Cost-Effectiveness of Sotagliflozin in SOLOIST-WHF.

BACKGROUND: The efficacy of sotagliflozin in patients with diabetes and recent worsening of heart failure was shown in the SOLOIST-WHF trial. However, the cost-effectiveness of sotagliflozin in these patients has not been previously investigated. OBJECTIVES: The authors sought to determine the cost-effectiveness of sotagliflozin in patients with diabetes and recent worsening of heart failure. METHODS: Based on SOLOIST-WHF trial data (N = 1,222), we constructed a Markov model to estimate the lifetime impact of sotagliflozin from a U.S. health care sector perspective. Cost data were sourced from the National Inpatient Sample. Life expectancy was modeled from census data and modified by the mortality rate in SOLOIST-WHF. Fatal and nonfatal event rates were carried forward from the trial data. Utility was assessed from the published reports. RESULTS: Lifetime quality-adjusted life-years (QALYs) were 4.43 and 4.04 in the sotagliflozin and placebo groups, respectively, and lifetime costs were $220,113 and $188,198 in the sotagliflozin and placebo groups, respectively. The point estimate incremental cost-effectiveness ratio was $81,823 per QALY gained. The probability of being cost-effective was 3.6%, 67.5%, and 89.4% at willingness-to-pay thresholds of $50,000, $100,000, and $150,000, respectively, per QALY gained. CONCLUSIONS: In patients with diabetes and recent worsening of heart failure, sotagliflozin is cost-effective in the U.S. using commonly accepted willingness-to-pay thresholds. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).

An incentive-based text-messaging intervention to reduce maternal alcohol use during pregnancy and lactation in South Africa (MaRISA study): Findings from a single-arm pilot study.

BACKGROUND: South Africa has the highest rate of fetal alcohol spectrum disorders (FASD) globally. As with alcohol use during pregnancy, alcohol consumption while breastfeeding adversely impacts infant development. We pilot tested an incentive-based text-messaging intervention to reduce alcohol use during pregnancy and lactation in South Africa. METHODS: A single-arm pilot trial was conducted over 3 months in healthcare facilities in Cape Town, South Africa. Pregnant and breastfeeding participants tested positive for recent alcohol use by urinalysis. The three-month intervention had two components, contingency management of alcohol abstinence confirmed by urinalysis twice weekly and weekly health-related text messaging from an evidence-based brief intervention. We collected twice weekly urine samples for measurement of ethyl glucuronide (EtG), an alcohol biomarker, and measures of self-reported alcohol and drug use, violence exposure, and mental health at six weeks and three months post-enrollment. RESULTS: Sixty participants were enrolled, of whom 31 were pregnant and 29 lactating. The number of days with four or more drinks in the past month decreased from 9 days at baseline, on average, to 1-3 days (p-value range: 0.144-0.010) at follow-up timepoints. There were statistically significant increases in the proportions of participants with alcohol-negative urine tests (p < 0.001). The percentages of participants breastfeeding while using alcohol decreased from baseline to the end of 3 months in the overall sample and among those enrolled postpartum, though these were not significant (p-value range: 0.255-0.147). Maternal depression scores also decreased among participants enrolled postpartum (p = 0.054). Emotional abuse by the main partner, but neither physical nor sexual abuse, significantly decreased at both follow-ups in the overall sample (p = 0.032) and among participants enrolled while pregnant (p = 0.015). CONCLUSIONS: This study is among the first to pilot test an incentive-based text-messaging intervention for maternal alcohol use and other outcomes such as depression and violence exposure. Further testing is warranted in a well-powered, randomized controlled trial.

Neighborhood Environment and Poor Maternal Glycemic Control-Associated Complications of Gestational Diabetes Mellitus.

