Relative Risk Of Death Research Articles

Divergent androgenic modulation of SARS-CoV-2 infection cooperates with dysregulated immune response to dictate worse COVID-19 outcomes in men

BackgroundSex-determined differences are rarely addressed in the management of diseases, despite well-known contrasting outcomes between female and male patients. In COVID-19 there is a remarkable disparity, with higher rates of mortality and more severe acute disease in men compared to women, who are mostly affected by long COVID-19. Furthermore, whether androgens play a protective or detrimental role in COVID-19 is still a matter of debate. Hence, the adequate management of the disease, especially regarding men presenting acute disease aggravation, still needs important data to elucidate the interplay between sex hormones and host immune responses that drive the worse evolution in male patients. MethodsA cohort of 92 controls and 198 non-severe and severe COVID-19 patients, from both sexes, was assessed for clinical outcomes, plasma steroids, gonadotropins, sex hormone binding globulin (SHBG) and immune mediators, before vaccination. These data were correlated with the global gene expression of blood leukocytes. The androgen receptor (AR) signaling pathway was investigated by transcriptomics and tracheal aspirate was obtained from severe patients for SARS-COV-2 quantification in the respiratory tract. The interplay among clinical, endocrine and immunological data deciphered the sex differences in COVID-19. Importantly, statistical analyses, using 95% confidence interval, considered confounding factors such as age and comorbidities, to definitely parse the role of androgens in the disease outcome. ResultsThere were notable contrasting levels of testosterone and dihydrotestosterone (DHT) throughout the disease course in male but not female patients. Inflammatory mediators presented significant negative correlations with testosterone, which was partially dependent on age and diabetes in men. Male subjects with severe COVID-19 had a significant up regulation of the AR signaling pathway, including modulation of TMPRSS2 and SRD5A1 genes, which are related to the viral infection and DHT production. Indeed, men had a higher viral load in the tracheal aspirate and levels of DHT were associated with increased relative risk of death. In contrast, the testosterone hormone, which was notably reduced in severe disease, was significantly related with susceptibility to COVID-19 worsening in male patients. Secondary hypogonadism was ruled out in the male severe COVID-19 subjects, as FSH, LH, and SHBG levels were not significantly altered. Instead, these subjects tended to have increased gonadotropin levels. Most interestingly, in this study we identified, for the first time, combined sets of clinical and immunoendocrine parameters that together predicted progression from non-severe to severe COVID-19 in men. One of the limitations of our study was the low or undetectable levels of DHT in many patients. Then, the evaluation of enzymes related to biosynthesis and signaling by androgens was mandatory and reiterated our findings. ConclusionsThese original results unraveled the disease immunoendocrine regulation, despite vaccination or comorbidities and pointed to the fundamental divergent role of the androgens testosterone and DHT in the determination of COVID-19 outcomes in men. Therefore, sex-specific management of the dysregulated responses, treatments or public health measures should be considered for the control of COVID-19 pandemic.

Non-Invasive Risk Assessment and Prediction of Mortality in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Objectives: Heart rate turbulence (HRT) and T-wave alternans (TWA), non-invasive markers of cardiac autonomic dysfunction, and ventricular repolarization abnormality, reportedly, predict the risk of cardiovascular death after myocardial infarction. We investigated whether pre-operative assessment of HRT and/or TWA could predict long-term mortality following coronary artery bypass graft (CABG) surgery. Methods: From May 2010 to December 2017, patients undergoing elective CABG and receiving 24 h ambulatory electrocardiogram monitoring 1 to 5 days prior to CABG surgery were prospectively enrolled. Pre-operative HRT and TWA were measured using a 24 h ambulatory electrocardiogram. The relative risk of cardiac or overall death was assessed according to abnormalities of HRT, TWA, or left ventricular ejection fraction (LV EF). Results: During the mean follow-up period of 4.6 ± 3.9 years, 40 adjudicated overall (5.9%/yr) and 5 cardiac deaths (0.9%/yr) occurred in 146 enrolled patients (64.9 ± 9.3 years; 108 males). Patients with abnormal HRT exhibited significantly higher relative risks of cardiac death (adjusted hazard ratio [HR] 24.9, 95% confidence interval [CI] 1.46-427) and all-cause death (adjusted HR 5.77, 95% CI 2.34-14.2) compared to those with normal HRT. Moreover, abnormal HRT plus abnormal TWA and LV EF < 50% was associated with a greater elevation in cardiac and overall mortality risk. The predictive role of abnormal HRT with/without abnormal TWA for all-cause death was likely more prominent in patients with mildly reduced (35 to 50%) or preserved (≥50%) LV EF. Abnormal HRT plus abnormal TWA and LV EF < 50% showed high negative predictive value in cardiac and overall mortality risk. Conclusions: Assessment of pre-operative HRT and/or TWA predicted mortality risk in patients undergoing elective CABG. Combined analysis of HRT, TWA, and LVEF enhanced the prognostic power. In particular, the predictive value of HRT was enhanced in patients with preserved or mid-range LV EF.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19

Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

Neonatal Admission Temperature in Middle- and High-Income Countries.

Despite being preventable, neonatal hypothermia remains common. We hypothesized that the proportion of newborns with hypothermia on admission would be high in all settings, higher in hospitals in middle-income countries (MIC) compared with high-income countries (HIC), and associated with morbidity and mortality. Using the Vermont Oxford Network database of newborns with birth weights 401 to 1500 g or 22 to 29 weeks' gestational age from 2018 to 2021, we analyzed maternal and infant characteristics, delivery room management, and outcomes by temperature within 1 hour of admission to the NICU in 12 MICs and 22 HICs. Among 201 046 newborns, hypothermia was more common in MIC hospitals (64.0%) compared with HIC hospitals (28.6%). Lower birth weight, small for gestational age status, and prolonged resuscitation were perinatal risk factors for hypothermia. The mortality was doubled for hypothermic compared with euthermic newborns in MICs (24.7% and 15.4%) and HICs (12.7% and 7.6%) hospitals. After adjusting for confounders, the relative risk of death among hypothermic newborns compared with euthermic newborns was 1.21 (95% confidence interval 1.09-1.33) in MICs and 1.26 (95% confidence interval 1.21-1.31) in HICs. Every 1°C increase in admission temperature was associated with a 9% and 10% decrease in mortality risk in MICs and HICs, respectively. In this large sample of newborns across MICs and HICs, hypothermia remains common and is strongly associated with mortality. The profound burden of hypothermia presents an opportunity for strategies to improve outcomes and achieve the neonatal 2030 Sustainable Development Goal.

Influenza Vaccination Decreases The Risk Of Cardiovascular Disease In End Stage Renal Disease Patients.

Madam, Influenza is a viral respiratory tract infection that causes symptoms such as fever, sore throat, cough and runny nose with a mostly self-limiting prognosis. However, it can cause an increased risk of hospitalization and mortality in high-risk groups such as those suffering from end-stage renal disease (ESRD) [1]. CVD is present in &gt;50% of cases of ESRD and is associated with a 20 times greater relative risk of death than in the general population, particularly with patients infected with influenza [2] [3]. This is due to the dysfunctional immunity in those affected by chronic kidney disease. The pathophysiology behind the influenza infection leading to CVD in ESRD patients is due to the rise of acute phase reactants in response to viral infection markers triggering a systemic inflammatory reaction. This reaction comprises damage to the endothelial cell lining of vessels, impaired vasodilation, dysfunctional platelet activation, and elevated pro-coagulation. In addition, the increased metabolic demand and altered coronary vascular tone can bring about disruption and instability of atherosclerotic plaques in coronary arteries, thus inducing an acute coronary syndrome. [1] Using influenza vaccine can significantly lower the risk of CVD in ESRD patients. Currently, available influenza vaccines include inactivated, recombinant, and live-attenuated (LAIVs).[4] Inactivated vaccines contain either surface glycoproteins such as hemagglutinin (HA) and neuraminidase (NA) or whole viral protein without the lipid envelope or chemically inactivated virus, whereas recombinant vaccines are composed of genetically synthesized HA subunits and LAIVs have the whole virus with weakened pathogenicity. These vaccines are produced as either trivalent (with both, influenza A subtypes H1N1 andH3N2 and dominant influenza B of either Yamagata or Victoria lineage) or quadrivalent (having both influenza B lineages) vaccines.[4] According to a population-based case-cohort study, annual influenza vaccinations have been seen to greatly reduce the hospitalisation rates for CVD in elderly patients with chronic kidney disease regardless of gender and influenza seasonality [5]. Moreover, it reduces the risk of CVD in patients with a hazard ratio of 0.74 for hospitalisation due to CVD among the vaccinated group compared to the non-vaccinated group, indicating a 26% lower risk and 35% reduction in overall mortality. [3] Therefore, the protective mechanism of influenza vaccination may be beneficial in reducing the risk of hospitalisations and morbidity in ESRD patients by reducing the likelihood of cardiovascular-associated complications. Thus, it should be incorporated as an integral part of the management of ESRD.

