The effect of vitamin d on aldosterone and health status in patients with heart failure.

BACKGROUND: Vitamin D deficiency is associated with heart failure (HF) events, and in animal models vitamin D down-regulates renin-angiotensin-aldosterone system hormones. METHODS: Patients with New York Heart Association (NYHA) functional class II-IV HF and a 25OH-D level ≤37.5 ng/mL received 50,000 IU vitamin D3 weekly (n = 31) or placebo (n = 33) for 6 months. Serum aldosterone, renin, echocardiography, and health status were determined at baseline and 6 months. RESULTS: Mean age of participants was 65.9 ± 10.4 years, 48% were women, 64% were African American, mean ejection fraction was 37.6 ± 13.9%, 36% were in NYHA functional class III, and 64% were in class II. The vitamin D group increased serum 25OH-D (19.1 ± 9.3 to 61.7 ± 20.3 ng/mL) and the placebo group did not (17.8 ± 9.0 to 17.4 ± 9.8 ng/mL). Aldosterone decreased in the vitamin D group (10.0 ± 11.9 to 6.2 ± 11.6 ng/dL) and not in the placebo group (8.9 ± 8.6 to 9.0 ± 12.4 ng/dL; P = .02). There was no difference between groups in renin, echocardiographic measures, or health status from baseline to 6 months. Modeling indicated that variables which predicted change in aldosterone included receiving vitamin D, increasing age, African American race, and lower glomerular filtration rate. CONCLUSIONS: Vitamin D3 repletion decreases aldosterone in patients with HF and low serum vitamin D. Vitamin D may be an important adjunct to standard HF therapy. Further study will assess if vitamin D provides long-term benefit for patients with HF.

Age, stress, and isolation in older adults living with HIV.

People living with HIV (PLWH) have increasingly longer life spans. This age group faces different challenges than younger PLWH, which may include increased stress and social isolation. The purpose of this study was to determine whether the age and sex of PLWH are associated with measures of physiologic stress, perceived stress, and social isolation. In this cross-sectional study, we enrolled 102 PLWH equally into four groups divided by age (younger or older than 50 years) and gender. Participants completed well-validated survey measurements of stress and isolation, and their heart rate variability over 60 minutes was measured by Holter monitor. The mean (SD) Perceived Stress Scale score was 17.4 (6.94), mean Visual Analog Stress Scale score was 3.51 (2.79), and mean Hawthorne Friendship Scale score, a measure of social isolation, was 17.03 (4.84). Mean heart rate variability expressed as the SD of successive N-N intervals was 65.47 (31.16) msec. In multivariable regression models that controlled for selected demographic variables, there was no relationship between the Perceived Stress Scale and age (coefficient = -0.09, p =-0.23) or female gender (coefficient = -0.12, p = 0.93); however, there was a modest relationship between female gender and stress using the Visual Analog Stress Scale (coefficient = 1.24, p = 0.05). Perceived Stress was negatively associated with the Hawthorne Friendship score (coefficient = -0.34, p = 0.05). Hawthorne Friendship score was positively associated with younger age (coefficient = 0.11, p = 0.02). Age was the only independent predictor of physiologic stress as measured by heart rate variability (coefficient = -1.3, p < 0.01). Our findings suggest that younger PLWH may experience more social isolation; however, age-related changes in heart rate variability do not appear to be related to perceived stress or social isolation. Future longitudinal research is required to more thoroughly understand this relationship and its impact on the health of PLWH.

Heparin bonding does not improve patency of polytetrafluoroethylene arteriovenous grafts.

