Medication use, renin-angiotensin system inhibitors, and acute care utilization after hospitalization in patients with chronic kidney disease.

OBJECTIVES: The aims of this secondary analysis were to: (a) characterize medication use following hospital discharge for patients with chronic kidney disease (CKD), and (b) investigate relationships of medication use with the primary composite outcome of acute care utilization 90 days after hospitalization. METHODS: The CKD-Medication Intervention Trial (CKD-MIT) enrolled acutely ill hospitalized patients with CKD stages 3-5 not dialyzed (CKD 3-5 ND). In this post hoc analysis, data for medication use were characterized, and the relationship of medication use with the primary outcome was evaluated using Cox proportional hazards models. RESULTS: Participants were taking a mean of 12.6 (standard deviation=5.1) medications, including medications from a wide variety of medication classes. Nearly half of study participants were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB). ACE inhibitor/ARB use was associated with decreased risk of the primary outcome (hazard ratio=0.51; 95% confidence interval 0.28-0.95; p=0.03) after adjustment for baseline estimated glomerular filtration rate, age, sex, race, blood pressure, albuminuria, and potential nephrotoxin use. CONCLUSIONS: A large number, variety, and complexity of medications were used by hospitalized patients with CKD 3-5 ND. ACE inhibitor or ARB use at hospital discharge was associated with a decreased risk of 90-day acute care utilization.

Medication Therapy Management after Hospitalization in CKD: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: CKD is characterized by remarkably high hospitalization and readmission rates. Our study aim was to test a medication therapy management intervention to reduce subsequent acute care utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The CKD Medication Intervention Trial was a single-blind (investigators), randomized clinical trial conducted at Providence Health Care in Spokane, Washington. Patients with CKD stages 3-5 not treated by dialysis who were hospitalized for acute illness were recruited. The intervention was designed to improve posthospitalization care by medication therapy management. A pharmacist delivered the intervention as a single home visit within 7 days of discharge. The intervention included these fundamental elements: comprehensive medication review, medication action plan, and a personal medication list. The primary outcome was a composite of acute care utilization (hospital readmissions and emergency department and urgent care visits) for 90 days after hospitalization. RESULTS: Baseline characteristics of participants (n=141) included the following: age, 69±11 (mean±SD) years old; women, 48% (67 of 141); diabetes, 56% (79 of 141); hypertension, 83% (117 of 141); eGFR, 41±14 ml/min per 1.73 m2 (serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation); and urine albumin-to-creatinine ratio median, 43 mg/g (interquartile range, 8-528) creatinine. The most common primary diagnoses for hospitalization were the following: cardiovascular events, 36% (51 of 141); infections, 18% (26 of 141); and kidney diseases, 12% (17 of 141). The primary outcome occurred in 32 of 72 (44%) of the medication intervention group and 28 of 69 (41%) of those in usual care (log rank P=0.72). For only hospital readmission, the rate was 19 of 72 (26%) in the medication intervention group and 18 of 69 (26%) in the usual care group (log rank P=0.95). There was no between-group difference in achievement of guideline-based goals for use of renin-angiotensin system inhibition or for BP, hemoglobin, phosphorus, or parathyroid hormone. CONCLUSIONS: Acute care utilization after hospitalization was not reduced by a pharmacist-led medication therapy management intervention at the transition from hospital to home.

Medication Intervention for Chronic Kidney Disease Patients Transitioning from Hospital to Home: Study Design and Baseline Characteristics.

