Publications

Laboratory and epidemiologic evidence suggests that pathogen-specific factors may affect multidrug-resistant (MDR) tuberculosis (TB) transmission and pathogenesis. To identify demographic and clinical characteristics of MDR TB case clustering and to estimate the effect of specific isoniazid resistance-conferring mutations and strain lineage on genotypic clustering, we conducted a population-based cohort study of all MDR TB cases reported in California from January 1, 2004, through December 31, 2007. Of 8,899 incident culture-positive cases for which drug susceptibility information was available, 141 (2%) were MDR. Of 123 (87%) strains with genotype data, 25 (20%) were aggregated in 8 clusters; 113 (92%) of all MDR TB cases and 21 (84%) of clustered MDR TB cases occurred among foreign-born patients. In multivariate analysis, the katG S315T mutation (odds ratio 11.2, 95% confidence interval 2.2-Yen; p = 0.004), but not strain lineage, was independently associated with case clustering.

AIMS

Individuals with asthma may be at increased risk of depression, but few studies have identified precursors to the onset of depression. The study goal was to identify risk factors for depression onset among a community-based sample of adults with asthma.

METHODS

Data were obtained from three telephone interviews conducted at 2-yearly intervals on a longitudinal cohort of adults with asthma (n=439). The Center for Epidemiologic Studies Depression scale (CESD) was used to measure depressive symptoms. Multiple regression analyses tested associations of sociodemographic and health-related variables with depression prevalence (cross-sectional analyses) and incident depression (longitudinal analyses).

RESULTS

15% of subjects were classified as "depressed" (CESD> or =23) at each interview. Individuals depressed at baseline were more likely to drop out (OR=1.76 [95% CI 1.05, 2.96]). Low perceived control of asthma (measured with the Perceived Control of Asthma Questionnaire [PCAQ]) exhibited the most consistent association with depression. Lower PCAQ was cross-sectionally associated with depression (OR=0.51 per 0.5 SD difference in PCAQ [0.35, 0.75]). Onset of depression was noted in 38 individuals. Decrease in perceived control at follow-up was associated with depression onset (OR=7.47 [2.15, 26.01]).

CONCLUSIONS

Low perceived control of asthma predicted depression onset among adults with asthma. This risk factor may respond to self-management education.

RATIONALE

Although cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), a substantial proportion of COPD cases cannot be explained by smoking alone.

OBJECTIVES

To evaluate the risk factors for COPD besides personal cigarette smoking.

METHODS

We constituted an ad hoc subcommittee of the American Thoracic Society Environmental and Occupational Health Assembly. An international group of members was invited, based on their scientific expertise in a specific risk factor for COPD. For each risk factor area, the committee reviewed the literature, summarized the evidence, and developed conclusions about the likelihood of it causing COPD. All conclusions were based on unanimous consensus.

MEASUREMENTS AND MAIN RESULTS

The population-attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%, but was less than 80% in most studies, indicating a substantial burden of disease attributable to nonsmoking risk factors. On the basis of our review, we concluded that specific genetic syndromes and occupational exposures were causally related to the development of COPD. Traffic and other outdoor pollution, secondhand smoke, biomass smoke, and dietary factors are associated with COPD, but sufficient criteria for causation were not met. Chronic asthma and tuberculosis are associated with irreversible loss of lung function, but there remains uncertainty about whether there are important phenotypic differences compared with COPD as it is typically encountered in clinical settings.

CONCLUSIONS

In public health terms, a substantive burden of COPD is attributable to risk factors other than smoking. To prevent COPD-related disability and mortality, efforts must focus on prevention and cessation of exposure to smoking and these other, less well-recognized risk factors.

PURPOSE

Personalized medicine is changing oncology practice and challenging decision making. A key challenge is the limited clinical evidence for many personalized medicine technologies. We describe the strategies private payers employed to develop coverage policy for personalized medicine using the example of the 21-gene assay in breast cancer.

METHODS

We examined the coverage policies of six private payers for the 21-gene assay. We then interviewed senior executives (n = 7) from these payers to elucidate factors informing coverage decisions. We additionally focused on the timing of payer decisions compared with the timing of evidence development, measured by publication of primary studies and relevant clinical guidelines.

