Veterinary drug therapies used for undesirable behaviours in UK dogs under primary veterinary care

Undesirable behaviours (UBs) in dogs are common and important issues with serious potential welfare consequences for both the dogs and their owners. This study aimed to investigate the usage of drug therapy for UBs in dogs and assess demographic risk factors for drug-prescribed UBs within the dog population under primary-care veterinary care in the UK in 2013. Dogs receiving drug therapy for UB were identified through the retrospective analysis of anonymised electronic patient records in VetCompass™. Risk factor analysis used multivariable logistic regression modelling. The study population comprised 103,597 dogs under veterinary care in the UK during 2013. There were 413 drug-prescribed UBs recorded among 404 dogs. The prevalence of dogs with at least one UB event treated with a drug in 2013 was 0.4%. Multivariable modelling identified 3 breeds with increased odds of drug-prescribed UB compared with crossbred dogs: Toy Poodle (OR 2.75), Tibetan Terrier (OR 2.68) and Shih-tzu (OR 1.95). Increasing age was associated with increased odds of drug-prescribed UB, with dogs ≥ 12 years showing 3.1 times the odds compared with dogs < 3 years. Neutered males (OR 1.82) and entire males (OR 1.50) had increased odds compared with entire females. The relatively low prevalence of dogs with at least one UB event that was treated with a drug in 2013 could suggest that opportunities for useful psychopharmaceutical intervention in UBs may be being missed in first opinion veterinary practice. While bodyweight was not a significant factor, the 3 individual breeds at higher odds of an UB treated with a behaviour modifying drug all have a relatively low average bodyweight. The current results also support previous research of a male predisposition to UBs and it is possible that this higher risk resulted in the increased likelihood of being prescribed a behaviour modifying drug, regardless of neuter status.

Utilisation of tracheostomy in patients with COVID-19 in England: patient characteristics, timing and outcomes

Objectives: We aimed to characterise the use of tracheostomy procedures for all COVID-19 critical care patients in England and to understand how patient factors and timing of tracheostomy affected outcomes. Design: A retrospective observational study using exploratory analysis of hospital administrative data. Setting: All 500 National Health Service hospitals in England. Participants: All hospitalised COVID-19 patients aged ≥ 18 years in England between March 1st and October 31st, 2020 were included. Main outcomes and measures: This was a retrospective exploratory analysis using the Hospital Episode Statistics administrative dataset. Multilevel modelling was used to explore the relationship between demographic factors, comorbidity and use of tracheostomy and the association between tracheostomy use, tracheostomy timing and the outcomes. Results: In total, 2,200 hospitalised COVID-19 patients had a tracheostomy. Tracheostomy utilisation varied substantially across the study period, peaking in April-June 2020. In multivariable modelling, for those admitted to critical care, tracheostomy was most common in those aged 40-79 years, in males and in people of Black and Asian ethnic groups and those with a history of cerebrovascular disease. In critical care patients, tracheostomy was associated with lower odds of mortality (OR: 0.514 (95% CI 0.443 to 0.596), but greater length of stay (OR: 41.143 (95% CI 30.979 to 54.642). In patients that survived, earlier timing of tracheostomy (≤ 14 days post admission to critical care) was significantly associated with shorter length of stay. Conclusions: Tracheostomy is safe and advantageous for critical care COVID-19 patients. Early tracheostomy may be associated with better outcomes, such as shorter length of stay, compared to late tracheostomy.

Quinolinic acid, a kynurenine/tryptophan pathway metabolite, associates with impaired cognitive test performance in systemic lupus erythematosus

