Interaction of Depot Medroxyprogesterone Acetate and Tenofovir Disoproxil Fumarate/Emtricitabine on Peripheral Blood Mononuclear Cells and Cervical Tissue Susceptibility to HIV Infection and Pharmacokinetics.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics. METHODS: Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4- and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIV BaL ), endocrine, immune cell phenotyping, and renal function. RESULTS: Compared with baseline, F/TDF (± DMPA) significantly decreased both %R5- and X4-infected CD4 T cells and F/TDF + DMPA decreased cervical explant p24 (all P < 0.05). The %R5- and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions. CONCLUSIONS: F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.

Effects of Maryland's Affordable Care Act Medicaid Health Home Waiver on Quality of Cardiovascular Care Among People with Serious Mental Illness.

BACKGROUND: Nineteen US states and D.C. have used the Affordable Care Act Medicaid health home waiver to create behavioral health home (BHH) programs for Medicaid beneficiaries with serious mental illness (SMI). BHH programs integrate physical healthcare management and coordination into specialty mental health programs. No studies have evaluated the effects of a BHH program created through the Affordable Care Act waiver on cardiovascular care quality among people with SMI. OBJECTIVE: To study the effects of Maryland's Medicaid health home waiver BHH program, implemented October 1, 2013, on quality of cardiovascular care among individuals with SMI. DESIGN: Retrospective cohort analysis using Maryland Medicaid administrative claims data from July 1, 2010, to September 30, 2016. We used marginal structural modeling with inverse probability of treatment weighting to account for censoring and potential time-dependent confounding. PARTICIPANTS: Maryland Medicaid beneficiaries with diabetes or cardiovascular disease (CVD) participating in psychiatric rehabilitation programs, the setting in which BHHs were implemented. To qualify for psychiatric rehabilitation programs, individuals must have SMI. The analytic sample included BHH and non-BHH participants, N = 2605 with diabetes and N = 1899 with CVD. MAIN MEASURES: Healthcare Effectiveness Data and Information Set (HEDIS) measures of cardiovascular care quality including annual receipt of diabetic eye and foot exams; HbA1c, diabetic nephropathy, and cholesterol testing; and statin therapy receipt and adherence among individuals with diabetes, as well as HEDIS measures of annual receipt of cholesterol testing and statin therapy and adherence among individuals with CVD. KEY RESULTS: Relative to non-enrollment, enrollment in Maryland's BHH program was associated with increased likelihood of eye exam receipt among individuals with SMI and co-morbid diabetes, but no changes in other care quality measures. CONCLUSIONS: Additional financing, infrastructure, and implementation supports may be needed to realize the full potential of Maryland's BHH to improve cardiovascular care for people with SMI.

Computer-aided stenosis detection at coronary CT angiography: effect on performance of readers with different experience levels.

OBJECTIVES: To evaluate the effect of a computer-aided detection (CAD) algorithm for coronary CT angiography (cCTA) on the performance of readers with different experience levels. METHODS: We studied 50 patients (18 women, 58 ± 11 years) who had undergone cCTA and quantitative coronary angiography (QCA). Eight observers with varying experience levels evaluated all studies for ≥50 % coronary artery stenosis. After 3 months, the same observers re-evaluated all studies, this time guided by a CAD system. Their performance with and without the CAD system (sensitivity, specificity, positive predictive value and negative predictive value) was assessed using the Likelihood Ratio Χ(2) test both at the per-patient and per-vessel levels. RESULTS: The sensitivity of the CAD system alone for stenosis detection was 71 % per-vessel and 100 % per-patient. There were 54 false positive (FP) findings within 199 analyzed vessels, most of them associated with non-obstructive (<50 %) lesions. With CAD, one (out of three, 33 %) inexperienced reader's per-patient sensitivity and negative predictive value significantly improved from 79 % to 100 % (P = 0.046) and from 90 % to 100 % (P = 0.034), respectively. Other readers' performance indices showed no statistically significant change. CONCLUSIONS: Our results suggest that CAD can improve some inexperienced readers' sensitivity for diagnosing coronary artery stenosis at cCTA.

Adenosine-stress dynamic myocardial volume perfusion imaging with second generation dual-source computed tomography: Concepts and first experiences.

Recent research suggests that multidetector-row CT may have potential as a standalone modality for integrative imaging of coronary heart disease, including the assessment of the myocardial blood supply. However, the technical prerequisites for volumetric, time-resolved imaging of the passage of a contrast medium bolus through the myocardium have only been met with latest generation wide-detector CT scanners. Second-generation dual-source CT enables performing electrocardiographic (ECG)-synchronized dynamic myocardial perfusion imaging by a dedicated "shuttle" mode. With this acquisition mode, image data can be acquired during contrast medium infusion at 2 alternating table positions with the table shuttling back and forth between the 2 positions covering a 73-mm anatomic volume. We applied this acquisition technique for detecting differences in perfusion patterns between healthy and diseased myocardium and for quantifying myocardial blood flow under adenosine stress in 3 patients with coronary heart disease. According to our initial experience, the addition of adenosine stress volumetric dynamic CT perfusion to a cardiac CT protocol comprising coronary artery calcium quantification, prospectively ECG-triggered coronary CT angiography, and delayed acquisition appears promising for the comprehensive assessment of coronary artery luminal integrity, cardiac function, perfusion, and viability with a single modality.

