A space for learning: An analysis of research on active learning spaces.

Active Learning Classrooms (ALCs) are learning spaces specially designed to optimize the practice of active learning and amplify its positive effects in learners from young children through university-level learners. As interest in and adoption of ALCs has increased rapidly over the last decade, the need for grounded research in their effects on learners and schools has grown proportionately. In this paper, we review the peer-reviewed published research on ALCs, dating back to the introduction of "studio" classrooms and the SCALE-UP program up to the present day. We investigate the literature and summarize findings on the effects of ALCs on learning outcomes, student engagement, and the behaviors and practices of instructors as well as the specific elements of ALC design that seem to contribute the most to these effects. We also look at the emerging cultural impact of ALCs on institutions of learning, and we examine the drawbacks of the published research as well as avenues for potential future research in this area.

Genome-wide association analysis of common genetic variants of resistant hypertension.

Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10-4 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES). A genetic risk score for RHTN was created by summing the risk alleles of replicated RHTN signals. rs11749255 in MSX2 was associated with RHTN in INVEST (odds ratio (OR) (95% CI) = 1.50 (1.2-1.8), p = 7.3 × 10-5) and replicated in SPS3 (OR = 2.0 (1.4-2.8), p = 4.3 × 10-5), with genome-wide significance in meta-analysis (OR = 1.60 (1.3-1.9), p = 3.8 × 10-8). Other replicated signals were in IFLTD1 and PTPRD. IFLTD1 rs6487504 was associated with RHTN in INVEST (OR = 1.90 (1.4-2.5), p = 1.1 × 10-5) and SPS3 (OR = 1.70 (1.2-2.5), p = 4 × 10-3). PTPRD rs324498, a previously reported RHTN signal, was among the top signals in INVEST (OR = 1.60 (1.3-2.0), p = 3.4 × 10-5) and replicated in SPS3 (OR = 1.60 (1.1-2.4), one-sided p = 0.005). Participants with the highest number of risk alleles were at increased risk of RHTN compared to participants with a lower number (p-trend = 1.8 × 10-15). Overall, we identified and replicated associations with RHTN in the MSX2, IFLTD1, and PTPRD regions, and combined these associations to create a genetic risk score.

Biopsy of CT-Occult Bone Lesions Using Anatomic Landmarks for CT Guidance.

OBJECTIVE: The purpose of this study is to evaluate the histopathologic diagnostic yield, sample size, procedural time, and dose-length product (DLP) for the biopsy of CT-occult lesions found at MRI or PET or both. MATERIALS AND METHODS: A retrospective review of our radiology information system for biopsies of CT-occult lesions using CT guidance from January 1, 2010, through December 31, 2014, was performed and compared with a selection of CT-guided biopsies of CT-evident bone lesions during the same period. The data were then evaluated for diagnostic yield of histopathologic diagnosis, procedural time, use of sedation medication, DLP, and size of specimens obtained. RESULTS: A total of 30 CT-occult biopsies met the inclusion criteria. Twenty-seven of those biopsies had results that were concordant with the patient's primary histopathologic diagnosis, imaging findings, and clinical course. In the CT-evident lesion group, concordant histopathologic abnormalities were identified in 27 of 30 patients. There was a statistically significant increase in number of samples obtained for the CT-evident lesions compared with CT-occult lesions. There was no statistically significant difference in total specimen length, DLP, number of CT scans, procedural time, or use of sedation medication between the CT-occult and CT-evident biopsy groups. CONCLUSION: Biopsy of CT-occult lesions using anatomic landmarks achieves diagnostic yields similar to those for CT-guided biopsy of CT-evident lesions.

Pharmacogenetic Associations of ß1-Adrenergic Receptor Polymorphisms With Cardiovascular Outcomes in the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes).

