Patient groups prone to polypharmacy and special subpopulations are susceptible to suboptimal treatment. Refined dosing in special populations is imperative to improve therapeutic response and/or ...lowering the risk of toxicity. Model‐informed precision dosing (MIPD) may improve treatment outcomes by achieving the optimal dose for an individual patient. There is, however, relatively little published evidence of large‐scale utility and impact of MIPD, where it is often implemented as local collaborative efforts between academia and healthcare. This article highlights some successful applications of bringing MIPD to clinical care and proposes strategies for wider integration in healthcare. Considerations are brought up herein that will need addressing to see MIPD become “widespread clinical practice,” among those, wider interdisciplinary collaborations and the necessity for further evidence‐based efficacy and cost–benefit analysis of MIPD in healthcare. The implications of MIPD on regulatory policies and pharmaceutical development are also discussed as part of the roadmap.
Dry periods of 40 to 60 d have been an industry standard because dry periods <40 d have resulted in reduced milk yields in the subsequent lactation by 10 to 30%. However, recent research has ...demonstrated no production losses for cows given a 30-d dry period. The current study evaluated milk production effects of shortened or omitted dry periods for cows at mature-equivalent production >12,000kg of milk and treated with bovine somatotropin (bST). The study used 2 commercial dairies and one university dairy and included 4 treatments. Five multiparous and 5 primiparous cows from each farm were assigned to each treatment: 1) 60-d dry period, label use of bST (60DD); 2) 30-d dry period, label use of bST (30DD); 3) continuous milking, label use of bST (CMLST); and 4) continuous milking with continuous use of bST (CMCST). Per label, bST use started at 57 to 70 d in milk and ended 14 d before drying (60DD and 30DD) or expected calving date (CMLST). In primiparous cows, average milk yields during the first 17 wk of lactation were reduced for cows on treatments 30DD, CMLST, and CMCST vs. the 60DD treatment. (38.3, 35.1, and 37.5 vs. 44.1±1.3kg/d, respectively). For multiparous cows, respective milk yields did not differ (46.6, 43.4, 46.5, and 47.7±2.1kg/d). Shortened or omitted dry periods may impede mammary growth in primiparous cows, resulting in reduced milk yield in the subsequent lactation. In contrast, a shortened or omitted dry period with either bST protocol did not alter production in multiparous cows treated with bST. Quality aspects of prepartum milk and colostrum require additional characterization. For multiparous cows, milk income generated for short dry periods or for continuous milking might increase their profitability. At 17 wk of the subsequent lactation, estimates of the cumulative net margins of multiparous cows on the 30DD treatment and continuous milking treatments exceeded those of cows on the 60DD treatment by $40 to $60 per cow.
Very long chain n-3 fatty acids such as eicosapentaenoic acid (EPA; 20:5n-3) are important in human cardiac health and the prevention of chronic diseases, but food sources are limited. Stearidonic ...acid (SDA; 18:4n-3) is an n-3 fatty acid that humans are able to convert to EPA. In utilizing SDA-enhanced soybean oil (SBO) derived from genetically modified soybeans, our objectives were to examine the potential to increase the n-3 fatty acid content of milk fat and to determine the efficiency of SDA uptake from the digestive tract and transfer to milk fat. Three multiparous, rumen-fistulated Holstein cows were assigned randomly in a 3 × 3 Latin square design to the following treatments: 1) control (no oil infusion); 2) abomasal infusion of SDA-enhanced SBO (SDA-abo); and 3) ruminal infusion of SDA-enhanced SBO (SDA-rum). The SDA-enhanced SBO contained 27.1% SDA, 10.4% α-linolenic acid, and 7.2% γ-linolenic acid. Oil infusions provided 57 g/d of SDA with equal amounts of oil infused into either the rumen or abomasum at 6-h intervals over a 7-d infusion period. Cow numbers were limited and no treatment differences were detected for DMI or milk production (22.9±0.5 kg/d and 32.3±0.9 kg/d, respectively; least squares means ± SE), milk protein percentage and yield (3.24±0.04% and 1.03±0.02 kg/d), or lactose percentage and yield (4.88±0.05% and 1.55±0.05 kg/d). Treatment also had no effect on milk fat yield (1.36±0.03 kg/d), but milk fat percentage was lower for the SDA-rum treatment (4.04±0.04% vs. 4.30±0.04% for control and 4.41±0.05% for SDA-abo). The SDA-abo treatment increased n-3 fatty acids to 3.9% of total milk fatty acids, a value more than 5-fold greater than that for the control. Expressed as a percentage of total milk fatty acids, values (least squares means ± SE) for the SDA-abo treatment were 1.55±0.03% for α-linolenic acid (18:3n-3), 1.86±0.02 for SDA, 0.23 ± <0.01 for eicosatetraenoic acid (20:4n-3), and 0.18±0.01 for EPA. Transfer efficiency of SDA to milk fat represented 39.3% (range=36.8 to 41.9%) of the abomasally infused SDA and 47.3% (range=45.0 to 49.6%) when the n-3 fatty acids downstream from SDA were included. In contrast, transfer of ruminally infused SDA to milk fat averaged only 1.7% (range=1.3 to 2.1%), indicating extensive rumen biohydrogenation. Overall, results demonstrate the potential to use SDA-enhanced SBO from genetically modified soybeans combined with proper ruminal protection to achieve impressive increases in the milk fat content of SDA and other n-3 fatty acids that are beneficial for human health.
