US Databases Research Articles

Premedication Prior to Peg-Asparaginase Is Cost-Effective for Pediatric Leukemia Patients

Background: Asparaginase is a critical therapy component for childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions and silent inactivation by neutralizing antibodies can lead to withholding further doses. Reactions occur in 10-20% of children receiving the commonly used, widely available pegylated asparaginase. The less immunogenic Erwinia asparaginase may allow continued administration, but requires more frequent dosing and is subject to limitations in availability. Inability to receive all recommended asparaginase doses decreases disease-free survival. Premedication with antihistamines, antipyretics and steroids decreases hypersensitivity reaction frequency, preventing the need for alternates. The cost-effectiveness of premedication strategies in childhood ALL is unclear. Methods: We used a Markov model to estimate strategy costs and quality-adjusted life years (QALYs) for two patient scenarios: a 3-year-old with standard-risk ALL receiving 2 asparaginase doses, and a 15-year-old with high-risk ALL receiving 7 asparaginase doses over a 5-year time horizon. Patients entering the model received premedication with serum asparaginase level monitoring, monitoring only, or no premedication/monitoring. Literature data were used for hypersensitivity reaction and silent inactivation risks following each asparaginase dose. Silent inactivation was not identified the non-monitoring strategy. Disease outcomes, therapy and associated additional care costs, and health state quality-of-life utilities were obtained from the literature and US databases. Evaluation took the societal perspective, with costs and effectiveness discounted at 3%/yr. Multiple sensitivity analyses were performed. Results: In both the standard-risk and high-risk analyses, premedication was the least costly strategy. In the standard-risk model, premedication with monitoring cost $4,586 less than monitoring alone, resulted in 8% fewer changes to Erwinia and 0.01 additional QALYs. It cost $1,993 less than no premedication/monitoring, resulted in 3% fewer changes and 0.08 additional QALYs. In the high-risk model, premedication cost $29,757 less than monitoring alone, resulted in 7% fewer medication changes and 0.01 fewer QALYS; thus, monitoring alone was expensive, costing >$2 million/QALY gained compared to premedication and monitoring. Premedication cost $11,255 less than no premedication/monitoring, resulted in 2% fewer changes and 0.07 additional QALYs. Individual variation of all model inputs did not change the favorability of premedication and monitoring for either model. In probabilistic sensitivity analyses varying all parameters simultaneously over distributions 1000 times, premedication and monitoring was favored in >86% of model iterations in both standard- and high-risk scenarios. Conclusion: Compared to other strategies, premedication use and asparaginase level monitoring in children with ALL is economically reasonable and potentially cost-saving. Disclosures No relevant conflicts of interest to declare.

Associations between Intake of Dietary Flavonoids and 10-Year Incidence of Age-Related Hearing Loss.

Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing status. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz > 25 dB hearing level (HL). Dietary data were collected through a semi-quantitative food frequency questionnaire. The flavonoid content of foods was estimated using US databases. During the 10-year follow-up, 260 (31.6%) new cases of hearing loss (incident) were observed. After multivariable adjustment, participants in the fourth versus first quartile (reference group) of intake of dietary isoflavone had 36% lower risk of incident hearing loss after 10 years: odds ratios (OR) 0.64 (95% confidence intervals, CI, 0.42–0.99); p-value for trend = 0.03. Nonsignificant associations were observed between the other five flavonoid subclasses and 10-year incidence of hearing loss. Our findings do not support the hypothesis that the intake of dietary flavonoids protect against long-term risk of hearing loss. The association with isoflavone intake needs to be confirmed by other population-based studies.

Glycemic Control Following GLP-1 RA or Basal Insulin Initiation in Real-World Practice: A Retrospective, Observational, Longitudinal Cohort Study.

