Predictors of high-intensity care at the end of life among older adults with solid tumors: A population-based study.

INTRODUCTION: High-intensity end-of-life (EoL) care can be burdensome for patients, caregivers, and health systems and does not confer any meaningful clinical benefit. Yet, there are significant knowledge gaps regarding the predictors of high-intensity EoL care. In this study, we identify risk factors associated with high-intensity EoL care among older adults with the four most common malignancies, including breast, prostate, lung, and colorectal cancer. MATERIALS AND METHODS: Using SEER-Medicare data, we conducted a retrospective analysis of Medicare beneficiaries aged 65 and older who died of breast, prostate, lung, or colorectal cancer between 2011 and 2015. We used multivariable logistic regression to identify clinical, demographic, socioeconomic, and geographic predictors of high-intensity EoL care, which we defined as death in an acute care hospital, receipt of any oral or parenteral chemotherapy within 14 days of death, one or more admissions to the intensive care unit within 30 days of death, two or more emergency department visits within 30 days of death, or two or more inpatient admissions within 30 days of death. RESULTS: Among 59,355 decedents, factors associated with increased likelihood of receiving high-intensity EoL care were increased comorbidity burden (odds ratio [OR]:1.29; 95% confidence interval [CI]:1.28-1.30), female sex (OR:1.05; 95% CI:1.01-1.09), Black race (OR:1.14; 95% CI:1.07-1.23), Other race/ethnicity (OR:1.20; 95% CI:1.10-1.30), stage III disease (OR:1.11; 95% CI:1.05-1.18), living in a county with >1,000,000 people (OR:1.23; 95% CI:1.16-1.31), living in a census tract with 10%-<20% poverty (OR:1.09; 95% CI:1.03-1.16) or 20%-100% poverty (OR:1.12; 95% CI:1.04-1.19), and having state-subsidized Medicare premiums (OR:1.18; 95% CI:1.12-1.24). The risk of high-intensity EoL care was lower among patients who were older (OR:0.98; 95% CI:0.98-0.99), lived in the Midwest (OR:0.69; 95% CI:0.65-0.75), South (OR:0.70; 95% CI:0.65-0.74), or West (OR:0.81; 95% CI:0.77-0.86), lived in mostly rural areas (OR:0.92; 95% CI:0.86-1.00), and had poor performance status (OR:0.26; 95% CI:0.25-0.28). Results were largely consistent across cancer types. DISCUSSION: The risk factors identified in our study can inform the development of new interventions for patients with cancer who are likely to receive high-intensity EoL care. Health systems should consider incorporating these risk factors into decision-support tools to assist clinicians in identifying which patients should be referred to hospice and palliative care.

Management of Oligometastatic and Locally Recurrent Urothelial Carcinoma.

PURPOSE OF REVIEW: To summarize and evaluate the literature on treatment approaches for oligometastatic and locally recurrent urothelial cancer. RECENT FINDINGS: There is no clear definition for oligometastatic urothelial cancers due to limited data. Studies focusing on oligometastatic and locally recurrent urothelial cancer have been primarily retrospective. Treatment options include local therapy with surgery or radiation, and generalized systemic therapy such as chemotherapy or immunotherapy. Oligometastatic and locally recurrent urothelial cancers remain challenging to manage, and treatment requires an interdisciplinary approach. Systemic therapy is nearly always a component of current care in the form of chemotherapy, but the role of immunotherapy has not been explored. Consideration of surgical and radiation options may improve outcomes, and no studies have compared directly between the two localized treatment options. The development of new prognostic and predictive biomarkers may also enhance the treatment landscape in the future.

Incidence and predictors of idiopathic pneumonia syndrome in hematopoietic stem cell transplant patients: a nationwide registry study.

