scholarly journals Randomised clinical non-inferiority trial comparing two formulations of desoxycortone pivalate for the treatment of canine primary hypoadrenocorticism

2020 ◽  
Vol 187 (2) ◽  
pp. e12-e12
Author(s):  
Hayley Farr ◽  
Beasley L Mason ◽  
Susan L Longhofer

BackgroundThis clinical trial compared two formulations of desoxycortone pivalate (DOCP) for treating the mineralocorticoid deficit in dogs with primary hypoadrenocorticism (PH).MethodsAt veterinary clinics in the USA and France, dogs with PH (n=152) were randomised (3:1) to receive approximately monthly treatments with either the test product, Zycortal (Dechra), administered subcutaneously (n=113), or the control product, Percorten-V (Novartis Animal Health), administered intramuscularly (n=39), both at an initial dose of 2.2 mg/kg DOCP. Treatment administrators were unblinded; veterinarians assessing clinical signs were blinded; owners were blinded until at least day 90, the primary end point. Veterinarians assessed treatment outcome based on all of the following: clinical signs; sodium concentrations; potassium concentrations. Dogs received concurrent glucocorticoid therapy throughout the trial. Non-inferiority was assessed using a generalised linear mixed model to compare success rates between groups.ResultsSuccess rates at day 90 were similar between groups (per-protocol population at day 90: Zycortal 87/101, 86.2 per cent, Percorten-V 29/34, 85.1 per cent). Zycortal was non-inferior to Percorten-V as the upper limit of the 95 per cent CI for the difference between groups was 13.6 per cent. Polydipsia and polyuria were the most common clinical observations.ConclusionBoth products, in combination with glucocorticoid therapy, were safe and effective in treating PH.

2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
M B Zazzara ◽  
P M Wells ◽  
R C E Bowyer ◽  
M N Lochlainn ◽  
E J Thompson ◽  
...  

Abstract Introduction Periodontitis is a chronic inflammatory disease affecting the periodontium, ultimately leading to looseness and/or loss of teeth. Sarcopenia refers to age-related reduction in muscle mass and strength. Similar to periodontitis, chronic low-grade inflammation is thought to play a key role in its development. In addition, both increase in prevalence with advancing age. Despite known associations with other diseases involving a dysregulated inflammatory response, for example rheumatoid arthritis,, the relationship between periodontitis and sarcopenia, and whether they could be driven by similar processes, remains uncertain. The aim of this study was to explore the association between periodontitis and sarcopenia. Methods Observational study of 2040 adult volunteers [age 67.18 (12.17)] enrolled in the TwinsUK cohort study. Presence of tooth mobility and number of teeth lost were used to assess periodontal health. A binary variable was created to define periodontitis. Measurements of muscle strength, muscle quality/quantity and physical performance were used to assess sarcopenia. A categorical variable was created according to the European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, to define sarcopenia (1: probable; 2: positive; 3: severe). Generalised linear mixed model analysis used on complete cases and age-matched (n = 1,288) samples to ascertain associations between periodontitis and sarcopenia. Results No significant association was found between periodontitis and sarcopenia in both the complete cases analysis and age-matched analysis. Results were consistent when analysis was adjusted for potential confounders including body mass index, frailty index, Mini Mental State Examination smoking, nutritional status and educational level. Conclusions This study found no significant association between periodontitis and sarcopenia in a cohort of 2040 adults. Although both periodontitis and sarcopenia have been linked to a dysregulated immune response and demonstrate an increase in prevalence with increasing age, our work is inconclusive due to the plethora of possible aetiopathogenetic pathways.