Introduction: Risk of complications due to gestational diabetes mellitus is increasing in the U.S., particularly among individuals from racial minorities. Research has focused largely on clinical interventions to prevent complications, rarely on individuals' residential environments. This retrospective cohort study aims to examine the association between individuals' neighborhoods and complications of gestational diabetes mellitus. Methods: Demographic and clinical data were extracted from electronic health records and linked to American Community Survey data from the U.S. Census Bureau for 2,047 individuals who had 2,164 deliveries in 2014-2018. Data were analyzed in 2021-2022 using Wilcoxon rank sum test and chi-square test for bivariate analyses and logistic regression for analysis of independent effects. All census tract-based variables used in the model were dichotomized at the median. Results: Bivariate analysis showed that the average percentage of adults earning <$35,000 was higher in neighborhoods where individuals with complications were living than in neighborhoods where individuals without complications were living (30.40%±12.05 vs 28.94%±11.71, p=0.0145). Individuals who lived in areas with ≥8.9% of residents aged >25 years with less than high school diploma had a higher likelihood of complications than those who lived in areas with <8.9% of such residents (33.43% vs 29.02%, p=0.0272). Individuals who lived in neighborhoods that had ≥1.8% of households receiving public assistance were more likely to have complications than those who lived in areas where <1.8% of households received public assistance (33.33% vs 28.97%, p=0.0287). Logistic regression revealed that the odds of deliveries with complications were 44% higher for individuals with obesity (OR=1.44; 95% CI=1.17, 1.77), 35% greater for individuals residing in neighborhoods with higher percentages of households living below the poverty level (OR=1.35; 95% CI=1.09, 1.66), and 28% lower for individuals from neighborhoods where a higher percentage of households had no vehicles available for transportation to work (OR=0.72; 95% CI=0.59, 0.89). Conclusions: Clinical interventions in concert with environmental changes could contribute to preventing maternal and neonatal complications of gestational diabetes mellitus.

Cost of Cardiovascular Disease Event and Cardiovascular Disease Treatment-Related Complication Hospitalizations in the United States.

BACKGROUND: Cardiovascular disease (CVD) is among the costliest conditions in the United States, and cost-effectiveness analyses can be used to assess economic impact and prioritize CVD treatments. We aimed to develop standardized, nationally representative CVD events and selected possible CVD treatment-related complication hospitalization costs for use in cost-effectiveness analyses. METHODS: Nationally representative costs were derived using publicly available inpatient hospital discharge data from the 2012-2018 National Inpatient Sample. Events were identified using the principal International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes. Facility charges were converted to costs using charge-to-cost ratios, and total costs were estimated by applying a published professional fee ratio. All costs are reported in 2021 US dollars. Mean costs were estimated for events overall and stratified by age, sex, and survival status at discharge. Annual costs to the US health care system were estimated by multiplying the mean annual number of events by the mean total cost per discharge. RESULTS: The annual mean number of hospital discharges among CVD events was the highest for heart failure (1 087 000 per year) and cerebrovascular disease (800 600 per year). The mean cost per hospital discharge was the highest for peripheral vascular disease ($33 700 [95% CI, $33 300-$34 000]) and ventricular tachycardia/ventricular fibrillation ($32 500 [95% CI, $32 100-$32 900]). Hospitalizations contributing the most to annual US health care costs were heart failure ($19 500 [95% CI, $19 300-$19 800] million) and acute myocardial infarction ($18 300, [95% CI, $18 200-$18 500] million). Acute kidney injury was the most frequent possible treatment complication (515 000 per year), and bradycardia had the highest mean hospitalization costs ($17 400 [95% CI, $17 200-$17 500]). CONCLUSIONS: The hospitalization cost estimates and statistical code reported in the current study have the potential to increase transparency and comparability of cost-effectiveness analyses for CVD in the United States.

Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT USA: Results From Patients Randomized in the United States.

BACKGROUND: In 3146 REDUCE-IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow-up. METHODS AND RESULTS: We used participant-level data from REDUCE-IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in-trial analysis was participant-level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost-effectiveness ratio (incremental costs divided by incremental quality-adjusted life-years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality-adjusted life-years with IPE compared with SC using in-trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in-trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost-effectiveness ratio <$50 000 per quality-adjusted life-year gained. At a medication cost of $11.48 per day, the cost per quality-adjusted life-year gained was $36 208 in trial and $9582 over the lifetime. CONCLUSIONS: In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost-effective at $11.48 per day for conventional willingness-to-pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE-IT USA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Primary care outreach and decision counseling for lung cancer screening.