Consumers are becoming increasingly health conscious, and food product choices have expanded. Choices in the dairy case include fluid milk labeled according to production management practices. Such ...labeling practices may be misunderstood and perceived by consumers to reflect differences in the quality or nutritional content of milk. Our objective was to investigate nutritional differences in specialty labeled milk, specifically to compare the fatty acid (FA) composition of conventional milk with milk labeled as recombinant bST (rbST)-free or organic. The retail milk samples (n=292) obtained from the 48 contiguous states of the United States represented the consumer supply of pasteurized, homogenized milk of 3 milk types: conventionally produced milk with no specialty labeling, milk labeled rbST-free, and milk labeled organic. We found no statistical differences in the FA composition of conventional and rbST-free milk; however, these 2 groups were statistically different from organic milk for several FA. When measuring FA as a percentage of total FA, organic milk was higher in saturated FA (65.9 vs. 62.8%) and lower in monounsaturated FA (26.8 vs. 29.7%) and polyunsaturated FA (4.3 vs. 4.8%) compared with the average of conventional and rbST-free retail milk samples. Likewise, among bioactive FA compared as a percentage of total FA, organic milk was slightly lower in trans 18:1 FA (2.8 vs. 3.1%) and higher in n-3 FA (0.82 vs. 0.50%) and conjugated linoleic acid (0.70 vs. 0.57%). From a public health perspective, the direction for some of these differences would be considered desirable and for others would be considered undesirable; however, without exception, the magnitudes of the differences in milk FA composition among milk label types were minor and of no physiological importance when considering public health or dietary recommendations. Overall, when data from our analysis of FA composition of conventional milk and milk labeled rbST-free or organic were combined with previous analytical comparisons of the quality and composition of these retail milk samples, results established that there were no meaningful differences that would affect public health and that all milks were similar in nutritional quality and wholesomeness.
Purpose: To compare the rates of complications and patient satisfaction among breast cancer patients treated with mastectomy and tissue expander/implant reconstruction with and without radiotherapy.
...Methods and Materials: As part of the Michigan Breast Reconstruction Outcome Study (MBROS), breast cancer patients undergoing mastectomy with reconstruction were prospectively evaluated with respect to complications, general patient satisfaction with reconstruction, and esthetic satisfaction. Included in this study was a cohort of women who underwent breast reconstruction using an expander/implant (E/I). A subset of these patients also received radiotherapy (RT). At 1 and 2 years postoperatively, a survey was administered which included 7 items assessing both general satisfaction with their reconstruction and esthetic satisfaction. Complication data were also obtained at the same time points using hospital chart review. Radiotherapy patients identified in the University of Michigan Radiation Oncology database that underwent expander/implant reconstruction but not enrolled in the MBROS study were also added to the analysis.