Disease severity and mortality in Alzheimer's disease: an analysis using the U.S. National Alzheimer’s Coordinating Center Uniform Data Set

BackgroundEvidence on the relative risk of death across all stages of Alzheimer’s disease (AD) is lacking but greatly needed for the evaluation of new interventions. We used data from the Uniform Data Set (UDS) of the National Alzheimer’s Coordinating Center (NACC) to assess the expected survival of a person progressing to a particular stage of AD and the relative risk of death for a person in a particular stage of AD compared with cognitively normal (CN) people.MethodsThis was a retrospective observational cohort study of mortality and its determinants in participants with incident mild cognitive impairment (MCI) due to AD or AD dementia compared with CN participants. Overall survival and hazard ratios of all-cause mortality in participants ≥ 50 years of age with clinically assessed or diagnosed MCI due to AD, or mild, moderate, or severe AD dementia, confirmed by Clinical Dementia Rating scores, versus CN participants were estimated, using NACC UDS data. Participants were followed until death, censoring, or until information to determine disease stage was missing.ResultsAged between 50 and 104 years, 12,414 participants met the eligibility criteria for the study. Participants progressing to MCI due to AD or AD dementia survived a median of 3–12 years, with higher mortality observed in more severe stages. Risk of death increased with the severity of AD dementia, with the increase significantly higher at younger ages. Participants with MCI due to AD and CN participants had a similar risk of death after controlling for confounding factors.ConclusionsRelative all-cause mortality risk increases with AD severity, more so at younger ages. Mortality does not seem to be higher for those remaining in MCI due to AD. Findings might imply potential benefit of lower mortality if preventing or delaying the progression of AD is successful, and importantly, this potential benefit might be greater in relatively younger people. Future research should replicate our study in other samples more representative of the general US population as well as other populations around the world.

Association of Maternal Cigarette Smoking with Neonatal Death: A Population-Based Cohort Study

Introduction: Maternal pregnancy smoking has adverse perinatal outcomes and the relationship between maternal smoking and neonatal death has not been fully elucidated. We aimed to examine the risk of neonatal death in relation to maternal smoking and to quantify potential mediators of these associations. Methods: We did a population-based cohort study using Period Linked Birth-Infant Death data from 2016 to 2019 in the US National Vital Statistics System. The exposure was maternal smoking status. The main outcome was neonatal death. Association between maternal smoking and neonatal death was estimated through logistic regression. Mediation analysis was performed to assess the extent to which the association between maternal smoking and neonatal death was mediated by neonatal complications. Results: The final sample consisted of 14,717,020 mothers with live singleton births. The overall neonatal mortality rate was 2.2 per 1,000 live births. Maternal pregnancy smoking was associated with an increased risk of neonatal death {adjusted odds ratio (aOR, 1.33 [95% CI, 1.28–1.38]; p < 0.001)}, while smoking cessation during the whole pregnancy showed a comparable risk of neonatal death with nonsmokers (aOR, 1.06 [95% CI, 0.99–1.14]; p = 0.116). Mediation analysis indicated that the association between pregnancy smoking and neonatal death might be mainly mediated by preterm birth and low Apgar score at 5 min. Conclusions: Maternal pregnancy smoking, regardless of pregnancy trimester and intensity, was associated with increased risk of neonatal death. Efforts are needed for policymakers to promote smoking cessation before pregnancy, and professional perinatal care should be provided for those who smoked during pregnancy.