INTRODUCTION: Lung cancer screening rates are very low despite a level B recommendation from the United States Preventive Services Task Force since 2013 and clear evidence that lung cancer screening reduces mortality. The Center for Medicare and Medicaid Services requires shared decision-making (SDM) for lung cancer screening reimbursement. The objective of this study was to determine the effect of an SDM intervention on lung cancer screening in primary care. METHODS: The study design was a single-arm clinical trial design. The intervention included phone contact outside of a primary care visit and the use of the Decision Counseling Program ®, an online interactive decision aid focused on determining the factors which influence patients to screen or not screen, prioritizing those factors, and determining a decision preference score. The primary outcome was the completion of low-dose computed tomography scan (LDCT) 1 year after the SDM session compared in participants versus nonparticipants. RESULTS: From six practices, there were 1359 potentially eligible patients in electronic medical record data, and 336 were reached to assess eligibility criteria. A total of 80 patients consented to be in the study, 64 completed a decision counseling session and 16 did not complete a session. Among the 64 people who agreed to have decision counseling, 45% had LDCT, higher than typically seen in routine clinical practice. Although not a comparable group, among the 16 people who declined decision counseling, none had LDCT. CONCLUSIONS: Decision counseling is a promising intervention that might support SDM in the context of improving uptake of lung cancer screening in primary care. However, further, larger studies are needed.

Telemedicine and health disparities: Association between the area deprivation index and primary care telemedicine utilization during the COVID-19 pandemic.

Introduction: The rapid implementation of telemedicine during the COVID-19 pandemic may have exacerbated the existing health disparities. This study investigated the association between the area deprivation index (ADI), which serves as a measure of socioeconomic deprivation within a geographic area, and the utilization of telemedicine in primary care. Methods: The study data source was electronic health records. The study population consisted of patients with at least one primary care visit between March 2020 and December 2021. The primary outcome of interest was the visit modality (office, phone, and video). The exposure of interest was the ADI score grouped into quartiles (one to four, with one being the least deprived). The confounders included patient sociodemographic characteristics (e.g., age, gender, race, ethnicity, insurance coverage, marital status). We utilized generalized estimating equations to compare the utilization of telemedicine visits with office visits, as well as phone visits with video visits. Results: The study population included 41,583 patients with 127,165 office visits, 39,484 phone visits, and 20,268 video visits. Compared to patients in less disadvantaged neighborhoods (ADI quartile = one), patients in more disadvantaged neighborhoods (ADI = two, three, or four) had higher odds of using phone visits vs office visits, lower odds of using video visits vs office visits, and higher odds of using phone visits vs video visits. Conclusions: Patients who resided in socioeconomically disadvantaged neighborhoods mainly relied on phone consultations for telemedicine visits with their primary care provider. Patient-level interventions are essential for achieving equitable access to digital healthcare, particularly for low-income individuals.

Identification of risk factors for infection after mitral valve surgery through machine learning approaches.

Background: Selecting features related to postoperative infection following cardiac surgery was highly valuable for effective intervention. We used machine learning methods to identify critical perioperative infection-related variables after mitral valve surgery and construct a prediction model. Methods: Participants comprised 1223 patients who underwent cardiac valvular surgery at eight large centers in China. The ninety-one demographic and perioperative parameters were collected. Random forest (RF) and least absolute shrinkage and selection operator (LASSO) techniques were used to identify postoperative infection-related variables; the Venn diagram determined overlapping variables. The following ML methods: random forest (RF), extreme gradient boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), AdaBoost, Naive Bayesian (NB), Logistic Regression (LogicR), Neural Networks (nnet) and artificial neural network (ANN) were developed to construct the models. We constructed receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) was calculated to evaluate model performance. Results: We identified 47 and 35 variables with RF and LASSO, respectively. Twenty-one overlapping variables were finally selected for model construction: age, weight, hospital stay, total red blood cell (RBC) and total fresh frozen plasma (FFP) transfusions, New York Heart Association (NYHA) class, preoperative creatinine, left ventricular ejection fraction (LVEF), RBC count, platelet (PLT) count, prothrombin time, intraoperative autologous blood, total output, total input, aortic cross-clamp (ACC) time, postoperative white blood cell (WBC) count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), PLT count, hemoglobin (Hb), and LVEF. The prediction models for infection after mitral valve surgery were established based on these variables, and they all showed excellent discrimination performance in the test set (AUC > 0.79). Conclusions: Key features selected by machine learning methods can accurately predict infection after mitral valve surgery, guiding physicians in taking appropriate preventive measures and diminishing the infection risk.