BACKGROUND: The hospital readmission rate in the population with chronic kidney disease (CKD) is high and strategies to reduce this risk are urgently needed. METHODS: The CKD-Medication Intervention Trial (CKD-MIT; www.clinicaltrials.gov; NCTO1459770) is a single-blind (investigators), randomized, clinical trial conducted at Providence Health Care in Spokane, Washington. Study participants are hospitalized patients with CKD stages 3-5 (not treated with kidney replacement therapy) and acute illness. The study intervention is a pharmacist-led, home-based, medication management intervention delivered within 7 days after hospital discharge. The primary outcome is a composite of hospital readmissions and visits to emergency departments and urgent care centers for 90 days following hospital discharge. Secondary outcomes are achievements of guideline-based targets for CKD risk factors and complications. RESULTS: Enrollment began in February 2012 and ended in May 2015. At baseline, the age of participants was 69 ± 11 years (mean ± SD), 50% (77 of 155) were women, 83% (117 of 141) had hypertension and 56% (79 of 141) had diabetes. At baseline, the estimated glomerular filtration rate was 41 ± 14 ml/min/1.73 m2 and urine albumin-to-creatinine ratio was 43 mg/g (interquartile range 8-528 mg/g). The most frequent diagnosis category for the index hospital admission was cardiovascular diseases at 34% (53 of 155), but the most common single diagnosis for admission was community-acquired acute kidney injury at 10% (16 of 155). CONCLUSION: Participants in CKD-MIT are typical of acutely ill hospitalized patients with CKD. A medication management intervention after hospital discharge is under study to reduce post-hospitalization acute care utilization and to improve CKD management.

Randomized controlled trial of contingency management for stimulant use in community mental health patients with serious mental illness.

OBJECTIVE: The primary objective of this study was to determine whether contingency management was associated with increased abstinence from stimulant drug use in stimulant-dependent patients with serious mental illness treated in a community mental health center. Secondary objectives were to determine whether contingency management was associated with reductions in use of other substances, psychiatric symptoms, HIV risk behavior, and inpatient service utilization. METHOD: A randomized controlled design was used to compare outcomes of 176 outpatients with serious mental illness and stimulant dependence. Participants were randomly assigned to receive 3 months of contingency management for stimulant abstinence plus treatment as usual or treatment as usual with reinforcement for study participation only. Urine drug tests and self report, clinician-report, and service utilization outcomes were assessed during the 3-month treatment period and the 3-month follow-up period. RESULTS: Although participants in the contingency management condition were significantly less likely to complete the treatment period than those assigned to the control condition (42% compared with 65%), they were 2.4 times (95% CI=1.9­3.0)more likely to submit a stimulant-negative urine test during treatment. Compared with participants in the control condition,they had significantly lower levels of alcohol use, injection drug use, and psychiatric symptoms and were one-fifth as likely as those assigned to the control condition to be admitted for psychiatric hospitalization during treatment. They also reported significantly fewer days of stimulant drug use during the 3-month follow-up. CONCLUSIONS: When added to treatment as usual, contingency management is associated with large reductions in stimulant,injection drug, and alcohol use.Reductions in psychiatric symptoms and hospitalizations are important secondary benefits.

Efficient driver drowsiness detection at moderate levels of drowsiness.

Previous research on driver drowsiness detection has focused primarily on lane deviation metrics and high levels of fatigue. The present research sought to develop a method for detecting driver drowsiness at more moderate levels of fatigue, well before accident risk is imminent. Eighty-seven different driver drowsiness detection metrics proposed in the literature were evaluated in two simulated shift work studies with high-fidelity simulator driving in a controlled laboratory environment. Twenty-nine participants were subjected to a night shift condition, which resulted in moderate levels of fatigue; 12 participants were in a day shift condition, which served as control. Ten simulated work days in the study design each included four 30-min driving sessions, during which participants drove a standardized scenario of rural highways. Ten straight and uneventful road segments in each driving session were designated to extract the 87 different driving metrics being evaluated. The dimensionality of the overall data set across all participants, all driving sessions and all road segments was reduced with principal component analysis, which revealed that there were two dominant dimensions: measures of steering wheel variability and measures of lateral lane position variability. The latter correlated most with an independent measure of fatigue, namely performance on a psychomotor vigilance test administered prior to each drive. We replicated our findings across eight curved road segments used for validation in each driving session. Furthermore, we showed that lateral lane position variability could be derived from measured changes in steering wheel angle through a transfer function, reflecting how steering wheel movements change vehicle heading in accordance with the forces acting on the vehicle and the road. This is important given that traditional video-based lane tracking technology is prone to data loss when lane markers are missing, when weather conditions are bad, or in darkness. Our research findings indicated that steering wheel variability provides a basis for developing a cost-effective and easy-to-install alternative technology for in-vehicle driver drowsiness detection at moderate levels of fatigue.

Dietary amino acids and blood pressure: a cohort study of patients with cardiovascular disease.

