A comprehensive review of economic evaluations of therapeutic drug monitoring interventions for cancer treatments.

Therapeutic drug monitoring (TDM) of cancer drugs has been shown to improve treatment effectiveness and safety. The aim of this paper was to comprehensively review economic evaluations of TDM interventions for cancer drugs. Searches were conducted in 4 electronic databases, Medline, EMBASE, and Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects and the NHS Economic Evaluation Database), from their inception to June 2019. Studies were included if they were economic evaluations of TDM interventions for an active cancer treatment. The quality of reporting of economic evaluations was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS checklist). Of the 11 publications identified, imatinib with TDM and 5-fluorouracil with TDM were the most commonly assessed interventions (4 publications each). Overall study quality was good, with publications meeting 61 to 91% (median 80%) of CHEERS checklist criteria. A variety of studies were used to estimate the clinical effectiveness inputs for the cost effectiveness models. All publications considered TDM to be cost-effective based on an incremental cost-effectiveness ratio below the willingness to pay threshold (64%) or being cost-saving (36%). TDM interventions were considered cost-effective across the economic evaluations. Further clinical research assessing the impact of TDM on overall survival or other long-term health outcomes may enhance the evidence base for TDM in oncology. Future economic evaluations of TDM should explicitly consider uncertainty in the underlying clinical evidence and incorporate changes in the use of newer targeted drugs that form the current standard of care.

Use of clinical vignette questionnaires to investigate the variation in management of keratoconjunctivitis sicca and acute glaucoma in dogs.

There is little peer-reviewed research assessing therapeutic effectiveness in canine eye disease. Current treatments used in first opinion and ophthalmology referral practices are also somewhat poorly documented. The aim of this study was to investigate the current management of canine keratoconjunctivitis sicca (KCS) and acute primary angle-closure glaucoma (PACG) by veterinary surgeons. Questionnaires using clinical vignettes were administered to a cross section of general practitioners ('GPs') and veterinarians engaged in or training for postgraduate ophthalmology practice ('PGs'). Similar treatment recommendations for KCS (topical cyclosporine, lubricant, antibiotic) were given by both groups of veterinarians with the single exception of increased topical antibiotic use by GPs. Treatment of acute glaucoma diverged between groups: PGs were much more likely to recommend topical prostaglandin analogues and a wider array of both topical and systemic treatments were recommended by both groups. Systemic ocular hypotensive agents were suggested infrequently. Our results suggest that treatments may vary substantially in ocular conditions, particularly in conditions for which neither guidelines nor high-quality evidence exists. This study highlights the need for novel strategies to address evidence gaps in veterinary medicine, as well as for better evaluation and dissemination of current treatment experience.

The cost-effectiveness of oral health interventions: A systematic review of cost-utility analyses.

OBJECTIVES: To assess the usage of cost-utility analysis (CUA) in oral health interventions and to evaluate the methods used and the reporting quality of CUA in publications on oral health interventions. METHODS: A systematic review was performed on literature published between 2000 and 2016 where cost-utility analyses of oral health interventions were included. The reporting quality of these oral health CUAs was assessed against the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Of the 6637 publications identified initially, 23 met the inclusion criteria. Of these, 14 (61%) had been published in the last 6 years. Included studies were on oral cancer (n = 6), provision of dental prosthesis (n = 6), dental caries (n = 4), periodontal diseases (n = 3), antibiotic prophylaxis (n = 2), dento-facial anomalies (n = 1) and dental service provision (n = 1). Twenty-one studies were able to identify the most cost-effective intervention among the different options compared. Of the 23 studies identified, 15 (65%) used quality-adjusted life years (QALY) as the outcome measure, and 18 (78%) reported an incremental cost-effectiveness ratio. The economic perspective was clearly stated in 13 articles (57%). Twenty studies (87%) reported the discount rate, and 22 (96%) undertook sensitivity analysis. The reporting quality of studies, appraised by the CHEERS checklist, varied from 75% to 100% (median 92%). CONCLUSION: The use of CUAs in evaluation of oral health interventions has been increasing recently, especially from 2011 to 2016. The majority of CUA articles were of good reporting quality as assessed by the CHEERS checklist and were able to provide conclusions regarding the most cost-effective intervention among the different options compared: this will assist in healthcare decision-making and resource allocation. These positive outcomes of our study encourage wider use of CUAs within the dental and oral health professions.

Understanding the context for pet cat and dog feeding and exercising behaviour among pet owners in Ireland: a qualitative study.

