Cox Proportional Hazards Analysis Research Articles

Long-term outcomes of laparoscopic versus open total gastrectomy in patients with advanced gastric cancer after neoadjuvant chemotherapy: a retrospective cohort study.

This study was conducted to investigate the long-term outcomes of laparoscopic total gastrectomy (LTG) versus open total gastrectomy (OTG) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NACT). Patients with AGC who received NACT before surgery were enrolled in either the LTG or OTG group. Propensity score matching (PSM) (1:2) was performed between the two groups based on the propensity score using a 0.15 calliper width. Three-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups before and after PSM. OS and DFS rates were calculated by the Kaplan‒Meier method, and any differences in survival were evaluated with a log-rank test. Univariate and multivariate Cox proportional hazards analyses were used to estimate the simultaneous effects of prognostic factors on survival and the hazard ratio (HR) between LTG and OTG patients. A total of 144 patients completed the follow-up, with 24patientsintheLTG group and 120 patients intheOTG group. After a mean follow-up of 64.40months, there were no significant differences in the 3-year OS or DFS rates between the two groups before (P = 0.453 and P = 0.362, respectively) or after PSM (P = 0.972 and P = 0.884, respectively). Multivariate Cox proportional hazards analysis indicated that ypN stage was an independent risk factor for worse OS (P = 0.013). This study showed that LTG with D2 lymphadenectomy performed by an experienced surgical team resulted in comparable 3-year OS and DFS compared with OTG in patients with AGC after NACT. This study is not registered.

Prognostic Factors in Japanese EGFR Mutation-Positive Non-Small-Cell Lung Cancer: A Real-World Single-Center Retrospective Cohort Study.

The prognosis of patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer has improved significantly since the advent of EGFR tyrosine kinase inhibitors (EGFR-TKIs). We aimed to investigate the relationship between patient characteristics, EGFR genotype, therapeutic agents, and the prognosis of the patients with EGFR mutation-positive lung cancer. This retrospective cohort study analyzed 198 Japanese patients with unresectable EGFR mutation-positive lung cancer who were treated with EGFR-TKIs at Toho University Sakura Medical Center from April 2006 to December 2021. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards analysis. Patients who received osimertinib had a significantly longer OS than did those not receiving it (median OS, 36.2 versus 20.7 months; p < 0.001).There were significant differences in OS between patients with EGFR mutation who received osimertinib as first-line treatment, T790M-positive patients who received osimertinib as second- or later-line treatment, and those who did not receive it (median OS, 28.2 versus 40.2 versus 20.7 months; p = 0.003). However, in T790M-negative patients, no significant difference in OS was noted between those who did and did not receive osimertinib as post-treatment (median OS, 28.0 versus 40.0 months; p = 0.619). Multivariate Cox proportional hazards analysis showed that osimertinib treatment was associated with longer OS (hazard ratio, 0.480; 95% confidence interval, 0.326-0.707; p < 0.001). The patients who were T790M-positive in the first-line treatment with first or second-generation EGFR-TKIs and were given osimertinib as the second or later line treatment had a better prognosis than the patients who were T790M-negative in the first-line treatment with first or second-generation EGFR-TKIs and could not receive osimertinib.

Weight Change After Cancer Diagnosis and Risk of Diabetes Mellitus: A Population-Based Nationwide Study.

Cancer survivors are at increased risk of diabetes mellitus (DM). Additionally, the prevalence of obesity, which is also a risk factor for DM, is increasing in cancer survivors. We investigated the associations between weight change after cancer diagnosis and DM risk. This retrospective cohort study used data from the Korean National Health Insurance Service. Participants who were newly diagnosed with cancer from 2010 to 2016 and received national health screening before and after diagnosis were included and followed until 2019. Weight change status after cancer diagnosis was categorized into four groups: sustained normal weight, obese to normal weight, normal weight to obese, or sustained obese. Cox proportional hazard analyses were performed to examine associations between weight change and DM. The study population comprised 264,250 cancer survivors. DM risk was highest in sustained obese (adjusted hazard ratios, 95% confidence interval: 2.17, 2.08-2.26), followed by normal weight to obese (1.66, 1.54-1.79), obese to normal weight (1.29, 1.21-1.39), and then sustained normal weight group (reference). In subgroup analyses according to cancer type, most cancers showed the highest risks in sustained obese group. Obesity at any time point was related to increased DM risk, presenting the highest risk in cancer survivors with sustained obesity. Survivors who changed from obese to normal weight had lower risk than survivors with sustained obesity. Survivors who changed from normal weight to obese showed increased risk compared to those who sustained normal weight. Our finding supports the significance of weight management among cancer survivors.

