A living lab approach to understanding dairy farmers' needs of technologies and data to improve herd health: Focus groups from 6 European countries.

For successful development and adoption of technology on dairy farms, farmers need to be included in the innovation process. However, the design of agricultural technologies usually takes a top-down approach with little involvement of end-users at the early stages. Living Labs offer a methodology that involve end-users throughout the development process and emphasize the importance of understanding users' needs. Currently, exploration of dairy farmers' needs of technologies has been limited to specific types of technology (e.g., smartphone apps) and adult cattle. The aim of this study was to use a Living Lab approach to identify dairy farmers' needs of data and technologies to improve herd health and inform innovation development. Eighteen focus groups were conducted with, in total, 80 dairy farmers from Belgium, Ireland, the Netherlands, Norway, Sweden, and the UK. Data were analyzed using Template Analysis and 6 themes were generated which represented the fundamental needs of autonomy, comfort, competence, community and relatedness, purpose, and security. Farmers favored technologies that provided them with convenience, facilitated their knowledge and understanding of problems on farm, and allowed them to be self-reliant. Issues with data sharing and accessibility, and usability of software were barriers to technology use. Furthermore, farmers were facing problems around recruitment and management of labor and needed ways to reduce stress. Controlling aspects of the barn environment, such as air quality, hygiene, and stocking density, was a particular concern in relation to youngstock management. In conclusion, the findings suggest that developers of farm technologies may want to include farmers in the design process to ensure a positive user experience and improve accessibility. The needs identified in this study can be used as a framework when designing farm technologies to strengthen need satisfaction and reduce any potential harm toward needs.

Short communication: Circadian variations and day-to-day variability of clinical signs used for the early diagnosis of pneumonia within and between calves.

For rational antimicrobial use, a timely and correct diagnosis of bovine respiratory disease, especially pneumonia, in calves is required. Current approaches often rely on clinical signs observed at a single time point, and do not take potential diurnal patterns in the manifestation of these clinical signs into account. Therefore, the aim of this pilot study was to investigate how clinical signs utilized for the (early) detection of pneumonia vary both within and between calves, throughout the day and across days. A longitudinal study was conducted in which 36 pre-weaned Holstein-Friesian calves were clinically examined eight times over the course of 48 h. The following parameters were considered: respiratory rate, type of respiration, dyspnea, stridor, induced cough (trachea reflex), spontaneous cough, eye and nasal discharge, ear positions, head tilt, rectal temperature, diarrhea, milk residue, body posture, Wisconsin and Davis BRD scorecard. The advent of thoracic ultrasonography (TUS) enables detection of (sub)clinical pneumonia in a more reliable way, compared to the diagnosis based solely on clinical signs. In this study, 14% (5/36) of the calves had an ultrasound confirmed pneumonia (consolidation ≥1 cm in depth). No variations were observed in the prevalence of clinical signs at the various time points of the day. However, we did observe a difference in the manifestation of clinical signs in individual calves (intra) and between (inter) them. Due to the significant intra-calf variability, diagnosing pneumonia based solely on a single observation of clinical signs, is likely to be insufficient. Hence, misdiagnosis might lead to incorrect use of antimicrobials.

Differences in the association of cough and other clinical signs with ultrasonographic lung consolidation in dairy, veal, and beef calves.