BACKGROUND: Pet cat and dog obesity contributes to increased risk of several diseases, including cancer and diabetes mellitus as well as a worsening of orthopaedic problems, and a reduction in survival rate. This study aims to develop a better understanding of cat and dog owners' self-reported beliefs and factors that influence owner behaviour around feeding and exercising their pet cat or dog, as there is a lack of in-depth understanding in this area. Seven focus group discussions, with 43 pet owners in total, were conducted. RESULTS: Pet owners often reported a perceived a low level of control over feeding; often undermined by other people feeding of their pet, their pets begging for food, and their pets attitude towards food. Treats were used in the absence of owner control over pet begging and emotional attachment, and to influence pet behaviour. The majority of participants had positive attitudes to pet exercise, which could be related to pet specific requirements, especially differences in cats and dogs. There were some negative experiences of stress associated with dog walking and fears over aggressive confrontations with other dogs. CONCLUSION: Feeding one's pet is influenced by beliefs about pet specific needs, pet food and pet health, pet owners' perceived control over feeding, and the implications for the pet owner. Pet exercise is influenced by beliefs about pet specific exercise needs, and the implications of exercising one's pet for the pet owner. Understanding owner behaviours on feeding and exercise allows for a more targeted approach to preventing and treating pet obesity.

Cost-effectiveness of dual-energy X-ray absorptiometry plus antiresorptive treatment in Australian women with breast cancer who receive aromatase inhibitors.

Postmenopausal women with breast cancer on aromatase inhibitor (AI) treatment are at increased risk of bone mineral density loss, which may lead to minimal trauma fractures. We examined the cost-effectiveness of dual energy X-ray absorptiometry (DXA) with antiresorptive (AR) therapy compared with fracture risk assessment, lifestyle advice, and vitamin supplementation. We used a hypothetical Markov cohort model of lifetime duration for 60-year-old women with early stage breast cancer receiving AIs. The data to inform the model came from medical literature, epidemiological reports, and costing data sets. Two eligibility scenarios for AR therapy were considered: (A) osteoporosis and (B) osteopenia or osteoporosis. The main outcomes were incremental cost per quality-adjusted life years gained and cumulative fractures per 1000 women, calculated relative to the comparator. Key aspects of the model were explored in sensitivity analyses. Due to relatively low effectiveness gains, the outcomes were primarily driven by the costs. The incremental cost per quality-adjusted life year gained was A$47,556 and A$253,000 for scenarios A and B, respectively. The numbers of fractures avoided were 56 and 77 per 1000 women, respectively. The results were most sensitive to the initial probability of osteoporosis, baseline risk of fracture, and cohort starting age. Compared with risk assessment and lifestyle advice only, a DXA scan followed by an AR treatment is potentially cost-effective for women aged 60 and over undergoing AI therapy for early breast cancer. However, the number of fractures averted through this intervention is small.

Comprehensive environmental management of asthma and pediatric preventive care.

Indoor environmental triggers can increase asthma morbidity. National guidelines recommend comprehensive use of environmental control practices (ECPs) as a component of asthma management. The purpose of this study was to examine the association between preventive asthma care and comprehensive ECP use among children with asthma. We used data from the National Asthma Survey, including 1,921 children with asthma. Comprehensive use was defined as using at least five of eight ECPs: (i) air filter, (ii) dehumidifier, (iii) mattress cover, (iv) pillow cover, (v) pet avoidance, (vi) smoke avoidance, (vii) removing carpets, and (viii) washing sheets in hot water. Univariate and multiple regression analyses were conducted to examine the association between comprehensive use of ECPs and receipt of preventive asthma care, as measured by number of routine asthma visits in the prior year and physician advice to modify the environment. Overall, 17% (95% CI: 14-19%) of participants had comprehensive ECP use. The most commonly used practices were 'smoke avoidance' (85%), 'pet avoidance' (59%), and 'washing sheets in hot water' (46%). Comprehensive use of ECPs was associated with having received physician advice [odds ratio (OR) 3.1, 95% CI: 2.2-4.4] and increased asthma visits (1-2 visits: OR 1.5, 95% CI: 1.0-2.4; 3-4 visits: OR 2.2, 95% CI: 1.3-3.8; ≥5 visits: OR 2.7, 95% CI: 1.5-4.8). Only a minority of parents implement comprehensive ECPs, and receipt of preventive asthma care is associated with comprehensive use. Further research is needed to determine the factors mediating these associations in order to inform more effective asthma counseling.

Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition.