Developing a tool to assess the health-related quality of life in calves with respiratory disease: content validation.

Bovine respiratory disease (BRD) is a major welfare and productivity issue for calves. Despite the extensive negative impacts on calf welfare and performance, BRD remains challenging to detect and treat effectively. However, the clinical signs of disease are only one aspect of the disease that is experienced by the individual. The assessment of emotional experience in animals is not straightforward, but it is increasingly recognised that the quality of behaviour and demeanour of an individual is a reflection of their internal emotional state. The aim of the present study was to complete the content validation stage of the development process for a health-related quality of life (HRQOL) tool. This was based around indicators from an existing conceptual framework containing twenty-three indicators in two domains (clinical signs and behavioural expression). The content validation stage involves engaging with key stakeholders. For this study, this took the form of a survey and discussions with focus groups, which are standard methods in this field. A survey and stakeholder focus groups were conducted to assess the usefulness of each indicator and its relevance for inclusion within a HRQOL tool. In the survey, participants were asked to rate the usefulness of each of the indicators using a 4-point scale which were then dichotomised into 'useful' and 'less useful'. Based on the 'useful' result, each indicator within the domains was ranked. A similar approach was taken with the responses from the focus groups. Focus group participants were asked to select indicators that they felt were of use and the result of this was used to rank each of the indicators. The ranks of the indicators from both the survey and the focus groups along with the transcripts from the focus groups were used to determine the indicators from each domain to include within the HRQOL tool. Indicators within the clinical signs domain that were included were nasal discharge, cough, respiratory effort, ocular appearance (discharge and vibrancy), body and head posture and ear carriage. For the domain of behavioural expression, the indicators included were movement to feed, responsiveness, spatial proximity, volume of feed intake, motivation at feed and vigour. The next stage will be to validate the construction of the HRQOL tool through its use in practice. The inclusion of indicators that allow the experiential aspects of disease to be recorded in health assessments will likely increase the ability of farmers and others to detect respiratory disease in calves.

Construction of a conceptual framework for assessment of health-related quality of life in calves with respiratory disease.

Bovine respiratory disease (BRD) is one of the most prevalent diseases affecting beef and dairy calves worldwide, with implications for lifetime productivity, antimicrobial use and animal welfare. Our objective was to construct a conceptual framework for assessment of health-related quality of life (HRQL) in calves with respiratory disease, based on indicators suitable for direct pen-side visual observation. Health-related quality of life measures aim to evaluate the subjective experience of the animal rather than any related pathology. A conceptual framework graphically represents the concepts to be measured and the potential relationships between them. A multistage, mixed method approach involving diverse data sources, collection methods and stakeholders was applied to promote comprehensiveness, understanding and validity of findings. A scoping review was conducted to identify, characterize and collate evidence of behavioural indicators of BRD. The indicators identified were mapped against the principal attributes of five prominent animal welfare assessment frameworks to appraise their correspondence with different characterizations of the dimensions of welfare. Forty-two semi-structured, individual, qualitative interviews with a purposeful sample of experienced veterinarians and stockpersons from UK, USA and Canada elicited in-depth descriptions of the visual observations of HRQL they make in diagnosing and assessing the response to treatment of calves with BRD. Verbatim interview transcripts were examined using inductive thematic analysis. Respondents provided insights and understanding of indicators of HRQL in BRD such as interaction with feed source, hair coat condition, specific characteristics of eye appearance, eye contact, rumen fill and stretching (pandiculation). In an on-farm pilot study to assess the value of potential HRQL behavioural indicators, there was a moderate positive correlation between behaviour and clinical scores (rs = 0.59) across the 5 days preceding veterinary treatment for BRD. Interestingly, the behaviours evaluated were observed a median of 1.0 (interquartile range: 1.0-3.5) days before clinical indicators used in the scoring system. The proposed conceptual framework for assessment of HRQL features 23 putative indicators of HRQL distributed across two interrelated domains - clinical signs and behavioural expressions of emotional well-being. It has potential applications to inform the development of new HRQL measures such as structured questionnaires and automated sensor technologies.

Burden of cytomegalovirus disease in allogeneic hematopoietic cell transplant recipients: a national, matched cohort study in an inpatient setting.