Bovine respiratory disease (BRD) continues to be a leading cause of economic loss, hampered animal welfare, and intensive antimicrobial use in cattle operations worldwide. Reduction of antimicrobial use is hindered because it is still unclear which clinical signs are best monitored to reliably detect pneumonia. Also, these clinical signs may vary according to age and between breeds. The objective of this cross-sectional study was to identify clinical signs associated with ultrasound-confirmed pneumonia (lung consolidation ≥1 cm depth) pre- and postweaning in different production types (dairy, beef, and veal) and breeds. A total of 956 calves (70% Holstein-Friesian dairy and 30% Belgian Blue beef) from 84 herds were clinically examined using 24 parameters, scored using the Wisconsin and California BRD clinical scoring systems and subjected to thoracic ultrasonography. Of the calves, 42.8% and 19.5% had a lung consolidation ≥1 cm and ≥3 cm, respectively. Cough, both spontaneous and induced, was the only and best-performing clinical sign statistically associated with lung consolidation in all production types. Fever (rectal temperature ≥39.4°C) was the second most promising factor, being significant in beef and veal calves but not in dairy calves. Postweaning, none of the clinical signs studied were statistically associated with pneumonia, with the exception of cough in dairy calves. Spontaneous or induced cough as a single clinical sign outperformed any combination of clinical signs, including the Wisconsin and California respiratory disease scoring systems, but sensitivity remained low. This information can be useful to select appropriate clinical signs for continuous monitoring in precision livestock applications, targeted to a given breed and age. As a cross-sectional measurement, diagnostic accuracy of spontaneous cough (accuracy = 65.1%, sensitivity = 37.4%, specificity = 85.7%) is too low to be used as a criterion to select animals with pneumonia for antimicrobial treatment. At the group level, cough monitoring holds potential as an early warning sign, after which lung ultrasonography should follow.

Three cases of alloimmune mediated pancytopenia in calves resembling bovine neonatal pancytopenia.

BACKGROUND: Between 2007 and 2011 several thousands of calves died from bovine neonatal pancytopenia (BNP), a bleeding syndrome triggered by vaccine induced alloantibodies from the dams. Following withdrawal of the involved bovine viral diarrhoea virus (BVDv) vaccine, the incidence of this condition rapidly decreased, with no reported cases in the last 5 years. Here, we report a recent immune-mediated pancytopenia in three calves from two different suckler herds, clinically indistinguishable from BNP. CASE PRESENTATION: Three Belgian Blue suckler calves from two different farms, aged around two weeks, showed multiple bleedings disseminated on the skin and petechiae and ecchymoses on the mucosae. Blood examination confirmed anaemia, leukopenia and thrombocytopenia. BVDv infection was excluded. Despite blood transfusion and cortisone therapy, all three animals died. Necropsy and histology confirmed bone marrow depletion. Binding of IgG from the dams on leukocytes of the calves was demonstrated by flow cytometry. Two calves, originating from the same farm, received colostrum from the same dam. None of the calves were given colostrum replacers or colostrum supplements. No link with the BNP causing BVDv vaccine could be evidenced. However, dams had been vaccinated against bovine herpesvirus 1, parainfluenza-3 virus, bovine respiratory syncytial virus and bluetongue virus serotype 8. CONCLUSIONS: Alloimmune mediated pancytopenia was evidenced in three animals, clinically and pathologically indistinguishable from BNP. Whether this disease is again vaccine mediated remains to be determined.

The aortic root in repaired tetralogy of Fallot: Serial measurements and impact of losartan treatment.

BACKGROUND: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan. METHODS AND RESULTS: We performed a prespecified analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 ± 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 ± 12 years, baseline aortic root 37 ± 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 ± 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (ß: 0.09 mm/ml (95% C.I.:0.02, 0.15), p = 0.010) and with aortic growth during follow-up (ß: 0.04 mm/ml (95% C.I.:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17). CONCLUSIONS: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population.

Short communication: Herd-level analysis of antimicrobial use and mortality in veal calves: Do herds with low usage face higher mortality?

The veal calf sector fears that a too-rapid and large decrease in antimicrobial use (AMU) as demanded by European authorities would increase mortality, causing economic and welfare issues. To determine whether this concern is justified, the relationship between AMU (total and different classes) and mortality in dairy-type white veal calves, managed by 2 large veal companies, was explored. A retrospective cohort study was performed on electronically collected antimicrobial consumption and mortality data from the largest Belgian veal practice during the period 2014 to 2016. Mixed linear [mortality (%) as continuous outcome] and generalized linear mixed models with binary outcome for event and trial approach were built to identify factors associated with mortality. Data consisted of 76 production cycles from 29 farms managed by 2 veal companies (1 and 2) and covering 45,001 calves. Average AMU was 30.1 ± 10.4 defined daily doses for animals per year (± standard deviation) and was higher in veal company 2 than in veal company 1 (35.9 ± 9.3 and 22.4 ± 5.7 defined daily doses for animals per year, respectively). In contrast, mean mortality was lower in veal company 2 (2.3 ± 1.4%) than in veal company 1 (4.1 ± 1.4%). Both models showed a positive association between AMU and mortality in veal company 1 and no association in veal company 2. The final linear model identified increasing herd size and the use of third- or fourth-generation cephalosporins as risk factors for mortality and the use of long-acting macrolides as a protective factor. The final logistic model identified an increased mortality risk with increased use of third- or fourth-generation cephalosporins and sulfonamides-trimethoprim and decreased mortality when using long-acting macrolides. Based on these data, at the current levels of AMU in Belgian veal calves, an increase in mortality when reducing AMU could not be evidenced. Differences in herd size and factors other than AMU likely better explain why one veal company faces almost double the mortality of another one. Abandoning the use of long-acting macrolides might have negative consequences for mortality under the current state of the industry. The most ethical way to further reduce AMU in veal calves is likely simultaneously monitoring AMU and animal welfare parameters, starting with, but not limited to, mortality.