RESULTS

The 21-gene assay became commercially available in 2004. The interviewed payers granted coverage between 2005 and 2008. Their policies varied in structure (eg, whether prior authorization was required). All payers reported clinical evidence as the most important factor in decision making, but all used some health care system factors (eg, physician adoption or medical society endorsement) to inform decision making as well. Payers had different perceptions about the strength of clinical evidence at the time of the coverage decision.

CONCLUSION

Coverage of the 21-gene assay is currently widespread, but policies differ in timing and structure. A key approach private payers use to develop coverage policies for novel technologies is considering both clinical evidence and health care system factors. Policy variation may emerge from the range of factors used and perception of the evidence. Future research should examine the role of health care system factors in policy development and related policy variations.

OBJECTIVES

The purpose of this paper is to analyze the social organization of caring as gendered work as it relates to meal preparation and consumption activities surrounding older adult cancer patients and their caregivers.

METHODS

Qualitative methods consisting of in-depth, semi-structured, face-to-face interviews with 30 older cancer patients (17 women and 13 men aged 68-90) and their caregivers were conducted separately. Participants were diagnosed with pancreatic, colon, breast, lymphoma, skin, and head and neck cancer.

RESULTS

Major findings were that both patients and caregivers experienced distress surrounding food preparation and mealtime activities, and these varied according to the gender of both patients and caregivers and the relationship that existed between patients and caregivers. Of particular note, female patients experienced distress over not being able to fully participate in meal planning and cooking activities that were central to their self-identity. Related to this, male spouses experienced frustration over not being able to engage in cooking activities that met their wives' expectations. Female caregivers expressed tremendous discontent that the one they were caring for did not eat like they 'should'.

DISCUSSION

Matters related to the organization of meals and food consumption activities may be a source of significant distress for patients and caregivers. Further research and greater attention from health care providers are warranted to evaluate the extent of such distress.

Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary research, but these efforts have great potential to improve care for patients with IPF.

BACKGROUND

Exercise testing to aid diagnosis of exercise-induced bronchoconstriction (EIB) is commonly performed. Reproducibility of the airway response to a standardized exercise protocol has not been reported in subjects being evaluated with mild symptoms suggestive of asthma but without a definite diagnosis. This study examined reproducibility of % fall in FEV1 and area under the FEV1 time curve for 30 minutes in response to two exercise tests performed with the same intensity and duration of exercise, and inspired air conditions.

METHODS

Subjects with mild symptoms of asthma exercised twice within approximately 4 days by running for 8 minutes on a motorized treadmill breathing dry air at an intensity to induce a heart rate between 80-90% predicted maximum; reproducibility of the airway response was expressed as the 95% probability interval.

RESULTS

Of 373 subjects challenged twice 161 were positive (≥ 10% fall FEV1 on at least one challenge). The EIB was mild and 77% of subjects had <15% fall on both challenges. Agreement between results was 76.1% with 56.8% (212) negative (< 10% fall FEV1) and 19.3% (72) positive on both challenges. The remaining 23.9% of subjects had only one positive test. The 95% probability interval for reproducibility of the % fall in FEV1 and AUC0-30 min was ± 9.7% and ± 251% for all 278 adults and ± 13.4% and ± 279% for all 95 children. The 95% probability interval for reproducibility of % fall in FEV1 and AUC0-30 min for the 72 subjects with two tests ≥ 10% fall FEV1 was ± 14.6% and ± 373% and for the 34 subjects with two tests ≥ 15% fall FEV1 it was ± 12.2% and ± 411%. Heart rate and estimated ventilation achieved were not significantly different either on the two test days or when one test result was positive and one was negative.

CONCLUSIONS

Under standardized, well controlled conditions for exercise challenge, the majority of subjects with mild symptoms of asthma demonstrated agreement in test results. Performing two tests may need to be considered when using exercise to exclude or diagnose EIB, when prescribing prophylactic treatment to prevent EIB and when designing protocols for clinical trials.