Safety of dietary nitrate supplementation by calcium nitrate for finishing pigs as measured by methemoglobin and serum and tissue nitrate levels.

Nitrate supplementation has been studied as a beneficial constituent of the human diet, particularly for its effects on vascular health through vasodilation. Recent studies have focused on the benefits of nitrate supplementation in animals, especially in swine. Up to 1,200 mg/kg dietary nitrate supplementation from Ca nitrate was beneficial in farrowing and lactating sows and their offspring, and up to 6,000 mg/kg supplemental nitrate showed no adverse health effects in sows or piglets. Controlled study data evaluating the safety of nitrate supplementation to growing swine of any weight class is scant. Therefore, an experiment was conducted to test the hypothesis that increased inclusion rates of dietary nitrate through the addition of Ca nitrate in diets would not influence concentrations of nitrate or nitrite in serum and tissue, nor blood hemoglobin and methemoglobin. Forty-eight individually housed pigs (initial weight 119.1 ±â€…5.3 kg) were randomly allotted to four dietary treatments containing 0, 500, 1,000, or 2,000 mg/kg dietary nitrate and fed experimental diets for 28 d. Growth performance was not influenced (P > 0.10) by dietary treatment. The most sensitive safety endpoint, methemoglobin, did not change (P > 0.10) with dietary nitrate exposure up to 2,000 mg/kg. Serum and tissue nitrate and nitrite levels, myoglobin, and hemoglobin were not adversely affected (P > 0.10). Total myoglobin in the loin linearly increased (P < 0.05) with greater dietary nitrate in the diet, which is correlated with the red color of meat. This work established the safety of up to 2,000 mg/kg dietary nitrate from Ca nitrate as an ingredient in food for finishing pigs.

Identification of Independent and Shared Metabolic Responses to High-Fiber and Antibiotic Treatments in Fecal Metabolome of Grow-Finish Pigs.

Feeding high-fiber (HF) coproducts to grow-finish pigs as a cost-saving practice could compromise growth performance, while the inclusion of antibiotic growth promoters (AGPs) may improve it. The hindgut is a shared site of actions between fiber and AGPs. However, whether the metabolic interactions between them could occur in the digestive tract of pigs and then become detectable in feces have not been well-examined. In this study, wheat middling (WM), a HF coproduct, and bacitracin, a peptide antibiotic (AB), were fed to 128 grow-finish pigs for 98 days following a 2 × 2 factorial design, including antibiotic-free (AF) + low fiber (LF); AF + HF; AB + LF, and AB + HF, for growth and metabolic responses. The growth performance of the pigs was compromised by HF feedings but not by AB. A metabolomic analysis of fecal samples collected on day 28 of feeding showed that WM elicited comprehensive metabolic changes, especially in amino acids, fatty acids, and their microbial metabolites, while bacitracin caused selective metabolic changes, including in secondary bile acids. Limited metabolic interactions occurred between fiber and AB treatments. Moreover, the correlations between individual fecal metabolites and growth support the usage of fecal metabolome as a source of biomarkers for monitoring and predicting the metabolic performance of grow-finish pigs.

Influence of feeding thermally peroxidized lipids on growth performance, lipid digestibility, and oxidative status in nursery pigs.