Risk factors for antimicrobial use in veal calves and the association with mortality.

The intensive use of antimicrobials in the veal industry is heavily criticized, but drivers for antimicrobial usage (AMU) are still poorly understood. The industry fears that a drastic reduction in AMU would increase mortality, creating an unacceptable welfare issue. The objectives of the present study were to identify risk factors for AMU and to explore the relationship between AMU and mortality. A retrospective cohort study was performed on the antimicrobial registration data from the largest Belgian veterinary veal practice. The data set contained 295 production cycles from 78 farms, representing 146,014 calves and 8 veal companies (also called integrations). The average AMU was 32.3 defined daily dose animal per year (standard deviation: 11.04), of which 76.2% was administered orally and 23.8% parentally. The AMU remained stable between 2014 and 2016 with only a slight, but significant increase in total AMU between 2015 (31.0 defined daily dose animal per year, standard deviation: 10.5) and 2016 (35.1, 10.8). Use of almost all antimicrobial classes decreased over 2014 to 2016; however, use of long-acting macrolides, doxycycline, and aminosides increased significantly. Analysis identified breed (higher use in beef calves compared with dairy and crossbreeds), month of arrival (lower use when arrived in April or May compared with winter months), and veal company as risk factors. The veal company not only significantly affected total AMU, but also affected the majority of the antimicrobial classes. Additionally, breed differences were present for oxytetracycline, colistin, and classic macrolides, and a month effect was present for doxycycline only. These data illustrate that this veterinary practice realized a reduction of 46% in total AMU and of 96% in critically important antibiotics (fluoroquinolones, cephalosporins of the third and fourth generation) compared with the Belgian benchmark from 2007 to 2009. Replacement of critically important drugs by an increased use of long-acting macrolides is worrisome. Mortality risk was very low compared with benchmarks referenced internationally and did not increase with decreasing AMU. Use of trimethoprim-sulfonamides was a risk factor, whereas use of oxytetracycline was a protective factor for mortality. The absence of a relationship with mortality at the current levels of AMU suggests that a further rational reduction is possible. Attention should be paid to consider different AMU benchmarks for different breeds and to include the veal company as a target for antibiotic awareness campaigns.

Clinical course of tricuspid regurgitation in repaired tetralogy of Fallot.

BACKGROUND: Little is known on the clinical course of tricuspid regurgitation (TR) in patients with repaired tetralogy of Fallot (rTOF) and which patients are at particular risk. This study aims to determine TR course, characteristics associated with TR progression, and the prognostic relevance of TR in rTOF patients. METHODS: In this dualcenter cohort study, rTOF patients from a prospective national registry with ≥1 cardiac magnetic resonance imaging study and ≥2 echocardiograms available were included. Clinical and imaging data were collected. Cox hazards regression analysis was used to assess patient characteristics associated with progression to severe TR and whether severe TR was associated with the combined clinical endpoint of tachyarrhythmia, heart failure, and death, as time-dependent factor. RESULTS: A total of 216 patients were included (57% men, age 34±12years); 11 patients (5%) had severe TR at baseline. During 7.6±3.5years of follow-up, progression to severe TR occurred in 15 patients (7%). NYHA class ≥2 (HR 5.38, 95%-C.I. 1.91-15.16, p=0.001) and moderate baseline TR (HR 13.10, 95%-C.I. 2.95-58.21, p=0.001) were independently associated with progression to severe TR. Adverse events occurred in 47 patients (22%). The occurrence of severe TR was independently associated with adverse events (HR 3.48, 95%-C.I. 1.68-7.21, p=0.001). CONCLUSIONS: In this study, severe TR was present in 12% of adult rTOF patients during 7.6years, and progression to severe TR was most likely in symptomatic patients with moderate baseline TR. In these patients, close surveillance is warranted, because the occurrence of severe TR was associated with worse prognosis.

