Invited review: The effect of milk feeding practices on dairy calf behavior, health, and performance-A systematic review.

The aim of this systematic review was to summarize the literature assessing the effects of milk feeding practices on behavior, health, and performance on dairy calves. Peer-reviewed, published articles, written in English, directly comparing the effects of milk allowance, milk feeding methods, or milk feeding frequency on dairy calves were eligible for inclusion. Outcome measures could include sucking behavior, sucking on a teat (nutritive sucking, non-nutritive sucking on a teat), abnormal sucking behavior (non-nutritive sucking on pen fixtures, other oral behaviors, or cross-sucking), signs of hunger (vocalizations or unrewarded visits at the milk feeder), activity (lying time or locomotor play), feeding behavior (milk intake, starter intake, milk meal duration, or starter meal duration), growth (body weight or average daily gain), and health (occurrence of diarrhea, respiratory disease, or mortality). We conducted 2 targeted searches using Web of Science and PubMed to identify key literature. The resulting articles underwent a 2-step screening process. This process resulted in a final sample of 94 studies. The majority of studies investigated milk allowance (n = 69). Feeding higher milk allowances had a positive or desirable effect on growth, reduced signs of hunger, and increased locomotor play behavior during the preweaning period, whereas starter intake was reduced. Studies addressing health pointed to no effect of milk allowance, with no consistent evidence indicating that higher milk allowances result in diarrhea. Studies addressing milk feeding methods (n = 14) found that feeding milk by teat reduced cross-sucking and other abnormal oral behaviors. However, results on the effect of access to a dry teat were few and mixed. Milk feeding frequency (n = 14 studies) appeared to have little effect on feed intakes and growth; however, there is some evidence that calves with lower feeding frequency experience hunger. Overall, findings strongly suggest feeding higher volumes of milk using a teat; however, further work is needed to determine the optimal feeding frequency for dairy calves.

Only few benefits from propylene glycol drench in early lactation for cows identified as physiologically imbalanced based on milk spectra analyses.

The main objective of this study was to test the efficiency of a management system combining metabolic clustering of cows based on Fourier-transform mid-infrared (FT-MIR) spectra of milk and targeted treatment of metabolically imbalanced cows with propylene glycol drench. We hypothesized that cows identified in a metabolically imbalanced status during early lactation were associated with subsequent impaired health, reproduction, and production, and that treatment with propylene glycol treatment would improve health, reproduction, and production relatively more in these cows than in control cows. We completed a prospective, randomized controlled trial with 356 early-lactation cows in 2 private dairy herds in Denmark from December 2017 to April 2018. Milk samples of cows were collected before treatment, from 4 to 9 d in milk, and after treatment, from 22 to 27 d in milk. Milk samples were analyzed using FT-MIR spectroscopy. We also measured 4 milk metabolites (ß-hydroxybutyrate, isocitrate, malate, and glutamate) and fat and protein contents. Based on FT-MIR spectra and cluster analyses, cows were clustered into groups of metabolically imbalanced and healthy cows. Within each group, cows were allocated randomly to treatment with propylene glycol (500 mL for 5 d) or no treatment. We analyzed the effect of the treatment on cow-level variables: metabolic cluster, milk metabolites, fat and protein contents, and fat-to-protein ratio at a milk sampling after the treatment. Furthermore, we analyzed daily milk yield, calving to first service interval, and disease occurrence. Results showed only a few effects of propylene glycol treatment and few interactions between treatment and metabolic clusters. We found no significant main effects of propylene glycol treatment in any of these analyses. A negative effect of the imbalanced metabolic cluster was found for the outcome of calving to first service interval for multiparous cows. In conclusion, we found a longer calving to first service interval in metabolically imbalanced cows, but we were not able to demonstrate overall benefits from the applied detection of cows in imbalanced metabolic status in early lactation and follow-up by treatment with propylene glycol.

Mortality, diarrhea and respiratory disease in Danish dairy heifer calves: Effect of production system and season.

