Optimizing clinical nutrition research: the role of adaptive and pragmatic trials.

Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally been the preferred method for determining the effects of nutritional interventions on health outcomes. Nevertheless, obtaining a holistic understanding of intervention efficacy and effectiveness in real-world settings is stymied by inherent constraints of efficacy RCTs. These limitations are further compounded by the complexity of nutritional interventions and the intricacies of the clinical context. Herein, we explore the advantages and limitations of alternative study designs (e.g., adaptive and pragmatic trials), which can be incorporated into RCTs to optimize the efficacy or effectiveness of interventions in clinical nutrition research. Efficacy RCTs often lack external validity due to their fixed design and restrictive eligibility criteria, leading to efficacy-effectiveness and evidence-practice gaps. Adaptive trials improve the evaluation of nutritional intervention efficacy through planned study modifications, such as recalculating sample sizes or discontinuing a study arm. Pragmatic trials are embedded within clinical practice or conducted in settings that resemble standard of care, enabling a more comprehensive assessment of intervention effectiveness. Pragmatic trials often rely on patient-oriented primary outcomes, acquire outcome data from electronic health records, and employ broader eligibility criteria. Consequently, adaptive and pragmatic trials facilitate the prompt implementation of evidence-based nutritional recommendations into clinical practice. Recognizing the limitations of efficacy RCTs and the potential advantages of alternative trial designs is essential for bridging efficacy-effectiveness and evidence-practice gaps. Ultimately, this awareness will lead to a greater number of patients benefiting from evidence-based nutritional recommendations.

Current Therapeutic Targets in Cancer Cachexia: A Pathophysiologic Approach.

Significant progress in our understanding of cancer cachexia has occurred in recent years. Despite these advances, no pharmacologic agent has achieved US Food and Drug Administration approval for this common and highly morbid syndrome. Fortunately, improved understanding of the molecular basis of cancer cachexia has led to novel targeted approaches that are in varying stages of drug development. This article reviews two major thematic areas that are driving these pharmacologic strategies, including those targeting signal mediators at the level of the CNS and skeletal muscle. Additionally, pharmacologic strategies are being tested in combination with targeted nutrients, nutrition therapy, and exercise to treat cancer cachexia. To this end, we highlight recently published and ongoing trials evaluating cancer cachexia therapies in these specific areas.

Association Between Antibiotic Prophylaxis Before Cystectomy or Stent Removal and Infection Complications: A Systematic Review.

CONTEXT: Patients undergoing radical cystectomy frequently suffer from infectious complications, including urinary tract infections (UTIs) and surgical site infections (SSIs) leading to emergency department visits, hospital readmission, and added cost. OBJECTIVE: To summarize the literature regarding perioperative antibiotic prophylaxis, ureteric stent usage, and prevalence of infectious complications after cystectomy. EVIDENCE ACQUISITION: A systematic review of PubMed/Medline, EMBASE, Cochrane Library, and reference lists was conducted. EVIDENCE SYNTHESIS: We identified 20 reports including a total of 55 306 patients. The median rates of any infection, UTIs, SSIs, and bacteremia were 40%, 20%, 11%, and 6%, respectively. Perioperative antibiotic prophylaxis differed substantially between reports. Perioperative antibiotics were used only during surgery in one study but were continued over several days after surgery in all other studies. Empirical use of antibiotics for 1-3 d after surgery was described in 12 studies, 3-10 d in two studies, and >10 d in four studies. Time to stent removal ranged from 4 to 25 d after cystectomy. Prophylactic antibiotics were used before stent removal in nine of 20 studies; two of these studies used targeted antibiotics based on urine cultures from the ureteric stents, and the other seven studies used a single shot or 2 d of empirical antibiotics. Studies with any prophylactic antibiotic before stent removal found a lower median percentage of positive blood cultures after stent removal than studies without prophylactic antibiotics before stent removal (2% vs 9%). CONCLUSIONS: We confirmed a high proportion of infectious complications after cystectomy, and a heterogeneous pattern of choice and duration of antibiotics during and after surgery or stent removal. These findings highlight a need for further studies and support quality prospective trials. PATIENT SUMMARY: In this review, we observed wide variability in the use of antibiotics before or after surgical removal of the bladder.

Sarcopenia in urologic oncology: Identification and strategies to improve patient outcomes.

