Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale.

Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR(1)-MR(4)), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR(4.5) level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR(4.5) sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms.

Geographic variation in hospice use prior to death.

OBJECTIVES: To examine national variation in use of the Medicare hospice benefit by older individuals before their death, and to identify individual characteristics and local market factors associated with hospice use. DESIGN: Retrospective analysis of Medicare administrative data. SETTING: Hospice care. PARTICIPANTS: Older Medicare enrollees who died in 1996. MEASUREMENTS: Rate of hospice use per 1,000 older Medicare beneficiary deaths. RESULTS: Overall, 155 of every 1,000 older Medicare beneficiaries who die use hospice before death. This rate is significantly higher among younger older persons (P < .001), non-blacks (P < .001), persons living in wealthier areas (P < .001), and persons in urban areas (P < .001). Areas with a higher proportion of non-cancer diagnoses among hospice users have higher rates of hospice use for both cancer and non-cancer reasons than areas with a majority of hospice users having cancer diagnoses (P < .001). Hospice use is higher in areas with fewer hospital beds per capita (P < .001), areas with lower in-hospital death rates (P < .001), and areas with higher HMO enrollment (P < .001). Rates of hospice use are also positively related to average reimbursements for health care (P < .001) and to physicians per capita (P < .001). In the largest metropolitan statistical areas (MSAs), rates of hospice use vary more than 11-fold from a low of 35.15 (Portland, ME) to a high of 397.2 per 1,000 deaths (Ft. Lauderdale, FL). CONCLUSIONS: The wide variation in hospice use suggests that there is great potential to increase the number of users of the Medicare hospice benefit.

Teaching medical students how to perform a clinical breast examination.

BACKGROUND: One challenge in medical education is to provide training in physical examination skills. The authors conducted a randomized study to compare standardized and unstandardized methods of teaching clinical breast examinations and to determine whether trained non-medical women could teach as well as medical faculty. METHOD: Sensitivity, specificity, and examination techniques were compared between first-year students at the University of Calgary Faculty of Medicine who in 1992-93 received standardized teaching from family medicine faculty or well women teachers and 70 second-year students who received unstandardized teaching during their clinical rotations. Standardized teaching included a specific examination technique using silicone breast models. The students taught by the well women teachers also examined the women's breasts. RESULTS: The standardized-teaching group had more consistent examination techniques and significantly higher sensitivity but lower specificity. The students taught by the well women teachers performed as well as those taught by the family medicine faculty. CONCLUSIONS: The teaching methods used by trained teachers and standardized models improved the students'accuracy of breast lump detection and examination skills.

Disenrollment from Medicare HMOs.

BACKGROUND: Since the program's inception, there has been great interest in determining whether beneficiaries who enter and subsequently leave Medicare health maintenance organizations (HMOs) are more or less costly than those remaining in fee-for-service (FFS) Medicare. OBJECTIVES: To examine whether relatively high-cost beneficiaries disenroll from Medicare HMOs (disenrollment bias) and whether disenrollment bias varies by Medicare HMO market characteristics. In addition, we compare rates of surgical procedures and hospitalizations for ambulatory care-sensitive conditions for disenrollees and continuing FFS beneficiaries. DESIGN: Cross-sectional analysis of 1994 Medicare data. PARTICIPANTS AND METHODS: Medicare beneficiaries were first sampled from the 124 counties with at least 1000 Medicare HMO enrollees. From this pool, HMO disenrollees and a sample of continuing FFS beneficiaries were drawn. The FFS beneficiaries were assigned dates of "pseudodisenrollment." Expenditures and inpatient service use were compared for 6 months after disenrollment or pseudodisenrollment. RESULTS: The HMO disenrollees were no more likely than the continuing FFS beneficiaries to have positive total expenditures (Part A plus Part B) or Part B expenditures in the first 6 months after disenrollment. However, disenrollees were more likely to have Part A expenditures. Among beneficiaries with spending, disenrollees had higher total and Part B expenditures than continuing FFS beneficiaries. Moreover, the disparity in total and Part B spending between disenrollees and continuing FFS beneficiaries increased with HMO market penetration. Although Part A spending was higher for disenrollees with spending, it was not sensitive to changes in market share. The HMO disenrollees received more surgical procedures and were hospitalized for more of the ambulatory care-sensitive conditions than the FFS beneficiaries. CONCLUSIONS: On several measures, Medicare HMOs experienced favorable disenrollment relative to continuing FFS beneficiaries as recently as 1994, which increased as HMO market share increased.

Increasing rates of hospitalization due to septicemia in the US elderly population, 1986-1997.

Rates of hospitalization due to septicemia (International Classification of Diseases, Ninth Revision, Clinical Modification, code 038) in the US elderly population for 1986-1997 were examined, using Medicare administrative data. Age group-, sex-, and race-adjusted rates more than doubled from 1986 through 1997, from 3.42 to 7.42 per 1000 beneficiaries. The 1997 rates of septicemia increased with age, from 4.47 per 1000 beneficiaries among persons 65-74 years old to 18.1 per 1000 beneficiaries among persons > or =85 years old. The rates of septicemia were slightly greater among men (7.46 per 1000 beneficiaries) than among women (7.39 per 1000 beneficiaries) and were higher among blacks (13.61 per 1000 beneficiaries) than among whites (6.89 per 1000 beneficiaries). The most likely sites of the origin of the septicemia were the urinary tract (40.1%) and lungs (15.3%). Escherichia coli and Staphylococcus species were the most frequently reported organisms. Diabetes was listed as a comorbidity in 24.5% of the hospitalizations. We estimate that the cost to Medicare for septicemia hospitalizations in 1997 was >$1.8 billion.