BACKGROUND: Dietary protein has been variably reported to either lower or raise blood pressure. The purpose of this study was to determine whether intakes of specific amino acids differentially associate with blood pressure. STUDY DESIGN: Observational cohort study by secondary analysis of clinical trial data. SETTING & PARTICIPANTS: Study of low-fat versus Mediterranean-style diets in patients with prevalent cardiovascular disease. PREDICTOR: Dietary amino acids. OUTCOMES: Systolic and diastolic blood pressure. MEASUREMENTS: Dietary nutrients and cardiovascular risk factors were assessed at baseline, 3 and 6 months, and then every 6 months for 2 years. RESULTS: Baseline blood pressure was 119 ± 16 (SD)/72 ± 10 (SD) mm Hg (n = 92) and dietary protein intake was 80 ± 31 g/d. Independent amino acid variables (quartiles of intake) were analyzed by generalized estimating equation models with prespecified covariates for time-varying systolic and diastolic blood pressure. The odds of each 1-SD higher systolic or diastolic blood pressure (ie, 16 and 10 mm Hg, respectively) were increased per quartile of intake for methionine (ORs of 1.29 [95% CI, 1.14-1.46] and 1.21 [95% CI, 1.05-1.39], respectively) and alanine (ORs of 1.17 [95% CI, 1.05-1.30] and 1.22 [95% CI, 1.07-1.38], respectively). Quartiles of intake for threonine (ORs of 0.84 [95% CI, 0.74-0.96] and 0.87 [95% CI, 0.75-1.01], respectively) and histidine (ORs of 0.92 [95% CI, 0.86-1.00] and 0.89 [95% CI, 0.82-0.97], respectively) had inverse associations with the same degree of difference in blood pressure. LIMITATIONS: Modest sample-size biases toward the chance of false-negative results; potential for residual confounding; colinearity between amino acids may obscure relevant relationships to blood pressure; associational findings do not establish causality. CONCLUSIONS: Intakes of methionine and alanine were associated positively with higher blood pressure, whereas intakes of threonine and histidine had inverse associations. These amino acids merit further study for advancing dietary approaches to blood pressure reduction.

Risks of subsequent hospitalization and death in patients with kidney disease.

BACKGROUND AND OBJECTIVES: Rates of hospitalization are known to be high in patients with kidney disease. However, ongoing risks of subsequent hospitalization and mortality are uncertain. The primary objective was to evaluate patients with kidney disease for long-term risks of subsequent hospitalization, including admissions resulting in death. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients hospitalized in Washington State between April of 2006 and December of 2008 who survived to discharge (n=676,343) were classified by International Classification of Disease codes into CKD (n=27,870), dialysis (n=6131), kidney transplant (n=1100), and reference (n=641,242) cohorts. Cox proportional hazard models controlling for age, sex, payer, comorbidity, previous hospitalization, primary diagnosis category, and length of stay were conducted for time to event analyses. RESULTS: Compared with the reference cohort, risks for subsequent hospitalization were increased in the CKD (hazard ratio=1.20, 99% confidence interval=1.18-1.23, P<0.001), dialysis (hazard ratio=1.76, 99% confidence interval=1.69-1.83, P<0.001), and kidney transplant (hazard ratio=1.85, 99% confidence interval=1.68-2.03, P<0.001) cohorts, with a mean follow-up time of 29 months. Similarly, risks for fatal hospitalization were increased for patients in the CKD (hazard ratio=1.41, 99% confidence interval=1.34-1.49, P<0.001), dialysis (hazard ratio=3.04, 99% confidence interval=2.78-3.31, P<0.001), and kidney transplant (hazard ratio=2.25, 99% confidence interval=1.67-3.03, P<0.001) cohorts. Risks for hospitalization and fatal hospitalization increased in a graded manner by CKD stage. CONCLUSIONS: Risks of subsequent hospitalization, including admission resulting in death, among patients with kidney disease were substantially increased in a large statewide population. Patients with kidney disease should be a focus of efforts to reduce hospitalizations and mortality.

Predicting drug court outcome among amphetamine-using participants.