Sarcopenia is the loss of muscle mass and function related to aging, undereating, disease conditions, or inactivity. Pre-existing sarcopenia diminishes the functional reserve of patients with cancer which increases their risk for frailty, cancer cachexia, and worse outcomes from treatments. The pathogenesis of sarcopenia is multi-factorial: opening opportunities for clinicians to work across disciplines to improve patient outcomes and quality of life. The purpose of this essay is to describe sarcopenia, discuss clinical screening and assessment for sarcopenia, and highlight potential interventions to manage sarcopenia in the urologic oncology population.

Rapid Escalation of High-Volume Exercise during Caloric Restriction; Change in Visceral Adipose Tissue and Adipocytokines in Obese Sedentary Breast Cancer Survivors.

Aerobic exercise reduces risk for breast cancer and recurrence and promotes visceral adipose tissue (VAT) loss in obesity. However, few breast cancer survivors achieve recommended levels of moderate to vigorous physical activity (MVPA) without supervision. In a two-cohort study, feasibility of 12 weeks of partially supervised exercise was started concomitantly with caloric restriction and effects on body composition and systemic risk biomarkers were explored. In total, 22 obese postmenopausal sedentary women (including 18 breast cancer survivors) with median age of 60 and BMI of 37 kg/m2 were enrolled. Using personal trainers twice weekly at area YMCAs, MVPA was escalated to ≥200 min/week over 9 weeks. For cohort 2, maintenance of effect was assessed when study provided trainer services were stopped but monitoring, group counseling sessions, and access to the exercise facility were continued. Median post-escalation MVPA was 219 min/week with median 12-week mass and VAT loss of 8 and 19%. MVPA was associated with VAT loss which was associated with improved adiponectin:leptin ratio. In total, 9/11 of cohort-2 women continued the behavioral intervention for another 12 weeks without trainers. High MVPA continued with median 24-week mass and VAT loss of 12 and 29%. This intervention should be further studied in obese sedentary women.

Exploration of biomarkers from a pilot weight management study for men undergoing radical prostatectomy.

BACKGROUND: Several biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (CaP) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have CaP recurrence post-prostatectomy. Obesity is related to inflammation and immune dysregulation; thus, weight loss may be an avenue to reduce inflammation and reverse these immune processes. OBJECTIVES: This study explores the reversibility of the biological mechanisms through intentional weight loss using a comprehensive weight management program in men undergoing prostatectomy. Outcomes include blood and tissue biomarkers, microtumor environment gene expression, inflammation markers and Dietary Inflammatory Index (DII) scores. METHODS: Twenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and 5 men chose the nonintervention group. The intervention consisted of a comprehensive weight loss program prior to prostatectomy and a weight maintenance program following surgery. Prostate tissue samples were obtained from diagnostic biopsies before the intervention and prostatectomy samples after weight loss. Blood samples and diet records were collected at baseline, pre-surgery after weight loss and at study end after weight maintenance. Immunohistochemistry and NanoString analysis were used to analyze the tissue samples. Flow cytometry was used to assess circulating immune markers. Inflammation markers were measured using Luminex panels. RESULTS: The intervention group lost >5% body weight prior to surgery. DII scores improved during the weight loss intervention from baseline to pre-surgery (P = 0.002); and between group differences were significant (P = 0.02). DII scores were not associated with IL-6 nor hsCRP. In the intervention, CXCL12, CXCR7, and CXCR4 (C-X-C motif chemokine ligand/receptor) and Ki67 expression decreased in the prostate tissue from biopsy to surgery (P = 0.06), yet plasma CXCL12 increased during the same timeframe (P = 0.009). The downregulation of several genes (FDR<0.001) was observed in the intervention compared to the non-intervention. Changes in immune cells were not significant in either group. CONCLUSION: This feasibility study demonstrates that in overweight men with localized CaP, weight loss alters blood, and tissue biomarkers, as well as tumor gene expression. More research is needed to determine the biological and clinical significance of these findings.

Feasibility of a Weight Management Program Tailored for Overweight Men with Localized Prostate Cancer - A Pilot Study.

