Medicare changes you need to know about.
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Centers for Medicare and Medicaid Services, U.S.↗
Biomedical subjects
D Murray
Publications and source records attributed to D Murray.
Nucleotide excision repair genes as determinants of cellular sensitivity to cyclophosphamide analogs.
UNLABELLED: The objective of this study was to determine the relative importance of the first six complementation groups of the nucleotide excision repair cross-complementing genes (ERCC1-ERCC6) and the first complementation group of the X-ray repair cross-complementing genes (XRCC1), in the repair of DNA damage induced by the in vitro active cyclophosphamide (CP) derivatives 4-hydroperoxycyclophosphamide (4HC) and phosphorodiamidic mustard (PM). We compared the sensitivity of the wild-type CHO cell line, AA8, with that of the CHO mutant cell lines UV4 and UV20 (ERCC1-), UV5 (ERCC2-), UV24 (ERCC3-), UV41 (ERCC4-), UV135 (ERCC5-), UV61 (ERCC6-), and EM9 (XRCC1-). Cell survival was determined using both growth inhibition and conventional clonogenic assays. The yield of DNA crosslinks in selected cell lines was determined using an ethidium bromide fluorescence assay. RESULTS: The rank ordering of sensitivity to both 4HC and PM, based on the combined survival data, was UV41/UV4/UV20 > > UV61/UV24/UV135/EM9 > or = UV5 approximately AA8. Thus mutations in the ERCC1 and ERCC4 genes impart a hypersensitivity to CP analogs. To confirm the importance of the ERCC1 gene for cellular resistance to 4HC and PM, UV20 cells were transfected with the human ERCC1 gene and subsequently exposed to 4HC and PM. The transfected cells displayed essentially wild-type resistance to both drugs. Furthermore, two interspecific hybrids derived from UV41, both of which retained the region of human chromosome 16 that harbors the ERCC4 gene, displayed essentially wild-type resistance to 4HC and PM, confirming the importance of ERCC4 for the repair of 4HC-induced DNA damage. When crosslinks were assayed after a 60-min treatment with 4HC or a 15-min treatment with PM, their yield paralleled the sensitivity of the cell lines to both drugs: UV41 cells showed markedly elevated levels of crosslinks, whereas AA8 and UV5 cells showed similar (low) levels of crosslinks. CONCLUSIONS: Our findings confirm the general pattern indicating that the ERCC1 and ERCC4 gene products are crucial for the repair of 4HC-induced DNA damage, while the other nucleotide excision repair genes examined are relatively unimportant. These data suggest that the hypersensitivity of ERCC1- and ERCC4- mutants to DNA crosslinking agents may reflect a defect in recombinational repair rather than nucleotide excision repair.
Animals↗
An improved statistical approach: can it clarify the role of new prognostic factors for breast cancer?
Recently, there has been a proliferation of new biomarkers, some of which may lead to an improved prognostic index or may influence treatment selection. However, there are methodological and statistical issues that require attention in assessing the role and use of these prognostic factors. Between 1977 and 1986, 1097 primary breast cancer patients were accrued for multidisciplinary research at the Henrietta Banting Breast Centre, Women's College Hospital; follow-up to 1990 is complete for 96% of the patients. Data for these patients are used here to illustrate strategies: (1) for the comparison of results from diverse assessments of biomarkers; (2) for the improved comparability of inter-laboratory results; (3) for the examination of the results from monoclonal or polyclonal antibody assays for possible clinically relevant bimodality; (4) for good statistical resolution of overlapping distributions; (5) that involve the use of quantitative values for prognostic factors whenever possible; and (6) for improved multivariate analyses. Good data handling and analyses may enable more accurate and rapid assessment of new prognostic factors, thereby expediting and improving their clinical application.
Analysis of Variance↗
Febrile urinary infection in the institutionalized elderly.
