Wendy J. Ungar

Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses.

BACKGROUND & AIMS The relative efficacies of licensed antiviral therapies for treatment-naive chronic hepatitis B (CHB) infection in randomized controlled trials have not been determined. We evaluated the relative efficacies of the first 12 months of CHB treatments. METHODS Drugs evaluated were lamivudine, pegylated interferon, adefovir, entecavir, telbivudine, and tenofovir, as monotherapies and combination therapies, in treatment-naive individuals. Databases were searched for randomized controlled trials of the first 12 months of therapy in hepatitis B e antigen (HBeAg)-positive and/or HBeAg-negative patients with CHB published in English before October 31, 2009. Bayesian mixed treatment comparisons were used to calculate the odds ratios, including 95% credible intervals and predicted probabilities of surrogate outcomes to determine the relative effects of each treatment. RESULTS In HBeAg-positive patients, tenofovir was most effective in inducing undetectable levels of HBV DNA (predicted probability, 88%), normalization of alanine aminotransferase (ALT) levels (66%), HBeAg seroconversion (20%), and hepatitis B surface antigen loss (5%); it ranked third in histologic improvement of the liver (53%). Entecavir was most effective in improving liver histology (56%), second for inducing undetectable levels of HBV DNA (61%) and normalization of ALT levels (70%), and third in loss of hepatitis B surface antigen (1%). In HBeAg-negative patients, tenofovir was the most effective in inducing undetectable levels of HBV DNA (94%) and improving liver histology (65%); it ranked second for normalization of ALT levels (73%). CONCLUSIONS In the first year of treatment for CHB, tenofovir and entecavir are the most potent oral antiviral agents for HBeAg-positive patients; tenofovir is most effective for HBeAg-negative patients.

Acute Appendicitis in Young Children: Cost-effectiveness of US versus CT in Diagnosis—A Markov Decision Analytic Model

PURPOSE To compare the cost-effectiveness of different imaging strategies in the diagnosis of pediatric appendicitis by using a decision analytic model. MATERIALS AND METHODS Approval for this retrospective study based on literature review was not required by the institutional Research Ethics Board. A Markov decision model was constructed by using costs, utilities, and probabilities from the literature. The risk of radiation-induced cancer was modeled by using the Biological Effects of Ionizing Radiation VII report, which is based primarily on data from atomic bomb survivors. The three imaging strategies were ultrasonography (US), computed tomography (CT), and US followed by CT if the initial US study was negative. The model simulated the short-term and long-term outcomes of the patients, calculating the average quality-adjusted life span and health care costs. RESULTS For a single abdominal CT study in a 5-year-old child, the lifetime risk of radiation-induced cancer would be 26.1 per 100,000 in female and 20.4 per 100,000 in male patients. In the base-case analysis, US followed by CT was the most costly and most effective strategy, CT was the second-most costly and second-most effective strategy, and US was the least costly and least effective strategy. The incremental cost-effectiveness ratios (ICERs) of CT to US and of US followed by CT to US were both well below the societal willingness-to-pay threshold of

A Randomized Controlled Trial of Laparoscopic Nissen Fundoplication Versus Proton Pump Inhibitors for Treatment of Patients With Chronic Gastroesophageal Reflux Disease: One-Year Follow-Up

50,000 (in U.S. dollars). The ICER of US followed by CT to CT was less than

Valuing Patient and Caregiver Time A Review of the Literature

10,000 in both male and female patients. CONCLUSION In a Markov-based decision model of pediatric appendicitis, the most cost-effective method of imaging pediatric appendicitis was to start with a US study and follow each negative US study with a CT examination.

Challenges in health state valuation in paediatric economic evaluation: are QALYs contraindicated?

A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year.

Measuring productivity loss days in asthma patients

As healthcare expenditures continue to rise, financial pressures have resulted in a desire for countries to shift resources away from traditional areas of spending. The consequent devolution and reform have resulted in increased care being provided and received within homes and communities, and in an increased reliance on unpaid caregivers. Recent empirical work indicates that costs incurred by care recipients and unpaid caregivers, including time and productivity costs, often account for significant proportions of total healthcare expenditures. However, many economic evaluations do not include these costs. Moreover, when indirect costs are assessed, the methods of valuation are inconsistent and frequently controversial.This paper provides an overview and critique of existing valuation methods. Current methods such as the human capital method, friction cost method and the Washington Panel approach are presented and critiqued according to criteria such as potential for inaccuracy, ease of application, and ethical and distributional concerns. The review illustrates the depth to which the methods have been theoretically examined, and highlights a paucity of research on costs that accrue to unpaid caregivers and a lack of research on time lost from unpaid labour and leisure. To ensure accurate and concise reporting of all time costs, it is concluded that a broad conceptual approach for time costing should be developed that draws on and then expands upon theoretical work to date.

Socioeconomic factors and asthma control in children.