Three experiments were conducted to evaluate oil source and peroxidation status (experiment 1) or peroxidized soybean oil (SO; experiments 2 and 3) on growth performance, oxidative stress, and digestibility of dietary ether extract (EE). In experiment 1, palm oil (PO), poultry fat (PF), canola oil (CO), and SO were evaluated, while in experiments 2 and 3, only SO was evaluated. Lipids were either an unheated control (CNT) or thermally processed at 90 °C for 72 hr, being added at 10%, 7.5%, or 3% of the diet in experiments 1, 2, and 3, respectively. In experiment 1, 288 pigs (body weight, BW, 6.1 kg) were fed 1 of 8 factorially arranged treatments with the first factor being lipid source (PO, PF, CO, and SO) and the second factor being peroxidation status (CNT or peroxidized). In experiment 2, 216 pigs (BW 5.8 kg) were fed 1 of 6 treatments consisting of 100%, 90%, 80%, 60%, 20%, and 0% CNT SO blended with 0%, 10%, 20%, 40%, 80%, and 100% peroxidized SO, respectively. In experiment 3, 72 pigs (BW 5.8 kg) were fed either CNT or peroxidized SO. Pigs were fed 21 d with feces collected on day 12 or 14 and pigs bled on day 12 blood collection. In experiment 1, an interaction between oil source and peroxidation status was observed for averaged daily gain (ADG) and average daily feed intake (ADFI; P = 0.10) which was due to no impact of feeding pigs peroxidized PO, PF, or SO on ADG or ADFI compared with feeding pigs CNT PO, PF, or SO, respectively; while pigs fed peroxidized CO resulted in reduced ADG and ADFI compared with pigs fed CNT CO. There was no interaction between oil source and peroxidation status, and no lipid source effect on gain to feed ratio (GF; P ≥ 0.84), but pigs fed the peroxidized lipids had a lower GF compared with pigs fed the CNT lipids (P = 0.09). In experiment 2, feeding pigs diets containing increasing levels of peroxidized SO resulted in reduced ADG (quadratic, P = 0.03), ADFI (linear, P = 0.01), and GF (quadratic, P = 0.01). In experiment 3, feeding peroxidized SO at 3% of the diet reduced ADG (P = 0.11) and ADFI (P = 0.13), with no observed change in GF (P = 0.62). Differences in plasma protein carbonyls, glutathione peroxidase, and vitamin E due to feeding peroxidized lipids were inconsistent across the 3 experiments. Digestibility of dietary EE was reduced in pigs fed peroxidized PO or SO (P = 0.01, experiment 1) and peroxidized SO in experiments 2 and 3 (P ≤ 0.02). In conclusion, the peroxidation status of dietary lipids consistently affects growth performance and EE digestibility but has a variable effect on measures of oxidative stress.

Analysis of Gastrointestinal Responses Revealed Both Shared and Specific Targets of Zinc Oxide and Carbadox in Weaned Pigs.

Antibiotics and pharmacological zinc supplementation were commonly used as growth promoters for several decades in the swine industry before being limited because of public health and environmental concerns. Further, the physiological and metabolic responses associated with their growth promotion effects are unclear. To characterize these responses induced by pharmacological zinc supplementation (2500 mg/kg) and carbadox (55 mg/kg), 192 post-weaning pigs were fed basal and test diets for 43 days. Compared with basal, pharmacological zinc and carbadox independently improved growth performance. Pharmacological zinc increased gastric mucosa thickness compared with basal zinc, while carbadox increased intestinal villus:crypt ratio compared with non-carbadox. Pharmacological zinc and carbadox independently reduced interleukin (IL)-1ß concentration compared with basal zinc and non-carbadox. Pharmacological zinc increased IL-1RA:IL-1 ratio by 42% compared with basal zinc, while carbadox tended to increase the IL-10 and IL10:IL-12 ratio compared with non-carbadox. Carbadox increased fecal concentrations of histidine and lysine compared with non-carbadox. The independent effect of pharmacological zinc and carbadox on morphology and nutrient metabolism, and their shared effect on immunity may contribute to the additive effect on growth promotion. These results further confirmed the concept that growth promotion is multifactorial intervention. Therefore, elucidating growth-promoting effects and searching for alternatives should include wide-spectrum evaluation.

Redefining Medication Management in Dialysis: A Kidney Pharmacy Quality Pyramid.

Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients.

Effects of Specialty Pharmacy Care on Health Outcomes in Multiple Sclerosis.

