Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

Racial and ethnic differences in breast cancer survival: how much is explained by screening, tumor severity, biology, treatment, comorbidities, and demographics?

BACKGROUND: The reasons for race/ethnicity (R/E) differences in breast cancer survival have been difficult to disentangle. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify 41,020 women aged > or =68 years with incident breast cancer between 1994-1999 including African American (2479), Hispanic (1172), Asian/Pacific Island (1086), and white women (35,878). A Cox proportional hazards model assessed overall and stage-specific (0/I, II/III, and IV) R/E differences in breast cancer survival after adjusting for mammography screening, tumor characteristics at diagnosis, biologic markers, treatment, comorbidity, and demographics. RESULTS: African American women had worse survival than white women, although controlling for predictor variables reduced this difference among all stage breast cancer (hazards ratio [HR], 1.08; 95% confidence interval [95% CI], 0.97-1.20). Adjustment for predictors reduced, but did not eliminate, disparities in the analysis limited to women diagnosed with stage II/III disease (HR, 1.30; 95% CI, 1.10-1.54). Screening mammography, tumor characteristics at diagnosis, biologic markers, and treatment each produced a similar reduction in HRs for women with stage II/III cancers. Asian and Pacific Island women had better survival than white women before and after accounting for all predictors (adjusted all stages HR, 0.61 [95% CI, 0.47-0.79]; adjusted stage II/III HR, 0.61 [95% CI, 0.47-0.79]). Hispanic women had better survival than white women in all and stage II/III analysis (all stage HR, 0.88; 95% CI, 0.75-1.04) and stage II/III analysis (HR, 0.88; 95% CI, 0.75-1.04), although these findings did not reach statistical significance. There was no significant difference in survival by R/E noted among women diagnosed with stage IV disease. CONCLUSIONS: Predictor variables contribute to, but do not fully explain, R/E differences in breast cancer survival for elderly American women. Future analyses should further investigate the role of biology, demographics, and disparities in quality of care.

Can Medicare billing claims data be used to assess mammography utilization among women ages 65 and older?

BACKGROUND: Medicare data may be a useful source for determining the utilization of mammography among elderly women, but the accuracy of these data has not been established. OBJECTIVE: We determined whether Medicare physician billing claims are an accurate reflection of mammography utilization among women ages 65 and older and whether they can be used to assess the use of screening as compared with diagnostic mammography. DATA SOURCES: Mammography use was assessed using Medicare billing claims and radiology reports from 2 mammography registries; the San Francisco Mammography Registry and the New Mexico Mammography Registry. METHODS: Completeness of the Medicare data was assessed by comparing mammography use based on Medicare, with radiology reports from the mammography registries, which served as the referent standard. Capture rates for Medicare claims for individual mammograms were examined, and women were characterized as having undergone at least 1 mammogram within each 2-year period based on the Medicare data, and these rates were compared with the referent standard. To determine whether Medicare data can distinguish between screening and diagnostic mammography, we performed a classification analysis using the mammography registries screening/diagnostic designation as the referent standard (dependent variable) and Medicare claim information as the independent/predictor variable. On the basis of the mammogram level classification analysis, women were categorized as having been frequently screened (at least 2 screening mammograms spaced by 12 to 36 months), screened (at least 1 screening mammogram), or not screened. SUBJECTS: Women ages 65 and older, diagnosed with breast cancer between 1992-1999, who had at least 1 mammogram between 1992-1999 were examined. RESULTS: A total of 3340 mammograms were obtained in 1371 women between 1992 and 1999. Overall, 83% of mammograms obtained by these women had a corresponding billing claim in Medicare. This increased from 65% in 1992 to 90% in 1999. Of women who underwent at least 1 mammogram during each 2-year period per the referent standard, 94% of women were accurately classified by Medicare claims as also having undergone mammography during the same 2-year period. In multivariable analysis, a mammogram was more likely to be associated with a billing claim over time, for women 80 years or older, and for white and Asian as compared with Hispanic women. Neither socioeconomic status nor screening/diagnostic designation affected the likelihood that a mammogram would be associated with a billing claim. The Medicare data accurately categorized a given mammogram as screening or diagnostic for 87.5% of mammograms. Lastly, there was moderate to substantial agreement in the categorization of women as frequently screened, screened or not screened between the 2 data sets (weighted kappa 0.74, 95% confidence interval 0.70-0.78). CONCLUSION: Medicare administrative claims are reliable for assessment of mammography utilization and have become more accurate over time. Medicare claims data also provide a mechanism for designating mammography as screening or diagnostic, which subsequently may allow accurate description of a woman's screening history.