IntroductionInjectable therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin (BI) are well-established agents for people with type 2 diabetes (T2D). This study aimed to investigate real-world effectiveness of GLP-1 RAs or BI in adults with T2D poorly controlled on oral antihyperglycemic drugs (OADs).MethodsThis was a retrospective, observational, longitudinal cohort study of adults with T2D from the US Optum Humedica® database and UK Clinical Practice Research Datalink, who initiated either injectable between January 1, 2010, and June 30, 2016. Baseline characteristics, glycated hemoglobin (HbA1c) change, and cumulative percentage reaching HbA1c < 7% in 24 months after initiation were analyzed in four patient cohorts.ResultsIn the US and UK databases, respectively, 20,836 and 5508 patients initiated GLP-1 RAs and 60,598 and 5083 initiated BI. Baseline mean HbA1c at initiation ranged between 8.8% and 10.3% across all cohorts. In all cohorts, a decrease of HbA1c occurred 3–6 months after initiation. The cumulative percentage of patients reaching HbA1c < 7% showed the greatest probability in the first 12 months (15–40% of patients across cohorts at 12 months), particularly in the first 6 months after initiation. The probability of reaching glycemic control diminished after the second quarter. The proportion of patients reaching HbA1c < 7% in both GLP-1 RA and BI cohorts at 12 months was < 25% if baseline HbA1c was ≥ 9%.ConclusionsFor adults with T2D inadequately controlled on OADs, this analysis reveals an unmet clinical need. Initiation of first injectable therapy did not occur until HbA1c was considerably above target, when control is harder to achieve. Results suggest that in individuals with baseline HbA1c ≥ 9.0%, only a minority are likely to achieve an HbA1c < 7% with a GLP-1 RA or BI alone.Graphic Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00905-y) contains supplementary material, which is available to authorized users.

The Cost of Postoperative Infection Following Orthopaedic Fracture Surgery

The objective of this paper is to describe the costs associated with postoperative infection following orthopedic fracture surgery. The data provided is based on a narrative review and an analysis of national claims and discharge databases in the United States. The narrative research specifically evaluated the costs associated with postoperative infections following the treatment of proximal femur, tibia, humerus, and ankle fractures. Two US databases were used to estimate the annual incidence of a deep surgical site infection following fracture treatment and the costs associated with that treatment. Previous studies suggest that the cost of treatment for an infected patient is likely to be at least twice the cost of treating an uninfected patient. However, the current literature is limited to small retrospective reviews focused narrowly on the direct health care sector costs of treatment. Further research is required to better estimate the costs of postoperative infection in orthopedic trauma patients, particularly the nonhealth care sector and indirect costs associated with impairment and lost productivity to the patient and caregiver.

The economic burden of Clostridioides difficile infection in patients with hematological malignancies in the United States: A case-control study.

The primary study aim was to describe all direct healthcare costs associated with Clostridioides difficile infection (CDI), both in and out of the hospital, in patients with hematologic malignancies in the United States. A retrospective analysis was conducted utilizing data from US databases of Truven Health Analytics. We analyzed health insurance claims between January 2014 and December 2017 of patients diagnosed with hematological cancer: acute myeloid leukemia (AML), acute lymphoblastic leukemia, Hodgkin's lymphoma, and non-Hodgkin's lymphoma (NHL). Patients with CDI after cancer diagnosis (CDI+, cases) were matched with patients without CDI reported (CDI-, controls). Matched cases and controls were compared to identify the CDI-associated costs in the 90 days following the onset of CDI. We matched 622 CDI+ patients with 11,111 CDI- patients. NHL (41.7%) and AML (30.9%) were the predominant underlying diseases in the CDI+ groups. During study period, the average time in-hospital of CDI+ patients was 23.1 days longer than for CDI- patients (P < 2×10-16). Overall, CDI onset increased costs of care by an average of US$57,159 per patient (P = 6×10-12), mainly driven by hospital costs. This study confirms the significant economic burden associated with CDI in the United States, especially in patients with hematological malignancies. These findings highlight the need for prevention of CDI in this specific patient population.