ObjectivesInterferon-alpha, an important contributor to SLE pathogenesis, induces the enzyme indoleamine 2,3-dioxygenase in the kynurenine/tryptophan (KYN/TRP) pathway. This leads to a potentially neurotoxic imbalance in the KYN/TRP pathway metabolites, quinolinic acid (QA), an N-methyl D-aspartate glutamatergic receptor (NMDAR) agonist, and kynurenic acid (KA), an NMDAR antagonist. We determined whether QA/KA ratios associate with cognitive dysfunction (CD) and depression in SLE.MethodsThis cross-sectional study included 74 subjects with SLE and 74 healthy control (HC) subjects; all without history of neuropsychiatric disorders. Serum metabolite levels (KYN, TRP, QA, KA) were measured concurrently with assessments of cognition (Automated Neuropsychological Assessment Metrics (ANAM), 2×2 array), mood and pain, and compared between SLE and HC. Multivariable modelling in SLE was used to evaluate associations of metabolites with cognitive performance and depression.ResultsSerum KYN/TRP and QA/KA ratios were elevated in SLE versus HC (p<0.0001). SLE performed worse than HC on four of five ANAM tests (all p≤0.02) and the 2×2 array (p<0.01), and had higher depression scores (p<0.01). In SLE, elevated QA/KA ratios correlated with poor performance on Match to Sample (MTS), a working memory and visuospatial processing task (p<0.05). Subjects with SLE with elevated QA/KA ratios also had slightly higher odds of depression, but this did not reach significance (p=0.09). Multivariable modelling in SLE confirmed an association between QA/KA ratios and poor MTS performance when considering potentially confounding factors (p<0.05).ConclusionsElevated serum KYN/TRP and QA/KA ratios confirm KYN/TRP pathway activation in SLE. The novel association between increased QA/KA ratios and poor cognitive performance supports further study of this pathway as a potential biomarker or therapeutic target for SLE-mediated CD.

Lymphocyte Predominance in Blood, Pleural Fluid, and Tumour Stroma; A Prognostic Marker in Pleural Mesothelioma

Background As promising novel treatments develop for malignant pleural mesothelioma (MPM), early prognostication has become increasingly important. Circulating and local inflammatory cells are known to play a significant role in other tumour types. We assessed the proportion of lymphocyte populations within blood, pleural fluid and tumour stroma to prognosticate patients with MPM at diagnosis. Methods Consecutive patients diagnosed with biopsy-proven MPM were prospectively recruited to an observational cohort study and followed up for a minimum of 7.5 years. Blood and pleural fluid results at presentation were extracted from the medical records. Biopsy specimens were independently reviewed by 2 pathologists who scored the degree of lymphocytic and neutrophilic infiltration. Results Baseline results were available for 184 patients. The predominant pleural fluid cell type was calculable for 84 patients and 118 patients had biopsy specimens available for review. A low blood neutrophil/lymphocyte ratio (NLR < 4) inferred a better prognosis with a median survival of 420 days versus 301 days (p < 0.01). Survival was better for patients with a lymphocyte-predominant pleural effusion (430 vs 306 days, p < 0.01). Lymphocyte infiltration of tumour stroma was also associated with improved survival (n = 92, survival 430 days) compared with neutrophilic or acellular samples (n = 26, survival 342 days p < 0.01). In multivariable modelling lymphocyte predominance in blood, pleural fluid and tumour stroma were all associated with a better prognosis. Conclusions Lymphocyte predominance within tumour stroma, pleural fluid or blood infers a better prognosis in patients with MPM.

Multivariable modelling of factors associated with criminal convictions among people experiencing homelessness and serious mental illness: a multi-year study

People experiencing homelessness and serious mental illness exhibit high rates of criminal justice system involvement. Researchers have debated the causes of such involvement among people experiencing serious mental illness, including what services to prioritize. Some, for example, have emphasized mental illness while others have emphasized poverty. We examined factors associated with criminal convictions among people experiencing homelessness and serious mental illness recruited to the Vancouver At Home study. Participants were recruited between October 2009 and June 2011. Comprehensive administrative data were examined over the five-year period preceding study baseline to identify risk and protective factors associated with criminal convictions among participants (n = 425). Eight variables were independently associated with criminal convictions, some of which included drug dependence (RR = 1.53; P = 0.009), psychiatric hospitalization (RR = 1.44; P = 0.030), an irregular frequency of social assistance payments (compared to regular payments; 1.75; P < 0.001), and prior conviction (RR = 3.56; P < 0.001). Collectively, findings of the present study implicate poverty, social marginalization, crises involving mental illness, and the need for long-term recovery-oriented services that address these conditions to reduce criminal convictions among people experiencing homelessness and serious mental illness.

