Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay.

OBJECTIVE: To establish breakpoint concentrations for the fluoroquinolones (moxifloxacin [MFX] and ofloxacin [OFX]) and injectable second-line drugs (amikacin [AMK], kanamycin [KM] and capreomycin [CPM]) using the microscopic observation drug susceptibility (MODS) assay. SETTING: A multinational study conducted between February 2011 and August 2012 in Peru, India, Moldova and South Africa. DESIGN: In the first phase, breakpoints for the fluoroquinolones and injectable second-line drugs (n = 58) were determined. In the second phase, MODS second-line drug susceptibility testing (DST) as an indirect test was compared to MGIT™ DST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS second-line DST directly from sputum. RESULTS: Breakpoints for MFX (0.5 µg/ml), OFX (1 µg/ml), AMK (2 µg/ml), KM (5 µg/ml) and CPM (2.5 µg/ml) were determined. In all phases, MODS results were highly concordant with MGIT DST. The few discrepancies suggest that the MODS breakpoint concentrations for some drugs may be too low. CONCLUSION: MODS second-line DST yielded comparable results to MGIT second-line DST, and is thus a promising alternative. Further studies are needed to confirm the accuracy of the drug breakpoints and the reliability of MODS second-line DST as a direct test.

The Medicaid Rx model: pharmacy-based risk adjustment for public programs.

BACKGROUND: Risk adjustment models typically use diagnoses from claims or encounter records to assess illness severity. However, concerns about the availability and reliability of diagnostic data raise the potential for alternative methods of risk adjustment. Here, we explore the use of pharmacy data as an alternative or complement to diagnostic data in risk adjustment. OBJECTIVES: To develop and test a pharmacy-based risk adjustment model for SSI and TANF Medicaid populations. RESEARCH DESIGN: Pharmacological review combined with empirical evaluation. We developed the Medicaid Rx model, a system that classifies a subset of the National Drug Codes into categories that can be used for risk-assessment and risk-adjusted payment. SUBJECTS: Subjects consisted of 362,370 persons with disability and 1.5 million AFDC and TANF beneficiaries in California, Colorado, Georgia, and Tennessee during 1990-1999. MEASURES: We compare pharmacy and diagnostic classification for three chronic diseases. We also compare R2 statistics and use simulated health plans to evaluate the performance of alternative models. RESULTS: Pharmacy and diagnostic classification vary in their ability to identify specific chronic disease. Using simulated plans, diagnostic models are better at predicting expenditures than are pharmacy-based models for disabled Medicaid beneficiaries, although the models perform similarly for TANF Medicaid beneficiaries. Models that combine diagnostic and pharmacy data have superior overall performance. CONCLUSIONS: The performance of risk adjustment models using a combination of pharmacy and diagnostic data are superior to that of models using either data source alone, particularly among TANF beneficiaries. Concerns regarding variations in prescribing patterns and the incentives that may follow from linking payment to pharmacy use warrant further research.

Assessing the impact of migraine on health-related quality of life: An additional use of the quality of well-being scale-self-administered.

OBJECTIVES: To compare the interviewer-administered Quality of Well-being Scale (QWB) with a self-administered form (QWB-SA) for patients with migraine, and to compare the health status of migraineurs to other medical populations. BACKGROUND: With the increasing need to document the cost-effectiveness of treatment for migraine, limitations with both the Medical Outcomes Study Short Form-36 items and the QWB have been an impediment to research using cost-effectiveness as an outcome. Demonstrating the sensitivity of an alternative instrument which addresses these limitations would facilitate cost-effectiveness analyses on treatments for migraine. METHODS: Eighty-nine adults (87% women) known to suffer from migraine were asked to complete both the interviewer-administered QWB and the self-administered version (QWB-SA) on three occasions. The first occasion was on a day when no migraine was experienced in the previous 7 days. The second and third assessments were completed within 48 hours of the onset of a migraine. RESULTS: While both the QWB and the QWB-SA successfully distinguished migraine from nonmigraine days, more migraines were reported on the QWB-SA. Overall, both instruments showed similar patterns of patient dysfunction during a migraine attack. Each component of the QWB-SA successfully distinguished migraine from nonmigraine days, and the QWB-SA showed a linear sensitivity to pain intensity and disability during a migraine episode. Both instruments are able to detect a migraine's effect on multiple domains of quality of life. Study participants scored significantly lower on the QWB-SA during a migraine episode than several comparison medical populations. CONCLUSIONS: The QWB and the QWB-SA appear to have sensitivity to migraine severity, and the ability to quantitate an effect in multiple quality-of-life domains. Both measures can be used to calculate quality-adjusted life-years, thus facilitating cost-effectiveness and health policy work in this important clinical area.

