Variable Selection in General Multinomial Logit Models

The use of the multinomial logit model is typically restricted to applications with few predictors, because in high-dimensional settings maximum likelihood estimates tend to deteriorate. In this paper we are proposing a sparsity-inducing penalty that accounts for the special structure of multinomial models. In contrast to existing methods, it penalizes the parameters that are linked to one variable in a grouped way and thus yields variable selection instead of parameter selection. We develop a proximal gradient method that is able to efficiently compute stable estimates. In addition, the penalization is extended to the important case of predictors that vary across response categories. We apply our estimator to the modeling of party choice of voters in Germany including voter-specific variables like age and gender but also party-specific features like stance on nuclear energy and immigration

Longevity and mortality of cats attending primary care veterinary practices in England

Enhanced knowledge on longevity and mortality in cats should support improved breeding, husbandry, clinical care and disease prevention strategies. The VetCompass research database of primary care veterinary practice data offers an extensive resource of clinical health information on companion animals in the UK. This study aimed to characterise longevity and mortality in cats, and to identify important demographic risk factors for compromised longevity. Crossbred cats were hypothesised to live longer than purebred cats. Descriptive statistics were used to characterise the deceased cats. Multivariable linear regression methods investigated risk factor association with longevity in cats that died at or after 5 years of age. From 118,016 cats attending 90 practices in England, 4009 cats with confirmed deaths were randomly selected for detailed study. Demographic characterisation showed that 3660 (91.7%) were crossbred, 2009 (50.7%) were female and 2599 (64.8%) were neutered. The most frequently attributed causes of mortality in cats of all ages were trauma (12.2%), renal disorder (12.1%), non-specific illness (11.2%), neoplasia (10.8%) and mass lesion disorders (10.2%). Overall, the median longevity was 14.0 years (interquartile range [IQR] 9.0–17.0; range 0.0–26.7). Crossbred cats had a higher median longevity than purebred cats (median [IQR] 14.0 years [9.1–17.0] vs 12.5 years [6.1–16.4]; P \u3c0.001), but individual purebred cat breeds varied substantially in longevity. In cats dying at or after 5 years (n = 3360), being crossbred, having a lower bodyweight, and being neutered and non-insured were associated with increased longevity. This study described longevity in cats and identified important causes of mortality and breed-related associations with compromised longevity

Characterization of the fecal microbiome in cats with inflammatory bowel disease or alimentary small cell lymphoma.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Both IBD and SCL in cats share features with chronic enteropathies such as IBD and monomorphic epitheliotropic intestinal T-cell lymphoma in humans. The aim of this study was to characterize the fecal microbiome of 38 healthy cats and 27 cats with CE (13 cats with IBD and 14 cats with SCL). Alpha diversity indices were significantly decreased in cats with CE (OTU p = 0.003, Shannon Index p = 0.008, Phylogenetic Diversity p = 0.019). ANOSIM showed a significant difference in bacterial communities, albeit with a small effect size (P = 0.023, R = 0.073). Univariate analysis and LEfSE showed a lower abundance of facultative anaerobic taxa of the phyla Firmicutes (families Ruminococcaceae and Turicibacteraceae), Actinobacteria (genus Bifidobacterium) and Bacteroidetes (i.a. Bacteroides plebeius) in cats with CE. The facultative anaerobic taxa Enterobacteriaceae and Streptococcaceae were increased in cats with CE. No significant difference between the microbiome of cats with IBD and those with SCL was found. Cats with CE showed patterns of dysbiosis similar to those in found people with IBD

Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease

BACKGROUND: Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age. HYPOTHESIS/OBJECTIVES: To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension. ANIMALS/SUBJECTS: Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified. METHODS: Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined. RESULTS: Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension. CONCLUSIONS AND CLINICAL IMPORTANCE: The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD

Evaluation and Diagnostic Potential of Serum Ghrelin in Feline Hypersomatotropism and Diabetes Mellitus

BACKGROUND: Ghrelin is a growth hormone secretagogue. It is a potent regulator of energy homeostasis. Ghrelin concentration is down‐regulated in humans with hypersomatotropism (HS) and increases after successful treatment. Additionally, ghrelin secretion seems impaired in human diabetes mellitus (DM). HYPOTHESIS: Serum ghrelin concentration is down‐regulated in cats with HS‐induced DM (HSDM) compared to healthy control cats or cats with DM unrelated to HS and increases after radiotherapy. ANIMALS: Cats with DM (n = 20) and with HSDM (n = 32), 13 of which underwent radiotherapy (RT‐group); age‐matched controls (n = 20). METHODS: Retrospective cross‐sectional study. Analytical performance of a serum total ghrelin ELISA was assessed and validated for use in cats. Differences in serum ghrelin, fructosamine, IGF‐1 and insulin were evaluated. RESULTS: Ghrelin was significantly higher (P < .001) in control cats (mean ± SD: 12.9 ± 6.8 ng/mL) compared to HSDM‐ (7.9 ± 3.3 ng/mL) and DM‐cats (6.7 ± 2.3 ng/mL), although not different between the HSDM‐ and DM‐cats. After RT ghrelin increased significantly (P = .003) in HSDM‐cats undergoing RT (from 6.6 ± 1.9 ng/mL to 9.0 ± 2.2 ng/mL) and the after RT ghrelin concentrations of HSDM cats were no longer significantly different from the serum ghrelin concentration of control cats. Serum IGF‐1 did not significantly change in HSDM‐cats after RT, despite significant decreases in fructosamine and insulin dose. CONCLUSION AND CLINICAL IMPORTANCE: Ghrelin appears suppressed in cats with DM and HSDM, although increases after RT in HSDM, suggesting possible presence of a direct or indirect negative feedback system between growth hormone and ghrelin. Serum ghrelin might therefore represent a marker of treatment effect

In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease.

