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To analyze temporal patterns of antiretroviral (ARV) prescribing practices relative to nationally defined guidelines in treatment-naive patients with HIV-1 infection. DESIGN: Retrospective cohort study. METHODS: We evaluated ARV prescribing patterns among ARV treatment-naive veterans who were receiving care within the US Department of Veterans Affairs (VA) from 1992 through 2004 in comparison to evolving adult HIV-1 treatment guidelines. RESULTS: A total of 15,934 patients initiated ARV treatment. Since 1999, >94% of patients initiated at least a 3-ARV medication combination, although the percentage of patients who initiated a guideline "preferred" or "alternative" regimen never rose to greater than 72% and was significantly associated with being black and with region of care. After 1999, 20% of patients started 4 or more active ARV agents in combination, which was significantly associated with lower baseline CD4 cell count, higher viral load, and receiving care in the western United States. The proportion of patients receiving guideline "not recommended" regimens (virologically undesirable or overlapping toxicities) was <1% after 1997. VA prescribing trends generally predated guideline recommendations by 6 to 12 months. CONCLUSIONS: VA prescribing patterns for ARV initiation adhere to treatment guidelines that maximize safety. Guidelines designed to maximize efficacy were not followed as stringently. Evaluating clinical practice patterns against contemporary treatment guidelines can inform guideline development.

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JAIDS
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Mark Holodniy
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Background: This chapter of the guidelines is intended to provide an evidence-based assessment of the initial evaluation of patients recognized as having lung cancer and the recognition of paraneoplastic syndromes.

Methods: The current medical literature that is applicable to this issue was identified by a computerized search and was evaluated using standardized methods. Recommendations were framed using the approach described by the Health and Science Policy Committee of the American College of Chest Physicians.

Results: Patients with lung cancer usually present with multiple symptoms, both respiratory related and constitutional. There is usually a time delay between symptom recognition by the patient and the ultimate diagnosis of lung cancer by the physician. Whether this time delay impacts prognosis is unclear, but delivering timely and efficient care is an important component in its own right. Lung cancer may be accompanied by a variety of paraneoplastic syndromes. These syndromes may not necessarily preclude treatment with a curative intent.

Conclusions: The initial evaluation of the patient with known or suspected lung cancer should include an assessment of symptoms, signs, and laboratory test results in a standardized manner as a screen for identifying those patients with paraneoplastic syndromes and a higher likelihood of metastatic disease.

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Chest
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Background: As many as 10% of Asian and Pacific Islander adults in the United States are chronically infected with hepatitis B virus (HBV), and up to two thirds are unaware that they are infected. Without proper medical management and antiviral therapy, up to 25% of Asian and Pacific Islander persons with chronic HBV infection will die of liver disease.

Objective: To assess the cost-effectiveness of 4 HBV screening and vaccination programs for Asian and Pacific Islander adults in the United States.

Design: Markov model with costs and benefits discounted at 3%.

Data Source: Published literature and expert opinion. TARGET

Population: Asian and Pacific Islander adults (base-case age, 40 years; sensitivity analysis conducted on ages 20 to 60 years).

Time Horizone: Lifetime.

Perspective: U.S. societal.

Interventions: A universal vaccination strategy in which all individuals are given a 3-dose vaccination series; a screen-and-treat strategy, in which individuals are given blood tests to determine whether they are chronically infected, and infected persons are monitored and treated; a screen, treat, and ring vaccinate strategy, in which all individuals are tested for chronic HBV infection and close contacts of infected persons are screened and vaccinated if needed; and a screen, treat, and vaccinate strategy, in which all individuals are tested and then vaccinated with a 3-dose series if needed. In all cases, persons found to be chronically infected are monitored and treated if indicated.

Outcome Measure: Costs (2006 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness.

Results of Base-case Analysis: Compared with the status quo, the screen-and-treat strategy has an incremental cost-effectiveness ratio of $36,088 per QALY gained. The screen, treat, and ring vaccinate strategy gains more QALYs than the screen and treat strategy and incurs modest incremental costs, leading to incremental cost-effectiveness of $39,903 per QALY gained compared with the screen and treat strategy. The universal vaccination and screen, treat, and vaccinate strategies were weakly dominated by the other 2 strategies.

Results of Sensitivity Analysis: Over a wide range of variables, the incremental cost-effectiveness ratios of the screen and treat and screen, treat, and ring vaccinate strategies were less than $50,000 per QALY gained.

Limitations: Results depend on the accuracy of the underlying data and assumptions. The long-term effectiveness of new and future HBV treatments is uncertain.

Conclusions: Screening programs for HBV among Asian and Pacific Islander adults are likely to be cost effective. Clinically significant benefits accrue from identifying chronically infected persons for medical management and vaccinating their close contacts. Such efforts can greatly reduce the burden of HBV-associated liver cancer and chronic liver disease in the Asian and Pacific Islander population.

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Annals of Internal Medicine
Authors
Margaret L. Brandeau
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Purpose: One-year adjuvant trastuzumab (AT) therapy, with or without anthracyclines, increases disease-free and overall survival in early-stage HER2/neu-positive breast cancer. We sought to evaluate the cost effectiveness of these regimens, which are expensive and potentially toxic.

Methods: We used a Markov health-state transition model to simulate three adjuvant therapy options for a cohort of 49-year-old women with HER2/neu-positive early-stage breast cancer: conventional chemotherapy without trastuzumab; anthracycline-based AT regimens used in the National Surgical Adjuvant Breast and Bowel Project B-31 and North Central Cancer Treatment Group N9831 trials; and the nonanthracycline AT regimen used in the Breast Cancer International Research group 006 trial. The base case used treatment efficacy measures reported in the randomized clinical trials of AT. We measured health outcomes in quality-adjusted life-years (QALYs) and costs in 2005 United States dollars (US$) and subjected results to probabilistic sensitivity analysis.

