A community-partnered approach for diversity in COVID-19 vaccine clinical trials.

Introduction: Communities of color have faced disproportionate morbidity and mortality from COVID-19, coupled with historical underrepresentation in US clinical trials, creating challenges for equitable participation in developing and testing a safe and effective COVID-19 vaccine. Methods: To increase diversity, including racial and ethnic representation, in local Los Angeles County NIH-sponsored Phase 3 SARS-CoV-2 vaccine clinical trials, we used deliberative community engagement approaches to form a Community Consultant Panel (CCP) that partnered with trial research teams. Thirteen members were recruited, including expertise from essential workers, community-based and faith-based organizations, or leaders from racial and ethnic minority communities. Results: Working closely with local investigators for the vaccine studies, the CCP provided critical insight on best practices for community trust building, clinical trial participation, and reliable information dissemination regarding COVID-19 vaccines. Modifying recruitment, outreach, and trial protocols led to majority-minority participants (55%-78%) in each of the three vaccine clinical trials. CCP's input led to cultural tailoring of recruitment materials, changes in recruitment messaging, and supportive services to improve trial accessibility and acceptability (transportation, protocols for cultural competency, and support linkages to care in case of an adverse event). Barriers to clinical trial participation unable to be resolved included childcare, requests for after-hours appointment availability, and mobile locations for trial visits. Conclusion: Using deliberative community engagement can provide critical and timely insight into the community-centered barriers to COVID-19 vaccine trial participation, including addressing social determinants of health, trust, clinical trial literacy, structural barriers, and identifying trusted messenger and reliable sources of information.

Dietary potassium intake, kidney function, and survival in a nationally representative cohort.

BACKGROUND: In healthy adults, higher dietary potassium intake is recommended given that potassium-rich foods are major sources of micronutrients, antioxidants, and fiber. Yet among patients with advanced kidney dysfunction, guidelines recommend dietary potassium restriction given concerns about hyperkalemia leading to malignant arrhythmias and mortality. OBJECTIVES: Given sparse data informing these recommendations, we examined associations of dietary potassium intake with mortality in a nationally representative cohort of adults from the NHANES. METHODS: We examined associations between daily dietary potassium intake scaled to energy intake (mg/1000 kcal), ascertained by 24-h dietary recall, and all-cause mortality among 37,893 continuous NHANES (1999-2014) participants stratified according to impaired and normal kidney function (estimated glomerular filtration rates <60 and ≥60 mL · min-1 · 1.73 m-2, respectively) using multivariable Cox models. We also examined the impact of the interplay between dietary potassium, source of potassium intake (animal- compared with plant-based sources), and coexisting macronutrient and mineral consumption upon mortality. RESULTS: Among participants with impaired and normal kidney function, the lowest tertile of dietary potassium scaled to energy intake was associated with higher mortality (ref: highest tertile) [adjusted HR (aHR): 1.18; 95% CI: 1.02, 1.38 and aHR: 1.17; 95% CI: 1.06, 1.28, respectively]. Compared with high potassium intake from plant-dominant sources, participants with low potassium intake from animal-dominant sources had higher mortality irrespective of kidney function. Among participants with impaired kidney function, pairings of low potassium intake with high protein, low fiber, or high phosphorus consumption were each associated with higher death risk. CONCLUSIONS: Lower dietary potassium scaled to energy intake was associated with higher mortality, irrespective of kidney function. There was also a synergistic relation of higher potassium intake, plant-based sources, and macronutrient/mineral consumption with survival. Further studies are needed to elucidate pathways linking potassium intake and coexisting dietary factors with survival in populations with and without chronic kidney disease.

Barriers to Healthy Eating and Diabetes Diet Education: Divergent Perspectives of Patients and Their Providers.

Patients report that adhering to diet is the most challenging aspect of diabetes management. Provision of diet education is often delegated to health care providers, despite a lack of nutrition education and training and limited awareness of environmental and cultural challenges faced by patients. Aim. We examined perceived barriers to diet self-management among low-income minority patients with type 2 diabetes and their health care providers within a single ecosystem, to test whether providers understood patient barriers. Method. We surveyed 149 members of a safety-net clinic (99 patients, 50 providers), using barriers derived from the literature. Binomial logistic regression was applied to investigate relationships between barriers and patients' sociodemographic variables and Pearson's χ2 was used to compare differences in perceived barriers between patients and providers. Results. Providers expressed divergent perceptions of patients' barriers to healthy eating, including more total barriers and little agreement with patients on their relative importance. Largest differences in providers' perceptions of patient barriers included poor motivation, high use of fast food, inadequate family support, and lack of cooking skills-all suggesting patient inadequacy. In contrast, patients showed evidence of high motivation-in rate of blood glucose measurement and desire for diet education. Patients identified primary care providers as a main source of nutrition education, yet providers indicated lack of time for diet discussion and preferred other staff do the teaching. Conclusion. The findings from this study strongly suggest that health systems need to consider patient, provider, and system barriers when implementing nutrition education and management programs.

Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11ß-MNTDC in healthy men.

BACKGROUND: Dimethandrolone (DMA) and 11ß-methyl-19-nortestosterone (11ß-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men. OBJECTIVE: Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens. MATERIALS/METHODS: In two clinical trials of DMA undecanoate (DMAU) and 11ß-MNT dodecylcarbonate (11ß-MNTDC), oral prodrugs of DMA and 11ß-MNT, healthy men received drug, or placebo for 28 days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo. RESULTS: Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11ß-MNTDC. An increase in LDL-C was seen with 11ß-MNTDC but not with DMAU. DISCUSSION: There were no significant changes in insulin resistance after 28 days of oral administration of these novel androgens despite a mild increase in weight. There may be subtle differences in their metabolic impacts that should be explored in future studies. CONCLUSION: Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

Initiating Dialogue in Community-Partnered Participatory Research to Address Obesity in South Los Angeles.

In South Los Angeles, a community-engaged research project on obesity was initiated between a translational research institute seeking to build community-based or partnered participatory research (CBPR/CPPR) capacity, and a community partner with extensive experience. This manuscript describes the partnership-building process and discusses results from a bi-directional knowledge transfer event.

Effect of high-protein meals during hemodialysis combined with lanthanum carbonate in hypoalbuminemic dialysis patients: findings from the FrEDI randomized controlled trial.

BACKGROUND: Inadequate protein intake and hypoalbuminemia, indicators of protein-energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high-protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels. METHODS: We conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin <4.0 g/dL recruited between July 2010 and October 2011 from eight Southern California dialysis units. Patients were randomly assigned to receive high-protein (50-55 g) meals during dialysis, providing 400-500 mg phosphorus, combined with lanthanum carbonate versus low-protein (<1 g) meals during dialysis, providing <20 mg phosphorus. Prescribed nonlanthanum phosphorus binders were continued over an 8-week period. The primary composite outcome was a rise in serum albumin of ≥0.2 g/dL while maintaining phosphorus between 3.5-<5.5 mg/dL. Secondary outcomes included achievement of the primary outcome's individual endpoints and changes in mineral and bone disease and inflammatory markers. RESULTS: Among 106 participants who satisfied the trial entrance criteria, 27% ( n = 15) and 12% ( n = 6) of patients in the high-protein versus low-protein hemodialysis meal groups, respectively, achieved the primary outcome (intention-to-treat P-value = 0.045). A lower proportion of patients in the high-protein versus low-protein intake groups experienced a meaningful rise in interleukin-6 levels: 9% versus 31%, respectively (P = 0.009). No serious adverse events were observed. CONCLUSION: In hypoalbuminemic hemodialysis patients, high-protein meals during dialysis combined with lanthanum carbonate are safe and increase serum albumin while controlling phosphorus.

Dietary energy requirements in relatively healthy maintenance hemodialysis patients estimated from long-term metabolic studies.

