Progression of experimental chronic Aleutian mink disease virus infection

BACKGROUND: Aleutian mink disease virus (AMDV) is found world-wide and has a major impact on mink health and welfare by decreasing reproduction and fur quality. In the majority of mink, the infection is subclinical and the diagnosis must be confirmed by serology or polymerase chain reaction (PCR). Increased knowledge based on a systematically description of clinical signs, pathology and histopathology might be a tool to reduce the risk of infection from subclinically infected mink to AMDV free herds. The aim of this study was to give a histopathological description of the progression of a chronic experimental infection with a currently circulating Danish strain of AMDV, Saeby/DEN/799.1/05. These results were compared with the pathogenesis of previously published AMDV stains. RESULTS: This experimental AMDV infection resulted in only decreased appetite and soft or discolored feces, primarily within the first 8 weeks after AMDV inoculation. Gross pathology revealed few and inconsistent findings mainly associated with the liver, spleen and kidneys. The majority of the AMDV inoculated wild type mink (n = 41) developed various histopathological changes consistent with AMDV infection in one or more organs: infiltrations of mononuclear cells in liver, kidney and brain, reduced density of lymphocytes and increased numbers of plasma cells in lymph nodes and spleen. Natural infection, as occurred in the sentinel sapphire mink (four of six mink), progressed similar to the experimentally inoculated mink. CONCLUSIONS: Experimental AMDV inoculation mainly resulted in subclinical infection with unspecific clinical signs and gross pathology, and more consistent histopathology appearing at any time after AMDV inoculation during the 24 weeks of observation. Thus, the observed histopathology substantiates AMDV infection and no correlation to time of inoculation was found. This confirms that diagnosing AMDV infection requires serology and/or PCR and the Saeby/DEN/799.1/05 AMDV strain results in histopathology consistent with other AMDV strains

Impact of obesity and type 2 diabetes on health-related quality of life in the general population in England

Stephen CL Gough,1 Nana Kragh,2 Uffe Jon Ploug,2 Mette Hammer21University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, UK; 2Novo Nordisk A/S Global Health Economics and Outcomes Research Krogshojvej 55, DK-2880 Bagsvaerd, DenmarkBackground: Weight gain can contribute towards the development of type 2 diabetes (T2D), and some treatments for T2D can lead to weight gain. The aim of this study was to determine whether having T2D and also being obese had a greater or lesser impact on health-related quality of life (HRQoL) than having either of the two conditions alone.Methods: The 2003 dataset of the Health Survey for England (HSE) was analyzed using multiple regression analyses to examine the influence of obesity and T2D on HRQoL, and to determine whether there was any interaction between these two disutilities.Results: T2D reduced HRQoL by 0.029 points, and obesity reduced HRQoL by 0.027 points. There was no significant interaction effect between T2D and obesity, suggesting that the effect of having both T2D and being obese is simply additive and results in a reduction in HRQoL of 0.056.Conclusions: Based on analysis of HSE 2003 data, people with either T2D or obesity experience significant reduction in HRQoL and people with both conditions have a reduction in HRQoL equal to the sum of the two independent effects. The effect of obesity on HRQoL in people with T2D should be considered when selecting a therapy.Keywords: diabetes, health-related quality of life, obesity, type 2 diabetes, Englan

Development and validation of the Treatment Related Impact Measure of Weight (TRIM-Weight)

