scholarly journals Cyclooxygenase inhibitor use is associated with increased COVID-19 severity

Author(s):  
Justin Reese ◽  
Ben Coleman ◽  
Lauren Chan ◽  
Tiffany J Callahan ◽  
Luca Cappelletti ◽  
...  

BACKGROUND Cyclooxygenase (COX) inhibitors including non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community acquired pneumonia and other respiratory tract infections (RTIs). Conclusive data are not available about potential beneficial or adverse effects of COX inhibitors on COVID-19 patients. METHODS We conducted a retrospective, multi-center observational study by leveraging the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative (N3C). Potential associations of eight COX inhibitors with COVID-19 severity were assessed using ordinal logistic regression (OLR) on treatment with the medication in question after matching by treatment propensity as predicted by age, race, ethnicity, gender, smoking status, comorbidities, and BMI. Cox proportional hazards analysis was used to estimate the correlation of medication use with morbidity for eight subcohorts defined by common indications for COX inhibitors. RESULTS OLR revealed statistically significant associations between use of any of five COX inhibitors and increased severity of COVID-19. For instance, the odds ratio of aspirin use in the osteoarthritis cohort (n=2266 patients) was 3.25 (95% CI 2.76 - 3.83). Aspirin and acetaminophen were associated with increased mortality. CONCLUSIONS The association between use of COX inhibitors and COVID-19 severity was consistent across five COX inhibitors and multiple indication subcohorts. Our results align with earlier reports associating NSAID use with complications in RTI patients. Further research is needed to characterize the precise risk of individual COX inhibitors in COVID-19 patients.

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252719
Author(s):  
Achal P. Patel ◽  
Suril S. Mehta ◽  
Alexandra J. White ◽  
Nicole M. Niehoff ◽  
Whitney D. Arroyave ◽  
...  

Background Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic compounds associated with chronic disease in epidemiologic studies, though the contribution of PAH exposure on fatal outcomes in the U.S. is largely unknown. Objectives We investigated urinary hydroxylated PAH metabolites (OH-PAHs) with all-cause and cause-specific mortality in a representative sample of the U.S. population. Methods Study participants were ≥20 years old from the National Health and Nutrition Examination Survey 2001–2014. Concentrations (nmol/L) of eight OH-PAHs from four parent PAHs (naphthalene, fluorene, phenanthrene, pyrene) were measured in spot urine samples at examination. We identified all-cause, cancer-specific, and cardiovascular-specific deaths through 2015 using the National Death Index. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ΣOH-PAHs and mortality endpoints. We assessed potential heterogeneity by age, gender, smoking status, poverty, and race/ethnicity. Additionally, we examined the overall mixture effect using quantile g-computation. Results In 9,739 eligible participants, there were 934 all-cause deaths, 159 cancer-specific deaths, and 108 cardiovascular-specific deaths (median 6.75 years follow-up). A log10 increase in ΣOH-PAHs was associated with higher all-cause mortality (HRadj = 1.39 [95%CI: 1.21, 1.61]), and possibly cancer-specific mortality (HRadj = 1.15 [95%CI: 0.79, 1.69]), and cardiovascular-specific mortality (HRadj = 1.49 [95%CI: 0.94, 2.33]). We observed substantial effect modification by age, smoking status, gender, and race/ethnicity across mortality endpoints. Risk of cardiovascular mortality was higher for non-Hispanic blacks and those in poverty, indicating potential disparities. Quantile g-computation joint associations for a simultaneous quartile increase in OH-PAHs were HRadj = 1.15 [95%CI: 1.02, 1.31], HRadj = 1.41 [95%CI: 1.05, 1.90], and HRadj = 0.98 [95%CI: 0.66, 1.47] for all-cause, cancer-specific, and cardiovascular-specific mortalities, respectively. Discussion Our results support a role for total PAH exposure in all-cause and cause-specific mortality in the U.S. population.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 505-506
Author(s):  
Dominika Seblova ◽  
Kelly Peters ◽  
Susan Lapham ◽  
Laura Zahodne ◽  
Tara Gruenewald ◽  
...  