Exploring causal effects of sarcopenia on risk and progression of Parkinson disease by Mendelian randomization.

Previous observational studies suggested that sarcopenia is associated with Parkinson disease (PD), but it is unclear whether this association is causal. The objective of this study was to examine causal associations between sarcopenia-related traits and the risk or progression of PD using a Mendelian randomization (MR) approach. Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (n = 461,089), left handgrip strength (n = 461,026), and appendicular lean mass (n = 450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach and pathway enrichment analysis using genotype data from the Parkinson's Progression Markers Initiative. MR results supported a significant causal influence of right handgrip strength (odds ratio [OR] = 0.152, 95% confidence interval [CI] = 0.055-0.423, adjusted P = 0.0036) and appendicular lean mass (OR = 0.597, 95% CI = 0.440-0.810, adjusted P = 0.0111) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR] = 0.225, 95% CI = 0.095-0.530, adjusted P = 0.0019) and left handgrip strength (HR = 0.303, 95% CI = 0.121-0.59, adjusted P = 0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates. Pathway enrichment analysis revealed that genome-wide significant single-nucleotide polymorphisms for right handgrip strength were substantially enriched in biological pathways involved in the control of synaptic plasticity. This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.

Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression.

The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5-10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100-129, 130-159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Slow Gait Speed Predicts Incident Dementia, Mortality, and Long-Term Functional Outcome in Cerebral Small-Vessel Disease.

Gait impairment is observed in patients with small vessel disease (SVD); however, the association between gait function and long-term outcome remains unclear. This study aimed to clarify the predictive value of gait function on incident dementia, survival and functional outcome. Data were derived from a Japanese cohort of patients with SVD. This study included 522 participants who underwent 3-m timed up and go test (TUG), and gait speed, TUG time, was divided into tertiles. Magnetic resonance imaging was used to evaluate severity of white matter hyperintensities, lacunes, and medial temporal atrophy. Primary outcome was dementia. All-cause death and functional outcome by modified Rankin scale at the last visit was also evaluated. The median age was 71 years, and median TUG time was 9.91 s. During follow-up period of 4.8 years, 32 cases of dementia occurred. Cox proportional hazard analysis revealed that slow gait speed (TUG time > 10.88 s) was associated with a significantly higher risk of incident dementia than fast (TUG time < 9.03) and middle (TUG time, 9.04-10.87 s) speeds after adjusting risk factors, Mini-Mental State Examination, SVD severity and brain atrophy (adjusted hazard ratio, 2.73; 95% confidence interval, 1.16-6.42, p = 0.022). Slow speed was also associated with mortality and poor functional outcome compared with other speeds (adjusted odds ratio, 4.19; 95% confidence interval 1.92-9.18, p < 0.001). Gait function was associated with incident dementia, mortality and poor functional outcome independently of cognitive function, brain atrophy, and SVD severity.

Recompensation of Chronic Hepatitis C-related decompensated cirrhosis following direct-acting antiviral therapy: Prospective Cohort study from an HCV elimination program.