Biomedical Applications of the Dynamic Nuclear Polarization and Parahydrogen Induced Polarization Techniques for Hyperpolarized 13C MR Imaging.

Since the first pioneering report of hyperpolarized [1-13C]pyruvate magnetic resonance imaging (MRI) of the Warburg effect in prostate cancer patients, clinical dissemination of the technique has been rapid; close to 10 sites worldwide now possess a polarizer fit for the clinic, and more than 30 clinical trials, predominantly for oncological applications, are already registered on the US and European clinical trials databases. Hyperpolarized 13C probes to study pathophysiological processes beyond the Warburg effect, including tricarboxylic acid cycle metabolism, intra-cellular pH and cellular necrosis have also been demonstrated in the preclinical arena and are pending clinical translation, and the simultaneous injection of multiple co-polarized agents is opening the door to high-sensitivity, multi-functional molecular MRI with a single dose. Here, we review the biomedical applications to date of the two polarization methods that have been used for in vivo hyperpolarized 13C molecular MRI; namely, dissolution dynamic nuclear polarization and parahydrogen-induced polarization. The basic concept of hyperpolarization and the fundamental theory underpinning these two key 13C hyperpolarization methods, along with recent technological advances that have facilitated biomedical realization, are also covered.

Excess burden associated with Clostridioides difficile infection in haematological patients occurring during hospitalization with induction chemotherapy in the USA

Patients with haematological diseases are at high risk of developing Clostridioides difficile infection (CDI). The study aim was to describe excess length of stay and costs associated with CDI during the hospital stay for induction chemotherapy in the United States (USA). A retrospective analysis was conducted utilizing data from US databases of Truven Health Analytics®. Comprehensive hospitalization data of patients with induction chemotherapy due to acute myeloid leukaemia (AML), acute lymphoblastic leukaemia, Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) were analysed. Patients with CDI occurring during the hospital stay were compared to controls through a case-control comparison of the direct treatment costs and length of stay was performed with an exact matching algorithm. A total of 2611 patients were included between January 2014 and December 2017. NHL (43.5%) and AML (38.4%) were the predominant underlying diseases and 15% of patients received a stem cell transplantation. During the matching, 105 CDI cases (CDI+) were compared with 801 controls (CDI-). On average, hospitalization costs were increased by US$36,113 in CDI+ compared to CDI- patients (P=0.009) and patients with CDI spent on average 8.9 additional days in hospital (P=0.003). The findings highlight a significant burden associated with CDI in haematological patients undergoing induction chemotherapy in the USA. There is an important need for prevention of CDI in this specific patient population.

Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus

Background: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. Methods: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. Results: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. Conclusion: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies.

PBI25 COST OF STANDARD HALF-LIFE VERSUS EXTENDED HALF-LIFE RECOMBINANT COAGULATION FACTOR VIII IN PATIENTS WITH HEMOPHILIA A IN SPAIN: RESULTS FROM A PROBABILISTIC MODEL

A US Real-World study found the median recombinant coagulation factor VIII (rFVIII) international units (IUs) dispensed were between 10% and 45% higher with extended half-life (EHL) versus standard half-life (SHL) products. The objective was to evaluate the cost of SHL versus EHL rFVIII in Spain. A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with hemophilia A and a time horizon of 1 year was carried out. The mean IUs dispensed quarterly with each rFVIII were taken from a Real-World study, conducted in two US databases, which included 776 patients with hemophilia A. The frequency of use of each recombinant rFVIII was obtained from sales estimation (IMS) of a 12-months period in Spain (BOE, 2018). rFVIII prices (€ 2019) were obtained from the Reference Price Order by the National Health System. A base case analysis, considering the use of rFVIII in the clinical practice in Spain and two sensitivity analyzes were performed. In the base case analysis, an average annual saving per patient treated with SHL of € 11,227 was obtained, with a 75.5% saving probability. The results were stable for sensitivity analyzes performed. In the event that there was no change in treatment from the SHL to the EHL, there would be a greater annual saving per patient (€ 53,078) with a 99.9% saving probability. When applying the rFVIII frequency of use in the clinical practice in the US, the annual savings per patient treated with SHL instead of EHL would amount to € 16,350, with a saving probability of 79.9%. The probabilistic model found higher expenditures over one year for hemophilia A patients using EHL versus SHL products. The use of SHL instead of EHL, would amount to cost savings to the National Health System in Spain.

