Trends in Antihypertensive Medication Discontinuation and Low Adherence Among Medicare Beneficiaries Initiating Treatment From 2007 to 2012

Low antihypertensive medication adherence is common. During recent years, the impact of low medication adherence on increased morbidity and healthcare costs has become more recognized, leading to interventions aimed at improving adherence. We analyzed a 5% sample of Medicare beneficiaries initiating antihypertensive medication between 2007 and 2012 to assess whether reductions occurred in discontinuation and low adherence. Discontinuation was defined as having no days of antihypertensive medication supply for the final 90 days of the 365 days after initiation. Low adherence was defined as having a proportion of days covered <80% during the 365 days after initiation among beneficiaries who did not discontinue treatment. Between 2007 and 2012, 41 135 Medicare beneficiaries in the 5% sample initiated antihypertensive medication. Discontinuation was stable during the study period (21.0% in 2007 and 21.3% in 2012; P-trend=0.451). Low adherence decreased from 37.4% in 2007 to 31.7% in 2012 (P-trend<0.001). After multivariable adjustment, the relative risk of low adherence for beneficiaries initiating treatment in 2012 versus in 2007 was 0.88 (95% confidence interval, 0.83-0.92). Low adherence was more common among racial/ethnic minorities, beneficiaries with Medicaid buy-in (an indicator of low income), and those with polypharmacy, and was less common among females, beneficiaries initiating antihypertensive medication with multiple classes or a 90-day prescription fill, with dementia, a history of stroke, and those who reached the Medicare Part D coverage gap in the previous year. In conclusion, low adherence to antihypertensive medication has decreased among Medicare beneficiaries; however, rates of discontinuation and low adherence remain high

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey)

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal ofmellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, \u3e1 g proteinuria, heart failure, estimated glomerular filtration ratemL·min RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events

Remembrances of Steve Ellmann, Still Present

In Memoriam: Steven Ellman

Rare Coding Variants in RCN3 Are Associated with Blood Pressure

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. RESULTS: Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10− 7). CONCLUSIONS: Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits

Response to PCV13 vaccination in patients with multiple myeloma versus healthy controls

Infections are a major cause of morbidity and mortality in individuals with multiple myeloma (MM). These individuals exhibit humoral dysfunction and show a suboptimal response to pneumococcal polysaccharide vaccine (PPV23). Since pneumococcal conjugate vaccine (PCV13) elicits a T cell dependent response, it is recommended in patients with multiple myeloma. This study compares the initial response to PCV13 and durability of the response at 6 months in patients with multiple myeloma versus normal controls. Seven patients with multiple myeloma and 18 control patients were enrolled in the study. Streptococcal pneumonia serotype IgG titers were drawn at baseline, day 30, and day 180 after MM patients and controls received PCV13. Although vaccination with PCV13 produced a similar initial response in patients with multiple myeloma compared to control subjects, the duration of response may have waned in patients with multiple myeloma as compared to control subjects

Screening for humoral immunodeficiency in patients with community-acquired pneumonia

