COVID-19 infections and outcomes in a live registry of heart failure patients across an integrated health care system.

BACKGROUND: Patients with comorbid conditions have a higher risk of mortality with SARS-CoV-2 (COVID-19) infection, but the impact on heart failure patients living near a disease hotspot is unknown. Therefore, we sought to characterize the prevalence and outcomes of COVID-19 in a live registry of heart failure patients across an integrated health care system in Connecticut. METHODS: In this retrospective analysis, the Yale Heart Failure Registry (NCT04237701) that includes 26,703 patients with heart failure across a 6-hospital integrated health care system in Connecticut was queried on April 16th, 2020 for all patients tested for COVID-19. Sociodemographic and geospatial data as well as, clinical management, respiratory failure, and patient mortality were obtained via the real-time registry. Data on COVID-19 specific care was extracted by retrospective chart review. RESULTS: COVID-19 testing was performed on 900 symptomatic patients, comprising 3.4% of the Yale Heart Failure Registry (N = 26,703). Overall, 206 (23%) were COVID- 19+. As compared to COVID-19-, these patients were more likely to be older, black, have hypertension, coronary artery disease, and were less likely to be on renin angiotensin blockers (P<0.05, all). COVID-19- patients tended to be more diffusely spread across the state whereas COVID-19+ were largely clustered around urban centers. 20% of COVID-19+ patients died, and age was associated with increased risk of death [OR 1.92 95% CI (1.33-2.78); P<0.001]. Among COVID-19+ patients who were ≥85 years of age rates of hospitalization were 87%, rates of death 36%, and continuing hospitalization 62% at time of manuscript preparation. CONCLUSIONS: In this real-world snapshot of COVID-19 infection among a large cohort of heart failure patients, we found that a small proportion had undergone testing. Patients found to be COVID-19+ tended to be black with multiple comorbidities and clustered around lower socioeconomic status communities. Elderly COVID-19+ patients were very likely to be admitted to the hospital and experience high rates of mortality.

Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

The original version of this article, published on 21 March 2019, unfortunately contains some typos in Figs. 2, 3, 4, and Supplemental Fig. 1. The corrected figures are given below.

Increasing the concentration of linolenic acid in diets fed to Jersey cows in late lactation does not affect methane production.

Although the inclusion of fat has reduced methane production in ruminants, relatively little research has been conducted comparing the effects of source and profile of fatty acids on methane production in lactating dairy cows. A study using 8 multiparous (325 ± 17 DIM; mean ± SD) lactating Jersey cows was conducted to determine effects of feeding canola meal and lard versus extruded byproduct containing flaxseed as a high-C18:3 fat source on methane production and diet digestibility in late-lactation dairy cows. A crossover design with 32-d periods (28-d adaptation and 4-d collections) was used to compare 2 different fat sources. Diets contained approximately 50% forage mixture of corn silage, alfalfa hay, and brome hay; the concentrate mixture changed between diets to include either (1) a conventional diet of corn, soybean meal, and canola meal with lard (control) or (2) a conventional diet of corn and soybean meal with an extruded byproduct containing flaxseed (EXF) as the fat source. Diets were balanced to decrease corn, lard, and canola meal and replace them with soybean mean and EXF to increase the concentration of C18:3 (0.14 vs. 1.20% of DM). Methane production was measured using headbox-style indirect calorimeters. Cattle were restricted to 95% ad libitum feed intake during collections. Milk production (17.4 ± 1.04 kg/d) and dry matter intake (15.4 ± 0.71 kg/d) were similar among treatments. Milk fat (5.88 ± 0.25%) and protein (4.08 ± 0.14%) were not affected by treatment. For methane production, no difference was observed for total production (352.0 vs. 349.8 ± 16.43 L/d for control vs. EXF, respectively). Methane production per unit of dry matter intake was not affected and averaged 23.1 ± 0.57 L/kg. Similarly, methane production per unit of energy-corrected milk was not affected by fat source and averaged 15.5 ± 0.68 L/kg. Heat production was similar, averaging 21.1 ± 1.02 Mcal/d. Digestibility of organic matter, neutral detergent fiber, and crude protein was not affected by diet and averaged 69.9, 53.6, and 73.3%, respectively. Results indicated that increasing C18:3 may not affect methane production or digestibility of the diet in lactating dairy cows.