Adenosine-stress dynamic myocardial CT perfusion imaging: initial clinical experience.

OBJECTIVE: To evaluate the feasibility of adenosine-stress dynamic myocardial volume perfusion imaging with second generation dual source computed tomography (CT) for the qualitative and quantitative assessment of myocardial blood flow (MBF) compared with stress perfusion and viability magnetic resonance imaging (MRI). MATERIAL AND METHODS: Ten patients (8 male, 2 female, mean age 62.7 +/- 7.1 years) underwent stress/rest perfusion and delayed-enhancement MRI, and a cardiac CT protocol comprising prospectively electrocardiogram -triggered coronary CT angiography, dynamic adenosine-stress myocardial perfusion imaging using a "shuttle" mode, and delayed enhancement acquisitions. Two independent observers visually assessed myocardial perfusion defects. For semi-quantitative evaluation, CT- and MRI-derived myocardial-to-left ventricular upslope indices were compared. Additionally, absolute MBF was quantified based on dynamic perfusion CT and correlated with semi quantitative CT measurements. Myocardial perfusion analysis was performed on a segmental basis. Analysis used paired t tests, Wilcoxon signed-rank test, linear correlation, and Bland-Altman statistics. RESULTS: A total of 149 segments (93.1%) were suitable for analysis. Sensitivity, specificity, positive and negative predictive values for detection of myocardial perfusion defects at CT compared with MRI were 86.1%, 98.2%, 93.9%, and 95.7%, respectively. Semiquantitative analysis of CT data showed significant differences between ischemic and nonischemic myocardium with a signal intensity upslope that was comparable with MRI-derived values (CT: 5.2 +/- 2 SI/s, MRI: 4.8 +/- 2.3 SI/s, P > 0.05). Moderate correlation was observed between absolute CT quantification of MBF and semi-quantitative CT measurements. Mean total dose length product for the entire cardiac CT protocol was 1290.4 +/- 233.3 mGy cm. CONCLUSION: Adenosine-stress volumetric first pass CT perfusion imaging is feasible and may enable the evaluation of qualitative and semi quantitative parameters of myocardial perfusion in a comparable fashion as MRI.

Diminished benefits of drug-eluting stents versus bare metal stents in patients with severe renal insufficiency.

BACKGROUND: Since their introduction, the use of drug-eluting stents (DES) has increasingly become standard practice due to their decreased rates of in-stent restenosis and target lesion revascularization (TLR) rates in comparison to bare metal stents (BMS). However, these benefits have not been reproduced in patients with severe renal disease (SRD). This study compared TLR rates in patients with severe renal insufficiency treated with DES vs. BMS. METHODS: Between 2003 and 2006, we collected data on 6,220 consecutive patients receiving either DES or BMS. Both groups were similar in angiographic and clinical variables. TLR rates at 270 days and 1 year were then compared between patients receiving DES or BMS with varying creatinine clearance (CrCl). RESULTS: At 1 year after PCI, TLR rates were significantly lower for DES in patients with CrCl >60 (5 vs. 9.3%; p < 0.0001). However, in patients with CrCl <40 ml/min or on dialysis there was no significant difference in TLR rates for DES vs. BMS. CONCLUSION: While DES showed improved clinical outcomes in patients with normal and mildly impaired renal function, they showed no benefit over BMS in patients with moderate to severe renal insufficiency. Coupled with the possibly increased risk of late stent thrombosis with DES, BMS may be a more appropriate and safer stent in this population.

Confidence intervals for the population mean tailored to small sample sizes, with applications to survey sampling.

The validity of standard confidence intervals constructed in survey sampling is based on the central limit theorem. For small sample sizes, the central limit theorem may give a poor approximation, resulting in confidence intervals that are misleading. We discuss this issue and propose methods for constructing confidence intervals for the population mean tailored to small sample sizes. We present a simple approach for constructing confidence intervals for the population mean based on tail bounds for the sample mean that are correct for all sample sizes. Bernstein's inequality provides one such tail bound. The resulting confidence intervals have guaranteed coverage probability under much weaker assumptions than are required for standard methods. A drawback of this approach, as we show, is that these confidence intervals are often quite wide. In response to this, we present a method for constructing much narrower confidence intervals, which are better suited for practical applications, and that are still more robust than confidence intervals based on standard methods, when dealing with small sample sizes. We show how to extend our approaches to much more general estimation problems than estimating the sample mean. We describe how these methods can be used to obtain more reliable confidence intervals in survey sampling. As a concrete example, we construct confidence intervals using our methods for the number of violent deaths between March 2003 and July 2006 in Iraq, based on data from the study "Mortality after the 2003 invasion of Iraq: A cross sectional cluster sample survey," by Burnham et al. (2006).