Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial.

BACKGROUND: Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF. OBJECTIVES: The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations. METHODS: This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%). RESULTS: A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin. CONCLUSIONS: Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.

Operative strategies to reduce cerebral embolic events during on- and off-pump coronary artery bypass surgery: A stratified, prospective randomized trial.

OBJECTIVE: To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). METHODS: Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy. Transcranial Doppler ultrasonography (TCD) was performed to identify high-intensity transient signals (HITS) in the middle cerebral arteries during periods of aortic manipulation. Neurocognitive testing was performed at baseline and 30-days postoperatively. The primary endpoint was total number of HITS detected by TCD. Groups were compared using the Mann-Whitney U test. RESULTS: In the off-pump group, the median number of total HITS were higher in the CFD subgroup (30.0; interquartile range [IQR], 22-43) compared with the partial clamp subgroup (7.0; IQR, 0-16; P < .0001). In the CFD subgroup, the median number of total HITS was significantly lower for patients with 1 CFD compared with patients with >1 CFD (12.5 [IQR, 4-19] vs 36.0 [IQR, 25-47]; P = .001). In the on-pump group, the median number of total HITS was 10.0 (IQR, 3-17) in the single-clamp group, compared with 16.0 (IQR, 4-49) in the double-clamp group (P = .10). There were no differences in neurocognitive outcomes across the groups. CONCLUSIONS: For patients with low-grade aortic disease, the use of CFDs was associated with an increased rate of cerebral embolic events compared with partial clamping during off-pump CABG. A single-clamp strategy during on-pump CABG did not significantly reduce embolic events compared with a double-clamp strategy.

Exercise Capacity, Heart Failure Risk, and Mortality in Older Adults: The Health ABC Study.

INTRODUCTION: Data on the association between exercise capacity and risk for heart failure (HF) in older adults are limited. METHODS: This study examined the association of exercise capacity, and its change over time, with 10-year mortality and incident HF in 2,935 participants of the Health, Aging, and Body Composition Study without HF at baseline (age, 73.6 [SD=2.9] years; 52.1% women; 41.4% black; 58.6% white). This cohort was initiated in 1997-1998 and exercise capacity was evaluated with a long-distance corridor walk test (LDCW) at baseline and Year 4. Outcomes were collected in 2007-2008 and initial analysis performed in 2014. RESULTS: Ten-year incident HF for completers (n=2,245); non-completers (n=331); and those excluded from LDCW for safety reasons (n=359) was 11.4%, 19.2%, and 23.0%, respectively. The corresponding 10-year mortality was 27.9%, 41.1%, and 42.4%. In models accounting for competing mortality, the adjusted subhazard ratio for HF was 1.37 (95% CI=1.00, 1.88; p=0.049) in non-completers and 1.41 (95% CI=1.06, 1.89; p=0.020) in those excluded versus completers. Non-completers (adjusted hazard ratio, 1.49; 95% CI=1.21, 1.84; p<0.001) and those excluded (hazard ratio, 1.27; 95% CI=1.04, 1.55; p=0.016) had elevated mortality. In adjusted models, LDCW performance variables were associated mainly with mortality. Only 20-meter walking speed and resting heart rate retained prognostic value for HF. Longitudinal changes in LDCW did not predict subsequent incident HF or mortality. CONCLUSIONS: Completing an LDCW is strongly associated with lower 10-year mortality and HF risk in older adults. Therefore, walking capacity may serve as an early risk marker.

Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT).

BACKGROUND: Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. METHODS: Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function. RESULTS: Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. CONCLUSIONS: In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.