Population-based time preferences for future health outcomes.

CONTEXT: Time preference (how preference for an outcome changes depending on when the outcome occurs) affects clinical decisions, but little is known about determinants of time preferences in clinical settings. OBJECTIVES: To determine whether information about mean population time preferences for specific health states can be easily assessed, whether mean time preferences are constant across different diseases, and whether under certain circumstances substantial fractions of the patient population make choices that are consistent with a negative time preference. DESIGN: Self-administered survey. SETTING: Family physician waiting rooms in four states. PATIENTS: A convenience sample of 169 adults. INTERVENTION: Subjects were presented five clinical vignettes. For each vignette the subject chose between interventions maximizing a present and a future health outcome. The options for individual vignettes varied among the patients so that a distribution of responses was obtained across the population of patients. MAIN OUTCOME MEASURE: Logistic regression was used to estimate the mean preference for each vignette, which was translated into an implicit discount rate for this group of patients. RESULTS: There were marked differences in time preferences for future health outcomes based on the five vignettes, ranging from a negative to a high positive (116%) discount rate. CONCLUSIONS: The study provides empirical evidence that time preferences for future health outcomes may vary substantially among disease conditions. This is likely because the vignettes evoked different rationales for time preferences. Time preference is a critical element in patient decision making and cost-effectiveness research, and more work is necessary to improve our understanding of patient preferences for future health outcomes.

Controlling blood glucose levels in patients with type 2 diabetes mellitus. An evidence-based policy statement by the American Academy of Family Physicians and American Diabetes Association.

OBJECTIVE: To review evidence about the benefit of intensive glycemic control for patients with type 2 diabetes and to develop practice recommendations. PARTICIPANTS: A 9-member panel composed of family physicians, general internists, endocrinologists, and a practice guidelines methodologist was assembled by the American Academy of Family Physicians, the American Diabetes Association, and the American College of Physicians. EVIDENCE: Admissible evidence included published randomized controlled trials and observational studies regarding the effects of glycemic control on microvascular and macrovascular complications and on adverse effects. We followed systematic search and data abstraction procedures. Greater weight was given to clinical trials and to evidence about health outcomes. CONSENSUS PROCESS: Interpretations of evidence and approval of documents were finalized by unanimous vote, with recommendations linked to evidence and not expert opinion. The full report was prepared by the chair and 2 panel members, representing each of the 3 organizations. The initial draft underwent external review by 14 diabetologists and family physicians and changes consistent with the evidence were incorporated. CONCLUSIONS: The evidence demonstrates that the risk of microvascular and neuropathic complications is reduced by lowering glucose concentrations. Whether glycemic control affects macrovascular outcomes is less clear. The potential benefits of glycemic control must be balanced against factors that either preempt benefits (eg, limited life expectancy, comorbid disease) or increase risk (eg, severe hypoglycemia). The magnitude of benefit is a function of individual clinical variables (eg, baseline glycated hemoglobin level, presence of preexisting microvascular disease). Appropriate targets for treatment should be determined by considering these factors, patients' risk profiles, and personal preferences.

What to do until the POEMs arrive. An endothelial example.

There is a growing trend toward evidence-based medicine, in which patient-oriented data are valued more highly than disease-oriented evidence (DOEs). In the vernacular of evidence-based medicine, the old DOEs are slowly being replaced by POEMs (patient-oriented evidence that matters). Unfortunately, POEMs do not yet exist to meet every family-practice need. When there are no POEMs to determine an appropriate therapeutic choice, another decision-making method must be used. This method includes liberal use of DOEs combined with thoughtful use of causal pathways to provide preliminary direction. This article applies that method to an example from the growing basic science surrounding endothelial functioning.

Epidemiological issues in perinatal outcomes research.

Outcomes research takes an expansive view of health and seeks to improve the science of evaluating the quality of health care by refining traditional clinical measures and including measures of overall patient well-being. This broader view of health (rather than disease) is especially appropriate in perinatal research. Attention to the perinatal period requires recognition that pregnancy is in most cases a healthy life event, that there is a predictable progression and time course with a key definable outcome (delivery) and that there are two patients, mother and infant. Two issues stand out as methodological challenges in the design and conduct of perinatal outcomes studies. The first is to establish baseline comparability across study groups with regard to case-mix or perinatal risk, and also comparability of services other than the one under study. The second is the refinement of traditional perinatal outcomes, such as low birthweight and Caesarean section, and the inclusion of patient-based health status measures, such as health-related quality of life, for the peripartum woman and her newborn.

Incremental cost-effectiveness analysis: the optimal strategy depends on the strategy set.

