ratio (RR) adjusted for potential confounders.ResultsOut of 1,856 women, 92 (4.95%) developed preeclampsia. The potential renal acid load (PRAL) score ranged from − 16.14 to 0.58, while the net endogenous acid production (NEAP) score ranged from 34.61 to 50.15. Multivariable analysis revealed a significant association between PRAL and preeclampsia in the first (aRR: 1.87, 95% CI: 1.01, 3.49, p = 0.048) and third (aRR: 2.01, 95% CI: 1.07, 3.81, p = 0.030) quartiles compared to the reference group (Q2). No significant linear association was found in continuous analyses. For chronic HTN, significant associations were observed in the first (aRR: 2.56, 95% CI: 1.21, 5.42, p = 0.014) and fourth (aRR: 4.79, 95% CI: 2.37, 9.71, p < 0.001) PRAL quartiles, with similar findings for NEAP. Continuous analysis showed a significant linear association between both PRAL and NEAP scores and chronic HTN. Regarding GHTN, significant associations were found in the first (aRR: 1.48, 95% CI: 1.02, 2.16, p = 0.041) and fourth (aRR: 1.88, 95% CI: 1.31, 2.70, p = 0.001) PRAL quartiles, and in Q4 for NEAP (aRR: 1.56, 95% CI: 1.10, 2.21, p = 0.012), with no significant linear association in continuous analysis.ConclusionExtremes in DAL, as indicated by PRAL and NEAP, are associated with an increased risk of preeclampsia, chronic HTN, and GHTN, particularly in the highest and lowest quartiles. These findings highlight the potential impact of DAL on HDPs.

Having two children might be best for women's mental health: Evidence from UK Biobank

BackgroundLimited research has examined the association between the number of live births and bipolar disorder and major depression (BDMD). This study aims to investigate the relationship between the number of live births and BDMD among women in the UK, providing a theoretical basis for reproductive decision-making. MethodsThis cross-sectional study utilized data from >55,000 women in the UK Biobank. Inverse probability treatment weighting (IPTW) logistic regression models were employed to reduce bias and confounding. Multivariate logistic regression was applied to examine the relationship between live births and BDMD, while restricted cubic spline regression was utilized to analyze the nonlinear association between the number of live births and BDMD. Subgroup analyses were conducted, stratifying by age, BMI, spontaneous abortion, induced abortion, and spontaneous abortion. ResultsThe IPTW-multivariate logistic regression analysis indicated that live births serve as an independent protective factor against BDMD. In IPTW-multivariate Model 4, the odds ratio (OR) for the live births group was 0.71 (95 % CI 0.69–0.73, P < 0.001). A significant nonlinear relationship was identified between the number of live births and the risk of BDMD. Additionally, it was found that women with two live births exhibited the lowest risk of BDMD. ConclusionOur study demonstrated that live births are an independent protective factor against BDMD. This research holds particular significance in the context of globally declining fertility rates and the increasing prevalence of mental disorders. It provides guidance for women on fertility decisions amid declining global fertility rates and increasing mental health issues.