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Background Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in United States infants aged Methods National (Nationwide) Inpatient Sample and National Emergency Department (ED) Sample data (2011–2019) were used to report RSV hospitalization (RSVH), bronchiolitis hospitalization (BH), and ED visit counts, percentage of total hospitalizations/visits, and rates per 1000 live births along with inpatient mortality, mechanical ventilation (MV), and total charges (2020 US dollars). Results Average annual RSVH and RSV ED visits were 56 927 (range, 43 845–66 155) and 131 999 (range, 89 809–177 680), respectively. RSVH rates remained constant over time (P = .5), whereas ED visit rates increased (P = .004). From 2011 through 2019, Medicaid infants had the highest average rates (RSVH: 22.3 [95% confidence interval {CI}, 21.5–23.1] per 1000; ED visits: 55.9 [95% CI, 52.4–59.4] per 1000) compared to infants with private or other/unknown insurance (RSVH: P Conclusions This study highlights the importance of ensuring access to RSV preventive measures for all infants.

Background This study describes leading causes of hospitalization, including respiratory syncytial virus (RSV), in United States infants ( Methods Within the National (Nationwide) Inpatient Sample (NIS) data, hospitalizations were determined by primary diagnosis using International Classification of Diseases, Ninth or Tenth Revision codes. RSV was defined as 079.6, 466.11, 480.1, B97.4, J12.1, J20.5, or J21.0. Bronchiolitis was defined as 466.19, J21.8, or J21.9. Leading causes overall and by sociodemographic variables were identified. The Kids’ Inpatient Database (KID) was used for confirmatory analyses. Results Acute bronchiolitis due to RSV (code 466.11 or J21.0) was the leading primary diagnosis, accounting for 9.6% (95% confidence interval [CI], 9.4%–9.9%) and 9.3% (95% CI, 9.0%–9.6%) of total infant hospitalizations from January 2009 through September 2015 and October 2015 through December 2019, respectively; it was the leading primary diagnosis in every year accounting for >10% of total infant hospitalizations from December through March, reaching >15% in January–February. From 2009 through 2011, acute bronchiolitis due to RSV was the leading primary diagnosis in every birth month. Acute bronchiolitis due to RSV was the leading cause among all races/ethnicities, except Asian/Pacific Islanders, and all insurance payer groups. KID analyses confirmed these results. Conclusions Acute bronchiolitis due to RSV is the leading cause of US infant hospitalizations.

Background Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood. Methods From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants Results Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4–7.5), 19.8 (95% CI, 18.9–20.8), and 6.2 (95% CI, 5.7–6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among Conclusions These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.

Background Multi-cancer early detection (MCED) next-generation-sequencing blood tests represent a potential paradigm shift in screening. Methods We estimated the impact of screening in the US and UK. We used country-specific parameters for uptake, and test-specific sensitivity and false-positive rates for current screening: breast, colorectal, cervical and lung (US only) cancers. For the MCED test, we used cancer-specific sensitivities by stage. Outcomes included the true-positive:false-positive (TP:FP) ratio; and the cost of diagnostic investigations among screen positives, per cancer detected (Diagcost). Outcomes were estimated for recommended screening only, and then when giving the MCED test to anyone without cancer detected by current screening plus similarly aged adults ineligible for recommended screening. Results In the US, current screening detects an estimated 189,498 breast, cervical, colorectal and lung cancers. An MCED test with 25–100% uptake detects an additional 105,526–422,105 cancers (multiple types). The estimated TP:FP (Diagcost) was 1.43 ($89,042) with current screening but only 1:1.8 ($7060) using an MCED test. For the UK the corresponding estimates were 1:18 (£10,452) for current screening, and 1:1.6 (£2175) using an MCED test. Conclusions Adding an MCED blood test to recommended screening can potentially be an efficient strategy. Ongoing randomised studies are required for full efficacy and cost-effectiveness evaluations.

Background Surveillance in 2020–2021 showed that seasonal respiratory illnesses were below levels seen during prior seasons, with the exception of interseasonal respiratory syncytial virus (RSV). Methods Electronic health record data of infants aged Results Pre–COVID-19, 88% of RSV and 92% of bronchiolitis encounters were seen in ambulatory settings. During COVID-19, 94% and 93%, respectively, occurred in ambulatory settings. Pre–COVID-19, the highest RSV proportion was observed in December–January (up to 38% in ED), while the peaks during COVID-19 were seen in July–September (up to 41% in ED) across all settings. RSV laboratory testing among RSV encounters was low during pre–COVID-19 (IP, 51%; ED, 51%; OP, 41%; UC, 84%) and COVID-19 outside of UC (IP, 33%; ED, 47%; OP, 47%; UC, 87%). Full-term, otherwise healthy infants comprised most RSV encounters (pre–COVID-19, up to 57% in OP; COVID-19, up to 82% in TM). Conclusions With the interruption of historical RSV epidemiologic trends and the emergence of interseasonal disease during COVID-19, continued monitoring of RSV is warranted across all settings as the changing RSV epidemiology could affect the distribution of health care resources and public health policy.