Statins and Mortality in COPD: A Methodological Review of Observational Studies

Randomized controlled trials and observational studies have reported conflicting results on the potential beneficial effects of statins on mortality in patients with chronic obstructive pulmonary disease (COPD). We performed a systematic search of the literature to review all observational studies reporting relative risks of death with statin use in COPD, focusing on potential sources of bias. We identified 15 observational studies, out of 2835, of which 12 were affected by time-related and other biases and the remaining 3 by confounding bias. All 15 studies were also subject to confounding bias due to lack of adjustment for important COPD-related factors. The risk of death associated with statin use was reduced across all 15 studies (pooled relative risk (PRR) 0.66; 95% CI: 0.59-0.74). The reduction was observed in 7 studies with immortal time bias (PRR 0.62; 95%: 0.53-0.72), two with collider-stratification bias (PRR 0.60; 95% CI: 0.45-0.80), one with time-window bias (RR 0.61; 95% CI: 0.38-0.98), one with immeasurable time bias (RR 0.50; 95% CI: 0.40-0.62), and one with exposure misclassification (RR 0.86; 95% CI: 0.72-1.03). The three studies that avoided these biases were, however, affected by confounding bias resulting in a PRR of 0.77 (95% CI: 0.61-0.98). In conclusion, the observational studies investigating statin use and mortality in COPD are affected by major biases, many of which can result in spurious protective effects. Well-designed observational studies that carefully emulate randomized trials are needed to resolve this uncertainty regarding the potential beneficial benefits of statins on mortality in patients with COPD.

Coupling the effects of extreme temperature and air pollution on non-accidental mortality in Rencheng, China.

Extreme temperatures and air pollution have raised widespread concerns about their impact on population health. To explore the quantitative exposure risks of high/low temperatures and types of air pollutants on the health of various populations in urban areas in China, this study assessed the effects of temperature and air pollutants on daily non-accidental deaths in Rencheng District, Jining City, China from 2019 to 2021. A combination of Poisson regression models and distributed lag non-linear models was used to examine the relationships between temperature, air pollutants, and daily non-accidental deaths. We found that temperature and air pollutants had a significant non-linear effect on non-accidental mortality. Both high and low temperatures had a noticeable impact on non-accidental deaths, with heat effects occurring immediately and lasting 2-3 days, while cold effects lasted for 6-12 days. The relative risks of non-accidental deaths from PM2.5, NO2, and SO2 were highest in winter and lowest in autumn. The relative risk of non-accidental deaths from O3 was highest in spring, with no significant variations in other seasons. Older adults (≥75) and outdoor workers were at the greatest risk from temperature and air pollutant exposure. Exposure to extreme temperatures and air pollutants in the Rencheng District was associated with an increased mortality rate. Under the influence of climate change, it is necessary for policymakers to take measures to reduce the risk of non-accidental deaths among residents.

Detection of Sarcopenia in Patients with Liver Cirrhosis Using the Bioelectrical Impedance Analysis.

Bioelectrical impedance analysis (BIA) is a body composition assessment method. We aimed to determine its accuracy in the detection of sarcopenia in patients with liver cirrhosis (LC), using skeletal muscle index (SMI) at the level of third lumbar vertebra (L3-SMI) obtained using multislice computed tomography as the reference method. Patients with LC were enrolled in the period October 2019-March 2022 and follow-ups were conducted until January 2023. Their BIA parameters were compared against L3-SMI, and BIA cut-off values were proposed using AUROC analysis. Patients underwent outcome analysis based on obtained clinical characteristics. A total of 106 patients were included. We found a fair correlation between BIA parameters with the L3-SMI. We determined cut-off values of ≤11.1 kg/m2 for BIA-SMI (Se 73%, Sp 66%, AUROC 0.737, p < 0.001) and ≤5.05° for phase angle (PA) (Se 79%, Sp 60%, AUROC 0.762, p < 0.001) in the detection of sarcopenia. The relative risk of death was 2.2 times higher in patients with skeletal muscle mass (SMM) ≤ 36.5 kg. SMM was significantly associated with outcome in Kaplan-Meier analysis. This non-invasive and simple method that showed fair performances and a very good outcome prediction could provide for the unmet need for fast and affordable detection of sarcopenia in patients with LC and should be further evaluated.

