scholarly journals Impact of Extended and Restricted Antibiotic Deescalation on Mortality

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Hwei Lin Teh ◽  
Sarimah Abdullah ◽  
Anis Kausar Ghazali ◽  
Rahela Ambaras Khan ◽  
Anitha Ramadas ◽  
...  

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.

Author(s):  
Keiichi Shimatani ◽  
Mayuko T. Komada ◽  
Jun Sato

Previous studies have shown that more frequent social participation was associated with a reduced risk of mortality. However, limited studies have explored the changes in the frequency of social participation in older adults. We investigated the impact of the changes in the frequency of social participation on all-cause mortality in Japanese older adults aged 60 years and older. The current study, conducted as a secondary analysis, was a retrospective cohort study using open available data. The participants were 2240 older adults (45.4% male and 54.6% female) sampled nationwide from Japan who responded to the interview survey. Changes in the frequency of social participation were categorized into four groups (none, initiated, decreased, and continued pattern) based on the responses in the baseline and last surveys. The Cox proportional-hazards model showed a decreased risk of all-cause mortality in decreased and continued patterns of social participation. Stratified analysis by sex showed a decreased risk of mortality in the continued pattern only among males. The results of the current study suggest that the initiation of social participation at an earlier phase of life transition, such as retirement, may be beneficial for individuals.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jia Wangping ◽  
Han Ke ◽  
Wang Shengshu ◽  
Song Yang ◽  
Yang Shanshan ◽  
...  

Objective: To evaluate the combined effects of anemia and cognitive function on the risk of all-cause mortality in oldest-old individuals.Design: Prospective population-based cohort study.Setting and Participants: We included 1,212 oldest-old individuals (men, 416; mean age, 93.3 years).Methods: Blood tests, physical examinations, and health questionnaire surveys were conducted in 2012 were used for baseline data. Mortality was assessed in the subsequent 2014 and 2018 survey waves. Cox proportional hazards models were used to evaluate anemia, cognitive impairment, and mortality risk. We used restricted cubic splines to analyze and visualize the association between hemoglobin (Hb) levels and mortality risk.Results: A total of 801 (66.1%) deaths were identified during the 6-year follow-up. We noted a significant association between anemia and mortality (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.54) after adjusting for confounding variables. We also observed a dose-response relationship between the severity of anemia and mortality (P < 0.001). In the restricted cubic spline models, Hb levels had a reverse J-shaped association with mortality risk (HR 0.88, 95% CI 0.84–0.93 per 10 g/L-increase in Hb levels below 130 g/L). The reverse J-shaped association persisted in individuals without cognitive impairment (HR 0.88, 95% CI 0.79–0.98 per 10 g/L-increase in Hb levels below 110 g/L). For people with cognitive impairment, Hb levels were inversely associated with mortality risk (HR 0.83, 95% CI 0.78–0.89 per 10 g/L-increase in Hb levels below 150 g/L). People with anemia and cognitive impairment had the highest risk of mortality (HR 2.60, 95% CI 2.06–3.27).Conclusion: Our results indicate that anemia is associated with an increased risk of mortality in oldest-old people. Cognitive impairment modifies the association between Hb levels and mortality.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5528-5528
Author(s):  
Sean Thomas McSweeney ◽  
Anna Prizment ◽  
Nathan Pankratz ◽  
Corinne E Joshu ◽  
Elizabeth A. Platz ◽  
...  

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.


Heart ◽  
2018 ◽  
Vol 104 (21) ◽  
pp. 1764-1771 ◽  
Author(s):  
Jin-Hu Fan ◽  
Jian-Bing Wang ◽  
Shao-Ming Wang ◽  
Christian C Abnet ◽  
You-Lin Qiao ◽  
...  