This paper presents the results of ASME Boiler and Pressure Vessel Code (BPVC) Section VIII Division 2 analyses on a containment pressure vessel system designed to host small-scale shock physics experiments containing hazardous materials. These shock physics experiments are imaged using proton radiography at Los Alamos Neutron Science Center (LANSCE). The pressure vessel system examined is separated into two subsystems, the Outer Pressure Containment Vessel (OPCV) and the Beam Pipe and Auxiliary Hardware (BPAH). The OPCV mates with the BPAH to transport the proton beam and form the outer containment pressure boundary. An Inner Pressure Confinement Vessel (IPCV) is mounted inside the containment pressure boundary. The IPCV can be used to host a variety of physics experiments, which can include high explosive and hazardous materials. The IPCV is an impulsively loaded pressure vessel, while the OPCV and beam pipes are statically loaded. The OPCV and BPAH are designed to satisfy ASME BPVC Section VIII Division 2 Alternative Rules, Part 5 Design by Analysis Requirements for all load conditions expected during service. The BPAH is a series of stainless-steel tubes with low-profile flange assemblies, bellows, and aluminum windows to allow for proton imaging. The low-profile flanges are required for clearance of magnet bores located periodically along the length of the BPAH. The bellows are included along the beamline for ease of installation. The OPCV is a pressure vessel designed to interface with the BPAH, IPCV, and proton imaging alignment system. The OPCV and BPAH are both designed to support full vacuum loads. Major considerations for the BPAH are thermal elongation, collapse of bellows, and stresses due to clamp supports. Lifting loads and static equivalent loads transmitted from the IPCV are additional considerations for the OPCV. Under ASME BPVC Section VIII Division 2 Part 5.2.4, Elastic-Plastic Stress Analysis Method, Paragraph 5.2.4.3(a), Global Criteria, the requirements for analysis and acceptance are defined for the load cases described. A finite element analysis (FEA) model, performed in ANSYS 2020 R1, evaluates the design of the OPCV and BPAH under the aforementioned ASME guidance and criteria.

Purpose Develop a prediction model to determine the impact of patient and lesion factors on freedom from target lesion revascularization (ffTLR) for patients who are candidates for Zilver PTX drug-eluting stent (DES) treatment for femoropopliteal lesions. Methods Patient factors, lesion characteristics, and TLR results from five global studies were utilized for model development. Factors potentially associated with TLR (sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, reference vessel diameter (RVD), popliteal involvement, total occlusion, calcification severity, prior interventions, and number of runoff vessels) were analyzed in a Cox proportional hazards model. Probability of ffTLR was generated for three example patient profiles via combinations of patient and lesion factors. TLR was defined as reintervention performed for ≥ 50% diameter stenosis after recurrent clinical symptoms. Results The model used records from 2227 patients. The median follow-up time was 23.9 months (range: 0.03–60.8). The Kaplan–Meier estimates for ffTLR were 90.5% through 1 year and 75.2% through 5 years. In a multivariate analysis, sex, age, Rutherford classification, lesion length, RVD, total occlusion, and prior interventions were significant factors. The example patient profiles have predicted 1-year ffTLRs of 97.4, 92.3, and 86.0% and 5-year predicted ffTLRs of 92.8, 79.5, and 64.8%. The prediction model is available as an interactive web-based tool (https://cooksfa.z13.web.core.windows.net). Conclusions This is the first prediction model that uses an extensive dataset to determine the impact of patient and lesion factors on ffTLR through 5 years and provides an interactive web-based tool for expected patient outcomes with the Zilver PTX DES. Clinical Trial Registrations Zilver PTX RCT unique identifier: NCT00120406; Zilver PTX single-arm study unique identifier: NCT01094678; Zilver PTX China study unique identifier: NCT02171962; Zilver PTX US post-approval study unique identifier: NCT01901289; Zilver PTX Japan post-market surveillance study unique identifier: NCT02254837. Levels of Evidence Zilver PTX RCT: Level 2, randomized controlled trial; Single-arm study: Level 4, large case series; China study: Level 4, case series; US post-approval study: Level 4, case series Japan PMS study: Level 4, large case series.

Introduction: Hemodialysis access complications are common. We hypothesize that many of these complications can be traced back to needle-related injury from routine cannulation practices or inadvertent cannulation injuries. We set out to compare the rates of hemodialysis access complications under prior and current diagnosis coding systems, determine the incidence of needle-related complications for hemodialysis access, and describe the association of needle-related complications and resulting interventions. Methods: Arteriovenous graft and arteriovenous fistula placements occurring in the first 6 months of 2014 and 2016 were identified in the United States Renal Data System Medicare claims data. Placements were followed until end of hemodialysis access life or end of the calendar year. Diagnoses and resulting interventions occurring during placement life were identified and mapped to needle-related complication terms. Results: Almost 30,000 placements for 27,000 patients were followed in each year, with 67% of all accesses placed being arteriovenous fistula and 33% arteriovenous graft. In both years, 75% of arteriovenous fistulae and arteriovenous grafts required one or more interventions. Stenosis and thrombosis were the most common complications diagnosed and treated (41% and 16%, respectively); however, potential needle-related complications accounted for 6% of this dataset. Discussion: International Classification of Diseases, 9th Revision, was inadequate for determining the incidence of specific hemodialysis access complications or needle-related complications. International Classification of Diseases, 10th Revision, introduced several more hemodialysis access diagnoses but is still subject to coding confusion and catch-all coding for a variety of common and otherwise well-defined complications, suggesting that the true incidence of needle-related complications is buried in the non-specific diagnosis codes. These findings mark the clear need for an improved diagnosis coding system that consistently represents all common hemodialysis access complications.

Background: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by immunoglobulin M autoantibodies that bind to the “I” antigen on erythrocytes. IgM binding results in either agglutination at ≤37°C, activation of the classical complement pathway, or both. Patients with CAD can have transient agglutination-mediated circulatory symptoms triggered by exposure to cold conditions. Separately, patients with CAD can experience complement-mediated symptoms such as anemia, hemolysis, and fatigue, but the effect of the season on these complement-mediated manifestations of CAD and clinical outcomes is not well understood. Methods: Using data from the Optum® de-identified Electronic Health Record dataset, we compared hemoglobin, markers of hemolysis (bilirubin and lactate dehydrogenase [LDH]), and healthcare resource utilization (HRU) between seasons for 594 patients (62% female; 66% aged ≥65 years) with CAD (defined as having CAD-related terms in their clinical notes on ≥3 separate occasions between December 2008 and May 2016). Laboratory parameters and HRU were compared between seasons using multivariate regression models. Results: Estimated median hemoglobin (9.87 g/dL in summer and 9.86 g/dL in winter; P = 0.944) and bilirubin (1.04 mg/dL in summer and 1.09 mg/dL in winter; P = 0.257) were similar in winter versus summer. While LDH was statistically significantly higher in winter compared with summer (P < 0.001), the estimated median value was above normal for both seasons (309 U/L in summer and 367 U/L in winter). HRU measures and transfusion and thromboembolism rates were similar across seasons. Conclusions: Patients with CAD had evidence of persistent chronic hemolysis, HRU, and thromboembolism risk year round.

