Serial measurement of cardiac troponin I in hospitalised dogs with canine parvoviral enteritis: Association with outcome and canine pancreas-specific lipase concentration.

The aim of this study was to serially evaluate serum cardiac troponin I (cTnI) concentrations in dogs with parvoviral enteritis (CPVE), and investigate the association with outcome and serum pancreas-specific lipase (Spec cPL) concentrations. Dogs with CPVE that were hospitalised for at least 5 days were included. cTnI and Spec cPL concentrations were measured on days 1, 3 and 5 of hospitalisation. Twenty-nine dogs (20 survivors, 9 non-survivors) were included. Spec cPL was indicative of pancreatitis (>400 µg/L) on at least one day in 10/29 (34.5%) dogs. Serum median (range) cTnI concentration was higher (P = 0.021) in non-survivors on day 5 [0.032 (0.001-0.395) ng/mL] compared to day 1 [0.012 (0.003-0.196) ng/mL]. Non-survivors had higher (P = 0.014) cTnI concentrations on day 5 [0.032 (0.001-0.395) ng/mL] compared to survivors [0.001 (0.001-0.042) ng/mL], but not at admission or on day 3 (P > 0.05). Serum cTnI concentrations were not significantly different (P = 0.465) between the three Spec cPL groups [group 1 (Spec cPL ≤ 200 µg/L): 0.007 (0.001-0.527) ng/mL; group 2 (Spec cPL: 201-399 µg/L): 0.0045 (0.001-0.196) ng/mL; group 3 (Spec cPL ≥ 400 µg/L): 0.011 (0.001-0.278) ng/mL]. cTnI and Spec cPL concentrations were not significantly correlated (rho = -0.043, P = 0.703). Serial measurement of cTnI had prognostic value in the examined cohort. However, cTnI was not correlated with spec cPL.

Prevalence, association with systemic inflammatory response syndrome and outcome of stress hyperglycaemia in sick cats.

OBJECTIVES: To determine the prevalence of stress hyperglycaemia in sick cats, and to investigate the association of stress hyperglycaemia with systemic inflammatory response syndrome and outcome. MATERIALS AND METHODS: Medical records (2004 to 2013) from sick cats admitted to the Medicine Unit of a Veterinary Teaching Hospital were retrospectively reviewed. Cases were enrolled if a serum glucose measurement and a complete medical record were available. Cats that were healthy, hypoglycaemic, diabetic, sedated or had a previous administration of drugs (apart from vaccination and deworming) were excluded. RESULTS: The study included 647 cats; stress hyperglycaemia (serum glucose >8.3 mmol/L) was found in 194 (30%) cats, while 453 (70%) cats were normoglycaemic. The prevalence of systemic inflammatory response syndrome was significantly higher in cats with stress hyperglycaemia (25/174, 14.4%) compared to normoglycaemic cats (26/399, 6.5%). Significantly, more cats with stress hyperglycaemia were hospitalised [97/194 (50.0%)] compared to normoglycaemic cats [171/453 (37.7%)]. However, the median duration of hospitalisation was not significantly different [4 (1 to 26) days and 4 (1 to 24) days, respectively]. The prevalence of cats with negative outcome was not significantly different between the two groups (cats with stress hyperglycaemia: 37.1%, normoglycaemic cats: 33.9%). Nonetheless, when modelling of outcome prediction included breed, age, stress hyperglycaemia and disease category as factors, cats with stress hyperglycaemia had 2.8 times the odds to have a negative outcome (95% confidence interval: 1.3 to 6.4). CLINICAL SIGNIFICANCE: Based on the cut-off employed in this study, Stress hyperglycaemia, as defined by the cut-off is common in sick cats. Stress hyperglycaemia is associated with systemic inflammatory response syndrome development and seem to be a negative prognostic indicator.

Serial measurement of thyroid hormones in hospitalised dogs with canine parvoviral enteritis: Incidence of non-thyroidal illness syndrome and its association with outcome and systemic inflammatory response syndrome.

