Background It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of Left ventricular hypertrophy (LVH) in patients with hypertension, and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population. Methods This analysis included 8,164 participants (mean age 67.9 years, 35.3% women, 31.2% blacks) with hypertension but no diabetes from the Systolic Blood Pressure Intervention (SPRINT) Trial; 4,086 randomly assigned to intensive BP lowering (target systolic BP<120mmHg) and 4,078 assigned to standard BP lowering (target systolic BP <140mmHg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead electrocardiograms recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (vs. standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjusting for LVH as a time-varying covariate. Results Among SPRINT participants without baseline LVH (n=7,559), intensive (vs. standard) BP lowering was associated with a 46% lower risk of developing LVH (HR=0.54, 95%CI: 0.43 to 0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (vs. standard) BP lowering were 66% more likely to regress/improve their LVH (HR=1.66, 95%CI: 1.31 to 2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (HR (95%CI) of intensive vs. standard BP lowering on CVD: 0.76(0.64,0.90) and 0.77(0.65,0.91) before and after adjusting for LVH as a time-varying covariate, respectively). Conclusions Among patients with hypertension but no diabetes, intensive BP lowering (target systolic BP<120 mmHg), compared with standard BP lowering (target systolic BP<140 mmHg), resulted in lower rates of developing new LVH in those without LVH, and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial.

Background The notion of anytime, anyplace communication is characteristic of the current generation of learners. Such communications have facilitated the growth and integration of a blended or hybrid learning platform in multiple educational settings. However, there are limited reports on the use of an anytime, anyplace communication platform in clinical inpatient medical education. Objective The setting of a high-demand inpatient clinical rotation is ideal for the use of collaborative software, and this integration is expected to positively influence medical education. The purpose of this study is to evaluate medical students’ and residents’ educational experiences with incorporating a simple, web-based content management and file sharing platform into an internal medicine inpatient rotation. Methods During an inpatient internal medicine rotation, faculty and learners jointly used collaborative software for educational purposes, and a postrotation survey tool was used to measure the educational influence of the software. Results Based on the results of the postrotation survey, the integration of a collaborative software application during clinical rotations improved the learning experience. Learning climate, the communication of rotation goals, and self-directed learning all scored favorably, but feedback from the survey participants was mixed. The learners enthusiastically accepted the practical use of this tool for both communication and information sharing. Conclusions This generation of learners is accustomed to frequent electronic communication. Based on our survey, these learners appear to be highly receptive to this web-based intervention design for improving clinical education during active patient care. Adding effective blended learning features to a traditional clinical setting is achievable.

Introduction The effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown. Aim To examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension. Methods We performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of &lt;120 mmHg) or a standard treatment group (SBP goal of &lt;140 mmHg). Main Outcome Measure The main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years. Results At baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction = 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference = 0.67; 95% CI = 0.03, 1.32; P = 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference = −1.17; 95% CI = −1.92, −0.41; P = 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P &gt; 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P = 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P = 0.53) and was without interaction by race-ethnicity. Clinical Implications The effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude. Strength & Limitations Although this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed. Conclusion In a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude.

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6-Mercaptopurine (MP) has been part of the backbone of ALL treatment for more than 50 years. Hepatic enzymes metabolize MP into two major intracellular metabolites, thioguanine nucleotides (TGN) and methylated mercaptopurines (mMP), which have been shown to be cytotoxic in vitro. The short plasma half-life and S-phase dependent pharmacokinetics of MP suggest that a biologically active concentration and longer exposure to MP may be important for maximum cell kill. We hypothesized that dividing the traditional once-daily (qd) MP dose into a twice-daily (bid) dose might produce higher levels of active MP metabolites and increase cell kill. In Pediatric Oncology Group (POG) protocol 9605, 1088 patients with standard risk ALL were randomized to qd or bid dosing. A subset of 242 patients in the continuation phase of the study had steady state red blood cell TGN and mMP levels measured as surrogates for levels in leukemic cells. 16 of these patients were ineligible because either the sample was unsatisfactory (2/16) or timing was unknown (4/16) or incorrect (10/16). 118/226 received MP 75 mg/m2 qd and 108/226 received MP 37.5 mg/m2 bid. Statistical inferences were made with univariate analysis of variance (ANOVA) with two sided P-values. The mean mMP concentration in the qd group was 691 ng/8×108 RBC greater than the bid group (P<.001) and the mean TGN concentration was 7.5 ng/8×108 RBC greater (P=.078) [Table 1]. Despite lower metabolite levels the bid dosing group trended towards a better patient outcome. Patients on bid dosing had a decrease of 5.7% in patient death rate (P=.067) and a decrease of 8.5% in patient bone marrow relapse (P=.063) [Table 1]. Analysis of the total POG 9605 patient population will be necessary to determine if these trends will become statistically significant. Patients on bid dosing had a slight increase of 3.4% in reported cases of toxicity* (P=.309) and only 0.13% more reported missed doses (P=.842). Table 1. Metabolite and Outcome Data (TGN and mMP measured in ng/8×108 RBC) Group N Mean TGN (SD) Mean mMP (SD) Death Rate (SD) BM Relapse Rate (SD) % Missed Doses (SD) *Toxic events were defined as a 3–4 on the NIH toxicity scale qd 118 47.54 (35) 2277.89 (1559) 8.5% (.280) 17.8% (.384) 4.38% (.055) bid 108 40.09 (27) 1586.58 (1240) 2.8% (.165) 9.3% (.291) 4.51% (.040) P-value 0.078 <.001 0.067 0.063 0.842 The patients were also examined according to the recommended MP metabolite levels used by current diagnostic laboratories which are based on an inflammatory bowl disease patient population. The patients within the recommended TGN range, 230–400 pmol/8×108 RBC (39–66 ng/8×108 RBC), did not show a statistically significant increase in outcome with a 2.89% decrease in bone marrow relapse (P=.545) and a 3.47% decrease in death rate (P=.281) compared to those outside the recommended range. In conclusion, bid MP dosing did not produce the expected elevation of metabolites but did produce a trend toward improvement in clinical outcome.