BACKGROUND: Studies that examined dietary energy requirements (DERs) of patients undergoing maintenance hemodialysis (MHD) have shown mixed results. Many studies reported normal DERs, but some described increased energy needs. DERs in MHD patients have been estimated primarily from indirect calorimetry and from nitrogen balance studies. The present study measured DERs in MHD patients on the basis of their dietary energy intake and changes in body composition. OBJECTIVE: This study assessed DERs in MHD patients who received a constant energy intake while changes in their body composition were measured. DESIGN: Seven male and 6 female sedentary, clinically stable MHD patients received a constant mean (±SD) energy intake for 92.2 ± 7.9 d while residing in a metabolic research ward. Changes in fat and fat-free mass, measured by dual-energy X-ray absorptiometry, were converted to calorie equivalents and added to energy intake to calculate energy requirements. RESULTS: The average DER was 31 ± 3 kcal · kg(-1) · d(-1) calculated from energy intake and change in fat and fat-free calories, which was 28 ± 197 kcal/d over the 92 d of the study. DERs of MHD patients correlated strongly with their body weight (r = 0.81, P = 0.002) and less closely with their measured resting energy expenditure expressed as kcal/d (r = 0.69, P = 0.01). Although the average observed DER in MHD patients was similar to published estimated values for normal sedentary individuals of similar age and sex, there was wide variability in DER among individual patients (range: 26-36 kcal · kg(-1) · d(-1)). CONCLUSIONS: Average DERs of sedentary, clinically stable patients receiving MHD are similar to those of sedentary normal individuals. Our data do not support the theory that MHD patients have increased DERs. Due to the high variability in DERs, careful monitoring of the nutritional status of individual MHD patients is essential. This trial was registered at clinicaltrials.gov as NCT02194114.

The Healthy Community Neighborhood Initiative: Rationale and Design.

OBJECTIVE: To describe the design and rationale of the Healthy Community Neighborhood Initiative (HCNI), a multi-component study to understand and document health risk and resources in a low-income and minority community. DESIGN: A community-partnered participatory research project. SETTING: A low-income, biethnic African American and Latino neighborhood in South Los Angeles. PARTICIPANTS: Adult community residents aged >18 years. MAIN OUTCOME MEASURES: Household survey and clinical data collection; neighborhood characteristics; neighborhood observations; and community resources asset mapping. RESULTS: We enrolled 206 participants (90% of those eligible), of whom 205 completed the household interview and examination, and 199 provided laboratory samples. Among enrollees, 82 (40%) were aged >50 years and participated in functional status measurement. We completed neighborhood observations on 93 street segments; an average of 2.2 (SD=1.6) study participants resided on each street segment observed. The community asset map identified 290 resources summarized in a Community Resource Guide given to all participants. CONCLUSIONS: The HCNI community-academic partnership has built a framework to assess and document the individual, social, and community factors that may influence clinical and social outcomes in a community at high-risk for preventable chronic disease. Our project suggests that a community collaborative can use culturally and scientifically sound strategies to identify community-centered health and social needs. Additional work is needed to understand strategies for developing and implementing interventions to mitigate these disparities.

Association between quality of life and anxiety, depression, physical activity and physical performance in maintenance hemodialysis patients.

OBJECTIVE: Maintenance hemodialysis (MHD) patients often have impaired quality of life (QOL), anxiety, depression, and reduced daily physical activity (DPA) and physical performance. The contributions of these latter factors to reduced QOL in MHD are poorly understood. We examined the association of QOL with anxiety, depression, DPA, and physical performance. METHODS: Seventy-two relatively healthy adult MHD patients, vintage ≥6 months, and 39 normals of similar age range and gender distribution were studied. QOL was assessed using the Kidney Disease Quality of Life-Short Form (KDQOL-SF). Anxiety and depression were each evaluated with two questionnaires. DPA and physical performance were assessed with a physical activity monitor, Human Activity Profile, and 6-minute walk, sit-to-stand, and stair-climbing tests. RESULTS: Most KDQOL components were reduced in MHD patients versus normals. KDQOL components in patients were commonly inversely correlated with measures of anxiety and depression (P < 0.05) and were more reduced in patients with both anxiety and depression. KDQOL was often impaired in patients with either anxiety or depression. However, most KDQOL scores did not differ between patients and normals without anxiety or depression. DPA, Human Activity Profile, and physical performance often correlated with KDQOL scores in adjusted models, but after further adjustment for anxiety and depression, DPA, Human Activity Profile, and physical performance correlated less frequently with KDQOL scores. This reduction in significant correlations after adjustment for anxiety and depression was particularly pronounced for the association between KDQOL and DPA. CONCLUSION: In relatively healthy MHD patients, KDQOL scores are usually decreased in those with anxiety and/or depression but are usually normal in those without anxiety or depression. Lower DPA in MHD patients with reduced KDQOL scores often appears to be associated with anxiety and depression. The relationship between QOL and physical performance appears to be less influenced by anxiety and/or depression. These data suggest that treatment of anxiety and depression in MHD patients may improve their QOL, DPA, and possibly physical performance.

Strategies to Build Trust and Recruit African American and Latino Community Residents for Health Research: A Cohort Study.