PURPOSE OF THE STUDY: No studies have compared the risk of mortality or graft-versus-host disease, in an inpatient setting in France, in allogeneic hematopoietic cell transplant recipients who develop cytomegalovirus disease with those who do not. This study assessed the impact of cytomegalovirus disease on clinical outcomes and healthcare resource utilization in allogeneic hematopoietic cell transplant recipients using the French Programme de Médicalisation des Systèmes d'Information database. PATIENTS AND METHODS: Recipients who had undergone allogeneic hematopoietic cell transplant in French hospitals between 2008 and 2011 were included in this retrospective, matched cohort study. Those with cytomegalovirus disease were each matched with two allogeneic hematopoietic cell transplant recipients without cytomegalovirus disease according to demographic and clinical characteristics. Probabilities of in-hospital mortality, graft rejection and/or graft-versus-host disease, and healthcare resource utilization were compared up to 12 months after cytomegalovirus disease diagnosis. RESULTS: Overall, 4884 transplant recipients were enrolled, of which 194 had cytomegalovirus disease. Of these, 165 recipients with cytomegalovirus disease were matched to 330 without cytomegalovirus disease (1:2 ratio). The development of cytomegalovirus disease was associated with a significantly higher risk of in-hospital mortality (relative risk = 1.7, p = 0.0005) and higher cumulative number of inpatient days (p < 0.0001), but was not associated with a significantly higher risk of graft rejection and/or graft-versus-host disease or healthcare costs. CONCLUSIONS: Due to the increased risk of in-hospital mortality and higher cumulative number of inpatient days in allogeneic hematopoietic cell transplant recipients with cytomegalovirus disease versus those without, new strategies to prevent and manage cytomegalovirus disease are warranted.

Evaluating the economic implications of non-adherence and antibody-mediated rejection in renal transplant recipients: the role of once-daily tacrolimus in the UK.

BACKGROUND AND AIMS: While short-term kidney graft survival has gradually improved over time, improvements in long-term graft survival have been more modest. One key clinical factor limiting improved longer-term outcomes is antibody-mediated rejection (AbMR), the incidence of which appears to be higher in patients who are non-adherent to immunosuppressants. Recent data show that adherence can be improved by reducing pill burden. The aim of the present study was to model the incidence and economic consequences of graft loss and AbMR in patients taking once- vs twice-daily tacrolimus in the UK. METHODS: A combined decision tree and Markov model was developed to estimate the incidence of graft failure, AbMR and mortality in renal transplant recipients taking once- vs twice-daily tacrolimus. Underlying rates of graft failure and mortality were derived from UK-specific sources. Proportions of patients adherent to once- vs twice-daily tacrolimus were taken from a recent randomized clinical trial and relative risks of graft failure and AbMR were taken from a prospective, multi-center analysis of 315 patients. Cost data were taken from the British National Formulary and National Health Service reference costs and reported in 2014 pounds sterling. RESULTS: Modeling results showed that improved adherence would be associated with reduced incidence of AbMR and graft failure in renal transplant recipients. Based on improvements in adherence resulting from switching from twice-daily to once-daily tacrolimus, the modeling analysis projected cost savings of GBP 4862 per patient over 5 years with Advagraf relative to Prograf, on absolute costs of GBP 40,974 and GBP 45,836, respectively. CONCLUSIONS: Using Advagraf in place of Prograf in renal transplant recipients was predicted to be associated with lower pharmacy, dialysis and AbMR treatment costs, with the reduction in AbMR and dialysis costs being driven by improved adherence to the Advagraf regimen and consequent reductions in graft failure and onset of AbMR.

Understanding the effects on HR-QoL of treatment for overactive bladder: a detailed analysis of EQ-5D clinical trial data for mirabegron.

BACKGROUND: Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB). DATA: Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4 mg was included as an active control in one study: (1) placebo, mirabegron 50 mg and 100 mg, and tolterodine 4 mg ER; (2) placebo, mirabegron 50 mg and 100 mg; (3) placebo, and mirabegron 25 mg and 50 mg. Data were collected at baseline, week 4, 8, and 12. METHODS: Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change. RESULTS: In modified ITT analyses, mirabegron 50 mg was superior to tolterodine 4 mg in changes from baseline utilities after 12 weeks (p < 0.05); similarly, AUC results showed mirabegron 50 mg to be superior to tolterodine (p < 0.05) and placebo (p < 0.05) with the benefit already apparent at 4 weeks (p < 0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms. CONCLUSION: Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4 mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.

Economic evaluation of maintenance treatment with tacrolimus 0.1% ointment in adults with moderate to severe atopic dermatitis.