The Association of Maternal Smoking and Drinking Changes During Pregnancy and Postpartum Breastfeeding Pattern and Duration.

Objectives: To conduct a secondary data analysis of how changes in smoking and drinking during pregnancy impact status of any breastfeeding and breastfeeding duration in a national cohort. Materials and Methods: A cross-sectional study was conducted using Pregnancy Risk Assessment Monitoring System (PRAMS) data between 2009 and 2017 (n = 334,203). Univariate and multivariate analyses were conducted on the status of any breastfeeding and breastfeeding duration. Results: A dose-dependent inverse relationship was found in which women who smoked the same or more or resumed smoking during pregnancy showed the lowest likelihood and shortest duration of breastfeeding, followed by reduced smokers, quitters, and nonsmokers. Women with a history of alcohol use were significantly more likely to breastfeed compared with women without a history of alcohol use. Conclusions: The profile of smoking change during pregnancy impacts the likelihood and duration of breastfeeding in a dose-dependent and inverse manner. No such relationship was found with drinking change during pregnancy. Public Health Implications: Significant public health efforts should focus on implementing and sustaining evidence-based interventions for prenatal smoking cessation and educating providers and maternal populations on the adverse effect of postpartum alcohol exposure.

Association of Area Deprivation With Primary Hypertension Diagnosis Among Youth Medicaid Recipients in Delaware.

Importance: The association between degree of neighborhood deprivation and primary hypertension diagnosis in youth remains understudied. Objective: To assess the association between neighborhood measures of deprivation and primary hypertension diagnosis in youth. Design, Setting, and Participants: This cross-sectional study included 65 452 Delaware Medicaid-insured youths aged 8 to 18 years between January 1, 2014, and December 31, 2019. Residence was geocoded by national area deprivation index (ADI). Exposures: Higher area deprivation. Main Outcomes and Measures: The main outcome was primary hypertension diagnosis based on International Classification of Diseases, Ninth Revision and Tenth Revision codes. Data were analyzed between September 1, 2021, and December 31, 2022. Results: A total of 65 452 youths were included in the analysis, including 64 307 (98.3%) without a hypertension diagnosis (30 491 [47%] female and 33 813 [53%] male; mean [SD] age, 12.5 (3.1) years; 12 500 [19%] Hispanic, 25 473 [40%] non-Hispanic Black, 24 565 [38%] non-Hispanic White, and 1769 [3%] other race or ethnicity; 13 029 [20%] with obesity; and 31 548 [49%] with an ADI ≥50) and 1145 (1.7%) with a diagnosis of primary hypertension (mean [SD] age, 13.3 [2.8] years; 464 [41%] female and 681 [59%] male; 271 [24%] Hispanic, 460 [40%] non-Hispanic Black, 396 [35%] non-Hispanic White, and 18 [2%] of other race or ethnicity; 705 [62%] with obesity; and 614 [54%] with an ADI ≥50). The mean (SD) duration of full Medicaid benefit coverage was 61 (16) months for those with a diagnosis of primary hypertension and 46.0 (24.3) months for those without. By multivariable logistic regression, residence within communities with ADI greater than or equal to 50 was associated with 60% greater odds of a hypertension diagnosis (odds ratio [OR], 1.61; 95% CI 1.04-2.51). Older age (OR per year, 1.16; 95%, CI, 1.14-1.18), an obesity diagnosis (OR, 5.16; 95% CI, 4.54-5.85), and longer duration of full Medicaid benefit coverage (OR, 1.03; 95% CI, 1.03-1.04) were associated with greater odds of primary hypertension diagnosis, whereas female sex was associated with lower odds (OR, 0.68; 95%, 0.61-0.77). Model fit including a Medicaid-by-ADI interaction term was significant for the interaction and revealed slightly greater odds of hypertension diagnosis for youths with ADI less than 50 (OR, 1.03; 95% CI, 1.03-1.04) vs ADI ≥50 (OR, 1.02; 95% CI, 1.02-1.03). Race and ethnicity were not associated with primary hypertension diagnosis. Conclusions and Relevance: In this cross-sectional study, higher childhood neighborhood ADI, obesity, age, sex, and duration of Medicaid benefit coverage were associated with a primary hypertension diagnosis in youth. Screening algorithms and national guidelines may consider the importance of ADI when assessing for the presence and prevalence of primary hypertension in youth.