<p>Abstract</p> <p>Background</p> <p>The use of prescription anti-obesity medication (AOM) is becoming increasingly common as treatment options grow and become more accessible. However, AOM may not be without a wide range of potentially negative impacts on patient functioning and well being. The Treatment Related Impact Measure (TRIM-Weight) is an obesity treatment-specific patient reported outcomes (PRO) measure designed to assess the key impacts of prescription anti-obesity medication. This paper will present the validation findings for the TRIM-Weight.</p> <p>Methods</p> <p>The online validation battery survey was administered in four countries (the U.S., U.K., Australia, and Canada). Eligible subjects were over age eighteen, currently taking a prescription AOM and were currently or had been obese during their life. Validation analyses were conducted according to an <it>a priori </it>statistical analysis plan. Item level psychometric and conceptual criteria were used to refine and reduce the preliminary item pool and factor analysis to identify structural domains was performed. Reliability and validity testing was then performed and the minimally importance difference (MID) explored.</p> <p>Results</p> <p>Two hundred and eight subjects completed the survey. Twenty-one of the 43 items were dropped and a five-factor structure was achieved: Daily Life, Weight Management, Treatment Burden, Experience of Side Effects, and Psychological Health. <it>A-priori </it>criteria for internal consistency and test-retest coefficients for the total score and all five subscales were met. All pre-specified hypotheses for convergent and known group validity were also met with the exception of the domain of Daily Life (proven in an ad hoc analysis) as well as the 1/2 standard deviation threshold for the MID.</p> <p>Conclusion</p> <p>The development and validation of the TRIM-Weight has been conducted according to well-defined principles for the creation of a PRO measure. Based on the evidence to date, the TRIM-Weight can be considered a brief, conceptually sound, valid and reliable PRO measure.</p

Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone

<p>Abstract</p> <p>Background</p> <p>Poor control of type 2 diabetes results in substantial long-term consequences. Studies of new diabetes treatments are rarely designed to assess mortality, complication rates and costs. We sought to estimate the long-term consequences of liraglutide and rosiglitazone both added to glimepiride.</p> <p>Methods</p> <p>To estimate long-term clinical and economic consequences, we used the CORE diabetes model, a validated cohort model that uses epidemiologic data from long-term clinical trials to simulate morbidity, mortality and costs of diabetes. Clinical data were extracted from the LEAD-1 trial evaluating two doses (1.2 mg and 1.8 mg) of a once daily GLP-1 analog liraglutide, or rosiglitazone 4 mg, on a background of glimepiride in type 2 diabetes. CORE was calibrated to the LEAD-1 baseline patient characteristics. Survival, cumulative incidence of cardiovascular, ocular and renal events and healthcare costs were estimated over three periods: 10, 20 and 30 years.</p> <p>Results</p> <p>In a hypothetical cohort of 5000 patients per treatment followed for 30 years, liraglutide 1.2 mg and 1.8 mg had higher survival rates compared to the group treated with rosiglitazone (15.0% and 16.0% vs. 12.6% after 30 years), and fewer cardiovascular, renal, and ocular events. Cardiovascular death rates after 30 years were 69.7%, 68.4% and 72.5%, for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively. First and recurrent amputations were lower in the rosiglitazone group, probably due to a 'survival paradox' in the liraglutide arms (number of events: 565, 529, and 507, respectively). Overall cumulative costs per patient, were lower in both liraglutide groups compared to rosiglitazone (US$38,963,$39,239, and $40,401 for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively), mainly driven by the costs of cardiovascular events in all groups.</p> <p>Conclusion</p> <p>Using data from LEAD-1 and epidemiologic evidence from the CORE diabetes model, projected rates of mortality, diabetes complications and healthcare costs over the long term favor liraglutide plus glimepiride over rosiglitazone plus glimepiride.</p> <p>Trial registration</p> <p>LEAD-1 NCT00318422; LEAD-2 NCT00318461; LEAD-3 NCT 00294723; LEAD-4 NCT00333151; LEAD-5 NCT00331851; LEAD-6 NCT00518882.</p

The influence of above-ground herbivory on the response of arctic soil methanotrophs to increasing ch4 concentrations and temperatures

Rising temperatures in the Arctic affect soil microorganisms, herbivores, and peatland vegetation, thus directly and indirectly influencing microbial CH4 production. It is not currently known how methanotrophs in Arctic peat respond to combined changes in temperature, CH4 concentration, and vegetation. We studied methanotroph responses to temperature and CH4 concentration in peat exposed to herbivory and protected by exclosures. The methanotroph activity was assessed by CH4 oxidation rate measurements using peat soil microcosms and a pure culture of Methylobacter tundripaludum SV96, qPCR, and sequencing of pmoA transcripts. Elevated CH4 concentrations led to higher CH4 oxidation rates both in grazed and exclosed peat soils, but the strongest response was observed in grazed peat soils. Furthermore, the relative transcriptional activities of different methanotroph community members were affected by the CH4 concentrations. While transcriptional responses to low CH4 concentrations were more prevalent in grazed peat soils, responses to high CH4 concentrations were more prevalent in exclosed peat soils. We observed no significant methanotroph responses to increasing temperatures. We conclude that methanotroph communities in these peat soils respond to changes in the CH4 concentration depending on their previous exposure to grazing. This “conditioning” influences which strains will thrive and, therefore, determines the function of the methanotroph community