Transcatheter Aortic Valve Replacement Results in Improvement of Pulmonary Function in Patients With Severe Aortic Stenosis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for morbidity and mortality after transcatheter aortic valve replacement (TAVR). We hypothesized that a portion of pulmonary dysfunction in patients with severe aortic stenosis may be of cardiac origin, and has potential to improve after TAVR. METHODS: A retrospective analysis was made of consecutive TAVR patients from April 2008 to October 2014. Of patients who had pulmonary function testing and serum B-type natriuretic peptide data available before and after TAVR, 58 were found to have COPD (26 mild, 14 moderate, and 18 severe). Baseline variables and operative outcomes were explored along with changes in pulmonary function. Multiple regression analyses were performed to adjust for preoperative left ventricular ejection fraction and glomerular filtration rate. RESULTS: Comparison of pulmonary function testing before and after the procedure among all COPD categories showed a 10% improvement in forced vital capacity (95% confidence interval: 4% to 17%) and a 12% improvement in forced expiratory volume in 1 second (95% confidence interval: 6% to 19%). There was a 29% decrease in B-type natriuretic peptide after TAVR (95% confidence interval: -40% to -16%). An improvement of at least one COPD severity category was observed in 27% of patients with mild COPD, 64% of patients with moderate COPD, and 50% of patients with severe COPD. There was no 30-day mortality in any patient group. CONCLUSIONS: In patients with severe aortic stenosis, TAVR is associated with a significant improvement of pulmonary function and B-type natriuretic peptide. After TAVR, the reduction in COPD severity was most evident in patients with moderate and severe pulmonary dysfunction.

Effect of Surgical Atrial Fibrillation Ablation at the Time of Cardiac Surgery on Risk of Postoperative Pacemaker Implantation.

The aim of this study was to retrospectively investigate whether performing surgical atrial fibrillation (AF) ablation in conjunction with cardiac surgery (CS) increases the risk for postoperative permanent pacemaker (PPM) requirement. The 30-day risk for PPM requirement was analyzed in consecutive patients who underwent CS from January 2007 to August 27, 2013. Patients were divided into 3 groups: (1) those who underwent AF ablation concomitant with CS (AF ABL), (2) patients with any history of AF who underwent surgery who did not undergo ablation (AF NO ABL), and (3) those with no histories of AF who underwent surgery (NO AF). Logistic regression analysis was performed adjusting for age, gender, and surgery type. Of 13,453 CS patients, 353 (3%) were in the AF ABL group, 1,701 (12%) in the AF NO ABL group, and 11,399 (85%) in the NO AF group. A total of 7,651 patients (57%) underwent coronary artery bypass grafting, 4,384 (33%) underwent valve surgery, and 1,418 (10%) underwent coronary artery bypass grafting and valve surgery. The overall PPM risk was 1.6% (212 of 13,453); risk was 5.7% (20 of 353) in the AF ABL group, 3.1% (53 of 1,701) in the AF NO ABL group, and 1.2% (139 of 11,399) in the NO AF group. The unadjusted and adjusted odds of PPM were higher in the AF ABL and AF NO ABL groups than in the NO AF group (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.7 to 4.4, and adjusted OR 1.7, 95% CI 1.2 to 2.4, respectively). The unadjusted OR comparing the AF ABL group and the AF NO ABL group was significant (unadjusted OR 1.9, 95% CI 1.9 to 3.2); however, the OR adjusted for surgery type, age, and gender showed a trend toward significance (adjusted OR 1.6, 95% CI 0.9 to 2.7). In conclusion, in this large cohort of patients who underwent CS, surgical AF ablation appeared to carry an increased risk for postoperative PPM implantation.

Consumption of less than 10% of total energy from added sugars is associated with increasing HDL in females during adolescence: a longitudinal analysis.

BACKGROUND: Atherosclerotic changes associated with dyslipidemia and increased cardiovascular disease risk are believed to begin in childhood. While previous studies have linked added sugars consumption to low high-density lipoprotein (HDL), little is known about the long-term impact of this consumption. This study aims to assess the association between added sugars intake and HDL cholesterol levels during adolescence, and whether this association is modified by obesity. METHODS AND RESULTS: We used data from the National Heart Lung and Blood Institute's Growth and Health Study, a 10-year cohort study of non-Hispanic Caucasian and African-American girls (N=2379) aged 9 and 10 years at baseline recruited from 3 sites in 1987-1988 with biennial plasma lipid measurement and annual assessment of diet using a 3-day food record. Added sugars consumption was dichotomized into low (0% to <10% of total energy) and high (≥10% of total energy). In a mixed model controlling for obesity, race, physical activity, smoking, maturation stage, age, and nutritional factors, low compared with high added sugar consumption was associated with a 0.26 mg/dL greater annual increase in HDL levels (95% CI 0.48 to 0.04; P=0.02). Over the 10-year study period, the model predicted a mean increase of 2.2 mg/dL (95% CI 0.09 to 4.32; P=0.04) among low consumers, and a 0.4 mg/dL decrease (95% CI -1.32 to 0.52; P=0.4) among high consumers. Weight category did not modify this association (P=0.45). CONCLUSION: Low added sugars consumption is associated with increasing HDL cholesterol levels throughout adolescence.