With the growth in the use of health economic evaluation to inform healthcare resource allocation decisions, the challenges in applying standard methods to child health have become apparent.Aunique limitation is the paucity of childspecific preference-based measures. A single, valid, preference-based measure of utility that can be used in children of all ages does not exist. Thus, the ability to derive a QALY for use in cost-utility analysis (CUA) is compromised. This paper presents and discusses existing and novel options for deriving utilities for paediatric health states for use in CUAs.While a direct elicitation may be preferred, a child’s ability to complete a standard gamble or time trade-off task is hampered by cognitive and age limitations. The abstract notions contained in indirect instruments such as the EQ-5D and Health Utilities Index may also pose challenges for young children. Novel approaches to overcome these challenges include the development of age-appropriate instruments such as the EQ-5D-Y, the development of new child-specific utility instruments such as the Child Health Utility-9D and the re-calibration of existing adult instruments to derive preference weights for health states from children themselves. For children aged <6 years, researchers have little choice but to use a proxy reporter such as parents. While parents may be reliable reporters for physical activity limitations and externally manifest symptoms, their ability to accurately report on subjective outcomes such as emotion is questionable. Catalogues of utility weights for a range of conditions are increasingly becoming available but retain many of the same limitations as valuing health states from children or from proxies.Given the dynamic relationship in quality of life (QOL) between family members when a child is ill, it seems appropriate to consider a family perspective rather than an individual perspective in child health state valuation. In a collective approach, health state utilities derived from multiple family members may be combined mathematically. Alternatively, in a unitary approach, a single utility estimate may be determined to represent the familys perspective. This may include deriving utilities through parent-child dyad estimation or by using a household model that combines the utility weights of the patient and family members, incorporating reciprocal QOL effects.While these various approaches to child health state valuation represent novel research developments, the measurement challenges and threats to validity persist. Given the importance of non-health benefits to child health, especially in the domains of education and public policy, it may be worthwhile to consider an approach that allows incorporation of externalities to produce a cost-benefit analysis. The use of discrete-choice methods to assess willingness to pay for novel child health interventions holds promise as a means to produce meaningful economic evidence.Regardless of the approach taken, the highest degree of methodological rigour is essential. The increasing attention being paid by health economic researchers to the measurement challenges of paediatric health state valuation can only increase the value of child health economic evidence for decision making.

Effect of Oximetry on Hospitalization in Bronchiolitis A Randomized Clinical Trial

In assessments of the cost of illness, productivity losses potentially constitute a large proportion. The present study objective was to develop a method to measure restricted days and to quantify total productivity loss days (PLDs) in adult asthma patients. Patient and disease characteristics, occupation, annual wage, work absences, restricted days, level of functioning on restricted days, and travel and waiting time were collected over 6 months in 892 adult asthma outpatients residing in southern Ontario. Annual PLDs varied from 12 in employed persons to 49 in disability pensioners. Homemakers reported 22 PLDs per year. Restricted days accounted for most PLDs and functional level during restricted days varied from 55% to 81%. Annual PLDs increased with increasing disease severity. Employed persons experienced the fewest PLDs and functioned at the highest level during restricted days, but also demonstrated a milder disease compared with other groups. Most productivity loss in asthma patients resulted from numerous restricted days, a category of PLD that is often ignored in economic assessments. The presentation of PLD results disaggregated by category of time loss and wage rate may provide valuable information to employers and health policy makers and may facilitate the application of multiple approaches to the calculation of indirect costs. Copyright

Reflections on the Cost of "Low-Cost" Whole Genome Sequencing: Framing the Health Policy Debate

The objective of this study was to evaluate the association between socioeconomic factors and asthma control in children, as defined by the Canadian Pediatric Asthma Consensus Guidelines.

Health Services Utilization Reporting in Respiratory Patients

IMPORTANCE Routine use of pulse oximetry has been associated with changes in bronchiolitis management and may have lowered the hospitalization threshold for patients with bronchiolitis. OBJECTIVE To examine if infants with bronchiolitis whose displayed oximetry measurements have been artificially elevated 3 percentage points above true values experience hospitalization rates at least 15% lower compared with infants with true values displayed. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, parallel-group trial conducted from 2008 to 2013 in a tertiary-care pediatric emergency department in Toronto, Ontario, Canada. Participants were 213 otherwise healthy infants aged 4 weeks to 12 months with mild to moderate bronchiolitis and true oxygen saturations of 88% or higher. INTERVENTIONS Pulse oximetry measurements with true saturation values displayed or with altered saturation values displayed that have been increased 3 percentage points above true values. MAIN OUTCOMES AND MEASURES The primary outcome was hospitalization within 72 hours, defined as inpatient admission within this interval or active hospital care for greater than 6 hours. Secondary outcomes included the use of supplemental oxygen in the emergency department, level of physician agreement with discharge from the emergency department, length of emergency department stay, and unscheduled visits for bronchiolitis within 72 hours. RESULTS Forty-four of 108 patients (41%) in the true oximetry group and 26 of 105 (25%) in the altered oximetry group were hospitalized within 72 hours (difference, 16% [95% CI for the difference, 3.6% to 28.4%]; P = .005). Using the emergency department physician as a random effect, the primary treatment effect remained significant (adjusted odds ratio, 4.0 [95% CI, 1.6 to 10.5]; P = .009). None of the secondary outcomes were significantly different between the groups. There were 23 of 108 (21.3%) subsequent unscheduled medical visits for bronchiolitis in the true oximetry group and 15 of 105 (14.3%) in the altered oximetry group (difference, 7% [95% CI, -0.3% to 0.2%]; P = .18). CONCLUSIONS AND RELEVANCE Among infants presenting to an emergency department with mild to moderate bronchiolitis, those with an artificially elevated pulse oximetry reading were less likely to be hospitalized within 72 hours or to receive active hospital care for more than 6 hours than those with unaltered oximetry readings. This suggests that oxygen saturation should not be the only factor in the decision to admit, and its use may need to be reevaluated. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00673946.