2014 ◽  
Vol 54 (10) ◽  
pp. 1853 ◽  
Author(s):  
N. G. McPhail ◽  
J. L. Stark ◽  
A. J. Ball ◽  
R. D. Warner

Chilled lamb meat exported from Australia has, on occasions, been rejected by importing countries due to greening, after only 6 weeks of storage time. Greening is known to be more prevalent in high ultimate pH (pHu) beef meat (>5.9). There are few data available for lamb carcasses in Australia on the occurrence of high pHu meat, which may have an impact on the understanding and control of quality and greening during storage. The aim of this project was to determine the prevalence of, and influencing factors for, high pHu meat in a range of muscle types in lamb carcasses in Australia. Muscle pHu data were collected from a total of 1614 carcasses from 78 lots at four lamb processing plants in Victoria and New South Wales in autumn and spring of 2013. The pHu of the knuckle (rectus femoris), rack (longissimus) and blade (infraspinatus) was measured and data on carcass and lot characteristics were recorded. Data were subjected to restricted maximum likelihood and generalised linear mixed model analysis. The mean pHu of the knuckle, rack and shoulder were 6.06, 5.79 and 6.12 respectively, and the main factors influencing muscle pHu and occurrence of dark-cutting were breed, season, electrical stimulation and carcass weight. Merino lambs had a higher pHu in the blade and knuckle than did other breeds (P < 0.05, P < 0.01 respectively). Lambs processed in autumn had a higher predicted pHu in the blade and knuckle and a higher percentage dark-cutting (DC; pHu >6.0) for those muscles, than did those processed in spring (P < 0.05). Carcasses that had been electrically stimulated had a higher %DC and a higher pHu in all three muscles (P < 0.05). Carcass weight had a significant effect on the pHu of all three muscles (P < 0.001), with heavier carcasses having a lower pHu and lower %DC. The pHu of the rack was not a reliable predictor for the pHu in other muscles of the lamb carcass. In conclusion, the high occurrence of DC in the muscles, particularly the blade and knuckle, suggests that these muscles may be at risk for producing greening in the vacuum bag during storage.


2018 ◽  
Vol 147 ◽  
Author(s):  
A. Aswi ◽  
S. M. Cramb ◽  
P. Moraga ◽  
K. Mengersen

AbstractDengue fever (DF) is one of the world's most disabling mosquito-borne diseases, with a variety of approaches available to model its spatial and temporal dynamics. This paper aims to identify and compare the different spatial and spatio-temporal Bayesian modelling methods that have been applied to DF and examine influential covariates that have been reportedly associated with the risk of DF. A systematic search was performed in December 2017, using Web of Science, Scopus, ScienceDirect, PubMed, ProQuest and Medline (via Ebscohost) electronic databases. The search was restricted to refereed journal articles published in English from January 2000 to November 2017. Thirty-one articles met the inclusion criteria. Using a modified quality assessment tool, the median quality score across studies was 14/16. The most popular Bayesian statistical approach to dengue modelling was a generalised linear mixed model with spatial random effects described by a conditional autoregressive prior. A limited number of studies included spatio-temporal random effects. Temperature and precipitation were shown to often influence the risk of dengue. Developing spatio-temporal random-effect models, considering other priors, using a dataset that covers an extended time period, and investigating other covariates would help to better understand and control DF transmission.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
R. Bhome ◽  
A. Zarkali ◽  
G. E. C. Thomas ◽  
J. E. Iglesias ◽  
J. H. Cole ◽  
...  

AbstractDepression is a common non-motor feature of Parkinson’s disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14–20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.


2021 ◽  
Author(s):  
David J Pascall ◽  
Guy Mollett ◽  
Rachel Blacow ◽  
Naomi Bulteel ◽  
Robyn Campbell ◽  
...  

Background The Alpha (B.1.1.7) SARS-CoV-2 variant of concern has been associated with increased transmission and increased 28-day mortality. We aimed to investigate the impact of infection on clinical severity of illness, including the need for oxygen or ventilation in a national cohort study. Methods In this prospective clinical cohort study, 1475 SARS-CoV-2 sequences were obtained from patients infected in Scotland, UK between the 1st November 2020 and 30th January 2021 and matched to clinical outcomes as the lineage became dominant in Scotland. We modelled the association between B.1.1.7 infection and severe disease using a cumulative generalised linear mixed model employing a 4-point scale of maximum severity based on requirement of respiratory support at 28 days. We also estimated the growth rate of B.1.1.7-associated infections as it emerged in Scotland using a phylogenetic exponential growth rate population model. Results The B.1.1.7 lineage was responsible for a third wave of SARS-CoV-2 infection in Scotland in association with a transmission rate 5-fold higher than the preceding second wave B.1.177 lineage. Of 1475 patients, 364 were infected with B.1.1.7, 1030 with B.1.177 and 81 with other lineages. Our analysis found a positive association between increased clinical severity and lineage (B.1.1.7 versus non-B.1.1.7; cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93). Viral load was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold (Ct) value (mean Ct change: -2.46, 95% CI: -4.22, -0.70). Conclusions The B.1.1.7 lineage was associated with more severe clinical disease in Scottish patients than co-circulating lineages.