Racial differences in arterial stiffness and microcirculatory function between Black and White Americans.

BACKGROUND: Compared with whites, black Americans suffer from a disproportionate burden of cardiovascular disease (CVD). We hypothesized that racial differences in the prevalence of CVD could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden. METHODS AND RESULTS: We assessed vascular function in 385 black and 470 white subjects (mean age, 48±11 years; 45% male). Using digital pulse amplitude tonometry (EndoPAT) we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function, and peripheral augmentation index (PAT-AIx). Central augmentation index (C-AIx) and pulse-wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively, using applanation tonometry (Sphygmocor). Compared with whites, blacks had lower RHI (2.1±0.6 versus 2.3±0.6, P<0.001), greater arterial wave reflections assessed as both PAT-AIx (20.4±21.5 versus 17.0±22.4, P=0.01) and CAIx (20.8±12.3 versus 17.5±13.3, P=0.001), and greater arterial stiffness, measured as PWV (7.4±1.6 versus 7.1±1.6 m/s, P=0.001). After adjustment for traditional CVD risk factors, black race remained a significant predictor of lower RHI and higher PAT-AIx and CAIx (all P<0.001) in all subjects and of higher PWV in men (P=0.01). Furthermore, these associations persisted in a subgroup analysis of "healthy" individuals free of CVD risk factors. CONCLUSION: Black race is associated with impaired microvascular vasodilatory function, and greater large arterial wave reflections and stiffness. Because impairment in these vascular indices may be associated with worse long-term outcomes, they may represent underlying mechanisms for the increased CVD risk in blacks.

Successful use of Plasma Preparation Tubes™ (PPTs) in the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 test.

BACKGROUND: Since switching to the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test, v. 1.0 from the Amplicor HIV-1 Monitor Test, v. 1.5, an increase in detectable viral load results was noted. We were concerned that this was due to the use of Plasma Preparation Tubes (PPT) in this test. OBJECTIVE: To assess the impact of different pre-analytical processing conditions on HIV-1 viral load results on the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test. STUDY DESIGN: Sixty-three HIV-infected patients were consented and had 3 PPTs and 1 K2EDTA drawn for HIV-1 viral load testing. Three methods of PPT processing were compared against the referent K2EDTA tube which was spun at 1100 × g for 20 min, poured off and frozen; PPT1 was refrigerated with an additional centrifugation prior to testing, PPT2 was processed similarly to EDTA, and PPT3 was centrifuged, frozen and centrifuged again prior to testing. RESULTS: PPT1 and PPT3 yielded results that were most similar to the referent EDTA processing, with a concordance correlation coefficient (CCC) of 0.80 and 0.85, compared to PPT2 with CCC of 0.37. Both PPT1 and PPT3 involved additional centrifugation prior to testing. In 26 patients with residual samples from the PPT2 processing, 9 (34.6%) were found to have the presence of proviral DNA, which likely contributed to the elevated HIV-1 RNA viral loads in these individuals. CONCLUSION: PPTs can be used in the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test with an additional centrifugation in order to avoid misleading elevated HIV-1 RNA viral loads that may change patient management.

Association of coronary wall shear stress with atherosclerotic plaque burden, composition, and distribution in patients with coronary artery disease.

BACKGROUND: Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition. METHODS AND RESULTS: Twenty-seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P<0.001). Segments distal to lesions or within bifurcations were more likely to have low WSS (P<0.001). However, the majority of segments distal to lesions (80%) and within bifurcations (89%) did not exhibit low WSS. After adjustment for plaque burden, there was a negative association between WSS and percent necrotic core and calcium. For every 10 dynes/cm(2) increase in WSS, percent necrotic core decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001). There was no significant association between WSS and percent of fibrous or fibrofatty plaque components (P=NS). CONCLUSIONS: IN PATIENTS WITH CORONARY ARTERY DISEASE: (1) Luminal geometry predicts calculated WSS only partially, which suggests that detailed computational techniques must be used to calculate WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent of plaque burden, which suggests a link between WSS and coronary plaque phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.).