BACKGROUND AND PURPOSE: Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and ß-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by ß-blocker treatment in patients with a history of stroke. METHODS: Nine hundred and twenty-six participants of the SPS3 trial's (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan-Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41 475 individuals of European and African ancestry in the NINDS (National Institute of Neurological Disorders and Stroke) SiGN (Stroke Genetics Network). RESULTS: MACE was higher in carriers of the Gly49 allele than in those with the Ser49Ser genotype (10.5% versus 5.4%, log-rank P=0.005). Gly49 carrier status was associated with MACE (hazard ratio, 1.62; 95% confidence interval, 1.00-2.68) and ischemic stroke (hazard ratio, 1.81; 95% confidence interval, 1.01-3.23) in SPS3 and with small artery ischemic stroke (odds ratio, 1.14; 95% confidence interval, 1.03-1.26) in SiGN. In SPS3, ß-blocker-treated Gly49 carriers had increased MACE versus non-ß-blocker-treated individuals and noncarriers (hazard ratio, 2.03; 95% confidence interval, 1.20-3.45). No associations were observed with the Arg389Gly polymorphism. CONCLUSION: Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among ß-blocker-treated individuals. Further research is needed to define ß-blocker benefit among ischemic stroke patients by ADRB1 genotype. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

CYP2C19 metabolizer status and clopidogrel efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) study.

BACKGROUND: The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel. METHODS AND RESULTS: CYP2C19*2 and CYP2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding. CONCLUSIONS: There were significant differences in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and warrant replication. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00059306.

Can blood pressure be lowered safely in older adults with lacunar stroke? The Secondary Prevention of Small Subcortical Strokes study experience.

OBJECTIVES: To determine safety and tolerability of lowering blood pressure in older adults with lacunar stroke. DESIGN: Cohort study. SETTING: The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy of two systolic blood pressure (SBP) targets (<130 mmHg and 130-149 mmHg) for secondary stroke prevention. PARTICIPANTS: Of 3,020 SPS3 participants, 494 aged 75 and older at baseline were used in these analyses. MEASUREMENTS: Rates of side effects related to lowering SBP and clinical outcomes, including stroke recurrence and vascular death, were examined. RESULTS: Older participants achieved SBP levels similar to those of younger participants (mean SBP of 125 mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least once during the approximately 3.5 years of follow-up, 21% reported dizziness, and 15% reported lightheadedness when standing; the only significant difference between the younger and older groups was unsteadiness when standing (23% vs 32% respectively, P < .001). There was no difference according to treatment group. In younger adults, recurrent stroke was less likely in the lower than the higher SBP group (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.59-1.01) but not in older participants (HR = 1.01, 95% CI = 0.59-1.73), although the interaction was not significant (P = .39). The lower SBP target was associated with a significant reduction in vascular death in older participants (HR = 0.42, 95% CI = 0.18-0.98), with a significant interaction between age and SBP group (P = .049). CONCLUSION: Except for unsteadiness when standing, there was no difference according to age in individuals with lacunar stroke with respect to side effects potentially related to lowering blood pressure. Although the lower SBP target was not associated with lower likelihood of recurrent stroke, these exploratory analyses suggested a possible benefit related to vascular death.

Recurrence of prostate cancer in patients receiving testosterone supplementation for hypogonadism.

PURPOSE: The relationship between recurrent prostate cancer risk and testosterone replacement therapy (TRT) for hypogonadal men is explored. SUMMARY: The medical literature was searched to identify articles evaluating the use of TRT in symptomatic hypogonadal men with a history of prostate cancer. Eight English-language articles investigating TRT use in hypogonadal men with a history of prostate cancer were analyzed. For evaluative purposes, the normal ranges used for prostate-specific antigen (PSA) and total testosterone levels were less than 4.0 ng/mL and 300-1000 ng/dL, respectively. Most trials were small and involved patients with localized prostate cancer treated with radical prostatectomy or radiotherapy, though patients with metastatic disease or a Gleason score of ≥8 were included in a few studies. TRT was administered in a variety of dosages and dosage forms for up to nine years to manage hypogonadal symptoms. Testosterone concentrations increased, as expected, after TRT, but serum PSA levels remained below 0.1 ng/mL in the majority of patients. PSA levels were found to increase in select patients with high-risk and metastatic disease, but these elevations were not accompanied by disease progression. These studies have suggested a potential benefit for TRT use in select symptomatic hypogonadal men with a history of prostate cancer. Data were limited, however, by the retrospective nature of most studies, the lack of control groups, small sample sizes, and short follow-up periods. CONCLUSION: There is insufficient evidence to withhold TRT in certain populations of men with a history of prostate cancer.

Achieved blood pressures in the secondary prevention of small subcortical strokes (SPS3) study: challenges and lessons learned.

