The case of a 52-yr-old female with rheumatoid arthritis and HIV who developed massive, progressive, cavitary pulmonary nodules is described. Multiple diagnostic bronchoscopies and lung biopsies failed to demonstrate the presence of any microorganisms. Pathological analysis showed palisading histiocytes with necrobiosis consistent with rheumatoid nodules. The effect of co-existing HIV infection on the course and prognosis of rheumatoid arthritis is discussed, and it is concluded that the complex relationship between these two disease processes warrants further investigation.

BACKGROUND: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. METHODS: Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. FINDINGS: In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0.89 to 1.09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0.95 to 1.08); there was little heterogeneity except for SNP rs7520966. INTERPRETATION: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease.

Objective: To compare and contrast proposed definitions of metabolic syndrome in pediatrics, and to determine prevalence of metabolic syndrome in preadolescent females when applying different criteria.

Study Design: A literature review on definitions of metabolic syndrome and cardiovascular "risk factor clustering" in children and adolescents published in the past decade. Pediatric definitions of metabolic syndrome were then applied to a community-based study of 261 black preadolescent females (Girls Health Enrichment MultiSite studies [GEMS]) and a school-based, cross-sectional study of 240 ethnically-diverse preadolescent females (Girls Activity, Movement and Environmental Strategy [GAMES]) who had a baseline physical examination and fasting morning blood sample.

Results: Agreement among pediatric definitions of metabolic syndrome was poor. The prevalence of MS and cardiovascular risk factor clustering ranged from 0.4% to 23.0% for GEMS and 2.0% to 24.6% for GAMES with definitions adapted from the National Cholesterol Education Program Adult Treatment Panel III, and 0% to 15.3% for GEMS and 0.4% to 15.8% for GAMES using modified criteria from the World Health Organization.

Conclusions: The prevalence of metabolic syndrome in preadolescent girls varies widely because of disagreement among proposed definitions of metabolic syndrome in pediatrics. Further investigation is needed to determine which metabolic factors and their respective cut points should be used to identify children at risk for development of clinical disease.

This issue of CHP/PCOR's quarterly newsletter, which covers news from the summer 2006 quarter, includes articles about:

• research by CHP/PCOR investigators that influenced the Centers for Disease Control and Prevention to recommend widespread voluntary HIV screening for all Americans ages 13 to 64 -- a significant change from the CDC's previous HIV screening guidelines;
• a CHP/PCOR study on patient safety culture in U.S. hospitals -- the largest effort to date to measure hospitals' safety culture and seek to improve it through an intervention that gets hospital executives out of their offices and on to the hospital floors;
• an early-stage project in which CHP/PCOR is collaborating with the Center on Democracy, Development and the Rule of Law to study the relationship between health interventions, governance and development;
• an evidence report examining the challenges of diagnosing and treating anthrax in children, prepared by the Stanford-UCSF Evidence-based Practice Center; and
• a study by CHP/PCOR fellow Kate Bundorf which found that depending on the definition of "affordability" that is used, health insurance is "affordable" to between one-quarter and three-quarters of the uninsured -- and many of those who can't afford insurance purchase it anyway.

The U.S. Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To date, testimony presented before the FDA has been overwhelmingly supportive. Advocates have argued enthusiastically that there is value in empowering individuals to manage their HIV risks and have suggested that the availability of a rapid home HIV test will dramatically increase rates of disease detection in communities that have proven difficult to reach and to link to appropriate care. The authors offer a more cautious perspective.

According to what is already known about the market demand for over-the-counter HIV testing kits, their costs, and the performance of rapid HIV tests in that market, the authors do not anticipate that the rapid home test will have a profound impact either on the HIV public health crisis or on the populations in greatest need. Home HIV testing will attract a predominantly affluent clientele, composed disproportionately of HIV-uninfected new couples and "worried well" persons, as well as very recently infected persons with undetectable disease. The authors illustrate how testing in these populations may have the perverse effect of increasing both false-positive and false-negative results. A poorly functioning home HIV test may thereby undermine confidence in the reliability of HIV testing more generally and weaken critical efforts to expand HIV detection and linkage to lifesaving care for the estimated 300 000 U.S. citizens with unidentified HIV infection.

Objectives:

To systematically review the literature about children with anthrax to describe their clinical course, treatment responses, and the predictors of disease progression and mortality.

Data Sources:

MEDLINE® (1966-2005), 14 selected journal indexes (1900-1966) and bibliographies of all retrieved articles.

Review Methods:

We sought case reports of pediatric anthrax published between 1900 and 2005 meeting predefined criteria. We abstracted three types of data from the English-language reports:

Patient information (e.g., age, gender, nationality).

Symptom and disease progression information (e.g., whether the patient developed meningitis).

Treatment information (e.g., treatments received, year of treatment).

We compared the clinical symptoms and disease progression variables for the pediatric cases with data on adult anthrax cases reviewed previously.

Results:

We identified 246 titles of potentially relevant articles from our MEDLINE® search and 2253 additional references from our manual search of the bibliographies of retrieved articles and the indexes of the 14 selected journals. We included 62 case reports of pediatric anthrax including two inhalational cases, 20 gastrointestinal cases, 37 cutaneous cases, and three atypical cases.

