Publications

BACKGROUND

Anti-tumor necrosis factor-α (TNF-α) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.

METHODS

We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-α agents.

RESULTS

Among the 8417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4200 (0.5%) who used anti-TNF-α during study follow-up, and 15 of 5423 (0.3%) who used only non-biologic therapies. The age-standardized and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 [95% confidence interval (CI) 0-0.43] for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared with the use of non-biologic therapies, use of anti-TNF-α therapy was not associated with a diagnosis of ILD among patients with rheumatoid arthritis (adjusted hazard ratio, 1.03; 95%CI 0.51-2.07), nor did head-to-head comparisons across anti-TNF-α agents suggest important differences in risk, although the number of cases available for analysis was limited.

CONCLUSION

The study provides evidence that compared with non-biologic therapies, anti-TNF-α therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD.

Natural history studies suggest increased risk for kidney function decline with HIV infection, but few studies have made comparisons with HIV-uninfected women. We examined whether HIV infection treated with highly active antiretroviral therapy (HAART) remains associated with faster kidney function decline in the Women's Interagency HIV Study. HIV-infected women initiating HAART with (n=105) or without (n=373) tenofovir (TDF) were matched to HIV-uninfected women on calendar and length of follow-up, age, systolic blood pressure, hepatitis C antibody serostatus, and diabetes history. Linear mixed models were used to evaluate differences in annual estimated glomerular filtration rate (eGFR). Person-visits were 4,741 and 11,512 for the TDF-treated and non-TDF-treated analyses, respectively. Mean baseline eGFRs were higher among women initiated on TDF-containing HAART and lower among those on TDF-sparing HAART compared to their respective HIV-uninfected matches (p<0.05 for both). HIV-infected women had annual rates of eGFR changes similar to HIV-uninfected matches (p-interaction >0.05 for both). Adjusting for baseline eGFR, mean eGFRs at 1 and 3 years of follow-up among women initiated on TDF-containing HAART were lower than their uninfected matches (-4.98 and -4.26 ml/min/1.73 m(2), respectively; p<0.05 for both). Mean eGFR of women initiated on TDF-sparing HAART was lower versus uninfected matches at 5 years (-2.19 ml/min/1.73 m(2), p=0.03). HAART-treated HIV-infected women had lower mean eGFRs at follow-up but experienced rates of annual eGFR decline similar to HIV-uninfected women. Tenofovir use in HIV-infected women with normal kidney function did not accelerate long-term kidney function decline relative to HIV-uninfected women.

BACKGROUND

Given the rising costs of health care, policymakers are increasingly interested in identifying the inefficiencies in our health care system. The objective of this study was to determine whether the overuse and misuse of health care services in the ambulatory setting has decreased in the past decade.

METHODS

Cross-sectional analysis of the 1999 and 2009 National Ambulatory Medical Care Survey and the outpatient department component of the National Hospital Ambulatory Medical Care Survey, which are nationally representative annual surveys of visits to non-federally funded ambulatory care practices. We applied 22 quality indicators using a combination of current quality measures and guideline recommendations. The main outcome measures were the rates of underuse, overuse, and misuse and their 95% CIs.

RESULTS

We observed a statistically significant improvement in 6 of 9 underuse quality indicators. There was an improvement in the use of antithrombotic therapy for atrial fibrillation; the use of aspirin, β-blockers, and statins in coronary artery disease; the use of β-blockers in congestive heart failure; and the use of statins in diabetes mellitus. We observed an improvement in only 2 of 11 overuse quality indicators, 1 indicator became worse, and 8 did not change. There was a statistically significant decrease in the overuse of cervical cancer screening in visits for women older than 65 years and in the overuse of antibiotics in asthma exacerbations. However, there was an increase in the overuse of prostate cancer screening in men older than 74 years. Of the 2 misuse indicators, there was a decrease in the proportion of patients with a urinary tract infection who were prescribed an inappropriate antibiotic.

CONCLUSIONS

We found significant improvement in the delivery of underused care but more limited changes in the reduction of inappropriate care. With the high cost of health care, these results are concerning.

α1-Adrenergic receptors (α1-ARs) elicit a negative inotropic effect (NIE) in the mouse right ventricular (RV) myocardium but a positive inotropic effect (PIE) in the left ventricular (LV) myocardium. Effects on myofilament Ca(2+) sensitivity play a role, but effects on Ca(2+) handling could also contribute. We monitored the effects of α1-AR stimulation on contraction and Ca(2+) transients using single myocytes isolated from the RV or LV. Interestingly, for both the RV and LV, we found heterogeneous myocyte inotropic responses. α1-ARs mediated either a PIE or NIE, although RV myocytes had a greater proportion of cells manifesting a NIE (68%) compared with LV myocytes (36%). Stimulation of a single α1-AR subtype (α1A-ARs) with a subtype-selective agonist also elicited heterogeneous inotropic responses, suggesting that the heterogeneity arose from events downstream of the α1A-AR subtype. For RV and LV myocytes, an α1-AR-mediated PIE was associated with an increased Ca(2+) transient and a NIE was associated with a decreased Ca(2+) transient, suggesting a key role for Ca(2+) handling. For RV and LV myocytes, α1-AR-mediated decreases in the Ca(2+) transient were associated with increased Ca(2+) export from the cell and decreased Ca(2+) content of the sarcoplasmic reticulum. In contrast, for myocytes with α1-AR-induced increased Ca(2+) transients, sarcoplasmic reticulum Ca(2+) content was not increased, suggesting that other mechanisms contributed to the increased Ca(2+) transients. This study demonstrates the marked heterogeneity of LV and RV cellular inotropic responses to stimulation of α1-ARs and reveals a new aspect of biological heterogeneity among myocytes in the regulation of contraction.