Background and AimsChronic hepatitis C(CHC) related decompensated cirrhosis is associated with lower SVR-12 rates and variable regression of disease severity following direct-acting antiviral agents (DAAs). We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. MethodsBetween July 2018-July 2023, patients with decompensated CHC-related cirrhosis post DAAs treatment, were evaluated for SVR-12 and then had 6-monthly follow-up. ResultsOf 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2±11.5 years,63% men, MELD-Na:16.5± 4.6,87% genotype 3) were enrolled. SVR-12 was 81.8% after one course; ultimately SVR was 90.8% following additional treatment. Decompensation events included ascites (1098,95.3%), hepatic encephalopathy (191,16.6%), and variceal bleeding (284,24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284(24.7%) at a median time of 16.5(IQR-14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin(aHR-0.6,95%CI-0.5-0.8,P<0.001), INR(aHR-0.2,95%CI:0.1-0.3,P<0.001), absence of large esophageal varices(aHR-0.4,95%CI:0.2-0.9,P=0.048), or gastric varices (aHR-0.5,95%CI:0.3-0.7,P=0.022) predicted recompensation. Portal hypertension (PHT) progressed in 158(13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR-1.6,95%CI:1.2-2.8, P=0.042), and presence of large varices (aHR-2.9,95%CI:1.3-6.5,P<0.001) were associated with PHT progression. Further decompensation was seen in 221(19%);145 patients died and 6 underwent liver transplant. A decrease in MELDNa of ≥3 was in 409(35.5%) and a final MELDNa score of <10 was in 335(29%), but 2.9% developed HCC despite SVR-12. ConclusionsSVR-12 in HCV-related decompensated cirrhosis in a predominant genotype 3 population, led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and HCC developed in 2.9% of patients.

Sex, Atrial Fibrillation, and Long-Term Mortality After Cardiac Surgery

There are limited data on the association of sex with the incidence of postoperative atrial fibrillation (poAF) and subsequent long-term mortality after cardiac surgery. To evaluate whether the incidence of poAF and associated long-term mortality after cardiac surgery differ by sex. This retrospective cohort study was conducted at 2 tertiary care centers in Massachusetts from January 1, 2002, until October 1, 2016, with follow-up until December 1, 2022. Adult (aged >20 years) women and men undergoing coronary artery bypass graft surgery, aortic valve surgery, mitral valve surgery, and combined procedures with cardiopulmonary bypass were examined using medical records. Patients who had data on poAF were included in data analyses. Sex and poAF. Primary outcomes were the incidence of poAF and all-cause mortality. poAF was defined as any atrial fibrillation detected on electrocardiogram (EKG) during the index hospitalization in patients presenting for surgery in normal sinus rhythm. Data on poAF were obtained from EKG reports and supplemented by information from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. All-cause mortality was assessed via hospital records. The hypotheses were formulated prior to data analysis. Among 21 568 patients with poAF data (mean [SD] age, 66.5 [12.4] years), 2694 of 6601 women (40.8%) and 5805 of 14 967 men (38.8%) developed poAF. In a multivariable logistic regression model, women had lower risk of poAF (odds ratio [OR], 0.85; 95% CI, 0.79-0.91; P < .001). During the follow-up study period, 1294 women (50.4%) and 2376 men (48.9%) in the poAF group as well as 1273 women (49.6%) and 2484 men (51.1%) in the non-poAF group died. Cox proportional hazards analysis found that the association between poAF and mortality was significantly moderated (ie, effect modified) by sex. Compared with same-sex individuals without poAF, men with poAF had a 17% higher mortality hazard (hazard ratio [HR], 1.17; 95% CI, 1.11-1.25; P < .001), and women with poAF had a 31% higher mortality hazard (HR, 1.31; 95% CI, 1.21-1.42; P < .001). In this retrospective cohort study of 21 568 patients who underwent cardiac surgery, women were less likely to develop poAF than men when controlling for other relevant characteristics; however, women who did develop poAF had a higher risk of long-term mortality than men who developed poAF. This observed elevated risk calls for a tailored approach to perioperative care in women undergoing cardiac surgery.

Prognostic Impact of Sarcopenia Assessed Using Modified Asian Working Group for Sarcopenia 2019 Criteria in Heart Failure

