Publications

PURPOSE

: The independent contribution of physical inactivity to disability in obstructive lung disease (OLD) is difficult to study, partly because inactivity may reflect disease severity. We examined the relationship of physical inactivity to disability progression over a 1-year period among a group of older adults with OLD.

METHODS

: A population-based cohort with self-reported physician-diagnosed emphysema, chronic obstructive pulmonary disease, or chronic bronchitis (n = 206) completed baseline interviews and in-person spirometry, with 1-year followup interviews. The Community Health Activities Model Program for Seniors physical activity questionnaire provided estimates of energy expenditure; we defined inactivity as no expenditure in moderate- or vigorous-intensity activities. Disability was measured with the Valued Life Activity (VLA) disability scale; increased disability was defined as a 10% or greater increase in VLA disability score over 1-year followup. Logistic regression tested the relationship between baseline inactivity and disability increase, controlling for age, sex, baseline VLA disability, comorbidities, smoking, and pulmonary function (forced expiratory volume in 1 second, % predicted).

RESULTS

: Of 206 subjects, 48 (27%) were physically inactive at baseline; 42.9% of individuals whose disability increased were inactive at baseline compared with 23.4% of those who did not experience a disability increase. With adjustment for covariates, increased disability after 1 year was significantly (P = .04) more likely among individuals who were inactive at baseline (Odds Ratio =2.4; 95% confidence interval, 1.02-5.9).

CONCLUSIONS

: Physically inactive individuals with OLD had more than double the odds of an increase in disability, even after controlling for baseline disability, lung function, and other covariates. These results provide strong support for the importance of maintaining physical activity among individuals with OLD.

OBJECTIVE

The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis.

METHODS

This study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association study to identify risk factors in other regions of the genome. A total of 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies.

RESULTS

Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (P=0.002), but not variants in CYP2C8 (P=0.073) or UGTs (P=0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (odds ratio: 1.89; 95% confidence interval: 1.40-2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (P<0.001). The genome-wide association study identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (P=1.74E-07). An additional copy of the minor allele of the RYR2 variant was associated with a reduced risk of rhabdomyolysis (odds ratio: 0.48; 95% confidence interval: 0.36-0.63).

CONCLUSION

We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin.

OBJECTIVE

Health technology assessment (HTA) plays an increasing role in translating emerging technologies into clinical practice and policy. Private payers are important users of HTA whose decisions impact adoption and use of new technologies. We examine the current use of HTA by private payers in coverage decisions for personalized medicine, a field that is increasingly impacting oncology practice.

STUDY DESIGN

Literature review and semistructured interviews.

METHODS

We reviewed 7 HTA organizations used by private payers in decision making and explored how HTA is used by major US private payers (n = 11) for coverage of personalized medicine.

RESULTS

All payers used HTA in coverage decisions, but the number of HTA organizations used by an individual payer ranged from 1 (n = 1) to all 7 (n = 1), with the majority of payers (n = 8) using 3 or more. Payers relied more extensively on HTAs for reviews of personalized medicine (64%) than for other technologies. Most payers (82%) equally valued expertise of reviewers and rigor of evaluation as HTA strengths, whereas genomic-specific methodology was less important. Key reported shortcomings were limited availability of reviews (73%) and limited inclusion of nonclinical factors (91%), such as cost-effectiveness or adoption of technology in clinical practice.

CONCLUSION

Payers use a range of HTAs in their coverage decisions related to personalized medicine, but the current state of HTA to comprehensively guide those decisions is limited. HTA organizations should address current gaps to improve their relevance to payers and clinicians. Current HTA shortcomings may also inform the national HTA agenda.

PURPOSE

Health technology assessment (HTA) plays an increasing role in translating emerging technologies into clinical practice and policy. Private payers are important users of HTA whose decisions impact adoption and use of new technologies. We examine the current use of HTA by private payers in coverage decisions for personalized medicine, a field that is increasingly impacting oncology practice.