BACKGROUND: Lowering blood pressure (BP) after stroke remains a challenge, even in the context of clinical trials. The Secondary Prevention of Small Subcortical Strokes (SPS3) BP protocol, BP management during the study, and achieved BPs are described here. METHODS: Patients with recent symptomatic lacunar stroke were randomized to 1 of 2 levels of systolic BP (SBP) targets: lower: <130mm Hg, or higher: 130-149mm Hg. SBP management over the course of the trial was examined by race/ethnicity and other baseline conditions. RESULTS: Mean SBP decreased for both groups from baseline to the last follow-up, from 142.4 to 126.7mm Hg for the lower SBP target group and from 143.6 to 137.4mm Hg for the higher SBP target group. At baseline, participants in both groups used an average of 1.7±1.2 antihypertensive medications, which increased to a mean of 2.4±1.4 (lower group) and 1.8±1.4 (higher group) by the end-study visit. It took an average of 6 months for patients to reach their SBP target, sustained to the last follow-up. Black participants had the highest proportion of SBP ≥150mm Hg at both study entry (40%) and end-study visit (17%), as compared with whites (9%) and Hispanics (11%). CONCLUSIONS: These results show that it is possible to safely lower BP even to a SBP goal <130mm Hg in a variety of patients and settings, including private and academic centers in multiple countries. This provides further support for protocol-driven care in lowering BP and consequently reducing the burden of stroke.

ASA failure: does the combination ASA/clopidogrel confer better long-term vascular protection?

OBJECTIVE: To assess whether adding clopidogrel to acetylsalicylic acid (ASA) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA. METHODS: Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort randomly allocated to aspirin (325 mg/day) and clopidogrel (75 mg/day) or placebo. Primary efficacy outcome was stroke recurrence (ischemic and intracranial hemorrhage) and main safety outcome was major extracranial hemorrhage. Patients were followed for a mean period of 3.5 years. RESULTS: The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non-ASA failure group (n = 2,151) in SPS3 (p = 0.03). Mean age was 65.6 years and 65% were men. The risk of recurrent stroke was not reduced in the dual antiplatelet group, 3.1% per year, compared to the aspirin-only group, 3.3% per year (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.61-1.37). There was also no difference between groups for ischemic stroke (HR 0.90; 95% CI 0.59-1.38). The risk of gastrointestinal bleeding was higher in the dual antiplatelet group (HR 2.7; 95% CI 1.1-6.9); however, the risk of intracranial hemorrhage was not different. CONCLUSIONS: In patients with a recent lacunar stroke while taking ASA, the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA, adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

BACKGROUND: Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. METHODS: Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. RESULTS: Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. CONCLUSIONS: In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.

Blood pressure after recent stroke: baseline findings from the secondary prevention of small subcortical strokes trial.

BACKGROUND: Hypertension is the most powerful risk factor for stroke. The aim of this study was to characterize baseline blood pressure in participants in the Secondary Prevention of Small Subcortical Strokes trial. METHODS: For this cross-sectional analysis, participants were categorized by baseline systolic blood pressure (SBP) < 120, 120-139, 140-159, 160-179, and ≥ 180 mm Hg and compared on demographic and clinical characteristics. Predictors of SBP < 140 mm Hg were examined. RESULTS: Mean SBP was 143±19 mm Hg while receiving an average of 1.7 antihypertensive medications; SBP ≥ 140 mm Hg for 53% and ≥ 160 mm Hg for 18% of the 3,020 participants. Higher SBP was associated with a history of hypertension and hypertension for longer duration (both P < 0.0001). Higher SBPs were associated with more extensive white matter disease on magnetic resonance imaging (P < 0.0001). There were significant differences in entry-level SBP when participants were categorized by race and region (both P < 0.0001). Black participants were more likely to have SBP ≥ 140 mm Hg. Multivariable logistic regression showed an independent effect for region with those from Canada more likely (odds ratio = 1.7; 95% confidence interval, 1.29, 2.32) to have SBP < 140 mm Hg compared with participants from United States. CONCLUSIONS: In this cohort with symptomatic lacunar stroke, more than half had uncontrolled hypertension at approximately 2.5 months after stroke. Regional, racial, and clinical differences should be considered to improve control and prevent recurrent stroke.

