Secukinumab treatment in new-onset psoriasis: aiming to understand the potential for disease modification - rationale and design of the randomized, multicenter STEPIn study.

BACKGROUND: To date, biological treatments have been assessed in subjects with a long-term history of psoriasis and previous failures to systemic and topical therapies. In rheumatoid arthritis and other immune-mediated inflammatory diseases, early intensive systemic treatment prolongs treatment-free remission. We hypothesize that, by treating patients with psoriasis early with an effective systemic therapy, we may be able to alter the clinical outcome and the natural course of the disease. The STEPIn study (NCT03020199) investigates early intervention with secukinumab versus narrow-band ultraviolet B (nb-UVB) phototherapy in subjects with new-onset psoriasis. OBJECTIVE: To determine whether early intervention with either nb-UVB treatment or secukinumab in subjects with new-onset plaque psoriasis might modify the natural course of the disease. METHODS: One hundred and sixty subjects aged 18-50 years with new-onset (≤12 months) moderate-to-severe plaque psoriasis and naïve to systemic treatment and phototherapy will be randomized to secukinumab 300 mg or nb-UVB. The Main Study has two treatment arms: Arm A1, subcutaneous secukinumab 300 mg at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter until and including Week 52; Arm B1, one/two cycles of nb-UVB for 12 weeks each (maximum 28-week break between cycles). After treatment discontinuation, patients will be followed up and monitored for disease activity up to Week 208. A Mechanistic Sub-study will assess immunological changes and pathogenic tissue-resident memory T cells in skin biopsies. CONCLUSIONS: STEPIn is the first study to investigate whether early intensive treatment in new-onset psoriasis can modify the long-term natural course of the disease and thus become a novel treatment strategy for patients with psoriasis.

The physiological consequences of crib-biting in horses in response to an ACTH challenge test.

Stereotypies are repetitive and relatively invariant patterns of behavior, which are observed in a wide range of species in captivity. Stereotypic behavior occurs when environmental demands produce a physiological response that, if sustained for an extended period, exceeds the natural physiological regulatory capacity of the organism, particularly in situations that include unpredictability and uncontrollability. One hypothesis is that stereotypic behavior functions to cope with stressful environments, but the existing evidence is contradictory. To address the coping hypothesis of stereotypies, we triggered physiological reactions in 22 horses affected by stereotypic behavior (crib-biters) and 21 non-crib-biters (controls), using an ACTH challenge test. Following administration of an ACTH injection, we measured saliva cortisol every 30 min and heart rate (HR) continuously for a period of 3h. We did not find any differences in HR or HR variability between the two groups, but crib-biters (Group CB) had significantly higher cortisol responses than controls (Group C; mean ± SD: CB, 5.84 ± 2.62 ng/ml, C, 4.76 ± 3.04 ng/ml). Moreover, crib-biters that did not perform the stereotypic behavior during the 3-hour test period (Group B) had significantly higher cortisol levels than controls, which was not the case of crib-biters showing stereotypic behavior (Group A) (B, 6.44 ± 2.38 ng/ml A, 5.58 ± 2.69 ng/ml). Our results suggest that crib-biting is a coping strategy that helps stereotypic individuals to reduce cortisol levels caused by stressful situations. We conclude that preventing stereotypic horses from crib-biting could be an inappropriate strategy to control this abnormal behavior, as it prevents individuals from coping with situations that they perceive as stressful.

[Stress parameters and behaviour of horses in walkers with and without the use of electricity]. / Stressbelastung und Verhalten von Pferden in stromführenden gegenüber nicht stromführenden Führanlagen.

In order to investigate stress responses of horses in walkers with and without electricity, 12 horses were trained during 3 weeks in a horse walker with and without the use of electricity (3.7 kV). To evaluate the stress response, cortisol levels in the blood were measured, the heart rate was monitored using the Polar® system and the behaviour was evaluated. Neither the cortisol levels nor the heart rates showed any relevant statistically significant difference between horses moved in the horse walker with or without the use of electricity. The highest cortisol levels and heart rates were recorded during the first week (habituation period). A significant difference could be observed regarding spontaneous compartment changes: while this happened mainly during the first week and before the first use of electricity, no horses changed compartments in the periods when electricity was used and thereafter. The results of this study indicate that the use of electricity in the horse walker does not seem to cause significant detectable stress in the horses.