Introduction: Hemodialysis (HD) in end-stage renal disease (ESRD) patients requires vascular access (VA) through an arteriovenous fistula (AVF), a prosthetic arteriovenous graft (AVG), or a central venous catheter. While AVF or AVG is commonly used for HD, the economic implications of AVF versus AVG use have not been fully established. We describe the healthcare resource utilization and costs of AVF and AVG use for incident ESRD patients in the United States. Methods: This observational cohort study of AVF and AVG placements used data from the United States Renal Data System to identify and follow access placements. AVF and AVG placements after ESRD onset for incident patients from 2012 to 2014 with continuous Medicare primary coverage were included. All-cause and access-related Medicare costs were averaged over the placement lifetime and expressed as per dialysis-month costs. Results: The analysis included 38,035 AVF placements and 12,789 AVG placements. Total all-cause monthly costs for AVF averaged USD 8,508; mean monthly costs were USD 3,027 for inpatient (IP), USD 3,139 for outpatient (OP), USD 1,572 for physician services, and USD 770 for other care settings. Access-related monthly costs averaged USD 1,699 and represented 20% of all-cause charges for AVFs. Mean all-cause monthly costs for AVG were USD 9,605; by setting monthly costs were USD 3,811 for IP, USD 3,034 for OP, USD 1,881 for physician services and USD 879 for other care settings. Access-related monthly costs averaged USD 2,656 and represented 28% of all-cause charges for AVGs. Discussion/Conclusions: This study indicates that costs due to VA are a significant burden on Medicare budgets and on patients. The factors driving access-related utilization and costs merit attention in future research. Both optimizing process of care and discovery innovation may significantly accelerate better stewardship of available healthcare resources.

Background: Chronic hemodialysis requires a mode of vascular access through an arteriovenous fistula (AVF), a prosthetic arteriovenous graft (AVG), or a central venous catheter (CVC). AVF is recommended over AVG or CVC due to increased patency and decreased intervention rates for those that mature. AVG are preferred over CVC due to decreased infection and mortality risk. The aims of this study were to evaluate the lifespan of AVF and AVG in maturation, sustained access use, and abandonment. Methods: The United States Renal Data System (USRDS), Medicare claims, and CROWNWeb were used to identify access placements. Patients with a first end-stage renal disease (ESRD) service from January 1, 2012 to June 30, 2014 with continuous coverage with Medicare as primary payer and ≥1 AVF or AVG placed after ESRD onset were included. Maturation was defined as the first use of the access for hemodialysis recorded in CROWNWeb. Sustained access use was defined as 3 consecutive months of use without catheter placement or replacement. Accesses that were never used at any time post-placement were considered abandoned. Results: The cohort included 38,035 AVF placements and 12,789 AVG placements. Sixty-nine percent of AVF and 72% of AVG matured. Fifty-two percent of AVF and 51% of AVG achieved sustained access use. One quarter of AVF and 14% of AVG were abandoned without use as recorded in CROWNWeb. Conclusion: Although considered the gold standard for vascular access, only half of AVF and AVG placements achieved sustained access use. The USRDS database has inherent limitations but provides useful clinical insight into maturation, sustained use, and abandonment.

CTLA-4 is a co-inhibitory molecule that functions to inhibit T cell functions, essentially acting as a break on the immune system. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including anti-tumor immunity. These antibodies likewise trigger an expansion of tumor infiltrating Th1-like CD4 T cells. CTLA-4 blockade has demonstrated benefits in overall survival and harm reduction in the treatment of metastatic melanoma, which accounts for 80% of the 66,000 annual skin cancer deaths. More recently, efforts to combine anti-CTLA-4 antibodies with other forms of cancer treatment like radiotherapy and chemotherapy have proven to be successful. This study has focused on the modeling and analysis of the effects of anti-CTLA-4 antibody therapy alone on tumor growth using impulsive differential equations. The Jacobian matrix was constructed, evaluated at a tumor-free equilibrium, and evaluated for stability using experimental data. This project is supported by the NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence.

Hexavalent chromium [Cr(VI)] exists in the ambient air at low concentrations (average upperbound ~0.1 ng/m3) yet airborne concentrations typically exceed EPA's Regional Screening Level for residential exposure (0.012 ng/m3) and other similar benchmarks, which assume a mutagenic mode of action (MOA) and use low-dose linear risk assessment models. We reviewed Cr(VI) inhalation unit risk estimates developed by researchers and regulatory agencies for environmental and occupational exposures and the underlying epidemiologic data, updated a previously published MOA analysis, and conducted dose-response modeling of rodent carcinogenicity data to evaluate the need for alternative exposure-response data and risk assessment approaches. Current research supports the role of non-mutagenic key events in the MOA, with growing evidence for epigenetic modifiers. Animal data show a weak carcinogenic response, even at cytotoxic exposures, and highlight the uncertainties associated with the current epidemiological data used in risk assessment. Points of departure from occupational and animal studies were used to determine margins of exposure (MOEs). MOEs range from 1.5 E+3 to 3.3 E+6 with a median of 5 E+5, indicating that current environmental exposures to Cr(VI) in ambient air should be considered of low concern. In this comprehensive review, the divergent results from default linear and MOE assessments support the need for more relevant and robust epidemiologic data, additional mechanistic studies, and refined risk assessment strategies.

CTLA-4 is a co-inhibitory molecule that functions to regulate T cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including anti-tumor immunity. CTLA-4 blockade has demonstrated benefits in treatment of metastatic melanoma. Prior research has found that antitumor immunity can be enhanced through the blocking of CLTA-4. More recently, efforts to combine anti-CTLA-4 antibodies with other forms of cancer treatment like radiotherapy and chemotherapy have proven to be successful. This study has thus focused on the modeling and analyzing the effects of anti-CTLA-4 antibody therapy on tumor growth using impulsive differential equations and mathematics analysis. This project is supported by the NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence.

