Dexamethasone in hospitalised coronavirus-19 patients not on intensive respiratory support

IntroductionDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.MethodsWe included patients admitted to Veterans Affairs hospitals between June 7, 2020-May 31, 2021 within 14-days after SARS-CoV-2 positive test. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weights (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.ResultsOf 19 973 total patients (95% men, median age 71, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514/9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472/5954 (75%) patients on low-flow nasal cannula (NC) received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.47 to 2.12); there was no association with mortality among patients on NC (HR 1.08, 95% CI 0.86 to 1.36).ConclusionIn patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.

Download Full-text

Association of pulse pressure with all-cause mortality in young adults

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-137070 ◽

2019 ◽

Vol 96 (1138) ◽

pp. 461-466

Author(s):

Jie LI ◽

Jia-Yi Huang ◽

Kenneth Lo ◽

Bin Zhang ◽

Yu-Qing Huang ◽

...

Keyword(s):

Young Adults ◽

Pulse Pressure ◽

Subgroup Analysis ◽

Proportional Hazards ◽

Continuous Variable ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

Cox Analysis

BackgroundPulse blood pressure was significantly associated with all-cause mortality in middle-aged and elderly populations, but less evidence was known in young adults.ObjectiveTo assess the association of pulse pressure (PP) with all-cause mortality in young adults.MethodsThis cohort from the 1999–2006 National Health and Nutrition Examination Survey included adults aged 18–40 years. All included participants were followed up until the date of death or 31 December 2015. PP was categorised into three groups: <50, 50~60, ≥60 mm Hg. Cox proportional hazards models and subgroup analysis were performed to estimate the adjusted HRs and 95% CIs for all-cause mortality.ResultsAfter applying the exclusion criteria, 8356 participants (median age 26.63±7.01 years, 4598 women (55.03%)) were included, of which 265 (3.17%) have died during a median follow-up duration of 152.96±30.45 months. When treating PP as a continuous variable, multivariate Cox analysis showed that PP was an independent risk factor for all-cause mortality (HR 1.94, 95% CI 1.02 to 3.69; p=0.0422). When using PP<50 mm Hg as referent, from the 50~60 mm Hg to the ≥60 mm Hg group, the risks of all-cause mortality for participants with PP ranging 50–60 mm Hg or ≥60 mm Hg were 0.93 (95% CI 0.42 to 2.04) and 1.15 (95% CI 0.32 to 4.07) (P for tend was 0.959). Subgroup analysis showed that PP (HR 2.00, 95% CI 1.05 to 3.82; p=0.0360) was associated with all-cause mortality among non-hypertensive participants.ConclusionAmong young adults, higher PP was significantly associated with an increased risk of all-cause mortality, particularly among those without hypertension.

Download Full-text

FC 080VARIABILITY IN SERUM PHOSPHATE ASSESSED BY DIRECTIONAL CHANGE IS ASSOCIATED WITH INCREASED MORTALITY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab123.005 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Xiaoling (Janice) Ye ◽

Karlien Ter Meulen ◽

Len A Usvyat ◽

Frank Van Der Sande ◽

Constantijn Konings ◽

...

Keyword(s):

Proportional Hazards ◽

Smoothing Splines ◽

Cox Proportional Hazards ◽

Serum Phosphate ◽

P Value ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

Directional Change ◽

Wide Variability

Abstract Background and Aims Prior studies showed that there is a wide variability between serial pre-dialysis measurements of serum phosphate (P). Serum P vary can be due to changes in nutritional intake, underlying bone disorders, medication use or inflammation. Various variability markers have been investigated to study the association between P variability and its association with outcomes, however, the directional trends have not been studied in depth. We aimed to study directional changes and investigated its association with outcomes. Method All adult incident HD patients treated in Fresenius Medical Care North America (FMCNA) clinics between 01/2010 and 10/2018 were included in this retrospective cohort study. Serum P levels were averaged from month 1 to 6 after the initiation of dialysis (baseline). Baseline absolute and directional range (DR) of serum P were calculated. DR of P was calculated as: P min/max (t2) – P max/min (t1), with P (t1) and P (t2) represents the timepoint when either the min P value or max P value was measured, whichever comes first, and with t2 happened after t1. It is positive when the minimum antedates the maximum, otherwise negative. All-cause mortality was recorded between months 7 and 18. Cox proportional hazards models with spline terms were applied to explore the association between absolute and DR of P and all-cause mortality. Additionally, tensor product smoothing splines were computed to study the interactions of P with absolute P and DR of P and their joint associations with outcomes, respectably. Results We studied 353,142 patients. The average age was 62.7 years, 58% were male, 64% were diabetic. Baseline P was 4.98 mg/dL, median absolute range was 2.40 mg/dL, median DR was 1.1 mg/dL. Across different levels of P, both higher levels of absolute range and DR of P were associated with higher risk of mortality (Figure 1, Figure 2). The associations even seemed stronger in patients with lower levels of serum P and with negative DR (Figure 1). Conclusion Lower levels of serum P are independently associated with an increased risk of all-cause mortality. Whereas both a positive and negative DR of P are in general associated with increased mortality, the effects of an increase are most predominant in patients with higher levels of serum P, whereas a negative directional range are most predominant in patients with low serum P. This could be explained by the fact that patients with lower levels of P are generally malnourished or inflamed, where a further reduction indicates nutritional deterioration.