Evaluating the incremental cost-effectiveness of a technology is critical to understanding the impact of its adoption. The purpose of this study was to evaluate, using a particular example, how the specific alternatives selected for a cost-effectiveness analysis may influence the results of the analysis. In this example, we analyzed the incremental cost-effectiveness of estriol screening for Down syndrome. Model assumptions of expected costs and effectiveness were based on previously published work involving four clinical strategies, including a "do nothing" (no screening) strategy. When the analysis started with all four strategies, two of the strategies could not be considered cost-effective because of extended dominance. However, when we eliminated the "do nothing" from the strategy set because of its clinical irrelevance, all three remaining strategies might be considered cost-effective from a policy perspective. We concluded that the incremental cost-effectiveness of clinical strategies could be strongly affected by the starting point for the analysis.

Comparison of Quality of Well-Being scale and NYHA functional status classification in patients with atrial fibrillation. New York Heart Association.

BACKGROUND: There is an increased need to provide appropriate outcomes evaluations. Although designed as a clinical assessment tool, the New York Heart Association (NYHA) classification is often used as an outcome measure. In this study the performance of the NYHA classification is compared with that of the Quality of Well-being scale (QWB), a standard outcome instrument. METHODS: Subjects from a clinical trial were administered both the NYHA classification and the QWB. Scores for patients with NYHA classification I, II, and III were compared by use of an ordinal regression model. RESULTS: There were significant differences in mean QWB score by NYHA classification (p < 0.0001). However, each NYHA classification score was associated with a wide range of QWB scores, limiting the potential usefulness of the NYHA classification as an outcome measure. CONCLUSIONS: The NYHA classification is not a sensitive measure of health-related quality of life, and its use as an outcome measure, although providing some insights, may result in misleading findings. The NYHA classification should not be used as the sole outcome measure.

Ultrasound-guided liver biopsy for parenchymal liver disease: an economic analysis.

The use of ultrasound (US) to assist in liver biopsy for nonfocal liver disease has been shown to significantly decrease the incidence of minor complications (defined as pain requiring treatment, hypotension, or bleeding). In this study, decision analysis was used to estimate the average additional net charge for US guidance. The risks for minor and major complications were extracted from the literature. The incidence of minor complications such as pain and bleeding not requiring hospitalization has been reported as 49% for blind liver biopsy and 39% for US-guided liver biopsy. Major complications requiring hospital admission occur in 4% of blind liver biopsies and 2% of US-guided liver biopsies. A decision tree was used to calculate the total charges of liver biopsy and its associated complications. The charge for treating an episode of minor complications was estimated at $605. The charge related to an episode of major complications was estimated at $1533. The total charge for an ultrasound-guided liver biopsy (except the added charge for the use of ultrasound) was $1770, or $102 less than the same charge for blind liver biopsy. The addition of ultrasound in performing liver biopsies for diffuse parenchymal liver disease is cost-saving if the additional charge of US is less than $102.

The Quality of Well-Being Scale: critical similarities and differences with SF-36.

PURPOSE: To summarize the development and application of a generic measure of health-related quality of life known as the Quality of Well-Being Scale (QWB). BACKGROUND: The QWB is part of a general health policy model. The measure includes functional components for mobility, physical activity, and social activity. In addition, it includes a comprehensive list of symptoms and problems. QWB scoring allows placement of each individual on a continuum of wellness ranging from 0 (for dead) to 1.0 for asymptomatic full function. The General Health Policy Model combines this point in time measure with information on prognosis and mortality to estimate quality-adjusted life-years (QALYs). Forming a ratio of program costs to QALYs yields estimates of cost per quality-adjusted life year. Evidence supports the validity of the QWB for a wide variety of applications in population monitoring, descriptive studies of patient populations, and clinical trials. We offer a variety of comparisons between the QWB and Medical Outcomes Study Short Form 36 (SF-36). MAIN FINDINGS: In comparison with the SF-36, the QWB provides less information on health profiles, but has the advantage of providing a metric that can be used for cost-utility or cost-effectiveness analysis. Although ceiling effects are common for some SF-36 subscales, perfect scores on the QWB are very rare. The QWB has an approximately normal distribution for populations of adults. Although, often criticized for not including a mental health component, we present evidence documenting the validity of the QWB for patients with psychological and psychiatric diagnoses. CONCLUSIONS: The QWB and SF-36 are alternative comprehensive measures of health outcomes.

A spectrum of health policy methods: lessons from the British.

Two vignettes about two health care systems (actually, one system and one non-system). Two different cancer screening programs. Two different approaches to developing a national health policy. This is not an issue of money; either approach could be used inside any budget. One approach looks at the entire health care delivery system, trying to maximize gain while assuring appropriate care is provided. The other approach tries to get votes. Is there any doubt which is the better method?