BACKGROUND: Heparin-bonded polytetrafluoroethylene (PTFE) grafts (hepPTFE) were developed to decrease rates of graft thrombosis. Our objective was to compare the patency of arteriovenous grafts (AVGs) for dialysis access with and without heparin bonding in a tertiary care setting. METHODS: Records of patients who had an AVG placed between January 2008 and June 2011 were retrospectively reviewed. Outcome measures were primary, assisted primary, and secondary patency. Marginal survival models (to account for correlation of accesses within subjects) using Cox proportional hazard regression were used for statistical comparisons. RESULTS: A total of 223 patients had 265 grafts placed. Of these, 62 (23%) were hepPTFE grafts. The average age was 66 ± 15 years in the hepPTFE group and 59 ± 17 years in the non-heparin-bonded control group (PTFE; P < 0.01). Of the hepPTFE group, 39% were men, 81% were African American, 63% were diabetic, and 81% had a tunneled catheter at the time of access placement. Of the PTFE group, 35% were men, 85% were African American, 56% were diabetic, and 83% had a tunneled catheter. HepPTFE grafts failed to improve rates of primary, assisted primary, or secondary patency based on univariate analysis (hazard ratio [HR]: 1.37 [95% confidence interval {CI}: 0.99-1.88]; HR: 1.39 [95% CI: 0.98-1.96]; and HR: 1.20 [95% CI: 0.73-1.96], respectively). The number of secondary interventions was similar in the 2 groups (1.1 interventions per person-year of follow-up PTFE versus 1.4 hepPTFE; P = 0.13). A multivariable model including age, diabetes, peripheral artery disease, tobacco use, previous access placement, and tunneled catheter found that the HR for hepPTFE was not significantly different than PTFE in primary, assisted primary, or secondary patency (HR: 1.32 [95% CI: 0.91-1.90]; HR: 1.35 [95% CI: 0.91-1.99]; and HR: 1.15 [95% CI: 0.62-2.16], respectively). CONCLUSIONS: hepPTFE AVGs failed to improve patency or decrease secondary interventions compared to standard PTFE grafts. Prospective studies are needed to confirm these results.

Spirituality and optimism: a holistic approach to component-based, self-management treatment for HIV.

For people living with HIV (PLWH), spirituality and optimism have a positive influence on their health, can slow HIV disease progression, and can improve quality of life. Our aim was to describe longitudinal changes in spirituality and optimism after participation in the SystemCHANGE™-HIV intervention. Upon completion of the intervention, participants experienced an 11.5 point increase in overall spiritual well-being (p = 0.036), a 6.3 point increase in religious well-being (p = 0.030), a 4.8 point increase in existential well-being (p = 0.125), and a 0.8 point increase in total optimism (p = 0.268) relative to controls. Our data suggest a group-based self-management intervention increases spiritual well-being in PLWH.

Home health care with telemonitoring improves health status for older adults with heart failure.

Home telemonitoring can augment home health care services during a patient's transition from hospital to home. Home health care agencies commonly use telemonitors for patients with heart failure although studies have shown mixed results in the use of telemonitors to reduce rehospitalizations. This randomized trial investigated if older patients with heart failure admitted to home health care following a hospitalization would have a reduction in rehospitalizations and improved health status if they received telemonitoring. Patients were followed up to 180 days post-discharge from home health care services. Results showed no difference in the time to rehospitalization or emergency visit between those who received telemonitoring versus usual care. Older heart failure patients who received telemonitoring had better health status by home health care discharge than those who received usual care. Therefore, for older adults with heart failure, telemonitoring may be an important adjunct to home health care services to improve health status.

Improving sleep hygiene behavior in adults living with HIV/AIDS: a randomized control pilot study of the SystemCHANGE(TM)-HIV intervention.

AIM: The aim of this study was to test the feasibility of a novel, evidence-based intervention SystemCHANGE-HIV on sleep outcomes. BACKGROUND: Insomnia and sleep disturbances affect an estimated 74% of people living with HIV (PLWH) and is a distressing consequence of HIV disease. METHODS: We conducted a two-group randomized control study with 40 PLWH. Outcomes included change in: sleep duration, sleep fragmentation index, sleep efficiency, and self-reported sleep quality. RESULTS: Participants rated the intervention as highly feasible. The intervention group experienced a 10minute/night increase in sleep time, a 2.3%-point increase in sleep efficiency, a 2.0%-point decrease in sleep fragmentation, relative to the control group, based on the model estimates of the treatment effect. CONCLUSIONS: A behavioral change intervention focusing on sleep is feasible in PLWH. The intervention group had improved sleep compared to the control group. Future work should test the efficacy of a refined SystemCHANGE-HIV on sleep.

