Association of polymorphisms in androgen production, uptake, and conversion chain (APUC) genes with mortality of prostate cancer patients.

5528 Background: Genes involved in APUC may affect prognosis in PC. We tested the association of four SNPs involved in the APUC pathway: hydroxy-delta-5-steroid dehydrogenase, 3 beta-and steroid delta-isomerase 1 ( HSD3B1), 5α reductase enzyme ( SRD5A), and solute carrier organic ion ( SLCO2B1) with all-cause and PC mortality 596 in the Atherosclerosis Risk in Communities (ARIC) study. Methods: Between 1987 & 2015 596 men were diagnosed with PC. Median age at diagnosis was 70 (range 53-86) years; 21% of all PC patients were African American. After diagnosis, follow-up was median 8.4 years (max 26.7 years) until PrC death (N = 60), death from any cause (N = 253), or end of 2015. SNPs were genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0 and imputed to the 1000 Genomes Phase 3 reference panel. To examine survival, we used Kaplan-Meier curves and Cox proportional hazards regression. Hazard ratios (HR) and 95% confidence intervals (CI) were adjusted for age, field center, stage and grade at diagnosis. We also controlled for confounding by ancestry by adjusting for genetic principal components. The analyses were conducted in all PrCa patients and in Whites PrCa patients only. Polymorphisms tested included rs1047303 (A = > C, also called 1245C); rs523349 (C = > G); and rs1789693 (A = > T) and rs12422149 (G = > A), located in the aforementioned genes. Results: The A allele for SLCO2B1 rs1789693 (A = > T) was significantly associated with an increased risk of PC mortality (versus T): multivariable-adjusted HRs (95%CI) were (2.06, 1.14-3.74; p = 0.02) and all-cause mortality (1.29, 1.00-1.66; p = 0.05) among Whites. The associations were similar when Whites and African-Americans were combined and when accounting for ancestry. The C allele for HSD3B1 rs1047303 (C = > A) was not statistically significantly associated with either PC or all-cause mortality in the whole cohort (which included localized disease), although HRs were increased for men diagnosed with stage 4 disease (n = 35) in both additive and dominant models. For carriers of the C allele (gain of function) versus AA, HRs were 5.32 (1.16-24.33; p = 0.03) and 6.13 (1.51-24.86; p = 0.01) for PC and all-cause mortality, respectively. All associations with SRDA2 (rs12422149) and SLCO2B1 (rs12422149) were not significant. Conclusions: The gain of function allele in HSD3B1 rs1047303 (1245C) was associated with increased PC and all-cause mortality in men diagnosed with metastatic PC, paralleling prior findings. Associations with SLCO2B1 SNP rs1789693 require validation in larger studies.

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Racial Disparities in Delivery Gestational Age among Twin Pregnancies

American Journal of Perinatology ◽

10.1055/s-0037-1603764 ◽

2017 ◽

Vol 34 (11) ◽

pp. 1065-1071

Author(s):

Catherine Vladutiu ◽

Tracy Manuck ◽

Jacqueline Grant

Keyword(s):

Gestational Age ◽

Proportional Hazards ◽

Secondary Analysis ◽

Neonatal Morbidity ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Hydroxyprogesterone Caproate

Objective This study aims to estimate the association between maternal race and delivery gestational age among women with twin gestations. Study Design Secondary analysis of a prospective, randomized control trial of 17-α hydroxyprogesterone caproate versus placebo for preterm birth (PTB) prevention in twin gestations. Non-Hispanic (NH) black and whites were included. Demographic and antenatal characteristics were compared. The primary outcome was delivery gestational age. Secondary outcomes included a composite of major neonatal morbidity. Kaplan–Meier curves estimated survival probabilities for delivery gestational age by race. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 535 women with twin gestations were included; 150 were NH black. NH blacks delivered earlier than NH whites (33.6 ± 4.8 weeks vs. 35.1 ± 3.5 weeks, p < 0.001). Differences in delivery gestational age between NH blacks and whites were consistent across gestation. In adjusted analyses, NH black race (HR: 1.24, 95% CI: 1.02–1.51), prior PTB (HR: 1.59, 95% CI: 1.15–2.19), and cerclage (HR: 3.90, 95% CI: 2.00–7.60) were associated with an increased risk of earlier delivery. Major neonatal morbidity was higher for NH blacks compared with NH whites (12.7 vs. 7.0%, p = 0.036). Conclusion NH blacks with twin gestations have an increased risk of early delivery and neonatal morbidity compared with NH whites.