Effect of intensive atorvastatin therapy on coronary atherosclerosis progression, composition, arterial remodeling, and microvascular function.

BACKGROUND: There is a discrepancy between the marked reduction in adverse events with statins and their modest effect on atheroma regression. We hypothesized that, in a Western population, high-dose atorvastatin will result in alterations in coronary atheroma composition, phenotype, and microvascular function. METHODS: Serial coronary radiofrequency intravascular ultrasound (VH-IVUS), coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) were performed at baseline and after 6 months of treatment with 80 mg atorvastatin in 20 patients with moderate coronary artery disease (CAD). For each VH-IVUS frame (n = 2249), changes in total plaque atheroma, composition, and phenotype (pathological intimal thickening, fibrotic plaque, fibroatheroma), and serial remodeling were assessed. RESULTS: Total serum cholesterol decreased from 186.0 mg/dL (interquartile range [IQR], 168.0 to 212.5 mg/dL) to 139.0 mg/dL (IQR, 124.3 to 151.3 mg/dL). Percent atheroma volume did not change significantly (-0.5% [IQR, -2.8% to 3.7%]; P=.90) and serial remodeling analysis demonstrated 40% constrictive, 24% incomplete, and 36% expansive patterns. There was a trend toward lower percent fibrous tissue (-3.47 ± 1.78%; P=.07) and percent fibro-fatty tissue (-2.52 ± 1.24%; P=.06) and increase in percent necrotic core (+2.74 ± 1.65%; P=.11) and percent dense calcium (+1.99 ± 0.81; P=.02), which translated into significantly less pathological intimal thickening (4% vs 12%; P<.0001) and more fibroatheromas (67% vs 57%; P<.0001) at follow-up compared to baseline. There were modest non-significant improvements in CFR (+0.26 [IQR, -0.37 to 0.76]; P=.23) and HMR (-0.22 [IQR, -0.56 to 0.28]; P=.12). CONCLUSIONS: In this pilot study of Western patients with moderate CAD, high-dose atorvastatin resulted in alterations in coronary atheroma composition with corresponding changes in plaque phenotype and modest improvement in coronary microvascular function.

Computer-aided diagnosis of renal obstruction: utility of log-linear modeling versus standard ROC and kappa analysis.

BACKGROUND: The accuracy of computer-aided diagnosis (CAD) software is best evaluated by comparison to a gold standard which represents the true status of disease. In many settings, however, knowledge of the true status of disease is not possible and accuracy is evaluated against the interpretations of an expert panel. Common statistical approaches to evaluate accuracy include receiver operating characteristic (ROC) and kappa analysis but both of these methods have significant limitations and cannot answer the question of equivalence: Is the CAD performance equivalent to that of an expert? The goal of this study is to show the strength of log-linear analysis over standard ROC and kappa statistics in evaluating the accuracy of computer-aided diagnosis of renal obstruction compared to the diagnosis provided by expert readers. METHODS: Log-linear modeling was utilized to analyze a previously published database that used ROC and kappa statistics to compare diuresis renography scan interpretations (non-obstructed, equivocal, or obstructed) generated by a renal expert system (RENEX) in 185 kidneys (95 patients) with the independent and consensus scan interpretations of three experts who were blinded to clinical information and prospectively and independently graded each kidney as obstructed, equivocal, or non-obstructed. RESULTS: Log-linear modeling showed that RENEX and the expert consensus had beyond-chance agreement in both non-obstructed and obstructed readings (both p < 0.0001). Moreover, pairwise agreement between experts and pairwise agreement between each expert and RENEX were not significantly different (p = 0.41, 0.95, 0.81 for the non-obstructed, equivocal, and obstructed categories, respectively). Similarly, the three-way agreement of the three experts and three-way agreement of two experts and RENEX was not significantly different for non-obstructed (p = 0.79) and obstructed (p = 0.49) categories. CONCLUSION: Log-linear modeling showed that RENEX was equivalent to any expert in rating kidneys, particularly in the obstructed and non-obstructed categories. This conclusion, which could not be derived from the original ROC and kappa analysis, emphasizes and illustrates the role and importance of log-linear modeling in the absence of a gold standard. The log-linear analysis also provides additional evidence that RENEX has the potential to assist in the interpretation of diuresis renography studies.