Idiopathic pneumonia syndrome (IPS) is a rare but deadly complication of hematopoietic stem cell transplantation (HSCT). This study characterized the incidence and risk factors for IPS after HSCT in Taiwan. Data from January 2009 to February 2019 was collected from the Taiwan Society of BMT national registry. Forty-three (1.1%) of 3924 HSCT patients who developed IPS were identified. Incidence of IPS was lower in patients who received autologous HSCT than patients who received allogeneic HSCT (0.68% vs 1.44%, P = 0.022). Multivariate analysis showed that use of TBI and intravenous busulfan in the conditioning regimen were each independent predictor of IPS after HSCT. In addition, development of IPS was significantly associated with increased risk of death in the first 120 days post-HSCT (HR, 2.09; 95% CI, 1.08 to 4.05, P = 0.029) and 2 years post-HSCT (HR, 1.65; 95% CI, 1.07 to 2.542, P = 0.023), but not beyond 2 years post-HSCT. However, survival outcomes did not differ significantly between patients with IPS who received autologous versus allogeneic HSCT (P = 0.52). In conclusion, despite the relatively low incidence of post-HSCT IPS in Taiwan, mortality remains high. The results of this study will help to identify high-risk patients for early intervention and guide future therapeutic research.

Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease.

BACKGROUND: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. OBJECTIVE: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. METHODS: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. RESULTS: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. CONCLUSION: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.

Functional Status and Survival in Older Nursing Home Residents With Advanced Non-Small-Cell Lung Cancer: A SEER-Medicare Analysis.

PURPOSE: Many older patients with advanced lung cancer have functional limitations and require skilled nursing home care. Function, assessed using activities of daily living (ADL) scores, may help prognostication. We investigated the relationship between ADL impairment and overall survival among older patients with advanced non-small-cell lung cancer (NSCLC) receiving care in nursing homes. METHODS: Using the SEER-Medicare database linked with Minimum Data Set assessments, we identified patients age 65 years and older with NSCLC who received care in nursing homes from 2011 to 2015. We used Cox regression and Kaplan-Meier survival curves to examine the relationship between ADL scores and overall survival among all patients; among patients who received systemic cancer chemotherapy or immunotherapy within 3 months of NSCLC diagnosis; and among patients who did not receive any treatment. RESULTS: We included 3,174 patients (mean [standard deviation] age, 77 [7.4] years [range, 65-102 years]; 1,664 [52.4%] of female sex; 394 [12.4%] of non-Hispanic Black race/ethnicity), 415 (13.1%) of whom received systemic therapy, most commonly with carboplatin-based regimens (n = 357 [86%] patients). The median overall survival was 3.1 months for patients with ADL score < 14, 2.8 months for patients with ADL score between 14 and 17, 2.3 months for patients with ADL score between 18-19, and 1.8 months for patients with ADL score 20+ (log-rank P < .001). The ADL score was associated with increased risk of death (hazard ratio [HR], 1.20; 95% CI, 1.16 to 1.25 per standard deviation). One standard deviation increase in the ADL score was associated with lower overall survival rate among treated (HR, 1.14; 95% CI, 1.02 to 1.27) and untreated (HR, 1.20; 95% CI, 1.15 to 1.26) patients. CONCLUSION: ADL assessment stratified mortality outcomes among older nursing home adults with NSCLC, and may be a useful clinical consideration in this population.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

Validation of a Post-Transplant Lymphoproliferative Disorder Risk Prediction Score and Derivation of a New Prediction Score Using a National Bone Marrow Transplant Registry Database.