Antibacterials as adjuncts to incision and drainage for adults with purulent methicillin-resistant Staphylococcus aureus (MRSA) skin infections.

The annual incidence of skin and soft tissue infections (SSTIs) has nearly tripled in the US since the early 1990s. Many purulent SSTIs in the community setting are caused by methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (I&D) are indicated for most purulent MRSA infections; however, the use of adjunctive antibacterials is controversial. The objective of this study was to systematically evaluate studies that have investigated whether or not antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs. We included articles from MEDLINE and The Cochrane Library that fulfilled the following criteria: (i) original research; (ii) English language; (iii) compared I&D alone versus I&D plus antibacterials for purulent MRSA SSTIs; and (iv) compared patient outcomes. We also reviewed the references of these articles to identify other relevant studies. Studies that solely examined paediatric patients were excluded. To facilitate cross-study comparison, we systematically evaluated the following study characteristics: (i) study design; (ii) patient population; (iii) comparator groups; (iv) sample size; (v) outcome measures; (vi) outcome definitions; (vii) duration of follow-up; and (viii) measurement and adjustment of potential confounding variables. Eleven studies, spanning more than 30 years, met inclusion criteria. Two of these were conducted prior to the emergence of MRSA in the community; another evaluated cephalexin versus placebo for MRSA. None of these found added benefit of adjunctive antibacterials. Four studies compared health outcomes between patients who received 'active' or 'appropriate' therapy and those who received 'inactive' or 'inappropriate' therapy after I&D for purulent MRSA SSTIs. Two of these studies found 'active' or 'appropriate' therapy to be beneficial, while two others did not. Four studies compared health outcomes between patients who received anti-MRSA antibacterials plus I&D with those who received alternative antibacterials plus I&D for purulent MRSA SSTIs. Three of these reported improved outcomes with anti-MRSA antibacterials, while another reported mixed findings. Presently, the bulk of the available evidence suggests anti-MRSA antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs; however, the current evidence is limited to small, case-control, observational studies.

Proliferative myositis: expanding the differential diagnosis of a soft tissue mass in infancy.

Proliferative myositis, a pseudosarcomatous lesion of skeletal muscle, is quite rare in the pediatric population. While benign, it is not always recognized as such, and may be treated with an extensive resection that can result in permanent disfigurement. We report a case of an infant with the diagnosis of proliferative myositis, who to our knowledge is the youngest patient to be evaluated with magnetic resonance imaging (MRI). Although the MRI findings are non-specific, we highlight the importance of considering proliferative myositis in the differential diagnosis of a soft tissue mass, which ultimately might prevent an overly aggressive resection in a child.

The Hispanic Diabetes Management Program: Impact of community pharmacists on clinical outcomes.

OBJECTIVE: To assess the impact of community pharmacists on clinical outcomes in Hispanic patients with type 2 diabetes. METHODS: 126 patients were enrolled in this longitudinal pre/post cohort study that took place in nine community and four workplace pharmacies in San Antonio, TX. Pharmacists provided education, point-of-care testing for glycemic and metabolic parameters, clinical assessment, goal setting, and drug therapy management with physicians. Study outcomes were changes in glycosylated hemoglobin (A1C) and accompanying metabolic parameters (blood pressure, lipid parameters, and body mass index) during a 1-year time frame. RESULTS: In the overall cohort, A1C was not reduced significantly from baseline to 12 months (7.8% vs. 7.6%, P = 0.516). However, statistically significant reductions occurred for fasting plasma glucose, triglycerides, and diastolic blood pressure. None of the other parameters was affected significantly. In the subgroup of patients not at target values at baseline, significant reductions occurred for A1C (9.2% vs. 8.6%, P = 0.001), systolic blood pressure (147 vs. 143 mm Hg, P = 0.031), diastolic blood pressure (91 vs. 87 mm Hg, P < 0.001), triglycerides (259 vs. 219 mg/dL, P < 0.001), LDL cholesterol (139 vs. 123 mg/dL, P < 0.001), and total cholesterol (237 vs. 222 mg/dL, P = 0.008). CONCLUSION: Interventions performed by community pharmacists are effective in improving clinical outcomes in a Hispanic cohort with diabetes. Pharmacists' efforts were most successful in patients not at target glycemic and metabolic levels.