BACKGROUND: This study used Community Partnered Participatory Research (CPPR) to address low participation of racial and ethnic minorities in medical research and the lack of trust between underrepresented communities and researchers. METHODS: Using a community and academic partnership in July 2012, residents of a South Los Angeles neighborhood were exposed to research recruitment strategies: referral by word-of-mouth, community agencies, direct marketing, and extant study participants. RESULTS: Among 258 community members exposed to recruitment strategies, 79.8% completed the study. Exposed individuals identified their most important method for learning about the study as referral by study participants (39.8%), community agencies (30.6%), word-of-mouth (17.5%), or direct marketing promotion (12.1%). Study completion rates varied by recruitment method: referral by community agencies (88.7%), referral by participants (80.4%), direct marketing promotion (86.2%), word of mouth (64.3%). CONCLUSIONS: Although African American and Latino communities are often described as difficult to engage in research, we found high levels of research participation and completion when recruitment strategies emerged from the community itself. This suggests recruitment strategies based on CPPR principles represent an important opportunity for addressing health disparities and our high rates of research completion should provide optimism and a road map for next steps.

Self-Reported Interview-Assisted Diet Records Underreport Energy Intake in Maintenance Hemodialysis Patients.

OBJECTIVES: Studies suggest that maintenance hemodialysis (MHD) patients report dietary energy intakes (EIs) that are lower than what is actually ingested. Data supporting this conclusion have several important limitations. The present study introduces a novel approach of assessing underreporting of EI in MHD patients. DESIGN: Comparisons of EI of free-living MHD patients determined from food records to their measured energy needs. SETTING: Metabolic research ward. SUBJECTS: Thirteen clinically stable MHD patients with unchanging weights whose EI was assessed by dietitian interview-assisted 3-day food records. INTERVENTION: EI was compared with (1) patients' resting energy expenditure (REE), measured by indirect calorimetry, and estimated total energy expenditure (TEE) and (2) patients' dietary energy requirements (DER) measured while patients underwent nitrogen balance studies and consumed a constant energy diet in a research ward for a mean duration of 89.5 days. DER was calculated as the actual EI during the research study corrected for changes in body fat and lean body mass measured by Dual X-Ray Absorptiometry. MAIN OUTCOME MEASURE: Underreporting of EI was determined by an EI:REE ratio <1.27 and an EI:TEE ratio or EI:DEE ratio <1.0. RESULTS: Seven of the 13 MHD patients studied were male. Patient's ages were 47.7 ± standard deviation 9.7 years; body mass index averaged 25.4 ± 2.8 kg/m2, and dialysis vintage was 53.3 ± 37.1 months. The EI:REE ratio (1.03 ± 0.23) was significantly less than the cutoff value for underreporting of 1.27 (P = .001); 12 of 13 patients had EI:REE ratios <1.27. The mean EI:TEE ratio was significantly less than the cutoff value of 1.0 (0.73 ± 0.17, P < .0001), and 12 MHD patients had EI:TEE ratios <1.0. The EI:DER ratio was also <1.0 (0.83 ± 0.25, P = .012), and 10 MHD had EI:DER ratios <1.0. CONCLUSIONS: Dietitian interview-assisted diet records by MHD patients substantially underestimate the patient's dietary EI.

Factors affecting daily physical activity and physical performance in maintenance dialysis patients.

Maintenance hemodialysis (MHD) patients display reduced daily physical activity (DPA) and physical performance (PP). Previous studies did not differentiate the effects of kidney failure and MHD treatments from comorbidities as causes for reduced DPA and PP. In relatively healthy MHD patients and normal adults, we evaluated DPA and PP and examined relationships between DPA and PP and possible associations between anxiety or depression and DPA and PP. DPA, 6-minute walk distance (6-MWD), sit-to-stand (STS), and stair-climbing tests were measured in 72 MHD patients (40% diabetics) with limited comorbidities and 39 normal adults of similar age and gender mix. Anxiety and depression were measured by the Beck anxiety and depression inventories. DPA, time-averaged over 7 days, and all 3 PP tests were impaired in MHD patients, to about 60% to 70% of normal values (P < .0001 for each measurement). MHD patients spent more time sleeping or physically inactive (P < .0001) and less time in ≥ moderate activity (P < .0001). Adjusted DPA correlated with 6-MWD but not STS or stair-climbing. Anxiety and depression were identified in 43% and 33% of MHD patients and 2.5% and 5.1% of normals (P < .0001 for each comparison). Most of the impairment in DPA and PP tests were also observed in MHD patients without anxiety or depression. However, MHD patients with both anxiety and depression generally had the most impaired DPA and PP. In MHD patients, higher adjusted anxiety scores were correlated with impaired 6-MWD and STS, whereas adjusted average DPA was negatively correlated with depression (r = -0.33, P = .006) but not anxiety. DPA on the hemodialysis day (P = .01), day after dialysis (P = .03), and day 2 after dialysis (P = .03) each correlated negatively with degree of depression but not with anxiety. MHD patients displayed negative-adjusted correlations between anxiety and 6-MWD (P = .03) and STS (P = .04). In relatively healthy MHD patients, DPA and PP are substantially impaired and correlated with each other, even in patients without evidence for anxiety or depression. Anxiety and depression are common in MHD patients and are associated with further impairment in DPA and PP.