Immune and non-immune cell subtypes identify novel targets for prognostic and therapeutic strategy: A study based on intratumoral heterogenicity analysis of multicenter scRNA-seq datasets in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and the leading cause of cancer incidence and mortality worldwide. Despite the improvement of traditional and immunological therapies, the clinical outcome of LUAD is still far from satisfactory. Patients given the same treatment regimen had different responses and clinical outcomes due to the heterogeneity of LUAD. How to identify the targets based on heterogeneity analysis is crucial for treatment strategies. Recently, the single-cell RNA-sequencing (scRNA-seq) technology has been used to investigate the tumor microenvironment (TME) based on cell-specific changes and shows prominently valuable for biomarker prediction. In this study, we systematically analyzed a meta-dataset from the multiple LUAD scRNA-seq datasets in LUAD, identified 15 main types of cells and 57 cell subgroups, and revealed a series of potential biomarkers in M2b, exhausted CD8+T, endothelial cells, fibroblast, and metabolic patterns in TME, which further validated with immunofluorescence in clinical cohorts of LUAD. In the prognosis analysis, M0 macrophage and T cell activation were shown correlated to a better prognosis (p<0.05). Briefly, our study provided insights into the heterogeneity of LUAD and assisted in novel therapeutic strategies for clinical outcome improvement.

The burden of cardiovascular disease attributable to high systolic blood pressure across China, 2005-18: a population-based study.

BACKGROUND: Temporal trends and geographical variations in cardiovascular disease attributable to high systolic blood pressure in China are not yet fully understood. The aim of this study was to quantify the cardiovascular disease burden attributable to high systolic blood pressure at national and provincial levels in China. METHODS: In this population-based study, we evaluated systolic blood pressure and estimated the number of deaths, age-standardised mortality rates, and years of life lost (YLLs) due to cardiovascular disease and its subcategories (including ischaemic heart disease, ischaemic stroke, haemorrhagic stroke, and other cardiovascular diseases) attributable to high systolic blood pressure, at the national level and by 31 provincial levels, in China, from 2005 to 2018. We pooled blood pressure data of 1·30 million adults aged 25 years and older from the China Chronic Disease and Risk Factor Surveillance project, the China National Nutrition Survey, and the China Hypertension Survey. We applied a temporal-spatial Bayesian hierarchical model to estimate age-specific, sex-specific, province-specific, and year-specific average systolic blood pressure, and a comparative risk assessment method to compute the cardiovascular disease burden attributable to high systolic blood pressure by age, sex, year, and province. FINDINGS: Nationally, age-standardised mean systolic blood pressure was 132·5 mm Hg (95% uncertainty interval [UI] 124·6-140·3) in men and 129·4 mm Hg (121·7 to 137·2) in women. 2·67 million (95% UI 2·61 to 2·72) cardiovascular disease deaths in China were attributable to high systolic blood pressure, including 1·12 million deaths (1·07 to 1·16) due to ischaemic heart disease, 0·63 million deaths (0·60 to 0·65) due to ischaemic stroke, 0·58 million deaths (0·57 to 0·60) due to haemorrhagic stroke, and 0·34 million deaths (0·32 to 0·36) due to other cardiovascular disease. The age-standardised cardiovascular disease mortality rates associated with high systolic blood pressure were 268·99 per 100 000 people (95% UI 264·11 to 273·51) in 2005 and 220·84 per 100 000 people (216·30 to 224·76) in 2018, a percentage change of -17·90%; the rate changed by an average of -1·50% (95% UI -1·55% to -1·45%) per year from 2005 to 2018 nationally. YLL rates for total cardiovascular disease caused by high systolic blood pressure varied substantially across provinces, ranging from 3078·33 (95% UI 2807·40 to 3303·57) per 100 000 people in Beijing to 7189·98 (95% UI 6817·18 to 7507·99) per 100 000 people in Heilongjiang in 2018. Age-standardised YLL rates for ischaemic heart disease and ischaemic stroke attributable to high systolic blood pressure were particularly high in northeastern provinces, including Heilongjiang, Liaoning, and Jilin. INTERPRETATION: The deaths and YLLs for cardiovascular disease attributable to high systolic blood pressure in China increased between 2005 and 2018, and age-standardised cardiovascular disease mortality rates decreased in the same timeframe. Our findings could help policy makers in promoting blood pressure control measures and implementing effective and locally adapted preventive interventions to reduce the prevalence of high systolic blood pressure and reduce the burden of systolic blood pressure-related cardiovascular disease in China. FUNDING: China National Key Research and Development Program, China National Science & Technology Pillar Program, and National Health Commission of the People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension.