The aim of this study was to serially evaluate the serum concentrations of total thyroxine (tT4), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) in dogs with canine parvoviral enteritis (CPVE) during a 5-day hospitalisation period and assess the association of these hormone concentrations with the outcome and the development of systemic inflammatory response syndrome (SIRS). Dogs with confirmed CPVE that were hospitalised for at least 5 days were included. The thyroid hormones concentrations were measured on days 1, 3 and 5 of hospitalisation. Twenty-eight dogs were included. All (28/28, 100%), 19/28 (69.7%) and 23/28 (82.1%) dogs had a low serum tT4, fT4 and TSH concentration, respectively, on at least 1 day during the hospitalisation period. Overall, 11/28 (39.3%) dogs were diagnosed with SIRS on at least 1 day. In survivors, serum tT4 concentration was significantly higher on day 5 (median, range: 11.8 nmol/L, <6.4-32.2 nmol/L) compared to those on days 1 (<6.4 nmol/L, <6.4-20.1 nmol/L; P = 0.010) or 3 (7.6 nmol/L, <6.4-25.2 nmol/L; P = 0.019). Survivors had a significantly higher tT4 concentration (median, range: 11.8 nmol/L, <6.4-32.2 nmol/L) on day 5 compared to non-survivors (<6.4 nmol/L, <6.4-7.2 nmol/L; P = 0.002). Regardless of the day of hospitalisation, dogs with SIRS had significantly lower tT4 (<6.4 nmol/L, <6.4-16.3 nmol/L) compared to dogs without SIRS (8.6 nmol/L, <6.4-32.2 nmol/L; P = 0.006). A significant difference was also found in fT4 between dogs with SIRS (<3.9 pmol/L, <3.9-16.2 pmol/L) and dogs without SIRS (15.1 pmol/L, <3.9-59.2; pmol/L; P < 0.001). Non-thyroidal illness syndrome was frequently observed in dogs with CPVE, and a negative association between tT4 and fT4 concentrations and SIRS was noted. Serial measurements of tT4 concentrations appeared to have prognostic value.

Complete clearance and Psoriasis Area and Severity Index response for brodalumab and ustekinumab by previous treatment history in AMAGINE-2 and AMAGINE-3.

BACKGROUND: The pathway for treatment of psoriasis is partly dependent upon disease severity, and patients may experience inadequate response at any point along the treatment pathway. Patients who repeatedly fail therapy represent a population in whom effective and well-tolerated treatment options are limited. OBJECTIVES: To investigate and describe patients achieving Psoriasis Area and Severity Index (PASI) 100 and cumulative treatment benefit over time in patients with moderate-to-severe psoriasis receiving brodalumab or ustekinumab by prior treatment. METHODS: We conducted a post hoc analysis of data from two phase 3, randomized, controlled, 52-week AMAGINE trials of brodalumab to describe patients who achieved complete clearance as measured by PASI 100 by prior treatment subgroup (naïve to systemic and biologic treatment, systemic-treated but biologic-naïve, biologic-treated without failure, and biologic-treated with failure). A competing risk model was used to assess cumulative incidence over a 52-week period with outcomes of PASI 100 or inadequate response. Cumulative clinical benefit of treatment was determined with an area under the curve analysis. RESULTS: The 52-week cumulative incidence of patients achieving PASI 100 was consistently higher for brodalumab vs. ustekinumab across treatment pathway subgroups (76% vs. 58% in systemic/biologic-naïve patients, 78% vs. 55% in systemic-treated/biologic-naïve patients, 75% vs. 41% in biologic-treated patients without failure, and 70% vs. 30% in biologic-treated patients with failure). Rates of inadequate response were lower with brodalumab compared with ustekinumab across all subgroups. Cumulative treatment benefit was also higher for all subgroups treated with brodalumab compared with those treated with ustekinumab. CONCLUSION: Treatment with brodalumab was associated with higher levels of complete clearance and greater cumulative benefit over time compared with ustekinumab, in patients with moderate-to-severe psoriasis, regardless of prior treatment experience.

Secukinumab treatment leads to normalization of quality of life and disease symptoms in psoriasis patients with or without prior systemic psoriasis therapy: the PROSE study results.