Diarrhea and respiratory disease are major health problems for dairy calves, often causing calf mortality. Previous studies have found calf mortality to be higher in organic dairy herds compared to conventional herds. The aim of this study was to investigate the association between production system (conventional/organic), season (summer/winter) and calf mortality risk, diarrhea, signs of respiratory disease and ocular discharge, respectively, for dairy heifer calves aged 0-180 days. Sixty Danish dairy herds, 30 conventional and 30 organic, were visited once during summer and once during winter. During the herd visits, calves were clinically examined for signs of diarrhea, hampered respiration, nasal discharge, coughing and ocular discharge. Data on mortality were obtained from the Danish Cattle Database. Data were analyzed using logistic regression models, with mortality risk and disease measures as outcome variables for each of three calf age groups: 0-28, 29-90 and 91-180 days. In organic herds, odds of mortality among calves aged 0-28 days were 2.09 (95% confidence interval (CI): 1.38-3.15) times higher during winter compared to summer. Odds of nasal discharge for calves 0-28 days in organic herds were 10.3 (95% CI: 2.27-46.6), 10.7 (95% CI: 2.40-40.0) and 5.97 (95% CI: 1.29-27.6) times higher for organic and conventional herds during winter (OW and CW) and conventional herds during summer (CS) respectively, compared to organic herds during summer (OS). For calves aged 29-90 days, odds of nasal discharge were 8.22 (95% CI: 3.88-17.4), 8.06 (95% CI: 3.18-20.4) and 2.86 (95% CI: 1.08-7.55) times higher for OW, CW and CS respectively, compared to OS. Odds of nasal discharge for calved aged 91-180 days were 7.03 (95% CI: 3.95-12.5) and 4.27 (95% CI: 1.81-10.1) times higher for OW and CW respectively compared to OS. For calves aged 29-90 days, odds of coughing were 2.23 (95% CI: 1.06-4.71) and 3.82 (95% CI: 1.76-8.21) times higher for OW and CW compared to OS, while odds of coughing for calves aged 91-180 days were 2.09 (95% CI: 1.19-3.67) and 2.55 (95% CI: 1.39.4.67) times higher for OW and CW compared to OS. Odds of ocular discharge for calves aged 29-90 days were 0.22 (95% CI: 0.10-0.52), 0.27 (95% CI: 0.11-0.66) and 0.42 (95% CI: 0.18-0.99) times higher for OW, CW and CS compared to OS. In conclusion, mortality and morbidity of Danish dairy heifer calves are, for some variables and in certain age groups, dependent on production system and season.

Register-based predictors of violations of animal welfare legislation in dairy herds.

The assessment of animal welfare can include resource-based or animal-based measures. Official animal welfare inspections in Denmark primarily control compliance with animal welfare legislation based on resource measures (e.g. housing system) and usually do not regard animal response parameters (e.g. clinical and behavioural observations). Herds selected for welfare inspections are sampled by a risk-based strategy based on existing register data. The aim of the present study was to evaluate register data variables as predictors of dairy herds with violations of the animal welfare legislation (VoAWL) defined as occurrence of at least one of the two most frequently violated measures found at recent inspections in Denmark, namely (a) presence of injured animals not separated from the rest of the group and/or (b) animals in a condition warranting euthanasia still being present in the herd. A total of 25 variables were extracted from the Danish Cattle Database and assessed as predictors using a multivariable logistic analysis of a data set including 73 Danish dairy herds, which all had more than 100 cows and cubicle loose-housing systems. Univariable screening was used to identify variables associated with VoAWL at a P-value<0.2 for the inclusion in a multivariable logistic regression analysis. Backward selection procedures identified the following variables for the final model predictive of VoAWL: increasing standard deviation of milk yield for first lactation cows, high bulk tank somatic cell count (⩾250 000 cells/ml) and suspiciously low number of recorded veterinary treatments (⩽25 treatments/100 cow years). The identified predictors may be explained by underlying management factors leading to impaired animal welfare in the herd, such as poor hygiene, feeding and management of dry or calving cows and sick animals. However, further investigations are required for causal inferences to be established.

Adjusting for multiple clinical observers in an unbalanced study design using latent class models of true within-herd lameness prevalence in Danish dairy herds.

The elimination of misclassification bias introduced by multiple observers was evaluated and discussed based on an illustrative example using lameness prevalence in 80 Danish dairy herds. Data from 5073 cows from loose-housed cubicle herds larger than 100 cows were included in the analysis. Four trained observers performed clinical scoring on cow level and undertook a calibration test with 39 video sequences. The calibration test served both the purpose of estimating inter-observer agreement (PABAK=0.69) in accordance with previous results and to estimate the sensitivity (Se) and specificity (Sp) for each observer. In the absence of a gold standard for the clinical observations, a latent class analysis (LCA) evaluating the true within-herd lameness prevalence was used. Sensitivity amongst observers was fairly low (0.24-0.81) inducing a general underestimation of the true prevalence. Comparative analyses were made to assess the effect of grazing on the lameness prevalence in order to demonstrate the consequences of using unadjusted apparent prevalences (AP) compared to the true prevalences (TP). Lameness prevalence was higher in grazing herds using AP estimates (19.0% zero-grazing, 20.2% grazing); while the TP estimates showed the expected higher lameness prevalence in zero-grazing herds (42.3% vs. 35.9%). Hence, this study emphasizes the importance of adjusting for observer Se and Sp to obtain true prevalence and avoid false interpretation.

Effect of grazing on the cow welfare of dairy herds evaluated by a multidimensional welfare index.

Structural development in the prime sector has led to increasing herd sizes and new barn systems, followed by less summer grazing for dairy cows in Denmark. Effects of grazing on single welfare measures in dairy cows - for example, the presence of integument alterations or mortality - have been studied under different conditions. However, the effect of grazing on welfare, conceptualised as the multidimensional physical and mental state of the animal, has not yet been studied in contemporary cubicle loose-housing systems. The aim of our study was to investigate, based on a Welfare Quality® inspired multidimensional dairy cow welfare assessment protocol, the within-herd effect of summer grazing compared with winter barn housing in Danish dairy herds with cubicle free-stall systems for the lactating cows. Our hypothesis was that cow welfare in dairy herds was better during summer grazing than during full-time winter housing. Furthermore, we expected improved welfare with an increase in daily summer grazing hours. In total, 41 herds have been visited once in the winter and once in the summer of 2010 to assess their welfare status with 17 different animal- and resource-based welfare measures. A panel of 20 experts on cattle welfare and husbandry evaluated the relative weight of the 17 welfare measures in a multidimensional assessment scheme. They estimated exact weights for a priori constituted severe compared with moderate scores of welfare impairment concerning each measure, as well as relevance of the measures in relation to each other. A welfare index (WI; possible range 0 to 5400) was calculated for each herd and season with a higher index indicating poorer welfare. The within-herd comparison of summer grazing v. winter housing considered all the 17 measures. The mean WI in summer was significantly lower (better) than in winter (mean 2926 v. 3330; paired t-test P = 0.0001) based on a better state of the integument, claw conformation and better access to water and food. Body condition and faeces consistence were worse in summer. Many daily grazing hours (range average above 3 to 9 h) turned out to be more beneficial than few daily grazing hours (range average above 9 to 21 h) for the welfare of the dairy herds. In conclusion, this study reports a positive within-herd effect of summer grazing on dairy cow welfare, where many daily grazing hours were more beneficial than few daily grazing hours.

Molecular testing in congenital adrenal hyperplasia due to 21α-hydroxylase deficiency in the era of newborn screening.