BACKGROUND: Increasingly, third-party payers are requiring patients with multiple sclerosis (MS) to participate in specialty pharmacy management programs to improve their adherence to their prescribed medications. The effects of specialty pharmacy care on MS clinical outcomes have not yet been comprehensively examined in the literature. OBJECTIVE: To compare the effectiveness of specialty pharmacy care and usual community pharmacy care MS outcomes. METHODS: Inpatient, outpatient, and pharmacy claims for patients with MS were extracted from a major national pharmacy benefit management company's databases for this retrospective cohort study. Enrollees with continuous medical and pharmacy benefits were followed for 3 years. MS relapse status was defined by a specific algorithm and was compared in patients who had specialty pharmacy care and those with usual community pharmacy care. The outcome measures included time to the first and second disease relapses and the number of relapses. Kaplan-Meier method and Cox proportional hazards regression analyses were performed on the time to first and second relapses, and generalized linear regression models were performed on the number of disease relapses. RESULTS: The study cohort included 1731 eligible patients with MS, of whom 1427 received specialty pharmacy care. During the study period, between 2006 and 2009, 1634 relapses were identified, with a mean annual relapse rate of 0.3 among the specialty pharmacy care group versus 0.4 among the usual pharmacy care group. Specialty pharmacy care was associated with a lower risk for disease relapse, with a hazard ratio (HR) of 0.73 (95% confidence interval [CI], 0.607-0.871) for the first relapse and HR of 0.78 (95% CI, 0.610-1.002) for the second relapse. When controlling for demographics, comorbidities, and index medications, specialty pharmacy care was associated with a lower risk for disease relapse with HR of 0.82 (95% CI, 0.680-0.985) for first relapse versus usual pharmacy care. The time to second relapse was not significantly different between the 2 groups in the unadjusted and adjusted Cox regression models. In addition, a generalized linear regression model showed that specialty pharmacy care, index age, geographic North region, 3-year Chronic Disease Score, and Elixhauser comorbidity measure were significantly associated with the number of disease relapses. CONCLUSION: These results show that specialty pharmacy care is associated with a significantly lower risk for disease relapse in patients with MS (specifically the first relapse) and fewer relapses compared with usual community pharmacy care.

Accessibility of antiretroviral therapy in Ghana: convenience of access.

The convenience of accessing antiretroviral therapy (ART) is important for initial access to care and subsequent adherence to ART. We conducted a qualitative study of people living with HIV/AIDS (PLWHA) and ART healthcare providers in Ghana in 2005. The objective of this study was to explore the participants' perceived convenience of accessing ART by PLWHA in Ghana. The convenience of accessing ART was evaluated from the reported travel and waiting times to receive care, the availability, or otherwise, of special considerations, with respect to the waiting time to receive care, for those PLWHA who were in active employment in the formal sector, the frequency of clinic visits before and after initiating ART, and whether the PLWHA saw the same or different providers at each clinic visit (continuity of care). This qualitative study used in-depth interviews based on Yin's case-study research design to collect data from 20 PLWHA and 24 ART healthcare providers as study participants. • Reported travel time to receive ART services ranged from 2 to 12 h for 30% of the PLWHA. • Waiting time to receive care was from 4 to 9 h. • While known government workers, such as teachers, were attended to earlier in some of the centres, this was not a consistent practice in all the four ART centres studied. • The PLWHA corroborated the providers' description of the procedure for initiating and monitoring ART in Ghana. • PLWHA did not see the same provider every time, but they were assured that this did not compromise the continuity of their care. Our study suggests that convenience of accessing ART is important to both PLWHA and ART healthcare providers, but the participants alluded to other factors, including open provider-patient communication, which might explain the PLWHA's understanding of the constraints under which they were receiving care. The current nation-wide coverage of the ART programme in Ghana, however, calls for the replication of this study to identify possible perception changes over time that may need attention. Our study findings can inform interventions to promote access to ART, especially in Africa.

Inflammation in response to n3 fatty acids in a porcine obesity model.