BackgroundA number of studies have demonstrated a J-shaped curve between blood pressure (BP) and all-cause mortality, but few studies have used longitudinal change in BP to study mortality in the Chinese population.MethodsWe performed a 30-year follow-up study to examine the association between BP (at baseline and longitudinal change) and risk of mortality in the Linxian General Population Trial Cohort. At baseline, a total of 29 584 healthy adults were enrolled in the Linxian General Population Trial in 1985 and followed through to the end of 2014. The final analysis was restricted to 29 439 participants (55% women) after exclusion of outliers. We also examined the potential effects of BP trajectory patterns during the period of 1985–1999 on sequent risk of mortality. Adjusted Cox proportional hazards models were used to estimate HRs and 95% CIs.ResultsCompared with participants with normal BP, patients with prehypertension, stage 1, stage 2 or stage 3 hypertension had an increased risk of all-cause mortality, with HRs of 1.09 (95% CI 1.05 to 1.14), 1.34 (95% CI 1.28 to 1.40), 1.69 (95% CI 1.60 to 1.79) and 2.14 (95% CI 2.01 to 2.28), respectively. Relative to stable BP of normotension, having a rise in BP from normotension to hypertension or from prehypertension to hypertension both conferred an increased risk of total and cardiovascular disease and stroke mortality (total: HRs 1.22 (95% CI 1.12 to 1.34) and 1.36 (95% CI 1.23 to 1.51); cardiovascular disease: HRs 1.42 (95% CI 1.17 to 1.73) and 1.55 (95% CI 1.24 to 1.93); stroke: HRs 2.29 (95% CI 1.88 to 2.80) and 2.61 (95% CI 2.11 to 3.24), respectively).ConclusionsThese findings emphasise that development of incident hypertension in middle age could increase the risk of total, cardiovascular disease and stroke mortality, and suggest that current BP targets could be revised.Trial registration numberNCT00342654;Post-results.


2021 ◽  
Author(s):  
Somaya Albhaisi ◽  
Rehan Qayyum

Abstract BACKGROUND & AIMS: Interpreting levels of liver enzymes is often challenging because they may be influenced by metabolic processes beyond the liver. Given their pathophysiologic roles in inflammation and oxidative stress, higher levels of these enzymes may be associated with increased risk of mortality. However, studies have found inconsistent results. Thus, we examined the association of liver enzymes levels with cancer mortality in the general U.S. adult population. METHODS: We used the US National Health and Nutrition Examination Survey from 1999 to 2016. Kaplan-Meier survival curve comparisons were examined across quartiles of liver enzymes. Cox proportional hazards models were built to examine the relationship between cancer mortality and liver enzymes quartiles without and with adjustment for potential confounding factors. RESULTS: During the 338,882 person-years follow-up, 1059 participants had cancer-related deaths. There was a nonlinear U-shaped relationship between serum alanine and aspartate aminotransferase (ALT and AST) levels and cancer mortality. There was no relationship between cancer mortality and gamma glutamyltransferase (GGT), however, each 10 IU/L increase in GGT after median was associated with 1% higher mortality risk (HR=1.01; 95% CI=1.00, 1.02; P=0.001). Only subjects with high levels of alkaline phosphatase (ALP) had higher cancer mortality (HR=1.63; 95CI=1.30, 2.05; P<0.001 and HR=1.52; 95%CI=1.20, 1.94; P=0.001 respectively).CONCLUSIONS: Only the lowest and highest serum ALT and AST levels are associated with increased cancer mortality. For ALP, the relationship is present at higher levels. The association with GGT was not robust to different analyses. The mechanisms underlying the observed relationships need further exploration.


2011 ◽  
Vol 24 (4) ◽  
pp. 624-630 ◽  
Author(s):  
Cristina Fortes ◽  
Simona Mastroeni ◽  
Sperati Alessandra ◽  
Juliana Lindau ◽  
Sara Farchi ◽  
...  

ABSTRACTBackground: Depression is a potential risk factor for mortality among the aged and it is also associated with other chronic diseases and unhealthy lifestyles that may also affect mortality. The purpose of this study was to investigate the association between depressive symptoms and mortality, controlling for health, nutritional status, and life-style factors.Methods: A cohort of elderly people (N = 167) was followed-up for ten years. Information on socio-demographic characteristics, medical history, smoking, and alcohol consumption was collected. The primary outcome was all-cause mortality; the secondary outcome was cancer-specific mortality. The Geriatric Depression Scale (GDS-15) was used to assess depression. Using a multivariable Cox proportional hazards regression, we examined the association between depressive symptoms and mortality.Results: Elderly people with depression (scoring above the depression cut-off of 7) had a 53% increased risk of mortality (relative risk (RR) 1.53; 95%CI: 1.05–2.24) compared to non-depressed subjects. The combination of depressive symptoms with smoking was associated with a particularly higher risk of mortality (RR: 2.61; 95%CI: 1.28–5.31), after controlling for potential confounders.Conclusions: Depressive symptoms are associated with a significantly increased risk of all-cause mortality. The combination of depressive symptoms and smoking shorten life expectancy among the aged.