Newborn screening (NBS) identifies the majority of classical [salt-wasting (SW) and simple-virilizing (SV)] cases of congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase (21α-OHase) during the first days of life. Diagnosis of classical CAH is confirmed by follow-up serum 17-hydroxyprogesterone and/or the adrenocorticotropin stimulation test; however, neither test definitively distinguishes between the classical subtypes. After confirmation, all newborns are started on hydrocortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) treatment. While initiating fludrocortisone treatment in classical CAH patients, independent of subtype and before SW signs or symptoms occur, prevents a life-threatening SW crisis, it may later complicate distinguishing between the classical subtypes. Genotype-phenotype correlations in 21α-OHase deficiency are excellent; however, molecular testing is not a regular part of the diagnostic workup. Molecular testing on 39 patients (25 identified by NBS) with an already established diagnosis of CAH identified 11 SW patients (8 identified by NBS) whose mutations suggested further biochemical and clinical reassessment of their subtype. Overall, SW accounted for 57.6% of our classical CAH patients, below the generally accepted figure that >75% of classical CAH are comprised of the SW form. In the era of NBS, molecular testing is a valuable supplemental tool identifying patients who may benefit from reassessment of their salt-retaining ability.

The revised Canadian Guidelines for the Economic Evaluation of Pharmaceuticals.

The first edition of the Guidelines for Economic Evaluation of Pharmaceuticals: Canada was published in November 1994. At that time, the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) was assigned the task of maintaining and regularly updating the Canadian Guidelines. Since their introduction, a great deal of experience has been gained with the practical application of the guidelines. Their role has also evolved over time, from being a framework for pharmacoeconomic research to the point where a wide variety of decision-makers use economic evaluations based on the principles set out in the guidelines as a means of facilitating their formulary decisions. In addition, methodologies in certain areas (and the body of related research literature in general) have developed considerably over time. Given these changes in the science and the experience gained, CCOHTA convened a multi-disciplinary committee to address the need for revisions to the guidelines. The underlying principles of the review process were to keep the guidance nature of the document, to focus on the needs of 'doers' (so as to meet the information needs of 'users') and to provide information and advice in areas of controversy, with sound direction in areas of general agreement. The purpose of this review is three-fold: (i) to outline the process which lead to the revision of the Canadian Guidelines; (ii) to describe the major changes made to the second edition of this document; and (iii) to consider the 'next steps' as they relate to the impact of such guidelines and the measurement of outcomes related to economic assessments of pharmaceuticals in general.

Use of economic evaluation guidelines: 2 years' experience in Canada.

Considerable effort has been expended in recent years in the development of methodology guidelines for economic evaluation of pharmaceutical products, driven in part by the desire to improve the rigour and quality of economic evaluations and to help decision making. Canada was one of the first countries to develop such guidelines and to encourage their use. This paper examines the extent to which the economic evaluations that were submitted to the Canadian Coordinating Office for Health Technology Assessment in the last two years adhered to Canadian guidelines. The analytic technique employed by twelve studies as well as the comparator used, the perspective taken, the outcome measure selected, the cost items that were taken into consideration and the extent of sensitivity analyses that were performed are reviewed in this paper. It can be concluded that although studies have been of variable quality, the majority of them were well presented, complete and transparent, due in part to the guidelines. Except for the perspective of the analysis, guidelines were, in many respects, adhered to and did not restrict investigators to specific methodologies or specific techniques. They were also instrumental in ensuring a minimum set of standards.

A Canadian perspective.