Weighing the risks: Thrombotic and bleeding events in adults with atrial arrhythmias and congenital heart disease.

INTRODUCTION: Atrial arrhythmias are associated to thromboembolism and anticoagulant treatment is installed according to risk profile. This study aimed to assess the rate of thrombotic events and major bleedings in adults with congenital heart disease (CHD) and atrial arrhythmias, as well as to determine the predictive value of specific clinical features and two risk scores for thromboembolism and bleeding. METHODS AND RESULTS: In this retrospective study, a total of 229 adult CHD patients with atrial arrhythmias, were included. Incidence and risk factors of thromboembolism were assessed in patients without a mechanical valve (n = 191), whereas bleeding incidence and risk factors were studied in patients receiving vitamin K antagonists (n = 164). In 13 patients without a mechanical valve thrombotic events occurred, the first thrombotic event rate per year being 1.4%. A total of 29 patients on vitamin K antagonists suffered from major bleedings, at an annual first event rate of 4.4%. CHA2DS2-VASc score and HAS-BLED score predicted thromboembolic and bleeding risk best in a dichotomized form. At a cut-off of ≥ 2 for high risk the rate of thrombotic events was 3.0% per year compared to 0.7% for a score of <2 (HR 3.7; 95%-CI 1.2-11.5; p = 0.021). A major bleeding rate of 10.8% per year was found in patients on vitamin K antagonists for HAS-BLED ≥ 2 as opposed to 3.5% with a score of <2 (HR 2.6; 95%-CI: 1.1-6.6; 0.017). CONCLUSION: In adult CHD patients, thrombotic events and major bleedings are important complications of atrial arrhythmias and anticoagulant treatment. Assessment of thromboembolic and bleeding risk in this patients group can be performed with dichotomized CHA2DS2-VASc and HAS-BLED scores respectively.

[Varicella: previously healthy children sometimes develop complications]. / Waterpokken: soms complicaties bij voorheen gezonde kinderen.

Three healthy boys, 3.5, 5 and 1.5 years of age, were admitted to hospital with a severe bacterial skin infection, cerebellar ataxia, and pneumonia, respectively, one week after the onset of varicella. They recovered completely after treatment. Studies in Europe report complications from varicella in 2.5% of healthy children. Most of these are neurological complications and secondary bacterial infections of skin and soft tissue. Last year, a European consensus was published that recommended that all healthy children be vaccinated against chickenpox. In The Netherlands, routine varicella zoster virus (VZV) vaccination has not (yet) been implemented. We propose a new discussion on the possible inclusion of VZV vaccination in the national vaccination programme.

[Agranulocytosis induced by an antithyroid drug in a 14-year-old girl]. / Thyreostaticumgeïnduceerde agranulocytose bij een 14-jarig meisje.

A 14-year-old girl with Graves' disease developed a fever, sore throat and a severe systemic infection after being treated with antithyroid drugs for 1 year. Agranulocytosis was diagnosed. After long-term antibiotic treatment and supportive therapy she recovered. Agranulocytosis is a known side-effect of antithyroid drugs and is seen in 0.2 to 0.5% of the patients. It usually occurs within the first 3 months of treatment. Patients above the age of 40 seem to be more susceptible. Since the onset of agranulocytosis is relatively acute, routine blood monitoring is not very useful. It is more important to instruct patients who use a thyreostatic to contact their physician in case of unexplained fever or a sore throat.

VSD, hypospadias and normal psychomotor development in a patient with inv dup 8(q13-q21.2).

This paper describes a patient with a de novo inverted duplication of chromosome 8(q13-q21.2). He was born with a ventricular septum defect, glandular hypospadias and protruding ears. At the age of 5 1/2 years he had normal psychomotor development. Review of the literature on partial duplications of 8q reveals that the associated phenotype may be mild. Normal psychomotor development, as in our patient, however appears to be uncommon.