Improving Medication Adherence through Graphically Enhanced Interventions in Coronary Heart Disease (IMAGE-CHD): a randomized controlled trial.

BACKGROUND: Up to 50 % of patients do not take medications as prescribed. Interventions to improve adherence are needed, with an understanding of which patients benefit most. OBJECTIVE: To test the effect of two low-literacy interventions on medication adherence. DESIGN: Randomized controlled trial, 2 × 2 factorial design. PARTICIPANTS: Adults with coronary heart disease in an inner-city primary care clinic. INTERVENTIONS: For 1 year, patients received usual care, refill reminder postcards, illustrated daily medication schedules, or both interventions. MAIN MEASURES: The primary outcome was cardiovascular medication refill adherence, assessed by the cumulative medication gap (CMG). Patients with CMG<0.20 were considered adherent. We assessed the effect of the interventions overall and, post-hoc, in subgroups of interest. KEY RESULTS: Most of the 435 participants were elderly (mean age=63.7 years), African-American (91 %), and read below the 9th-grade level (78 %). Among the 420 subjects (97 %) for whom CMG could be calculated, 138 (32.9 %) had CMG<0.20 during follow-up and were considered adherent. Overall, adherence did not differ significantly across treatments: 31.2 % in usual care, 28.3 % with mailed refill reminders, 34.2 % with illustrated medication schedules, and 36.9 % with both interventions. In post-hoc analyses, illustrated medication schedules led to significantly greater odds of adherence among patients who at baseline had more than eight medications (OR=2.2; 95 % CI, 1.21 to 4.04) or low self-efficacy for managing medications (OR=2.15; 95 % CI, 1.11 to 4.16); a trend was present among patients who reported non-adherence at baseline (OR=1.89; 95 % CI, 0.99 to 3.60). CONCLUSIONS: The interventions did not improve adherence overall. Illustrated medication schedules may improve adherence among patients with low self-efficacy, polypharmacy, or baseline non-adherence, though this requires confirmation.

The rate of bloodstream infection is high in infants with short bowel syndrome: relationship with small bowel bacterial overgrowth, enteral feeding, and inflammatory and immune responses.

OBJECTIVE: This pilot study in parenteral nutrition-dependent infants with short bowel syndrome (SBS) evaluated the impact of feeding route and intestinal permeability on bloodstream infection (BSI), small bowel bacterial overgrowth (SBBO), and systemic immune responses, as well as fecal calprotectin as a biomarker for SBBO. STUDY DESIGN: Ten infants (ages 4.2-15.4 months) with SBS caused by necrotizing enterocolitis were evaluated. Nutritional assessment, breath hydrogen testing, intestinal permeability, fecal calprotectin, serum flagellin- and lipopolysaccharide-specific antibody titers, and proinflammatory cytokine concentrations (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta, -6, and -8) were performed at baseline and at 60 and 120 days. Healthy, age-matched control subjects (n = 5) were recruited. RESULTS: BSI incidence was high (80%), and SBBO was common (50%). SBBO increased the odds for BSI (>7-fold; P = .009). Calprotectin levels were higher in children with SBS and SBBO versus those without SBBO and healthy control subjects (P < .05). Serum TNF-alpha, was elevated at baseline versus controls. Serum TNF-alpha and interleukin-1 beta, -6, and -8 levels diminished with increased enteral nutrition. Anti-flagellin and anti-lipopolysaccharide immunoglobulin G levels in children with SBS were lower versus control subjects and rose over time. CONCLUSION: In children with SBS, SBBO increases the risk for BSI, and systemic proinflammatory response decreases with increasing enteral feeding and weaning parenteral nutrition.

Effect of a pharmacy-based health literacy intervention and patient characteristics on medication refill adherence in an urban health system.