Reducing methane production with corn oil and calcium sulfate: Responses on whole-animal energy and nitrogen balance in dairy cattle.

The addition of fat and calcium sulfate to diets fed to ruminants has resulted in a reduction in methane production, but the effects on energy balance have not been studied. A study using indirect calorimetry and 16 multiparous (8 Holstein and 8 Jersey; 78 ± 15 d in milk; mean ± standard deviation) lactating dairy cows was conducted to determine how mitigating methane production by adding corn oil or calcium sulfate to diets containing reduced-fat distillers grains affects energy and nitrogen balance. A replicated 4 × 4 Latin square design with 35-d periods (28 d of adaption and 4 d of collections) was used to compare 4 different dietary treatments. Treatments were composed of a control (CON) diet, which did not contain reduced-fat distillers grain and solubles (DDGS), and treatment diets containing 20% (dry matter basis) DDGS (DG), 20% DDGS with 1.38% (dry matter basis) added corn oil (CO), and 20% DDGS with 0.93% (dry matter basis) added calcium sulfate (CaS). Compared with CON, dry matter intake was not affected by treatment, averaging 29.6 ± 0.67 kg/d. Milk production was increased for diets containing DDGS compared with CON (26.3 vs. 27.8 ± 0.47 kg/d for CON vs. DDGS, respectively), likely supported by increased energy intake. Compared with CON, energy-corrected milk was greater in DG and CO (30.1 vs. 31.4, 31.7, and 31.0 ± 0.67 kg/d for CON, DG, CO, and CaS, respectively). Compared with CON, the addition of calcium sulfate and corn oil to diets containing DDGS reduced methane production per kg of dry matter intake (22.3, 19.9, and 19.6 ± 0.75 L/kg per d for CON, CO, and CaS, respectively). Similarly, methane production per kilogram of energy-corrected milk was reduced with the addition of calcium sulfate and corn oil to diets containing DDGS (14.2, 12.5, and 12.4 ± 0.50 L/kg per d for CON, CO, and CaS, respectively). Compared with CON and CaS, the intake of digestible energy was greater for DG and CO treatments (57.7, 62.1, 62.0, and 59.0 ± 1.38 Mcal/d for CON, DG, CO, and CaS, respectively). Intake of metabolizable energy was greater in all treatments containing DDGS compared with CON (50.5 vs. 54.0 ± 1.08 Mcal/d for CON vs. DDGS, respectively). Net balance (milk plus tissue energy) per unit of dry matter was greater in CO (containing DDGS and oil) than CON (1.55 vs. 1.35 ± 0.06 Mcal/kg for CO vs. CON, respectively). Tissue energy was greater in DG and CO compared with CON (6.08, 7.04, and 3.16 ± 0.99 Mcal/d for DG, CO, and CON, respectively. Results of this study suggest that the addition of oil and calcium sulfate to diets containing DDGS may be a viable option to reduce methane production and in the case of oil also improve net energy balance in lactating dairy cows.

Elevated S100A8 protein expression in breast cancer cells and breast tumor stroma is prognostic of poor disease outcome.

PURPOSE: Elevated S100A8 expression has been observed in cancers of the bladder, esophagus, colon, ovary, and breast. S100A8 is expressed by breast cancer cells as well as by infiltrating immune and myeloid cells. Here we investigate the association of elevated S100A8 protein expression in breast cancer cells and in breast tumor stroma with survival outcomes in a cohort of breast cancer patients. PATIENTS AND METHODS: Tissue microarrays (TMA) were constructed from breast cancer specimens from 417 patients with stage I-III breast cancer treated at the University of Michigan Comprehensive Cancer Center between 2004 and 2006. Representative regions of non-necrotic tumor and distant normal tissue from each patient were used to construct the TMA. Automated quantitative immunofluorescence (AQUA) was used to measure S100A8 protein expression, and samples were scored for breast cancer cell and stromal S100A8 expression. S100A8 staining intensity was assessed as a continuous value and by exploratory dichotomous cutoffs. Associations between breast cancer cell and stromal S100A8 expression with disease-free survival and overall survival were determined using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: High breast cancer cell S100A8 protein expression (as indicated by AQUA scores), as a continuous measure, was a significant prognostic factor for OS [univariable hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.00-1.55, p = 0.05] in this patient cohort. Exploratory analyses identified optimal S100A8 AQUA score cutoffs within the breast cancer cell and stromal compartments that significantly separated survival curves for the complete cohort. Elevated breast cancer cell and stromal S100A8 expression, indicated by higher S100A8 AQUA scores, significantly associates with poorer breast cancer outcomes, regardless of estrogen receptor status. CONCLUSIONS: Elevated breast cancer cell and stromal S1008 protein expression are significant indicators of poorer outcomes in early stage breast cancer patients. Evaluation of S100A8 protein expression may provide additional prognostic information beyond traditional breast cancer prognostic biomarkers.