Abstract Having more years of education is independently associated with lower mortality, but it is unclear whether other attributes of schooling matter. We examined the association of high school quality and all-cause mortality across race/ethnicity. In 1960, about 5% of US high schools participated in Project Talent (PT), which collected information about students and their schools. Over 21,000 PT respondents were followed for mortality into their eighth decade of life using the National Death Index. A school quality factor, capturing term length, class size, and teacher qualifications, was used as the main predictor. First, we estimated overall and sex-stratified Cox proportional hazards models with standard errors clustered at the school level, adjusting for age, sex, composite measure of parental socioeconomic status, and 1960 cognitive ability. Second, we added an interaction between school quality and race/ethnicity. Among this diverse cohort (60% non-Hispanic Whites, 23% non-Hispanic Blacks, 7% Hispanics, 10% classified as another race/s) there were 3,476 deaths (16.5%). School quality was highest for Hispanic respondents and lowest for non-Hispanic Blacks. Non-Hispanic Blacks also had the highest mortality risk. In the whole sample, school quality was not associated with mortality risk. However, higher school quality was associated with lower mortality among those classified as another race/s (HR 0.75, 95% CI: 0.56-0.99). For non-Hispanic Blacks and Whites, the HR point estimates were unreliable, but suggest that higher school quality is associated with increased mortality. Future work will disentangle these differences in association of school quality across race/ethnicity and examine cause-specific mortality.


Author(s):  
Laurie Grieshober ◽  
Stefan Graw ◽  
Matt J. Barnett ◽  
Gary E. Goodman ◽  
Chu Chen ◽  
...  

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroki Yoshikawa ◽  
Kosaku Komiya ◽  
Takashi Yamamoto ◽  
Naoko Fujita ◽  
Hiroaki Oka ◽  
...  

AbstractErector spinae muscle (ESM) size has been reported as a predictor of prognosis in patients with some respiratory diseases. This study aimed to assess the association of ESM size on all-cause in-hospital mortality among elderly patients with pneumonia. We retrospectively included patients (age: ≥ 65 years) admitted to hospital from January 2015 to December 2017 for community-acquired pneumonia who underwent chest computed tomography (CT) on admission. The cross-sectional area of the ESM (ESMcsa) was measured on a single-slice CT image at the end of the 12th thoracic vertebra and adjusted by body surface area (BSA). Cox proportional hazards regression models were used to assess the influence of ESMcsa/BSA on in-hospital mortality. Among 736 patients who were admitted for pneumonia, 702 patients (95%) underwent chest CT. Of those, 689 patients (98%) for whom height and weight were measured to calculate BSA were included in this study. Patients in the non-survivor group were significantly older, had a greater frequency of respiratory failure, loss of consciousness, lower body mass index, hemoglobin, albumin, and ESMcsa/BSA. Multivariate analysis showed that a lower ESMcsa/BSA independently predicted in-hospital mortality after adjusting for these variables. In elderly patients with pneumonia, quantification of ESMcsa/BSA may be associated with in-hospital mortality.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259212
Author(s):  
Joungyoun Kim ◽  
Sang-Jun Shin ◽  
Hee-Taik Kang

Background The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs and mortality. Methods This retrospective study included 114,603 subjects. The TyG index was categorized into four quartiles by sex: Q1, <8.249 and <8.063; Q2, 8.249‒<8.614 and 8.063‒<8.403; Q3, 8.614‒< 8.998 and 8.403‒<8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality) and secondary outcomes (cardiovascular diseases [CVDs], cerebrovascular diseases [CbVDs], CCVD-related deaths, or all-cause deaths), Cox proportional hazards regression models were adopted. Results Compared to Q1, the HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.062 (0.981‒1.150), 1.110 (1.024−1.204), and 1.151 (1.058−1.252) in men and 1.099 (0.986−1.226), 1.046 (0.938−1.166), and 1.063 (0.954−1.184) in women, respectively, after adjusted for age, smoking status, drinking status, physical activity, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, economic status, and anti-hypertensive medications. Fully adjusted HRs (95% CIs) for CVDs of Q2, Q3, and Q4 were 1.114 (0.969−1.282), 1.185 (1.031−1.363), and 1.232 (1.068−1.422) in men and 1.238 (1.017−1.508), 1.183 (0.971−1.440), and 1.238 (1.018−1.505) in women, respectively. The adjusted HRs (95% CIs) for ischemic CbVDs of Q2, Q3, and Q4 were 1.005 (0.850−1.187), 1.225 (1.041−1.441), and 1.232 (1.039−1.460) in men and 1.040 (0.821−1.316), 1.226 (0.981−1.532), and 1.312 (1.054−1.634) in women, respectively, while the TyG index was negatively associated with hemorrhagic CbVDs in women but not in men. The TyG index was not significantly associated with CCVD-related death or all-cause death in either sex. Conclusions Elevated TyG index was positively associated with the primary outcomes (CCVDs and all-cause mortality) in men and predicted higher risk of CVDs and ischemic CbVDs in both sexes.