BACKGROUND: Limited health literacy is associated with poor understanding of medication instructions and may be related to medication adherence. OBJECTIVE: To evaluate a 3-part intervention (automated telephone reminder calls to refill prescriptions, picture prescription card, and clear health communication training for pharmacists) intended to increase refill adherence through attention to health literacy. METHODS: Three pharmacies that serve a primarily indigent, minority population served as the intervention sites, and one pharmacy served as the control site. To evaluate the impact of the 6-month intervention on medication adherence, pharmacy refill data were used to calculate the cumulative medication gap (CMG), in which values close to zero indicate better adherence. The primary measure of treatment effect was a comparison of the change in refill adherence within each group, from baseline to follow-up. RESULTS: A total of 173 patients were enrolled in the intervention group and 102 patients in the control group. Medication adherence was significantly different between intervention (CMG = 0.25) and control (CMG = 0.18) groups at baseline (p = 0.004). Refill adherence in the intervention group improved slightly during follow-up (CMG = 0.23), while it worsened slightly in the control group (CMG = 0.21), but the change in adherence between intervention and control groups was not significantly different (p = 0.4). Between 80% and 90% of intervention participants indicated that receiving the picture prescription and phone call interventions helped them remember when and how to take their medications and refill their prescriptions. No patient characteristics, including health literacy, were consistently associated with adherence. CONCLUSIONS: Implementation of a 3-part intervention--automated telephone reminders, picture prescription card, and pharmacist communication skills training--did not significantly improve refill adherence among inner-city patients. Further study should explore whether other aspects of medication management, such as dosing or adverse events, can be improved through these types of interventions, implemented either alone or in combination.

Formulation preference, tolerability and quality of life assessment following a switch from lopinavir/ritonavir soft gel capsule to tablet in human immunodeficiency virus-infected patients.

BACKGROUND: Lopinavir/ritonavir (LPV/r) tablet compared to the soft gel capsule (SGC) formulation has no oleic acid or sorbitol, has no refrigeration or food-restriction requirements, and has less pharmacokinetic variability. We compared the tolerability, quality of life (QoL), and formulation preference after switching from LPV/r SGC to the tablet formulation. METHODS: In a prospective, single-arm, cohort study-design, 74 human immunodeficiency virus (HIV) infected subjects stable on LPV/r-based therapy were enrolled prior to (n = 25) or 8 weeks (n = 49) after switching from SGC to tablet. Baseline data included clinical laboratory tests, bowel habit survey (BHS) and QoL questionnaire (recalled if enrolled post-switch). Global Condition Improvement (GCI)-score, BHS-score, QoL-score, and formulation preference data were captured at weeks 4 and 12. RESULTS: At week 12 post-enrollment; the tablet was preferred to the SGC (74% vs. 10%, p < 0.0001). GCI-overall-tolerability score was 2.46 +/- 3.30 on a scale of -7 to +7, with 90% admitting to feeling better or about the same. Stool frequency, consistency, volume, and +/- blood improved, however the improvement was significant in "consistency" only (p = 0.03). Aggregate Bowel Habit-Profile improved (BHS-score change = -0.227, p = 0.01). Inverse relationship existed between GCI and BHS (slope = -1.2, p = 0.02) at week-4, suggesting that improved overall-tolerability was related to better gastrointestinal (GI)-tolerance. QoL-scores were stable. Mean reductions in total cholesterol of 9.20 mg/dL (p = 0.02), in triglycerides of 33 mg/dL (p = 0.04), and in HDL of 4.50 mg/dL (p = 0.01) unrelated to lipid-lowering therapy, were observed at week 12. CONCLUSIONS: LPV/r-tablet was well tolerated and preferred to the SGC in HIV infected subjects, with stable QoL and appreciable improvement in GI-tolerability. The unexpected changes in lipid profile deserve further evaluation.

Increases in adiponectin predict improved liver, but not peripheral, insulin sensitivity in severely obese women during weight loss.