[2 patients with atypical manifestations of cat-scratch disease]. / Twee patiënten met atypische manifestaties van kattenkrabziekte.

In 2 boys aged 8 years and 10 months, respectively, uncommon manifestations of cat scratch disease were seen. The first patient had acute encephalopathy: coma and generalized tonic-clinic convulsions. The second patient was presented with fever and peripheral lymphadenopathy in combination with hypodense lesions in the liver on ultrasound. Diagnosis was established on the clinical picture and the positive results of serological testing of antibody titres for Bartonella henselae. Both patients recovered completely within 2 months.

[Adrenal cortex suppression attributed to the use of budesonide]. / Bijnierschorsremming toegeschreven aan het gebruik van budesonide.

The Netherlands Centre for Monitoring of Adverse Reactions to Drugs received two reports of adrenal suppression, attributed to inhaled budesonide. In the first patient, a 7-year-old girl, there were growth retardation, centripetal weight gain and a Cushingoid moonface with unmeasurable serum levels of cortisol after long-term treatment with 600, and later 1000 micrograms daily. In the second patient, an 8-year-old boy, there was malaise with onset a few months after start of treatment with 400 micrograms budesonide daily. There was a lowered serum level of cortisol which returned to normal after discontinuation of budesonide. Although inhaled corticosteroids cause systemic adverse effects less frequently than orally administered corticosteroids, such effects may occur occasionally.

An optical study of the conformation of the aminofluorene-DNA complex.

Calf thymus DNA was modified with 2-aminofluorene (AF) to different extents by treatment with N-hydroxy-2-aminofluorene. The AF-modified DNAs together with free AF, the AF-modified guanine (Gua-C8-AF) and the AF-modified deoxyguanosine (dGuo-C8-AF) were subsequently studied by u.v. absorbance, linear dichroism and fluorescence spectroscopy. The emission and absorption properties of double-stranded DNA-AF and single-stranded DNA-AF closely resemble those of dGuo-C8-AF. The emission spectra of these three compounds show a broad, red-shifted emission, characteristic for exciplex formation. The linear dichroism and circular dichroism spectra of double-stranded DNA-AF show that the AF moiety forms a well-defined, regular structure. The dichroic ratio in the 310-340 nm region is constant, which indicates the presence of only one type of adduct. The long-wavelength transition moment of this adduct makes an angle of 72-74 degrees with the DNA helix axis. The binding of AF to double-stranded is DNA is accompanied by a destabilization of the DNA helix structure, a strong quenching of the AF emission quantum yield, intense AF circular dichroism and an apparent immobilization of the dGuo-C8-AF complex. In single-stranded DNA-AF, the AF conformation appears more random, although the interactions between AF and the surrounding bases persist. The strong interactions between AF and the surrounding bases which dominate the optical properties of the studied complexes, the significant destabilization of the DNA double helix after modification with AF, and the relatively small angle between AF and the base planes support a model in which the adduct is inserted into the DNA helix.

[What does the family think? Results of a survey among visitors to the medical care department of a nursing home]. / Wat vindt de familie ervan? Resultaten van een onderzoek onder bezoekers van de somatische afdeling van een verpleeghuis.

In order to obtain a fuller understanding of the various ideas behind the evaluation of care as provided by nursing homes, 42 regular and frequent visitors of a nursing home, participated in 'open-attitude' interviews. These people had to a great extent adapted their way of life to their regular visits to the nursing home. These relatives of nursing home residents clearly have one common denominator in their various considerations of such care and that is the strong emphasis which in every aspect was placed upon the extent of individual attention given to the residents. The combined functions fulfilled by the nursing home physician, both as a manager of the nursing home and as a general practitioner for the residents, was more than once a subject for discussion by the relatives. These visitors feel the need for the institution of a 'hostess function' (as the investigators formulate it) on the nursing ward. This function should be used in order to provide particular attention to the residents of the nursing home, and should not be too rigidly tied to the (otherwise necessary) institutional routine. A further participation of relatives in certain aspects of care seems quite attainable.