Fatty acids have distinct cellular effects related to inflammation and insulin sensitivity. Dietary saturated fat activates toll-like receptor 4, which in turn can lead to chronic inflammation, insulin resistance, and adipose tissue macrophage infiltration. Conversely, n3 fatty acids are generally antiinflammatory and promote insulin sensitivity, in part via peroxisome proliferator-activated receptor γ. Ossabaw swine are a useful biomedical model of obesity. We fed Ossabaw pigs either a low-fat control diet or a diet containing high-fat palm oil with or without additional n3 fatty acids for 30 wk to investigate the effect of saturated fats and n3 fatty acids on obesity-linked inflammatory markers. The diet did not influence the inflammatory markers C-reactive protein, TNFα, IL6, or IL12. In addition, n3 fatty acids attenuated the increase in inflammatory adipose tissue CD16(-)CD14(+) macrophages induced by high palm oil. High-fat diets with and without n3 fatty acids both induced hyperglycemia without hyperinsulinemia. The high-fat only group but not the high-fat group with n3 fatty acids showed reduced insulin sensitivity in response to insulin challenge. This effect was not mediated by decreased phosphorylation of protein kinase B. Therefore, in obese Ossabaw swine, n3 fatty acids partially attenuate insulin resistance but only marginally change inflammatory status and macrophage phenotype in adipose tissue.

African American patients' attitudes toward proactive health behaviors after exposure to direct-to-consumer advertising.

BACKGROUND: Previous research on direct-to-consumer advertising (DTCA) has not focused exclusively on the African American population. PURPOSES: The purpose of this study was to explore African Americans' attitudes toward proactive health behaviors following exposure to DTCA of atorvastatin calcium (Lipitor, Pfizer Inc). MATERIALS AND METHODS: One-hundred fifty African American patients participated in the study. Participants' functional health literacy and health locus of control were assessed. The participants were asked to view a DTCA of Lipitor, followed by face-to-face interviews. RESULTS: After watching the DTCA of Lipitor, 89.4% of participants agreed that they would talk to their physician about their cholesterol, 88.6% agreed that they would ask their physician to test their cholesterol level, and 47.3% agreed that they would ask their physician to write them a prescription for Lipitor. Those who had a history of high cholesterol were more likely to agree to ask their physician to test their cholesterol levels. Low household income, having public health insurance, and prior experience with taking Lipitor were significant positive predictors of patients agreeing to ask their physician to write a prescription of the advertised drug. CONCLUSIONS: African American patients showed favorable attitudes toward proactive health behaviors after exposure to DTCA of Lipitor.

Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective, cohort study.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is a chronic disease affecting about 400 000 people in the US characterized by increasing patient disability and burden on society. While there is no cure for multiple sclerosis (MS), pharmaceutical treatments exist that can limit the number of relapses a patient experiences, and slow disease progression. One such class of agents used to treat RRMS are the interferons: interferon-beta-1a (Rebif and Avonex and interferon-beta-1b (Betaseron and Extavia). Patients must take these injectable medications regularly to achieve the optimal outcomes. However, patient issues and potential adverse effects of the medication may prevent the patient from taking the medication as directed and lower adherence. To date, limited evidence exists regarding the effect of patient adherence to interferon-beta therapies on clinical and economic outcomes. OBJECTIVE: The purpose of this study was to explore the impact of patient adherence to interferon-beta therapy on MS relapse rates and healthcare resource utilization. METHODS: Using a non-experimental, retrospective cohort design, a sample population (n = 1606) was drawn from patients identified in a database that includes both pharmacy and medical claims data. The study population was separated into two groups based on a measure of medication possession ratio (MPR)-adherent and non-adherent patients, and adherence was defined as MPR > or =85% in a given year during the study period (2006-8). Key outcome variables included MS relapses and healthcare resource utilization. Data were analysed using parametric and non-parametric statistics, and regression modeling. RESULTS: During the study period, the average MPR for all patients on interferon-beta therapy varied from 72% to 76%. Only 27-41% of patients in each year were considered adherent (i.e. MPR > or =85%) and only 4% of patients had an MPR of > or =85% throughout the 3-year study period (2006-8). Patients who were adherent tended to have a lower risk of relapses over 3 years than non-adherent patients. A significantly lower risk of relapses was found in 2006 (risk ratio [RR] 0.89; 95% CI 0.81, 0.97). Furthermore, an increasingly larger effect emerged between adherence and relapses when comparing adherent patients (MPR > or =85%) with subgroups of non-adherent patients (<80%, <75%, <70%, <65% and <60%). The impact of adherence on emergency room (ER) visits also tended to suggest a lower risk during 2006, 2007 and 2006-8. During 2008, the risk for an ER visit was significantly lower for patients adherent in 2007 (RR 0.78; 95% CI 0.61, 0.99). Inpatient admissions followed the ER trends, as patients considered adherent in 2006 and 2007 tended to have a lower risk over 3 years. This result was significant for patients adherent in 2007 (RR 0.79; 95% CI 0.65, 0.98). CONCLUSION: The findings of low patient adherence and the impact of adherence on relapses and healthcare resource utilization strongly suggest opportunities to reduce healthcare resource utilization and healthcare costs among RRMS patients taking interferon-beta therapy. Efforts should be undertaken to understand and improve medication-taking behaviour in this population so as to minimize the negative impacts of RRMS on patients while reducing unnecessary direct and indirect costs to treat disease exacerbations.

