Impact of Achieved Blood Pressures on Mortality Risk and End-Stage Renal Disease Among a Large,Diverse Hypertension Population

Background

Medical data or clinical guidelines have not adequately addressed the ideal blood pressure (BP) treatment targets for survival and renal outcome.

Objectives

This study sought to evaluate ranges of treated BP in a large hypertension population and compare risk of mortality and end-stage renal disease (ESRD).

Methods

A retrospective cohort study within the Kaiser Permanente Southern California health system was performed from January 1, 2006, to December 31, 2010. Treated hypertensive subjects ≥18 years of age were studied. Cox proportional hazards regression models were used to evaluate the risks (hazard ratios) for mortality and/or ESRD among different BP categories with and without stratification for diabetes mellitus and older age.

Results

Among 398,419 treated hypertensive subjects (30% with diabetes mellitus), mortality occurred in 25,182 (6.3%) and ESRD in 4,957 (1.2%). Adjusted hazard ratios (95% confidence intervals [CI]) for composite mortality/ESRD in systolic BP <110, 110 to 119, 120 to 129, 140 to 149, 150 to 159, 160 to 169, and ≥170 compared with 130 to 139 mm Hg were 4.1 (95% CI: 3.8 to 1.3), 1.8 (95% CI: 1.7 to 1.9), 1.1 (95% CI: 1.1 to 1.1), 1.4 (95% CI: 1.4 to 1.5), 2.3 (95% CI: 2.2 to 2.5), 3.3 (95% CI: 3.0 to 3.6), and 4.9 (95% CI: 4.4 to 5.5) respectively. Diastolic BP 60 to 79 mm Hg were associated with the lowest risk. The nadir systolic and diastolic BP for the lowest risk was 137 and 71 mm Hg, respectively. Stratified analyses revealed that the diabetes mellitus population had a similar hazard ratio curve but a lower nadir at 131 and 69 mm Hg but age ≥70 had a higher nadir (140 and 70 mm Hg).

Conclusions

Both higher and lower treated BP compared with 130 to 139 mm Hg systolic and 60 to 79 mm Hg diastolic ranges had worsened outcomes. Our study adds to the growing uncertainty about BP treatment targets.     

The rs594445 in MOCOS gene is associated with risk of autism spectrum disorder

Metabolic Brain Disease - Molybdenum cofactor sulfurase (MOCOS) gene encodes an enzyme which is involved in purine metabolism. Recent experiments have shown down-regulation of MOCOS in adult nasal...     

Bone and mineral disorders after kidney transplantation: Therapeutic strategies

Mineral and bone diseases (MBD) are common in patients with chronic kidney disease who undergo kidney transplantation. The incidence, types and severity of MBD vary according to the duration of chronic kidney disease, presence of comorbid conditions and intake of certain medications. Moreover, multiple types of pathology may be responsible for MBD. After successful reversal of uremia by kidney transplantation, many bone and mineral disorders improve, while immunosuppression, other medications, and new and existing comorbidities may result in new or worsening MBD. Chronic kidney disease is also common after kidney transplantation and may impact bone and mineral disease. In this article, we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant outcomes. We also discussed the diagnostic approach; immunosuppression management and potential treatment of MBD in kidney transplant recipients.     

Syringe exchange, injecting and intranasal drug use

Objective   To assess trends in injecting and non-injecting drug use after implementation of large-scale syringe exchange in New York City. The belief that implementation of syringe exchange will lead to increased drug injecting has been a persistent argument against syringe exchange.
Methods   Administrative data on route of administration for primary drug of abuse among patients entering the Beth Israel methadone maintenance program from 1995 to 2007. Approximately 2000 patients enter the program each year.
Results   During and after the period of large-scale implementation of syringe exchange, the numbers of methadone program entrants reporting injecting drug use decreased while the numbers of entrants reporting intranasal drug use increased ( P  < 0.001).
Conclusion   While assessing the possible effects of syringe exchange on trends in injecting drug use is inherently difficult, these may be the strongest data collected to date showing a lack of increase in drug injecting following implementation of syringe exchange.     

HIV incidence among injection drug users in New York City, 1990 to 2002: use of serologic test algorithm to assess expansion of HIV prevention services

OBJECTIVES: We sought to estimate HIV incidence among injection drug users (IDUs) in New York City from 1990 to 2002 to assess the impact of an expansion of syringe exchange services. Syringe exchange increased greatly during this period, from 250,000 to 3,000,000 syringes exchanged annually. METHODS: Serum samples were obtained from serial cross-sectional surveys of 3,651 IDUs. HIV-positive samples were tested with the Serologic Test Algorithm for Recent HIV Seroconversion (STARHS) assay to identify recent HIV infections and to estimate HIV incidence. Consistency with other incidence studies was used to assess strengths and limitations of STARHS. RESULTS: HIV incidence declined from 3.55/100 person-years at risk (PYAR) from 1990-1992, to 2.63/100 PYAR from 1993-1995, to 1.05/100 PYAR from 1996-1998, and to 0.77/100 PYAR from 1999-2002 (P<.001). There was a very strong negative linear relationship (r= -.99, P<.005) between the annual numbers of syringes exchanged and estimated HIV incidence. These results were highly consistent with a large number of shorter incidence studies among IDUs conducted during the time period. CONCLUSIONS: STARHS testing of samples from large serial cross-sectional surveys can provide important data for the assessment of community-level HIV prevention.     