The Secondary Prevention of Small Subcortical Strokes (SPS3) study.

BACKGROUND: Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events. METHODS: Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n = 3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy--325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind--and to one of two levels of systolic blood pressure targets--'intensive' (<130 mmHg) vs. 'usual' (130-149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment. CONCLUSIONS: Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.

Pravastatin versus simvastatin for prevention of contrast-induced nephropathy.

Contrast-induced nephropathy (CIN) is associated with long-term morbidity, mortality, and increased health care costs. It has been suggested that statins have pleiotropic effects countering inflammatory and oxidative stress involved in CIN. Several studies support this theory; however, previously published studies have not evaluated the potential differences between statins in reducing the incidence of CIN. The purpose of this retrospective, single-center trial was to compare the incidence of CIN in patients receiving simvastatin or pravastatin therapy undergoing percutaneous coronary intervention (PCI). A total of 261 patients were included (145 received simvastatin and 116 received pravastatin) with the majority undergoing elective PCI. The population was predominantly male (65%), Hispanic (65%), and diabetic (62%), with a mean age of 59 years and a low-density lipoprotein (LDL) of 85 mg/dL. No significant differences were found between groups for risk factors or prophylactic strategies (eg, hydration). Contrast-induced nephropathy occurred in 26 patients (17.9%) in the simvastatin group versus 10 (8.6%) in the pravastatin group (P < .05). No patients required dialysis as a result of contrast administration. Acute kidney injury (AKI) occurred in 21 patients (14.5%) in the simvastatin group compared to 8 (6.9%) in the pravastatin group (P < .05). In multivariate analysis, the difference between statins remained an independent predictor for the development of CIN. In conclusion, patients on pravastatin had a significantly lower incidence of CIN compared to patients on simvastatin.

EMG and MRI are independently related to shoulder external rotation function in neonatal brachial plexus palsy.

BACKGROUND: Few studies exist with regard to the ability of electromyography (EMG) and volumetric magnetic resonance imaging (MRI) of the infraspinatus muscle to complement the physical assessment of active global shoulder external rotation (GER) in the neonatal brachial plexus palsy (NBPP) population. Therefore, the purpose of this study was to evaluate the relationships of EMG and MRI with active GER based on analysis of the infraspinatus muscle. METHODS: Seventy-four NBPP patients (mean age, 5 y 1 m; range, 1 y 1 m to 13 y 3 m) who had undergone physical examination of the shoulder, EMG evaluation of the infraspinatus muscle, and shoulder MRI were included in this study. The outcome variable active GER was dichotomized into <0 degree active GER (poor) and ≥0 degree active GER (good). The interference pattern on EMG of the infraspinatus muscle was graded on a 6-point scale and dichotomized into ≤4 and ≥5. On shoulder MRI, infraspinatus muscle volume was measured. The infraspinatus muscle interference pattern and volume were compared with active GER. RESULTS: Interference pattern on EMG of the infraspinatus muscle was significantly related to the Mallet Score (P=0.0022), with a poor interference pattern associated with an approximately 7 times higher likelihood [odds ratio=7.391; 95% confidence interval (2.054, 26.588)] of poor active GER. Infraspinatus muscle volume decrease on MRI was also significantly related to active GER (P=0.0413), with each percent volume decrease corresponding to an increase of 0.094 in the odds of having a poor Mallet Score for active GER [odds ratio=1.094; 95% confidence interval (1.004, 1.193)]. CONCLUSIONS: The interference pattern of the infraspinatus muscle on EMG and the infraspinatus muscle volume on MRI are strongly related to active GER as assessed by the Mallet Score. Integrating clinical assessment with electrophysiological and imaging findings may improve the accuracy in evaluating shoulder dysfunction in NBPP and provide improved guidance in selecting interventions specific to the patient's pattern of deficits. LEVEL OF EVIDENCE: Diagnostic study, level II.

Preclinical evaluation of tacrolimus colloidal dispersion for inhalation.