Improving digestibility of soy flour by reducing disulfide bonds with thioredoxin.

The Kunitz trypsin inhibitor (KTI) and the Bowman-Birk inhibitor (BBI) of trypsin and chymotrypsin contain disulfide bonds. Glycinin, the major storage protein in soybeans also contains disulfide bonds. Treatment of soy white flour with a NADP-thioredoxin system (NTS) effectively reduced disulfide bonds in soy flour and increased protein digestibility by trypsin and pancreatin as measured by the pH stat method. Treatment of soy flour with NTS increased the digestibility compared to soy white flour by 29.3 and 60.6% for trypsin and pancreatin, respectively. NTS-treated soy flour had similar digestibility by trypsin to autoclaved soy flour and casein, but digestibility by pancreatin was less than autoclaved soy flour and casein. The degree of reduction by NTS was highly correlated to the degree of hydrolysis (DH) by trypsin (R(2) = 0.93) and pancreatin (R(2) = 0.99). The DH of NTS-treated soy flour by trypsin is reflective of both inactivation of trypsin inhibitors and overall protein digestibility while pancreatin hydrolysis is reflective of only overall protein digestibility.

Perceived importance of pharmacy management skills.

PURPOSE: U.S. and Canadian health-system pharmacists' perceptions of the importance of managerial skills and self-ratings of skills were studied. METHODS: A questionnaire asking recipients to rate the importance of 61 pharmacy management skills and to rate their own skill levels was prepared. The instrument was mailed in 2000 to pharmacy managers in Canada. Participants in the Leadership in Healthcare Administration for Pharmacists conference in Phoenix, Arizona, received the survey at the end of the 2001 and 2002 conferences. Participants in the 2002 Department of Veterans Affairs pharmacists' conference in Memphis, Tennessee, received the survey eight weeks before the conference. RESULTS: The net response rates for the Canadian, Arizona, and Tennessee surveys were 52.7%, 56.9%, and 38.4%, respectively. The five skills rated most important in each of the three surveys were all practice foundation skills and tended to be required by all health care managers. Skills rated least important were also generally similar among the surveys. Only five skills demonstrated a significant mean difference in perceived importance among the surveys. In all three surveys, demonstrating ethical conduct was rated the most important skill and was judged by participants to be their greatest strength. Using an organized system for staying current with managerial literature was cited as the greatest weakness by the Tennessee sample and the second greatest weakness by the Canadian sample. CONCLUSION: Surveys in the United States and Canada found differences and similarities in pharmacy managers' opinions of the importance of managerial skills and in self-rated managerial strengths. Also identified were gaps in training.