Key variables for interpreting 99mTc-mercaptoacetyltriglycine diuretic scans: development and validation of a predictive model.

OBJECTIVE: The purpose of this study was to facilitate interpretation of (99m)Tc-mercaptoacetyltriglycine (MAG3) diuretic scans by identifying key interpretative variables and developing a predictive model for computer-assisted diagnosis. MATERIALS AND METHODS: Ninety-seven studies were randomly selected from an archived database of MAG3 baseline and furosemide acquisitions and scan interpretations (obstruction, equivocal finding, or no obstruction) derived from a consensus of three experts. Sixty-one studies (120 kidneys) were randomly chosen to build a predictive model for diagnosing or excluding obstruction. The other 36 studies (71 kidneys) composed the validation group. The probability of normal drainage (no obstruction) at the baseline acquisition and the probability of no obstruction, equivocal finding, or obstruction after furosemide administration were determined by logistic regression analysis and proportional odds modeling of MAG3 renographic data. RESULTS: The single most important baseline variable for excluding obstruction was the ratio of postvoid counts to maximum counts. Renal counts in the last minute of furosemide acquisition divided by the maximum baseline acquisition renal counts and time to half-maximum counts after furosemide administration in a pelvic region of interest were the critical variables for determining obstruction. The area under the receiver operating characteristic curve (AUC) for predicting normal drainage in the validation sample was 0.93 (standard error, 0.02); sensitivity, 85%; specificity, 93%. The AUC for the diagnosis of obstruction after furosemide administration was 0.84 (standard error, 0.06); sensitivity, 82%; specificity, 83%. CONCLUSION: A predictive system has been developed that provides a promising computer-assisted diagnosis approach to the interpretation of MAG3 diuretic renal scans; this system has also identified the key variables required for scan interpretation.

Culturally-adapted and audio-technology assisted HIV/AIDS awareness and education program in rural Nigeria: a cohort study.

BACKGROUND: HIV-awareness programs tailored toward the needs of rural communities are needed. We sought to quantify change in HIV knowledge in three rural Nigerian villages following an integrated culturally adapted and technology assisted educational intervention. METHODS: A prospective 14-week cohort study was designed to compare short-term changes in HIV knowledge between seminar-based education program and a novel program, which capitalized on the rural culture of small-group oral learning and was delivered by portable digital-audio technology. RESULTS: Participants were mostly Moslem (99%), male (53.5%), with no formal education (55%). Baseline HIV knowledge was low (<80% correct answers for 9 of the 10 questions). Knowledge gain was higher (p < 0.0001 for 8 of 10 questions) in the integrated culturally adapted and technology-facilitated (n = 511) compared with the seminar-based (n = 474) program. CONCLUSIONS: Baseline HIV-awareness was low. Culturally adapted, technology-assisted HIV education program is a feasible cost-effective method of raising HIV awareness among low-literacy rural communities.

Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study.

OBJECTIVE: To investigate the efficacy of cholecalciferol (vitamin D3) in raising serum 25-hydroxyvitamin D (25[OH)]D) levels and reducing parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD). METHODS: In this double-blind, randomized controlled pilot study, participants with CKD stage 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2), vitamin D insufficiency (serum 25[OH]D <30 ng/mL), and serum intact PTH levels >70 pg/mL were randomly assigned to receive either 50 000 IU of cholecalciferol or placebo once weekly for 12 weeks. Primary outcomes (25[OH]D and PTH levels) were measured at baseline, week 6, and week 12. Secondary outcomes (1,25-dihydroxvitamin D and bone turnover markers) were measured at baseline and week 12. Because of skewed data distribution, statistical analyses were performed on a logarithmic scale. The difference between the group means was exponentiated to provide the geometric mean ratio. A linear mixed model using an unstructured variance-covariance matrix was used to examine change in the primary and secondary outcomes over time. RESULTS: Geometric mean serum 25(OH)D concentrations of the study groups were similar at baseline (P = .77). At week 6, a significant difference between the treatment and placebo groups was detected (P = .001); this difference was maintained at week 12 (P = .002). Among cholecalciferol-treated participants, serum 25(OH)D concentration increased on average from 17.3 ng/mL (95% confidence interval [CI], 11.8-25.2) at baseline to 49.4 ng/mL (95% CI, 33.9-72.0) at week 12. As-treated analysis indicated a trend toward lower PTH levels among cholecalciferol-treated participants (P = .07). CONCLUSION: Weekly cholecalciferol supplementation appears to be an effective treatment to correct vitamin D status in patients with CKD.