Download Full-text

Pre-ESRD Dementia and Post-ESRD Mortality in a Large Cohort of Incident Dialysis Patients

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000471761 ◽

2017 ◽

Vol 43 (5-6) ◽

pp. 281-293 ◽

Cited By ~ 5

Author(s):

Miklos Z. Molnar ◽

Keiichi Sumida ◽

Abduzhappar Gaipov ◽

Praveen K. Potukuchi ◽

Tibor Fülöp ◽

...

Keyword(s):

Mortality Rate ◽

Proportional Hazards ◽

International Classification Of Diseases ◽

Cox Proportional Hazards ◽

Dialysis Initiation ◽

Entire Cohort ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

Stage Renal Disease

Background: Conservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless. Methods: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period. We examined the association of prelude dementia with all-cause mortality within the first 6 months following transition to dialysis, using a propensity-matched cohort and Cox proportional hazards models. Results: In the entire cohort, the overall mean ± standard deviation age at baseline was 72 ± 11 years, 95% were male, 23% were African-American, and 66% were diabetic. There were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403-421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia-positive group in the entire cohort in the first 6 months after dialysis initiation. Presence of dementia was associated with higher risk of all-cause mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia-free patients in the first 6 months after dialysis initiation. Conclusion: Pre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.

Download Full-text

Faster Transport Status and Mortality in Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Blood Purification ◽

10.1159/000433416 ◽

2015 ◽

Vol 40 (2) ◽

pp. 160-166 ◽

Cited By ~ 2

Author(s):

Liping Xiong ◽

Li Fan ◽

Qingdong Xu ◽

Qian Zhou ◽

Huiyan Li ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

History Of ◽

The Relationship

Background: There are limited data regarding the relationship between transport status and mortality in anuric continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: According to the dialysate to plasma creatinine ratio (D/P Cr), 292 anuric CAPD patients were stratified to faster (D/P Cr ≥0.65) and slower transport groups (D/P Cr <0.65). The Cox proportional hazards models were used to evaluate the association of transport status with mortality. Results: During a median follow-up of 22.1 months, 24% patients died, 61.4% of them due to cardiovascular disease (CVD). Anuric patients with faster transport were associated with an increased risk of all-cause mortality (HR (95% CI) = 2.16 (1.09-4.26)), but not cardiovascular mortality, after adjustment for confounders. Faster transporters with pre-existing CVD had a greater risk for death compared to those without any history of CVD. Conclusion: Faster transporters were independently associated with high all-cause mortality in anuric CAPD patients. This association was strengthened in patients with pre-existing CVD.

Download Full-text

Early initiation of corticosteroids in patients hospitalized with COVID-19 not requiring intensive respiratory support: cohort study

10.1101/2021.07.06.21259982 ◽

2021 ◽

Author(s):

Kristina Crothers ◽

Rian DeFaccio ◽

Janet Tate ◽

Patrick R Alba ◽

Matthew Goetz ◽

...

Keyword(s):