The Impact of the COVID-19 Pandemic on Outcomes in Acute Pancreatitis: A Propensity Score Matched Study Comparing before and during the Pandemic.

We aimed to evaluate the outcomes and survival of patients with acute pancreatitis who shared the same clinical form, age, and sex before the pandemic, during the pandemic, and among those with confirmed COVID-19 infection upon hospital admission. This consideration used the sparse data in the existing literature on the influence of the pandemic and COVID-19 infection on patients with acute pancreatitis. To accomplish this, we conducted a multicentric, retrospective case-control study using propensity score matching with a 2:1 match of 28 patients with SARS-CoV-2 infection and acute pancreatitis, with 56 patients with acute pancreatitis pre-pandemic, and 56 patients with acute pancreatitis during the pandemic. The study outcome demonstrated a six-fold relative risk of death in patients with acute pancreatitis and SARS-CoV-2 infection compared to those with acute pancreatitis before the pandemic. Furthermore, restrictive measures implemented during the pandemic period led to a partial delay in the care of patients with acute pancreatitis, which likely resulted in an impairment of their immune state. This, in certain circumstances, resulted in a restriction of surgical treatment indications, leading to a three-fold relative risk of death in patients with acute pancreatitis during the pandemic compared to those with acute pancreatitis before the pandemic.

Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease.

Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS-COVID-19 (International Survey of Acute Coronavirus Syndromes-COVID-19) registry. Patients with a confirmed diagnosis of SARS-CoV-2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06-2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69-1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42-0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75-2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (Pinteraction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34-3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

The global burden of alcoholic liver disease: a systematic analysis of the global burden of disease study 2019.

Alcohol use is a major risk factor for the burden of mortality and morbidity. Alcoholic cirrhosis (AC) and alcoholic liver cancer (ALC) are most important and severe liver disease outcomes caused by alcohol use. The objectives of the current study were to investigate the global prevalence and burden of disease in disability-adjusted life years (DALYs) for AC and ALC, based on data from the Global Burden of Disease (GBD). Incidence, prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. The correlations between the age-standardized incidence rate or age-standardized death rate and gender, sociodemographic index (SDI), and alcohol usage were conducted by Generalized Linear Models. Globally, the changes of age-standardized rates of indicators were not much significant over the 30-year period. However, the changes varied widely across regions. Central Asia and East Europe contributed the highest age-standardized incidence, prevalence, death, and DALYs and increased sharply by past 30years. Generalized Linear Models (GLMs) showed male gender as a risk factor of AC, with the relative risk of incidence of 1.521 and relative risk of death of 1.503. Globally, there were improvements in overall health with regard to GBDs over the 30years. However, the prevention of AC and ALC should be promoted in middle and middle-high SDI regions, especially Central Asia and East Europe, whereas more medical resources should be provided to improve treatment levels in low SDI region.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study

Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. Bill & Melinda Gates Foundation.

Risk prediction of covid-19 related death or hospital admission in adults testing positive for SARS-CoV-2 infection during the omicron wave in England (QCOVID4): cohort study

ObjectivesTo derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period...