Amphetamine use and abuse carry with it substantial social costs. Although there is a perception that amphetamine users are more difficult to treat than other substance users, drug courts have been used to effectively address drug-related crimes and hold the potential to lessen the impact of amphetamine abuse through efficacious treatment and rehabilitation. The objective of this study was to identify predictors of drug court outcome among amphetamine-using participants. A drug court database was obtained (N = 540) and amphetamine-using participants (n= 341) identified. Multivariate binary regression models run for the amphetamine-using participants identified being employed and being a parent as predictive of successful completion of the program, whereas being sanctioned to jail during the program was inversely related to program completion.

Modulation of advanced glycation end products by candesartan in patients with diabetic kidney disease--a dose-response relationship study.

Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria ≥500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure. At baseline and after each dosing period, blood pressure measurements and 24-hour urine collections were obtained. Urinary carboxymethyl lysine, an AGE biomarker, was reduced over the 12-week dose escalation protocol (r = 0.38, P = 0.01) in DKD participants. Creatinine clearance increased slightly, but albuminuria was unaffected by candesartan administration. Baseline urinary transforming growth factor-ß1 excretion was lower in DKD participants than in controls and did not change during the study period. Reducing kidney exposure to AGEs may be a mechanism of protection by angiotensin receptor blockade in DKD. AGEs may also impact the diabetic kidney through mechanisms independent of transforming growth factor-ß1.

Longitudinal relationships among coronary artery calcification, serum phosphorus, and kidney function.

BACKGROUND AND OBJECTIVES: Coronary artery calcification (CAC) is common in advanced chronic kidney disease (CKD), yet its onset and time course are uncertain. The study objective was to assess longitudinal relationships among CAC, kidney function, and traditional and putative cardiovascular disease (CVD) risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a prospective cohort analysis from the Spokane Heart Study, a long-term observational study of community-dwelling adults who were assessed every 2 yr for CAC (electron-beam computed tomography), CVD risk factors, and laboratory testing. Estimated GFR (eGFR) was determined by the reexpressed Modification of Diet in Renal Disease equation. RESULTS: CAC was present in 28% (245 of 883) at baseline. After 6 yr, new-onset CAC developed in 33% (122 of 371); severity increased from a median CAC score of 38 to 152 in those with baseline CAC. Neither eGFR (101 +/- 34 versus 104 +/- 31 ml/min per 1.73 m(2), respectively) nor serum phosphorus (3.25 +/- 0.49 versus 3.29 +/- 0.48 mg/dl, respectively) differed by CAC presence or absence at baseline; however, multivariate models (generalized estimating equations for incidence and prevalence) revealed that independent predictors of CAC over time were greater baseline CAC scores, higher serum phosphorus levels, lower eGFR levels, and traditional CVD risk factors. Each 1-mg/dl increase in phosphorus imparted odds ratios for CAC of 1.61 (incidence) and 1.54 (prevalence), risks comparable to traditional CVD risk factors. CONCLUSIONS: CAC becomes more frequent and severe over time. Higher levels of serum phosphorus and reduced kidney function independently predicted CAC.

Should albuminuria be a focus of antihypertensive therapy goals?

Albuminuria has been recognized as a risk marker for both chronic kidney disease and cardiovascular disease in large observational cohorts. In addition, post hoc analyses of many large randomized trials have found a positive relationship between albu-minuria and adverse renal and cardiovascular outcomes, leading some to suggest that albuminuria may be a potential therapeutic target for antihypertensive treatment. However, direct clinical evidence linking albuminuria reduction to reduction in adverse renal and cardiovascular events is scarce. This paper reviews the evidence in the current literature to address whether albuminuria can be used as a credible predictor of risk for chronic kidney disease and cardiovascular disease and also reviews the clinical trial evidence to appraise the prospect of using albuminuria as a therapeutic target to prevent adverse renal and cardiovascular events.

Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial).

Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain. The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infarction (MI) in a randomized, controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis. First MI survivors were randomized to a low-fat (n = 50) or Mediterranean-style (n = 51) diet. The 2 diets were low in saturated fat (< or =7% kcal) and cholesterol (< or =200 mg/day); the Mediterranean-style diet was distinguished by greater omega-3 fat intake (>0.75% kcal). Participants received individual dietary counseling sessions, 2 within the first month and again at 3, 6, 12, 18, and 24 months, along with 6 group sessions. Combined dietary intervention groups (cases, n = 101) were compared with a usual-care group (controls, n = 101) matched for age, gender, MI type and treatment, and status of diabetes mellitus and hypertension. Primary-outcome-free survival (a composite of all-cause and cardiac deaths, MI, hospital admissions for heart failure, unstable angina pectoris, or stroke) did not differ between low-fat (42 of 50) and Mediterranean-style (43 of 51) diet groups over a median follow-up period of 46 months (range 18 to 72; log-rank p = 0.81). Patients receiving dietary intervention had better primary-outcome-free survival (85 of 101) than usual-care controls (61 of 101) (log-rank p <0.001), with unadjusted and adjusted odds ratios of 0.33 (95% confidence interval 0.18 to 0.60, p <0.001) and 0.28 (95% confidence interval 0.13 to 0.63, p = 0.002), respectively. In conclusion, active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI.

Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study.

OBJECTIVE: To evaluate the effect of vaginal lubricants Pre-Seed, FemGlide, Astroglide, and Replens on human sperm motility and chromatin integrity. DESIGN: Prospective, comparative, in vitro study. SETTING: Andrology laboratory at tertiary care hospital. PATIENT(S): Thirteen normozoospermic donors. INTERVENTION(S): Semen samples from 13 subjects were incubated in human tubal fluid media (HTF) controls and 10% (vol/vol) of Pre-Seed, FemGlide, Astroglide, and Replens lubricants. After 30 minutes, progressive sperm motility was assessed by light microscopy. Semen samples of 12 patients were placed in positive control (HTF), negative control (10% K-Y Jelly lubricant), and 10% vol/vol Pre-Seed and FemGlide lubricants. After 4 hours culture, spermatozoa were analyzed for percent DNA fragmentation index with use of the acridine orange-based sperm chromatin structure assay. MAIN OUTCOME MEASURE(S): Sperm motility and percent DNA fragmentation index. RESULTS: Percent motility did not differ significantly between HTF controls and Pre-Seed, whereas FemGlide, Replens, and Astroglide lubricants demonstrated a significant decrease in motility. There was no significant difference in percent DNA fragmentation index between the HTF controls and Pre-Seed, but a significant decline in sperm chromatin quality occurred with FemGlide and K-Y Jelly. CONCLUSION: Pre-Seed does not cause a significant decrease in progressive sperm motility or chromatin integrity in contrast to other lubricants used by couples.

Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach.

OBJECTIVES: To determine the efficacy of varicocelectomy in improving semen parameters. METHODS: A meta-analysis was performed to evaluate both randomized controlled trials and observational studies using a new scoring system. This scoring system was developed to adjust and quantify for various potential sources of bias, including selection bias, follow-up bias, confounding bias, information or detection bias, and other types of bias, such as misclassification. Of 136 studies identified through the electronic and hand search of references, only 17 studies met our inclusion criteria. The study population was infertile men with clinically palpable unilateral or bilateral varicocele and at least one abnormal semen parameter who had undergone surgical varicocelectomy (high ligation or inguinal microsurgery). Only those studies that had at least three semen analyses (ie, sperm count, motility, and morphology) per patient, before and after surgical varicocelectomy, were included. RESULTS: The combined analysis demonstrated that the sperm concentration increased by 9.71 x 10(6)/mL (95% confidence interval [CI] 7.34 to 12.08, P <0.00001) and motility increased by 9.92% (95% CI 4.90 to 14.95, P = 0.0001) after microsurgical varicocelectomy. Similarly, the sperm concentration increased by 12.03 x 10(6)/mL (95% CI 5.71 to 18.35, P = 0.0002) and motility increased by 11.72% (95% CI 4.33 to 19.12, P = 0.002) after high ligation varicocelectomy. The improvement in World Health Organization sperm morphology was 3.16% (95% CI 0.72 to 5.60, P = 0.01) after both microsurgery and high ligation varicocelectomy. CONCLUSIONS: Surgical varicocelectomy significantly improves semen parameters in infertile men with palpable varicocele and abnormal semen parameters.

Adapting multiple-family group treatment for brain and spinal cord injury intervention development and preliminary outcomes.