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events.

BACKGROUND: Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. METHODS: We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup per day), and regular (≥1 cup per day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome, with coefficients exponentiated to reflect coronary artery calcium progression ratio versus the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. RESULTS: Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup per day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup per day tea drinkers (adjusted hazard ratio 0.71; 95% confidence interval 0.53-0.95). Compared with never coffee drinkers, regular coffee intake (≥1 cup per day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted hazard ratio 0.97; 95% confidence interval 0.78-1.20). Caffeine intake was marginally inversely associated with coronary artery calcium progression. CONCLUSIONS: Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake.

Body composition, tissue deposition, and lysine utilization for protein deposition of barrows and gilts fed crystalline or protein-bound lysine.

An experiment with 2 trials (28 d/trial) was conducted to determine body composition, tissue deposition, and utilization of Lys for protein deposition (PD) of barrows and gilts fed -Lys·HCl (CLys) or protein-bound Lys in soybean meal (SBM). Thirty-two growing pigs (16 barrows and 16 gilts; average initial BW of 18.6 kg) were used in each of 2 trials. Four pigs (2 barrows and 2 gilts) were euthanized at the start of each trial to determine initial body composition. The remaining pigs were euthanized at the end of the trials to determine empty-body composition and deposition rates of water, protein, fat, ash, and AA. Pigs were randomly allotted to 1 of 7 dietary treatments. There were 2 replications per treatment in each trial for a total of 4 replications. Dietary treatments consisted of a corn-SBM basal diet (0.48% Lys) and diets containing 0.56%, 0.65%, and 0.74% standardized ileal digestible (SID) Lys that were achieved by adding Lys to the basal diet from either SBM or CLys. Pigs fed the CLys-supplemented diets at 0.65% SID Lys had more ( < 0.05) body water (663 vs. 624 g/kg) and less ( < 0.01) body protein (153 vs. 160 g/kg) than pigs fed the SBM-supplemented diets. Body fat content decreased ( < 0.01) as the dietary Lys increased similarly for pigs fed Lys from SBM and pigs fed CLys. Gilts had greater ( = 0.05) body Lys content in body protein than barrows (7.68 vs. 7.52 g/100 g). Empty-body ash contents were not different between pigs fed CLys or SBM-supplemented diets. Water deposition and PD increased linearly ( < 0.01) with dietary Lys and were least ( < 0.01) in pigs fed the basal diet but were similar when comparing pigs fed CLys and SBM-supplemented diets at the same dietary Lys concentration. Lysine deposition showed a linear increase ( < 0.01) with dietary Lys but was not different between pigs fed the 2 Lys sources at the same concentration. Barrows and gilts did not differ in tissue deposition rates. Overall, empty-body contents and deposition rates of essential and nonessential AA were not different between pigs fed CLys and pigs fed SBM-bound Lys. The amount of SID Lys required for PD ranged between 0.09 and 0.13 g/g for both sources of Lys. The Lys deposition:SID Lys intake ratio was greater ( < 0.01) in gilts than barrows (0.62 vs. 0.56). Body composition, tissue deposition, and utilization of Lys for PD and Lys deposition were not different in pigs fed diets supplemented with -Lys·HCl with respect to protein-bound Lys in SBM.

Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study.

