Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility.

BACKGROUND: Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment. RESULTS: Atropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 µg/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7 L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9 L/h‧kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8 h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1 mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols. CONCLUSIONS: Taking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24 h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 µg/kg/24 h offers a safe alternative.

Increased susceptibility to infections before the diagnosis of immune thrombocytopenia.

BACKGROUND: Infections after diagnosis of primary chronic immune thrombocytopenia (cITP) have mostly been connected to the immunomodulation treatment. Infections may trigger autoimmune diseases and may be a complication of an already impaired immune system. OBJECTIVES: To investigate the association of cITP with infection before diagnosis. We also estimated the incidence of cITP based on the new definition by the International ITP Working Group. METHODS: We identified 1087 adults with primary cITP between 2006 and 2012 using the Swedish Patient Register. Data on infections not already associated with secondary ITP were also retrieved from the register. The standardized incidence ratios (SIRs), using the rates from the general population, and 95% confidence intervals (CIs) were estimated as a measure of relative risk. We used data from the Prescribed Drug Register to estimate SIR for anti-infective treatment. RESULTS: The incidence of cITP was 2.30 per 100 000 person-years (95% CI, 2.15-2.45). cITP was associated with an increased risk of serious infections requiring inpatient or outpatient care within 5 years before cITP diagnosis (SIR = 8.74; 95% CI, 7.47-10.18). Higher magnitude SIRs were observed for candidiasis, viral infection at an unspecified site and acute upper respiratory infections. For anti-infective drugs the SIR was 1.37 (1.25-1.50) and the highest SIRs were observed for amoxicillin, macrolides, nitrofurantoin and antivirals. CONCLUSION: Patients with cITP have increased risks of infection and anti-infective treatments before their cITP diagnosis, with a more marked risk for candidiasis and viral infections. The findings indicate that infection is not only related to the immunomodulation treatment but also to the disease itself.

A quantitative approach to analysing cortisol response in the horse.

The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 µg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57 µg/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24 µg/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65 ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test.

Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate.

Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 µg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 µg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 µg/L and in urine 4.2 ± 0.9 µg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 µg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.

Acute bucket-handle tear of the medial meniscus in a golfer.

This is the first case report of an acute bucket-handle tear in an amateur golfer. The injury occurred during the follow-through phase of the golf swing. The rate of incidence of knee injuries in golfers is only 10%. There is a difference in the injury pattern between amateur and professional golfers; amateurs are more likely to sustain injuries related to poor swing technique. Professional golfers, on the other hand, report more injuries related to overuse. Although forces in the knee are relatively minor in this sport, acute injuries can happen when poor technique is used.

Temporal aspects of foot-pad dermatitis in Swedish broilers.

This study aimed at analysing the temporal aspects of foot-pad dermatitis in Swedish broilers. The information on disease prevalence and severity was based on a 2-year foot-health surveillance programme where information on producer, breed, feed manufacturer, region, abattoir, date of slaughter and several other variables was recorded. The seasonal effects were evaluated using classical multiplicative decomposition time series analysis. This study shows that there has been a significantly consistent decrease in the prevalence of severe foot-pad lesions during the first 2 years of the programme. Looking at the development over time we found a trend-cycle component of 10.4% and a seasonal component of 48.7% resulting in a total adjusted R-square value of 58.5% for the total foot-pad score. This means that almost 60% of the variation in flock foot-pad score can be explained by the variable 'time', and that this variation was mainly related to seasonal effects but also to a general decreasing trend over the study period. However, substantial differences in temporal patterns among slaughterhouses, feed suppliers and regions were found. The time series analysis approach was found to be useful for this type of investigation when evaluating the effects of an intervention programme, and it can also be applied for projecting the future development of disease status in a stable population.

Spatial aspects of foot-pad dermatitis in Swedish broilers.

This study aimed at analysing spatial and spatio-temporal aspects of foot-pad dermatitis in Swedish broilers. The information on disease prevalence and severity was based on a two-year foot-health surveillance programme where information on producer, breed, feed manufacturer, region, abattoir, date of slaughter and several other variables was recorded. The level of clustering in space was analysed on 2-digit zipcode level using Moran's I test which measures similarity of location. The level of clustering in space was also analysed using the Ipop test, which takes the population at risk into consideration. The examination of time-space interaction was carried out using the Barton method and the Knox method. We found a significant (p < 0.001) clustering of regions with respect to foot-pad dermatitis score using Moran's I test, and a significant (p < 0.0001) clustering in space also when related to the number of flocks delivered from each region. The flocks with very high prevalence of foot-pad dermatitis were significantly (p < 0.05) clustered in both time and space, i.e. the flocks with high prevalence of lesions came from the same geographic area during the same time periods. This information will permit us to focus the control efforts within the foot-health surveillance programme on specific regions in specific time periods, thus making the programme more effective.

Prevalence and control of foot-pad dermatitis in broilers in Sweden.