BACKGROUND: Overweight men with prostate cancer are more likely to suffer from recurrence and death following prostatectomy compared with healthy weight men. This study tested the feasibility of delivering a comprehensive program to foster weight loss before and weight maintenance after surgery in overweight men with localized prostate cancer. METHODS: Twenty overweight men scheduled for prostatectomy elected either the intervention (n = 15) or the nonintervention (n = 5). Anthropometrics, biomarkers, diet quality, nutrition literacy, quality of life, and long-term follow-up were assessed in both groups. RESULTS: The intervention led to 5.55 kg of weight loss including 3.88 kg of fat loss from baseline to surgery (mean = 8.3 weeks). The intervention significantly increased fiber, protein, fruit, nut, and vegetable intake; and decreased trans fats intake during weight loss. The intervention significantly reduced insulin, C-peptide, systolic blood pressure, leptin:adiponectin ratio, and visceral adiposity compared to the nonintervention. Post-surgically, weight loss was maintained. Changes in lipid profiles, nutrition literacy, and follow-up were not statistically significant in either group. CONCLUSION: Significant weight loss (≥5%) is feasible with a coaching intervention in overweight men preparing for prostatectomy and is associated with favorable cardiometabolic effects. This study is registered under NCT02252484 (www.clinicaltrials.gov).

Rural breast cancer survivors are able to maintain diet quality improvements during a weight loss maintenance intervention.

PURPOSE: Obesity and poor diet quality (DQ) are associated with increased risk of morbidity/mortality among breast cancer survivors. This study explored DQ changes during a weight loss maintenance intervention in a cohort of rural female breast cancer survivors (n = 131) who lost ≥ 5% body weight in a weight loss intervention. Previous analyses demonstrated significant DQ improvements during weight loss. METHODS: DQ was calculated using the alternate Healthy Eating Index (aHEI)-2010. Differences in scores across time for the cohort and between those that maintained weight loss within 5% (low regainers) and those that regained > 5% (high regainers) were analyzed by linear mixed models. RESULTS: Significant improvements in aHEI total score were observed from baseline (M = 52.3 ± 11) to 6 months (M = 60.7 ± 8; p < 0.001); these improvements were sustained from 6 to 18 months (M = 58.4 ± 11; p = 0.16). Total aHEI-2010 score at 18 months was higher in low regainers, compared with high regainers (60.7 vs. 56.0, p = 0.03), with healthier component scores for red meat (p = 0.01) and fruit (p = 0.04), and a trend for a healthier score for sugar-sweetened beverages (p = 0.08). CONCLUSIONS: Overall DQ improvements made during a weight loss intervention for rural breast cancer survivors were sustained during a weight loss maintenance intervention; this intervention was effective in helping low regainers maintain healthier scores in fruit, red meat, and sugar-sweetened beverage components. IMPLICATIONS FOR CANCER SURVIVORS: Maintaining higher DQ may help breast cancer survivors maintain weight loss, thereby reducing risk of breast cancer recurrence and premature death from comorbidities.

Nutrition risk and assessment process in patients with bladder cancer undergoing radical cystectomy.

Malnutrition and depleted muscle stores adversely affect bladder cancer patients and contribute to poorer outcomes. These nutrition-related problems are often not addressed, in part because they are not being identified with screening and assessment tools. In this essay, we discuss validated nutrition screening and assessment tools such as the Patient-Generated Subjective Global Assessment; however, each healthcare team must decide on the one which will work best for their clinic. Patients with bladder cancer may be at risk for specific nutrient deficiencies which should be monitored and corrected to improve outcomes and overall health.

The Feasibility of a Health Care Application in the Treatment of Patients Undergoing Radical Cystectomy.

PURPOSE: Patients who undergo radical cystectomy of bladder cancer are at high risk for complications and hospital readmissions. Studies indicate insufficient preoperative education and perioperative monitoring. The aim of this study was to demonstrate the feasibility of implementing a health care application to provide more patient education and more thorough monitoring perioperatively. MATERIALS AND METHODS: Participants with home Wi-Fi access who were undergoing radical cystectomy were recruited for this pilot trial. Each subject was provided a tablet preloaded with the m.Care (LifeScience Technologies, Leawood, Kansas) health care application, an accelerometer and vital sign equipment. Participants were asked to watch educational videos, use the provided accelerometer and perform vital sign monitoring. RESULTS: In 1 year 20 participants enrolled in the study and 15 completed it. The most frequently viewed videos were "Ileal Conduit versus Neobladder" and "Comprehensive Care Pathway." All participants used the accelerometer and 60% kept up with syncing the data regularly. The average step count preoperatively was 5,679 reflecting a sedentary population. Step counts decreased during the inpatient stay (1,351 steps) and trended toward baseline during the postoperative period (3,156 steps). Vital signs were recorded on 85% of assigned days and generated 33 triggers for intervention. While most triggers led to repeat assessment, education and encouragement, 4 participants underwent outpatient treatment, including cultures, intravenous fluids, antibiotics or dronabinol prescription, without the need for hospital readmission. CONCLUSIONS: Providing more education and monitoring perioperatively is feasible using a health care application. Testing is warranted to determine the extent to which implementation will improve patient triaging and reduce readmissions.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.

PURPOSE: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS: In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS: Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.

Emerging Impact of Malnutrition on Surgical Patients: Literature Review and Potential Implications for Cystectomy in Bladder Cancer.

PURPOSE: Malnutrition is emerging as a significant factor in patient outcomes. A contemporary review of malnutrition has not been performed for the urologist. We review the available literature and current standards of care for malnutrition screening, assessment and intervention, focusing on patients with bladder cancer treated with cystectomy. MATERIALS AND METHODS: Our multidisciplinary team searched PubMed® for available literature on malnutrition, focusing on definition and significance, importance to urologists, screening, assessment, diagnosis, immunological and economic impacts, and interventions. RESULTS: The prevalence of malnutrition in hospitalized patients is estimated to range from 15% to 60%, reaching upward of 71% in those with cancer. Malnutrition has been shown to increase inflammatory markers, further intensifying catabolism and weight loss. Bladder cancer is catabolic and patients undergoing cystectomy have increased resting energy expenditure postoperatively. Data are emerging on the impact of malnutrition in the cystectomy population. Recent studies have identified poor nutritional status based on low albumin or sarcopenia (loss of muscle) as having an adverse impact on length of hospitalization, complications and survival. The current standard of care malnutrition assessment tool, the 2012 consensus statement of the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition, has not been evaluated in the urological literature. Perioperative immunonutrition in patients undergoing colorectal surgery has been associated with significant decreases in postoperative complications, and recent pilot work has identified the potential for immunonutrition to positively impact the cystectomy population. CONCLUSIONS: Malnutrition has a significant impact on surgical patients, including those with bladder cancer. There are emerging data in the urological literature regarding how best to identify and improve the nutritional status of patients undergoing cystectomy. Additional research is needed to identify malnutrition in these patients and interventions to improve surgical outcomes.

Diet and polycystic kidney disease: A pilot intervention study.

BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals consumed their usual diet for one week then for four weeks followed an isocaloric diet lower in sodium and protein and higher in fruits, vegetables, and water. Three-day diet records and two 24-h urine samples were collected at baseline, week 2, and week 4 visits; blood pressure, weight, and serum were obtained at all three visits. A modified nutrition hassles questionnaire was completed on the last visit. RESULTS: During the dietary intervention, subjects (n = 11) consumed less sodium, protein, and dietary acid precursors 36%, 28%, and 99%, respectively, and increased fluid intake by 42%. Urinary sodium, urea, net acid excretion, osmoles, and osmolality decreased 20%, 28%, 20%, 37%, and 15%, respectively; volume increased 35%. Urine changes were in accord with the diet record. Ninety-one percent of participants reported that none of the hassles were worse than "somewhat severe", and most participants felt "somewhat confident" or "very confident" that they could manage the new diet. CONCLUSIONS: A majority of adult patients with ADPKD successfully prepared and followed a composite diet prescription with decreased sodium, protein, acid precursors, and increased fluid intake. This trail was registered at ClinicalTrials.gov (NCT01810614).

Weight Management to Reduce Prostate Cancer Risk: A Survey of Men's Needs and Interests.