Sarcopenia is a substantial therapeutic target, yet the validity of risk stratification values per the latest Asian Working Group for Sarcopenia in 2019 (AWGS 2019) remains unconfirmed in patients with heart failure. We hypothesized that using the 6-minute walk test (6MWT) to assess physical performance improves risk stratification. The study included 832 hospitalized patients with heart failure who could walk at discharge. Sarcopenia was diagnosed using both the original AWGS 2019 criteria (AWGS 2019 model) and an alternative method, in which physical performance components were replaced with the 6MWT (modified model). An <300 m 6MWT indicated low physical performance in the modified model. The primary outcome was 2-year mortality. Sarcopenia and severe sarcopenia were identified in 45 and 150 patients with the AWGS 2019 model and in 75 and 108 patients with the modified model, respectively. Over the 2-year follow-up period, 145 (17.4%) deaths occurred. Adjusted Cox proportional hazard analysis showed both sarcopenia and severe sarcopenia were significantly associated with 2-year mortality in the modified model. In the AWGS 2019 model, only severe sarcopenia was significantly related to 2-year mortality. The modified model demonstrated significant net reclassification improvement (NRI) over the AWGS 2019 model (NRI, 0.396; 95% CI, 0.214-0.578; P < 0.001). In patients with heart failure who were ambulatory at discharge, sarcopenia assessment with the modified AWGS 2019 model using the 6MWT as a physical performance component improved risk stratification compared with the original AWGS 2019 model. Reconsidering the current criteria to improve risk stratification is necessary to ensure timely, appropriate treatment.

Recurrence-Free Survival after Postoperative Hormone Therapy for Catamenial Pneumothorax.

Catamenial pneumothorax (CP) is a rare form of spontaneous pneumothorax that is linked to endometriosis; thus, it predominantly manifests in women of reproductive age. Considerable research has explored the potential benefits of postoperative hormone therapy following various surgical interventions. This study was performed to examine the clinical implications of postoperative hormone treatment in patients with CP. The study included patients who underwent surgical intervention for CP between November 2009 and February 2023. These procedures included wedge resection, diaphragm resection, and total pleural coverage. Recurrence-free survival was analyzed using the Kaplan-Meier log-rank test to assess the impact of hormone therapy. Additionally, Cox proportional hazards analysis was employed to identify risk factors associated with postoperative CP recurrence. The study included 41 patients, with a median age of 38.4 years. Among them, 27 individuals received hormone therapy, 8 of whom experienced recurrence during a median follow-up period of 1 year. Patients who received hormone therapy exhibited a lower rate of recurrence than those who did not; however, the difference was not statistically significant, likely due to the small sample size. Side effects of hormone therapy included depression (6.8%), excessive sweating (3.4%), and headache (3.4%). In the analysis of risk factors for postoperative recurrence, diaphragm resection emerged as a protective factor (hazard ratio, 0.16; 95% confidence interval, 0.03-0.77; p=0.022). Hormone treatment combined with surgery did not significantly impact recurrence in patients with CP. The application of diaphragm resection was the sole factor that displayed significance in preventing CP recurrence.

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival.

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

Diabetes mellitus with poor glycemic control is a risk factor for pneumonia in COPD

BackgroundPneumonias are events of great prognostic significance in COPD, so it is important to identify predictive factors. ObjectiveTo determine whether poor glycemic control is related to an increased risk of pneumonia in COPD. MethodA historical cohort study conducted in a COPD clinic. The first severe exacerbation after the first visit was analyzed. Exacerbations that presented with pulmonary infiltrates were identified. A Cox proportional hazards analysis was performed including the values of glycosylated hemoglobin (Hb1Ac) in patients with diabetes mellitus (DM) and variables that could plausibly be related to the risk of pneumonia. The best Hb1Ac value to predict pneumonia was assessed using receiver-operating characteristics analysis. ResultsThere were 1124 cases included in the study. A total of 411 patients were admitted to the hospital at least once and 87 were diagnosed with pneumonia. Variables associated with the risk of pneumonia were previous admissions due to COPD and Hb1Ac values (HR: 2.33, 95% CI: 1.06 – 5.08, p = 0.03). A higher body mass index (BMI) was associated with a lower risk of pneumonia. The optimal cutoff point for Hb1Ac to predict pneumonia risk was 7.8 %. The patients were classified into 3 groups: (1) no DM, (2) controlled DM (Hb1AC < 7.8 %), (3) uncontrolled DM (Hb1AC ≥ 7.8 %). The risk of pneumonia for group 2 was not different from group 1, while the risk for group 3 was significantly higher than for groups 1 and 2 (HR: 4.52, 95 % CI: 1.57 – 13.02). ConclusionsPoor control of DM is a predictor of the risk of pneumonia in COPD. The cutoff point of 7.8 % for this variable seems to be the most useful to identify patients at risk.

Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma.

Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a "low-risk" group, but some low-risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression values in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. This was a retrospective, international, multicenter cohort study that included WHO grade 1 meningiomas that underwent GTR, as first treatment, based on postoperative magnetic resonance imaging. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low-risk meningiomas. In total, 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. The median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence was 90.5%, and median time to recurrence was 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. Of these genes, PGK1 had the largest effect size. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low-risk meningiomas with significant differences in local freedom from recurrence (hazard ratio 2.5, 95% CI 1.2-5.1, P = .016). Gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Addressing the Neck: An NCDB Study of Clinically Node-Negative Supraglottic Squamous Cell Carcinoma.

Identify the proportion of patients undergoing elective neck dissection (END) in surgically managed supraglottic squamous cell carcinoma (SCCa), assess associations between patient, tumor, and treatment factors with END, and assess associations between neck management and overall survival (OS). Retrospective study. National Cancer Database (NCDB) 2019 Participant User File. Patients with previously untreated, clinically node-negative (cN0) supraglottic SCCa treated with partial laryngectomy were queried from NCDB. Patients without known neck management and who underwent total laryngectomy were excluded. Patient and tumor factors associated with END were evaluated by logistic regression analysis. Univariable Cox proportional hazard analysis was used to examine associations between patient factors and OS, and factors with P < .05 were included on multivariable analysis. A total of 1352 patients met eligibility criteria. Eight hundred eleven (60%) patients had END performed with occult nodal metastasis identified in 177 (22%) patients. END was more likely to be performed at academic centers than nonacademic centers (odds ratio: [1.66], 95% confidence interval [CI]: 1.32-2.09, P < .001). On multivariable analysis, patients who underwent adjuvant radiation had worse OS (hazard ratio [HR]: 1.45, 95% CI: 1.13-3.29, P = .017). END was associated with improved OS overall on univariable analysis (HR: 0.83, 95% CI: 0.69-0.98, P = .026), but not on multivariable analysis. In this NCDB study, 22% of cN0 supraglottic SCCa patients had occult nodal metastatic disease. Despite this, 40% of patients do not receive END at the time of primary resection. Patients who receive END for supraglottic SCCa are more likely to avoid adjuvant radiation without impacting OS.

Concomitant sarcopenia and undernutrition: Impact on clinical outcomes in patients undergoing hemodialysis

BackgroundSarcopenia and undernutrition are crucial in the cycle of frailty in patients requiring hemodialysis therapy, and their deleterious clinical consequences are well documented. However, little attention has been directed towards examining their combined impact on clinical outcomes. ObjectiveThis study aimed to elucidate the effects of concomitant sarcopenia and undernutrition on clinical outcomes in patients undergoing hemodialysis. MethodsThis prospective cohort study recruited outpatients undergoing hemodialysis from four facilities. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia, 2019. Undernutrition was determined using the Geriatric Nutritional Risk Index, with a score of < 92 classified as undernutrition. Patients were classified into four groups according to the presence or absence of sarcopenia and undernutrition. Cox proportional hazards analysis was used to assess the independent association between concomitant sarcopenia and undernutrition, all-cause mortality, and cardiovascular (CV) events after adjusting for baseline characteristics. ResultsWe included 450 patients in this analysis. Of the 450 patients, 69 (15.3%) had concomitant sarcopenia and undernutrition. The mean follow-up period was 1,067 days, and there were 61 deaths and 60 CV events. The cumulative survival rate was significantly lower in the sarcopenia with undernutrition group (P=0.011). The overlap of sarcopenia and undernutrition was significantly associated with a risk of mortality (hazard ratio 2.10; 95% confidence interval 1.05-4.21; P=0.037). However, no association was observed between the co-occurrence of sarcopenia and undernutrition and the risk of CV events. ConclusionsConcomitant sarcopenia and undernutrition were significantly associated with an increased mortality risk among patients undergoing hemodialysis. This finding reaffirms the importance of managing sarcopenia and undernutrition in patients undergoing hemodialysis in daily clinical practice.