A low lymphocyte percentage is a predictor of mortality and hospitalization in hemodialysis patients

OBJECTIVES: Lymphocyte percentage (LYM%), an independently measured value to reflect peripheral lymphocyte count and a possible nutritional marker, may be related to clinical outcome in maintenance dialysis (MHD) patients. STUDY DESIGN AND SETTING: We examined the associations of the baseline white blood cell count (WBC) and LYM% with 12-month mortality and three measures of hospitalization in a cohort of 1,283 MHD patients from 10 outpatient DaVita dialysis clinics in Los Angeles County, as well as in a subcohort of 372 MHD patients with additional measures of inflammation, nutrition and comorbidity. Multi-variate Cox and Poisson models that included 13 co-variates including case-mix features, dialysis dose, blood hemoglobin and serum albumin were explored. RESULTS: Patients, aged 57.8 +/- 15.2 years, included 49% men and 49% diabetics. Baseline WBC was 7,353 +/- 2.427 per microl, and LYM% was 21.2 +/- 7.3%. LYM% had significant correlations with "malnutrition-inflammation score" and inverse correlations with serum interleukin-6. The WBC and LYM% had significant but opposite predicting values for mortality and hospitalization, indicating that a high WBC and a low LYM% were each independently associated with increased mortality. After dividing each variable into four quartiles, only the highest WBC quartile (> or = 8,500) but not the other middle two quartiles, predicted increased mortality. However, all three lower quartiles of LYM% vs. the highest quartile (based on quartile cutoffs of 16%, 20.3% and 25.5%) were significantly and progressively associated with greater risks of mortality and hospitalizations. The absolute lymphocyte count (LYM% times WBC/100) exhibited somewhat similar trends but its outcome predictability was not as strong as LYM%. CONCLUSIONS: A high WBC and a low LYM% are associated with significant increase in mortality and hospitalization in MHD patients. Lymphocyte percentage, compared to absolute lymphocyte count, appears to be a better nutritional and anti-inflammatory marker and a more sensitive predictor of mortality and hospitalization in MHD patients.     

Sexual receptivity is reduced in the female mu-opioid receptor knockout mouse

Activation of mu-opioid receptors is critical to steroid regulation of female sexual behavior, lordosis, in rodents. Estrogen treatment activates mu-opioid receptors in the medial preoptic area inhibiting lordosis, but ultimately appears important for progesterone facilitation of lordosis. We investigated the role of mu-opioid receptors in the expression of sexual receptivity in mice lacking mu-opioid receptors. Although estrogen and progesterone facilitated lordosis in mu-opioid receptor knockout mice, they exhibited deficits in lordosis quotient and score compared with wild-type females, indicating reduced sexual receptivity. In contrast, wild-type and mu-opioid receptor knockout female mice did not differ in either active or passive avoidance of the male. These data are most consistent with the hypothesis that mu-opioid receptor activation is necessary for estrogen and progesterone to maximally facilitate lordosis.     

Efficacy of saccharomyces boulardii with antibiotics in acute amoebiasis

AIM: To compare the efficacy of antibiotics therapy alone with antibiotics and saccharomyces boulardii in treatment of acute amebiasis.METHODS: In a double blind, random clinical trial on patients with acute intestinal amoebiasis, 57 adult patients with acute amoebiasis, diagnosed with clinical manifestations (acute mucous bloody diarrhea) and amebic trophozoites engulfing RBCs found in stool were enrolled in the study.Regimen 1 induded metronidazole (750 mg Tid) and iodoquinol (630 mg Tid) for 10 days. Regimen 2 contained capsules of lyophilized saccharomyces boulardii (250 mg Tid) orally in addition to regimen 1. Patients were re-examined at two and four weeks after the treatment, and stool examination was performed at the end of week 4. Student′s t-test, χ2and McNemar′s tests were used for statistical analysis.RESULTS: Three patients refused to participate. The other 54 patients were randomized to receive either regimen 1 or regimen 2 (Groups 1 and 2 respectively, each with 27patients). The two groups were similar regarding their age,sex and clinical manifestations. In Group 1, diarrhea lasted 48.0±18.5 hours and in Group 2,12.0±3.7 hours (P＜0.0001).In Group 1, the durations of fever and abdominal pain were 24.0±8.8 and 24.0±7.3 hours and in Group 2 they were 12.0±5.3 and 12.0±3.2 hours, respectively (P＜0.001).Duration of headache was similar in both groups. At week 4, amebic cysts were detected in 5 cases (18.5 %) of Group 1 but in none of the Group 2 (P＜0.02).CONCLUSION: Adding saccharomyces boulardii to antibiotics in the treatment of acute amebiasis seems to decrease the duration of clinical symptoms and cyst passage.     

Inflammation and nutrition in renal insufficiency

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.