Obesity-related glucose intolerance is a function of hepatic (homeostatic model assessment-insulin resistance [HOMA-IR]) and peripheral insulin resistance (S(i)) and beta-cell dysfunction. We determined relationships between changes in these measures, visceral (VAT) and subcutaneous (SAT) adipose tissue, and systemic adipocytokine biomarkers 1 and 6 months after surgical weight loss. HOMA-IR decreased significantly (-50%) from baseline by 1 month and decreased further (-67%) by 6 months, and S(i) was improved by 6 months (2.3-fold) weight loss. Plasma concentrations of leptin decreased and adiponectin increased significantly by 1 month, and decreases in interleukin-6, C-reactive protein (CRP), and tumor necrosis factor-alpha were observed at 6 months of weight loss. Longitudinal decreases in CRP (r = -0.53, P < 0.05) were associated with increases in S(i), and decreases in HOMA-IR were related to increases in adiponectin (r = -0.37, P < 0.05). Decreases in VAT were more strongly related to increases in adiponectin and decreases in CRP than were changes in general adiposity or SAT. Thus, in severely obese women, specific loss of VAT leads to acute improvements in hepatic insulin sensitivity mediated by increases in adiponectin and in peripheral insulin sensitivity mediated by decreases in CRP.

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.

A population-based comparison of CIREN and NASS cases using similarity scoring.

The Crash Injury Research and Engineering Network (CIREN) provides significant details on injuries, and data on patient outcomes that is unavailable in the National Automotive Sampling System (NASS). However, CIREN cases are selected from specific Level I trauma centers with different inclusion criteria than those used for NASS, and the assertion that a given case is similar to the population of NASS cases is often made qualitatively. A robust, quantitative method is needed to compare CIREN to weighted NASS populations. This would greatly improve the usefulness and applicability of research conducted with data from the CIREN database. Our objective is to outline and demonstrate the utility of such a system to compare CIREN and NASS cases. This study applies the Mahalanobis distance metric methodology to determine similarity between CIREN and NASS/CDS cases. The Mahalanobis distance method is a multivariate technique for population comparison. Independent variables considered were total delta V, age, weight, height, maximum AIS, ISS, model year, gender, maximum intrusion, number of lower and upper extremity injuries, and number of head and chest injuries. The technique provides a unit-independent quantitative score which can be used to identify similarity of CIREN and NASS cases. Weighted NASS data and CIREN data were obtained for the years 2001-2005. NASS cases with Maximum AIS 3 resulted in a subset of 1,869 NASS cases, and 2,819 CIREN cases.

Genetic polymorphisms of flavin monooxygenase 3 in sulindac-induced regression of colorectal adenomas in familial adenomatous polyposis.

Sulindac is a nonsteroidal antiinflammatory drug with a chemopreventive effect in patients with familial adenomatous polyposis (FAP). In vivo, the active form of sulindac is sulindac sulfide, which is inactivated by the hepatic microsomal enzyme, flavin monooxygenase 3 (FMO3). In humans, numerous polymorphisms exist in FMO3, which alter enzymatic activity and subsequent substrate metabolism. We recently showed that certain polymorphic forms of FMO3 with reduced activity were associated with a more favorable response to sulindac in preventing the formation of adenomas in patients with FAP without polyps at baseline. Here, we determined whether these FMO3 polymorphisms correlated with the ability of sulindac to regress polyposis in patients with FAP who had polyps prior to treatment. Nineteen patients were treated with 150 mg sulindac twice a day for 6 months. The size and number of polyps in each patient was assessed at baseline (prior to the administration of sulindac), and at 3 and 6 months. Genotyping was done on seven established FMO3 polymorphisms with functional significance-M66I, E158K, P153L, V257M, E305X, E308G, and R492W. Statistical analyses were done with Wilcoxon rank sum test. Of the loci examined, only E158K and E308G showed polymorphic changes. Six patients exhibited polymorphisms in both E158K and E308G loci and were designated as genotype combination 1. The remaining patients were designated as genotype combination 2. Over the course of treatment, patients with genotype combination 1 had a greater reduction in both the size and number of polyps than those with genotype combination 2. These results suggest that combined polymorphic changes in the E158K and E308G alleles may protect against polyposis in patients with FAP treated with sulindac.

Polysensitization and individual susceptibility to allergic contact dermatitis.