Agriculture ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 319
Author(s):  
Ariane Horst ◽  
Marvin Gertz ◽  
Mario Hasler ◽  
Joachim Krieter

Documented lesions of slaughtered pigs provide a high-density data-pool that could be valuable for the purpose of animal health monitoring and breeding. However, data quality and structure hamper the application of statistical methods. The present study provides an approach that enables statistical analysis and evaluates the comparability of lesion prevalence among abattoirs. The German Quality and Safety database provided data of recorded lung, pleura, liver, and heart lesions. Filter criteria were used to improve the data structure. Data of n = 8,004,769 animals, recorded in nine abattoirs over a period of 18 months, were analyzed. Lesion prevalences were successfully modeled by applying a generalized linear mixed model. To examine prevalence differences, the coefficient of variation (CV) on a six-monthly basis was calculated, and a grand mean test (GMT) of significance was applied. High variations in estimated prevalence occurred on abattoir, six-monthly and organ basis. The highest variation occurred in the lung (CV = 64.7%), whereas liver lesions showed the lowest variation (CV = 21.8%). The GMT enabled the visualization of these variations between abattoirs, organs and over time. Concerning the assessment of the comparability of prevalences, it provides a promising tool to monitor changes in lesion examination and to address divergent abattoirs.


2018 ◽  
Vol 126 (09) ◽  
pp. 546-552 ◽  
Author(s):  
Rolf Larisch ◽  
John Midgley ◽  
Johannes Dietrich ◽  
Rudolf Hoermann

Abstract Aim Patients on levothyroxine-treatment frequently have complaints although TSH is within the reference range. Moreover, FT3 is often low in these patients. The clinical significance of this disequilibrium is studied here. Patients, methods We conducted a retrospective longitudinal study including 319 patients with differentiated thyroid carcinoma on LT4-medication (1.8 [1.6,2.1] µg/kg body weight). Patients were followed at 2309 visits for at median 63 [46,81] months. Association of reported complaints during follow-up with changes in thyroid parameters were analysed using a generalised linear mixed model accounting for within-variability and intra-subject correlations. Results 26% of patients expressed hypothyroid and 9.7% hyperthyroid complaints at any one visit, rates per visit being 6.5% and 2%, respectively. During follow-up, median changes in spans were as follows, LT4-dose 0.49 [IQR 0.29,0.72] µg/kg, FT3 1.77 [1.25,2.32] pmol/l, FT4 9.80 [6.70,12.8] pmol/l and TSH 1.25 [0.42,2.36] mIU/l. While rates of both hypothyroid or hyperthyroid symptoms were significantly related to all three thyroid parameters, the relationship of hypothyroid symptoms with FT3 extended to a below reference TSH range. Hypothyroid symptom relief was associated with both a T4 dose giving TSH-suppression below the lower reference limit and FT3 elevated further into the upper half of its reference range. In multivariable analysis, relationships between complaints and FT3 concentrations remained significant after adjusting for gender, age and BMI. Conclusion Residual hypothyroid complaints in LT4-treated patients are specifically related to low FT3 concentrations. This supports an important role of FT3 for clinical decision making on dose adequacy, particularly in symptomatic athyreotic patients.