Cold agglutinin disease (CAD), a rare disease and subtype of autoimmune hemolytic anemia, is characterized by autoantibodies that bind to red blood cells at low temperatures. There is no established standard of care for CAD treatment and CAD cohort studies are limited by the rarity of the condition. The objectives of this study are to present the longitudinal experience of a CAD cohort from the United States, with a focus on anemia severity, use of medications and transfusions, and health care resource utilization. The Stanford Translational Research Integrated Database Environment database was used to retrospectively identify CAD patients diagnosed and treated at Stanford Health Care from 2000 to 2016. Twenty-nine patients were included in this analysis. There were 7.1 severe anemia events per patient-year observed over the follow-up time. For CAD patients treated at Stanford, there was a mean of 3.5 therapies per patient. Transfusions were given in at least 65% of the cohort with a mean of 11 transfusions per patient-year. For CAD-related health care use in the first year after disease onset, 93% used outpatient services with a median of 26 outpatient visits per patient. The data presented here likely represent the minimum number of events for these patients during this timeframe, as this single-center experience does not capture care from other providers. This longitudinal study of CAD patients demonstrates the severity of anemia and relapsing nature of the disease, even after administration of multiple therapies and transfusions.

Background: While indirect calorimetry (IC) is the gold standard used to calculate specific calorie needs in the critically ill, predictive equations are frequently utilized at many institutions for various reasons. Prior studies suggest these equations frequently misjudge actual resting energy expenditure (REE) in medical and mixed intensive care unit (ICU) patients; however, their utility for surgical ICU (SICU) patients has not been fully evaluated. Therefore, the objective of this study was to compare the REE measured by IC with REE calculated using specific calorie goals or predictive equations for nutritional support in ventilated adult SICU patients. Materials and Methods: A retrospective review of prospectively collected data was performed on all adults (n = 419, 18-91 years) mechanically ventilated for >24 hours, with an Fio2 ≤ 60%, who met IC screening criteria. Caloric needs were estimated using Harris-Benedict equations (HBEs), and 20, 25, and 30 kcal/kg/d with actual (ABW), adjusted (ADJ), and ideal body (IBW) weights. The REE was measured using IC. Results: The estimated REE was considered accurate when within ±10% of the measured REE by IC. The HBE, 20, 25, and 30 kcal/kg/d estimates of REE were found to be inaccurate regardless of age, gender, or weight. The HBE and 20 kcal/kg/d underestimated REE, while 25 and 30 kcal/kg/d overestimated REE. Of the methods studied, those found to most often accurately estimate REE were the HBE using ABW, which was accurate 35% of the time, and 25 kcal/kg/d ADJ, which was accurate 34% of the time. This difference was not statistically significant. Conclusion: Using HBE, 20, 25, or 30 kcal/kg/d to estimate daily caloric requirements in critically ill surgical patients is inaccurate compared to REE measured by IC. In SICU patients with nutrition requirements essential to recovery, IC measurement should be performed to guide clinicians in determining goal caloric requirements.

Background Urinary tract infections (UTIs) in nursing homes are common, costly, and morbid. Purpose Systematic literature review of strategies to reduce UTIs in nursing home residents. Data sources Ovid MEDLINE, Cochrane Library, CINAHL, Web of Science and Embase through June 22, 2015. Study selection Interventional studies with a comparison group reporting at least 1 outcome for: catheter-associated UTI (CAUTI), UTIs not identified as catheter-associated, bacteriuria, or urinary catheter use. Data extraction Two authors abstracted study design, participant and intervention details, outcomes, and quality measures. Data synthesis Of 5794 records retrieved, 20 records describing 19 interventions were included: 8 randomized controlled trials, 10 pre-post nonrandomized interventions, and 1 nonrandomized intervention with concurrent controls. Quality (range, 8-25; median, 15) and outcome definitions varied greatly. Thirteen studies employed strategies to reduce catheter use or improve catheter care; 9 studies employed general infection prevention strategies (eg, improving hand hygiene, surveillance, contact precautions, reducing antibiotics). The 19 studies reported 12 UTI outcomes, 9 CAUTI outcomes, 4 bacteriuria outcomes, and 5 catheter use outcomes. Five studies showed CAUTI reduction (1 significantly); 9 studies showed UTI reduction (none significantly); 2 studies showed bacteriuria reduction (none significantly). Four studies showed reduced catheter use (1 significantly). Limitations Studies were often underpowered to assess statistical significance; none were pooled given variety of interventions and outcomes. Conclusions Several practices, often implemented in bundles, such as improving hand hygiene, reducing and improving catheter use, managing incontinence without catheters, and enhanced barrier precautions, appear to reduce UTI or CAUTI in nursing home residents. Journal of Hospital Medicine 2017;12:356-368.

Background. For infants who are partially or exclusively fed infant formula, many options exist with compositional differences between formulas making choices difficult for caregivers and healthcare professionals. The protein in routine infant formulas differs by the source, fraction of cow’s milk protein used, and degree of hydrolysis. All commercially available regulated infant formulas support growth and development, but different stool patterns have been observed based on formula composition. A pooled analysis of seven clinical trials was conducted to examine growth, stool consistency, and stool frequency of infants fed an intact cow’s milk-based formula (CMF) or a partially hydrolyzed whey formula (PHF-W) from a single manufacturer. Methods. Individual subject data from seven infant formula growth studies (3 CMF, 4 PHF-W) were pooled and analyzed. All studies included healthy, full-term, formula-fed infants enrolled at 14 days of age with outcomes assessed over 4 months. Gains in weight and length to 4 months were analyzed using linear regression accounting for clustering within study. Outcomes of caregiver-reported stool consistency and frequency were analyzed using a longitudinal multinomial model. Results. Data from 511 infants were included (197 CMF, 314 PHF-W). There were no differences in weight gain between groups. There was no difference in length gain in girls fed PHF-W while boys fed PHF-W had a significant difference of +0.016 cm/month compared to boys fed CMF. Infants fed PHF-W had a significantly higher probability of soft and lower probability of hard stools as compared to infants fed CMF at each time point (p Conclusions. Infants fed CMF and PHF-W exhibit appropriate growth with comparable gains in weight and length through 4 months. More soft and fewer hard stools are observed in infants fed PHF-W compared to CMF. This difference could help to inform decision-making when choosing an infant formula.