2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091150
Author(s):  
Zongying Li ◽  
Cheng Xing ◽  
Tingting Li ◽  
Linxiang Du ◽  
Na Wang

Objective Serum chloride disorders have been gaining increased attention. We aimed to assess the impact of serum chloride on all-cause mortality in critically ill patients in coronary care units (CCUs). Methods We extracted clinical data from the Multiparameter Intelligent Monitoring in Intensive Care III database. We used data for the first CCU admission of each patient; baseline data were extracted within 24 hours after CCU admission. Statistical methods included the Lowess smoothing technique, Cox proportional hazards model, and subgroup analyses. Results A total 5616 patients who met the inclusion criteria were included. We observed a U-shaped relationship between admission chloride levels and 30-day all-cause mortality. In multivariate analysis adjusted for age, ethnicity, and sex, both hyper- and hypochloremia were significant predictors of risk of 30-day, 90-day, and 365-day all-cause mortality. After adjusting additional clinical characteristics, hypochloremia remained a significant predictor of risk of 30-day all-cause mortality (hazard ratio, 1.47; 95% confidence interval, 1.19–1.83). For 90-day and 365-day all-cause mortality, similar significant robust associations were found. Conclusions We observed a U-shaped relationship between admission chloride levels and 30-day all-cause mortality among patients in the CCU. Hypochloremia was associated with increased risk of all-cause mortality in these patients.


2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas

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.


2021 ◽  
pp. 1-11
Author(s):  
Dongying Fu ◽  
Jiani Shen ◽  
Wei Li ◽  
Yating Wang ◽  
Zhong Zhong ◽  
...  

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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4142-4142
Author(s):  
Lucy Xiaolu Ma ◽  
Gun Ho Jang ◽  
Amy Zhang ◽  
Robert Edward Denroche ◽  
Anna Dodd ◽  
...  

4142 Background: KRAS mutations (m) (KRASm) are present in over 90% of pancreatic adenocarcinomas (PDAC) with a predominance of G12 substitutions. KRAS wildtype (WT) PDAC relies on alternate oncogenic drivers, and the prognostic impact of these remains unknown. We evaluated alterations in WT PDAC and explored the impact of specific KRASm and WT status on survival. Methods: WGS and RNAseq were performed on 570 patients (pts) ascertained through our translational research program from 2012-2021, of which 443 were included for overall survival (OS) analyses. This included 176 pts with resected and 267 pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657). The latter cohort underwent biopsies prior to treatment with first line gemcitabine-nab-paclitaxel or mFOLFIRINOX as per physician choice. The Kaplan-Meier and Cox proportional hazards methods were used to estimate OS. Results: KRAS WT PDAC (n = 52) represented 9% of pts, and these cases trended to be younger than pts with KRASm (median age 61 vs 65 years p = 0.1). In resected cases, the most common alterations in WT PDAC (n = 23) included GNASm (n = 6) and BRAFm/fusions (n = 5). In advanced WT PDAC (n = 27), alterations in BRAF (n = 11) and ERBB2/3/4 (n = 6) were most prevalent. Oncogenic fusions (NTRK, NRG1, BRAF/RAF, ROS1, others) were identified in 9 pts. The BRAF in-frame deletion p.486_491del represented the most common single variant in WT PDAC, with organoid profiling revealing sensitivity to both 3rd generation BRAF inhibitors and MEK inhibition. In resected PDAC, multivariable analyses documented higher stage (p = 0.043), lack of adjuvant chemotherapy (p < 0.001), and the KRAS G12D variant (p = 0.004) as poor prognostic variables. In advanced disease, neither WT PDAC nor KRAS specific alleles had an impact on prognosis (median OS WT = 8.5 mths, G12D = 8.2, G12V = 10.0, G12R = 12.0, others = 9.2, p = 0.73); the basal-like RNA subtype conferred inferior OS (p < 0.001). A targeted therapeutic approach following first line chemotherapy was undertaken in 10% of pts with advanced PDAC: MMRd (n = 1), homologous recombination deficiency (HRD) (n = 19), KRASG12C (n = 1), CDK4/6 amplification (n = 3), ERBB family alterations (n = 2), BRAF variants (n = 2). OS in this group was superior (14.7 vs 8.8 mths, p = 0.04), mainly driven by HRD-PDAC where KRASm were present in 89%. Conclusions: In our dataset, KRAS G12D is associated with inferior OS in resected PDAC, however KRAS mutational status was not prognostic in advanced disease. This suggests that improved OS in the WT PDAC population can only be achieved if there is accelerated access to targeted drugs for pts.


Sign in / Sign up

Export Citation Format

Share Document