PURPOSE: Bacteriuria is common among institutionalized elderly populations, but the contribution of urinary infection to febrile morbidity is unknown because of difficulties in clinical ascertainment. This study was undertaken to febrile morbidity using both clinical and serologic criteria. METHODS: Episodes of fever in residents of two long-term care institutions were identified prospectively for 2 years. Serum and urine specimens were obtained initially and at 4 weeks. The proportion of episodes attributable to urinary infection was determined by both standard clinical criteria proposed for use in these populations and serum antibody response to uropathogens. RESULTS: For 372 fewer episodes, 211 met clinical criteria for infection: 147 (40%) of the respiratory tract; 26 (7%) of the genitourinary tract; 25 (6%) of the gastrointestinal tract; and 13 (3%) of skin and soft tissue. Of the remaining 161 fever episodes, 2 (1%) were noninfectious and 159 (43%) were of unknown origin. The prevalence of bacteriuria for residents with nongenitourinary sources of fever varied from 32% to 75%. An antibody response meeting serologic criteria for urinary infection occurred in 26 (8.3%) of 314 episodes with paired sera obtained; 10 (43%) of 23 identified clinically as genitourinary infection, 14 (11%) of 132 unknown, 1 (4%) of 25 gastrointestinal, and 1 (0.8%) of 122 respiratory. The positive predictive value of bacteriuria for febrile urinary infection identified by clinical criteria was was 11% (95% confidence interval [CI] 4%, 18%) and identified by serologic criteria was 12% (95% CI 7%, 17%). CONCLUSIONS: Urinary infection contributes to less than 10% of episodes of clinically significant fever in this high-prevalence bacteriuric population. A restrictive clinical definition for genitourinary infection has poor sensitivity and specificity compared with serologic criteria for identification of fever of urinary source, and bacteriuria has a low predictive value for identifying febrile urinary infection.
Adult↗
Outcome and risk factors of ischemic heart disease in chronic uremia.
To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals. Twenty-two percent of patients (N = 95) had either a history of angina pectoris or myocardial infarction on starting dialysis therapy. Median time to onset of heart failure was 24 months in those with ischemic heart disease on initiation of dialysis, compared to 55 months in those without (P < 0.0001). This effect was independent of age, diabetes and underlying cardiomyopathy. Median survival was 44 months in those with ischemic disease compared to 56 months in those without (P = 0.0001). This adverse impact was independent of age and diabetes mellitus but, when cardiac failure was added to the Cox's model, ischemic heart disease was no longer an independent predictor of survival. De novo ischemic heart disease, not evident on starting dialysis therapy, occurred in 41 (9%) patients. When compared to patients who never developed ischemic disease (N = 296; 69%), significant and independent predictors of de novo disease were older age (P = 0.0007), diabetes mellitus (P = 0.0001), high blood pressure during follow up on dialysis (P = 0.02) and hypoalbuminemia (P = 0.03), whereas anemia was not an independent predictor. LV mass index was 174 +/- 7 g/m2 in those who developed de novo ischemic disease compared to 155 +/- 3 g/m2 (P < 0.001) in those who did not. Concentric LV hypertrophy, LV dilation and systolic dysfunction were independent risk factors for de novo ischemic heart disease. We conclude that ischemic heart disease occurs frequently in dialysis patients, that its adverse impact is mediated through the development of heart failure, and that the most important, potentially reversible risk factors are hypertension, hypoalbuminemia, and underlying cardiomyopathy.
Adult↗
ERCC1/ERCC4 5'-endonuclease activity as a determinant of hypoxic cell radiosensitivity.
In this study, the relationships between cellular oxygen enhancement ratios (OER) and nucleotide excision repair capability were examined using the UV20 mutant cell line (which has a defective ERCC1 gene). Using a clonogenic survival assay, the OER for the killing of wild-type AA8 cells was 3.2 +/- 0.1, whereas that for UV20 cells was only 2.35 +/- 0.05; the decreased OER of UV20 cells was the result of their significantly greater radiosensitivity relative to wild-type cells under hypoxic conditions. In AA8 cells, hypoxia protected against DNA double-strand break (dsb) induction (determined by pulsed-field gel electrophoresis) by a factor 3.5 +/- 0.3; i.e. to a similar extent that it modulated cell killing. However, this correlation was not apparent in UV20 cells, where hypoxia protected against dsb induction to a similar extent as in wild-type cells (approximately 3.2-fold). Stably transfected UV20 cells over-expressing a full-length ERCC1 cDNA clone displayed a normal OER (3.5 +/- 0.1) in addition to wild-type resistance to UV light. Our data suggest that the hypoxic radiosensitivity of UV20 cells is a direct result of their ERCC1 deficiency and reflects their inability to process some type of DNA damage (not dsbs) that is induced preferentially in hypoxic cells.