Background The objective of this study was to conduct an indirect treatment comparison between cabazitaxel, abiraterone and enzalutamide to determine the clinical efficacy and safety of cabazitaxel relative to comparators in the treatment of patients with metastatic castrate-resistant prostate cancer who progress on docetaxel-based therapies. Methods A systematic literature review was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm of best supportive care were included in the analysis. Overall survival, progression-free survival, and adverse events were compared within both Bayesian and Frequentist frameworks. The ratios for survival outcomes were estimated using hazard ratios (HR), and the ratios for adverse events between groups were estimated using odds ratios (ORs); uncertainty was reported as 95% confidence (Frequentist) and credible (Baysesian) Intervals. Results Three of thirteen trials identified for abstraction were relevant for analyses. Median overall survival was not statistically significantly different for abiraterone (HR = 1.04; 95% CI = 0.83–1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69–1.11) when compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI = 1.01–10.44), diarrhoea (OR = 16.60; 95% CI = 1.41–75.31) and haematuria (OR = 3.88; 95% CI = 1.03–10.09) were more likely to occur in the cabazitaxel group than the abiraterone group, while pyrexia risk was higher in cabazitaxel compared to enzalutamide (OR = 36.23; 95% CI = 1.14–206.40). Frequentist analyses produced similar results. Conclusions The scarcity of clinical studies and lack of a common comparator limited analyses. The adverse event results must be interpreted with caution as many were based on small numbers. The results from this analysis indicate comparable survival outcomes and adverse event profiles. As these pivotal studies may not reflect the contemporary treatment landscape and patient profiles, additional research, including head-to-head clinical trials and real world observational studies, should be conducted to further elucidate the beneficial effects of these therapies.

To characterize patterns of emergency department (ED) utilization for ambulatory care-sensitive conditions (ACSCs) among patients with established care within a patient-centered medical home.Retrospective chart review using Michigan Medicine's (formerly University of Michigan Health System) electronic health record.Ten general medicine (GM) physicians reviewed 256 ambulatory care-sensitive ED encounters that occurred between January 1, 2014, and December 31, 2014, among patients of a GM medical home. Physician reviewers abstracted from the medical record the day and time of ED presentation and the source of ED referral (eg, patient self-referral vs physician referral). Physicians assessed the appropriateness of the care location (eg, ED vs primary care). Interrater reliability was assessed using the kappa statistic, and the χ2 test was used to assess differences in the appropriateness of the care location according to ED referral source.Compared with all other days of the week, the fewest number of ED visits occurred on weekend days, and nearly half of patients (48%) presented to the ED after daytime hours, which were defined as 8 am to 3:59 pm. The majority (n = 185; 72%) of patients were self-referred to the ED. The ED was considered the appropriate care location in more than half (53%) of the reviewed cases. Among the 119 cases considered appropriate for GM management, the majority (86%) were self-referred to the ED.Patients with ACSCs often presented to the ED without contacting their medical home. Frequently, the ED is the most appropriate location given symptoms at presentation.

Objectives To assess the financial effect of the 2008 Hospital-Acquired Conditions Initiative (HACI) pressure ulcer payment changes on Medicare, other payers, and hospitals. Design Retrospective before-and-after study of all-payer statewide administrative data for more than 2.4 million annual adult discharges in 2007 and 2009 using the Healthcare Cost and Utilization Project State Inpatient Datasets for California. How often and by how much the 2008 payment changes for pressure ulcers affected hospital payment was assessed. Setting Nonfederal acute care California hospitals (N = 311). Participants Adults discharged from acute-care hospitals. Measurements Pressure ulcer rates and hospital payment changes. Results Hospital-acquired pressure ulcer rates were low in 2007 (0.28%) and 2009 (0.27%); present-on-admission pressure ulcer rates increased from 2.3% in 2007 to 3.0% in 2009. According to clinical stage of pressure ulcer (available in 2009), hospital-acquired Stage III and IV ulcers occurred in 603 discharges (0.02%); 60,244 discharges (2.42%) contained other pressure ulcer diagnoses. Payment removal for Stage III and IV hospital-acquired ulcers reduced payment in 75 (0.003%) discharges, for a statewide payment decrease of $310,444 (0.001%) for all payers and $199,238 (0.001%) for Medicare. For all other pressure ulcers, the Hospital-Acquired Conditions Initiative reduced hospital payment in 20,246 (0.81%) cases (including 18,953 cases with present-on-admission ulcers), reducing statewide payment by $62,538,586 (0.21%) for all payers and $47,237,984 (0.32%) for Medicare. Conclusion The total financial effect of the 2008 payment changes for pressure ulcers was negligible. Most payment decreases occurred by removal of comorbidity payments for present-on-admission pressure ulcers other than Stages III and IV. The removal of payment for hospital-acquired Stage III and IV ulcers by implementation of the HACI policy was 1/200th that of the removal of payment for other types of pressure ulcers that occurred in implementation of the Hospital-Acquired Conditions Initiative.