Alcoholic Liver Disease Epidemiology in the United States: A Retrospective Analysis of 3 US Databases.

Alcoholic liver disease (ALD) prevalence, particularly the subset with advanced liver disease, is not well defined. Herein, we aim to provide a comprehensive assessment of ALD epidemiology across the spectrum of disease severity and across different settings using 3 unique US databases. We performed a retrospective, observational study of US adults with ALD using 2001-2016 National Health and Nutrition Examination Survey (NHANES), 2007-2014 Nationwide Inpatient Sample (NIS), and 2007-2017 United Network for Organ Sharing (UNOS) registry. ALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67 defined stage ≥3 fibrosis. Alcoholic cirrhosis (AC) in the NIS was identified using International Classification of Diseases, Ninth Revision codes. ALD in the UNOS was identified using UNOS coding. From 2001-2002 to 2015-2016, the overall weighted ALD prevalence was stable from 8.8% to 8.1% (P = 0.102), whereas the proportion of ALD with stage ≥3 fibrosis increased from 2.2% (95% CI: 0.4-4.0) to 6.6% (95% CI: 2.0-9.9; P = 0.007) (NHANES). From 2007 to 2014, the number of hospitalizations among patients with AC per 1,000 increased by 32.8%, and the proportion of hospitalizations among the patients with AC with ≥3 cirrhosis complications increased from 11.6% in 2007 to 25.8% in 2014 (Ptrend < 0.0001) (NIS). From 2007 to 2017, the total number of adults with ALD listed for liver transplant increased by 63.4% and the proportion with concurrent hepatocellular carcinoma increased by 178% (UNOS). Among these 3 US databases, consistent observations of increasing ALD severity emphasize the urgent need for greater awareness about the consequences of unhealthy alcohol use and interventions aimed specifically at addressing alcohol use disorders.

Deriving literature-based benchmarks for pediatric appendectomy and cholecystectomy complications from national databases in high-income countries: A systematic review and meta-analysis

BackgroundHealth systems must identify preventable adverse outcomes to improve surgical safety. We conducted a systematic review to determine national rates of postoperative complications associated with two common pediatric surgery operations in High-Income Countries (HICs). MethodsNational database studies of complication rates associated with pediatric appendectomies and cholecystectomies (2000–2016) in Canada, the US, and the UK were included. Outcomes included mortality, length of hospital stay (LOS), and other surgical complications. Outcome data were extracted and comparisons made between countries and databases. ResultsThirty-three papers met inclusion criteria (1 Canadian, 1 UK, and 4 US Databases). Mean LOS was 3.00 (±1.42) days and 3.44 (±1.55) days for appendectomy and cholecystectomy, respectively. Mortality was 0.06% after appendectomy and 0.24% after cholecystectomy. Readmission and reoperation rates were 6.79% and 0.32% for appendectomy, and 1.37% and 0.71% for cholecystectomy. For appendectomies, LOS was shorter in Canadian and UK studies compared to US studies, and mortality and readmission rates were lower (OR 0.46 95%CI 0.23 to 0.93, OR 3.63 to 3.77 95%CI) in UK studies compared to US studies. ConclusionsOutcomes after pediatric appendectomy and cholecystectomy are good but vary between HICs. Understanding national outcomes and intercountry differences is essential in developing health system approaches to pediatric surgical safety. Level of evidenceII