1. A cross-sectional observational study was carried out to investigate spatial, temporal and management aspects of foot-pad dermatitis in Swedish broilers. The efficacy of a control programme was evaluated. 2. Flock information on producer, breed, foodstuff manufacturer, region, abattoir, date of slaughter, age at slaughter, planned and actual stocking density was recorded. A total of 6988 flocks, representing approximately 110 million broilers was examined. A total of 175 broiler producers from 15 geographical regions is represented. 3. The total foot-pad score per flock ranged from 0 to 200, with a mean of 34.7 and a standard deviation of 40.9. 4. Simple linear regression analysis showed that the mean total score on a weekly basis decreased (P < 0.001) over time, mainly because of a decrease in the prevalence of severe foot-pad lesions. 5. There was an association (P < 0.05) between slaughterhouse, foodstuff supplier and geographic region respectively and the mean total foot pad score of the flocks slaughtered.

Wet litter and perches as risk factors for the development of foot pad dermatitis in floor-housed hens.

1. An experiment was conducted to determine whether different moisture levels of litter and perches with different hygienic conditions are involved in the manifestation of foot pad dermatitis in White Leghorn layers. 2. Four different treatments were compared: dry litter and dry perches; dry litter and wet perches; wet litter and dry perches; and wet litter and wet perches. Temperature, pH, air humidity and ammonia changes in the pens were monitored. 3. The mean prevalence of foot pad lesions in groups 1, 2, 3 and 4 was 17%, 13%, 49% and 48% respectively. The overall incidence of foot pad lesions in birds reared on dry litter was 38%, and in birds reared on wet litter 92%. 4. When the air temperature was above 20 degrees C, an increasing moisture content in the litter was associated with an increasing incidence of foot pad dermatitis. However, when the air temperature was below 20 degrees C there were no new cases of dermatitis in any of the 4 treatments. There were no significant differences in litter pH or ammonia between the 4 treatments when compared over the whole experiment. 5. Although the incidence of lesions was not significantly affected by the presence of wet perches, the area of the lesions tended to be in groups with wet patches than in groups with dry perches. 6. It is suggested that moisture and temperature are important contributing factors for the occurrence of foot pad dermatitis in laying hens. Wet perches may contribute to the severity of such lesions.

Using a tobit regression model to analyse risk factors for foot-pad dermatitis in commercially grown broilers.

A model was developed to explain the influence of different local and regional factors on the prevalence of foot-pad dermatitis in broilers at the time of slaughter. Data from a recent two-year study of broiler foot-health in Sweden were used to construct the model. The model was based on regression analysis, using a Tobit model for censored data. This type of Tobit regression model has been used for several decades in econometrics and can also be found in the medical-scientific literature. It has, however, reportedly not been used in veterinary medicine although there appears to be several situations where it should be considered useful. Week of slaughter was significantly (p < 0.001) associated with total foot-pad score, which decreased over time. The birds' age at slaughter was also significantly (p < 0.01) associated with total foot-pad score. Five out of the 11 slaughterhouses included in the study were included as significant (p < 0.01) variables in the final model. Three feed suppliers (p < 0.05) and four regions (p < 0.01) were also included as significant variables in the model. There were also significant (p < 0.001) interactions between several of these factors (mainly, between the time variable and specific slaughterhouses, feed suppliers or regions, respectively). The information gathered in this study regarding the influence of a number of risk factors for the development of foot-pad dermatitis and their reciprocal interactions will enable us to modify the Swedish broiler foot-health programme.

Rearing conditions and foot-pad dermatitis in Swedish broiler chickens.

A method of classification of broiler foot-health status was developed to estimate the prevalence of foot-pad dermatitis in Swedish broilers. Data on foot health were collected from 101 commercial broiler flocks at slaughter. The producers were asked to fill in a questionnaire on rearing conditions and equipment for every flock. Lesions were commonly observed; only 62% of the birds were classified as being without lesions, 32% had mild lesions only (discoloration, erosions) and 6% had severe lesions (ulcers). Flocks reared in houses equipped with small water cups had significantly (P < 0.05) higher prevalences of foot-pad dermatitis than flocks reared with water nipples. Thick layers of litter, regardless of litter material, also resulted in significantly (P < 0.05) higher prevalences of foot-pad dermatitis than litter layers thinner than 5 cm.

Rearing conditions and foot-pad dermatitis in Swedish turkey poults.

A method previously developed for classification of broiler foot health status was used in order to estimate the prevalence of foot-pad dermatitis in Swedish turkey poults. Data on foot health were collected from 53 commercial turkey flocks at slaughter. The producers were asked to fill in a questionnaire on rearing conditions and equipment for every flock. Lesions were very commonly observed, only 2% of the feet were classified as being without lesions, 78% had mild lesions (discoloration, erosions), and 20% had severe lesions (ulcers). There was a significant (p < 0.01) effect of litter material on the presence of severe foot-pad dermatitis, flocks reared on straw showing higher prevalence than flocks reared on wood shavings. There was also a significant (p < 0.001) effect of the type of water system, severe foot-pad dermatitis being more common in flocks reared in houses equipped with bell drinkers compared with flocks reared with small cups. The addition of extra litter during the rearing period resulted in significantly (p < 0.01) lower prevalence of lesions compared with flocks where no extra litter had been added.

Using public health nursing data for program advocacy.

Developing and maintaining public health nursing programs in an era of funding cutbacks is a challenge faced by all public health nursing administrators today. The authors describe the development, testing, and implementation of a public health nursing data collection method, which proved to be invaluable in describing and justifying public health nursing services to policy makers, legislative representatives, and community residents.