Anthrax is a relatively common and historically well-recognized disease and yet rarely reported among children, suggesting the possibility of significant under-diagnosis, underreporting, and/or publication bias. Children with anthrax present with a wide range of clinical signs and symptoms, which differ somewhat from the presenting features of adults with anthrax. Like adults, children with gastrointestinal anthrax have two distinct clinical presentations:

Upper tract disease characterized by dysphagia and oropharyngeal findings.

Lower tract disease characterized by fever, abdominal pain, and nausea and vomiting.

Additionally, children with inhalational disease may have "atypical" presentations including primary meningoencephalitis. Children with inhalational anthrax have abnormal chest roentgenograms; however, children with other forms of anthrax usually have normal roentgenograms. Nineteen of the 30 children (63%) who received penicillin-based antibiotics survived; whereas nine of 11 children (82%) who received anthrax antiserum survived.

Conclusions:

There is a broad spectrum of clinical signs and symptoms associated with pediatric anthrax. The limited data available regarding disease progression and treatment responses for children infected with anthrax suggest some differences from adult populations. Preparedness planning efforts should specifically address the needs of pediatric victims.

BACKGROUND: Cost-effectiveness analyses (CEAs) can provide useful information to policymakers concerned with the broad allocation of resources as well as to local decision makers choosing between different options for reducing the burden from a single disease. For the latter, it is important to use country-specific data when possible and to represent cost differences between countries that might make one strategy more or less attractive than another strategy locally. As part of a CEA of cervical cancer screening in five developing countries, we supplemented limited primary cost data by developing other estimation techniques for direct medical and non-medical costs associated with alternative screening approaches using one of three initial screening tests: simple visual screening, HPV DNA testing, and cervical cytology. Here, we report estimation methods and results for three cost areas in which data were lacking. METHODS: To supplement direct medical costs, including staff, supplies, and equipment depreciation using country-specific data, we used alternative techniques to quantify cervical cytology and HPV DNA laboratory sample processing costs. We used a detailed quantity and price approach whose face validity was compared to an adaptation of a US laboratory estimation methodology. This methodology was also used to project annual sample processing capacities for each laboratory type. The cost of sample transport from the clinic to the laboratory was estimated using spatial models. A plausible range of the cost of patient time spent seeking and receiving screening was estimated using only formal sector employment and wages as well as using both formal and informal sector participation and country-specific minimum wages. Data sources included primary data from country-specific studies, international databases, international prices, and expert opinion. Costs were standardized to year 2000 international dollars using inflation adjustment and purchasing power parity. RESULTS: Cervical cytology laboratory processing costs were I$1.57-3.37 using the quantity and price method compared to I$1.58-3.02 from the face validation method. HPV DNA processing costs were I$6.07-6.59. Rural laboratory transport costs for cytology were I$0.12-0.64 and I$0.14-0.74 for HPV DNA laboratories. Under assumptions of lower resource efficiency, these estimates increased to I$0.42-0.83 and I$0.54-1.06. Estimates of the value of an hour of patient time using only formal sector participation were I$0.07-4.16, increasing to I$0.30-4.80 when informal and unpaid labor was also included. The value of patient time for traveling, waiting, and attending a screening visit was I$0.68-17.74. With the total cost of screening for cytology and HPV DNA testing ranging from I$4.85-40.54 and I$11.30-48.77 respectively, the cost of the laboratory transport, processing, and patient time accounted for 26-66% and 33-65% of the total costs. From a payer perspective, laboratory transport and processing accounted for 18-48% and 25-60% of total direct medical costs of I$4.11-19.96 and I$10.57-28.18 respectively. CONCLUSION: Cost estimates of laboratory processing, sample transport, and patient time account for a significant proportion of total cervical cancer screening costs in five developing countries and provide important inputs for CEAs of alternative screening modalities.

Background:

Unlike medicines prescribed for Food and Drug Administration-approved indications, off-label uses may lack rigorous scientific scrutiny. Despite concerns about patient safety and costs to the health care system, little is known about the frequency of off-label drug use or the degree of scientific evidence supporting this practice.

Methods:

We used nationally representative data from the 2001 IMS Health National Disease and Therapeutic Index (NDTI) to define prescribing patterns by diagnosis for 160 commonly prescribed drugs. Each reported drug-diagnosis combination was identified as Food and Drug Administration-approved, off-label with strong scientific support, or off-label with limited or no scientific support. Outcome measures included (1) the proportion of uses that were off-label and (2) the proportion of off-label uses supported by strong scientific evidence. Multivariate analyses were used to identify drug-specific characteristics predictive of increased off-label use.

Results:

In 2001, there were an estimated 150 million (95% confidence interval, 127-173 million) off-label mentions (21% of overall use) among the sampled medications. Off-label use was most common among cardiac medications (46%, excluding antihyperlipidemic and antihypertensive agents) and anticonvulsants (46%), whereas gabapentin (83%) and amitriptyline hydrochloride (81%) had the greatest proportion of off-label use among specific medications. Most off-label drug mentions (73%; 95% confidence interval, 61%-84%) had little or no scientific support. Although several functional classes were associated with increased off-label use (P.05), few other drug characteristics predicted off-label prescription.

Conclusions:

Off-label medication use is common in outpatient care, and most occurs without scientific support. Efforts should be made to scrutinize underevaluated off-label prescribing that compromises patient safety or represents wasteful medication use.