Prediction of Resistance to 177Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers.

177Lu-PSMA-617 and 177Lu-PSMA I&T (collectively termed 177Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET-positive disease, but biomarkers for these agents remain incompletely understood. Methods: Pretreatment circulating tumor DNA (ctDNA) samples were collected from 44 mCRPC patients receiving 177Lu-PSMA treatment. Prostate-specific antigen responders and nonresponders were assessed relative to the ctDNA findings at baseline. Results: The ctDNA findings indicated that nonresponders were more likely to have gene amplifications than were responders (75% vs. 39.2%, P = 0.03). In particular, amplifications in FGFR1 (25% vs. 0%, P = 0.01) and CCNE1 (31.2% vs. 0%, P = 0.001) were more likely to be present in nonresponders. CDK12 mutations were more likely to be present in nonresponders (25% vs. 3.6%, P = 0.05). Conclusion: Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for 177Lu-PSMA-treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.

Timely estimation of National Admission, readmission, and observation-stay rates in medicare patients with acute myocardial infarction, heart failure, or pneumonia using near real-time claims data.

BACKGROUND: To estimate, prior to finalization of claims, the national monthly numbers of admissions and rates of 30-day readmissions and post-discharge observation-stays for Medicare fee-for-service beneficiaries hospitalized with acute myocardial infarction (AMI), heart failure (HF), or pneumonia. METHODS: The centers for Medicare & Medicaid Services (CMS) Integrated Data Repository, including the Medicare beneficiary enrollment database, was accessed in June 2015, February 2017, and February 2018. We evaluated patterns of delay in Medicare claims accrual, and used incomplete, non-final claims data to develop and validate models for real-time estimation of admissions, readmissions, and observation stays. RESULTS: These real-time reporting models accurately estimate, within 2 months from admission, the monthly numbers of admissions, 30-day readmission and observation-stay rates for patients with AMI, HF, or pneumonia. CONCLUSIONS: This work will allow CMS to track the impact of policy decisions in real time and enable hospitals to better monitor their performance nationally.

Telehealth Intervention Programs for Seniors: An Observational Study of a Community-Embedded Health Monitoring Initiative.

Background:Chronic disease in older adults is estimated to account for 84% of annual health care spending in the United States, with many preventable costs expected to rise as the population continues to age.Introduction:Telehealth Intervention Programs for Seniors (TIPS) is a community-embedded program targeting low-income older adults, providing weekly assessment of vital signs and subjective wellness, and wrap-around aging services.Materials and Methods:TIPS recruited 765 volunteers over 55 years, who were Medicaid and/or Medicare eligible. Data were collected from 2014 to 2016 [median enrollment 343 days (105-435)] using 12 TIPS sites. This observational study evaluated the efficacy of TIPS by measuring within-subject changes in self-reported hospital visits and <30-day readmissions, before and during TIPS participation. Data of 617 participants (median age 74.3; interquartile range 16) were analyzed.Results:Self-reported hospital visits were reduced by 28.9% (p = 0.0013). Medicare participants benefited the most, with a 50% (p < 0.0001) reduction in hospital visits, and a 75.5% (p = 0.017) reduction in <30-day readmissions. Multivariate analysis revealed that participants (1) Medicaid-registered (odds ratio [OR] = 2.72, 95% confidence interval [CI] 0.392-1.611), (2) reporting feeling unwell (OR = 1.33, 95% CI 0.118-0.459), and (3) living alone (OR = 2.34, 95% CI 0.115-1.592) were significantly more likely than other participants to experience a hospital visit.Discussion:TIPS demonstrates that community-embedded health services can reduce rates of hospital visits in older adults.Conclusion:The success of TIPS highlights the potential of successfully deployed remote patient-monitoring initiatives in reducing the utilization of costly health services.

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors.