Administrative data for public health surveillance and planning.

Electronically available administrative data are increasingly used by public health researchers and planners. The validity of the data source has been established, and its strengths and weaknesses relative to data abstracted from medical records and obtained via survey are documented. Administrative data are available from a variety of state, federal, and private sources and can, in many cases, be combined. As a tool for planning and surveillance, administrative data show great promise: They contain consistent elements, are available in a timely manner, and provide information about large numbers of individuals. Because they are available in an electronic format, they are relatively inexpensive to obtain and use. In the United States, however, there is no administrative data set covering the entire population. Although Medicare provides health care for an estimated 96% of the elderly, age 65 years and older, there is no comparable source for those under 65.

Nipple candidiasis among breastfeeding mothers. Case-control study of predisposing factors.

OBJECTIVE: To investigate factors that predispose breastfeeding mothers to nipple candidiasis. DESIGN: A retrospective case-control study of women attending the Calgary Breastfeeding Clinic. SETTING: Ambulatory breastfeeding referral centre. PARTICIPANTS: All women (105) who attended the clinic during a 3.5-month study period. All were referred for problems with breastfeeding; 27 (the case group) had positive diagnostic criteria for nipple candidiasis. The other 78 formed a control group. MAIN OUTCOME MEASURE: A patient information sheet, completed while taking a medical history, recorded the presence or absence of four possible predisposing factors. Two infant variables were also noted on physical examination. Patients were diagnosed as having or not having nipple candidiasis on the basis of specific clinical criteria, and statistics on other variables were compared for those with positive and with negative diagnoses. RESULTS: A statistically significant correlation (P < 0.05) was found between nipple candidiasis and three factors: vaginal candidiasis (P = 0.001), previous antibiotic use (P = 0.036), and nipple trauma (P = 0.001). CONCLUSIONS: Further research is required to establish clear causality. However, we recommend that physicians be suspicious of nipple candidiasis; avoid antibiotics or use the shortest effective course; treat yeast vaginitis during the third trimester and after delivery aggressively; and treat mothers for nipple yeast if babies have oral or diaper candidiasis. Breastfeeding mothers can also be counseled in preventive measures.

Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage.

Mothers of children with phenylketonuria have a significantly lower miscarriage rate than a matched control population in Ireland and west Scotland. This protective effect of the gene against some factor causing foetal death would seem to constitute a heterozygote advantage which might account for the previously observed polymorphism for phenylketonuria. It is suggested that the decrease in foetal mortality is mediated by the higher concentration of phenylalanine in the heterozygous mother's blood, but that this is not a simple nutritional effect of an increased supply of an essential amino acid leading to increased protein deposition.

Medicare beneficiaries: adverse outcomes after hospitalization for eight procedures.

Rehospitalization following surgery is widely recognized as an important outcome measure. The purpose of this study was to identify rehospitalizations for adverse events following 8 procedures, using diagnosis and procedure codes contained in Medicare claims files. Adverse events were broadly defined as: 1) complications; 2) failure of the procedure to achieve its therapeutic goal; and 3) untoward events associated with the natural history of the disease being treated with the procedure. Expert panels identified specific diagnosis and procedure codes that might indicate an adverse event if they appeared on the Medicare record of a rehospitalization. Among patients undergoing percutaneous transluminal coronary angioplasty, almost 36% were rehospitalized for an adverse event within a year of surgery; among patients undergoing coronary artery bypass graft surgery, 20% were rehospitalized for an adverse event. Following the other 6 procedures (cholecystectomy, partial excision of the large intestine, total knee replacement, total hip replacement, replacement of the head of the femur, and reduction of fracture of the femur) between 4% and 9% of patients were rehospitalized for an adverse event. Findings from this exploratory study indicate that rehospitalizations for adverse events appear to be a useful outcome measure for the cardiac procedures; they appear to be less useful for the other procedures, at least at the individual hospital or small area level, because of their relative rarity. Future studies should investigate procedures associated with more frequent rehospitalizations, and medical admissions, which often tend to be associated with higher rehospitalization levels.

Birth weight and pathogenesis in phenylketonuria.

The birthweights of an ethnically homogeneous sample of infants with phenylketonuria, their unaffected siblings, and control infants were compared after adjusting for the effects of: mother's age, mother's date of birth, mother's height and obstetric history, the length of gestation, the infant's sex, the place and date of birth. There were no significant differences between the infants with phenylketonuria and their unaffected siblings either in adjusted or unadjusted birthweights. Control infants had slightly, but statistically significant, greater adjusted and unadjusted birthweights than the combined phenylketonuria and unaffected sibling groups. This effect of the phenylketonuria gene is a previously unreported finding but unlikely to be related to the pathogenesis of phenylketonuria. Our results do not provide support for the "justification" hypothesis that the mental and neurological defects in phenylketonuria result from prenatal tyrosine deprivation which would be reflected in lower birthweights.