Obese men have a higher rate of prostate cancer-related death than non-obese men, and obesity increases the risk of prostate cancer progression and biochemical recurrence. The purpose of this study was to assess needs and interests of men for a technology-driven weight loss intervention to reduce prostate cancer risk. We distributed a survey collecting demographic characteristics, health history, exercise and eating habits (and perception of those habits), current and prior attempts of health behavior change, and technology use. Survey answers were summarized by count and percent of total respondents. Completed surveys (N = 109) described men with a family history of prostate cancer (25%), a history of elevated prostate specific antigen (26%), and prostate cancer survivors (22%). We compared body mass index (BMI) to perception of weight; overweight and obese men perceived their weight as more normal than their BMI category suggests. Most men reported their diet needed minor improvement (74%), and 65% of men reported they are either currently trying to lose weight or interested in weight loss. Most respondents access the internet (92%), while text messaging (60%) and smartphone application use (40%) are less frequent, especially in men over 60. Our results revealed a need and willingness for lifestyle modification and suggest a need for evidence-based weight loss strategies and for addressing the misperception of weight status. A male-tailored intervention that implements technology could improve energy balance, hold men accountable to healthy behavior change, and promote dietary patterns in order to reduce prostate cancer risk.

Experiences and Perspectives of Polycystic Kidney Disease Patients following a Diet of Reduced Osmoles, Protein, and Acid Precursors Supplemented with Water: A Qualitative Study.

BACKGROUND: Salt, protein, acid precursors, and fluid intake have been identified as factors that influence cyst growth in ADPKD. Unfortunately, the feasibility of following these dietary restrictions/enhancements from a patient's point-of-view has yet to be studied. The purpose of this study is to understand better the experiences of patients following a relatively complex dietary prescription targeting these factors. METHODS: Twelve adults with ADPKD and kidney function >30ml/min/1.73m2 were recruited from the University of Kansas Medical Center Polycystic Kidney Disease clinic. In a qualitative design, semi-structured interviews of participants were conducted following a four week dietary intervention (experimental diet lower in sodium, protein, and acid precursors, and supplemented with water) either face-to-face or by telephone. All interviews were recorded, transcribed verbatim, and checked for accuracy. Transcripts were analyzed thematically for emerging themes. RESULTS: Participants reported that eating less meat and more fruits and vegetables were the easiest components of the diet, whereas reaching the daily goal amount of fruits and vegetables and tracking the diet constantly were the most difficult components. Participants had little difficulty with fluid intake and reported the prescribed fluid goal as achievable. The tracking system for fruits and vegetables and protein was reported to be both helpful and intuitive, but tracking their intake on paper was tedious. Eating out was the most significant barrier to following the diet with some individuals avoiding restaurants in order to comply with the dietary prescription. CONCLUSION: Participants on the experimental diet heightened their awareness of the consumption of dietary salt, protein, acid precursors, and fluid intake. Additionally, most participants believed adherence to the prescribed diet was feasible. However, participants wanted less cumbersome ways to track and monitor the diet, especially given that the prescribed diet is designed for lifelong adherence. Future studies should focus on targeting these specific dietary factors in larger groups of more ethnically and culturally diverse populations to help inform clinicians and how best to help diverse populations adhere to the dietary intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01810614.

Effects of Immunonutrition for Cystectomy on Immune Response and Infection Rates: A Pilot Randomized Controlled Clinical Trial.

UNLABELLED: After radical cystectomy (RC), patients are at risk for complications including infections. The expansion of myeloid-derived suppressor cells (MDSCs) after surgery may contribute to the lower resistance to infection. Immune response and postoperative complications were compared in men consuming either specialized immunonutrition (SIM; n=14) or an oral nutrition supplement (ONS; n=15) before and after RC. MDSC count (Lin- CD11b+ CD33+) was significantly different between the groups over time (p=0.005) and significantly lower in SIM 2 d after RC (p<0.001). MDSC count expansion from surgery to 2 d after RC showed a weak association with an increase in infection rate 90 d after surgery (p=0.061). Neutrophil:lymphocyte ratio was significantly lower in SIM compared with ONS 3h after the first incision (p=0.039). Participants receiving SIM had a 33% reduction in postoperative complication rate (95% confidence interval [CI], 1-64; p=0.060) and a 39% reduction in infection rate (95% CI, 8-70; p=0.027) during late-phase recovery. The small sample size limits the study findings. PATIENT SUMMARY: Results show that the immune response to surgery and late infection rates differ between radical cystectomy patients receiving specialized immunonutrition versus oral nutrition supplement in the perioperative period. TRIAL REGISTRATION: ClinicalTrials.gov NCT01868087.

Renal formulas pretreated with medications alters the nutrient profile.