BACKGROUND: Patients with allergic contact dermatitis to 1 antigen have been shown to be at increased risk of developing delayed type hypersensitivity reactions to additional antigens. Both environmental and genetic factors likely influence the risk of sensitization. OBJECTIVE: The aim of this study was to determine whether polysensitization occurs at a higher frequency than would be expected based on chance and whether polysensitization occurs more often in subsets of patients with hand involvement and atopic dermatitis. METHODS: From a database of patch test results from a single practitioner, the probability of having positive reactions to 3 or more unrelated allergens was calculated under the assumption that positive reactions are independent and compared with the observed proportion having positive reactions to 3 or more unrelated allergens. The analysis was repeated excluding patients with leg involvement as a proxy for venous insufficiency dermatitis. The proportion of patients from the polysensitized and nonpolysensitized cohorts with either hand involvement or a history of atopic dermatitis was also calculated. CONCLUSIONS: Polysensitization occurs more often than expected based on chance. Polysensitized patients were more likely to have hand dermatitis. Atopic dermatitis was not significantly associated with polysensitization in this analysis. Polysensitized individuals may represent a phenotype with increased genetic susceptibility to sensitization.

Improving medication understanding among Latinos through illustrated medication lists.

OBJECTIVES: Strategies are needed to improve medication management among vulnerable populations. We tested the effect of providing illustrated, plain-language medication lists on medication understanding, adherence, and satisfaction among Latino patients with diabetes in a safety net clinic. STUDY DESIGN: Randomized controlled trial. METHODS: Intervention patients received a PictureRx illustrated medication list that depicted the medication, indication, and dosing instructions, accompanied by plain language bilingual text. Usual care patients received a written list of their medications in their preferred language, with indication but no images. Outcomes were assessed by telephone approximately 1 week later. The Medication Understanding Questionnaire measured patients' ability to report the indication, strength, dosing, and frequency for their medication regimen. Self-reported adherence and satisfaction were secondary outcomes. Analysis was performed by intention to treat. RESULTS: Of 200 enrolled participants, 197 (98.5%) completed follow-up. Most (71%) had not graduated high school, and 59% had low health literacy. Patients randomized to illustrated medication instructions had better overall understanding of their medications (P<.001), including greater ability to report the drug indication (P<.01), strength (P<.05), dosing (P<.01), and frequency of administration (P<.001). Self-reported adherence did not differ significantly between study groups. Patients who received illustrated medication lists were very satisfied with them. CONCLUSIONS: In this randomized controlled trial, patients who received illustrated, plain-language medication lists demonstrated significantly greater understanding of their medication regimen. Such tools have the potential to improve medication use and chronic disease control, as well as reduce health disparities-although this requires further study.

Arteriovenous grafts have higher secondary patency in the short term compared with autologous fistulae.

BACKGROUND: To estimate patency of arteriovenous fistulas (AVFs) and grafts (AVGs) for dialysis access. METHODS: Records of all adult patients who had a dialysis access placed from January 2008 to June 2011 were retrospectively reviewed. RESULTS: A total of 494 patients with 655 accesses (390 AVFs, 265 AVGs) were examined. We found that AVG fared worse in assisted primary patency. But AVG had superior secondary patency up to 1.2 years (hazard ratio [HR] .6, confidence interval [CI]: [.4 to .8]) and was no different than AVF after 1.2 years. (HR 1.6, CI: [.9 to 3.1]). On univariate analysis, dialysis catheters negatively impacted assisted primary patency (HR 1.4, CI: [1.09 to 1.77]). CONCLUSIONS: AVG can be maintained with higher rates of secondary patency in the short term and are no different in the long term. This result suggests that in patients with limited life expectancy an AVG may be an effective alternative to an AVF to reduce both catheter time and associated complications.

Stem cell homing factor, CCL7, expression in mouse models of stress urinary incontinence.