Tandem autologous stem cell transplantation (ASCT) improves long-term survival of platinum-refractory germ cell tumors (GCT) patients. Studies, predominantly in lymphoma, showed that CD34+ cell doses > 5.0 × 106/kg/single transplant led to decreased resource utilization. Because most GCT patients have received prior cisplatin-based treatment, collecting >10 × 106 CD34+ cells/kg is challenging. We analyzed the effect of CD34+ cell dose on resource utilization and outcome in 131 GCT patients, median age 29.5 years (range, 16 to 58), undergoing tandem ASCT. Of 262 individual transplants performed, 120 were performed as inpatient and 142 as planned outpatient. Overall, median CD34+ dose per transplant was 3.1 × 106/kg (range, 0.8 to 16.0), with no significant difference between inpatient and outpatient transplants. Patients were divided into quartiles based on the CD34 cell dose infused: Q1, 0.8 to 1.9 × 106/kg; Q2, 2.0 to 2.9 × 106/kg; Q3, 3.0 to 4.1 × 106/kg; and Q4, 4.2 to 16.0 × 106/kg. For all patients higher CD34+ cell doses were associated with significantly shorter times to neutrophil (P <.001) and platelet recovery (P <.001). For inpatient transplants higher CD34+ doses were significantly associated with shorter length of hospital stay (P <.001), fewer days of filgrastim (P <.001), i.v. antibiotic (P = .012) and antifungal (P = .03) usage; and fewer RBC (P = .001) and platelet units transfused (P <.001), resulting in overall lower cost of care (P < .001). Of the 142 planned outpatient transplants, 100 admissions were required for a median length of hospital stay of 7.0 days (range, 1 to 18). Although there was no significant difference in the rates of hospitalization between patients in different CD34+ cell dose quartiles, a significant trend was observed for shorter hospitalization (P = .01) and fewer RBC (P = .002) and platelet (P = .005) transfusions with higher CD34+ cell dose quartile. Patients receiving CD34+ cell doses in the lowest dose quartile (Q1) had significantly worse progression-free survival and overall survival compared with patients receiving higher CD34+ cell doses. Overall, resource utilization, including cost of care, is significantly reduced when patients receive higher CD34+ cell doses, indicating greater efforts to improve peripheral blood stem cell collection in this population are needed.

Incorporating Stroke Severity Into Hospital Measures of 30-Day Mortality After Ischemic Stroke Hospitalization.

BACKGROUND AND PURPOSE: The Centers for Medicare & Medicaid Services publicly reports a hospital-level stroke mortality measure that lacks stroke severity risk adjustment. Our objective was to describe novel measures of stroke mortality suitable for public reporting that incorporate stroke severity into risk adjustment. METHODS: We linked data from the American Heart Association/American Stroke Association Get With The Guidelines-Stroke registry with Medicare fee-for-service claims data to develop the measures. We used logistic regression for variable selection in risk model development. We developed 3 risk-standardized mortality models for patients with acute ischemic stroke, all of which include the National Institutes of Health Stroke Scale score: one that includes other risk variables derived only from claims data (claims model); one that includes other risk variables derived from claims and clinical variables that could be obtained from electronic health record data (hybrid model); and one that includes other risk variables that could be derived only from electronic health record data (electronic health record model). RESULTS: The cohort used to develop and validate the risk models consisted of 188 975 hospital admissions at 1511 hospitals. The claims, hybrid, and electronic health record risk models included 20, 21, and 9 risk-adjustment variables, respectively; the C statistics were 0.81, 0.82, and 0.79, respectively (as compared with the current publicly reported model C statistic of 0.75); the risk-standardized mortality rates ranged from 10.7% to 19.0%, 10.7% to 19.1%, and 10.8% to 20.3%, respectively; the median risk-standardized mortality rate was 14.5% for all measures; and the odds of mortality for a high-mortality hospital (+1 SD) were 1.51, 1.52, and 1.52 times those for a low-mortality hospital (-1 SD), respectively. CONCLUSIONS: We developed 3 quality measures that demonstrate better discrimination than the Centers for Medicare & Medicaid Services' existing stroke mortality measure, adjust for stroke severity, and could be implemented in a variety of settings.