BACKGROUND: Pretreating renal formulas with medications to lower the potassium and phosphorus content is common in clinical practice; however, the effect of this treatment on other nutrients is relatively unstudied. We examine whether nutrient composition is affected by pretreating renal formulas with sodium polystyrene sulfonate (SPS) suspension and sevelamer carbonate. METHODS: Fixed medication doses and treatment times were utilized to determine changes in the nutrient composition of Suplena® and Similac® PM 60/40. The effect of simultaneously adding both medications (co-administration) to the formula on the nutrient composition of Suplena® was also evaluated. RESULTS: Pretreatment of Suplena® with SPS reduced the concentrations of calcium (11-38 %), copper (3-11 %), manganese (3-16 %), phosphorus (0-7 %), potassium (6-34 %), and zinc (5-20 %) and increased those of iron (9-34 %), sodium (89-260 %), and sulfur (19-45 %) and the pH (0.20-0.50 units). Pretreatment of Similac® PM 60/40 with SPS reduced the concentrations of calcium (8-29 %), copper (5-19 %), magnesium (3-26 %), and potassium (33-63 %) and increased those of iron (13-87 %) and sodium (86-247 %) and the pH (0.40-0.81 units). Pretreatment of both formulas with the SPS suspension led to significant increases in the aluminum concentration in both formulas (507-3957 %). No differences in potassium concentration were observed between treatment times. Unexpectedly, the levels of neither phosphorus nor potassium were effectively reduced in Suplena® pretreated with sevelamer carbonate alone or when co-administered with SPS. CONCLUSIONS: Pretreating formula with medications alters nutrients other than the intended target(s). Future studies should be aimed at predicting the loss of these nutrients or identifying alternative methods for managing serum potassium and phosphorus levels in formula-fed infants. The safety of pretreating formula with SPS suspension should also be examined.

Patient-centered perspectives on the access to educational opportunities specific to lifestyle modification in men at risk for primary or secondary prostate cancer.

Educating men at risk for primary or secondary prostate cancer on lifestyle modification may help prevent the development of the disease, reduce the risk of recurrence in those treated for cancer, and slow the progression of active disease. To date, substantial literature on male patient attitudes towards risk modification does not exist. In this project, we evaluate the attitudes and educational needs of men at high-risk for primary or secondary prostate cancer to assess the need for a dedicated clinic focused on education and prevention. Two clinic nurses administered surveys to 76 male patients seen at the University Kansas Cancer Center (KUCC) and Urology clinics. Survey responses showed the patients' perspectives and desire for more support and education regarding late effects of treatment, management of risk, and lifestyle modification. Findings from this survey inspired the establishment of the Burns & McDonnell High-Risk Prostate Cancer Prevention Program at KUCC.

Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial.

PURPOSE: We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n=42) or placebo (n=44) for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM). Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant. CONCLUSIONS/SIGNIFICANCE: These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00255125.

Drug-vitamin D interactions: a systematic review of the literature.

Extensive media coverage of the potential health benefits of vitamin D supplementation has translated into substantial increases in supplement sales over recent years. Yet, the potential for drug-vitamin D interactions is rarely considered. This systematic review of the literature was conducted to evaluate the extent to which drugs affect vitamin D status or supplementation alters drug effectiveness or toxicity in humans. Electronic databases were used to identify eligible peer-reviewed studies published through September 1, 2010. Study characteristics and findings were abstracted, and quality was assessed for each study. A total of 109 unique reports met the inclusion criteria. The majority of eligible studies were classified as class C (nonrandomized trials, case-control studies, or time series) or D (cross-sectional, trend, case report/series, or before-and-after studies). Only 2 class C and 3 class D studies were of positive quality. Insufficient evidence was available to determine whether lipase inhibitors, antimicrobial agents, antiepileptic drugs, highly active antiretroviral agents, or H2 receptor antagonists alter serum 25(OH)D concentrations. Atorvastatin appears to increase 25(OH)D concentrations, whereas concurrent vitamin D supplementation decreases concentrations of atorvastatin. Use of thiazide diuretics in combination with calcium and vitamin D supplements may cause hypercalcemia in the elderly or those with compromised renal function or hyperparathyroidism. Larger studies with stronger study designs are needed to clarify potential drug-vitamin D interactions, especially for drugs metabolized by cytochrome P450 3A4 (CYP3A4). Healthcare providers should be aware of the potential for drug-vitamin D interactions.