#6715 COGNITIVE IMPAIRMENT IS ASSOCIATED WITH INCREASED MORTALITY IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Patients on dialysis are at substantially higher risk for developing cognitive impairment compared with the general population. At the same time cognitive impairment is a strong and independent risk factor for all-cause mortality. Given that the approaches used to access the prevalence of cognitive disfunction widely vary in different patient populations, their true burden in hemodialysis patients remains poorly understood. The aim of our study was to determine the association between cognitive impairment and overall survival and mortality in patients undergoing hemodialysis treatment. Method A total of 69 chronic hemodialysis patients (47 men and 22 women) were included. The median age of patients was 61 [47-69] years. The median duration of hemodialysis treatment was 32 [21-72] months. The study of cognitive status was conducted using the Montreal Cognitive Assessment (MoCA) questionnaire. The test results are between 0 and 30 points. A score of 26 points or more is considered the norm, less than 26 indicates the presence of cognitive impairment. The end point was a fatal outcome from acute pathology or progression of a chronic disease. The analysis of survival and mortality was evaluated using survival tables, the construction of Kaplan-Mayer curves with the Mantel-Cox log–rank criterion. The risks of the influence of cognitive impairment on mortality were assessed using Cox regression. Results During the 24-month follow-up period, 23 patients died. Structure of mortality over the observation period: acute coronary syndrome – 6 (26 %), COVID-19 – 6 (26 %), acute cerebrovascular accident – 2 (9%), thromboembolic complications – 3 (13%), another causes – 6 (26 %). In patients with cognitive impairment on hemodialysis, the average survival value was 16.33 months ± 1.70 months [CI 95% 12.99-19.66] and 20.48 months±1.32 months [CI 95% 17.88-23.07] in patients without cognitive impairment. According to the Mantel-Cox log-rank criterion, there was a statistically significant decrease in overall survival in patients with cognitive impairment, P = .02. The mortality rate of dialysis patients with cognitive impairment was 51%, without cognitive impairment – 19%. Relative risk of death in the group of patients with cognitive impairment using Cox regression: Hazard ratio (HR) :2.90 [95% CI 1.11-7.37, P = .03]. Conclusion Our results support the notion that cognitive impairment may be an independent predictor of all-cause mortality in hemodialysis patients. There are limitations on the sample size of patients in our study. Further larger-scale observations a large cohort of patients are required.

Complications in hospitalized patients with SARS-CoV2 infection

OBJECTIVES: The present study aimed to assess the prevalence of complications during hospitalization in patients diagnosed with COVID-19, as well as the association with mortality and prognosis. METHODS: A retrospective cohort study involved 306 patients admitted to a COVID ward and ICU aged 18 years or older with confirmed SARS-CoV2 infection admitted to a Brazilian Tertiary Hospital. Demographic, clinical, biochemical, radiological and outcome data were collected from the patients' charts. RESULTS: According to the data analyzed during hospitalization, 230 (75.2%) patients developed complications, 281 (91.8%) patients had comorbidities and 169 (55.2%) patients died. There are no differences regarding the sex of the patients. The most prevalent complication was ventilator-associated pneumonia, present in 130 (42.5%) patients, followed by acute kidney injury or chronic kidney disease requiring hemodialysis, presented by 100 (32.7%) patients. The calculation of the relative risk of death according to the occurrence of complications showed p&lt;0.0001 for acute renal failure, p&lt;0.0001 for orotracheal intubation and p=0.0434 for acute myocardial infarction. CONCLUSION: The relative risk of death in COVID-19 is significant, showing an increase in relation to age, length of hospital stay and complications. Prevention, early diagnosis and appropriate treatment are essential to reduce the mortality rate in patients with SARS-CoV-2 infection.

A nomogram for predicting mortality of patients initially diagnosed with primary pulmonary tuberculosis in Hunan province, China: a retrospective study.

According to the Global Tuberculosis Report for three consecutive years, tuberculosis (TB) is the second leading infectious killer. Primary pulmonary tuberculosis (PTB) leads to the highest mortality among TB diseases. Regretfully, no previous studies targeted the PTB of a specific type or in a specific course, so models established in previous studies cannot be accurately feasible for clinical treatments. This study aimed to construct a nomogram prognostic model to quickly recognize death-related risk factors in patients initially diagnosed with PTB to intervene and treat high-risk patients as early as possible in the clinic to reduce mortality. We retrospectively analyzed the clinical data of 1,809 in-hospital patients initially diagnosed with primary PTB at Hunan Chest Hospital from January 1, 2019, to December 31, 2019. Binary logistic regression analysis was used to identify the risk factors. A nomogram prognostic model for mortality prediction was constructed using R software and was validated using a validation set. Univariate and multivariate logistic regression analyses revealed that drinking, hepatitis B virus (HBV), body mass index (BMI), age, albumin (ALB), and hemoglobin (Hb) were six independent predictors of death in in-hospital patients initially diagnosed with primary PTB. Based on these predictors, a nomogram prognostic model was established with high prediction accuracy, of which the area under the curve (AUC) was 0.881 (95% confidence interval [Cl]: 0.777-0.847), the sensitivity was 84.7%, and the specificity was 77.7%.Internal and external validations confirmed that the constructed model fit the real situation well. The constructed nomogram prognostic model can recognize risk factors and accurately predict the mortality of patients initially diagnosed with primary PTB. This is expected to guide early clinical intervention and treatment for high-risk patients.