2019 ◽  
Author(s):  
Inger van Heijl ◽  
Valentijn A. Schweitzer ◽  
C.H. Edwin Boel ◽  
Jan Jelrik Oosterheert ◽  
Susanne M. Huijts ◽  
...  

BackgroundObservational studies have demonstrated that de-escalation of antimicrobial therapy is independently associated with lower mortality. This most probably results from confounding by indication. Reaching clinical stability is associated with the decision to de-escalate and with survival. However, studies rarely adjust for this confounder. We quantified the potential confounding effect of clinical stability on the estimated impact of de-escalation on mortality in patients with community-acquired pneumonia.MethodsData were used from the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). The primary outcome was 30-day mortality. We performed Cox proportional-hazards regression with de-escalation as time-dependent variable and adjusted for baseline characteristics using propensity scores. The potential impact of unmeasured confounding was quantified through simulating a variable representing clinical stability on day three, using data on prevalence and associations with mortality from the literature.ResultsOf 1,536 included patients, 257 (16.7%) were de-escalated, 123 (8.0%) were escalated and in 1156 (75.3%) the antibiotic spectrum remained unchanged. The adjusted hazard ratio of de-escalation for 30-day mortality (compared to patients with unchanged coverage), without adjustment for clinical stability, was 0.36 (95%CI: 0.18-0.73). If 90% to 100% of de-escalated patients were clinically stable on day three, the fully adjusted hazard ratio would be 0.53 (95%CI: 0.26-1.08) to 0.90 (95%CI: 0.42-1.91), respectively. The simulated confounder was substantially stronger than any of the baseline confounders in our dataset.ConclusionsWith plausible, literature-based assumptions, clinical stability is a very strong confounder for the effects of de-escalation. Quantification of effects of de-escalation on patient outcomes without proper adjustment for clinical stability results in strong negative bias. As a result, the safety of de-escalation remains to be determined.


OBJECTIVE The challenges of posterior cervical fusions (PCFs) at the cervicothoracic junction (CTJ) are widely known, including the development of adjacent-segment disease by stopping fusions at C7. One solution has been to cross the CTJ (T1/T2) rather than stopping at C7. This approach may have undue consequences, including increased reoperations for symptomatic nonunion (operative nonunion). The authors sought to investigate if there is a difference in operative nonunion in PCFs that stop at C7 versus T1/T2. METHODS A retrospective analysis identified patients from the authors’ spine registry (Kaiser Permanente) who underwent PCFs with caudal fusion levels at C7 and T1/T2. Demographics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Operative nonunion was adjudicated via chart review. Patients were followed until validated operative nonunion, membership termination, death, or end of study (March 31, 2020). Descriptive statistics and 2-year crude incidence rates and 95% confidence intervals for operative nonunion for PCFs stopping at C7 or T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox proportional hazards models were used to evaluate operative nonunion rates. RESULTS The authors identified 875 patients with PCFs (beginning at C3, C4, C5, or C6) stopping at either C7 (n = 470) or T1/T2 (n = 405) with a mean follow-up time of 4.6 ± 3.3 years and a mean time to operative nonunion of 0.9 ± 0.6 years. There were 17 operative nonunions, and, after adjustment for age at surgery and smoking status, the cumulative incidence rates were similar between constructs stopping at C7 and those that extended to T1/T2 (C7: 1.91% [95% CI 0.88%–3.60%]; T1/T2: 1.98% [95% CI 0.86%–3.85%]). In the crude model and model adjusted for age at surgery and smoking status, no difference in risk for constructs extended to T1/T2 compared to those stopping at C7 was found (adjusted HR 1.09 [95% CI 0.42–2.84], p = 0.86). CONCLUSIONS In one of the largest cohort of patients with PCFs stopping at C7 or T1/T2 with an average follow-up of > 4 years, the authors found no statistically significant difference in reoperation rates for symptomatic nonunion (operative nonunion). This finding shows that there is no added risk of operative nonunion by extending PCFs to T1/T2 or stopping at C7.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S914-S915
Author(s):  
Kengo Inagaki ◽  
Chad Blackshear ◽  
Charlotte V Hobbs

