Baseline Drug Treatments as Indicators of Increased Risk of COVID-19 Mortality in Spain and Italy

This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice.

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Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for Prostate Cancer

Prostate Cancer ◽

10.1155/2014/230812 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Lior Z. Braunstein ◽

Ming-Hui Chen ◽

Marian Loffredo ◽

Philip W. Kantoff ◽

Anthony V. D'Amico

Keyword(s):

Prostate Cancer ◽

Weight Gain ◽

Androgen Deprivation Therapy ◽

Cancer Control ◽

Androgen Deprivation ◽

Study Cohort ◽

Survival Difference ◽

Risk Of Mortality ◽

Increased Risk ◽

Baseline Bmi

Background. Increasing body mass index (BMI) is associated with increased risk of mortality; however, quantifying weight gain in men undergoing androgen deprivation therapy (ADT) for prostate cancer (PC) remains unexplored.Methods. Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the survival difference of adding 6 months of ADT to radiation therapy (RT). BMI measurements were available in 171 men comprising the study cohort. The primary endpoint was weight gain of ≥10 lbs by 6-month followup. Logistic regression analysis was performed to assess whether baseline BMI or treatment received was associated with this endpoint adjusting for known prognostic factors.Results. By the 6-month followup, 12 men gained ≥10 lbs, of which 10 (83%) received RT + ADT and, of these, 7 (70%) were obese at randomization. Men treated with RT as compared to RT + ADT were less likely to gain ≥10 lbs (adjusted odds ratio (AOR): 0.18 [95% CI: 0.04–0.89];P=0.04), whereas this risk increased with increasing BMI (AOR: 1.15 [95% CI: 1.01–1.31];P=0.04).Conclusions. Consideration should be given to avoid ADT in obese men with low- or favorable-intermediate risk PC where improved cancer control has not been observed, but shortened life expectancy from weight gain is expected.

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The Role of Neutrophil Extracellular Traps in Cancer-Associated Arterial Thrombosis

Blood ◽

10.1182/blood-2018-99-116104 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2508-2508

Author(s):

Ella Grilz ◽

Lisa-Marie Mauracher ◽

Oliver Königsbrügge ◽

Florian Posch ◽

Irene Lang ◽

...

Keyword(s):

Overall Survival ◽

Neutrophil Extracellular Traps ◽

Categorical Variables ◽

Study Cohort ◽

Patients With Cancer ◽

Extracellular Traps ◽

Kaplan Meier ◽

Risk Of Mortality ◽

Increased Risk ◽

Unit Increase

Abstract Introduction: Prior studies have indicated that Neutrophil extracellular traps (NETs) trigger arterial thromboembolism (ATE) and play a role in the pathogenesis of cancer-associated venous thrombosis. We investigated the association between NET biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE in patients with cancer. Methods: In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for objectively confirmed, symptomatic ATE and death. Fine&Gray competing-risk regression was used to model risk of ATE. Overall survival (OS) was analyzed with Kaplan-Meier estimators. Results: Nine-hundred and fifty-eight patients with cancer (median age: 61 years; 46.8% female; Table 1) were recruited. ATE occurred in 22 patients; the cumulative 6-, 12-, and 24-month risks of ATE were 1.1%, 1.8%, and 2.3%, respectively. The subdistribution hazard ratios (SHR) for ATE of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (95% confidence interval [CI]: 1.0-1.0, p=.882), 1.0 (1.0-1.0, p=.639), and 1.1 (1.0-1.2, p=.246) respectively. The 6-, 12-, and 24-month ATE probability was 1.3%, 1.7%, and 2.6% in patients with a H3Cit level ≤ 75thpercentile, and 0.8%, 1.3%, and 1.7% in patients above this cut-off (SHR=0.7, 0.2-2.0, p=.460). The 6-, 12-, 24-month overall survival of the study cohort was 87.0% (95%CI: 84.6-89.0), 73.6% (70.6-76.3), and 57.6% (54.3-60.8), respectively. The hazard ratio (HR) for mortality of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (1.0-1.0, p<.001), 1.0 (1.0-1.0, p<.001), and 1.0 (1.0-1.1, p=.181) respectively. For better illustration we defined two groups of patients with elevated or non-elevated NET biomarkers. Therefore, we set an empiric cut-off at the 75thpercentile of the study cohort. Elevated H3Cit (HR=1.7, 1.3-2.1, p<.001), and cfDNA levels (HR=1.4, 1.1-1.7, p=.008) were associated with an increased risk of mortality after adjusting for age, and sex (Figure 1A&B). No association was found between higher nucleosome levels and the risk of all-cause mortality in patients with cancer (HR=1.2, 1.0-1.5, p=.088, Figure 1C). Conclusion: There was no significant association between H3Cit, cfDNA, and nucleosomes and ATE occurrence in patients with cancer. However, elevated levels of H3Cit, and cfDNA, were independently associated with an increased risk of mortality in patients with cancer. Table 1. Baseline characteristics of the total study population. Continuous data is reported as medians with first and third quartiles. Categorical variables are given as absolute frequencies and percentages. Data on body mass index, and cancer stage are missing in 2, and 76 patients, respectively. aPatients with brain and hematologic cancer Figure 1. Kaplan-Meier estimated for overall survival probability of patients with cancer according to baseline H3Cit, cfDNA, and nucleosome levels. MoM = Multiple-of-the-mean (i.e. Nucleosome results were compared to pooled plasma from 5 young male healthy controls to obtain a multiple-of-the-median) Disclosures No relevant conflicts of interest to declare.

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MO872INFLUENCE OF SARS-COV-2 INFECTION ON MORTALITY IN PATIENTS UNDER RENAL SUBSTITUTE TREATMENT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab098.0064 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Guillermo Ferrer García ◽

Luis Guillermo Piccone Saponara ◽

Patricia Sanchez Escudero ◽

Maria Paz Castro Fernández ◽

Nancy Giovanna Uribe Heredia ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Replacement Therapy ◽

Statistical Significance ◽

Demographic Variables ◽

Categorical Variables ◽

Risk Of Mortality ◽

Increased Risk ◽

Coronavirus Infection ◽

Student’S T ◽

Transversal Study

Abstract Background and Aims Dialysis patients constitute a risk group for coronavirus infection due to their immunosuppressed condition, with the increased risk of morbidity and mortality that this entails. We analyzed the factors associated with mortality from coronavirus infection in a cohort of patients undergoing renal replacement therapy at our center. Method Transversal study. We included patients in renal replacement therapy (RRT) in our center. Demographic variables (age, sex), associated comorbidity, RRT technique, clinical and laboratory parameters were collected. Statistical analysis with SPSS 25.0. Categorical variables are expressed in percentages and are compared using the Chi2 test. The quantitative variables are expressed as mean ± standard deviation and compared using Student's T-test. Statistical significance p <0.05. Results 38 patients, mean age 66 ± 18 years, 51.4% men. 92.1% had arterial hypertension, 39.5% diabetes mellitus (DM). 63.2% on hemodialysis, 2.6% peritoneal dialysis, 34.2% transplanted. 84.2% presented fever, 63.2% cough, 73.7% pneumonia, 34.2% dyspnea, 15.8% digestive symptoms. 21.1% leukopenia, 73.7% lymphopenia, money D 1509 ± 1351, CRP 12.45 ± 19.47, sodium 136 ± 5.5. 81.% were admitted to hospitalization, of which 2.6% required admission to the ICU. 44% died. Mortality was statistically significantly related to DM (56.3% vs 43.8% p = 0.05), and with the need for hospitalization (93.8 vs 6.3% p = 0.054). Conclusion In our experience, DM patients and those who required hospitalization had a higher risk of mortality.

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Advances and challenges in the management of advanced fibrosis in nonalcoholic steatohepatitis

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818811508 ◽

2018 ◽

Vol 11 ◽

pp. 175628481881150 ◽

Cited By ~ 9

Author(s):

Mehmet Sayiner ◽

Brian Lam ◽

Pegah Golabi ◽

Zobair M. Younossi

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Nonalcoholic Steatohepatitis ◽

Metabolic Diseases ◽

Lifestyle Modification ◽

Visceral Obesity ◽

Nonalcoholic Fatty Liver ◽

Risk Of Mortality ◽

Increased Risk ◽

Risk Of Progression

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common type of chronic liver disease worldwide. From the spectrum of NAFLD, it is nonalcoholic steatohepatitis (NASH) that predominantly predisposes patients to higher risk for development of cirrhosis and hepatocellular carcinoma. There is growing evidence that the risk of progression to cirrhosis and hepatocellular carcinoma is not uniform among all patients with NASH. In fact, NASH patients with increasing numbers of metabolic diseases such as diabetes, hypertension, visceral obesity and dyslipidemia are at a higher risk of mortality. Additionally, patients with higher stage of liver fibrosis are also at increased risk of mortality. In this context, NASH patients with fibrosis are in the most urgent need of treatment. Also, the first line of treatment for NASH is lifestyle modification with diet and exercise. Nevertheless, the efficacy of lifestyle modification is quite limited. Additionally, vitamin E and pioglitazone may be considered for subset of patients with NASH. There are various medications targeting one or more steps in the pathogenesis of NASH being developed. These drug regimens either alone or in combination, may provide potential treatment option for patients with NASH.

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Risk of mortality associated with concomitant antidepressant and benzodiazepine therapy among patients with depression: a population-based cohort study

BMC Medicine ◽

10.1186/s12916-020-01854-w ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Han Eol Jeong ◽

Ha-Lim Jeon ◽

In-Sun Oh ◽

Woo Jung Kim ◽

Ju-Young Shin

Keyword(s):

Cohort Study ◽

Population Based ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Therapeutic Effects ◽

Healthcare Database ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

Baseline Characteristics

Abstract Background With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. However, with mortality risks associated with this concomitant use yet to be examined, it remains unclear as to whether this concomitant therapy offers any benefits in treating depression. Methods We conducted a population-based cohort study using South Korea’s nationwide healthcare database from 2002 to 2017. Of 2.6 million patients with depression, we identified 612,729 patients with incident depression and newly prescribed ADs or BZDs, by excluding those with a record of diagnosis or prescription within the 2 years prior to their incident diagnosis. We classified our study cohort into two discrete groups depending on the type of AD treatment received within 6 months of incident diagnosis—AD monotherapy and AD plus BZD (AD+BZD) therapy. We matched our study cohort in a 1:1 ratio using propensity scores to balance baseline characteristics and obtain comparability among groups. The primary outcome was all-cause mortality, and patients were followed until the earliest of outcome occurrence or end of the study period. We conducted multivariable Cox proportional hazards regression analysis to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) for the risk of mortality associated with AD+BZD therapy versus AD monotherapy. Results The propensity score-matched cohort had 519,780 patients with 259,890 patients in each group, where all baseline characteristics were well-balanced between the two groups. Compared to AD monotherapy, AD+BZD therapy was associated with an increased risk of all-cause mortality (adjusted HR, 1.04; 95% CI, 1.02 to 1.06). Conclusions Concomitantly initiating BZDs with ADs was associated with a moderately increased risk of mortality. Clinicians should therefore exercise caution when deciding to co-prescribe BZDs with ADs in treating depression, as associated risks were observed.

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SP3.2.14 Does the “weekend effect” exist in those patients that require emergency laparotomy?