Animals↗
Percutaneous feeding tube changes in long-term-care facility patients.
OBJECTIVE: To compare patient outcomes when percutaneous feeding tubes were changed routinely each month or only when necessary (prn). DESIGN: Prospective, randomized, nonblinded crossover study of 6 months of routine monthly changes compared with 6 months of prn changes. SETTING: 416-bed long-term-care facility. PATIENTS: 26 permanent residents with nutrition managed through percutaneous gastrostomy or jejunostomy feeding tubes. The median age was 61.5 years; 8 (31%) also had tracheostomies, and 3 (12%) had indwelling urinary catheters. RESULTS: The frequency of feeding tube changes was 40 per 1,000 patient-days during the 6 months of routine tube changes and 14 per 1,000 when tubes were changed prn (P < .001). There were no differences between the two study periods in frequency of stoma site infections, fever, episodes of emesis, and total antibiotic courses. The median duration in situ of feeding tubes with prn changes was 104 days. For both periods, feeding tubes were significantly more likely to fall out and require replacement with-in 24 hours of previous tube replacement. CONCLUSION: There were no observed differences in clinical outcomes in long-term-care facility patients when feeding tubes were changed only as necessary as compared to routine monthly changes.
Adult↗
AG8 cells, which are highly resistant to hydrogen peroxide, display collateral sensitivity to the combination of hydrogen peroxide and L-histidine.
The results obtained in the present study indicate that AG8 cells, which are highly resistant to H2O2, are not cross-resistant to the combination of H2O2/L-histidine. In fact, once the influence of elevated catalase on the AG8 pheno-type has been circumvented (by treatment of AG8 cells with aminotriazole), AG8 cells display essentially no cross-resistance to the H2O2/L-histidine cocktail while retaining considerable resistance to H2O2 alone (when compared to wild-type AA8 cells). Although H2O2 alone dose not produce DNA double strand breaks (DSBs), this type of lesion was readily detected upon exposure of sensitive or resistant cells to the oxidant in the presence of the amino acid. Interestingly, similar levels of DNA DSBs were detected in AA8 and catalase-depleted AG8 cells. An excellent correlation was found when the cytotoxicity and the level of DNA DSBs obtained in sensitive and resistant cells (with normal or reduced catalase levels) challenged with the cocktail H2O2/L-histidine were compared. This would suggest that DSBs produced on a per cell basis always result in an equal level of toxicity, regardless of the cell type (resistant versus sensitive cell line), the lethality of each of these cell lines being dependent on the number of induced DSBs. In conclusion, the results presented here provide further evidence in support of the hypothesis that cell killing elicited by the combination of H2O2/L-histidine involves a mechanism distinct from that following treatment with H2O2 alone. The fact that H2O2-resistant AG8 cells, which are not cross-resistant to agents promoting cell death via DNA DSB-induction, display collateral sensitivity to the cocktail H2O2/L-histidine, strongly suggests that cell killing triggered by this treatment is mediated by DNA double strand breakage.
Animals↗
Dynamic lymphoscintigraphy to identify the sentinel and satellite nodes.
Lymphoscintigraphy is increasingly used to identify the first draining node (sentinel node) in patients with malignant melanoma or breast cancer. If the sentinel node is tumor free then the remainder of the nodes in that specific nodal bed are likely to be free of metastases. Localization and biopsy of the sentinel node with an intraoperative surgical probe may obviate more radical lymph node dissection. Lymphoscintigraphy is conventionally performed by injecting the radioactive tracer in the four quadrants around the primary tumor and imaging the appropriate nodal beds approximately 30 minutes later. The visualized node nearest the tumor usually is assumed to represent the sentinel node. To test this assumption, a dynamic acquisition was obtained in 16 patients with malignant melanoma to determine if the node nearest the tumor was actually the first draining node. In one of 16 patients, the radioactive tracer injected around a thigh melanoma drained first to an inguinal node and then drained inferiorly to a second inguinal node located closer to the tumor. The distinction between the sentinel and satellite (secondary draining nodes) may have important clinical implications regarding the number of nodes that require surgical excision. In summary, static images do not define the pattern of lymph flow and the node nearest the tumor is not necessarily the sentinel node. Failure to obtain dynamic images may lead to misdiagnosis of the sentinel node in a small percentage of patients.
