A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops.

BACKGROUND: Uncontrolled hypertension is a major problem among non-Hispanic black men, who are underrepresented in pharmacist intervention trials in traditional health care settings. METHODS: We enrolled a cohort of 319 black male patrons with systolic blood pressure of 140 mm Hg or more from 52 black-owned barbershops (nontraditional health care setting) in a cluster-randomized trial in which barbershops were assigned to a pharmacist-led intervention (in which barbers encouraged meetings in barbershops with specialty-trained pharmacists who prescribed drug therapy under a collaborative practice agreement with the participants' doctors) or to an active control approach (in which barbers encouraged lifestyle modification and doctor appointments). The primary outcome was reduction in systolic blood pressure at 6 months. RESULTS: At baseline, the mean systolic blood pressure was 152.8 mm Hg in the intervention group and 154.6 mm Hg in the control group. At 6 months, the mean systolic blood pressure fell by 27.0 mm Hg (to 125.8 mm Hg) in the intervention group and by 9.3 mm Hg (to 145.4 mm Hg) in the control group; the mean reduction was 21.6 mm Hg greater with the intervention (95% confidence interval, 14.7 to 28.4; P<0.001). A blood-pressure level of less than 130/80 mm Hg was achieved among 63.6% of the participants in the intervention group versus 11.7% of the participants in the control group (P<0.001). In the intervention group, the rate of cohort retention was 95%, and there were few adverse events (three cases of acute kidney injury). CONCLUSIONS: Among black male barbershop patrons with uncontrolled hypertension, health promotion by barbers resulted in larger blood-pressure reduction when coupled with medication management in barbershops by specialty-trained pharmacists. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT02321618 .).

Lack of FGF23 response to acute changes in serum calcium and PTH in humans.

CONTEXT: 1,25-Dihydroxyvitamin D (1,25D) administration and long-term increases in phosphate, PTH, and calcium concentrations are associated with increases in circulating fibroblast growth factor 23 (FGF23); however, whether or not acute changes in serum calcium modulate short-term FGF23 release is unknown. OBJECTIVE/DESIGN: To assess the direct effect of acute changes in calcium and PTH on circulating FGF23 levels. SETTING: A university clinical and translational research center. PATIENTS/PARTICIPANTS: Twelve healthy volunteers and 10 dialysis patients. INTERVENTIONS: Calcium gluconate and sodium citrate were infused for 120 minutes on 2 consecutive days. MAIN OUTCOME MEASURES: Serum levels of ionized calcium, phosphorus, PTH, 1,25D, and plasma C-terminal FGF23 levels were obtained at 0, 13, 30, 60, 90, and 120 minutes during the infusions. RESULTS: During the calcium infusion, serum calcium concentrations increased from 1.33 ± 0.01 to 1.57 ± 0.04 mmol/L (P < .05 from baseline) and from 1.20 ± 0.05 to 1.50 ± 0.03 mmol/L (P < .05 from baseline) in healthy subjects and in dialysis patients, respectively, whereas serum calcium values decreased from 1.33 ± 0.01 to 1.03 ± 0.02 mmol/L (P < .05 from baseline) and from 1.26 ± 0.04 to 1.07 ± 0.03 mmol/L (P < .05 from baseline) in the two groups, respectively during the sodium citrate infusion. PTH levels decreased from 35 (29, 57) to 8 (2,10) pg/mL (healthy subjects) (P < .05 from baseline) and from 292 (109, 423) to 44 (28, 86) pg/mL (dialysis patients) (P < .05 from baseline) during the calcium infusion and rose from 31 (25, 56) to 122 (95, 157) pg/mL and from 281 (117, 607) to 468 (169, 928) pg/mL (P < .05 from baseline) during sodium citrate infusion. Serum 1,25D levels and plasma FGF23 values remained unchanged during both infusions in both groups. CONCLUSIONS: Short-term changes in calcium and PTH levels do not affect FGF23 concentrations in either healthy volunteers or dialysis patients.

Online self-report data for duchenne muscular dystrophy confirms natural history and can be used to assess for therapeutic benefits.