Exploring the potential public health benefits of universal influenza vaccine

ABSTRACT Background: Broadly protective, long-lasting universal influenza vaccines are under development in response to low-moderate seasonal vaccine effectiveness, frequent genetic changes in circulating viruses and extended turnaround for vaccine manufacture. Because a long-lasting vaccine might be less effective than a seasonal vaccine that has been matched to current circulating strains, the public health impact of its introduction should be evaluated. Methods: A modified agent-based model (ABM) examined multi-year effects of a universal vaccine among 18 to 49-year-olds, given in Year 1 only. The proportion of vaccinated 18 to 49-year-olds who received universal vaccine was varied from 0% to 100%. Model parameters were drawn from US databases and the medical literature. Outcomes were 4-year cumulative and annual influenza cases as well as annual cases averted/100,000 population for 3 age groups, 0–17 years, 18–49 years and 50+ years. Results: In Year 1 when universal vaccine was given to 50% or 100% of all vaccinated 18 to 49-year-olds, more influenza cases occurred, compared to no universal vaccine, but fewer cases occurred in Years 2–4 as overall protection increased. Cumulative averted cases over 4 years in 18 to 49-year-olds were 892/100,000 and 1,687/100,000 population for the 50% and 100% universal vaccine for 18 to 49-year-olds scenarios, respectively, with additional benefits to children and older adults through indirect effects. Conclusions: In ABM, the universal vaccine with a conservative VE estimate given once to 18 to 49-year-olds reduced influenza cases among all age groups in Years 2–4 following its introduction. Reduced influenza burden may occur sooner if VE of universal vaccines exceeds that assumed in these models.

Exploring the Introduction of Plug-In Hybrid Flex-Fuel Vehicles in Ecuador

In Europe, diesel combustion is being banned due to the NOx and PM2.5 emissions impact on air quality. The bus sector is being electrified and is increasing its use of alternative fuels, such as natural gas (in spark ignition engines) and bioethanol (in compression ignition engines), to reduce such harmful emissions. Even if a diesel bus is equipped with selective catalytic reduction (SCR), its NOx emissions are reduced its but produces more NH3 emissions that are PM2.5 precursors. In developing countries, the air quality is still barely monitored, however, the air quality issue is well known and is being addressed. Moreover, the Ecuadorian sugar cane industry is seeking ways to increase its ethanol production. This is the ideal framework to explore a new technology and energy source in developing economies such as Ecuador. This paper explores the impact of the Ecuadorian diesel bus fleet conversion to hybrid compression ignition ethanol (HEV-ED95), hybrid diesel and plug-in hybrid flex-fuel using electricity and internal combustion engine ICE-E20 and ICE-E100. The impacts are measured in terms of final energy consumption, criteria pollutant emissions (NH3, NOx, PM2.5) and 100 years global warming potential in a well-to-wheels framework. For the tank-to-wheels data the method follows the typical values of conversion efficiency from final to useful energy (cross checked with a microsimulation model), the Tier 2 European Environmental Agency approach combined with ethanol influence on compression ratio, lower heating value, criteria emissions taken from a literature review, and well-to-tank emission factors for electricity (10–58% thermal natural gas or coal powerplant contribution), for ethanol from banana industry wastes (ED95, E20 and E100), gasoline and diesel from US databases. A discussion on whether sugarcane biorefineries are necessary is highlighted in the results. All input parameters have an uncertainty range between a minimum and a maximum and the probability for each is giving by a uniform distribution.