Humans↗
Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury.
The usual initial life-threatening effect of injury is hypovolemic shock. In the hierarchical physiologic response to hypovolemia, perfusion of peripheral tissues is sacrificed early and restored late. But the usual hemodynamic and metabolic measurements of blood pressure, urine output, and base deficit are not reliable indices of peripheral perfusion. Although the Clark electrode can quantitate tissue oxygen pressure and thereby serve as an index of perfusion, its use is compromised by several technical deficiencies. Recently, an optical method (optode) using fluorescent technology has been developed for measurement of oxygen tension in subcutaneous tissue (P sgO2). Our studies compared this device with the Clark electrode in the laboratory and tested its value in both animal and clinical studies of hypovolemic shock. The results of these several studies demonstrated that: (1) the new oximeter tracked a rapid fall or rapid rise of oxygen tension between room air (150 mm Hg) and 0 mm Hg ( a glucose oxidase/catalase solution) as well as the Clark electrode without encountering its technical problems; (2) with an acute hemorrhage to 20% of base line, the PsgO2 was found to decline rapidly in parallel with the decline of mean arterial pressure (MAP). Although the MAP rapidly returned to normal after immediate complete return of all shed blood, the PsgO2 did not reach normal levels for at least 2 hours, suggesting persistent peripheral vasoconstriction. (3) Studies in progress suggest that between 35 and 78% of trauma patients (n = 18) adequately resuscitated for hypovolemia b customary criteria have a decreased level of PsgO2 for as long as 60 hours after resuscitation for injury. If care is taken to prevent other causes of catecholamine induced vasoconstriction such as pain, fear, cold, and arterial hypoxia, these several results suggest that a certain number of injured patients are inadequately resuscitated despite the return to normal of conventional hemodynamic measurements. The serial analysis of PsgO2 may assist in managing patients and promote better understanding of the responses to injury.
Animals↗
Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody.
Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.
Adult↗
Comparison of measures to assess outcomes in total hip replacement surgery.
OBJECTIVES: To compare the performance of a disease specific and a general health questionnaire in assessing changes resulting from total hip replacement. DESIGN: Two stage prospective study of patients undergoing total hip replacement surgery involving an assessment at a clinic before and six months after surgery. 60(32%) patients were followed up by post. SETTING: Outpatient departments at a specialist orthopaedic hospital and peripheral clinics within Oxfordshire. PATIENTS: 188 patients admitted for unilateral total hip replacement between February and mid-August 1994. MAIN MEASURES: Patients' self assessed scores with the 12 item Oxford hip score and SF-36 general health questionnaire together with surgeons' assessment with Charnley hip score obtained before and again at six months after surgery. RESULTS: 186 patients were followed up six months after total hip replacement; a subsample (n=60) by post. Of the 60 postal patients, 59(98.3%) fully completed the Oxford hip score compared with 44(73.3%) who fully completed the SF-36. For the followup sample as a whole, post operative changes in scores produced a large effect size of 2.75 on the Oxford hip score, compared with -1.89 physical function (SF-36), -2.13 pain (SF-36). With the exception of physical function and role (physical), postoperative SF-36 scores were shown to be similar to or better than those found by two population surveys on patients of comparable age. The responsiveness of a disease specific questionnaire, the Oxford hip score, and relevant sections of a general questionnaire, SF-36, were found to be similar as assessed by three different criteria. CONCLUSIONS: A disease specific questionnaire, the Oxford hip score, and a general state of health questionnaire, SF-36, performed similarly in assessing outcomes of total hip replacement except that the disease specific questionnaire resulted in a higher completion rate and greater responsiveness in some sections. On the other hand the general health questionnaire drew attention to broader problems of physical function not considered by the Oxford hip score. The health questionnaires examined here offer a valid and practical means of monitoring outcomes of hip replacement surgery.
England↗
The problem of 'noise' in monitoring patient-based outcomes: generic, disease-specific and site-specific instruments for total hip replacement.