UNLABELLED: The efficacy and safety of weekly oral odanacatib (ODN) 50 mg for up to 8 years were assessed in postmenopausal women with low bone mineral density (BMD). Treatment with ODN for up to 8 years resulted in continued or maintained increases in BMD at multiple sites and was well tolerated. INTRODUCTION: ODN is a selective inhibitor of cathepsin K. In a 2-year phase 2b study (3/10/25/50 mg ODN once weekly [QW] or placebo) and extensions (50 mg ODN QW or placebo), ODN treatment for 5 years progressively increased BMD and decreased bone resorption markers in postmenopausal women with low BMD ( ClinicalTrials.gov NCT00112437). METHODS: In this prespecified interim analysis at year 8 of an additional 5-year extension (years 6 to 10), patients (n = 117) received open-label ODN 50 mg QW plus weekly vitamin D3 (5600 IU) and calcium supplementation as needed. Primary end points were lumbar spine BMD and safety. Patients were grouped by ODN exposure duration. RESULTS: Mean (95 % confidence interval [CI]) lumbar spine BMD changes from baseline were 4.6 % (2.4, 6.7; 3-year continuous ODN exposure), 12.9 % (8.1, 17.7; 5 years), 12.8 % (10.0, 15.7; 6 years), and 14.8 % (11.0, 18.6; 8 years). Similar patterns of results were observed for BMD of trochanter, femoral neck, and total hip versus baseline. Geometric mean changes from baseline to year 8 for bone resorption markers were approximately -50 % (uNTx/Cr) and -45 % (sCTx), respectively (all groups); bone formation markers remained near baseline levels. No osteonecrosis of the jaw, delayed fracture union, or morphea-like skin reactions were reported. CONCLUSIONS: Treatment with ODN for up to 8 years resulted in gains in BMD at multiple sites. Bone resorption markers remained reduced, with no significant change observed in bone formation markers. Treatment with ODN for up to 8 years was well tolerated.

Supplementation of organic and inorganic selenium to diets using grains grown in various regions of the United States with differing natural Se concentrations and fed to grower-finisher swine.

Grains grown in various regions of the United States vary in their innate or natural Se contents. A regional study evaluated the effects of adding inorganic Se (sodium selenite) or organic Se (Se yeast) to diets with differing innate Se contents. A 2 × 2 + 1 factorial experiment evaluating 2 Se sources (organic or inorganic) at 2 Se levels (0.15 or 0.30 mg/kg) in 18 total replicates (n = 360 total pigs). A basal diet was fed without supplemental Se and served as the negative (basal) control. The study was conducted as a randomized complete block design in 9 states (Georgia, Illinois, Kentucky, Nebraska, North Carolina, Ohio, South Dakota, Texas, and Wisconsin) with each station conducting 2 replicates. Pigs were fed from 25 to approximately 115 kg BW. Similar dietary formulations were used at each station, incorporating a common source of trace mineral and Se premixes. Three pigs per treatment in 16 replicates (n = 240) were bled at 55, 85, and 115 kg BW and serum Se and glutathione peroxidase (GSH-Px) activities were determined. Three pigs (n = 260) from each treatment pen were killed at 115 kg BW and issues (liver, loin, and hair) were analyzed for Se. The corn Se content from the various states ranged from 0.026 to 0.283 mg Se/kg while the soybean meal Se content ranged from 0.086 to 0.798 mg Se/kg. Tissue and serum Se concentrations were greater (P < 0.01) when supplemental organic Se was fed, whereas serum GSH-Px was greater (P < 0.01) as Se level increased. There were linear increases (P < 0.01) in loin and quadratic increases (P < 0.01) in liver and hair Se concentrations as dietary Se level increased within each state. There was a source × level interaction (P < 0.01) for each tissue resulting in a greater increase when organic Se was fed. Serum Se and GSH-Px activity increased (P < 0.01) when both Se sources were fed and plateaued at each state at 0.15 mg Se/kg. There was a high and significant correlation between each tissue Se, serum Se, and GSH-Px activity to dietary Se level indicating that those states having greater grain natural Se contents also had greater tissue Se concentrations. These results indicate that a large difference in corn and soybean meal Se concentrations exists between states, that the addition of organic or inorganic Se to these grains increased tissue and serum Se in each state, and that organic Se was incorporated at greater concentrations in the loin, liver, and hair tissues of grower-finisher pigs than inorganic Se.

Effects of spray-dried porcine plasma on growth performance, immune response, total antioxidant capacity, and gut morphology of nursery pigs.