To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from DuchenneConnect, an online registry. Data collected were compared to prior natural history data in regard to age at diagnosis, mutation spectrum, and age at loss of ambulation. Because registrants reported differences in steroid and other medication usage, as well as age and ambulation status, we could explore these data for correlations with age at loss of ambulation. Using multivariate analysis, current steroid usage was the most significant and largest independent predictor of improved wheelchair-free survival. Thus, these online self-report data were sufficient to retrospectively observe that current steroid use by patients with DMD is associated with a delay in loss of ambulation. Comparing commonly used steroid drugs, deflazacort prolonged ambulation longer than prednisone (median 14 years and 13 years, respectively). Further, use of Vitamin D and Coenzyme Q10, insurance status, and age at diagnosis after 4 years were also significant, but smaller, independent predictors of longer wheelchair-free survival. Nine other common supplements were also individually tested but had lower study power. This study demonstrates the utility of DuchenneConnect data to observe therapeutic differences, and highlights needs for improvement in quality and quantity of patient-report data, which may allow exploration of drug/therapeutic practice combinations impractical to study in clinical trial settings. Further, with the low barrier to participation, we anticipate substantial growth in the dataset in the coming years.

Patient education integrated with acupuncture for relief of cancer-related fatigue randomized controlled feasibility study.

BACKGROUND: Cancer-related fatigue (CRF) is a prominent clinical problem. There are calls for multi-modal interventions. METHODS: We assessed the feasibility of delivering patient education integrated with acupuncture for relief of CRF in a pilot randomized controlled trial (RCT) with breast cancer survivors using usual care as control. Social cognitive and integrative medicine theories guided integration of patient education with acupuncture into a coherent treatment protocol. The intervention consisted of two parts. First, patients were taught to improve self-care by optimizing exercise routines, improving nutrition, implementing some additional evidence-based cognitive behavioral techniques such as stress management in four weekly 50-minute sessions. Second, patients received eight weekly 50-minute acupuncture sessions. The pre-specified primary outcome, CRF, was assessed with the Brief Fatigue Inventory (BFI). Secondary outcomes included three dimensions of cognitive impairment assessed with the FACT-COGv2. RESULTS: Due to difficulties in recruitment, we tried several methods that led to the development of a tailored recruitment strategy: we enlisted oncologists into the core research team and recruited patients completing treatment from oncology waiting rooms. Compared to usual care control, the intervention was associated with a 2.38-point decline in fatigue as measured by the BFI (90% Confidence Interval from 0.586 to 5.014; p <0.10). Outcomes associated with cognitive dysfunction were not statistically significant. CONCLUSIONS: Patient education integrated with acupuncture had a very promising effect that warrants conducting a larger RCT to confirm findings. An effective recruitment strategy will be essential for the successful execution of a larger-scale trial. TRIAL REGISTRATION: NCT00646633.

The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84).

CONTEXT: Factors contributing to PTH resistance in dialysis patients remain elusive. OBJECTIVES: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients. DESIGN: The study was a prospective, controlled assessment of response to PTH(1-34). SETTING: The study was performed at the University of California, Los Angeles, General Clinical Research Center. PARTICIPANTS: Nineteen dialysis patients and 17 healthy volunteers were studied. INTERVENTION: PTH(1-34) was infused at a rate of 8 pmol/kg x h for 46 h. Bone biopsy was performed in all dialysis patients. MAIN OUTCOME MEASURES: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion. RESULTS: Serum calcium levels rose in healthy volunteers (9.2 +/- 0.1 to 11.9 +/- 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 +/- 0.3 to 10.7 +/- 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 +/- 0.1 to 3.5 +/- 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 +/- 0.4 to 8.0 +/- 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover. CONCLUSIONS: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.

Response of different PTH assays to therapy with sevelamer or CaCO3 and active vitamin D sterols.

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 +/- 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO(3)) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 +/- 0.1 to 9.7 +/- 0.1 mg/dl during CaCO(3) therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO(3) and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 +/- 75 and 932 +/- 89 pg/ml, and levels declined to 491 +/- 55 and 543 +/- 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO(3). The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.