Relation between anxiety, depression, and physical activity and performance in maintenance hemodialysis patients.

OBJECTIVE: Maintenance hemodialysis (MHD) patients have a high prevalence of anxiety and depression and decreased daily physical activity (DPA) and exercise capacity. Because affective disorders may affect DPA and physical performance, we investigated possible relationships between anxiety or depression and DPA and physical performance in relatively healthy MHD patients. DESIGN AND METHODS: This cross-sectional study included 72 relatively healthy MHD patients and 39 normal adults. DPA was measured for 7 days with an Actigraph Activity Monitor®. Physical performance was assessed using the 6-minute walk (6-MWT), sit-to-stand (STS), and stair-climbing tests. Subjects completed the Beck Anxiety Inventory (BAI), the Beck Depression Inventory-II (BDI), and the Hospital Anxiety and Depression Scale (HADS). Main outcome measures were physical activity counts (expressed as vector magnitude), in the 6-MWT, STS, stair-climbing test, BAI, BDI, and HADS scores. RESULTS: Anxiety and depression by BAI and BDI were identified in 43% and 33% of MHD patients and 2.5% and 5% of normals, respectively (P < .0001 for each comparison). MHD patients without anxiety or depression had decreased DPA and physical performance compared with normals, indicating that these disorders were also independent of anxiety or depression. MHD patients with anxiety and depression generally had the most impaired DPA and physical performance. Higher BAI and BDI scores were each associated with impaired physical performance. In fully adjusted analyses, DPA in MHD patients was negatively correlated with the BDI (r = -0.33, P = .01) but not with the BAI. DPA on the day of hemodialysis (P = .01), and day 1 (P = .03) and day 2 (P = .03) after dialysis each correlated negatively with degree of depression by BDI. In MHD patients, BAI was negatively correlated with 6-MWT (P = .03) and STS (P = .04). CONCLUSIONS: In relatively healthy adult MHD patients, anxiety and depression are common and are associated with impaired physical performance. There was a trend toward stronger negative associations between BDI scores and DPA than between BAI scores and DPA.

Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients (AIONID) study: results of the pilot-feasibility, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Low serum albumin is common and associated with protein-energy wasting, inflammation, and poor outcomes in maintenance hemodialysis (MHD) patients. We hypothesized that in-center (in dialysis clinic) provision of high-protein oral nutrition supplements (ONS) tailored for MHD patients combined with anti-oxidants and anti-inflammatory ingredients with or without an anti-inflammatory appetite stimulator (pentoxifylline, PTX) is well tolerated and can improve serum albumin concentration. METHODS: Between January 2008 and June 2010, 84 adult hypoalbuminemic (albumin <4.0 g/dL) MHD outpatients were double-blindly randomized to receive 16 weeks of interventions including ONS, PTX, ONS with PTX, or placebos. Nutritional and inflammatory markers were compared between the four groups. RESULTS: Out of 84 subjects (mean ± SD; age, 59 ± 12 years; vintage, 34 ± 34 months), 32 % were Blacks, 54 % females, and 68 % diabetics. ONS, PTX, ONS plus PTX, and placebo were associated with an average change in serum albumin of +0.21 (P = 0.004), +0.14 (P = 0.008), +0.18 (P = 0.001), and +0.03 g/dL (P = 0.59), respectively. No related serious adverse events were observed. In a predetermined intention-to-treat regression analysis modeling post-trial serum albumin as a function of pre-trial albumin and the three different interventions (ref = placebo), only ONS without PTX was associated with a significant albumin rise (+0.17 ± 0.07 g/dL, P = 0.018). CONCLUSIONS: In this pilot-feasibility, 2 × 2 factorial, placebo-controlled trial, daily intake of a CKD-specific high-protein ONS with anti-inflammatory and anti-oxidative ingredients for up to 16 weeks was well tolerated and associated with slight but significant increase in serum albumin levels. Larger long-term controlled trials to examine hard outcomes are indicated.