BACKGROUND: For hypertensive patients without a history of stroke or myocardial infarction (MI), the China Stroke Primary Prevention Trial (CSPPT) demonstrated that treatment with enalapril-folic acid reduced the risk of primary stroke compared with enalapril alone. Whether folic acid therapy is an affordable and beneficial treatment strategy for the primary prevention of stroke in hypertensive patients from the Chinese healthcare sector perspective has not been thoroughly explored. METHODS: We performed a cost-effectiveness analysis alongside the CSPPT, which randomized 20,702 hypertensive patients. A patient-level microsimulation model based on the 4.5-year period of in-trial data was used to estimate costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for enalapril-folic acid vs. enalapril over a lifetime horizon from the payer perspective. RESULTS: During the in-trial follow-up period, patients receiving enalapril-folic acid gained an average of 0.016 QALYs related primarily to reductions in stroke, and the incremental cost was $706.03 (4553.92 RMB). Over a lifetime horizon, enalapril-folic acid treatment was projected to increase quality-adjusted life years by 0.06 QALYs or 0.03 life-year relative to enalapril alone at an incremental cost of $1633.84 (10,538.27 RMB), resulting in an ICER for enalapril-folic acid compared with enalapril alone of $26,066.13 (168,126.54 RMB) per QALY gained and $61,770.73 (398,421.21 RMB) per life-year gained, respectively. A probabilistic sensitivity analysis demonstrated that enalapril-folic acid compared with enalapril would be economically attractive in 74.5% of simulations at a threshold of $37,663 (242,9281 RMB) per QALY (3x current Chinese per capita GDP). Several high-risk subgroups had highly favorable ICERs < $12,554 (80,976 RMB) per QALY (1x GDP). CONCLUSIONS: For both in-trial and over a lifetime, it appears that enalapril-folic acid is a clinically and economically attractive medication compared with enalapril alone. Adding folic acid to enalapril may be a cost-effective strategy for the prevention of primary stroke in hypertensive patients from the Chinese health system perspective.

An efficient approach for optimizing the cost-effective individualized treatment rule using conditional random forest.

Evidence from observational studies has become increasingly important for supporting healthcare policy making via cost-effectiveness analyses. Similar as in comparative effectiveness studies, health economic evaluations that consider subject-level heterogeneity produce individualized treatment rules that are often more cost-effective than one-size-fits-all treatment. Thus, it is of great interest to develop statistical tools for learning such a cost-effective individualized treatment rule under the causal inference framework that allows proper handling of potential confounding and can be applied to both trials and observational studies. In this paper, we use the concept of net-monetary-benefit to assess the trade-off between health benefits and related costs. We estimate cost-effective individualized treatment rule as a function of patients' characteristics that, when implemented, optimizes the allocation of limited healthcare resources by maximizing health gains while minimizing treatment-related costs. We employ the conditional random forest approach and identify the optimal cost-effective individualized treatment rule using net-monetary-benefit-based classification algorithms, where two partitioned estimators are proposed for the subject-specific weights to effectively incorporate information from censored individuals. We conduct simulation studies to evaluate the performance of our proposals. We apply our top-performing algorithm to the NIH-funded Systolic Blood Pressure Intervention Trial to illustrate the cost-effectiveness gains of assigning customized intensive blood pressure therapy.