Bathing With 2% Chlorhexidine Gluconate: Evidence and Costs Associated With Central Line-Associated Bloodstream Infections.

In a coordinated national effort reported by the Agency for Healthcare Research and Quality, the use of 2% chlorhexidine gluconate (CHG) has reduced the central line-associated bloodstream infection (CLABSI) rate by 40%. Conversely, a recent randomized clinical trial determined that chlorhexidine bathing did not reduce the CLABSI rate. The objectives of this study were to conduct meta-analysis and clarify the effectiveness of 2% CHG bathing by nurses on CLABSIs in adult intensive care unit patients and to determine the contributing costs attributable to CLABSIs and 2% CHG bathing. Eligible studies that included the outcome of bloodstream infection rate for central lines were considered. A rigorous systematic review protocol and software tools available from the Joanna Briggs Institute via OvidSP were used. Agency for Healthcare Research and Quality tools assisted with identifiable CHG bathing costs. Four studies were included in the meta-analysis for the outcome of primary bloodstream infections, and 2 studies narratively supported the meta-analysis. A relative risk of 0.46 with 95% confidence interval (0.34-0.63) was determined. This significant effect is seen in an overall z-score of 4.84 (P < .0001). This meta-analysis supports that 2% CHG reduces CLABSIs. The estimated cost increase of 2% CHG-impregnated cloths is $4.10 versus nonmedicated bathing cloths. The cost associated with a single CLABSI is 10 times more than the cost of using 2% CHG-impregnated cloths. Nursing provides significant influence for the prevention of CLABSIs in critical care via evidence-based best practices.

Accuracy of patient perception of their prevailing rhythm: a comparative analysis of monitor data and questionnaire responses in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) guidelines recommend that symptom relief be a primary goal in management. However, patient perception of their prevailing rhythm is often inaccurate, complicating symptom-targeted treatment. OBJECTIVE: The purpose of this study was to evaluate the accuracy of patient perception of their prevailing rhythm and identify factors that predict inaccuracies. METHODS: Demographic and health status data were captured by questionnaires for 458 outpatients with documented AF. AF burden (%) was captured by 1-week continuous heart monitors. Patients estimated the length and frequency of their AF episodes by completing the AF Symptom Severity questionnaire. Patient reports were compared to AF burden, and outliers were identified and broken into 2 groups: patients with AF burden <10% who indicated near-continuous AF (overestimators) and patients with AF burden >90% who estimated little to no AF (underestimators). Multinomial logistic regression was used to identify predictors of inaccuracies (over- or underestimators). RESULTS: By continuous monitor, 15% of patients were found to be over- or underestimators. Persistent AF, female sex, older age, anxiety, and depression were predictive of inaccurate patient perception. Persistent AF, female sex, and older age were predictive of underestimating, while mood disorders (anxiety and depression) were predictive of overestimating. The prevalence of underestimators was nearly twice that of overestimators. CONCLUSION: Sex, age, and mood disorders are among factors that lead to inaccurate patient perception of their prevailing rhythm in patients with AF. Such modulating factors should be considered when evaluating treatment strategies. Consideration should be given to more liberal use of heart monitors in these patient populations to better target therapy.

Exploring the potential for internet-based interventions for treatment of overweight and obesity in college students.

OBJECTIVE: To assess the use of internet-enabled technology for seeking health information and resources in overweight/obese college students. PARTICIPANTS: College students (N = 706) in Vancouver, Canada surveyed in April 2012. METHODS: An online survey assessed socio-demographics, health behaviors, and use of internet-enabled technology. RESULTS: Eating habits, dieting and/or exercising to lose weight, and weight satisfaction differed by weight status (all p < 0.05). Of overweight/obese participants, 48% reported they would use online student health resources. When seeking general health information, 91% would use websites; 45% would use online videos; and 75% trusted information from government or health organizations. CONCLUSIONS: Overweight/obesity is prevalent among college students. The majority of overweight/obese students reported trying to lose weight and would use the internet for health information, especially if a website is associated with a health organization. The internet is a cost-effective channel for screening coupled with the delivery of tailored, evidence-based interventions for college students.