Diagnostic performance of an expert system for interpretation of 99mTc MAG3 scans in suspected renal obstruction.

UNLABELLED: The purpose of the study was to compare diuresis renography scan interpretation generated by a renal expert system with the consensus interpretation of 3 expert readers. METHODS: The expert system was evaluated in 95 randomly selected furosemide-augmented patient studies (185 kidneys) obtained for suspected obstruction; there were 55 males and 40 females with a mean age +/- SD of 58.6 +/- 16.5 y. Each subject had a baseline (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) scan followed by furosemide administration and a separate 20-min acquisition. Quantitative parameters were automatically extracted from baseline and furosemide acquisitions and forwarded to the expert system for analysis. Three experts, unaware of clinical information, independently graded each kidney as obstructed/probably obstructed, equivocal, and probably nonobstructed/nonobstructed; experts resolved differences by a consensus reading. These 3 expert categories were compared with the obstructed, equivocal, and nonobstructed interpretations provided by the expert system. Agreement was assessed using weighted kappa, and the predictive accuracy of the expert system compared with expert readers was assessed by the area under receiver-operating-characteristic (ROC curve) curves. RESULTS: The expert system agreed with the consensus reading in 84% (101/120) of nonobstructed kidneys, in 92% (33/36) of obstructed kidneys, and in 45% (13/29) of equivocal kidneys. The weighted kappa between the expert system and the consensus reading was 0.72 and was comparable with the weighted kappa between experts. There was no significant difference in the areas under the ROC curves when the expert system was compared with each expert using the other 2 experts as the gold standard. CONCLUSION: The renal expert system showed good agreement with the expert interpretation and could be a useful educational and decision support tool to assist physicians in the diagnosis of renal obstruction. To better mirror the clinical setting, algorithms to incorporate clinical data must be designed, implemented, and tested.

Use of classification and regression trees in diuresis renography.

RATIONALE AND OBJECTIVES: Decision support systems have the capacity to improve diagnostic performance and reduce physician errors. The purpose of this study was to evaluate the use of classification and regression trees (CART) with bootstrap aggregation as a decision support system in the baseline plus furosemide (F + 20) diuresis renography protocol to determine when obstruction can be excluded without the furosemide acquisition and to identify the key parameters for making this determination. MATERIALS AND METHODS: Patients with suspected ureteral obstruction were randomly assigned to a training set (80 patients, 157 kidneys) and a validation set (64 patients, 124 kidneys). Forty quantitative parameters (curve parameters, MAG3 clearance and voiding indices) were generated from each baseline Tc-99m mercaptoacetyltriglycine (MAG3) scan. Three expert readers independently evaluated each kidney regarding the need for furosemide and resolved differences by majority vote. CART with bootstrap aggregation was applied to the training set to generate prediction algorithms which were tested in the validation set. RESULTS: The algorithm agreed with the expert decision on the necessity of furosemide in 90% (111 of 124 kidneys), with misclassification rates of 10.0% and 10.9% for the left and right kidneys, respectively. The most important discriminators were the postvoid-to-maximum count ratio, the cortical 20-minute-to-maximum count ratio, and the postvoid-to-1-to-2-minute count ratio. CONCLUSION: CART can identify the key parameters for discriminating between nonobstruction and possible obstruction, has the potential to serve as a decision support tool to avoid unnecessary furosemide imaging, and can be applied to more complex imaging problems.