Real-world impact of glycated hemoglobin reduction on treatment intensification and glycated hemoglobin goal attainment in type 2 diabetes mellitus patients initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i)

Objective: To evaluate the impact of a 0.2% reduction in glycated hemoglobin (HbA1c) on treatment intensification, poor HbA1c control and HbA1c goal attainment in patients with type 2 diabetes mellitus (T2DM) initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).Methods: IQVIATM Health Plan Claims Data – US and IQVIATM Ambulatory EMR Data – US databases (29 October 2012–31 March 2016) were used to identify adults with T2DM initiated on an SGLT2i (index date) who had HbA1c measurements pre- and post-index, and ≥6 months of eligibility pre-index (baseline). HbA1c change was defined as the difference between the first post-index and the last pre-index measurements. Cox regression models were used to assess treatment intensification, poor HbA1c control (i.e. HbA1c > 9%, among patients <9% at baseline) and goal attainment (HbA1c < 7%, <8%; among patients with HbA1c above goal at baseline) adjusting for HbA1c change and baseline characteristics. Patients were observed up to one year after the first HbA1c measurement or end of eligibility. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.Results: A total of 938 patients (mean age 54.9, 42.5% female, mean HbA1c 8.5%) were selected. Following SGLT2i initiation, each 0.2% reduction in HbA1c levels was associated with a decreased risk of treatment intensification (HR [95% CI] = 0.90 [0.86–0.92]), a decreased likelihood of reaching HbA1c > 9% (HR [95% CI] = 0.85 [0.79–0.88]) and higher likelihoods of achieving a treatment goal of HbA1c < 7% (HR [95% CI] = 1.17 [1.12–1.21]) and HbA1c < 8% (HR [95% CI] = 1.08 [1.04–1.10]).Conclusions: In T2DM patients, each HbA1c reduction of 0.2% following the initiation of an SGLT2i was associated with a significant positive impact on treatment intensification and HbA1c goal attainment.

Abstract 23: Patient Level Prediction Models Developed With Large Observational Databases Outperformed Existing Clinical Prediction Scores For Stratifying Bleeding Risk In Patients With Atrial Fibrillation

Background: Vitamin K antagonists (e.g., warfarin) and direct oral anticoagulants (DOACs; e.g., rivaroxaban, apixaban, dabigatran, edoxaban) are effective therapies for lowering the risk of thrombotic outcomes including stroke in patients with atrial fibrillation (AF). Like all anticoagulants, they are associated with an increased risk of bleeding. Several models (e.g., ATRIA, ORBIT, HAS-BLED, CHADS 2 and CHA 2 DS 2 -VASc) are available to predict the risk of major bleeding but their performance has not been widely evaluated in observational databases. Objective: To develop patient-level bleeding risk prediction models and evaluate their performance compared to existing clinical models of bleeding. Methods: Based on tools available through the Observational Health Data Science and Informatics Collaborative and Observed Medical Outcomes Partnership Common Data Model framework, we developed patient-level prediction (PLP) models to predict the risk of major bleeding events in patients with non-valvular AF who were new users of warfarin or DOACs. A LASSO regularized logistic regression technique including over 100,000 baseline covariates was performed across each of 4 US databases: IBM MarketScan ® (Commercial (CCAE), Medicaid (MDCD), and Medicare Supplemental (MDCR)) and Optum Clinformatics ® Extended Data Mart (Optum). We evaluated the performance of the PLP models compared with the existing models using the Area Under the Curve (AUC), with 75% training and 25% testing sets. The models were then externally validated by applying them to the other three databases. Results: In each database, all the PLP models achieved higher internal validity (AUCs 0.69 - 0.83) compared with the existing clinical models. The highest AUC among the existing clinical models was 0.76 for CHA 2 DS 2 -VASc run on the DOACs new user population in the CCAE database; the comparative AUC for the PLP model was 0.79. The external validation of the PLP models was somewhat lower, the lowest being the new user DOACs models learned on the MDCD database and applied to the other three databases with AUCs between 0.56 and 0.58. This is possibly in part due to differences between patients in MDCD versus other databases (e.g., age, disability, socioeconomic status). The highest performing was the new user warfarin model learned on the Optum database validated on the CCAE database with an AUC of 0.75. Conclusion: A patient level prediction model outperforms many existing clinical bleeding risk models currently in use.