Association between household exposure and cycle threshold in COVID-19 infected health care workers

Objective Household SARS-COV-2 contact constitutes a high-risk exposure for health care workers (HCWs). Cycle threshold (Ct) of reverse transcriptase–polymerase chain reaction testing provides an estimate of COVID-19 viral load, which can inform clinical and workplace management. We assessed whether Ct values differed between HCWs with COVID-19 with and without household exposure. Methods We analyzed HCW COVID-19 cases whose Ct data could be compared. We defined low Ct at a cut-point approximating a viral load of 4.6 × 106 copies per ml. Logistic regression tested the association of household exposure and symptoms at diagnosis with a low Ct value. Results Of 77 HCWs with COVID-19, 20 were household exposures cases and 34 were symptomatic at testing (7 were both household-exposed and symptomatic at testing). Among household exposures, 9 of 20 (45%) manifested lower Ct values compared to 14 of 57 (25%) for all others. In a bivariate model, household exposure was not statistically associated with lower Ct (Odds Ratio [OR] 1.20; 95% Confidence Interval [CI] 0.97–1.51). In multivariable modelling both household exposure (OR] 1.3; 95% CI 1.03–1.6) and symptoms at diagnosis (OR 1.4; 95% CI 1.15–1.7) were associated with a low Ct value. Discussion Household exposure in HCWs with newly diagnosed COVID-19 was associated with lower Ct values, consistent with a higher viral load, supporting the hypothesis that contracting COVID-19 in that manner leads to a greater viral inoculum.

Patient functional independence and occupational therapist time-use in inpatient services: Patient demographic and clinical correlates

Introduction Health care expenditure has rapidly increased in Australia. Effective management of occupational therapy services is required to meet clinical demand. Improving our understanding of factors which influence occupational therapy service delivery is a vital step to manage workload distribution and optimise service efficiency. This study aims to examine the influence of patient sociodemographic characteristics, diagnosis and functional independence on the utilisation of occupational therapy resources in hospital inpatients over 18 years old. Methods Prospective, cross-sectional, observational cohort study of 4549 inpatients from three hospital sites in Melbourne, Australia. Data extracted from organisational databases and included in this study were: patient demographics, diagnosis, functional level assessed using the SMAF (Functional Autonomy Measurement System) and occupational therapy time-use. Data were analysed using univariable and multivariable modelling. Results Occupational therapy time-use was significantly associated with all variables included in analysis ( p < 0.05). For each variable the amount and direction of effect differed between hospital sites. The SMAF was the only variable consistently associated with occupational therapy time-use. Higher occupational therapy time-use was associated with lower functional independence (leading to a 3.5 min increase in median occupational therapy time for every unit decrease in SMAF score). Conclusions Management of resources within busy hospitals require knowledge of factors associated with occupational therapist time-use. This study identified that time-use could in part be predicted by functional independence, diagnosis and sociodemographic characteristics. Occupational therapy managers can use this information to support decision making while acknowledging other patient and therapist level factors also influence time-use.

Evaluation of the effectiveness of remdesivir in treating severe COVID-19 using data from the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, national cohort study.

Background Remdesivir was given UK early-access approval for use in COVID-19 in people aged 12 years and older on 26th May 2020 on the basis of unmet clinical need. Evidence on the side effects, complications of therapy and effectiveness of this therapy is lacking or conflicting. Methods Adults with severe COVID-19 treated with remdesivir were compared with propensity-score matched controls, identified from the ISARIC WHO Clinical Characterisation Protocol study of UK hospitalised patients with COVID-19. Remdesivir patients were matched to controls according to baseline underlying 14-day mortality risk. The effect of remdesivir on short-term outcomes was investigated (primary outcome: 14-day mortality). Effect sizes were estimated and adjusted for potential confounders using multivariable modelling. Results 1,549 patients given remdesivir and 4,964 matched controls were identified satisfying inclusion and exclusion criteria. The balance diagnostic threshold was achieved. Patients had symptoms for a median of 6 days prior to baseline; 62% were male, with mean (SD) age 63.1 (15.6) years, and 80% categorised as White ethnicity. Fourteen-day mortality was not statistically significantly associated with treatment (9.3% remdesivir vs. 11.9% controls, odds-ratio 0.80, [95% CI 0.60-1.07], p=0.116, adjusted for age, sex, number of key comorbidities, dexamethasone use, and diagnosis of viral pneumonia. Findings Treatment with remdesivir was not associated with a reduction in mortality in our primary endpoint at 14 days. Interpretation Remdesivir did not significantly improve mortality in this study. The findings are subject to the limitations of an observational study. Balance was achieved for measured baseline factors, but unmeasured confounders may account for observed treatment effect sizes. Funding Medical Research Council UK & National Institute of Health Research