Abstract Background Race/ethnicity is currently not considered a risk factor for bronchiolitis, except for indigenous populations in western countries. We sought to determine the incidence of hospitalization with bronchiolitis among different races/ethnicities, because such information can lead to more tailored preventive care. Methods We performed a population-based longitudinal observational study using the State Inpatient Database from New York state. Infants born between 2009 and 2013 at term without comorbidities were followed for the first 2 years of life, up to 2015. We calculated incidence among different race/ethnicity groups, and evaluated risks by developing Cox proportional hazards regression models. Results Of 877,465 healthy term infants, 10 356 infants were hospitalized with bronchiolitis. Overall, incidence was 11.8 per 1,000 births. Substantial difference in infants born in different seasons was observed (Figure 1). The incidence in non-Hispanic white, non-Hispanic black, Hispanic, and Asian infants was 8.6, 15.4, 19.1, and 6.5 per 1,000 births, respectively (table). On multivariable analysis adjusting for socioeconomic status, the risks remained substantially high among non-Hispanic black (hazard ratio [HR] 1.42, 95% confidence interval [CI]: 1.34–1.51) and Hispanic infants (HR 1.77, 95% CI: 1.67–1.87), particularly beyond 2–3 months of age, whereas Asian race was protective (HR 0.62, 95% CI: 0.56–0.69) (Figure 2, 3). Conclusion The risks of bronchiolitis hospitalization in the first 2 years of life was substantially higher among infants with non-Asian minority infants, particularly beyond 2–3 months of age. Further research efforts to identify effective public health interventions in each race/ethnic groups with varied socioeconomic status, such as improvement in access to care and anticipatory guidance, is warranted to overcome health disparity. Disclosures All authors: No reported disclosures.


2016 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Giuseppe Grosso ◽  
Urszula Stepaniak ◽  
Agnieszka Micek ◽  
Denes Stefler ◽  
Martin Bobak ◽  
...  

AbstractObjectiveTo test the association between coffee consumption and risk of all-cause, CVD and cancer death in a European cohort.DesignProspective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used.SettingCzech Republic, Russia and Poland.SubjectsA total of 28561 individuals followed for 6·1 years.ResultsA total of 2121 deaths (43·1 % CVD and 35·7 % cancer mortality) occurred during the follow-up. Consumption of 3–4 cups coffee/d was associated with lower mortality risk in men (HR=0·83; 95 % CI 0·71, 0·99) and women (HR=0·63; 95 % CI 0·47, 0·84), while further intake showed non-significant reduced risk estimates (HR=0·71; 95 % CI 0·49, 1·04 and HR=0·51; 95 % CI 0·24, 1·10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0·71; 95 % CI 0·54, 0·93) for consumption of 3–4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0·61; 95 % CI 0·43, 0·87) and cancer mortality (HR=0·59; 95 % CI 0·35, 0·99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake.ConclusionsCoffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed.


Author(s):  
Francesca Ghilotti ◽  
Rino Bellocco ◽  
Weimin Ye ◽  
Hans-Olov Adami ◽  
Ylva Trolle Lagerros

Abstract Background Previous studies have shown an association between body mass index (BMI) and infections, but the literature on type-specific community acquired infections is still limited. Methods We included 39 163 Swedish adults who completed a questionnaire in September 1997 and were followed through record-linkages until December 2016. Information on BMI was self-reported and infections were identified from the Swedish National Patient Register using International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes. We fitted multivariable Cox proportional hazards models for time-to-first-event analysis, and we used extensions of the standard Cox model when repeated events were included. Results During a 19-year follow-up 32% of the subjects had at least one infection requiring health care contact, leading to a total of 27 675 events. We found an increased incidence of any infection in obese women [hazard ratio (HR) = 1.22; 95% confidence interval (CI) = 1.12; 1.33] and obese men (HR = 1.25; 95% CI = 1.09; 1.43) compared with normal weight subjects. For specific infections, higher incidences were observed for skin infections in both genders (HR = 1.76; 95% CI = 1.47; 2.12 for obese females and HR = 1.74; 95% CI = 1.33; 2.28 for obese males) and gastrointestinal tract infections (HR = 1.44; 95% CI = 1.19; 1.75), urinary tract infections (HR = 1.30; 95% CI = 1.08; 1.55) and sepsis (HR = 2.09; 95% CI = 1.46; 2.99) in obese females. When accounting for repeated events, estimates similar to the aforementioned ones were found. Conclusions Obesity was associated with an increased risk of infections in both genders. Results from multiple-failure survival analysis were consistent with those from classic Cox models.


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