Effect of lipid-lowering medications in patients with coronary artery bypass grafting surgery outcomes.

BACKGROUND: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: After IRB approval, we reviewed charts of 9,518 patients who underwent cardiac surgery with CPB at three medical centers between July 2001 and June 2015. The relationship between perioperative lipid-lowering treatment and postoperative outcome was investigated. 3,988 patients who underwent CABG met inclusion criteria and were analyzed. Patients were divided into lipid-lowering or non-lipid-lowering treatment groups. RESULTS: A total of 3,988 patients were included in the final analysis. Compared to the patients without lipid-lowering medications, the patients with lipid-lowering medications had lower postoperative neurologic complications and overall mortality (P < 0.05). Propensity weighted risk-adjustment showed that lipid-lowering medication reduced in-hospital total complications (odds ratio (OR) = 0.856; 95% CI 0.781-0.938; P < 0.001); all neurologic complications (OR = 0.572; 95% CI 0.441-0.739; P < 0.001) including stroke (OR = 0.481; 95% CI 0.349-0.654; P < 0.001); in-hospital mortality (OR = 0.616; 95% CI 0.432-0.869; P = 0.006; P < 0.001); and overall mortality (OR = 0.723; 95% CI 0.634-0.824; P < 0.001). In addition, the results indicated postoperative lipid-lowering medication use was associated with improved long-term survival in this patient population. CONCLUSIONS: Perioperative lipid-lowering medication use was associated with significantly reduced postoperative adverse events and improved overall outcome in elderly patients undergoing CABG surgery with CPB.

Comprehensive analysis of pyroptosis regulation patterns and their influence on tumor immune microenvironment and patient prognosis in glioma.

BACKGROUND: Glioma is the most common intracranial malignancy with a poor prognosis. Although remarkable advances have been made in the study of diagnostic and prognostic biomarkers, the efficacy of current treatment strategies is still unsatisfactory. Therefore, developing novel and reliable targets is desperately needed for glioma patients. Pyroptosis reshapes tumor immune microenvironment (TME) and promotes the destruction of the tumor by the immune system. Moreover, pyroptosis levels correlate with prognosis and immunotherapy response in many cancer patients. This study performed a comprehensive analysis of pyroptosis in the glioma, unveiling its potential value in glioma prognosis prediction and therapy efficacy. METHODS: Firstly, the pyroptosis regulation patterns were comprehensively evaluated on 33 pyroptosis-related genes in 1716 glioma samples. The correlations were analyzed between pyroptosis regulation patterns and TME immune cell infiltration properties. Next, pyroptosis regulation patterns were measured by the PSscore model based on principal component analysis algorithms. The correlations were analyzed between PSscore and tumor mutational burden (TMB), immune checkpoint blockade (ICB) therapeutic advantages. Last, the findings were validated in an independently collected external clinical cohort. RESULTS: We determined two distinct pyroptosis regulation patterns. The cluster-A was high immune cell infiltration with a poor prognosis (p < 0.001), whereas the cluster-B was low immune cell infiltration with a better prognosis (p < 0.001). We developed the PSscore as a measure for pyroptosis regulation patterns. The high PSscore with an inflamed TME phenotype, a high TMB (p < 0.0001), increased innate immune response, and a poor prognosis (p < 0.001). It was in stark contrast to the low PSscore (p < 0.001). Analysis of PSscore with checkpoint therapy indicated high PSscore were correlated with enhanced response to anti-PD-1 immunotherapy (p = 0.0046). For validation, we utilized in vitro experiments on an external clinical cohort. The results demonstrated that GSDMD expression level in the high PSscore group was significantly upregulated compared to the low PSscore group (p < 0.001); the CD3+ T cells and the CD3+PD-1+ cells significantly increased in the high PSscore group compared to the low PSscore group (p < 0.01). CONCLUSIONS: The PSscore of pyroptosis regulation pattern is a reliable biomarker, and it is valuable to predict prognosis, TME, and ICB therapeutic efficiency in glioma patients.