Objectives To identify facility- and individual-level predictors of nursing home safety culture. Design Cross-sectional survey of individuals within facilities. Setting Nursing homes participating in the national Agency for Healthcare Research and Quality Safety Program for Long-Term Care: Healthcare-Associated Infections/Catheter-Associated Urinary Tract Infections Project. Participants Responding nursing home staff (N = 14,177) from 170 (81%) of 210 participating facilities. Measurements Staff responses to the Nursing Home Survey on Patient Safety Culture (NHSOPS), focused on five domains (teamwork, training and skills, communication openness, supervisor expectations, organizational learning) and individual respondent characteristics (occupation, tenure, hours worked), were merged with data on facility characteristics (from the Certification and Survey Provider Enhanced Reporting): ownership, chain membership, percentage residents on Medicare, bed size. Data were analyzed using multivariate hierarchical models. Results Nursing assistants rated all domains worse than administrators did (P < .001), with the largest differences for communication openness (24.3 points), teamwork (17.4 points), and supervisor expectations (16.1 points). Clinical staff rated all domains worse than administrators. Nonprofit ownership was associated with worse training and skills (by 6.0 points, P =.04) and communication openness (7.3 points, P =.004), and nonprofit and chain ownership were associated with worse supervisor expectations (5.2 points, P =.001 and 3.2 points, P =.03, respectively) and organizational learning (5.6 points, P =.009 and 4.2 points, P = .03). The percentage of variation in safety culture attributable to facility characteristics was less than 22%, with ownership having the strongest effect. Conclusion Perceptions of safety culture vary widely among nursing home staff, with administrators consistently perceiving better safety culture than clinical staff who spend more time with residents. Reporting safety culture scores according to occupation may be more important than facility-level scores alone to describe and assess barriers, facilitators, and changes in safety culture.

Voluntary Leapfrog Safe Practices Score (SPS) measures were among the first public reports of hospital performance. Recently, Medicare's Hospital Compare website has reported compulsory measures. Leapfrog's Hospital Safety Score (HSS) grades incorporate SPS and Medicare measures. We evaluate associations between Leapfrog SPS and Medicare measures, and the impact of SPS on HSS grades. Using 2013 hospital data, we linked Leapfrog HSS data with central line-associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) standardized infection ratios (SIRs), and Hospital Readmission and Hospital-Acquired Condition (HAC) Reduction Program penalties incorporating 2013 performance. For SPS-providing hospitals, we used linear and logistic regression models to predict CLABSI/CAUTI SIRs and penalties as a function of SPS. For hospitals not reporting SPS, we simulated change in HSS grades after imputing a range of SPS. In total, 1089 hospitals reported SPS; >50% self-reported perfect scores for all but 1 measure. No SPS measures were associated with SIRs. One SPS (feedback) was associated with lower odds of HAC penalization (odds ratio, 0.86; 95% confidence interval, 0.76-0.97). Among hospitals not reporting SPS (N=1080), 98% and 54% saw grades decline by 1+ letters with first and 10th percentile SPS imputed, respectively; 49% and 54% saw grades improve by 1+ letter with median and highest SPS imputed. Voluntary Leapfrog SPS measures skew toward positive self-report and bear little association with compulsory Medicare outcomes and penalties. SPS significantly impacts HSS grades, particularly when lower SPS is reported. With increasing compulsory reporting, Leapfrog SPS seems limited for comparing hospital performance.

Background Arteriovenous fistulae are the currently recommended gold standard vascular access modality for haemodialysis because of their prolonged patency, improved durability, and low risk of infection for those that mature. However, notable disadvantages are observed in terms of protracted maturation time, associated high rates of catheter use, and substantial abandonment rates. The aim of this study was to quantitatively summarize the outcomes of fistula patency, infection, maturation, and abandonment published in the scientific literature. Methods This was a systematic review and meta-analyses of studies evaluating fistula outcomes. Literature searches were conducted in multiple databases to identify observational and interventional studies of mean fistula patency rates at 1 year, infection risk, maturation time, and abandonment. Digitisation software was used to simulate individual patient level data from Kaplan–Meier survival plots. Results Over 8000 studies were reviewed, and from these, 318 studies were included comprising 62,712 accesses. For fistulas the primary unassisted, primary assisted, and secondary patency rates at one year were 64%, 73% and 79% respectively, however not all fistulas reported as patent could be confirmed as being clinically useful for dialysis (i.e. functional patency). For fistulas that were reported as mature, mean time to maturation was 3.5 months, however only 26% of created fistulas were reported as mature at 6 months and 21% of fistulas were abandoned without use. Overall risk of infection in fistula patients was 4.1% and the overall rate per 100 access days was 0.018. Conclusions Reported fistula patency rates may overstate their potential clinical utility when time to maturation, maturation rate, abandonment and infection are considered. Protracted maturation times, abandonment and infection all have a significant impact on evaluating the clinical utility of fistula creation. A rigorous and consistent set of outcomes definitions for hemodialysis access are necessary to clarify factors contributing to fistula success and the clinical consequence of fistula failure.

Background Retrospective medical record review is used to categorize urinary tract infections (UTIs) as symptomatic, catheter-associated, and/or healthcare-associated to generate National Healthcare Safety Network (NHSN) surveillance and claims data. We assessed how often patients with UTI diagnoses in claims data had a catheter in place, had documented symptoms, or met the NHSN criteria for catheter-associated UTI (CAUTI). Methods Two physicians retrospectively reviewed medical records for 294 randomly selected patients hospitalized with UTI as a secondary diagnosis, discharged between October 2008 and September 2009 from the University of Michigan. We applied a modification of recent NHSN criteria to estimate how often UTIs in claims data may be an NHSN CAUTI. Results The 294 patients included 193 women (66%). The mean patient age was 63 years, and the median length of hospital stay was 7.5 days. Catheter use was noted for 216 of 294 postadmission records (74%), including 126 (43%) with a Foley catheter. NHSN symptoms were noted in 113 records (38%); 62 (21%) had symptoms other than fever. Of 136 hospitalizations meeting urine culture criteria, 17 (5.8%) met the criteria for a potential NHSN CAUTI. Conclusions Retrospective medical record review to identify symptoms and catheter use is complicated and resource-intensive. Requiring standard documentation of symptoms and catheter status when ordering urine cultures could simplify and improve CAUTI surveillance and its fidelity as a hospital quality indicator.