BACKGROUND: We externally validated Fujimoto's post-transplant lymphoproliferative disorder (PTLD) scoring system for risk prediction by using the Taiwan Blood and Marrow Transplant Registry Database (TBMTRD) and aimed to create a superior scoring system using machine learning methods. MATERIALS AND METHODS: Consecutive allogeneic hematopoietic cell transplant (HCT) recipients registered in the TBMTRD from 2009 to 2018 were included in this study. The Fujimoto PTLD score was calculated for each patient. The machine learning algorithm, least absolute shrinkage and selection operator (LASSO), was used to construct a new score system, which was validated using the fivefold cross-validation method. RESULTS: We identified 2,148 allogeneic HCT recipients, of which 57 (2.65%) developed PTLD in the TBMTRD. In this population, the probabilities for PTLD development by Fujimoto score at 5 years for patients in the low-, intermediate-, high-, and very-high-risk groups were 1.15%, 3.06%, 4.09%, and 8.97%, respectively. The score model had acceptable discrimination with a C-statistic of 0.65 and a near-perfect moderate calibration curve (HL test p = .81). Using LASSO regression analysis, a four-risk group model was constructed, and the new model showed better discrimination in the validation cohort when compared with The Fujimoto PTLD score (C-statistic: 0.75 vs. 0.65). CONCLUSION: Our study demonstrated a more comprehensive model when compared with Fujimoto's PTLD scoring system, which included additional predictors identified through machine learning that may have enhanced discrimination. The widespread use of this promising tool for risk stratification of patients receiving HCT allows identification of high-risk patients that may benefit from preemptive treatment for PTLD. IMPLICATIONS FOR PRACTICE: This study validated the Fujimoto score for the prediction of post-transplant lymphoproliferative disorder (PTLD) development following hematopoietic cell transplant (HCT) in an external, independent, and nationally representative population. This study also developed a more comprehensive model with enhanced discrimination for better risk stratification of patients receiving HCT, potentially changing clinical managements in certain risk groups. Previously unreported risk factors associated with the development of PTLD after HCT were identified using the machine learning algorithm, least absolute shrinkage and selection operator, including pre-HCT medical history of mechanical ventilation and the chemotherapy agents used in conditioning regimen.

Neuroprognostic Accuracy of Quantitative Versus Standard Pupillary Light Reflex for Adult Postcardiac Arrest Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: An automated infrared pupillometer measures quantitative pupillary light reflex using a calibrated light stimulus. We examined whether the timing of performing quantitative pupillary light reflex or standard pupillary light reflex may impact its neuroprognostic performance in postcardiac arrest comatose patients and whether quantitative pupillary light reflex may outperform standard pupillary light reflex in early postresuscitation phase. DATA SOURCES: PubMed and Embase databases from their inception to July 2020. STUDY SELECTION: We selected studies providing sufficient data of prognostic values of standard pupillary light reflex or quantitative pupillary light reflex to predict neurologic outcomes in adult postcardiac arrest comatose patients. DATA EXTRACTION: Quantitative data required for building a 2 × 2 contingency table were extracted, and study quality was assessed using standard criteria. DATA SYNTHESIS: We used the bivariate random-effects model to estimate the pooled sensitivity and specificity of standard pupillary light reflex or quantitative pupillary light reflex in predicting poor neurologic outcome during early (< 72 hr), middle (between 72 and 144 hr), and late (≧ 145 hr) postresuscitation periods, respectively. We included 39 studies involving 17,179 patients. For quantitative pupillary light reflex, the cut off points used in included studies to define absent pupillary light reflex ranged from 0% to 13% (median: 7%) and from zero to 2 (median: 2) for pupillary light reflex amplitude and Neurologic Pupil index, respectively. Late standard pupillary light reflex had the highest area under the receiver operating characteristic curve (0.98, 95% CI [CI], 0.97-0.99). For early standard pupillary light reflex, the area under the receiver operating characteristic curve was 0.80 (95% CI, 0.76-0.83), with a specificity of 0.91 (95% CI, 0.85-0.95). For early quantitative pupillary light reflex, the area under the receiver operating characteristic curve was 0.83 (95% CI, 0.79-0.86), with a specificity of 0.99 (95% CI, 0.91-1.00). CONCLUSIONS: Timing of pupillary light reflex examination may impact neuroprognostic accuracy. The highest prognostic performance was achieved with late standard pupillary light reflex. Early quantitative pupillary light reflex had a similar specificity to late standard pupillary light reflex and had better specificity than early standard pupillary light reflex. For postresuscitation comatose patients, early quantitative pupillary light reflex may substitute for early standard pupillary light reflex in the neurologic prognostication algorithm.

Temporal Trends in Sepsis Incidence and Mortality in Patients With Cancer in the US Population.