Cost consideration in the clinical guidance documents of physician specialty societies in the United States.

IMPORTANCE: Despite increasing concerns regarding the cost of health care, the consideration of costs in the development of clinical guidance documents by physician specialty societies has received little analysis. OBJECTIVE: To evaluate the approach to consideration of cost in publicly available clinical guidance documents and methodological statements produced between 2008 and 2012 by the 30 largest US physician specialty societies. DESIGN: Qualitative document review. MAIN OUTCOMES AND MEASURES: Whether costs are considered in clinical guidance development, mechanism of cost consideration, and the way that cost issues were used in support of specific clinical practice recommendations. RESULTS: Methodological statements for clinical guidance documents indicated that 17 of 30 physician societies (57%) explicitly integrated costs, 4 (13%) implicitly considered costs, 3 (10%) intentionally excluded costs, and 6 (20%) made no mention. Of the 17 societies that explicitly integrated costs, 9 (53%) consistently used a formal system in which the strength of recommendation was influenced in part by costs, whereas 8 (47%) were inconsistent in their approach or failed to mention the exact mechanism for considering costs. Among the 138 specific recommendations in these guidance documents that included cost as part of the rationale, the most common form of recommendation (50 [36%]) encouraged the use of a specific medical service because of equal effectiveness and lower cost. CONCLUSIONS AND RELEVANCE: Slightly more than half of the largest US physician societies explicitly consider costs in developing their clinical guidance documents; among these, approximately half use an explicit mechanism for integrating costs into the strength of recommendations. Many societies remain vague in their approach. Physician specialty societies should demonstrate greater transparency and rigor in their approach to cost consideration in documents meant to influence care decisions.

Gender differences in drunk driving prevalence rates and trends: a 20-year assessment using multiple sources of evidence.

This research tracked women's and men's drunk driving rates and the DUI sex ratio in the United States from 1982-2004 using three diverse sources of evidence. Sex-specific prevalence estimates and the sex ratio are derived from official arrest statistics from the Federal Bureau of Investigation, self-reports from the Centers for Disease Control and Prevention, and traffic fatality data from the National Highway and Transportation Safety Administration. Drunk driving trends were analyzed using Augmented Dickey Fuller time series techniques. Female DUI arrest rates increased whereas male rates declined then stabilized, producing a significantly narrower sex ratio. According to self-report and traffic data, women's and men's drunk driving rates declined and the gender gap was unchanged. Women's overrepresentation in arrests relative to their share of offending began in the 1990s and accelerated in 2000. Women's arrest gains, contrasted with no systematic change in DUI behavior, and the timing of this shift suggest an increased vulnerability to arrest. More stringent laws and enforcement directed at less intoxicated offenders may inadvertently target female offending patterns.

Getting patients to the right healthcare sources: from real-world questions to strategy hubs.

To address the growing problem of novices accessing incomplete and unreliable information on the Web, this paper begins by probing the nature of strategic knowledge known by expert healthcare searchers. The analysis reveals the existence of a strategy that is focused to a specific type of healthcare question. To investigate whether there exist other similar strategies, we conduct two pilot studies. The first leads to the development of a taxonomy for skin cancer questions based on real-world questions. This taxonomy has high inter-rater agreement when tested with new real-world questions. The second pilot helps to identify 6 strategies that are specific to question types in the taxonomy. We demonstrate how these strategies can be made available to a wide range of users through a prototypical system referred to as a Strategy Portal. In conclusion, we briefly describe our current and future research to test if such a system can make patients more effective and efficient in the retrieval of reliable and relevant healthcare information on the Web.