Results: Eighty-one patients underwent mastectomy and E/I reconstruction. Nineteen patients received RT and 62 underwent reconstruction without RT. The median dose delivered to the reconstructed breast/chest wall, including boost, was 60.4 Gy (range, 50.0–66.0 Gy) in 1.8- to 2.0-Gy fractions. With a median follow-up of 31 months from the date of surgery, complications occurred in 68% (13/19) of the RT patients compared to 31% (19/62) in the no RT group (
p = 0.006). Twelve of 81 patients (15%) had a breast reconstruction failure. Reconstruction failure was significantly associated with experiencing a complication (
p = 0.0001) and the use of radiotherapy (
p = 0.005). The observed reconstruction failure rates were 37% (7/19) and 8% (5/62) for patients treated with and without radiotherapy, respectively. Tamoxifen was associated with a borderline risk of complications (
p = 0.07) and a significant risk of reconstruction failure (
p = 0.01). Sixty-six patients of the study group completed the satisfaction survey; 15 patients did not. To offset potential bias for patients not completing the survey, we analyzed satisfaction data assuming “dissatisfaction” scores for surveys not completed. In the analysis of patients with unilateral E/I placement, reconstruction failure was significantly associated with a lower general satisfaction (
p = 0.03). Ten percent of patients experiencing a reconstruction failure were generally satisfied compared to 23% who completed E/I reconstruction. In addition, tamoxifen use was associated with a significantly decreased esthetic satisfaction (
p = 0.03). Radiotherapy was not associated with significantly decreased general or esthetic satisfaction.
Conclusion: Irradiated patients had a higher rate of expander/implant reconstruction failure and complications than nonirradiated patients. Despite these differences, our pilot data suggest that both general satisfaction and patient esthetic satisfaction were not significantly different following radiotherapy compared to patients who did not receive RT. Although statistical power was limited in the present study and larger patient numbers are needed to validate these results, this study suggests comparable patient assessment of cosmetic outcome with or without radiotherapy in women who successfully complete expander/implant reconstruction.
The objective of this study was to determine the effects of altering dry period length in multiparous dairy cows (n=341) on milk production for a full lactation (294 d). The study used 3 commercial ...herds in the western United States. Cows producing greater than 8,400kg of mature-equivalent milk were assigned to treatments 60 d before their due dates. The 4 treatments were 1) 60-d dry period, label use of recombinant bovine somatotropin (rbST; 60d-L); 2) 32-d dry period, label use of rbST (32d-L); 3) 0-d dry period, label use of rbST (0d-L); and 4) 0-d dry period, continuous use of rbST (0d-C). Cows with shortened dry periods produced 625, 1,000, and 1,042kg of milk during the prepartum period for treatments 2 to 4, respectively. During the postpartum period, cows on the 32d-L treatment produced similar amounts of milk compared with the 60d-L treatment (11,490 vs. 11,968kg, respectively). However, cows on the 0d-L (10,316kg) and 0d-C (10,195kg) treatments produced significantly lower amounts of milk during the postpartum period compared with the 60d-L treatment. Total milk production from the prepartum and postpartum periods was not altered significantly and was 11,974, 12,112, 11,310, and 11,230kg for treatments 1 to 4, respectively. The concentrations of β-hydroxybutyrate and nonesterified fatty acids in serum after calving were decreased for cows on the 32d-L, 0d-L, and 0d-C treatments compared with cows on the 60d-L treatment, which may indicate improved metabolic status.
Abstract
Animal agriculture is challenged with societal issues such as animal welfare, antibiotic use, food vs feed, nutritional needs of humans for animal protein, and sustainability. Some of these ...issues can be emotional and accurate information is required to engage on these topics. Agriculture, both crop and animal ag, is considered a major contributor to greenhouse gases (GHG); however, agriculture can be a solution for storing GHG. Cropping systems are major decisions for dairy farms and most farms in the US rely in large part on genetically modified (GM) crops. In the US, more than 90% of corn, soybean and cotton are GM and animals are a major consumer of these crops. Current benefits of GM crops are from input traits, such as herbicide tolerance and insect resistance. Even though trusted organizations, like the National Academies of Sciences, have concluded that GM foods are as safe as conventional foods, consumers don’t always perceive the value of these traits. This has affected consumer acceptance of GM technology as well as how meat, milk and eggs are produced. To better understand the ecosystem impacts associated with various management practices applied to both GM and conventional hybrid corn and soybean cropping systems, a model-based analysis was performed across 12 states in the U.S. corn-belt. The analysis generated potential erosion and GHG emissions estimates associated with the implementation of several practices based on public SSURGO data, NASS crop productivity data, and spatially explicit weather data. Rill and inter-rill erosion resulting from rainfall and surface runoff were modeled and sediment loss and deposition due to wind was simulated. In addition to erosion, soil organic carbon (SOC) change and nitrous oxide flux (N2O) were modeled using the Denitrification-Decomposition model (DNDC). Based on the analysis, average GHG emissions associated with corn production across the 12-state region could be reduced by an estimated 8.7 kg CO2e/bu and 14.3 kg CO2e/bu by switching from conventional hybrid production to a reduced till and no-till GMO system, respectively. A corresponding average reductions in soil loss of 10.9tn/ac and 13.6 tn/ac due to water and wind erosion were also estimated based on a change to a reduced till or no-till GMO system. Based on the model estimates, feeding GM crops makes production of meat, milk and eggs more sustainable with respect to GHG emissions and erosion.