Pour comparer le stress ressenti par les chevaux dans les marcheurs, on a placé 12 chevaux durant 3 semaines dans un marcheur avec ou sans courant électrique (3.7 kV) dans les séparations. On a mesuré le taux de cortisol sanguin et la fréquence cardiaque au moyen d'un appareil Polar® et noté le comportement des chevaux. Ni les taux de cortisol ni les fréquences cardiaques ne présentaient de différences significatives entre les chevaux placés dans un marcheur avec ou sans courant électrique dans les séparations. Les taux de cortisol et les fréquences cardiaques les plus élevés ont été observés dans la première semaine (phase d'accoutumance). Des différences significatives de comportement ont par contre été constatées quant aux paramètres «changement spontané de compartiment¼ et «contact avec la séparation¼: alors que ces faits se produisaient particulièrement durant la première semaine et avant le premier usage du courant électrique, les chevaux ne changeaient plus de compartiment pendant et après l'emploi de l'électricité. Les résultats de cette étude indiquent que l'emploi de l'électricité dans les séparations des marcheurs ne cause pas de stress mesurable significatif pour les chevaux.

Risk factors associated with behavioural disorders of crib-biting, weaving and box-walking in Swiss horses.

REASONS FOR PERFORMING STUDY: Studies on the prevalence of behavioural disorders in horses and on associated risk factors have revealed inconsistent results. There are many studies on the neuropharmacological, surgical or mechanical therapy of stereotypies, but little is known about their causation. OBJECTIVES: To explore risk factors associated with the occurrence of behavioural disorders in horses. METHODS: A sample of horse owners, selected randomly and representative for Switzerland, was contacted in a postal survey. Answers were provided for 622 stables (response rate 35.2%). Individual data of 2,341 horses were examined with path analysis (multivariable linear and logistic regression), and adjustment made for possible confounding effects due to age and breed. RESULTS: Out of 60 possible risk factors, 11 were associated with the outcome at the univariable level (null-hypothesis path model) and 3 factors remained after the backward logistic regression procedure. Mature Warmbloods and Thoroughbreds, assessed by the owners to be reactive, fed 4 times a day and without daily pasture, had increased odds of displaying crib-biting, weaving and box-walking. Furthermore, indirect associations of 5 factors with the outcome were identified. CONCLUSIONS: The final logistic regression model of risk factors leads to the hypotheses that causal prevention of stereotypic behaviours should be based upon housing and management conditions which allow tactile contact with other horses (e.g. mutual grooming), daily free movement (paddock or pasture), as well as the provision of high amounts of roughage but of little or no concentrates. POTENTIAL CLINICAL RELEVANCE: It is one of the aims of population medicine to prevent the development of behavioural disorders. Further research is needed to test the concluding hypotheses in experimental studies or to verify them in the context of similar observational studies.

[Housing and use of horses in Switzerland: a representative analysis of the status quo]. / Haltung und Nutzung von Pferden in der Schweiz: Eine repräsentative Erfassung des Status quo.

Out of a representative sample of 1861 Swiss horse yards, 622 horse keepers (35.2%) with 2536 horses, ponies and donkeys sent back a questionnaire about general farm characteristics, their horse-specific training, horse stock, housing conditions, intraspecific social contacts, feeding, ability to move freely, use of the horses and management. 83.5% of horses were kept individually (thereof 18.3% tethered, 32.3% in a loose box indoors, 28.4% in a loose box outdoors, and 4.5% in a loose box with permanent access to a paddock or an individual pasture), and 16.5% lived in group housing systems. 36% of the horses had daily access to a pasture, 62.8% depending on the weather, and 1.2% never at all. Individually housed horses pastured significantly less than horses kept in groups. The mean use per week was 4.5 hours, depending on breed, type of use and housing system. Only 50% of the horse keepers were trained with respect to horses or farm animals (e.g. professional training graduation, license, military service, veterinarian, farmer). In Switzerland, horses are still housed and fed in a traditional way, despite considerable recent changes in the amount and type of use (65.1% leisure horses, 34.9% sport and working horses); this may result in health and behavioural problems. Therefore, information and education of horsewomen and horsemen should be emphasized in the future. For the transfer of knowledge, veterinarians are of high importance.