2019 ◽  
Vol 23 (11) ◽  
pp. 4763-4781 ◽  
Author(s):  
Juan Ossa-Moreno ◽  
Greg Keir ◽  
Neil McIntyre ◽  
Michela Cameletti ◽  
Diego Rivera

Abstract. The accuracy of hydrological assessments in mountain regions is often hindered by the low density of gauges coupled with complex spatial variations in climate. Increasingly, spatial datasets (i.e. satellite and other products) and new computational tools are merged with ground observations to address this problem. This paper presents a comparison of approaches of different complexities to spatially interpolate monthly precipitation and daily temperature time series in the upper Aconcagua catchment in central Chile. A generalised linear mixed model (GLMM) whose parameters are estimated through approximate Bayesian inference is compared with simpler alternatives: inverse distance weighting (IDW), lapse rates (LRs), and two methods that analyse the residuals between observations and WorldClim (WC) data or Climate Hazards Group Infrared Precipitation with Station data (CHIRPS). The assessment is based on a leave-one-out cross validation (LOOCV), with the root-mean-squared error (RMSE) being the primary performance criterion for both climate variables, while the probability of detection (POD) and false-alarm ratio (FAR) are also used for precipitation. Results show that for spatial interpolation of temperature and precipitation, the approaches based on the WorldClim or CHIRPS residuals may be recommended as being more accurate, easy to apply and relatively robust to tested reductions in the number of estimation gauges. The GLMM has comparable performance when all gauges were included and is better for estimating occurrence of precipitation but is more sensitive to the reduction in the number of gauges used for estimation, which is a constraint in sparsely monitored catchments.


2017 ◽  
Vol 117 (02) ◽  
pp. 277-285 ◽  
Author(s):  
Edward D. Gomperts ◽  
John Schwarz ◽  
Sharyne M. Donfield ◽  
Alice E. Lail ◽  
Jan Astermark ◽  
...  

SummaryHaemophilia A is a congenital bleeding disorder characterised by recurrent haemorrhages into the major joints. Haemophilic arthropathy is a well-established outcome of recurrent joint bleeding; however, it is clear that multiple factors determine the extent and severity of its occurrence. We sought to identify genetic factors related to abnormalities in range of motion (ROM) in the knees, ankles and elbows in a cohort of children and adolescents with haemophilia A not treated primarily with regular prophylaxis. Using data from the Haemophilia Growth and Development Study, we examined associations between 13,342 genetic markers and ROM scores measured at six-month intervals for up to seven years. As a first step, ordered logistic regression models were fit for each joint separately. A subset of SNP markers showing significant effects (p<0.01) on the right and left sides for at least two joints were included in a full model fit using a multivariate generalised linear mixed model assuming an ordinal response. The models contained all ROM scores obtained at all visits. Twenty-five markers analysed in the full model showed either increased or decreased risk of ROM abnormalities at the p<0.001 level. Several genes identified at either the first or second stage of the analysis have been associated with arthritis in a variety of large studies. Our results support the likelihood that risk for haemophilic arthropathy is associated with genetic factors, the identification of which holds promise for further advancing the individualisation of treatment.


2019 ◽  
Vol 70 (3) ◽  
pp. 395 ◽  
Author(s):  
N. C. S. Marques ◽  
L. Rattis ◽  
F. Nomura

In this study, we investigated the environmental variables that best explained tadpole occurrence, as well as associations between environmental variables and the morphological traits of tadpoles. We modelled the occurrence of tadpoles to evaluate the significance of trait–environment relationships by sampling in 86 ponds, measuring a set of environmental descriptors of these ponds, determining the tadpoles’ external-morphology changes and using a generalised linear mixed model approach. The best fitting model predicting tadpole occurrence included all the environmental variables measured (pond dimensions, pond margin type, pond bottom substrate, vegetation type inside the pond, vegetation type in the pond margins, landscape descriptors) and seven morphology–environment interactions. Tadpoles are capable of fine-tuning their morphology according to the environmental traits of the pond and land use changes around the pond. Vegetation heterogeneity of ponds interacts with tadpole morphology primarily on tail size and deviations in the mean position of the eye, nostril and mouth. Moreover, there are increases in body size and tail length in smaller ponds, as well as in ponds surrounded vegetation changes from forest to pasture or short crops. Changes in environmental variables as a result of land use change can affect the dispersion of adult frogs and, consequently, the occurrence of and morphological variations in tadpoles. Local environmental variables play important roles driving tadpoles’ microhabitat choice; once tadpoles cannot select the site of their developmental, they need to compensate for any mismatching by induced morphological adaptations.


Sign in / Sign up

Export Citation Format

Share Document