Dietary fat modulates the testosterone pharmacokinetics of a new self-emulsifying formulation of oral testosterone undecanoate in hypogonadal men.

This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat. Serial blood samples were collected from 2 hours predose to 25 hours postdose to determine serum T and dihydrotestosterone (DHT) by liquid chromatography tandem mass spectrometry. Administering TU with a meal increased serum T concentrations, with the magnitude of the increase being directly dependent on the amount of fat in the meal. Average and peak serum T concentrations and area under the curve increased as the fat content of the meal was increased. Neither the high-fat meal (50% fat) nor the lower-fat meal (20% fat) showed a significant food effect relative to the normal-fat (Western diet) meal (30% fat). However, administering TU while fasting resulted in 50% or less of the cumulative exposure obtained when administered with 20%- to 50%-fat meals (albeit still substantial). A very-low-fat meal (10% fat) showed a significant food effect relative to the normal meal, but still exceeded the fasting condition by approximately 50%. Serum DHT concentrations showed corresponding increases to the serum T. As expected with the maximum anticipated clinical dose of TU (300 mg T), oral administration of this new formulation with food containing 20% to 50% dietary fat produced T levels at or above the upper range of adult men, and T levels trended higher as dietary fat content increased. Only with a very-low-fat diet (10%) or in a fasted state did a clinically significant food effect occur, but even then sufficient TU was absorbed with the self-emulsifying TU formulation to produce average serum T concentration predicted to be in the normal reference range (10 to 35 nmol/L).

Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation.

Many hypogonadal men prefer oral testosterone (T) treatment. Oral T undecanoate (TU) is available in many countries, but not in the United States. We aimed to assess the pharmacokinetics of oral TU in a new self-emulsifying drug delivery system formulation. Pharmacokinetics studies were conducted in 3 parts: 12 hypogonadal men were enrolled in 2 centers for a 1-day dosing study; 29 participants were enrolled from 3 centers for a 7-day dosing study; and 15 participants were enrolled from 1 center for a 28-day dosing study. Serial blood samples for serum sex hormone measurements by liquid chromatography-tandem mass spectrometry were drawn for up to 36 hours after oral TU administration. Mean serum T levels (C(avg)) after oral dosing of T 200 mg as TU twice daily with food were within the adult male range in most participants in the 1-, 7-, and 28-day dosing studies but were much lower in the fasting state. The dose-proportional increase in C(avg) of serum T after oral T 300 mg twice daily resulted in more participants with supraphysiologic serum T levels. In the 28-day study, trough serum T reached a steady state at day 7. Serum dihydrotestosterone and estradiol levels tracked serum T concentration. Dihydrotestosterone-testosterone ratios increased 3-fold after oral TU administration. Oral T 200 mg twice daily as TU in a new SEDDS formulation may be a viable therapy for hypogonadal men.

Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients.