BACKGROUND: Few population-based studies assess the impact of cancer on sepsis incidence and mortality. OBJECTIVES: To evaluate epidemiological trends of sepsis in patients with cancer. METHODS: This retrospective cohort study included adults (≥20 years old) identified using sepsis-indicator International Classification of Diseases codes from the Nationwide Inpatient Sample database (2006-2014). A generalized linear model was used to trend incidence and mortality. Outcomes in patients with cancer and patients without cancer were compared using propensity score matching. Cox regression modeling was used to calculate hazard ratios for mortality rates. RESULTS: The study included 13 996 374 patients, 13.6% of whom had cancer. Gram-positive infections were most common, but the incidence of gram-negative infections increased at a greater rate. Compared with patients without cancer, those with cancer had significantly higher rates of lower respiratory tract (35.0% vs 31.6%), intra-abdominal (5.5% vs 4.6%), fungal (4.8% vs 2.9%), and anaerobic (1.2% vs 0.9%) infections. Sepsis incidence increased at a higher rate in patients with cancer than in those without cancer, but hospital mortality rates improved equally in both groups. After propensity score matching, hospital mortality was higher in patients with cancer than in those without cancer (hazard ratio, 1.25; 95% CI, 1.24-1.26). Of patients with sepsis and cancer, those with lung cancer had the lowest survival (hazard ratio, 1.65) compared with those with breast cancer, who had the highest survival. CONCLUSIONS: Cancer patients are at high risk for sepsis and associated mortality. Research is needed to guide sepsis monitoring and prevention in patients with cancer.

The low level of O antigen in Salmonella enterica Paratyphi A is due to inefficiency of the glycosyltransferase WbaV.

The group A O antigen is the major surface polysaccharide of Salmonella enterica serovar Paratyphi A (SPA), and the focal point for most current vaccine development efforts. The SPA O-antigen repeat (O unit) is structurally similar to the group D1 O unit of S. enterica serovar Typhi, differing only in the presence of a terminal side-branch paratose (Par) in place of tyvelose (Tyv), both of which are attached by the glycosyltransferase WbaV. The two O-antigen gene clusters are also highly similar, but with a loss-of-function mutation in the group A tyv gene and the tandem amplification of wbaV in most SPA strains. In this study, we show that SPA strains consistently produce less O antigen than their group D1 counterparts and use an artificial group A strain (D1 Δtyv) to show this is due to inefficient Par attachment by WbaV. We also demonstrate that group A O-antigen production can be increased by overexpression of the wbaV gene in both the D1 Δtyv strain and two multi-wbaV SPA strains. These findings should be broadly applicable in ongoing vaccine development pipelines, where efficient isolation and purification of large quantities of O antigen is of critical importance.

Use of Opioids and Outcomes of Pneumonia: Results From the US Nationwide Inpatient Sample.

BACKGROUND: Opioids have been shown to increase risk of pneumonia among susceptible population. However, the effect of opioid abuse on the outcome of pneumonia has not been evaluated at the population level. We aimed to compare the outcomes of pneumonia among patients with opioid use disorder and patients without substance use disorder using a large population database. METHODS: We assembled a pneumonia cohort composed of 11,186,564 adult patients from the National Inpatient Sample (NIS; 2005-2014). Patients with opioid disorder were identified using the International Classification of Diseases, 9th Revision, Clinical Modification codes. We compared health-related and economic outcomes between patients with and without opioid disorders using propensity score matching (PSM) analysis to balance baseline differences. The survival differences between two groups of patients were assessed using a Cox proportional hazard model. We further explored the possibility of effect modification by interaction analyses in different populations. RESULTS: After PSM, patients with opioid use disorder were at increased risk of ventilator use (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.08 to 1.38, p = 0.0014) and associated with increased length of hospital stay by 0.59 days (95% CI: 0.35 to 0.83, p < 0.001), compared with those without substance use disorder. Patients with opioid use also had higher daily (228.00 USD, 95% CI: 180.51 to 275.49, p < 0.001) and total (1,875.72 USD, 95% CI: 1,259.63 to 2,491.80, p < 0.001) medical costs. Subgroup analyses showed similar results. CONCLUSIONS: Compared with patients without any drug dependence, patients with opioid use disorders had increased risk of complications and resource utilization. This study adds evidence for increased risk for pneumonia complications in the growing patients with opioid use disorders.