INTRODUCTION: Psoriatic disease is associated with considerable impairment of quality of life (QoL). The PROSE study (NCT02752776) investigated the impact of secukinumab treatment on patient-reported outcomes (PRO) in patients with moderate to severe psoriasis stratified by their treatment history. METHODS: PROSE was a prospective, non-randomised, multicentre study. Patients were categorized at baseline according to treatment history as naïve [naïve to any systemic therapy (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic (CS) therapy (N = 673)] and biologics [previously exposed to ≥1 biologic therapy (N = 324)]. QoL PROs, efficacy and safety of secukinumab 300 mg were assessed for a period of 52 weeks. RESULTS: The primary objective was met with 70.8% patients achieving a Dermatology Life Quality Index (DLQI) 0/1 response at Week 16 (naϊve, 74.7%; CS, 71.3%; biologic, 61.7%), with effects sustained up to Week 52. Mean Family DLQI (FDLQI) score decreased from 11.5 at baseline (naϊve, 11.3; CS, 11.4; biologic, 12.1) to 2.5 at Week 16 (naϊve, 2.5; CS, 2.3; biologic: 3.5). Substantial improvements in EuroQoL 5-Dimension Health Questionnaire, Numeric Rating Scale for pain, itching and scaling, Health Assessment Questionnaire-Disability Index, Treatment Satisfaction Questionnaire for Medication, and Patient Benefit Index were also observed at Week 16. The QoL gains were associated with substantial improvements in Psoriasis Area and Severity Index and Investigator Global Assessment mod 2011 0/1 response. No meaningful difference was observed in the efficacy or QoL improvements across patient subpopulations. All QoL and efficacy parameter improvements were sustained up to Week 52. Secukinumab treatment was well-tolerated, and no new safety signals were observed. CONCLUSION: Secukinumab treatment resulted in complete normalization of QoL in a substantial proportion of psoriasis patients, and their families, regardless of their prior treatment history.

Secukinumab efficacy in reducing the severity and the psychosocial impact of moderate-to-severe psoriasis as assessed by the Simplified Psoriasis Index: results from the IPSI-PSO study.

BACKGROUND: The utility of the Simplified Psoriasis Index (SPI), a recently developed multidomain tool for assessing psoriasis, was investigated in a study assessing response to secukinumab. METHODS: In an open-label, multicentre study involving 17 French centres, patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously once weekly from baseline to W4, then every 4 weeks until W48. Dermatologist-scored SPI psoriasis severity (proSPI-s) was compared with Psoriasis Area and Severity Index (PASI). Patient self-assessed severity (saSPI-s) and psychosocial impact (SPI-p) were compared with PASI and Dermatology Life Quality Index (DLQI), respectively. RESULTS: We included 120 patients (69.2% male; mean age 45.9 years; mean duration of psoriasis 21.6 years). Mean baseline scores were as follows: proSPI-s 24.9, saSPI-s 23.5, PASI 23.1, SPI-p 8.2 and DLQI 13.6. Severity scores achieved by 16 weeks (proSPI-s 2.3, saSPI-s 2.2 and PASI 2.2) were maintained to W52. Reductions in mean psychosocial impact scores were maintained to W52 (SPI-p and DLQI, respectively, 2.1 and 1.5 at W16; 1.5 and 1.9 at W52). CONCLUSIONS: Decrease of PASI scores in response to secukinumab was closely correlated with proSPI-s, supporting the latter's suitability for assessing response to therapy. Although the correlation between PASI and saSPI-s was slightly weaker, patients were able to complete a valid assessment of their psoriasis independently, and thus potentially remotely. With the added benefit of psychosocial impact assessment (SPI-p), SPI provides a valid tool enabling patients to assess their own psoriasis, remotely if necessary.

Baseline characteristics of patients with moderate-to-severe psoriasis according to previous systemic treatment exposure: the PROSE study population.

INTRODUCTION: Psoriatic disease is associated with considerable impairment of Quality of Life (QoL). The PROSE study (NCT02752776) examined the impact of secukinumab on patient-reported outcomes in patients with moderate-to-severe psoriasis (PsO) stratified by previous exposure to systemic treatment. METHODS: In this prospective, non-randomized, multicentre study, patients were categorized at baseline according to previous exposure to systemic treatment: naïve [naïve to any systemic treatment (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic therapy (N = 673)] and biologics [previously exposed to ≥1 biologic (N = 324)]. Baseline demographics including age, gender, race, body weight and body mass index, disease characteristics and patient-reported QoL outcomes [Dermatology Life Quality Index (DLQI), Family DLQI (F-DLQI)] of patients enrolled in the study are reported here. RESULTS: Baseline demographic characteristics were well balanced across the three subpopulations. Naïve patients had a shorter time since diagnosis (15.5 ± 12.1 years) compared with the conventional systemic (19.1 ± 12.5 years) and biologic patients (23.0 ± 12.5 years), and lower rates of psoriatic arthritis (6.6% vs. 17.4% and 27.8%, respectively). Metabolic syndrome (37.6-43.5%), obesity (16.9-19.1%), hyperlipidaemia (15.3-21.9%) and diabetes mellitus (6.8-14.2%) were reported at numerically higher rate in the biologic group. The mean PASI (19.7 ± 7.9), affected Body Surface Area (28.2 ± 15.3%) as well as the Investigator Global Assessment score (patients with score 4: 33.7%) indicated severe disease at baseline and were comparable for the three groups. QoL impairment was evident from mean DLQI (14.1 ± 7.1: naïve = 13.5 ± 6.8; conventional systemic = 14.3 ± 7.0; biologic = 14.8 ± 7.7) and mean F-DLQI (11.5 ± 7.0: naïve = 11.3 ± 7.1; conventional systemic = 11.4 ± 6.7; biologic = 12.1 ± 7.7) also indicated derangement of QoL of patients and their families. CONCLUSION: Patients naïve to systemic treatment had shorter disease journey compared with patients previously exposed to systemic treatments; despite this, the severe impact of disease on patient and family QoL outcomes can be as apparent in naïve patients as in systemically treated patients at baseline.