Results: In the base case, the anthracycline-based AT arm has an incremental cost-effectiveness ratio (ICER) of $39,982/QALY, whereas the nonanthracycline AT arm is more expensive and less effective; this result is insensitive to changes in recurrence rates, but if there is no benefit after 4 years, ICERs exceed $100,000/QALY for both AT arms. Results are moderately sensitive to variation in breast cancer survival rates and trastuzumab cost, and less sensitive to variations in cardiac toxicity.

Conclusion: AT has an ICER comparable to those for other widely used interventions. Longer clinical follow-up is warranted to evaluate the long-term efficacy and toxicity of different AT regimens.

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Journal of Clinical Oncology
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Elsevier Sciences in "Nelson's Textbook of Pediatrics", 17th Edition
Authors
Paul H. Wise
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Objectives: We examined the utility of the Veterans Health Administration (VHA) universal screening program for military sexual violence.

Methods: We analyzed VHA administrative data for 185 880 women and 4139888 men who were veteran outpatients and were treated in VHA health care settings nationwide during 2003.

Results: Screening was completed for 70% of patients. Positive screens were associated with greater odds of virtually all categories of mental health comorbidities, including posttraumatic stress disorder (adjusted odds ratio [AOR]=8.83; 99% confidence interval [CI] = 8.34, 9.35 for women; AOR = 3.00; 99% CI = 2.89, 3.12 for men). Associations with medical comorbidities (e.g., chronic pulmonary disease, liver disease, and for women, weight conditions) were also observed. Significant gender differences emerged.

Conclusions: The VHA policies regarding military sexual trauma represent a uniquely comprehensive health care response to sexual trauma. Results attest to the feasibility of universal screening, which yields clinically significant information with particular relevance to mental health and behavioral health treatment. Women’s health literature regarding sexual trauma will be particularly important to inform health care services for both male and female veterans.

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American Journal of Public Health
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Mark W. Smith
Susan M. Frayne
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Context: Without detailed evidence of their effectiveness, pedometers have recently become popular as a tool for motivating physical activity.

Objective: To evaluate the association of pedometer use with physical activity and health outcomes among outpatient adults.

Data Sources: English-language articles from MEDLINE, EMBASE, Sport Discus, PsychINFO, Cochrane Library, Thompson Scientific (formerly known as Thompson ISI), and ERIC (1966-2007); bibliographies of retrieved articles; and conference proceedings.

Study Selection: Studies were eligible for inclusion if they reported an assessment of pedometer use among adult outpatients, reported a change in steps per day, and included more than 5 participants.

Data Extraction and Data Synthesis: Two investigators independently abstracted data about the intervention; participants; number of steps per day; and presence or absence of obesity, diabetes, hypertension, or hyperlipidemia. Data were pooled using random-effects calculations, and meta-regression was performed.

Results: Our searches identified 2246 citations; 26 studies with a total of 2767 participants met inclusion criteria (8 randomized controlled trials [RCTs] and 18 observational studies). The participants' mean (SD) age was 49 (9) years and 85% were women. The mean intervention duration was 18 weeks. In the RCTs, pedometer users significantly increased their physical activity by 2491 steps per day more than control participants (95% confidence interval [CI], 1098-3885 steps per day, P .001). Among the observational studies, pedometer users significantly increased their physical activity by 2183 steps per day over baseline (95% CI, 1571-2796 steps per day, P .0001). Overall, pedometer users increased their physical activity by 26.9% over baseline. An important predictor of increased physical activity was having a step goal such as 10,000 steps per day (P = .001). When data from all studies were combined, pedometer users significantly decreased their body mass index by 0.38 (95% CI, 0.05-0.72; P = .03). This decrease was associated with older age (P = .001) and having a step goal (P = .04). Intervention participants significantly decreased their systolic blood pressure by 3.8 mm Hg (95% CI, 1.7-5.9 mm Hg, P .001). This decrease was associated with greater baseline systolic blood pressure (P = .009) and change in steps per day (P = .08).

Conclusions: The results suggest that the use of a pedometer is associated with significant increases in physical activity and significant decreases in body mass index and blood pressure. Whether these changes are durable over the long term is undetermined.

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Journal of the American Medical Association
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To relate the changing epidemiology of childhood to current patterns of pediatric practice in the United States, a critical literature review and selected analyses of national datasets, including the National Health Interview Survey, the National Hospital Discharge Survey, and National Vital Statistics System, were conducted. Trends over the past several decades suggest that the incidence of serious acute illness in children has fallen while the prevalence of chronic disease has risen. These trends have resulted in a growing concentration of serious childhood morbidity and mortality into chronic disorders. Current pediatric practice structures appear to be poorly suited to meet the growing demands of chronic disease in children and likely will require major reform in organization, financing, and training.

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Journal of Pediatrics
Authors
Paul H. Wise
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BACKGROUND: To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. METHODS: We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. RESULTS: Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69-82%) and 69% (60-77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV infection. The uncertainty surrounding the model-predicted reduction in cervical cancer incidence narrowed substantially when vaccination was combined with every-5-year screening, with a mean reduction of 89% and range of 83% to 95%. CONCLUSION: We demonstrate an approach to parameterization, calibration and performance evaluation for a U.S. cervical cancer microsimulation model intended to provide qualitative and quantitative inputs into decisions that must be taken before long-term data on vaccination outcomes become available. This approach allows for a rigorous and comprehensive description of policy-relevant uncertainty about health outcomes under alternative cancer prevention strategies. The model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the U.S.

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Population Health Metrics
Authors
Jeremy Goldhaber-Fiebert
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