Reporting of 3Rs Approaches in Preclinical Animal Experimental Studies-A Nationwide Study.

The 3Rs aim to refine animal welfare, reduce animal numbers, and replace animal experiments. Investigations disclose that researchers are positive towards 3Rs recommendations from peers. Communication of 3Rs approaches via primary preclinical animal experimental literature may become a fast-forward extension to learn relevant 3Rs approaches if such are reported. This study investigates 3Rs-reporting in peer-reviewed preclinical animal research with at least one author affiliated to a Danish university. Using a systematic search and random sampling, we included 500 studies from 2009 and 2018. Reporting was low and improvement over time limited. A word search for 3R retrieved zero results in 2009 and 3.2% in 2018. Reporting on 3Rs-related sentences increased from 6.4% in 2009 to 18.4% in 2018, "reduction" increased from 2.4% to 8.0%, and "refinement" from 5.2% to 14.4%. Replacement was not reported. Reporting of the methodology was missing. For "reduction", methodology was mentioned in one study in 2009 and 11 studies in 2018, and for "refinement" in 9 and 21, respectively. Twenty-one studies stated compliance with ARRIVE-guidelines or similar without disclosure of details. Reporting of 3Rs approaches in preclinical publications is currently insufficient to guide researchers. Other strategies, e.g., education, interdisciplinary collaboration, and 3Rs funding initiatives, are needed.

Transition of Farm Pigs to Research Pigs using a Designated Checklist followed by Initiation of Clicker Training - a Refinement Initiative.

Implementation of 3R initiatives is important. To refine the life of laboratory pigs, we focused on the time period prior to inclusion of animals in experiments. We improved the checklist during the development. By using the checklist each individual pig's progress was documented. This aids the caretakers so they remain focused on the actions necessary to socialize the animals and limit the animal's stress and anxiety level. During this phase, the pigs become calm and ready to commence additional clicker training to further limit stress during the experimental period. The pigs will readily allow basic outcome measures to be collected without sedation or fixation. The protocol is divided in two. First the transition phase that begins as the pigs arrive at the research facility. Introducing treats and gradually closer contact to the caretakers are the first steps. Then, the caretaker introduces actions to be able to touch the head and hind, to mimic e.g. manipulating the ear to take a blood sample or the hind to obtain a rectal temperature. A strong foundation is established in the animal-caretaker relationship and this swiftly minimizes the stress the pigs express after arrival. Secondly, the positive reinforcement training commences to teach the animal how to carry out more complex tasks without becoming stressed. A clicker is introduced as a secondary reinforcer. Time, structure, education and thorough communication seem to be the most important criteria to succeed in the application of this protocol. In addition to having calm and compliant pigs, the caretakers report that they enjoy the focus they are allowed to give each individual pig, adding to their overall job satisfaction. Having caretakers with a strong commitment, and a focus on the transition progress and welfare of each pig, additionally strengthens the department's Culture of Care.

ALFAXALONE ANESTHESIA IN THE BENGALESE FINCH ( LONCHURA DOMESTICA).

The objective of this study was to evaluate the use of alfaxalone in a small passerine species. A dose-response trial was conducted whereby 10, 30, and 50 mg/kg alfaxalone was administered subcutaneously (SC) to 10 Bengalese finches ( Lonchura domestica) in a randomized complete crossover study design. Subsequently, a similar protocol was used to compare 30 mg/kg alfaxalone alone or combined with either 0.7 mg/kg midazolam or 1 mg/kg butorphanol SC. Induction and recovery times were recorded and depth of anesthesia monitored at 5-min intervals throughout each procedure. Functional oxygen saturation and pulse rates were measured with a pulse oximeter at 15 min after administration of the anesthetic agent(s). Dose-dependent decreases in induction time and prolongation of anesthetic duration were seen with increasing alfaxalone dosage. Alfaxalone combined with midazolam resulted in faster inductions, and the addition of both midazolam and butorphanol resulted in longer durations of anesthesia than alfaxalone alone. The addition of midazolam significantly decreased the pulse rate at 15 min compared with alfaxalone alone. Alfaxalone was found to be an effective agent for inducing anesthesia when administered subcutaneously, and no complications were observed. Increasing the dose, and combining with a benzodiazepine or opioid increased the duration of anesthesia with minimal or no effects on respiratory or pulse rates, within the dose range investigated.

Aquatic Bird Bornavirus 1 in Wild Geese, Denmark.

To investigate aquatic bird bornavirus 1 in Europe, we examined 333 brains from hunter-killed geese in Denmark in 2014. Seven samples were positive by reverse transcription PCR and were 98.2%-99.8% identical; they were also 97.4%-98.1% identical to reference strains of aquatic bird bornavirus 1 from geese in North America.

[The risk of affective disorders among patients with adrenocortical insufficiency: secondary publication]. / Risiko for udvikling af affektive lidelser hos patienter med binyrebarkinsufficiens--sekundaerpublikation.

The aim was to investigate the risk of affective disorders among patients with adrenocortical insufficiency. Two cohorts were identified with admission data recorded in Danish hospital registers from 1977 to 1999: one comprising all patients who were first-time hospitalised with adrenocortical insufficiency, the other a control cohort of patients with osteoarthritis. The patients with adrenocortical insufficiency had a 2.68 (95% CI: 1.62-4.42) greater rate of depression or mania than the control patients. Thus, adrenocortical insufficiency seems to be linked to an increased risk of affective disorders.

The risk of affective disorders in patients with adrenocortical insufficiency.