Two experiments were conducted to evaluate the effects of spray-dried porcine plasma (SDPP) on growth performance, immunity, antioxidant capacity, and gut morphology of nursery pigs. In Exp. 1, 96 weaned pigs (Nebraska female × Danbred sire; 20 ± 1 d of age; initial BW = 6.06 ± 0.02 kg) were assigned to 16 pens and randomly allotted to the control (CTL; no SDPP) or the CTL + SDPP treatment in 2 phases (phase 1: d 0 to 14, 5% SDPP; phase 2: d 14 to 28, 2.5% SDPP). Blood samples were collected on d 0 and weekly thereafter to quantify IgG, IgA, and total antioxidant capacity. On d 14, pigs (n = 16; 8 pigs/treatment) were selected and euthanized for small intestine tissue and alveolar macrophage collection. On d 7, pigs fed SDPP had greater ADG, ADFI (P = 0.001), and G:F (P = 0.019) compared with CTL pigs. On d 28, pigs fed SDPP had greater BW (P = 0.024) and tended to have greater ADG (P = 0.074) and ADFI (P = 0.062) compared with CTL pigs. There were no differences between treatments for serum IgG, IgA, and total antioxidant capacity. On d 14, greater villus height (P = 0.011) and villus:crypt (P = 0.008) were observed in duodenal tissue sections obtained from SDPP-fed pigs compared with CTL pigs. To evaluate effects of SDPP on immune biomarkers, alveolar macrophages collected from 3 pigs/treatment on d 14 were cultured in vitro and challenged with lipopolysaccharide (LPS; 10 ng/mL). Therefore, 4 treatments included 1) CTL diet with no LPS, 2) CTL diet with LPS (CTL+), 3) SDPP diet with no LPS, and 4) SDPP diet with LPS. There were no diet effects on tumor necrosis factor-α gene expression or secretion by alveolar macrophages. For IL-10 gene expression, a diet × LPS interaction (P = 0.009) was observed where CTL+ had greater (P < 0.05) IL-10 mRNA abundance compared with other treatments. A second experiment was conducted to evaluate the in vitro effects of porcine plasma using model porcine jejunal epithelial cells (IPEC-J2). The treatments applied to the IPEC-J2 cells were 1) CTL, 2) CTL + 10% porcine plasma, 3) CTL + 5% porcine plasma, 4) CTL + 2.5% porcine plasma, or 5) CTL + 5% fetal bovine serum. The addition of porcine plasma increased (P < 0.001) proliferation of IPEC-J2 cells at 24 and 48 h following exposure to the respective treatments. In conclusion, dietary SDPP increased growth performance of nursery pigs during the first week postweaning and provide benefits to gut morphology possibly via increased proliferation of enterocytes.

PINP as a biological response marker during teriparatide treatment for osteoporosis.

Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.

Effect of dam parity on litter performance, transfer of passive immunity, and progeny microbial ecology.

Litter performance and progeny health status may be decreased in progeny derived from primiparous sows but improve with increasing parity. The objective was to evaluate litter performance, the production and passive transfer of Ig, and fecal microbial populations in progeny derived from first parity (P1) compared with fourth parity (P4) dams. Litter performance was recorded for P1 (n = 19) and P4 (n = 24) dams including number of pigs/litter (total born, born live, stillbirths, mummified fetuses, prewean mortality, and pigs weaned) and average litter and piglet BW at birth (d 0), d 7, d 14, and at weaning (average d 19). Blood samples were collected from all dams on d 90 and 114 of gestation and d 0 of lactation. Colostrum and milk samples were collected from each dam on d 0, 7, and 14 of lactation for quantification of IgG and IgA. Blood and fecal samples were collected from each litter (n = 6 pigs/litter) on d 1, 7, and 14 after parturition. Circulating IgG and IgA concentrations were quantified in all blood samples. Denaturing gradient gel electrophoresis (DGGE) was used to characterize similarity and diversity of fecal microbes among progeny. Progeny of P1 dams had decreased average litter BW at d 7 (25.7 vs. 30.0 kg; P < 0.03) and decreased average piglet BW throughout the experiment (d 0, 7, 14, and 19; P < 0.001) compared with P4 progeny. No parity × day interactions were observed with respect to immunoglobulin or microbial analyses. Concentrations of IgA tended to be greater (P = 0.09) in samples of colostrum and milk obtained from P4 compared with P1 dams. Serum IgG concentrations were greater (P < 0.02) in P4 progeny compared with P1 progeny. Results of DGGE revealed that P1 progeny had increased (P < 0.001) microbial similarity on d 7 and decreased (P < 0.03) microbial similarity on d 14 compared with P4 progeny. Progeny of P1 dams tended (P = 0.07) to have a greater Shannon's diversity index compared with P4 progeny on d 1, and P1 progeny had a greater (P < 0.03) Shannon's diversity index compared with P4 progeny on d 7. Litter performance, passive transfer of immunity, and progeny microbial ecology were affected by dam parity.