Differences in the quality of breast cancer care among vulnerable populations.

BACKGROUND: It is unknown whether differences in the quality of breast cancer care among women from racial and ethnic minority groups, the elderly, and rural areas have changed over time across the continuum of care. METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database identified 22,701 women ages 66-79 years diagnosed with early stage breast cancer from 1992-1999. Multiple breast cancer processes of care were measured, including breast-conserving surgery, radiation therapy, documentation of estrogen receptor status, surveillance mammography, and a combined measure of "adequate care". RESULTS: African-American and Hispanic women were significantly less likely to receive adequate care than White women in unadjusted comparisons (54.7% and 58.0% vs. 68.4% for African-American and Hispanic vs. White women) and adjusted comparisons (adjusted odds ratio [AOR] 0.67; 95% confidence interval [95% CI] 0.59-0.76, and AOR 0.77; 95% CI 0.66-0.90 for African-American and Hispanic women, respectively). The proportion of Asian/Pacific Islander women receiving adequate care was similar to White women. When considering only women diagnosed with breast cancer from 1997-1999, African-American women remained less likely than White women to receive adequate care (AOR 0.63; 95% CI 0.50-0.79). Women ages 75-79 years were less likely to receive adequate care compared with women ages 66-69 years (AOR 0.74; 95% CI 0.69-0.80), and women from rural (vs. metropolitan) areas were less likely to receive adequate care (AOR 0.81; 95% CI 0.73-0.89). CONCLUSIONS: The quality of breast cancer care is lower among vulnerable populations across the continuum of care, and many of these differences have not improved in more recent years.

Physician predictors of mammographic accuracy.

BACKGROUND: The association between physician experience and the accuracy of screening mammography in community practice is not well studied. We identified characteristics of U.S. physicians associated with the accuracy of screening mammography. METHODS: Data were obtained from the Breast Cancer Surveillance Consortium and the American Medical Association Master File. Unadjusted mammography sensitivity and specificity were calculated according to physician characteristics. We modeled mammography sensitivity and specificity by multivariable logistic regression as a function of patient and physician characteristics. All statistical tests were two-sided. RESULTS: We studied 209 physicians who interpreted 1,220,046 screening mammograms from January 1, 1995, through December 31, 2000, of which 7143 (5.9 per 1000 mammograms) were associated with breast cancer within 12 months of screening. Each physician interpreted a mean of 6011 screening mammograms (95% confidence interval [CI] = 4998 to 6677), including a mean of 34 (95% CI = 28 to 40) from women diagnosed with breast cancer. The mean sensitivity was 77% (range = 29%-97%), and the mean false-positive rate was 10% (range = 1%-29%). After adjustment for the patient characteristics of those whose mammograms they interpreted, physician characteristics were strongly associated with specificity. Higher specificity was associated with at least 25 years (versus less than 10 years) since receipt of a medical degree (for physicians practicing for 25-29 years, odds ratio [OR] = 1.54, 95% CI = 1.14 to 2.08; P = .006), interpretation of 2500-4000 (versus 481-750) screening mammograms annually (OR = 1.30, 95% CI = 1.06 to 1.59; P = .011) and a high focus on screening mammography compared with diagnostic mammography (OR = 1.59, 95% CI = 1.37 to 1.82; P<.001). Higher overall accuracy was associated with more experience and with a higher focus on screening mammography. Compared with physicians who interpret 481-750 mammograms annually and had a low screening focus, physicians who interpret 2500-4000 mammograms annually and had a high screening focus had approximately 50% fewer false-positive examinations and detected a few less cancers. CONCLUSION: Raising the annual volume requirements in the Mammography Quality Standards Act might improve the overall quality of screening mammography in the United States.