Testosterone treatment in multiple sclerosis: a pilot study.

OBJECTIVE: To study the effect of testosterone supplementation on men with multiple sclerosis (MS). DESIGN, SETTING, AND PARTICIPANTS: Men are less susceptible to many autoimmune diseases, including MS. Possible causes for this include sex hormones and/or sex chromosome effects. Testosterone treatment ameliorates experimental allergic encephalomyelitis, an animal model of MS, but the effect of testosterone supplementation on men with MS is not known. Therefore, 10 men with relapsing-remitting MS were studied using a crossover design whereby each patient served as his own control. There was a 6-month pretreatment period followed by a 12-month period of daily treatment with 10 g of the gel containing 100 mg of testosterone. MAIN OUTCOME MEASURES: Clinical measures of disability and cognition (the Multiple Sclerosis Functional Composite and the 7/24 Spatial Recall Test) and monthly magnetic resonance imaging measures of enhancing lesion activity and whole brain volumes. RESULTS: One year of treatment with testosterone gel was associated with improvement in cognitive performance (P = .008) and a slowing of brain atrophy (P <.001). There was no significant effect of testosterone treatment on gadolinium-enhancing lesion numbers (P = .31) or volumes (P = .94). Lean body mass (muscle mass) was increased (P = .02). CONCLUSION: These exploratory findings suggest that testosterone treatment is safe and well tolerated and has potential neuroprotective effects in men with relapsing-remitting MS.

Dietary mineral and trace element intake and squamous cell carcinoma of the esophagus in a Chinese population.

Few studies have been conducted in low-selenium areas of China to assess the relationships between dietary intake of selenium and zinc and the risk of squamous cell carcinoma of the esophagus (SCCE). We studied dietary mineral and trace element intake and risk of SCCE in a population- based, case-control study in Taixing, China, in 2000. A total of 218 SCCE patients and 415 population healthy controls were interviewed using a standard dietary and health questionnaire. The median and quartiles were calculated to represent the average level and distribution of selected dietary minerals and trace elements estimated by the Chinese Standard Tables of Food Composition. The adjusted odds ratios (ORs) comparing the highest with the lowest quartiles were 0.30 (95% confidence intervals, CIs = 0.13-0.67) for selenium intake and 0.28 (95% CI = 0.11-0.70) for zinc intake with obvious dose-dependent patterns (P values for trend = 0.01). The adjusted OR for the combined effect of selenium and zinc intake was 0.53 (95% CI = 0.29-0.96) after controlling for potential confounding factors, including age, gender, educational level, body mass index, and total energy intake. Our results suggested that the potential joint effect of zinc and selenium might contribute to SCCE risk. Increased dietary intake of selenium and zinc may decrease the risk of SCCE in a low-selenium area of China.

Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.

PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.

A pilot clinical study of short-term isoflavone supplements in breast cancer patients.

Many laboratory-based studies have shown that soy can suppress breast cancer proliferation. However, given the recent controversy generated by animal experiments that soy may under certain conditions stimulate breast cancer growth, we decided to carry out a pilot clinical trial in order to elucidate any interaction(s) between short-term isoflavone supplement administration and breast cancer growth. After a core-needle biopsy established the diagnosis of breast cancer, 17 patients were administered soy isoflavone tablets for two weeks. This surgically based study provided the unique opportunity to make objective observations based on human breast cancer tissues and blood obtained prior to and after isoflavone supplement treatment in the same patient. Twenty-six historical control cases with similar characteristics to the experimental patients were selected for comparison. We observed that the apoptosis/mitosis ratios in isoflavone-treated cancer specimens were not significantly different from those of control untreated cancer specimens. Furthermore, there appeared to be a statistically nonsignificant trend towards cancer growth inhibition in the isoflavone treatment group, as manifested by higher apoptosis/mitosis ratios compared with those from the control untreated group. Ex vivo/in vitro assays using serum from breast cancer patients prior to and at the conclusion of soy treatment reveal no significant proliferative changes on both breast cancer cells and endothelial cells. We concluded that the effect of soy on breast cancer deserves further studies in larger clinical trials.

cDNA microarray analysis of endothelial cells in response to green tea reveals a suppressive phenotype.

Green tea may prevent cancer, partially by inhibiting tumor angiogenesis. Our previous studies showed that green tea extract was effective in inhibiting breast cancer and endothelial cell proliferation in vitro, and suppressed xenograft size and decreased the tumor vessel density in vivo. Here, we set out to further investigate the molecular mechanisms of this observed angiogenesis suppression. We utilized cDNA microarray technology to profile the global changes in endothelial cellular gene expression in response to green tea. HUVEC (human umbilical vein endothelial cells) were exposed in vitro to green tea for either 6 or 48 h. Only statistically significantly differentially expressed genes were analyzed. Gene profiling demonstrated a global down-regulation of multiple genes involved in endothelial cell growth, signal transduction and oxidation, accompanied by up-regulation of several apoptotic genes. We validated these observations by showing positive correlations with biological assays of cellular proliferation, cell cycle, and apoptosis. The anti-oxidant characteristics of green tea and its metabolites were confirmed in the ORAC (oxygen radical absorbance capacity) assay. cDNA microarray revealed that green tea has an overall suppressive effect on multiple pathways in endothelial cells. This study contributes to the comprehensive analysis of the molecular effects of green tea on endothelial cells, and provides insight into genes that may be important in chemoprevention.

Sevelamer hydrochloride: an effective phosphate binder in dialyzed children.

This pilot study was designed to evaluate the efficacy and acceptability of sevelamer hydrochloride as a phosphate binder in pediatric patients treated with dialysis. A 6-month open-label trial of sevelamer hydrochloride (Renagel) was initiated in 17 patients, aged 11.8+/-3.7 years, undergoing hemodialysis ( n=3) or peritoneal dialysis ( n=14). Following a 2-week washout period of the phosphate binders, serum phosphorus increased from 5.2+/-1.3 mg/dl to 7.5+/-2.2 mg/dl ( P<0.0002). After initiation of therapy with sevelamer hydrochloride, serum phosphorus levels decreased to 6.2+/-1.2 mg/dl ( P<0.01) during the first 8 weeks and final values were 6.3+/-1.5 mg/dl. Serum calcium concentration decreased during the washout period from 9.4+/-0.9 mg/dl to 8.9+/-1.5 mg/dl ( P<0.01); values remained unchanged thereafter. The serum calcium-phosphorus ion product decreased during the first 8 weeks and values did not change subsequently. Serum bicarbonate, parathyroid hormone, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride levels did not change. The initial prescribed dose of sevelamer hydrochloride was 121+/-50 mg/kg (4.5+/-5 g/day) and the final prescribed dose was 163+/-46 mg/kg (6.7+/-2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug.

Inhibition of fibroblast growth factors by green tea.

Investigators have shown that green tea may decrease the risk of cancer. It is widely accepted that the main active component of green tea is EGCG (epigallocatechin-3-gallate). In our previous study, we examined the effect of green tea on breast cancer growth and endothelial cells both in in vitro assays and in animal models. Our data show that both mixed green tea extract (GTE) as well as its individual catechin components are effective in inhibiting breast cancer and endothelial cell proliferation in vitro, and that GTE suppresses breast cancer xenograft size and decreases the tumor blood vessel density in vivo. In the present study, we further demonstrate that 40 microg/ml GTE or EGCG can decrease the levels of the angiogenic factor bFGF (basic fibroblast growth factor) levels in the cells. This phenomenon is observed in both human umbilical vein endothelial cells (HUVECs) and in human breast cancer cells MDA-MB231. This effect is dose dependent. Furthermore, GTE and EGCG decrease the transcript levels of bFGF and aFGF (acidic fibroblast growth factor) in HUVECs and MDA-MB231 cells. Our findings suggest that the inhibition of the angiogenic fibroblast growth factors could account for one of the mechanisms of green tea's actions. Since cancer is angiogenesis dependent, this may partially explain the antineoplastic effects associated with green tea consumption.