BACKGROUND: Rational health care decision-making based on outcomes and economic evidence is essential to provide the best possible care for individual patients with atopic dermatitis (AD). OBJECTIVES: To describe treatment outcomes and to evaluate resource utilization and associated cost of maintenance use of tacrolimus ointment (MU) vs. standard use of tacrolimus ointment (SU) in adults with AD. METHODS: A pan-European, phase III multicentre randomized clinical trial was conducted. Patients with mild to severe AD were randomized to tacrolimus 0.1% ointment (MU) or vehicle (SU) twice per week for 12 months. Disease exacerbations were treated by using open-label tacrolimus 0.1% ointment twice daily. Resource utilization data were collected prospectively alongside the clinical trial. Costs of pooled resource data were determined using German unit cost data. Direct and indirect costs were considered from third party payer, patient and societal perspectives. RESULTS: All patients with moderate and severe AD were included in a subanalysis, 75 patients in the MU arm (57% moderately affected) and 59 patients in the SU arm (59% moderately affected). In patients with moderate AD, the number of disease exacerbations in the MU arm was 2.4 vs. 5.5 in the SU arm (P<0.001); in patients with severe AD corresponding figures were 2.3 vs. 7.4 (P<0.001), respectively. Mean+/-SD total annual cost per patient was euro1525+/-1081 (MU) vs. euro1729+/-1209 (SU) in patients with moderate AD and euro2045+/-2013 (MU) vs. euro2904+/-1510 (SU) in patients with severe AD. CONCLUSIONS: Maintenance treatment with 0.1% tacrolimus ointment is more effective and leads to cost savings and improved health-related quality of life in comparison with standard use of 0.1% tacrolimus ointment, especially in patients with severe AD.

Economic analysis of micafungin versus liposomal amphotericin B for treatment of candidaemia and invasive candidiasis in Germany.

OBJECTIVE: To investigate the economic impact of micafungin (MICA) for treatment of invasive candidiasis and candidaemia (systemic Candida infections), a health economic analysis was conducted comparing MICA with liposomal amphotericin B (L-AMB). RESEARCH DESIGN AND METHODS: The model was based on a phase III, randomised, double-blind, clinical trial which compared MICA with L-AMB. The model entailed a period of 14-20 weeks starting from initiation of treatment and was analysed from a German hospital perspective. MAIN OUTCOME MEASURES: The main outcome measures were defined as the percentage of patients achieving clinical and mycological response after initial treatment and who were alive at the end of the study (EOS), and the total treatment-associated costs over the study period. RESULTS: The health economic analysis shows that with MICA, 52.9% of patients are successfully treated and were alive at EOS compared to 49.1% for L-AMB. In addition, MICA has, on average, lower treatment-associated costs than L-AMB with euro43 243 and euro49 216 per patient, respectively. Because the costs are lower and the effectiveness is higher for MICA in comparison with L-AMB, MICA is more cost-effective than L-AMB. However, the results of the probabilistic sensitivity analysis show that the differences cannot be considered significant due to a large variance, although MICA remained the most cost-effective option throughout the one-way sensitivity analyses. CONCLUSIONS: The lower costs and higher effectiveness reported for MICA versus L-AMB in this analysis indicate that MICA may be a more cost-effective therapy in the treatment of invasive candidiasis and candidaemia when compared with L-AMB.

Epidemiology, prescribing patterns and resource use associated with overactive bladder in UK primary care.

This study aimed to estimate the incidence and prevalence of overactive bladder (OAB) symptoms in the UK and analyse the use of anticholinergic/antispasmodic medications and other healthcare resources within UK general practice. Patients with a record of urinary frequency, urgency, nocturia, urge incontinence or irritable/unstable bladder between 1987 and 2004 were identified from the General Practice Research Database. Demographic characteristics, referrals, consultations, investigations and prescriptions for medications licensed for use in OAB were identified. Regression analyses were used to identify the factors determining switches between medications, referrals and use of healthcare resources. The overall prevalence of OAB-related symptoms was 3.87 per 1000 persons, with an incidence of 2.79 per 1000 person-years. Among 68,910 patients with OAB symptoms, 19,444 (28.2%) received anticholinergic medication, of whom 14,454 (74.3%) received one drug and 4055 (20.9%) received two medications sequentially. Overall, 59.1% of patients were referred to relevant secondary care specialities, 2.8% underwent urinary tests/investigations in primary care and 0.2% were seen by a continence nurse. Resource use was higher among patients who tried several different medications. In conclusion, this study suggests that OAB may be under-diagnosed in the UK and that current guidelines recommending use of anticholinergic medication, continence nurse consultations and urinary tests/investigations are inadequately followed.