Identifying value arguments and deployment avenues of primary care innovations using a deliberative multidimensional approach.

Context: The increasing pressure on primary care services calls for efficient approaches to assess the potential value of innovations and identify facilitators to their deployment in local contexts. Objective: To explore the value arguments of innovations in primary care identified as promising during Quebec College of Family Physicians' Symposia on Innovations and to propose avenues for their improvement and deployment. Methods: Ten innovations were selected using their ranking at the Symposia and pre-established criteria to ensure diversity. An evidence-informed multidimensional deliberative approach (clinical, populational, economic, organizational and sociocultural dimensions) was applied by a panel of 12 clinicians, managers, patients and citizens. Using data synthesized by dimension, each participant identified arguments on the value of each innovation and appraised them on a numerical scale. The arguments were discussed by the group, and a qualitative analysis with inter-rater validation of the deliberation was performed and the mean appraisal scores at the group level were calculated. These qualitative and quantitative data were synthesized and used as a basis for a second discussion with the group during which avenues for deployment were organized by thematic analysis. Results: Innovations fell into three categories: support for clinical processes (n=5), adaptation of the organization of care to vulnerable populations (n=3), and support for quality improvement (n=2). Innovations aiming at adapting the organization of care for vulnerable populations were considered of highest value overall. Quality improvement innovations received mixed appraisals and needed to be further developed in terms of their value proposition and organizational fit. Innovations to support clinical processes also received mixed appraisals; proposals for further development included keeping them up to date and integrating them with information systems. Conclusions: This study highlights the factors that influence the value of certain categories of primary care innovations as well as avenues for their improvement and implementation that can guide innovators. This work demonstrates that exploring complex innovations with a multidimensional deliberative approach including patients and citizens is useful to identify their value arguments from a comprehensive standpoint, which is essential to identify the best implementation avenues to optimize the creation of value in real life.

Economic benefits of subcutaneous rapid push versus intravenous immunoglobulin infusion therapy in adult patients with primary immune deficiency.

OBJECTIVE: The objective of this study is to evaluate the economic benefits of immunoglobulin replacement therapy achieved subcutaneously (subcutaneous immunoglobulin, SCIG) by the rapid push method compared to intravenous infusion therapy (intravenous immunoglobulin, IVIG) in primary immune deficiency (PID) patients from the healthcare system perspective in the context of the adult SCIG home infusion program based at St Paul's Hospital, Vancouver, Canada. MATERIALS AND METHODS: SCIG and IVIG options were compared in cost-minimisation and budget impact models (BIMs) over 3 years. Sensitivity analyses were performed for both models to evaluate the impact of varying modality of IVIG treatments and proportion of patients switching from IVIG to SCIG. RESULTS: The cost-minimisation model estimated that SCIG treatment reduced cost to the healthcare system per patient of $5736 over 3 years, principally because of less use of hospital personnel. This figure varied between $5035 and $8739 depending on modality of IVIG therapy. Assuming 50% of patients receiving IVIG switched to SCIG, the BIM estimated cost savings for the first 3 years at $1·308 million or 37% of the personnel and supply budget. These figures varied between $1·148 million and $2·454 million (36 and 42%) with varying modalities of IVIG therapy. If 75% of patients switched to SCIG, the reduced costs reached $1·962 million or 56% of total budget. CONCLUSION: This study demonstrated that from the health system perspective, rapid push home-based SCIG was less costly than hospital-based IVIG for immunoglobulin replacement therapy in adult PID patients in the Canadian context.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Inhibition of polyphenol oxidase by copper-metallothionein from Aspergillus niger.

Metallothionein from Aspergillus niger was found to be an inhibitor, in a model system, for the enzymic activity of a commercially purified mushroom tyrosinase. The inhibitory effect of metallothionein was higher on catechin oxidation compared with that on chlorogenic acid. The degree of inhibition of enzymic colour formation by metallothionein, using catechin as substrate, was lower than that of oxygen uptake; however, a reverse pattern was observed with chlorogenic acid as substrate. The demetallization of metallothionein did not increase its inhibitory effect on polyphenol oxidase whereas pre-incubation of the enzyme and metallothionein increased this inhibitory effect.

Economic evaluation of high-dose (80 mg/day) atorvastatin treatment compared with standard-dose (20 mg/day to 40 mg/day) simvastatin treatment in Canada based on the Incremental Decrease in End-Points Through Aggressive Lipid-Lowering (IDEAL) trial.

BACKGROUND: The Incremental Decrease in End-Points Through Aggressive Lipid-Lowering (IDEAL) trial demonstrated incremental cardiovascular benefit of treatment with high-dose atorvastatin (80 mg/ day) versus standard-dose simvastatin (20 mg/day to 40 mg/day) in 8888 patients with a previous myocardial infarction (MI) over a median follow-up period of 4.8 years. OBJECTIVES: To assess the cost-effectiveness of high-dose atorvastatin versus standard-dose simvastatin treatment in patients with a history of MI from a Canadian societal perspective. METHODS: In a within-trial analysis, end point-related events, resources used and productivity losses occurring during the IDEAL trial were aggregated by treatment arm on an intention-to-treat basis to calculate the incremental cost per event avoided. Additionally, quality-adjusted survival was projected using a lifetime Markov model. Transition probabilities, workdays lost, use of study medication and cardiovascular hospitalization rates were based on IDEAL trial data. Hospitalization, study medication and productivity costs were included. Probabilistic and deterministic sensitivity analyses were performed. RESULTS: Compared with standard-dose simvastatin, atorvastatin 80 mg led to 0.099 fewer events per patient and cost savings over 4.8 years of treatment. Over a lifetime horizon, atorvastatin 80 mg led to 0.023 qualityadjusted life years (QALYs) gained per patient at an incremental cost of $26,795/QALY gained. The incremental cost-effectiveness ratio remained below $50,000/QALY in 78% of 1000 simulations. Exclusion of indirect costs resulted in an incremental cost-effectiveness ratio of $38,834/QALY. Results were relatively sensitive to baseline age, but robust with respect to sex, baseline low-density lipoprotein cholesterol levels, diabetes status and hospitalization costs. CONCLUSION: From a Canadian societal perspective, high-dose atorvastatin is cost-effective compared with standard-dose simvastatin in patients with a previous MI.

Towards a European consensus on conducting and reporting health economic evaluations--a report from the ISPOR Inaugural European Conference.

This report is a summary of key issues in consensus development regarding the conduct and reporting of health economic research in the European context, presented and discussed at the ISPOR Inaugural European Conference in Cologne, Germany, December 1998. Recommendations of the Harmonization by Consensus of the Methodology for Economic Evaluation of Health Care Technologies in the European Union (HARMET) project were presented, as well as two instruments under development: software for Reporting Economic Evaluation Results (REER) and software for collecting and managing cost data called the Health Cost Database Software (HCDS). Working independently, but interrelated with the objectives of the HARMET initiative, preliminary results from the ongoing European Network on Methodology and Application of Economic Evaluation Techniques (EUROMET) project were presented. Each presentation was followed by an expert discussion panel with audience participation. Issues raised included the development of standards and related topics such as usefulness to European decision-makers, and education and training in health economics in Europe.

Purification and characterization of copper-metallothionein from Aspergillus niger by affinity chromatography.

Biomass of Aspergillus niger was obtained from a microbial culture and a copper (Cu) induction was performed after 72 h of fermentation. The crude induced metallothionein extract was obtained by cell disruption and partly purified by a heat treatment and ultrafiltration. The purification of metallothionein by affinity chromatography resulted in three major fractions: FIVa, FIVb and FIVc3. Cu analysis demonstrated that only fraction FIVc contained the Cu-metallothionein. Spectrophotometric analyses of FIVc demonstrated the presence of a peak at 259 nm and a ratio of 78 mol of Cu per mol of protein. Electrophoretic analyses of FIVc, performed under denaturing conditions, showed the presence of one band with molecular mass of 21 kDa; however, two isoforms were observed under native conditions with molecular masses of 9.5 and 10.5 kDa and isoelectric points of 6.2 and 6.5, suggesting a recombination process due to denaturation.