BACKGROUND: Mortality in long-term hemodialysis patients is high, mostly attributed to cardiovascular events, and may be related to chronic inflammation. We hypothesized that the anti-inflammatory benefits of higher dietary intake of omega-3 compared with omega-6 polyunsaturated fatty acids may modulate the inflammatory processes and decrease death risk. STUDY DESIGN: Prospective cohort study using linear and Cox proportional regressions. SETTING & PARTICIPANTS: 145 hemodialysis patients from 8 DaVita dialysis clinics in Southern California in 2001-2007. PREDICTORS: Intake of dietary omega-3 and ratio of omega-6 to omega-3 using 3-day food record supplemented by dietary interview. OUTCOMES: 1-year change in serum C-reactive protein (CRP) level and 6-year survival. RESULTS: Patients were aged 53 ± 14 years (mean ± SD) and included 43% women and 42% African Americans. Median dietary omega-3 intake, ratio of omega-6 to omega-3 intake, baseline serum CRP level, and change in CRP level over 1 year were 1.1 (25th-75th percentile, 0.8-1.6) g/d, 9.3 (25th-75th percentile, 7.6-11.3), 3.1 (25th-75th percentile, 0.8-6.8) mg/L, and +0.2 (25th-75th percentile, -0.4 to +0.8) mg/L, respectively. In regression models adjusted for case-mix, dietary calorie and fat intake, body mass index, and history of hypertension, each 1-unit higher ratio of omega-6 to omega-3 intake was associated with a 0.55-mg/L increase in serum CRP level (P = 0.03). In the fully adjusted model, death HRs for the first (1.7-<7.6), second (7.6-<9.3), third (9.3-<11.3), and fourth (11.3-17.4) quartiles of dietary omega-6 to omega-3 ratio were 0.39 (95% CI, 0.14-1.18), 0.30 (95% CI, 0.09-0.99), 0.67 (95% CI, 0.25-1.79), and 1.00 (reference), respectively (P for trend = 0.06). LIMITATIONS: 3-day food record may underestimate actual dietary fat intake at an individual level. CONCLUSIONS: Higher dietary omega-6 to omega-3 ratio appears to be associated with both worsening inflammation over time and a trend toward higher death risk in hemodialysis patients. Additional studies including interventional trials are needed to examine the association of dietary fatty acids with clinical outcomes in these patients.

Quality-of-life and mortality in hemodialysis patients: roles of race and nutritional status.

BACKGROUND AND OBJECTIVES: Maintenance hemodialysis (MHD) patients often have protein-energy wasting, poor health-related quality of life (QoL), and high premature death rates, whereas African-American MHD patients have greater survival than non-African-American patients. We hypothesized that poor QoL scores and their nutritional correlates have a bearing on racial survival disparities of MHD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined associations between baseline self-administered SF36 questionnaire-derived QoL scores with nutritional markers by multivariate linear regression and with survival by Cox models and cubic splines in the 6-year cohort of 705 MHD patients, including 223 African Americans. RESULTS: Worse SF36 mental and physical health scores were associated with lower serum albumin and creatinine levels but higher total body fat percentage. Spline analyses confirmed mortality predictability of worse QoL, with an almost strictly linear association for mental health score in African Americans, although the race-QoL interaction was not statistically significant. In fully adjusted analyses, the mental health score showed a more robust and linear association with mortality than the physical health score in all MHD patients and both races: death hazard ratios for (95% confidence interval) each 10 unit lower mental health score were 1.12 (1.05-1.19) and 1.10 (1.03-1.18) for all and African American patients, respectively. CONCLUSIONS: MHD patients with higher percentage body fat or lower serum albumin or creatinine concentration perceive a poorer QoL. Poor mental health in all and poor physical health in non-African American patients correlate with mortality. Improving QoL by interventions that can improve the nutritional status without increasing body fat warrants clinical trials.

Racial and ethnic differences in mortality of hemodialysis patients: role of dietary and nutritional status and inflammation.

BACKGROUND: Racial/ethnic disparities prevail among hemodialysis patients. We hypothesized that significant differences exist between Black and non-Hispanic and Hispanic White hemodialysis patients in nutritional status, dietary intake and inflammation, and that they account for racial survival disparities. METHODS: In a 6-year (2001-2007) cohort of 799 hemodialysis patients, we compared diet and surrogates of nutritional-inflammatory status and their mortality-predictabilities between 279 Blacks and 520 Whites using matched and regression analyses and Cox with cubic splines. RESULTS: In age-, gender- and diabetes-matched analyses, Blacks had higher lean body mass and serum prealbumin, creatinine and homocysteine levels than Whites. In case-mix-adjusted analyses, dietary intakes in Blacks versus Whites were higher in energy (+293 ± 119 cal/day) and fat (+18 ± 5 g/day), but lower in fiber (-2.9 ± 1.3 g/day) than Whites. In both races, higher serum albumin, prealbumin and creatinine were associated with greater survival, whereas CRP and IL-6, but not TNF-α, were associated with increased mortality. The highest (vs. lowest) quartile of IL-6 was associated with a 2.4-fold (95% CI: 1.3-3.8) and 4.1-fold (2.2-7.2) higher death risk in Blacks and Whites, respectively. CONCLUSIONS: Significant racial disparities exist in dietary, nutritional and inflammatory measures, which may contribute to hemodialysis outcome disparities. Testing race-specific dietary and/or anti-inflammatory interventions is indicated.