Impact of pharmacist-driven antimicrobial stewardship interventions in a secondary care facility in Japan: A pragmatic quasi-experimental study

BackgroundEfforts to promote antimicrobial stewardship aimed at reducing antimicrobial resistance are necessary regardless of hospital scale owing to delays in new antimicrobial development. We aimed to evaluate the effects of pharmacist-driven interventions on broad-spectrum antimicrobial usage and the prognosis of patients with bacteremia in a medium-sized hospital lacking infectious disease physicians and a microbiology laboratory. MethodsThis single-center, retrospective, pragmatic, quasi-experimental study was conducted to compare pre- and post-intervention effects at Saiseikai Futsukaichi Hospital. We analyzed the days of therapy (DOT) for carbapenems and days of antibiotic spectrum coverage (DASC) for antimicrobials using an interrupted time series analysis. Cox proportional hazards analysis was performed to assess 30-day mortality using propensity score and inverse probability of treatment weighting in patients with bacteremia. ResultsPharmacist-driven intervention significantly reduced the DOT (incidence rate ratio [IRR]: 0.53, 95% confidence intervals [CI]: 0.33−0.81, p = 0.003) and DASC (IRR: 0.87, 95% CI: 0.78−0.97, p = 0.016). The 30-day mortality due to bacteremia did not significantly differ between pre- and post-intervention in all patients (adjusted hazard ratio [HR]: 0.92, 95% CI: 0.56−1.51, p = 0.74). Conversely, pharmacist-driven intervention significantly reduced the 30-day mortality owing to bacteremia with Pitt bacteremia score (PBS) ≥ 4 (adjusted HR: 0.52, 95% CI: 0.28−0.99, p = 0.047). ConclusionsPharmacist-driven interventions may represent a valuable approach for optimizing antimicrobial treatment and improving prognosis, especially in patients with PBS ≥ 4, which will potentially benefit patients in similar healthcare environments facing challenges related to antimicrobial stewardship and patient prognosis.

Optimal Medical Therapy and OutcomesAmong Patients With ChronicHeartFailure With Reduced EjectionFraction.

Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. CHAMP-HF (Change the Management of Patients with HeartFailure) included U.S. outpatients with chronic HFrEF receiving≥1 GDMT. OMT subgroups were defined as suboptimal (score<3), acceptable (score=3), and optimal (score≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P< 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95%CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95%CI: 0.65-0.96) than those with suboptimal treatment. Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

Life-course socioeconomic status and all-cause mortality among older adults

ObjectivesWe investigated the association of life-course socioeconomic status (SES) with all-cause mortality among older Singaporeans (aged ≥60 years) by applying three conceptual life-course models – critical period, accumulation of risk and social mobility. MethodsData from a nationally representative longitudinal survey of older Singaporeans (n=4,518), coupled with mortality information, was utilized. Dichotomous (low/high) childhood (family financial status), adulthood (highest education) and older adulthood (current housing) SES indicators informed the operationalization of the models, which were evaluated through Cox proportional hazards analysis. ResultsAdulthood SES was associated with mortality (critical period). The mortality risk increased with increasing cumulative SES disadvantage (accumulation of risk). Stable low SES and downward SES mobility from childhood to adulthood increased mortality risk (social mobility). DiscussionImproving adulthood SES and facilitating upward SES mobility, from childhood to adulthood, are promising for reducing mortality. Addressing SES disparities during childhood and older adulthood may also help.

Non-adherence to recommended adjuvant radiation after total laryngectomy

ObjectivesInvestigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). MethodsPreviously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. ResultsAmong 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72–0.93) analysis. ConclusionsWithin the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Predictors of functional cure of chronic hepatitis B virus infection – A long-term follow-up study

Functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg)-seroconversion. We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients, who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg-seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per perperson-year, and increased to 0.96% per person-year after HBeAg-seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg-seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazard analysis of the cohort revealed that HBeAg-seroconversion at < 18 years of age, high genetic barrier nucleos(t)ide analogue(s) therapy before HBeAg-seroconversion, and a serum HBsAg titer < 1,000 IU/mL at 18 months after HBeAg-seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg-seroconversion in childhood, high genetic barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg-seroconversion were significant predictors of functional cure.