Publications

OBJECTIVES

To estimate rates and predictors of clinical laboratory test completion by patients with diabetes after provider referral.

STUDY DESIGN

Prospective cohort study.

METHODS

Among 186,306 adult members with diabetes in Kaiser Permanente Northern California, we searched the electronic medical records (July 1, 2008, to June 30, 2009) of each patient for the first outpatient order to obtain the following laboratory tests commonly used to measure risk factor control or adverse effects of pharmacotherapy: levels of glycosylated hemoglobin, low density lipoprotein cholesterol, serum creatinine, urinary albumin, or creatine kinase (the latter only among persons using statins). We measured laboratory test attendance as completion of an order (including time to results) within 6 months of the referral date and looked for variations by subgroups.

RESULTS

Laboratory test attendance ranged from 86% for glycosylated hemoglobin level to 73% for serum creatinine level. Time to laboratory test attendance was a median of 7 to 11 days and a mean of 25 to 30 days. Laboratory test attendance was more likely for women and older patients or for orders after a face-to-face provider visit and was less likely for orders by a pharmacist. However, most variations (even by laboratory copayment) were small or not clinically substantive. In subanalyses, we observed no clinically significant variations by race/ethnicity, socioeconomic status, trust in provider, or patient-provider communication and found no association with depressive symptoms, health literacy, or English fluency.

CONCLUSION

The fact that 1 in 7 patients did not complete laboratory tests within 6 months of the provider referral may help explain why healthcare services seem to fall short of optimal diabetes care.

Microscopy remains the gold standard for malaria diagnosis. However, quality microscopy services are severely lacking in most African countries. To improve capacity for malaria microscopy in Uganda, a 3-day refresher training program was conducted in four districts. Training impact was measured through a written examination and evaluation of the quality of blood-slide preparation and accuracy of field microscopy. A total of 184 of 192 (96%) identified laboratory personnel participated in the training. Average test scores improved from 41% to 75% (P < 0.001). A total of 1,079 and 1,190 routinely made thick blood smears were collected before and after the training, respectively. Sensitivity improved from 84% to 95% (P < 0.001), and specificity improved from 87% to 97% (P < 0.001). The proportion of well-prepared blood smears improved from 6% to 75% (P < 0.001). Supplemental training can have a significant impact on the knowledge of staff, accuracy of microscopy, and quality of blood-slide preparation.

The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.

In this article, The Future of Nursing: Leading Change, Advancing Health report is summarized, and opportunities for occupational health nursing are proposed.

The 53rd annual Thomas L. Petty Aspen Lung Conference focused on the dramatic progress that has been made in the past several years in applying large-scale, unbiased data acquisition ("omics") to the study of lung biology and disease. The conference organizers, Mark Geraci, Ivor Douglas, Stephen Rennard, and David Schwartz, put together a terrific program, and the invited speakers and participants presented data describing the rapid evolution of experimental approaches that should encourage pulmonary scientists to begin to think about a true molecular systems biology of the lung.

Messenger RNAs (mRNAs) contain prominent untranslated regions (UTRs) that are increasingly recognized to play roles in mRNA processing, transport, stability, and translation. 3' UTRs are believed to harbor recognition sites for a diverse set of RNA-binding proteins that regulate gene expression as well as most active microRNA target sites. Although the roles of 3' UTRs in the normal and diseased lung have not yet been studied extensively, available evidence suggests important roles for 3' UTRs in lung development, inflammation, asthma, pulmonary fibrosis, and cancer. Systematic, genome-wide approaches are beginning to catalog functional elements within 3' UTRs and identify the proteins and microRNAs that interact with these elements. Application of new data sets and experimental approaches should provide powerful insights into how 3' UTR-mediated regulatory events contribute to disease and may inspire novel therapeutic approaches.

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.