Effect of dietary acids on growth performance of nursery pigs: a cooperative study.

An experiment involving 854 crossbred pigs (20 replicate pens of 4 to 8 pigs per pen) was conducted at 8 experiment stations to determine the effects of acids in nursery pig diets and their inclusion amounts on growth performance using diets and weaning ages typical of those used in the United States commercial pork industry. Diets were formulated to have constant a ME and contain 1.45, 1.45, and 1.30% standardized ileal digestible Lys for phases 1, 2, and 3, respectively. The basal diets were supplemented with various types and concentrations of acid at the expense of corn (Zea mays). Treatment diets included 0% acid (control), 0.1 or 0.2% phosphoric acid, 1 or 2% organic acids, and 0.1% phosphoric acid plus 1% organic acids with or without an antibiotic. The organic acids consisted of 50% citric acid and 50% fumaric acid by weight. All but the final diet contained the antibiotic carbadox. All diets contained 3,000 mg of Zn/kg diet from zinc oxide during phases 1 and 2 and had limited acid buffering capacity, ranging from 142, 127, and 122 mEq/kg of feed for phases 1, 2, and 3, respectively. At each participating station, pigs were randomly allotted to dietary treatments on the basis of their initial BW. Sex and ancestry were equally distributed across the treatments. Results indicated that treatment effects on pig performance were observed in phases 1 and 2 but not in phase 3. In phase 1, ADG of pigs fed 0.2% phosphoric acid was greater than that of pigs fed the combination of acids with no antibiotic (P = 0.041). In phase 2, pigs fed treatments containing an antibiotic had a greater ADG than those fed the combination of acids without antibiotic (P < 0.05). Addition of acids to diets did not affect growth performance during any phase or the overall period. Over the 4-wk study, growth rate was slowest on the treatment without antibiotic, with specific differences that were often statistically significant (P < 0.05). In summary, under the conditions of this experiment, the acid treatments had no effect but the antibiotic improved growth performance.

Concentration of dietary calcium supplied by calcium carbonate does not affect the apparent total tract digestibility of calcium, but decreases digestibility of phosphorus by growing pigs.

A regional experiment was conducted to test the hypothesis that the concentration of dietary Ca does not affect the digestibility of Ca or P in diets fed to growing pigs. Six diets based on corn, potato protein isolate, cornstarch, and soybean oil were formulated. All diets also contained monosodium phosphate, crystalline AA, salt, and a vitamin-micromineral premix. The only difference among the diets was that varying concentrations of calcium carbonate were used to create diets containing 0.33, 0.46, 0.51, 0.67, 0.92, and 1.04% Ca. All diets contained between 0.40 and 0.43% P. Six universities participated in the experiment and each university contributed 2 replicates to the experiment for a total of 12 replicates (initial BW: 23.1 ± 4.4 kg). Pigs were placed in metabolism cages that allowed total, but separate, collection of feces and urine from the pigs. Pigs within each replicate were randomly allotted to the 6 diets and fed experimental diets for 14 d with urine and feces being collected over a 5-d period. Diets, feces, and urine samples were analyzed for Ca and P, and the daily balance, the apparent total tract digestibility (ATTD), and the retention of Ca and P were calculated. Results indicated that intake, fecal excretion, and urinary excretion of Ca increased (linear, P<0.05) as dietary Ca concentration increased. The daily intake of P was not affected by the dietary concentration of Ca, but fecal excretion of P increased (linear, P<0.05) as dietary Ca concentrations increased. In contrast, urinary P output was decreased (linear, P<0.05) as dietary Ca increased. The retention of Ca increased (linear, P<0.05) from 1.73 to 4.60 g/d, whereas the retention of P decreased (linear, P<0.05) from 1.98 to 1.77 g/d as dietary Ca concentrations increased. However, if calculated as a percentage of intake, both Ca and P retention were decreased (linear, P<0.05) as dietary Ca concentration increased (from 55.4 to 46.1% and from 48.4 to 43.5%, respectively). The ATTD of Ca was not affected by the dietary concentration of Ca, but the ATTD of P was decreased (linear, P<0.05) from 56.9 to 46.2% as dietary Ca concentration increased. It is concluded that the dietary concentration of Ca does not affect the ATTD of Ca in calcium carbonate, but increased concentrations of dietary Ca may decrease the ATTD of P in diets based on corn, potato protein isolate, and monosodium phosphate.