BackgroundLiver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats.Hypothesis/objectivesTo determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.AnimalsEleven LD and 11 age-matched control cats.MethodsCase-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.ResultsThere was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P = .03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P &lt; .002). Mirtazapine half-life was correlated with ALT (P = .002; r = .76), ALP (P &lt; .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (-0.0022 min-1 , CI: -0.0050 to 0.00054 min-1 ) and cats without LD (0.01849 min-1 , CI: -0.025 to -0.012 min-1 ; P = .002).Conclusions and clinical importanceCats with LD might require less frequent administration of mirtazapine than normal cats

Serum N-Terminal Type III Procollagen Propeptide: An Indicator of Growth Hormone Excess and Response to Treatment in Feline Hypersomatotropism

BACKGROUND: N‐terminal type III procollagen propeptide (PIIINP) is a biomarker of soft tissue proliferation. Hypersomatotropism (HS) is associated with soft tissue proliferation. HYPOTHESIS: Serum PIIINP is increased in cats with HS and decreases with effective treatment, and may be an additional tool in the diagnosis and treatment of feline HS. ANIMALS: Cats with uncomplicated diabetes mellitus (DM; n = 30) and with HS‐induced DM (HSDM; n = 30). Pre‐ and posttreatment samples were available from 5 cats undergoing radiotherapy (RT) and 16 cats undergoing hypophysectomy (HPX). METHODS: Retrospective and prospective cross‐sectional study. Analytical performance of a serum PIIINP ELISA was assessed and validated for use in cats. PIIINP and insulin‐like growth factor 1 (IGF‐1) radioimmunoassays (RIA) were performed pre‐ and post‐treatment in cats with DM and HSDM. PIIINP and IGF‐1 were compared between cats treated by RT and HPX. RESULTS: Serum PIIINP concentrations were significantly higher (P < .001) in HSDM cats (median, 19.6 ng/mL; range, 1.7–27.9) compared to DM cats (median, 5.0 ng/mL; range, 2.1–10.4). A cut‐off of 10.5 ng/mL allowed differentiation between DM and HSDM cats with 87% sensitivity and 100% specificity (area under the curve [AUC], 0.91; 95% confidence interval [CI], 0.82‐1). After RT, PIIINP increased significantly (P = .043) with no significant change in IGF‐1 concentrations. After HPX, serum PIIINP (P = .034) and IGF‐1 concentrations (P < .001) decreased significantly. CONCLUSION AND CLINICAL IMPORTANCE: PIIINP concentrations are increased in cats with untreated HSDM compared to those with DM, demonstrating the effect of excess GH on soft tissue. PIIINP concentrations decreased after HPX in most HSDM cats

Prospective evaluation of a protocol for transitioning porcine lente insulintreated diabetic cats to human recombinant protamine zinc insulin

Objectives The objective was to evaluate a nadir-led protocol for transitioning porcine lente insulin suspension (PLIS)-treated diabetic cats onto human recombinant protamine zinc insulin (PZIR). Methods Recently diagnosed (<5 months) diabetic cats, treated with PLIS q12h for 6 weeks, were recruited. Fructosamine, 24 h blood glucose curve (BGC), quality of life assessment (DIAQoL-pet score) and Diabetic Clinical Score (DCS) were assessed at enrolment (PLIS-treated) and 2, 4 and 12 weeks after transitioning to PZIR (starting dose 0.2-0.7 U/kg q12h). Short duration of insulin action was defined as <9 h. Linear mixed effects modelling assessed for change in fructosamine, mean blood glucose (MBG) during BGCs, DIAQoL-pet score, DCS and q12h insulin dose. McNemar's tests compared the proportion of cats with hypoglycaemia at week 0 (PLIS-treated) and week 4 (PZIR-treated). Results Twenty-two cats were recruited. Median PLIS dose at enrolment was 0.5 U/kg (interquartile range 0.3-0.7 U/kg) q12h, equalling median PZIR starting dose (0.5 U/kg; interquartile range 0.3-0.7 U/kg q12h). Transitioning was followed by significant decreases in fructosamine (P = 0.00007), insulin dose (P = 0.02), DCS (P = 8.1 x 10(-8)) and DIAQoL-pet score (P = 0.003), indicating improved quality of life. MBG did not alter significantly (P = 0.1). Five cats (22.7%) achieved remission. Hypoglycaemia was recorded in 30/190 12 h BGCs (15.8%) and five cats experienced clinical hypoglycaemia. The proportion of cats with hypoglycaemia did not differ between PLIS (week 0) and PZIR (week 4) (P = 1.0). Duration of action was analysed in 19 cats. Six cats (31.6%) showed short duration of action on PLIS, compared with two cats (10.5%) after 4 weeks on PZIR. All six cats with short PLIS duration showed duration of 9 h on PZIR. Conclusions and relevance Used alongside a low-carbohydrate diet, transitioning to PZIR was associated with significantly improved clinical signs and quality of life, with some cats achieving remission. Transition to PZIR should be considered for cats with short duration of action on PLIS