Substantial improvements in transplant therapy have been made in the past four decades resulting in the acceptance of organ transplantation as a viable treatment for late-stage disease and organ failure. More recently, lung transplantation has gained acceptance; however, high incidence of chronic rejection and opportunistic infections has limited success rates in comparison with other transplant procedures. To achieve more targeted therapy, pulmonary administration of nebulized tacrolimus (TAC) colloidal dispersion once daily for 28 consecutive days in Sprague Dawley (SD) rats has been investigated for safety and systemic elimination. A liquid dispersion of colloidal TAC and lactose (1:1 ratio by weight) was aerosolized using a vibrating mesh nebulizer and administered via a nose-only dosing chamber. Blood chemistry and histological comparisons to saline-dosed animals showed no clinically significant differences in liver and kidney function or lung tissue damage. Maximum blood and lung concentrations sampled 1h after the final dose showed TAC concentrations of 10.1 ± 1.4 ng/mL and 1758.7 ± 80.0 ng/g, respectively. Twenty-four hours after the final dose, systemic TAC concentrations measured 1.0 ± 0.5 ng/mL, which is well below clinically accepted trough concentrations (5-15 ng/mL) for maintenance therapy, and therefore, would not be expected to induce toxic side effects. The propensity for pulmonary retention seen when compared to single dose lung levels may be due to macrophage uptake and the lipophilic nature of TAC. Additionally, three month stability testing of TAC powder for reconstitution showed no changes in amorphous nature or drug potency when stored at ambient conditions. TAC colloidal dispersion proved to be non-toxic when administered by pulmonary inhalation to SD rats over 28 days while providing therapeutic concentrations locally. This delivery strategy may prove safe and effective for the prevention of lung allograft rejection in lung transplant recipients.

Retrospective cohort study of hospitalized adults treated with vancomycin or clindamycin for methicillin-resistant Staphylococcus aureus skin infections.

BACKGROUND: Vancomycin alternatives, including clindamycin, have in vitro activity against current strains of methicillin-resistant Staphylococcus aureus (MRSA), but clinical evidence of their effectiveness is needed. OBJECTIVE: The aim of this work was to compare health outcomes for hospitalized adult patients treated with vancomycin and clindamycin for skin and soft- tissue infections caused by MRSA. METHODS: This was a retrospective chart review of patients admitted to University Hospital (San Antonio, Texas) with culture-proven MRSA skin or soft-tissue infections from July 1, 2006, to December 31, 2006. Patients were subdivided into groups according to antibiotics received on the first day of hospital admission. The primary outcome was composite failure, which was defined as having an additional positive MRSA culture 5 to 90 days after initial culture or requiring an additional intervention (eg, new course of antibiotics or additional incision and drainage within 90 days after initiation of therapy). Descriptive statistics were used to characterize each group; χ(2), Fisher exact, and Wilcoxon rank sum tests were used to assess differences between the vancomycin and clindamycin groups. RESULTS: Ninety-one patients received vancomycin (n = 40) or clindamycin (n = 51) for a MRSA skin infection. Most vancomycin-treated patients received 1 g IV q12h (92.5% [37/40]), whereas most clindamycintreated patients received 600 mg IV q8h (51.0% [26/51]) or 900 mg IV q8h (27.5% [14/51]). The vancomycin and clindamycin groups had no significant differences with regard to median age (38 vs 37 years, respectively), male sex (62.5% [25/40] vs 74.5% [38/51]), or Hispanic ethnicity (77.5% [31/40] vs 78.4% [40/51]). All MRSA isolates were susceptible to vancomycin and trimethoprimsulfamethoxazole. Few patients who received clindamycin were resistant to clindamycin (3.9% [2/51]). No patients died in the hospital. There were no significant differences between the vancomycin (n = 40) and clindamycin (n = 51) groups with respect to composite failure (15.0% [6/40] vs 7.8% [4/51], respectively), microbiologic failure (2.5% [1/40] vs 3.9% [2/51]), additional inpatient interventions (5.0% [2/40] vs 3.9% [2/51]), or additional outpatient interventions (12.5% [5/40] vs 3.9% [2/51]). Most patients (93.4% [85/91]) received incision and drainage. When those who did not were excluded from the analyses, all trends remained unchanged. CONCLUSIONS: In a single institution with a low rate of clindamycin resistance, there were no significant differences between vancomycin and clindamycin for the treatment of these hospitalized patients with MRSA skin infections, on the basis of clinical outcomes data. This finding warrants further investigation in a randomized controlled trial.