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Impact of Extended and Restricted Antibiotic Deescalation on Mortality

Antibiotics ◽

10.3390/antibiotics11010022 ◽

2021 ◽

Vol 11 (1) ◽

pp. 22

Author(s):

Hwei Lin Teh ◽

Sarimah Abdullah ◽

Anis Kausar Ghazali ◽

Rahela Ambaras Khan ◽

Anitha Ramadas ◽

...

Keyword(s):

Proportional Hazards ◽

Survival Curve ◽

Survival Rates ◽

Pressure Sore ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

The Impact

Background: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. This study aims to compare the survival curve of patient de-escalated (early or late) against those not de-escalated on antibiotics, to determine the association of patient related, clinical related, and pressure sore/device related characteristics on all-cause 30-day mortality and determine the impact of early and late antibiotic de-escalation on 30-day all-cause mortality. Methods: This is a retrospective cohort study on patients in medical ward Hospital Kuala Lumpur, admitted between January 2016 and June 2019. A Kaplan–Meier survival curve and Fleming–Harrington test were used to compare the overall survival rates between early, late, and those not de-escalated on antibiotics while multivariable Cox proportional hazards regression was used to determine prognostic factors associated with mortality and the impact of de-escalation on 30-day all-cause mortality. Results: Overall mortality rates were not significantly different when patients were not de-escalated on extended or restricted antibiotics, compared to those de-escalated early or later (p = 0.760). Variables associated with 30-day all-cause mortality were a Sequential Organ Function Assessment (SOFA) score on the day of antimicrobial stewardship (AMS) intervention and Charlson’s comorbidity score (CCS). After controlling for confounders, early and late antibiotics were not associated with an increased risk of mortality. Conclusion: The results of this study reinforce that restricted or extended antibiotic de-escalation in patients does not significantly affect 30-day all-cause mortality compared to continuation with extended and restricted antibiotics.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis

Blood Purification ◽

10.1159/000512962 ◽

2021 ◽

pp. 1-11

Author(s):

Dongying Fu ◽

Jiani Shen ◽

Wei Li ◽

Yating Wang ◽

Zhong Zhong ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Proportional Hazards ◽

Elevated Serum ◽

Ultra Performance Liquid Chromatography ◽

Cox Proportional Hazards ◽

Serum Samples ◽

Entire Cohort ◽

Increased Risk ◽

All Cause Mortality ◽

Male Patients

Background: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. Methods: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. Results: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8–61.0) μM. During a median follow-up of 63.7 months (IQR, 43.9–87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01–1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07–1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02–1.94; p = 0.038) in men but not in women. Conclusions: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.

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Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block

European Heart Journal ◽

10.1093/ehjci/ehaa946.3358 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Kochav ◽

R.C Chen ◽

J.M.D Dizon ◽

J.A.R Reiffel

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Class I ◽

Class Iii ◽

Bundle Branch Block ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

History Of ◽

Propensity Score Stratification

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None

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Comorbidity between types of eating disorder and general medical conditions

The British Journal of Psychiatry ◽

10.1192/bjp.2021.104 ◽

2021 ◽

pp. 1-8

Author(s):

Natalie C. Momen ◽

Oleguer Plana-Ripoll ◽

Cynthia M. Bulik ◽

John J. McGrath ◽

Laura M. Thornton ◽

...