What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?

Pharmacologic osteoporosis therapy, particularly anti-resorptives, is recommended in postmenopausal women with clinical risk factors for fracture. Treatment decisions should be made based on the relative benefit-risk profile in different patient populations. Emerging options [e.g., selective estrogen receptor modulators (SERMs) and denosumab] may hold promise for providing protection from bone loss and for fracture risk reduction.Osteoporosis, the most common clinical disorder of bone metabolism, is characterized by low bone mineral density, deterioration of microarchitecture, and a consequent increase in bone fragility and risk of fracture. Pharmacologic therapy is recommended in postmenopausal women with clinical risk factors for fracture and includes anti-resorptive agents such as bisphosphonates, hormone therapy, SERMs, and calcitonin. The anabolic agent teriparatide (parathyroid hormone) is usually reserved for high-risk patients or those with glucocorticoid-induced osteoporosis. Strontium ranelate, available outside the USA, has both anti-resorptive and anabolic properties. Supplementation with calcium and vitamin D is recommended for all women aged 50 years and older. Bisphosphonates are often considered first-line therapy for osteoporosis and have the largest base of clinical trial data showing efficacy for global fracture risk reduction. Low-dose hormone therapy is appropriate for younger women who are experiencing other menopausal symptoms. In women for whom bisphosphonates are not appropriate or not tolerated or in younger postmenopausal women who have a low risk for hip fracture, SERMs are a suitable treatment option. Calcitonin is designated for patients who are unable or unwilling to tolerate other osteoporosis agents. Emerging options, including newer SERMs (e.g., bazedoxifene and lasofoxifene) and the monoclonal antibody denosumab, may hold promise for providing protection from bone loss and for fracture risk reduction. Because no single agent is appropriate for all patients, treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations.

Effect of phytase on apparent total tract digestibility of phosphorus in corn-soybean meal diets fed to finishing pigs.

Five experiments were conducted to investigate the ability of different phytase products to improve P digestibility in finishing pigs. A corn-soybean meal basal diet containing 0.50% Ca, 0.32% P, and 0.40% Cr(2)O(3) was used to calculate apparent P and GE digestibility. Pigs were individually penned and fed their respective diet for ad libitum intake for 12 d before fecal sampling on d 13 and 14 and blood collection on d 14 for plasma P determination. Experiments 1 through 4 used gilts with across-trial average initial and final BW of 84 and 97 kg, respectively. Pigs were fed Natuphos (Exp. 1), OptiPhos (Exp. 2), Phyzyme (Exp. 3), or RonozymeP (Exp. 4) at 0, 200, 400, 600, 800, or 1,000 phytase units (FTU)/kg (where 1 FTU is defined as the quantity of enzyme required to liberate 1 micromol of inorganic P per min, at pH 5.5, from an excess of 15 micromol/L of sodium phytate at 37 degrees C). Experiment 5 used barrows with initial and final BW of 98 and 111 kg, respectively, and were fed diets containing 0, 500, or 1,000 FTU/kg of Natuphos, OptiPhos, Phyzyme, or RonozymeP. Pigs fed Natuphos (Exp. 1) and OptiPhos (Exp. 2) exhibited a linear and quadratic (P < 0.01) improvement in P digestibility with increasing levels of dietary phytase, whereas pigs fed Phyzyme (Exp. 3) and RonozymeP (Exp. 4) exhibited a linear (P < 0.01) improvement in apparent P digestibility with increasing levels of dietary phytase. In Exp. 5, the improvement in apparent P digestibility with increasing levels of dietary phytase was linear (P < 0.01) for Natuphos, Phyzyme, and RonozymeP, but was linear and quadratic (P < 0.01) for OptiPhos. Based on regression analysis, inorganic P release at 500 FTU/kg was predicted to be 0.070, 0.099, 0.038, and 0.030% for Natuphos, OptiPhos, Phyzyme, and RonozymeP, respectively. These estimates are comparable with those of pigs in Exp. 5, for which the estimated inorganic P release at 500 FTU/kg was 0.102, 0.039, and 0.028% for OptiPhos, Phyzyme, and RonozymeP, respectively, but not for the 0.034% value determined for Natuphos. The effect of dietary phytase on GE digestibility was inconsistent with a linear (P < 0.01) improvement in GE digestibility noted for OptiPhos (Exp. 2 and 5) and RonozymeP (Exp. 4), but the quadratic (P < 0.01) improvement for Natuphos. There was no effect of dietary phytase on plasma inorganic P. The data presented show clear improvements in P digestibility, with the estimated level of inorganic P release being dependent on phytase source and level.

Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis.

SUMMARY: The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. INTRODUCTION: The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. METHODS: Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 microg (TPTD20; N = 541), or teriparatide 40 microg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. RESULTS: Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. CONCLUSIONS: These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy.

Influence of dietary phosphorus concentration on the digestibility of phosphorus in monocalcium phosphate by growing pigs.

An experiment was conducted to test the hypothesis that the dietary inclusion rate of P does not influence the digestibility of P. The experiment was conducted at 4 experiment stations where the same protocol was followed. A total of 60 growing pigs (initial BW: 22.22 +/- 2.13 kg) were allotted to 6 dietary treatments with 10 replications per treatment. All pigs were placed in metabolism cages that allowed for the total, but separate, collection of urine and fecal materials. Six diets were formulated. The basal diet was based on corn (54.2%), soybean meal (20%), and cornstarch. No inorganic P was used, and the total concentration of P in the basal diet was calculated to be 0.29%. Five additional diets were formulated by adding monocalcium phosphate (MCP) in increments of 0.34% to the basal diet and thereby creating diets that were calculated to contain 0.36, 0.43, 0.50, 0.57, and 0.64% total P, respectively. Ground limestone was also added to these diets to maintain a calculated Ca:P ratio of 1.2:1. The balances of Ca and P and the apparent total tract digestibility (ATTD) of Ca and P were calculated for each diet. The contribution of P from the basal diet was then subtracted from the MCP-containing diets to calculate the balance and ATTD for P in MCP. Results of the experiment showed that the absorption and retention of both Ca and P increased (linear, P < 0.001) with increasing concentrations of Ca and P in the diet. The ATTD for Ca ranged from 62.3 to 66.8% and was not influenced by the dietary concentration of Ca. However, the ATTD for P increased from 38.4 to 65.2% as increasing levels of MCP were added to the diet (linear, P < 0.001). Increasing P intake from MCP increased (linear, P < 0.001) the excretion of P in the feces, but the quantity of P that was absorbed and retained also increased (linear, P < 0.001) as more P from MCP was added to the diet. When measured as a percentage of P intake, P retention was not influenced by the dietary P concentration. The ATTD for P in MCP ranged from 79.5 to 88.5% and was not affected by the concentration of P in the diet. Results of this experiment demonstrated that the digestibility and absorption of P from MCP are not influenced by the dietary concentration of P.

Osteoporosis practice patterns in 2006 among primary care physicians participating in the NORA study.

UNLABELLED: This study investigated osteoporosis management trends from 1998 to 2006 among 808 primary care physicians involved in the US-based NORA (National Osteoporosis Risk Assessment) study. These results suggest some significant improvements in osteoporosis management over the past eight years. INTRODUCTION: The purpose of this study was to investigate osteoporosis management trends among a large cohort of primary care physicians (PCPs) involved in the US-based NORA (National Osteoporosis Risk Assessment) study. METHODS: In 2006, we undertook a resurvey of the 2,836 NORA PCPs who completed a baseline survey in 1998. Of the 2,199 PCPs for whom we had current contact information and who were still practicing, we collected usable surveys from 808 (37% response rate). RESULTS: From 1998 to 2006, more than double the percentage of NORA PCPs reported using BMDs "often" (35% vs. 87%). There was a doubling of the percentage of NORA PCPs who reported that a T-score of < or = -2.5 was the threshold indicating the presence of osteoporosis (34% vs. 67%). The percentage of NORA PCPs who reported using bone turnover markers to screen, diagnosis, or monitor osteoporosis almost tripled (19% vs. 55%). The percentage of patients prescribed or recommended hormone therapy dropped sixfold (67% to 11%), and the percentage of patients prescribed bisphosphonates increased fourfold from 15% to 59%. CONCLUSION: These results suggest some significant improvements in osteoporosis management over the past eight years.