BACKGROUND: Immunodeficiency is an underrecognized risk factor for infections, such as community-acquired pneumonia (CAP). OBJECTIVE: We evaluated patients admitted with CAP for humoral immunodeficiency. DESIGN: Prospective cohort study SETTING: Inpatients PATIENTS, INTERVENTION, AND MEASUREMENTS: We enrolled 100 consecutive patients admitted with a diagnosis of CAP from February 2017 to April 2017. Serum IgG, IgM, IgA, and IgE levels were obtained within the first 24 hours of admission. CURB-65 score and length of hospital stay were calculated. The Wilcoxon rank-sum test, Kruskal-Wallis test, and simple linear regression analysis were used in data analysis. RESULTS: The prevalence of hypogammaglobinemia in patients with CAP was 38% (95% CI: 28.47% to 48.25%). Twenty-seven of 100 patients had IgG hypogammaglobinemia (median: 598 mg/dL, IQ range: 459-654), 23 of 100 had IgM hypogammaglobinemia (median: 38 mg/dL, IQ range: 25-43), and 6 of 100 had IgA hypogammaglobinemia (median: 36 mg/dL, IQ range: 18-50). The median hospital length of stay for patients with IgG hypogammaglobinemia was significantly higher when compared to patients with normal IgG levels (five days, IQ range [3-10] vs three days, IQ range [2-5], P = .0085). Fourteen patients underwent further immune evaluation, resulting in one diagnosis of multiple myeloma, three patients diagnosed with specific antibody deficiency, and one patient diagnosed with selective IgA deficiency. CONCLUSION: There is a high prevalence of hypogammaglobinemia in patients hospitalized with CAP, with IgG and IgM being the most commonly affected classes. IgG hypogammaglobinemia was associated with an increased length of hospitalization. Screening immunoglobulin levels in CAP patients may also uncover underlying humoral immunodeficiency or immuno-proliferative disorders

A framework for cost based optimization of hybrid CPU/GPU query plans in database systems

Current database research identified the use of computational power of GPUs as a way to increase the performance of database systems. As GPU algorithms are not necessarily faster than their CPU counterparts, it is important to use the GPU only if it is beneficial for query processing. In a general database context, only few research projects address hybrid query processing, i.e., using a mix of CPU- and GPU-based processing to achieve optimal performance. In this paper, we extend our CPU/GPU scheduling framework to support hybrid query processing in database systems. We point out fundamental problems and propose an algorithm to create a hybrid query plan for a query using our scheduling framework. Additionally, we provide cost metrics, accounting for the possible overlapping of data transfers and computation on the GPU. Furthermore, we present algorithms to create hybrid query plans for query sequences and query trees

Pharmacokinetics of Vancomycin in Critically Ill Patients Undergoing Sustained Low-Efficiency Dialysis

Introduction : Vancomycin pharmacokinetic data in critically ill patients receiving sustained low-efficiency dialysis (SLED) is limited. Published data using vancomycin with intermittent hemodialysis and continuous renal replacement therapy may not be applicable to hybrid dialysis modalities such as SLED. Current drug references lack recommendations for vancomycin dosing in patients receiving SLED. Objective : The objective of this study was to determine vancomycin pharmacokinetics during SLED. Methods : A total of 20 patients who were critically ill with oliguric or anuric renal failure who received vancomycin and SLED were included in the study. Surrounding one SLED session, serum vancomycin blood samples were drawn before the initiation of SLED, at the termination of SLED, and 4 hours after completion of SLED treatment. Following this, patients received vancomycin, dosed to target a goal peak of 20–30 mcg/ml. A vancomycin peak level was drawn 1 hour after the end of the infusion. SLED treatment duration was at least 7 hours. Continuous data are reported as median (interquartile range) and categorical data as percentage. Results : The vancomycin elimination rate and half-life were 0.051 hours (0.042–0.074 hours) and 13.6 hours (9.4–16.6 hours), respectively. SLED reduced vancomycin serum concentrations by 35.4% (31.5–43.8%), and vancomycin rebound was 9.8% (2.5–13.7%). The vancomycin dose administered post-SLED was 1000 mg (875–1125 mg). For 18 patients, the patient-specific volume of distribution was 0.88 L/kg (0.67–1.1 L/kg), vancomycin clearance was 3.5 L/hr (2.2–5.2 L/hr), and the area under the concentration-time curve during the study time period was 280.8 mg·hr/L (254.7–297.3 mg·hr/L). Conclusion : Vancomycin is significantly removed during SLED with little rebound in serum concentrations 4 hours after completion of SLED. Based on study findings, patients who are critically ill require additional vancomycin dosing after each SLED session to maintain therapeutic post-SLED vancomycin concentrations. Therapeutic drug monitoring of vancomycin is recommended during SLED