Long-term continuation with secukinumab in psoriasis: association with patient profile and initial psoriasis clearance.

BACKGROUND: There are limited data regarding the long-term continuation with biological therapy for patients with psoriasis. In particular, the reasons for secukinumab discontinuation have not been thoroughly investigated. AIM: To better ascertain the real-life continuation of secukinumab in psoriasis, we conducted a retrospective study to evaluate the incidence, causes and factors of secukinumab discontinuation in patients with psoriasis. METHODS: All patients treated with secukinumab for psoriasis in the Department of Dermatology (Toulouse University and Larrey Hospital, Toulouse, France), between September 2011 and June 2017, were enrolled in the study. RESULTS: Of the 91 patients in the study, 22 (24.2%) discontinued secukinumab. In 14 (15%) patients, the discontinuation was due to loss of efficacy. Two patients stopped treatment because they planned a pregnancy and five patients stopped because of adverse events. A longer disease duration (P = 0.01) and presence of palmoplantar psoriasis (P = 0.01) seem to be predictive factors for treatment failure. Patients reaching 90 or 100% improvement in Psoriasis Area and Severity Index (PASI90 and PASI100, respectively) at weeks 12-16 had a lower risk of long-term treatment discontinuation compared with patients who had less complete clearance (P = 0.04). CONCLUSION: Long-term persistence of secukinumab appears to be good, as only 24.2% (n = 22) of the patients in this study discontinued secukinumab over the follow-up period. Loss of efficacy prompted discontinuation in about 14% of patients by the 2-year follow-up. Persistence appears to be lower in patients with palmoplantar psoriasis and in patients previously exposed to many systemic treatments. Optimal therapeutic response at 12-16 weeks as defined by reaching PASI90-100 seems to be predictive of long-term treatment persistence.

Validation, reference intervals and overlap performance of a new commercially available automated capillary electrophoresis assay for the determination of the major fraction of glycated haemoglobin (HbA1c) in dogs.

Haemoglobin A1c (HbA1c), the major fraction of glycated haemoglobin, is widely used for the diagnosis and monitoring of diabetes mellitus in human beings. However, there is a paucity of literature on the most reliable methods available for measurement of canine HbA1c. The aim of this study was to validate a new automated capillary electrophoresis assay for canine HbA1c, to generate a reference interval and to assess the overlap performance of the assay for the diagnosis of diabetes mellitus. Eighty-three blood samples treated with EDTA were included in the study, comprising 63 from healthy dogs and 20 from diabetic dogs. Linearity was assessed by mixing canine samples of known HbA1c percentage in different proportions, precision was assessed by repeated (n=8) measurement of five canine samples, and stability was assessed by measuring canine samples stored at 4°C for 96h and -20°C for 4 weeks. The robust method was used to determine the reference interval. The assay was demonstrated to be linear (R2=0.943). Intra-assay and inter-assay coefficients of variation (CVs) were 4.8% and 7.0%, respectively. CVs for blood samples stored at 4°C and -20°C were 7.2% and 11.2%, respectively. The reference interval was 0.6-2.7%. Dogs with diabetes mellitus had significantly (P<0.001) higher mean HbA1c (5.24±0.88%) compared to the reference population (1.64±0.55%), with no overlap between results. A HbA1c cut-off of 3.3% clearly differentiated diabetic from healthy dogs. The capillary electrophoresis assay was properly validated for canine HbA1c and the reference interval was determined, while the overlap performance of the assay was excellent.