British Journal of Surgery ◽

10.1093/bjs/znab361.078 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

Lee Creedon ◽

Hannah Boyd-Carson ◽

Aarti Varma ◽

Gillian Tierney

Keyword(s):

Operative Mortality ◽

Weekend Effect ◽

Emergency Laparotomy ◽

Study Cohort ◽

Inpatient Mortality ◽

Risk Of Death ◽

Risk Of Mortality ◽

Increased Risk ◽

Acute Hospitals ◽

National Emergency

Abstract Aims Multiple studies have concluded that the “Weekend effect” results in worser outcomes for patients admitted during the weekend, when compared to weekday admissions. Patient presenting that require emergency laparotomy are, by default, high risk. It may be assumed that their risk of death is higher should they present during the weekend. The aim of this study was to identify if this cohort of admissions is at an increased risk of death should they present at the weekend. Methods All patients entered into the National Emergency Laparotomy Audit database from December 2013 up to and including November 2017 from two independent acute hospitals were included. Adjusted regression analysis (NELA risk score, grade of surgeon and anaesthetist, post-operative admission to critical care and procedure performed) was performed investigating the association between day of admission to hospital and 60-day post-operative mortality. Sunday was used as comparator variable. Results Study cohort included 1346 patients, overall 60-day inpatient mortality was 9.63% (134 patients). Following risk adjustment there was no increased risk of mortality when investigating day of admission to hospital; Monday Odds Ratio (OR 1.60, 95% Confidence Intervals (CI) 0.69-3.71), Friday (OR 2.01, 95% CI 0.85-4.7). Conclusion Risk of death in those that require emergency laparotomy is not affected by day of presentation to hospital.

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Evaluating the “holiday season effect” of hospital care on the risk of mortality from pulmonary embolism: a nationwide analysis in Taiwan

Scientific Reports ◽

10.1038/s41598-021-98845-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Duan-Pei Hung ◽

Shu-Man Lin ◽

Peter Pin-Sung Liu ◽

I-Min Su ◽

Jin-Yi Hsu ◽

...

Keyword(s):

Pulmonary Embolism ◽

Hospital Mortality ◽

Hospital Admissions ◽

Multivariable Analysis ◽

Research Database ◽

Logistic Regression Models ◽

Mortality Risks ◽

Holiday Period ◽

Risk Of Mortality ◽

Increased Risk

AbstractWe aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15–2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05–1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality.

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PIK3 mutation as a predictor of immune checkpoint inhibitor response.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15257 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15257-e15257

Author(s):

Aasems Jacob ◽

Jianrong Wu ◽

Aman Chauhan

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Study Cohort ◽

Chemotherapy Response ◽

Real World Data ◽

Recist 1.1 ◽

Increased Risk ◽

Significant Difference

e15257 Background: Although several biomarkers predicting response to immune checkpoint inhibitor (ICI) therapy have been evaluated, the emerging data is conflicting. There is a lack of real-world data that might help identify biomarkers in diverse populations. Methods: Patients with solid tumors who received ICI and underwent tumor tissue next generation sequencing (NGS) in our institution between 2016-2019 were included in the study. Response to ICI was assessed based on RECIST 1.1 and median progression free survival (mPFS), radiologic response and immune-related adverse events (IRAEs) were analyzed in relation to various molecular biomarkers. Results: 69 patients had complete NGS and RECIST 1.1 data required for analysis. Study cohort included 14 different cancer types. 78% of the patients were smokers. TP53 (62%), CDKN2A (44%), NOTCH1/2 and PIK3 (33%) were the most common mutations identified. 42% patients had CR/PR with ICI and mPFS was 38 weeks (w). A statistically significant improvement in PFS was observed in patients with PIK3 mutated cancers (mPFS 123 weeks vs. 23 weeks, p = 0.012). These patients also had a higher percentage of response (60.9% vs 39.1%, p = 0.5), and were also associated with increased risk of immune related adverse events (IRAEs) (73.9% vs. 37%, p = 0.004). PIK3 mutation had no association with PDL1 status or tumor mutational burden (TMB). Mean TMB was 12.59, and 29% patients had positive PDL1 expression. There was significant difference in mPFS between high (≥20mut/Mb) and low/intermediate TMB (0-19mut/Mb) (mPFS 18w vs. 65 w, p = 0.049) as well as PDL1 positive and negative tumors (40w vs. 18w, p = 0.059). BRAF mutation was associated with early progression in all cancers (mPFS 17w vs 39w, p = 0.033). Conclusions: Conventionally, a marker of poor survival and chemotherapy response, PIK3 mutation was associated with positive ICI response in our study. High incidence of IRAEs in PIK3 mutants also point towards increased ICI activity. High TMB, as expected was associated with ICI response.