A novel approach for pharmacological substantiation of safety signals using plasma concentrations of medication and administrative/healthcare databases: A case study using Danish registries for an FDA warning on lamotrigine

PHARMACOM-EPI is a novel framework to predict plasma concentrations of drugs at the time of occurrence of clinical outcomes. In early 2021, the U.S. Food and Drug Administration (FDA) issued a warning on the antiseizure drug lamotrigine claiming that it has the potential to increase the risk of arrhythmias and related sudden cardiac death due to a pharmacological sodium channel-blocking effect. We hypothesized that the risk of arrhythmias and related death is due to toxicity. We used the PHARMACOM-EPI framework to investigate the relationship between lamotrigine’s plasma concentrations and the risk of death in older patients using real-world data. Danish nationwide administrative and healthcare registers were used as data sources and individuals aged 65 years or older during the period 1996 – 2018 were included in the study. According to the PHARMACOM-EPI framework, plasma concentrations of lamotrigine were predicted at the time of death and patients were categorized into non-toxic and toxic groups based on the therapeutic range of lamotrigine (3–15 mg/L). Over 1 year of treatment, the incidence rate ratio (IRR) of all-cause mortality was calculated between the propensities score matched toxic and non-toxic groups. In total, 7286 individuals were diagnosed with epilepsy and were exposed to lamotrigine, 432 of which had at least one plasma concentration measurement The pharmacometric model by Chavez et al. was used to predict lamotrigine’s plasma concentrations considering the lowest absolute percentage error among identified models (14.25 %, 95 % CI: 11.68–16.23). The majority of lamotrigine associated deaths were cardiovascular-related and occurred among individuals with plasma concentrations in the toxic range. The IRR of mortality between the toxic group and non-toxic group was 3.37 [95 % CI: 1.44–8.32] and the cumulative incidence of all-cause mortality exponentially increased in the toxic range. Application of our novel framework PHARMACOM-EPI provided strong evidence to support our hypothesis that the increased risk of all-cause and cardiovascular death was associated with a toxic plasma concentration level of lamotrigine among older lamotrigine users.

Abstract 60: Low-Income is a Negative Prognostic Factor in Patients With MPNST: An NCDB Analysis

Abstract Purpose: Malignant Peripheral Nerve Sheath Tumors (MPNST) are a form of soft tissue tumor that forms from the Schwann cell lineage. Previous studies have noted that treatment at income is generally associated with improved survival in cancer patients. Thus, the objective of this study was to investigate the influence of patient income level on overall survival for patients with MPNST. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with MPNST from 2004 to 2019 using the ICD-O-3 histology code 9540. Median Income Quartiles were identified as assigned by the Commission on Cancer Accreditation program and re-classified into three categorical variables: high (HI= &amp;gt;$46,000) middle (MI =$30,000 – $45,999) and low (LI =&amp;lt;$29,000). Descriptive statistics and Kaplan Meier curves were used to measure survival in these patients and Chi-square analyses were used to evaluate differences in demographics. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: Of the 2222 patients with MPNST queried, 2,023 met selection criteria for Kaplan-Meier analysis. Patients in the high-income bracket experienced the longest median survival (83.6 months) compared to 47 and 37 months for the median- and low-income groups, respectively. A Log-Rank test found the difference in survival by income groups to be statistically significant. A Cox Proportional Hazards Model revealed that increased income was not significantly associated with decreased hazard (death), however being in the lowest income bracket was associated with a 41% increase in the relative risk of death (HR 1.41; 95% CI 1.19-1.67). Low-income patients did not present with more advanced disease, however, they experienced a longer average delay in the onset of treatment and were significantly more likely to be uninsured and of Black or Native American) race. Conclusion: This retrospective cohort study found that for patients with MPNST, low income was independently associated with inferior survival. These patients were more likely to be a minority race and presented with less insurance coverage. They thus experienced a longer duration between diagnosis and the initiation of therapy compared to patients with higher incomes. Citation Format: Jared Kennard, Marco Braaten, Peter Silberstein. Low-Income is a Negative Prognostic Factor in Patients With MPNST: An NCDB Analysis [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 60.