Equine Responses to Acceleration and Deceleration Cues May Reflect Their Exposure to Multiple Riders

It is logical to assume that horses with multiple riders encounter variation in application of training cues. When training cues are inconsistent, we expect to see a decrease in trained responses or an increase in conflict behaviours. This study investigated the relationship between the number of people that regularly ride or handle a horse and the horse’s response to operant cues. Data on 1819 equids were obtained from the Equine Behavior Assessment and Research Questionnaire (E-BARQ), an online global survey of horse owners and caregivers. Three mutually independent indices (acceleration, deceleration, and responsiveness) were derived from a parallel analysis of E-BARQ items related to acceleration and deceleration cues. These indices were then subjected to multivariable modelling against a range of dependent variables including horse and human demographics, horse management, and the number of riders or handlers. The number of riders or handlers was a significant predictor for two out of three indices. As the number of riders or handlers increased, horses were more difficult to accelerate (regression coefficient = 0.0148 ± 0.0071; p = 0.0366) and less difficult to decelerate (regression coefficient = −0.017 ± 0.008; p = 0.030) than those with fewer riders or handlers. These findings suggest that horses’ responses to rein tension cues are more persistent than their responses to leg pressure or whip cues. Alternatively, horses with these responses may be actively selected for multiple rider roles. Longitudinal studies of this sort should reveal how the number of riders or handlers affects horse behaviour and could lead to safer and more humane equestrian practices.

Age-Related Changes in the Behaviour of Domestic Horses as Reported by Owners

The broad traits of boldness and independence in domestic horses can affect their usefulness and, indirectly, their welfare. The objective of the current study was to explore associations between attributes that reflect equine boldness and independence with both the age of horses and the age at which they were started under saddle, as well as other variables including breed, colour and primary equestrian discipline. All data were sourced from responses (n = 1940) to the 97-question online Equine Behaviour Assessment and Research Questionnaire (E-BARQ). Twenty E-BARQ items from the dataset were selected to reflect boldness and independence and were tested for univariate significance at p < 0.2. Multivariable modelling of the effect of age on remaining traits was assessed by an ordinal logistic regression, using a cumulative log odds model. This revealed that older horses were bolder (p = 0.012). However, horses started under saddle at an older age were less bold and less independent (p = 0.040 and p = 0.010, respectively). Australian Stock Horses were bolder and more independent (p = 0.014 and p = 0.007, respectively) than crossbreed horses. Horses used for breeding conformation (p = 0.039), working equitation (p = 0.045), eventing (p = 0.044) and traditional working horses (p = 0.034) were bolder than those used for other disciplines. Dressage (p = 0.039) and therapy (p = 0.040) horses were less bold than horses used for other disciplines. Stallions were bolder (p = −0.034) than geldings. Brown (p = 0.049) and chestnut (p = 0.027) horses were less bold than bay horses. Compared to crossbreed horses, Thoroughbreds (p = 0.000) and companion horses (p = 0.017) were less bold whilst heavy horses (p = 0.029) and ponies (p = 0.044) were bolder. Compared to pleasure horses, mounted games horses (p = 0.033) were less independent whereas working equitation horses (p = 0.020) were more independent. Riders with more than eight years’ experience reported more independence in their horses (p = 0.015) than those who had ridden their whole lives. The study findings suggest that boldness and independence are separate traits and only boldness was associated with the age of the horse. Factors that relate to desirable boldness and independence are important in ridden horses because they can affect rider safety. Results from this study should improve horse–rider matching and thereby potentially enhance horse welfare.