Are Urinary Biomarkers Better Than Acute Kidney Injury Duration for Predicting Readmission?

Acute kidney injury (AKI) is a common complication of cardiac surgery. Postprocedural AKI is a risk factor for 30-day readmission. We sought to examine the association of AKI and kidney injury biomarkers with readmission after cardiac surgery. Patients alive at discharge who underwent cardiac surgery from the Translational Research Investigating Biomarker Endpoints-AKI cohort were enrolled from six medical centers in the United States and Canada. AKI duration was defined as the total number of days AKI was present during index admission (no AKI, 1-2, 3-6, and 7+ days). Preoperative and postoperative urinary levels were collected for interleukin-18, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, liver-fatty-acid-binding protein, cystatin C, microalbumin, creatinine, and albumin-to-creatinine ratio. Readmission and death events were identified through US (Medicare) and Canadian administrative databases at 30 days and 365 days after discharge. Of 968 patients 15.9% were readmitted or died within 30 days of discharge and 35.9% were readmitted or died within 365 days. AKI duration of 3 to 6 days was significantly associated with 30-day readmission or death (adjusted odds ratio, 1.82%; 95% confidence interval, 1.08-3.05). Patients with AKI duration ≥ 7 days had increased odds of readmission or death at both 30 days (adjusted odds ratio, 2.49%; 95% confidence interval, 1.15-5.43) and 365 days (adjusted odds ratio, 3.67%; 95% confidence interval, 1.73-7.79). Urinary biomarkers had no association with readmission and death. AKI duration ≥ 3 days, and not kidney biomarkers, was strongly associated with readmission or death. These clinical outcomes are potentially due to cardiovascular or hemodynamic causes rather than intrinsic injury to the kidney parenchyma.

Age and Crime in South Korea: Cross-National Challenge to Invariance Thesis

By using US and Western databases, Hirschi and Gottfredson (HG) projected that the age distribution of crime always and everywhere has (a) a spiked adolescent peak and (b) a continuous decline thereafter into old age. In the study described here, we investigated these two core postulates of the age-crime invariance thesis by comparing age-crime distributions in South Korea (SK) with the inverted J-shaped norm proposed by HG. Our analysis considered age-crime schedules for a number of offense types (e.g. homicide) and indexes (e.g. total, violent, and property) and across a variety of measures or statistical tests. The findings revealed considerable divergence in South Korea’s age-crime patterns compared with the HG invariance norm. Instead, SK age-crime patterns parallel those for Taiwan (also a collectivist Asian country) as reported recently by Steffensmeier and colleagues (2017). Implications for research and theory on the age-crime relation more broadly are discussed.

Cost-effectiveness of adult pneumococcal vaccination policies in underserved minorities aged 50–64 years compared to the US general population

BackgroundChanging pneumococcal disease epidemiology due to childhood vaccination has prompted re-examination of US adult pneumococcal vaccination policies, as have considerations of greater pneumococcal disease incidence and higher prevalence of conditions that increase risk in underserved minority populations. Prior analyses suggest routine pneumococcal vaccination at age 50 could be considered, which could disproportionately benefit underserved populations. MethodsA Markov cohort model estimated the cost-effectiveness of US pneumococcal vaccination policies in hypothetical 50-year-old underserved minority and general population cohorts. Strategies included receiving one or both available pneumococcal vaccines based on age- or chronic condition-specific criteria. US databases and medical literature data calibrated pneumococcal illness incidence, vaccine serotype distributions, age- and race-specific chronic condition distributions, and costs. Black population data were used as a proxy for underserved minorities. We took a US healthcare perspective, discounting at 3%/year. One-way and probabilistic sensitivity analyses were performed and scenarios modeling differing vaccine assumptions were examined. ResultsIn both black and general population 50-year-olds, giving both pneumococcal vaccines to all 50-year-olds prevented the most disease, but cost >$250,000 per quality adjusted life year (QALY) gained. Current CDC recommendations (both vaccines for the immunocompromised, polysaccharide vaccine for other high-risk conditions) were economically favorable in either population when analyses assumed polysaccharide vaccine was ineffective against nonbacteremic pneumococcal pneumonia (NBP). If polysaccharide vaccine is effective against NBP or if less complex age-based vaccination recommendations result in increased vaccine uptake, giving polysaccharide vaccine to all 50-year-olds cost <$100,000/QALY; this effect was more pronounced in black cohorts. Results were robust in 1-way and probabilistic sensitivity analyses. ConclusionsDespite changes in pneumococcal epidemiology, current CDC recommendations were favored in underserved minority and general population cohorts. Polysaccharide vaccine for all 50-year-olds could be considered under some vaccine uptake and effectiveness assumptions, particularly if mitigating racial health disparities in pneumococcal disease is a priority.