OBJECTIVES: Animal models of vaginal distention (VD) have demonstrated increased expression of chemokine (C-C motif) ligand 7 (CCL7) In this study, we investigated the expression of CCL7 in mice models of simulated birth trauma-induced urinary incontinence using VD and pudendal nerve transection (PNT). METHODS: Forty-nine mice were divided into 6 groups: VD, sham VD, PNT, sham PNT, anesthesia, and age-matched controls. The urethra, vagina, and rectum were harvested for the expression of CCL7 immediately or 24 hours after assigned procedure. Venous sampling for quantification of serum CCL7 was also performed. An analysis of variance model was used to compare the relative expression of CCL7 in each group. RESULTS: Urethral CCL7 expression in the VD group was significantly higher than control group after 24 hours (P < 0.01). There was no difference in the urethral CCL7 expression in PNT, sham PNT, sham VD, or anesthesia groups compared with the controls. No statistically significant difference was noted in the vaginal and rectal expression of CCL7 between any of the groups except for sham PNT. Statistically significant differences were noted in the serum CCL7 expression in the VD, PNT, and sham PNT (P < 0.01 in all) groups after 24 hours compared with the control group. CONCLUSIONS: This study demonstrates overexpression of urethral CCL7 after VD but not PNT. This suggests that nerve injury does not contribute to the CCL7 overexpression. The overexpression of CCL7 in the serum of mice after VD suggests a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery.

A randomized controlled trial of high dose vitamin D3 in patients with heart failure.

OBJECTIVE: To investigate the effect of Vitamin D3 on physical performance in patients with HF. BACKGROUND: HF is associated with functional decline and frailty. Vitamin D deficiency is associated with loss of muscle strength and poor outcomes in patients with HF. METHODS: Sixty-four patients participated in a 6-month parallel design double blind RCT to test the hypothesis that oral vitamin D3 would improve physical performance. Vitamin D3 50,000 IU or placebo was given weekly; all received daily calcium. Patients were included regardless of EF and 25OHD ≤ 37.5 ng/ml. The primary outcome was peak VO2, and secondary outcomes were the 6MW, TGUG and knee isokinetic muscle strength. Between group comparisons were made using ANCOVA models that adjust for baseline measures. RESULTS: Patients were age 65.9 ± 10.4 years old, 48% women, 64% African American, EF 37.6±13.9, 36% NYHA III, the remainder NYHA II. At baseline the vitamin D group 25OHD was 19.1 ± 9.3 ng/ml and increased to 61.7 ± 20.3 ng/ml; in the placebo group baseline 25OHD was 17.8 ± 9.0 ng/ml and decreased to 17.4 ± 9.8 ng/ml at 6 months (between groups p<0.001). There was no significant change from baseline to 6 months in peak VO2, 6MW, TGUG or isokinetic muscle strength. CONCLUSIONS: Vitamin D3 did not improve physical performance for patients with HF despite a robust increase in serum 25OHD. Vitamin D repletion in patients with HF should conform to standard adult guidelines for vitamin D supplementation.

Body mass index and 25 hydroxyvitamin D status in patients with and without heart failure.

The purpose of this pilot study was to assess the association between 25-hydroxyvitamin D (25[OH]D) concentrations, vitamin D intake, and sunlight exposure in patients with heart failure (HF) compared with healthy volunteers. Fourteen healthy volunteers 50 and older were recruited to compare with 14 patients with HF. Healthy volunteers were compared with HF patients by serum 25(OH)D concentrations, dietary vitamin D intake, weekly sunlight exposure, and other covariates. Independent sample t tests and linear regression models were used to compare differences between healthy volunteers and patients with HF. The mean serum 25(OH)D concentration was not significantly different between groups (healthy volunteers 25.7 ± 11.1 ng/mL, patients with HF 20.4 ± 10.2 ng/mL; P=.2) and no group effect was found in any multivariable models. Body mass index regardless of group was found to be inversely associated with serum 25(OH)D concentrations (P=.025). There was no difference in the dietary intake of vitamin D or calcium between groups. The healthy volunteers had a significantly greater amount of sunlight exposure but this did not result in higher 25(OH)D when compared with those with HF. Our findings suggest that body mass index has an important relationship with 25(OH)D concentrations regardless of a person being healthy or having HF.