STUDY DESIGN

Literature review and semistructured interviews.

METHODS

We reviewed seven HTA organizations used by private payers in decision making and explored how HTA is used by major US private payers (n = 11) for coverage of personalized medicine.

RESULTS

All payers used HTA in coverage decisions, but the number of HTA organizations used by an individual payer ranged from one (n = 1) to all seven (n = 1), with the majority of payers (n = 8) using three or more. Payers relied more extensively on HTAs for reviews of personalized medicine (64%) than for other technologies. Most payers (82%) equally valued expertise of reviewers and rigor of evaluation as HTA strengths, whereas genomic-specific methodology was less important. Key reported shortcomings were limited availability of reviews (73%) and limited inclusion of nonclinical factors (91%), such as cost-effectiveness or adoption of technology in clinical practice.

CONCLUSION

Payers use a range of HTAs in their coverage decisions related to personalized medicine, but the current state of HTA to comprehensively guide those decisions is limited. HTA organizations should address current gaps to improve their relevance to payers and clinicians. Current HTA shortcomings may also inform the national HTA agenda.

PURPOSE

Given the likely proliferation of targeted testing and treatment strategies for cancer, a better understanding of the utilization patterns of human epidermal growth factor receptor 2 (HER2) testing and trastuzumab and newer gene expression profiling (GEP) for risk stratification and chemotherapy decision making are important.

STUDY DESIGN

Cross-sectional.

METHODS

We performed a medical record review of women age 35 to 65 years diagnosed between 2006 and 2007 with invasive localized breast cancer, identified using claims from a large national health plan (N = 775).

RESULTS

Almost all women received HER2 testing (96.9%), and 24.9% of women with an accepted indication received GEP. Unexplained socioeconomic differences in GEP use were apparent after adjusting for age and clinical characteristics; specifically, GEP use increased with income. For example, those in the lowest income category (< $40,000) were less likely than those with an income of $125,000 or more to receive GEP (odds ratio, 0.34; 95% CI, 0.16 to 0.73). A majority of women (57.7%) with HER2-positive disease received trastuzumab; among these women, differences in age and clinical characteristics were not apparent, although surprisingly, those in the lowest income category were more likely than those in the high-income category to receive trastuzumab (P = .02). Among women who did not have a positive HER2 test, 3.9% still received trastuzumab. Receipt of adjuvant chemotherapy increased as GEP score indicated greater risk of recurrence.

CONCLUSION

Identifying and eliminating unnecessary variation in the use of these expensive tests and treatments should be part of quality improvement and efficiency programs.

Data from this multiyear qualitative study of the effects of Hurricane Katrina and flooding in New Orleans suggest differences in how the elderly cope with disaster. At the time of the disaster, the elderly of New Orleans were at greater risk than other groups, and more elderly died than any other group during the storm and in the first year after. Those who did survive beyond the first year report coping with the long-term disaster aftermath better than the generation below them, experiencing heightened stresses, and feeling as if they are "aging" faster than they should. We offer insight on how we might define and characterize disasters, and illustrate that long-term catastrophes "age" in specific ways.

BACKGROUND

Patients with head and neck cancers (HNCs) are at increased risk of experiencing malnutrition, which is associated with poor outcomes. Advances in the treatment of HNCs have resulted in improved outcomes that are associated with severe toxic oral side effects, placing patients at an even greater risk of malnutrition. Prophylactic placement of percutaneous endoscopic gastrostomy (PEG) tubes before treatment may be beneficial in patients with HNC, especially those undergoing more intense treatment regimens. PEG tube placement, however, is not without risks.

METHODS

A comprehensive review of the literature was conducted.

RESULTS

Systematic evidence assessing both the benefits and harm associated with prophylactic PEG tube placement in patients undergoing treatment for HNC is weak, and benefits and harm have not been established.

CONCLUSIONS

More research is necessary to inform physician behavior on whether prophylactic PEG tube placement is warranted in the treatment of HNC.