The current status of clinical trials in emergency gastrointestinal surgery: A systematic analysis of contemporary clinical trials.

Emergency gastrointestinal surgery (EGS) conditions represent a significant healthcare burden globally requiring emergency operations that are associated with mortality rates as high as 80%. EGS is currently focused on quality improvement and internal audits, which occurs at a national or local level. An appreciation of what EGS trials are being conducted is important to reduce research wastage and develop coordinated research strategies in surgery. The primary aim of this study was to identify and quantify recent and active trials in EGS. The secondary aim was to identify conditions of interest and which aspects of care were being modified. A systematic search of WHO, UK, US, Australian, and Canadian trials databases was undertaken using broad terms to identify studies addressing emergency abdominal surgery and specific high-risk diagnoses. Studies registered between 2013 and 2018 were eligible for inclusion. Data on study topic, design, and funding body were collected. Interventions were classified into "perioperative", "procedural", "postoperative", "non-surgical", and "other" categories. Searches identified 5603 registered trials. After removal of duplicates, 4492 studies remained and 42 were eligible for inclusion. Almost 50% of trials were located in Europe and 17% (n = 7) in the United States. The most common condition addressed was acute appendicitis (n = 11), with the most common intervention being procedure based (n = 23). Hospital-based funding was the most common funder (n = 30). There is large disparity in the number of surgical trials in emergency surgery, which are primarily focused on high-volume conditions. More research is needed into high-mortality conditions. Systematic review, level III.

Geographic Disparities in the Incidence of Stroke among Patients with Atrial Fibrillation in the United States

Aim: To determine whether regional variation in stroke incidence exists among individuals with AF. Methods: Using healthcare utilization claims from 2 large US databases, MarketScan (2007-2014) and Optum Clinformatics (2009-2015), and the 2010 US population as the standard, we estimated age-, sex-, race- (only in Optum) standardized stroke incidence rates by the 9 US census divisions. We also used Poisson regression to examine incidence rate ratios (IRR) of stroke and the probability of anticoagulation prescription fills across divisions. Results: Both databases combined included 970,683 patients with AF who experienced 15,543 strokes, with a mean follow-up of 23 months. In MarketScan, the age- and sex-standardized stroke incidence rate was highest in the Middle Atlantic and East South Central divisions at 3.8/1000 person-years (PY) and lowest in the West North Central at 3.2/1000 PY. The IRR of stroke and the probability of anticoagulation fills were similar across divisions. In Optum Clinformatics, the age-, sex-, and race-standardized stroke incidence rate was highest in the East North Central division at 5.0/1000 PY and lowest in the New England division at 3.3/1000 PY. IRR of stroke and the probability of anticoagulation fills differed across divisions when compared to New England. Conclusions: These findings suggest regional differences in stroke incidence among AF patients follow a pattern that differs from the hypothesized trend found in the general population and that other factors may be responsible for this new pattern. Cross-database differences provide a cautionary tale for the identification of regional variation using health claims data.