OBJECTIVE: There is a need for interventions that assist in managing the multiple adjustments of persons with spinal cord and brain injuries and their families. The purpose of the present field-initiated development project was to adapt a family psychoeducation model, multiple-family group treatment (MFGT), for persons with brain and spinal cord injury and their families. DESIGN: The experiences of survivors and caregivers in MFGT were evaluated using quantitative and qualitative methods. Twenty-seven survivors and 28 caregivers participated in MFGT for 12-18 mos. Reliable and valid quantitative measures were used to assess a variety of target outcomes. Additionally, semistructured interviews and focus groups were conducted with participants. RESULTS: Survivors reported a decrease in depressive symptoms and anger expression toward others as well as an increase in life satisfaction. Caregivers reported a significant reduction in burden. The themes derived from the qualitative analysis addressed the normalization of the caregiving experience, importance of socialization, improvement in a variety of coping skills, and education about the injuries. CONCLUSIONS: The findings support the adaptation of MFGT for brain and spinal cord injuries.

Reassessing the value of varicocelectomy as a treatment for male subfertility with a new meta-analysis.

OBJECTIVE: To determine the efficacy of varicocelectomy as a treatment for male factor infertility by improving the chance of spontaneous pregnancy. DESIGN: Meta-analysis. SETTING: Cleveland Clinic's Glickman Urological Institute. PATIENT(S): Infertile men with abnormal results on semen analyses and a palpable varicocele. INTERVENTION(S): Surgical varicocelectomy. MAIN OUTCOME MEASURE(S): Spontaneous pregnancy outcome. RESULT(S): The odds of spontaneous pregnancy after surgical varicocelectomy, compared with no or medical treatment for palpable varicocele, were 2.87 (95% confidence interval [CI], 1.33-6.20) with use of a random-effects model or 2.63 (95% CI, 1.60-4.33) with use of a fixed-effects model. The number needed to treat was 5.7 (95% CI, 4.4-9.5). CONCLUSION(S): Surgical varicocelectomy in infertile men with palpable lesions and at least one abnormal semen parameter improves the odds of spontaneous pregnancy in their female partners. Five studies were included (two randomized, three observational). All were scored for bias. Our study suggests that varicocelectomy in selected patients does indeed have beneficial effects on fertility status.

Multiple-family group treatment of outpatients with schizophrenia: impact on service utilization.

The impact of multiple-family group treatment (MFGT) on outpatient and inpatient mental health service utilization of 97 persons with schizophrenia was investigated. Participants were randomly assigned to standard care (n = 44) or standard care plus MFGT (n = 53). Service use for a year prior to randomization, the 2-year study period, and a 1-year follow-up were examined. Relative to standard care participants, the MFGT group had reduced community hospitalization during year 1 of the intervention and reduced state hospitalization at follow-up. During the intervention period, MFGT participants demonstrated a significant increase in outpatient utilization as a direct consequence of the intervention. However, when service use was summed across 3 years post-randomization, no group differences were observed. Results suggest that implementation of MFGT in a community mental health setting reduces inpatient service at specific time periods, without significantly increasing outpatient service utilization. These findings add to other outcomes from this study that demonstrate decreased psychiatric symptoms and caregiver distress.

Implications of chronic kidney disease for dietary treatment in cardiovascular disease.

Chronic kidney disease (CKD) often accompanies cardiovascular disease (CVD). Trends foretelling a greater burden of CKD and CVD are largely a result of increasing frequencies of obesity, hypertension, and diabetes. Nutritional therapy occupies a critical role in reducing risk factors and preventing progressive damage to the kidneys and heart. Nutritional assessment and treatment should take into account both health concerns. This review examines several diet components and eating styles for efficacy in the treatment of these conditions. A variety of dietary regimens claim to provide health benefits, but rigorous scientific validation of long-term efficacy is frequently lacking. An urgent need exists for eating styles that reduce risk of chronic diseases and that are acceptable and achievable in free-living populations. We describe our ongoing study, a randomized controlled trial comparing the American Heart Association Step II diet and a Mediterranean diet, in survivors of a first myocardial infarction. The primary end point is a composite of mortality and major CVD events. Because many in this population have CKD, indicators of kidney damage and function are prespecified secondary end points. Results of this trial should provide insight into optimal dietary interventions for persons with both CVD and CKD.

A causal role for uric acid in fructose-induced metabolic syndrome.

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.