Associations of road traffic noise with cardiovascular diseases and mortality: Longitudinal results from UK Biobank and meta-analysis.

BACKGROUND: Epidemiological evidence suggests potential associations of road traffic noise exposure with cardiovascular disease (CVD) and mortality, but uncertainty remains. OBJECTIVES: We examined the association of road traffic noise with the risk of CVD and mortality in a large longitudinal cohort study and meta-analysis. METHODS: We analyzed 342, 566 participants from the UK Biobank who were free of CVD at baseline and had complete covariate data. We also performed a meta-analysis of road traffic noise effects on CVD and mortality by including qualified cohort studies published before April 2021. RESULTS: After adjustment for potential confounders, the odds for the risk of stroke, CVD, and all-cause mortality increased by 1.07 (95%CI: 1.01-1.13, P = 0.019), 1.13 (95%CI: 1.04-1.22, P = 0.003) and 1.08 (95%CI: 1.04-1.12, P < 0.001) times per 10 dB increases in road traffic noise, respectively. Among men, high road traffic noise exposure was significantly associated with an increased risk in stroke (HR = 1.08 per 10 dB increase, 95%CI: 1.00-1.16, P = 0.043), CVD (HR = 1.12 per 10 dB increase, 95%CI: 1.02-1.23, P = 0.020) and all-cause mortality (HR = 1.12 per 10 dB increase, 95%CI: 1.07-1.17 P < 0.001), whereas we did not find a significant association in women. The meta-analysis showed that road traffic noise exposure was significantly associated with a high risk of stroke (risk ratio [RR]: 1.06, 95% CI: 1.02-1.11), CVD mortality (RR: 1.03, 95% CI: 1.00-1.05), all-cause mortality (RR: 1.05, 95% CI: 1.02-1.07). CONCLUSIONS: This study provides more evidence of increased risk of stroke, CVD, and all-cause mortality in association with exposure to road traffic noise pollution, especially in men.

Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.

Importance: The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. Objective: To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. Design, Setting, and Participants: An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Interventions: Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main Outcomes and Measures: Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. Results: A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. Conclusions and Relevance: This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

Perioperative dexmedetomidine and 5-year survival in patients undergoing cardiac surgery.

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.

Nutritional assessment and comparison of nutritional indices in predicting adverse outcomes in patients undergoing left ventricular assist device implantation.

BACKGROUND: Preoperative malnutrition has been correlated to postoperative complications in patients with advanced heart failure undergoing placement of a left ventricular assist device (LVAD). We sought to determine whether nutritional risk scores could identify a subset of patients with an LVAD who were at high risk of adverse events. METHODS: We conducted a retrospective cohort study of all patients undergoing LVAD placement at a single center. The prognostic nutritional index (PNI), nutritional risk index (NRI), and nutrition risk in the critically ill (NUTRIC) score were calculated retrospectively from data abstracted from chart review. The primary endpoint was a composite of mortality and other adverse events associated with LVAD implantation. We used χ2 or Fisher exact tests to compare these three indices against the primary outcome. RESULTS: A total of 41 patients with a mean age of 57.2 ± 13.7 y and a mean body mass index of 29.3 ± 6.3 kg/m2 underwent LVAD placement between 2011 and 2019. The composite outcome at 1 y occurred in 31 (76%) patients. Preoperatively, 3 patients were identified as at high nutritional risk by the PNI score and 39 by the NRI score but none by the NUTRIC score. Most patients received nutritional interventions. The nutritional risk scores did not differ significantly between patients who experienced the composite outcome and those who did not. CONCLUSIONS: The NRI, NUTRIC, and PNI scores did not identify a subset of patients at high risk for the composite outcome. Further studies are needed to determine how to better assess the true nutritional risk of the LVAD population. However, until better risk stratification is available, all patients with an LVAD should be consider at high risk and given appropriate nutritional interventions.