Although the healthcare program in Canada is in many ways universal, there are several differences between the provinces. Two key federal bodies (the Health Protection Branch of Health Canada and the Patented Medicine Prices Review Board) are involved in the drug review process. In addition, the Canadian Coordinating Office for Health Technology Assessment (CCOHTA), an organization funded jointly by provinces and the federal government, reviews new or existing drugs at the request of provinces. Each province or territory and the federal government has its own drug plan or plans. The 10 Canadian provinces require a notice of compliance, information on pricing, and clinical and comparative information for submission of a new drug. Over the last 3 years, 8 of the 10 provinces have required pharmacoeconomic analyses to be added to the submissions. Four of the eight provinces requiring pharmacoeconomic evaluations have specified that these evaluations should be made according to the Canadian Coordinating Office for Health Technology Assessment guidelines. A review of the utilization patterns of lipid-lowering therapies is presented in this Canadian context. Statins comprised 80% of the lipid-lowering drug market in 1995. Prescribers use statins available in Canada interchangeably for all approved and nonapproved indications. The newest statin, atorvastatin, has attained a market share for new prescriptions equivalent to simvastatin and pravastatin, despite the lack of clinical outcome studies. CCOHTA reviewed the evidence of efficacy and effectiveness of statins, evaluated whether significant differences existed between statins, and analyzed published economic evaluations. It found that treatment of higher-risk patients with statins is more cost-effective than that of lower-risk subjects. The evaluation also concluded that the statins, as a class, probably act in reducing LDL and raising HDL, resulting in beneficial clinical outcomes.

Health economics of gastroesophageal reflux disease.

The present study provides an overview of the current state of health economics studies of gastroesophageal reflux disease (GERD). It indicates the strengths and weaknesses of individual studies, and the state of health economics analysis in general as they apply to GERD. Specifically, this study adopts a pharmacoeconomic perspective, which is a subsection of health economics analytical methods, to provide a comparative analysis of alternative courses of action based on cost and consequence. The pharmacoeconomic outlook is most effective when it considers a comprehensive societal perspective, with special consideration given to other relevant viewpoints, such as the payer, the primary provider and, most important, the patient. Pharmacoeconomics provides several specific analytical techniques for GERD-related health economics analysis. The Canadian Association of Gastroenterology consensus conference on GERD in 1996 thought that a cost effective analysis was the most appropriate technique to assess the pharmacoeconomics of GERD. Six previous studies on GERD health economics have been performed comparing omeprazole with H2 receptor antagonists. These studies vary in cost data collected and in analytical techniques. In general, the existing outcome measurements of these previous health economics studies are not ideal. Namely, they combine various GERD grades, use randomized controls, are endoscopically based, assess pharmaceutical therapy only and are short term. More appropriate health economic trials in GERD, which focus on GERD management strategies and therapeutic treatment of GERD, need to be designed and conducted. These economic assessments, however, should not replace detailed thinking, careful observation, good judgement and common sense.

An economic evaluation of finasteride for treatment of benign prostatic hyperplasia.

This evaluation was conducted at the request of a Canadian provincial government considering finasteride for formulary inclusion. The comparator therapies, in accordance with Canadian pharmacoeconomic guidelines, were the most prevalent treatment [transurethral resection of the prostate (TURP)] and the lowest cost treatment (watchful waiting). All costs were measured in 1994 Canadian dollars ($Can), and both costs and outcomes were discounted at 5% per annum. Cost-effectiveness and cost-utility ratios were calculated, and were found to be dependent on initial symptom severity and the anticipated duration of treatment with finasteride. The drug was shown to be the dominant alternative compared with both TURP and watchful waiting for patients with moderate symptoms, when the duration of drug therapy is 3 years or less. However, finasteride is a weak alternative for patients with severe symptoms who are treated for 4 years or more. For other groups of patients (i.e. moderate symptoms and on finasteride for 4 years or more; severe symptoms and on treatment for 3 years or less), the drug can improve health-related quality of life, but at a cost of between $Can3000 and $Can97,000 per incremental quality-adjusted life year (1994 dollars). Our study also indicated that it would cost between $Can2.7 million and $Can5.6 million, depending on the severity mix of the patients, to treat cohort of 10,000 men aged 60 years or older with finasteride.

Experimental treatment of equine sarcoid using a xanthate compound and recombinant human tumour necrosis factor alpha.