OBJECTIVE: To investigate the risk of affective disorders among patients hospitalised with adrenocortical insufficiency in the study period: 1977-1999. METHOD: Using data from Danish registers, two study cohorts were identified by their ICD diagnoses at discharge from hospital: one comprising all patients with a first hospital admission with an index diagnosis of adrenocortical insufficiency; the other a control cohort comprising all patients with a first hospital admission with an index diagnosis of osteoarthritis. Subsequent admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorders were used as events of interest. Rates of readmission were estimated using Poisson regression models in survival analyses. Age, sex, duration of time after index discharge, and calendar time were included as co-variables. The primary analysis included all patients with adrenocortical insufficiency. Thereafter, the subgroup of patients with primary adrenocortical insufficiency (Addison's disease) was investigated separately in a secondary analysis. RESULTS: A study sample of 989 patients with adrenocortical insufficiency and 124,854 patients with osteoarthritis was identified. Eight hundred and fifty-two patients were subsequently readmitted with a diagnosis of affective disorder. Patients with adrenocortical insufficiency had a 2.68 (95% CI: 1.62-4.42) times greater rate of affective disorders and a 2.12 (95% CI: 1.16-3.86) times greater rate of depressive disorder when compared with the rate for patients with osteoarthritis. Patients with Addison's disease had a 2.14 (95% CI: 1.14-4.03) times greater rate of affective disorders, and a 1.71 (95% CI: 0.81-3.63) times greater rate of depressive disorder compared with the rate of patients with osteoarthritis. CONCLUSION: Patients with adrenocortical insufficiency may be at increased risk of developing severe affective disorders. Conventional replacement therapy with hydrocortisone may not be sufficient to ensure the psychiatric well-being of these patients.

Increased risk of developing affective disorder in patients with hypothyroidism: a register-based study.

BACKGROUND: Links between thyroid function and depression have been noted in many contexts. We assessed whether hospitalization with hypothyroidism was a risk factor for developing affective disorder. METHODS: We conducted a prospective cohort study using historical data from Danish registers. The observational period was 1977-1999. Three study cohorts were identified: all patients with a first hospital admittance with the resulting index discharge diagnoses hypothyroidism, osteoarthritis, or nontoxic goiter. A later hospitalization with a resulting discharge diagnosis of affective disorder was used as event of interest, and rates of readmission were estimated and compared using competing risk models in survival analyses. FINDINGS: We identified 165,307 patients discharged with an index diagnosis. In the observational period, 1041 events occurred. An index diagnosis of hypothyroidism was associated with an increased risk of hospitalization with affective disorder when compared to the control diseases. The risk of hospitalization with affective disorder was greatest in the first year after index hospitalization. CONCLUSION: Patients hospitalized with hypothyroidism have a greater risk of readmission with depression or bipolar disorder than control patients. This renders epidemiologic support to theories linking thyroid dysfunction with mood disturbances.

Increased risk of hyperthyroidism among patients hospitalized with bipolar disorder.

OBJECTIVES: Hyperthyroidism has been associated with affective disorder in many cross-sectional studies, but longitudinal studies in this connection are scarce. We assessed whether hospitalization with depressive disorder or bipolar disorder was a risk factor for development of hyperthyroidism. METHODS: We conducted a historical cohort study using the Danish register data. The observational period was 1977--99. Three study cohorts were identified: all patients with a first hospital admission with resulting index discharge diagnoses of depression, bipolar disorder, or osteoarthritis. The risks of subsequently being readmitted with a resulting discharge diagnosis of hyperthyroidism were estimated in survival analyses. RESULTS: A study sample of 133,570 patients discharged with an index diagnosis was identified. Exactly 610 patients were later readmitted following diagnoses of hyperthyroidism. Patients with depressive disorder did not have an increased risk of hyperthyroidism, whereas patients with bipolar disorder had an increased of risk on the margin of statistical significance, when compared to patients with osteoarthritis. Patients with bipolar disorder had a significantly increased risk of hyperthyroidism when compared to patients with depression. LIMITATIONS: The results apply only to hospitalized patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients hospitalized with bipolar disorder tend to be at greater risk of readmission with hyperthyroidism than suitable control patients.

Increased risk of affective disorder following hospitalisation with hyperthyroidism - a register-based study.

OBJECTIVE: The pattern of comorbidity between thyroid disorders and affective disorder is not fully known. We assessed whether hospitalisation with hyperthyroidism was a risk factor for hospitalisation with affective disorder and evaluated the temporal relationship between these events. DESIGN: A historical prospective cohort study comparing patients with hyperthyroidism with patients with non-toxic goitre or osteoarthritis, using existing data from Danish registers. The observational period was from 1 January 1977 to 31 December 1999. METHODS: Three study cohorts were identified by their International Classification of Diseases (ICD) diagnoses at discharge from hospital and consisted of all patients with a first hospital admission with the index diagnoses of hyperthyroidism, osteoarthritis, or non-toxic goitre. Later admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorder were used as events of interest. Rates of re-admission were estimated using competing risks models in survival analyses. Age, sex, substance abuse, and calendar time were included as co-variables. RESULTS: A study sample of 183 647 patients discharged with an index diagnosis was identified. In total 1374 events occurred in the observational period. An index diagnosis of hyperthyroidism was associated with an increased risk of hospitalisation with affective disorder for both sexes and for all age-bands investigated, compared with the other index diagnoses. The risk was greatest in the first six months after index hospitalisation (rate ratio, 95% confidence interval: 3.60 (2.58-5.04)). CONCLUSIONS: Patients hospitalised with hyperthyroidism are at greater risk of re-admission with depressive disorder or bipolar disorder than control patients. This suggests that hyperthyroidism is associated with long-term mood disturbances.