Cohort Study ◽

Proportional Hazards ◽

Medical Center ◽

Veterans Affairs ◽

Cox Proportional Hazards ◽

Early Initiation ◽

Respiratory Support ◽

Sensitivity Analyses ◽

Low Flow ◽

Increased Risk

Objectives: To determine whether early oral or parenteral corticosteroids compared to no corticosteroids are associated with decreased mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who are not on intensive respiratory support (IRS) within 48 hours of admission. Design: Observational cohort study Setting: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated US national healthcare system Participants: 9,058 patients admitted to a Veterans Affairs Medical Center between June 7, 2020-December 5, 2020 within 14-days after SARS-CoV-2 positive test; exclusion criteria include less than a 48 hour stay, receipt of prior systemic corticosteroids, and no indication of acute medical care for COVID-19. Main outcome measure: 90-day all-cause mortality Results: Of 9,058 total patients (95% men, median age 71 years, 27% black), 6,825 (75%) were not on IRS within 48 hours. Among the 3,025 patients on no oxygen, 598 (20%) received corticosteroids and 283 (9%) died; of 3,800 patients on low-flow nasal cannula oxygen (NC), 2,808 (74%) received corticosteroids and 514 (13%) died. In stratified, inverse probability weighted Cox proportional hazards models comparing those who did and did not receive corticosteroids, patients on no oxygen experienced an 89% increased risk for 90-day mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.33 to 2.68); there was weak evidence of increased mortality among patients on NC (HR 1.21, 95% CI 0.94 to 1.57). Results were robust in subgroup analyses including restricting corticosteroids to dexamethasone, and in sensitivity analyses employing different modeling approaches. Conclusions: In patients hospitalized with COVID-19, we found no evidence of a mortality benefit associated with early initiation of corticosteroids among those on no oxygen or NC in the first 48 hours, though there was evidence of potential harm. These real-world findings support that clinicians should consider withholding corticosteroids in these populations and further clinical trials may be warranted.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

The Journals of Gerontology Series A ◽

10.1093/gerona/glab272 ◽

2021 ◽

Author(s):

Ma Cherrysse Ulsa ◽

Xi Zheng ◽

Peng Li ◽

Arlen Gaba ◽

Patricia M Wong ◽

...

Keyword(s):

Sleep Disturbances ◽

Proportional Hazards ◽

Time Lag ◽

Cox Proportional Hazards ◽

Poor Sleep ◽

Cardiovascular Risks ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

Download Full-text

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Frontiers in Medicine ◽

10.3389/fmed.2021.639970 ◽

2021 ◽

Vol 8 ◽

Author(s):

Augusto Di Castelnuovo ◽

Simona Costanzo ◽

Andrea Antinori ◽

Nausicaa Berselli ◽

Lorenzo Blandi ◽

...

Keyword(s):

Observational Study ◽

Propensity Scores ◽

Proportional Hazards ◽

Real Life ◽

Cox Proportional Hazards ◽

Event Analysis ◽

Multicenter Observational Study ◽

Protein Levels ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Download Full-text

Dietary Omega-3 Fatty Acid Intake and Mortality in CKD Population: A 1999–2014 NHANES Analysis

American Journal of Nephrology ◽

10.1159/000520027 ◽

2021 ◽

pp. 1-10

Author(s):

Wei-Lan Li ◽

Nan-Hui Zhang ◽

Shu-Wang Ge ◽

Gang Xu

Keyword(s):

Cardiovascular Disease ◽

Fatty Acid ◽

Proportional Hazards ◽

Early Death ◽

Cox Proportional Hazards ◽

Omega 3 ◽

Pufa Intake ◽

Dietary Recall ◽

Cox Proportional Hazards Models ◽

All Cause Mortality

Introduction: High risk of early death, especially contributed to cardiovascular disease, exists in patients who have chronic kidney disease (CKD). And the burden of cardiovascular disease is able to be lightened by an increase in omega-3 polyunsaturated fatty acid (omega-3 PUFA). A diet high in omega-3 PUFA in the general population is protective, although it is inconclusive about its beneficial role in the CKD population. Methods: From the 1999 to 2014 National Health and Nutrition Examination Surveys (NHANES), we can collect 2,990 participants who suffered from CKD, who were classified into 4 groups: <0.86, 0.87–1.30, 1.31–1.92, and 1.93–9.65 g/day based on NHANES 24-h dietary recall questionnaire dietary omega-3 PUFA. Moreover, their mortality details were available to be obtained by linking NHANES to the National Death Index. The associations between dietary omega-3 PUFA and mortality were evaluated by constructing multivariable Cox proportional hazards models. Results: Over 8 years of a median follow-up, 864 deaths were recorded. The adjusted hazard ratios (95% confidence interval) for all-cause mortality of the diseased people with CKD in the 2nd (0.87–1.30 g/day), 3rd (0.87–1.30 g/day), and 4th (1.93–9.65 g/day) quartiles of dietary omega-3 PUFA were 0.94 (0.72, 1.23), 0.74 (0.54, 1.02), and 0.67 (0.48, 0.93), respectively, versus those with the lowest quartile of dietary omega-3 PUFA intake (<0.86 g/day) (p for trend = 0.011). Conclusion: There may be a inverse relation of dietary omega-3 PUFA intake and all-cause mortality in patients with CKD. Therefore, an increase of dietary omega-3 PUFA may be encouraged to be used clinically in patients with CKD.

Download Full-text