Human milk oligosaccharides are important components of breast milk. We evaluated feeding tolerance of the human milk oligosaccharide 2′-fucosyllactose (2′FL) in a 100% whey, partially hydrolyzed infant formula with the probiotic Bifidobacterium animalis ssp lactis strain Bb12 ( B lactis; Test) as compared with the same formula without 2′FL (Control) in a randomized controlled trial of healthy infants enrolled at 2 weeks of age (±5 days). After 6 weeks of feeding the assigned formula, the primary outcome of tolerance was assessed using the Infant Gastrointestinal Symptom Questionnaire. Stooling, vomiting, spit-up, crying, and fussing were compared between groups. Seventy-nine infants were enrolled and 63 completed the study per protocol (30 Test, 33 Control). Infant Gastrointestinal Symptom Questionnaire scores were similar between groups (Test 20.9 ± 4.8, Control 20.7 ± 4.3, P = .82). Partially hydrolyzed infant formula with 2′FL and B lactis is tolerated well, as confirmed by a validated multi-symptom index.

Self-administration of surveys has been shown to increase respondents� reporting of sensitive information, and audio computer-assisted self-interviewing (ACASI) has become the self-administration method of choice for many social surveys. The study reported here, a laboratory experiment with 235 respondents, examines why ACASI seems to promote disclosure. It compares responses in a voice-only (self-administered) interface with responses to a face-to-face (FTF) human interviewer and to two automated interviewing systems that presented animated virtual interviewers with more and less facial movement. All four modes involved the same human interviewer�s voice, and the virtual interviewers� facial motion was captured from the same human interviewer who carried out the FTF interviews. For the ten questions for which FTF-ACASI mode differences (generally, more disclosure in ACASI than FTF) were observed, we compared response patterns for the virtual interviewer conditions. Disclosure for most questions was greater under ACASI than in any of the other modes, even though the two virtual interview modes involved computerized self-administration. This suggests that the locus of FTF-ACASI effects is particularly tied to the absence of facial representation in ACASI. Additional evidence suggests that respondents� affective experience (e.g., comfort) during the interview may mediate these mode effects

Readmission rates after pneumonia, heart failure, and acute myocardial infarction hospitalizations are risk-adjusted for age, gender, and medical comorbidities and used to penalize hospitals. To assess the impact of disability and social determinants of health on condition-specific readmissions beyond current risk adjustment. Retrospective cohort study of Medicare patients using 1) linked Health and Retirement Study-Medicare claims data (HRS-CMS) and 2) Healthcare Cost and Utilization Project State Inpatient Databases (Florida, Washington) linked with ZIP Code-level measures from the Census American Community Survey (ACS-HCUP). Multilevel logistic regression models assessed the impact of disability and selected social determinants of health on readmission beyond current risk adjustment. Outcomes measured were readmissions ≤30 days after hospitalizations for pneumonia, heart failure, or acute myocardial infarction. HRS-CMS models included disability measures (activities of daily living [ADL] limitations, cognitive impairment, nursing home residence, home healthcare use) and social determinants of health (spouse, children, wealth, Medicaid, race). ACS-HCUP model measures were ZIP Code-percentage of residents ≥65 years of age with ADL difficulty, spouse, income, Medicaid, and patient-level and hospital-level race. For pneumonia, ≥3 ADL difficulties (OR 1.61, CI 1.079–2.391) and prior home healthcare needs (OR 1.68, CI 1.204–2.355) increased readmission in HRS-CMS models (N = 1631); ADL difficulties (OR 1.20, CI 1.063–1.352) and ‘other’ race (OR 1.14, CI 1.001–1.301) increased readmission in ACS-HCUP models (N = 27,297). For heart failure, children (OR 0.66, CI 0.437–0.984) and wealth (OR 0.53, CI 0.349–0.787) lowered readmission in HRS-CMS models (N = 2068), while black (OR 1.17, CI 1.056–1.292) and ‘other’ race (OR 1.14, CI 1.036-1.260) increased readmission in ACS-HCUP models (N = 37,612). For acute myocardial infarction, nursing home status (OR 4.04, CI 1.212–13.440) increased readmission in HRS-CMS models (N = 833); ‘other’ patient-level race (OR 1.18, CI 1.012–1.385) and hospital-level race (OR 1.06, CI 1.001–1.125) increased readmission in ACS-HCUP models (N = 17,496). Disability and social determinants of health influence readmission risk when added to the current Medicare risk adjustment models, but the effect varies by condition.

In this report we describe a preliminary concept for a Tritium Removal System (TRS) to remove tritium that is generated in the ⁹⁹Mo production process. Preliminary calculations have been performed to evaluate an approximate size for the system. The concept described utilizes well-established detritiation technology based on catalytic oxidation of tritium and tritiated hydrocarbons to water in a high temperature (400 °C) reactor and capture of water in a molecular sieve bed. The TRS concept involves use of a single system that would cycle through each of the seven online target systems and remove tritium that has been accumulated after one week’s run time. The TRS would perform cleanup operations on each target system for a period of approximately 24 hours. This would occur while the system is still online and just prior to target replacement, so tritium levels would at their minimum values for target replacement. In the concept, during normal operation a small fraction (1%) of the helium recirculating in the system would be diverted through the TRS and returned to the flow loop. With this approach sufficient levels of detritiation can be accomplished in a 24 hour period. In the study it was found that because ofmore » the need to maintain low oxygen levels in the system (

Digital amputation in children is a very strong indication for replantation, but little is known about the epidemiology and distribution of care for pediatric finger amputation injuries in the United States. The specific aims of this study were to examine trends in the surgical management of pediatric finger amputation injuries in the United States from 2000 to 2006, and to identify potential treatment disparities among various demographic groups.Data from the 2000, 2003, and 2006 Healthcare Cost and Utilization Project Kids' Inpatient Database were used to identify discharge records containing at least one ICD-9-CM procedure code corresponding to digit amputation or replantation. National estimates were generated using weighted frequency calculations, and a weighted logistic regression model was used to examine the influence of various demographic factors on treatment.There were 1,321 weighted discharge records that satisfied our inclusion criteria. From 2000 to 2006, the rate of attempted digit replantation for pediatric finger amputation injuries has remained stable at approximately 40%. The majority of injuries were treated at nonchildren's (86%) and teaching (76%) hospitals; 52% of digit replantations were performed at hospitals with a volume of 1 to 2 digit replantations per year. We found that blacks (odds ratio [OR] 0.47), Hispanics (OR 0.37), and children without insurance (OR 0.38) were less likely to receive attempted replantation (all p0.05), even after controlling for potential confounding factors.The proportion of pediatric digit amputation injuries managed by replantation remained stable between 2000 and 2006. Whites and children with private health insurance were more likely to receive replantation than blacks, Hispanics, and children without health insurance, even after controlling for confounding factors.