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The Effect of Hypertensive Disorders of Pregnancy on the Risk of ADHD in the Offspring

Journal of Attention Disorders ◽

10.1177/1087054717690230 ◽

2017 ◽

Vol 23 (7) ◽

pp. 692-701 ◽

Cited By ~ 8

Author(s):

Stefanie Böhm ◽

Eileen A. Curran ◽

Louise C. Kenny ◽

Gerard W. O’Keeffe ◽

Deirdre Murray ◽

...

Keyword(s):

Regression Models ◽

Behavioral Difficulties ◽

Study Cohort ◽

Hypertensive Disorders Of Pregnancy ◽

Perinatal Factors ◽

Adhd Diagnosis ◽

Logistic Regression Models ◽

Hypertensive Disorders ◽

Increased Risk ◽

Objective Evidence

Objective: Evidence suggests that perinatal factors may contribute to the development of ADHD. Our objective was to examine the association between hypertensive disorders of pregnancy (HDP) and ADHD, and behavioral difficulties among 7-year-old children. Method: The study cohort consisted of 13,192 children (weighted = 13,500) who participated in the Millennium Cohort Study (MCS) at age 7. HDP (raised blood pressure, preeclampsia, eclampsia, and toxemia) were reported by mothers 9 months postdelivery. ADHD was reported by parents at age 7 years. Weighted logistic regression models were used to assess the association. Results: In all, 1,069 (7.9%) women reported HDP and 166 (1.2%) children had an ADHD diagnosis. There was a significant association between HDP and ADHD (adjusted odds ratio [OR] = 1.78, 95% confidence interval [CI] = [1.03, 3.07]). Conclusion: These findings suggest that HDP is associated with an increased risk of ADHD. It is important to confirm this in larger cohorts and to understand the biological basis of this association.

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Homocysteine increases the risk of mortality in elderly individuals

British Journal Of Nutrition ◽

10.1017/s0007114507691958 ◽

2007 ◽

Vol 97 (6) ◽

pp. 1138-1143 ◽

Cited By ~ 23

Author(s):

Sonia González ◽

José M. Huerta ◽

Serafina Fernández ◽

Ángeles M. Patterson ◽

Cristina Lasheras

Keyword(s):

Cox Regression ◽

Elderly Care ◽

The Elderly ◽

Elderly Subjects ◽

Vitamin B ◽

Study Cohort ◽

Risk Of Death ◽

Risk Of Mortality ◽

Increased Risk

Although total plasma homocysteine (tHcy) has been extensively studied as a risk factor of CVD, longitudinal evidence on its association with mortality is scarce, especially among the elderly. The study cohort consisted of 215 subjects (eighty-eight male and 127 female), aged 60 years or older, recruited in fourteen elderly care institutions from Asturias (Spain). All participants were free of major chronic pathology and took no vitamin and/or mineral supplements. Baseline determinations included tHcy in plasma and folate, vitamin B12and Se in serum. Survival analyses were performed by quintiles of these factors after 6 years (mean follow-up time 4·3 years) by means of Cox regression models. During follow-up time sixty participants died. tHcy above 16·7 μmol/l was associated with an increased risk of mortality in the sample (relative risk 2·30 (95 % CI 1·02, 5·17)). Among the nutritional determinants of tHcy evaluated, folate and Se were not predictive of death risk of the cohort, while vitamin B12showed inconsistent results. Nevertheless, mortality was significantly lower at higher serum Se levels (upper quintile), but this effect was restricted to women. Higher tHcy in both sexes and lower serum Se in women were found to be independently associated with an increased risk of death in elderly subjects.

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