Animal agriculture is challenged with societal issues such as animal welfare, antibiotic use, food vs feed, nutritional needs of humans for animal protein, and sustainability. Some of these issues ...can be emotional and accurate information is required to engage on these topics. Agriculture, both crop and animal ag, is considered a major contributor to greenhouse gases (GHG); however, agriculture can be a solution for storing GHG. Cropping systems are major decisions for dairy farms and most farms in the US rely in large part on genetically modified (GM) crops. In the US, more than 90% of corn, soybean and cotton are GM and animals are a major consumer of these crops. Current benefits of GM crops are from input traits, such as herbicide tolerance and insect resistance. Even though trusted organizations, like the National Academies of Sciences, have concluded that GM foods are as safe as conventional foods, consumers don't always perceive the value of these traits. This has affected consumer acceptance of GM technology as well as how meat, milk and eggs are produced. To better understand the ecosystem impacts associated with various management practices applied to both GM and conventional hybrid corn and soybean cropping systems, a model-based analysis was performed across 12 states in the U.S. corn-belt. The analysis generated potential erosion and GHG emissions estimates associated with the implementation of several practices based on public SSURGO data, NASS crop productivity data, and spatially explicit weather data. Rill and inter-rill erosion resulting from rainfall and surface runoff were modeled and sediment loss and deposition due to wind was simulated. In addition to erosion, soil organic carbon (SOC) change and nitrous oxide flux (N2O) were modeled using the Denitrification-Decomposition model (DNDC). Based on the analysis, average GHG emissions associated with corn production across the 12-state region could be reduced by an estimated 8.7 kg CO2e/bu and 14.3 kg CO2e/bu by switching from conventional hybrid production to a reduced till and no-till GMO system, respectively. A corresponding average reductions in soil loss of 10.9tn/ac and 13.6 tn/ac due to water and wind erosion were also estimated based on a change to a reduced till or no-till GMO system. Based on the model estimates, feeding GM crops makes production of meat, milk and eggs more sustainable with respect to GHG emissions and erosion.
Four multiparous cows with cannulas in the rumen and proximal duodenum were used in early lactation in a 4×4 Latin square experiment to investigate the effect of method of application of a fibrolytic ...enzyme product on digestive processes and milk production. The cows were given ad libitum a total mixed ration (TMR) composed of 57% (dry matter basis) forage (3:1 corn silage:grass silage) and 43% concentrates. The TMR contained (g/kg dry matter): 274 neutral detergent fiber, 295 starch, 180 crude protein. Treatments were TMR alone or TMR with the enzyme product added (2 kg/1000kg TMR dry matter) either sprayed on the TMR 1h before the morning feed (TMR-E), sprayed only on the concentrate the day before feeding (Concs-E), or infused into the rumen for 14h/d (Rumen-E). There was no significant effect on either feed intake or milk yield but both were highest on TMR-E. Rumen digestibility of dry matter, organic matter, and starch was unaffected by the enzyme. Digestibility of NDF was lowest on TMR-E in the rumen but highest postruminally. Total tract digestibility was highest on TMR-E for dry matter, organic matter, and starch but treatment differences were nonsignificant for neutral detergent fiber. Corn silage stover retention time in the rumen was reduced by all enzyme treatments but postruminal transit time was increased so the decline in total tract retention time with enzymes was not significant. It is suggested that the tendency for enzymes to reduce particle retention time in the rumen may, by reducing the time available for fibrolysis to occur, at least partly explain the variability in the reported responses to enzyme treatment.
PDF