Associations between biosecurity and outbreaks of canine distemper on Danish mink farms in 2012–2013

BACKGROUND: During 8 months from July 2012 to February 2013, a major outbreak of canine distemper involving 64 mink farms occurred on the Danish peninsula of Jutland. The canine distemper outbreak was associated with exposure of farmed mink to infected wild carnivores and could represent a deficit in biosecurity on the mink farms. The aim of this study was to investigate the extent and association of specific biosecurity measures with the outbreak. The study was carried out in an epidemiological case–control design. The case group consisted of the 61 farms, which had a confirmed outbreak of canine distemper from July 2012 to February 2013. The control group included 54 farms without an outbreak of canine distemper in 2012 or 2013, selected as the closest geographical neighbour to a case farm. RESULTS: The results showed that significantly more control than case farms had vaccinated their mink against canine distemper virus. Mortality was only assessed on the case farms, and there was a non-significantly lower mortality on vaccinated farms than on the non-vaccinated farms. Furthermore, the proportion of farms with observations of wild red foxes (Vulpes vulpes) inside the farm enclosures were larger for case farms, indicating that the control farms had a better biosecurity or were not equally exposed to canine distemper virus. Generally, all farms had very few specific precautions at the gate entrance in respect to human visitors as well as animals. The use of biosecurity measures was very variable in both case and control farms. Not using plastic boot covers, presence of dogs and cats, presence of demarcated area for changing clothes when entering and leaving the farm area and presence of hand washing facilities significantly lowered the odds of the farm having a canine distemper virus outbreak. CONCLUSIONS: The results of the study indicate that consistent use of correct vaccination strategies, implementation of biosecurity measures and limiting human and animal access to the mink farm can be important factors in reducing the risk for canine distemper outbreaks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0159-2) contains supplementary material, which is available to authorized users

Influenza A virus H10N7 detected in dead harbor seals (Phoca vitulina) at several locations in Denmark 2014.

Influenza A virus (IAV) affects a wide range of species, though waterfowl is regarded the natural host for most IAV subtypes. Avian influenza (AI) viruses replicate in the intestinal tract of birds and are mainly transmitted by the fecal-oral route. Pinnipeds share the same shoreline habitats as many waterfowl species and are therefore potentially exposed to AIV. Outbreaks of AI in seals have been described in North America and Asia but prior to 2014 never in Europe. In 2014 massive deaths of harbor seals (Phoca vitulina) were reported in Northern Europe. In Denmark, harbor seals were initially found dead on the Danish island Anholt in Kattegat, which is the sea surrounded by Denmark, Norway and Sweden. Between June and August, 152 harbor seals were found dead. Four seals were submitted to the National Veterinary Institute in Dennmark and diagnosed with severe pneumonia. Influenza A virus of the subtype H10N7 was detected in two out of four seals. Subsequently IAV was detected in dead harbor seals at several locations in Denmark. The IAV outbreak appeared to move with time to the west through the Limfjord to the North Sea and further down south along the west coast of Jutland to the Wadden Sea. Outbreaks were subsequently reported from Germany and The Netherlands. The aim of this study was to characterize the viruses detected at the several locations by molecular and phylogenetic analysis. All viruses were subtyped as H10N7 with genes of avian origin. The HA and NA genes of the viruses were highly similar to H10N7 IAV detected in harbor seals in Sweden in the spring of 2014 and in Germany in the autumn of 2014, suggesting that the same strain of virus had spread from Sweden to Denmark and further on to Germany