Keyword(s):

Eating Disorders ◽

Eating Disorder ◽

Proportional Hazards ◽

Medical Condition ◽

Detailed Examination ◽

Cox Proportional Hazards ◽

Medical Conditions ◽

Relative Risks ◽

Hazard Ratios ◽

Increased Risk

Background Comorbidity with general medical conditions is common in individuals with eating disorders. Many previous studies do not evaluate types of eating disorder. Aims To provide relative and absolute risks of bidirectional associations between (a) anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified and (b) 12 general medical conditions. Method We included all people born in Denmark between 1977 and 2010. We collected information on eating disorders and considered the risk of subsequent medical conditions, using Cox proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered risks for prior medical conditions and subsequent eating disorders. Results An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a medical condition ranged from 0.94 (95% CI 0.57−1.55) to 2.05 (95% CI 1.86−2.27). For those with a prior medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI 1.26–1.45) to 1.98 (95% CI 1.71–2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared with reference groups. Conclusions This is the largest and most detailed examination of eating disorder–medical condition comorbidity. The findings indicate that medical condition comorbidity is increased among those with eating disorders and vice versa. Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly.

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Supper Timing and Cardiovascular Mortality: The Japan Collaborative Cohort Study

Nutrients ◽

10.3390/nu13103389 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3389

Author(s):

Jingyun Tang ◽

Jia-Yi Dong ◽

Ehab S. Eshak ◽

Renzhe Cui ◽

Kokoro Shirai ◽

...

Keyword(s):

Hemorrhagic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Mortality ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk ◽

Study Participants

Evidence on the role of supper timing in the development of cardiovascular disease (CVD) is limited. In this study, we examined the associations between supper timing and risks of mortality from stroke, coronary heart disease (CHD), and total CVD. A total of 28,625 males and 43,213 females, aged 40 to 79 years, free from CVD and cancers at baseline were involved in this study. Participants were divided into three groups: the early supper group (before 8:00 p.m.), the irregular supper group (time irregular), and the late supper group (after 8:00 p.m.). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for stroke, CHD, and total CVD according to the supper time groups. During the 19-year follow-up, we identified 4706 deaths from total CVD. Compared with the early supper group, the multivariable HR of hemorrhagic stroke mortality for the irregular supper group was 1.44 (95% confidence interval [CI]: 1.05–1.97). There was no significant association between supper timing and the risk of mortality from other types of stroke, CHD, and CVD. We found that adopting an irregular supper timing compared with having dinner before 8:00 p.m. was associated with an increased risk of hemorrhagic stroke mortality.

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Serum cholinesterase levels to predict all-cause mortality in a community-based study: The Takahata study

Annals of Nutrition and Metabolism ◽

10.1159/000521536 ◽

2021 ◽

Author(s):

Makoto Saegusa ◽

Yumi Matsuda ◽

Tsuneo Konta ◽

Takafumi Saitoh ◽

Kaori Sakurada ◽

...

Keyword(s):

Proportional Hazards ◽

Independent Predictor ◽

Correlation Coefficients ◽

Cox Proportional Hazards ◽

Serum Cholinesterase ◽

Community Based ◽

Baseline Serum ◽

Middle Group ◽

Kaplan Meier ◽

All Cause Mortality

Introduction: Serum albumin (Alb) levels have been found to be independent predictors of all-cause mortality in a community-based population, but whether this is the case for serum cholinesterase (ChE) levels is uncertain. This study aimed to determine whether serum ChE levels are independent predictors of all-cause mortality in a community-based population. Methods: A total of 3,504 subjects (mean age 62.5 years) from Takahata, Japan participated and were followed up for 13.5 years (median 13.2 years). Based on baseline serum Alb and ChE levels, subjects were stratified by interquartile range as low, middle, and high. The correlation between serum Alb and ChE levels was examined by calculating correlation coefficients. The association between each group and all-cause mortality was examined by Kaplan-Meier and Cox proportional hazards analysis. Results: During follow-up, 568 subjects died. There was a positive correlation between serum Alb and ChE levels (r=0.30). Kaplan-Meier analysis showed that all-cause mortality in the low group was significantly higher for both serum Alb and ChE levels (log-rank P<0.01). Adjusted Cox proportional hazards analysis showed that the serum Alb level was not an independent predictor of all-cause mortality (hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.95-1.46 for all-cause mortality in the low group compared to the middle group), whereas the serum ChE level was an independent predictor of all-cause mortality (HR 1.30, 95% CI 1.06-1.59 for all-cause mortality in the low group compared to the middle group). Conclusion: The serum ChE level is an independent predictor of all-cause mortality in the general community-based population.

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