[Prevalence of behavioral disorders in the Swiss horse population]. / Prävalenz von Verhaltensstörungen in der Schweizer Pferdepopulation.

In the Swiss horse population, the prevalence of conspicuous behaviours (behavioural disorders and stable vices) was recorded with a written questionnaire in a representative survey among 1861 horse yards, and the occurrence of the stereotypic behavioural disorders crib-biting, weaving and boxwalking was analysed with emphasis on their association with horse specific (breed, age, sex) and environmental factors (e.g. housing system, nutrition, management and utilisation). 622 horse yards with a total number of 2536 horses answered to the questionnaire, and conspicuous behaviours were described for 418 horses (16.5%). Thereof, the most common stereotypic behavioural disorders with a potential negative impact on animal welfare, crib-biting, weaving, and/or boxwalking were named for 89 horses (3.5%). Stable vices (e.g. shying, bucking, aggressivity against humans) were noted for 47 horses (1.9%). For 281 horses (11.1%) conspicuous behaviours such as pawing, lip-liking, head shacking, kicking stall were given; these can be categorised as behavioural disorders or as stable vices depending on their intensity and causation. Data analysis data revealed a number of statistically significant associations between genetic factors (breed), housing, management practices, utilisation and the three stereotypies. The strongest influence on the degree of behavioural disorders had the breed as well as the extent of direct social contact with other horses, free movement on pasture, feeding pattern and regular utilisation.

Effective prevention of chemotherapy--induced phlebitis by low-dose heparin: a prospective randomised trial.

In a prospective randomised trial patients receiving multiple-day chemotherapy and heparin had significantly fewer local complications at the site of venous access than patients who had chemotherapy alone. The need to move peripheral venous catheters to other sites was decreased significantly, from 36% to 6%. Prophylaxis of phlebitis with low-dose continuous heparin is safe, simple, cheap and effective. It facilitates administration of multiple-day chemotherapy for the patients, the nurses and the physicians.

Cyclic nucleotides in human epidermis--diurnal variations.

In 12 healthy, adult males, the epidermal content of both cAMP and cGMP was determined radioimmunologically every 6 h over a period of 30 h, avoiding any ischemia, which can alter unphysiologically the in vivo levels of epidermal cyclic nucleotides. For cAMP a diurnal fluctuation with maximal level at midnight could be proved (p less than 0.05), whereas cGMP, in contrast to experiments in mice, revealed no significant variation during the test period. The presented results describe for the first time the diurnal course of human epidermal cGMP.

[Atypical spermatogonias as precancerous conditions]. / Atypische Spermatogonien als Präkanzerose

Atypical spermatogonia are relatively frequent in the vicinity of testicular teratomas or seminomas. These voluminous cells are seminoma-like, showing broad and clear cytoplasm borders, big nuclei and peculiarly enlarged nucleoli. Atypical spermatogonia usually line the tubules and displace the remaining Sertoli cells towards the middle of the tubules. Recently, such atypical spermatogonia have been described in testicular biopsies performed for fertility disturbances. Two patients showing atypical spermatogonia developed, years later, malignant testicular tumors. Therefore, were checked all of our histological specimens from testicular biopsies over the period 1950-1976 for atypical spermatogonia. They originated from 1935 adult patients in whom biopsy had been performed, in general bilaterally, for fertility disturbances. In fact, atypical spermatogonia were found in the specimens of 9 patients, that is, 0.55%. Five of these patients developed malignant testicular tumours within periods ranging from months to six years, viz. three seminomas, one teratoma and one combined tumor, i.e. a teratoma and seminoma. The remaining four patients with atypical spermatogonia have shown no sign of tumor to date. As the results of our investigation show, atypical spermatogonia in testicular biopsies should not be taken lightly. We therefore strongly advise checks at short intervals on such patients in view of the high risk of their developing malignant testicular tumors.