In a survey of acute care hospitals across the United States, we found that many hospitals use indwelling urinary catheters for reasons that are not medically necessary (eg, urinary incontinence without outlet obstruction and patient/family requests). Our findings highlight an opportunity to reduce unnecessary catheter use through promoting awareness of appropriate use.

Background The Agency for Healthcare Research and Quality (AHRQ) has funded national collaboratives using the Comprehensive Unit-based Safety Program to reduce rates of two catheter-associated infections—central-line-associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI), using evidence-based intervention bundles to improve technical aspects of care and socioadaptive approaches to foster a culture of safety. Objective Examine the association between hospital units9 results for the Hospital Survey on Patient Safety Culture (HSOPS) and catheter-associated infection rates. Methods We analysed data from two prospective cohort studies from acute-care intensive care units (ICUs) and non-ICUs participating in the AHRQ CLABSI and CAUTI collaboratives. National Healthcare Safety Network catheter-associated infections per 1000 catheter-days were collected at baseline and quarterly postimplementation. The HSOPS was collected at baseline and again 1 year later. Infection rates were modelled using multilevel negative binomial models as a function of HSOPS components over time, adjusted for hospital-level characteristics. Results 1821 units from 1079 hospitals (CLABSI) and 1576 units from 949 hospitals (CAUTI) were included. Among responding units, infection rates declined over the project periods (by 47% for CLABSI, by 23% for CAUTI, unadjusted). No significant associations were found between CLABSI or CAUTI rates and HSOPS measures at baseline or over time. Conclusions We found no association between results of the HSOPS and catheter-associated infection rates when measured at baseline and postintervention in two successful large national collaboratives focused on prevention of CLABSI and CAUTI. These results suggest that it may be possible to improve CLABSI and CAUTI rates without making significant changes in safety culture, particularly as measured by instruments like HSOPS.

Preparations are currently underway at the OMEGA laser at the University of Rochester Laboratory for Laser Energetics (UR/LLE) to conduct direct drive laser implosion campaigns with inertial confinement fusion targets containing deuterium-tritium (DT) cryogenic ice layers. The OMEGA Cryogenic Target Handling System will fill plastic targets with high-pressure DT (150 MPa) at 300 to 500 K, cool them down to cryogenic temperature (

Diversification of production agriculture has received much attention in recent years. As producers and customers adapt to technologically advanced production and marketing systems, it is important to consider opportunities available for adding value to raw grain through alternative handling and transportation options. One such opportunity that has been more widely recognized in recent years is marketing grain products via container. It has been estimated that this option is currently used in marketing about 1% of U.S. grain production, with growth to 3% expected in the next 5 years. A profile is presented of the U.S. containerized grain and oilseed export industry, including marketing activities, future expectations, information needs, and business practices. Information developed concerning shipment origins, commodity volumes, and market destinations provides an industry profile that might be used as a tool in research, development, planning, and enhancement of opportunities for containerized marketing of grain products.

Value-based purchasing programs use administrative data to compare hospitals by rates of hospital-acquired pressure ulcers (HAPUs) for public reporting and financial penalties. However, validation of these data is lacking.To assess the validity of the administrative data used to generate HAPU rates by comparing the rates generated from these data with those generated from surveillance data.Retrospective analysis of 2 million all-payer administrative records from 448 California hospitals and quarterly hospitalwide surveillance data from 213 hospitals from the Collaborative Alliance for Nursing Outcomes (as publicly reported on the CalHospitalCompare Web site).196 acute care hospitals with at least 6 months of available administrative and surveillance data.Nonobstetric adults discharged in 2009.Hospital-specific HAPU rates were computed as the percentage of discharged adults (from administrative data) or examined adults (from surveillance data) with at least 1 stage II or greater HAPU (HAPU2+). Categorization of hospital performance based on administrative data was compared with the grade assigned when surveillance data were used.When administrative data were used, the mean hospital-specific HAPU2+ rate was 0.15% (95% CI, 0.13% to 0.17%); when surveillance data were used, the rate was 2.0% (CI, 1.8% to 2.2%). Among the 49 hospitals with HAPU2+ rates in the highest (worst) quartile from administrative data, use of the surveillance data set resulted in performance grades of "superior" for 3 of these hospitals, "above average" for 14, "average" for 15, and "below average" for 17.Data are from 1 state and 1 year.Hospital performance scores generated from HAPU2+ rates varied considerably according to whether administrative or surveillance data were used, suggesting that administrative data may not be appropriate for comparing hospitals.Agency for Healthcare Research and Quality.

A wide spectrum of quality exists among deceased donor organs available for liver transplantation. It is unknown whether some transplant centers systematically use more low quality organs, and what factors might influence these decisions. We used hierarchical regression to measure variation in donor risk index (DRI) in the United States by region, organ procurement organization (OPO) and transplant center. The sample included all adults who underwent deceased donor liver transplantation between January 12, 2005 and February 1, 2009 (n = 23 810). Despite adjusting for the geographic region and OPO, transplant centers’ mean DRI ranged from 1.27 to 1.74, and could not be explained by differences in patient populations such as disease severity. Larger volume centers and those having competing centers within their OPO were more likely to use higher risk organs, particularly among recipients with lower model for end-stage liver disease (MELD) scores. Centers using higher risk organs had equivalent waiting list mortality rates, but tended to have higher post-transplant mortality (hazard ratio 1.10 per 0.1 increase in mean DRI). In conclusion, the quality of deceased donor organ patients receive is variable and depends in part on the characteristics of the transplant center they visit.