OBJECTIVES: To compare the performance of three types of patient-based health status instrument--generic, disease-specific and site-specific--in assessing changes resulting from total hip replacement (THR). METHODS: A two-stage prospective study of patients undergoing surgery for THR involving an assessment at a pre-surgical clinic and a follow-up clinic at 6 months. 173 patients with a diagnosis of arthritis and being admitted for unilateral THR were recruited in the outpatient departments of a specialist orthopaedic hospital and peripheral clinics within Oxfordshire. Patients' health status was assessed using the 12-item Oxford Hip Score, the Arthritis Impact Measurement Scales (AIMS) and SF-36 general health questionnaire together with their surgeons' assessment using Charnley hip score obtained before and 6 months after surgery. RESULTS: Effect sizes, used to compare change scores, revealed that pain and function domains changed most following THR on both the AIMS and the SF-36. 71 patients (41%) were assessed as having symptoms or problems currently affecting lower limb joints other than the hip recently replaced. Change scores were compared between these patients and all other patients who reported no current problems with other joints. The Oxford Hip Score found no significant difference between change scores for these two groups of patients while both AIMS and SF-36 physical and pain dimensions recorded significant differences of similar magnitude (physical P < 0.01, pain P < 0.05). Likely reasons for this were apparent on closer inspection of the item content of each instrument. CONCLUSIONS: Assessment of outcomes in THR is necessarily long-term. Within studies of this kind, a hip-specific instrument (Oxford Hip Score) is likely to be more able to distinguish between symptoms and functional impairment produced by the index joint, as compared with other joints and conditions, than either a disease-specific instrument (AIMS) or a generic health status measure (SF-36). This is important given the high probability of existing and subsequent co-morbidity affecting such populations of patients. This consideration is likely to be relevant to any long-term assessment programme following treatment for a condition which threatens bilateral expression over time.
Activities of Daily Living↗
Cocaine use and characteristics of young adult users from 1987 to 1992: the CARDIA Study. Coronary Artery Risk Development in Young Adults.
OBJECTIVES: This study examined the relationship of sociodemographic factors and use of substances other than cocaine to cocaine use from 1987 to 1992 in a cohort of Black and White men and women 20 to 32 years of age. METHODS: Data were collected as part of the Coronary Artery Risk Development in Young Adults study. Self-reported cocaine use was analyzed through chi-square tests and repeated measures analyses of variance to determine the bivariate and multivariate relationships of sociodemographics and substance use behaviors to cocaine use over the 5-year period. RESULTS: Cocaine use declined in Whites but remained stable in Blacks from 1987 to 1992. Cross-sectional results showed that use was related to being Black, male and in the older half of the cohort, single, and unemployed; it was also related to higher levels of other substance use in 1987 and 1992. Over time, the magnitude and strength of the relationship were consistent for each variable except for increased odds of cocaine use among the unemployed and Blacks in 1992. CONCLUSIONS: Sociodemographic characteristics and substance use behavior consistently identify individuals at risk for cocaine use. As a result, intervention programs should be targeted at these high-risk groups.
Adult↗
In their own words. Surgeon representatives discuss legislative and regulatory issues.
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Centers for Medicare and Medicaid Services, U.S.↗
Questionnaire on the perceptions of patients about total hip replacement.
We developed a 12-item questionnaire for completion by patients having total hip replacement (THR). A prospective study of 220 patients was undertaken before operation and at follow-up six months later. Each completed the new questionnaire as well as the SF36, and some the Arthritis Impact Measurement Scales (AIMS). An orthopaedic surgeon assessed the Charnley hip score. The single score derived from the questionnaire had a high internal consistency. Reproducibility was examined by test-retest reliability and was found to be satisfactory. The validity of the questionnaire was established by obtaining significant correlation in the expected direction with the Charnley scores and relevant scales of the SF36 and the AIMS. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at the follow-up. The standardised effect size for the new questionnaire compared favourably with that for the SF36 and the AIMS. The new questionnaire provides a measure of outcome for THR which is short, practical, reliable, valid and sensitive to clinically important changes.
Activities of Daily Living↗
Seven ways to prepare for managed care.
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Financial Management↗
Decision analysis and screening for Down's syndrome. Estimate of uptake of amniocentesis is overoptimistic.
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Adult↗