A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on 5 healthy horses showed that the compounds were well-tolerated; apart from a local, temporary oedema at the injection site, no other clinical symptoms were observed after subcutaneous administration of volumes from 0.1 to 10 ml per injection. The tested concentrations of D609 and KC12 (5 mg/ml solution) and of rh-TNF alpha (50 micrograms/ml) were used for the treatment experiments. The repeated injections of the compounds to 11 sarcoid affected horses were also well-tolerated, except by one horse. In this case the treatment had to be interrupted after two injections because of severe reaction, i.e. fever and lameness due to oedemas. Five horses (n = 6 sarcoids) were treated by local, subcutaneous injection of D609 and KC12 under the tumour at intervals of 3 weeks. On one periocular sarcoid the compounds were applied as an ointment. After a follow-up period of 18 months, 5 tumours did completely regress and one remained unchanged. The periocular tumour showed a reduction in size. Five horses (n = 9 sarcoids) were then treated with a combination of D609, KC12 and rh-TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA of bovine papillomavirus type 1 and 2 in equine sarcoids: PCR detection and direct sequencing.

Nucleotide sequences of bovine papillomavirus (BPV) DNA amplified by the polymerase chain reaction (PCR) from samples of equine sarcoid skin tumours were determined. All naturally occurring sarcoids (n = 58 tumours from 32 horses and 2 donkeys) contained BPV-DNA. All but 3 of the genome fragments belonged to the BPV type 1 strain (BPV-1); the remaining were BPV type 2. Similar results were obtained with cutaneous bovine papillomas used as controls (n = 20). One of the horses, carrying 2 sarcoids, was particularly interesting; one tumour contained BPV-1 DNA whilst the other sarcoid yielded BPV-2 DNA, suggesting that horses are not immune to super-infection. BPV-DNA was even amplified from the sarcoid samples which had yielded negative results in previous investigations when DNA isolated from the lesions was used in Southern blot hybridization with BPV probes. In addition, there was no detectable BPV-DNA in any equine or bovine tissue examined other than sarcoids or cutaneous bovine papillomas. Biopsies of normal skin surrounding lesions yielded exclusively negative results. The described nucleotide differences represent a natural genomic variation of this BPV type between geographically distant locations. The identical variations recovered from cattle and horses in Switzerland, a finding of great epidemiological interest, strongly suggest that a uniform variant of BPV-1 is one of the etiologic agents of equine sarcoid and bovine papilloma in a given region.

Effect of interventions on prescribing of antimicrobials for prophylaxis in obstetric and gynecologic surgery.

The effect of interventions on the conformity of physicians with guidelines for the appropriate use of antimicrobial prophylaxis in obstetric and gynecologic surgery is reported. Guidelines on the appropriate use of antimicrobial prophylaxis in common obstetric and gynecologic surgical procedures were developed in late 1986 by the antibiotic subcommittee at a 1100-bed tertiary-care teaching facility. The guidelines were not adopted immediately by the department of obstetrics and gynecology (OB-GYN). An audit of the medical records of women who had received antimicrobial therapy for abdominal and vaginal hysterectomies and emergency cesarean sections during January through March 1987 showed that cefoxitin was used in 68% of the cases instead of the less expensive and equally efficacious cefazolin as recommended in the guidelines. The projected annual cost of this nonconformity was $26,500. After the subcommittee informed the physicians about the guidelines and the audit results, the OB-GYN department adopted the guidelines. A second audit performed one year later showed that cefazolin was used in the recommended manner in 93% of cases; projected annual cost savings were $25,000. Both audits showed that prophylactic treatment was inappropriately prolonged in 6% of cases. Substantial cost savings were realized by minimizing inappropriate antimicrobial drug use through efforts to promote rational and cost-effective therapy.

Product evaluation and purchase.

The product evaluation committee has not only been successful in managing new product evaluation and purchase, but it has also kept the nursing department informed and updated on available new items. It provides for participation by staff most likely to use the product. Finally, the committee contributes to the hospital goal of providing cost-effective quality patient care.