Can coalitions expand coverage? Progress on two fronts yields advances on a third.
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Biomedical subjects
Publications and source records attributed to S Sullivan.
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OBJECTIVE: We sought to estimate the impact of individual dimensions of hospitals' managed care strategies on the cost per hospital discharge. STUDY SETTING/DATA SOURCES: Thirty-seven member hospitals of seven health systems in the Pacific, Rocky Mountain, and Southwest regions of the United States were studied. STUDY DESIGN: Separate cross-sectional regression analyses of 21,135 inpatient discharges were performed in 1991 and 23,262 discharges in 1992. The multivariate model was estimated with hospital cost per discharge as the dependent variable. Model robustness was checked by comparing regression results at the individual discharge level with those at the level of the hospital/clinical condition pair. DATA COLLECTION/EXTRACTION METHODS: Information on hospitals' managed care strategies was provided by mail and phone survey of key informants in 1991 and 1992. Other hospital characteristics were collected from AHA Annual Survey data, and discharge data from hospital abstracting systems. PRINCIPAL FINDINGS: The pooled discharge analysis indicated three dimensions of hospital managed care strategy that consistently related to lower costs per hospital discharge: the proportion of hospital revenues derived from per case or capitation payment, the hospital's mechanisms for sharing information on resource consumption with clinicians, and the use of formalized, systematic care coordination mechanisms. CONCLUSIONS: Three strategies appear to hold promise for enhancing the efficiency of inpatient resource use: (1) "fixed price" hospital payment incentives, (2) hospital approaches to sharing resource use information with clinicians, and (3) the application of formal care management mechanisms for specific clinical conditions.
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We report here on two retrospective studies conducted between 1982 and 1995 in 137 patients with clinical evidence of chronic paronychia or onycholysis. The purpose of the studies was to determine what factors played a role in these nail disorders. The culture results indicated that yeast commonly grew from the cultured material. Significant contact irritant exposure was frequently found. These findings and our experience suggest that the resolution of chronic paronychia and onycholysis depends on avoiding exposure to contact irritants and on appropriate treatment of any underlying fungal infection. To accomplish this latter goal, it is important to select a broad-spectrum antifungal agent that is effective against yeasts as well as other fungal pathogens.
Twenty-six patients with stable non-alcoholic cirrhosis and normal neurological examination were investigated by brain MRI (inversion recovery sequences) and compared with 16 controls. Brain MRI findings were correlated with the clinical and metabolic status of the patients and analysis of variance and, when necessary, co-variance was performed. Five of the patients (19%) and all 16 controls showed no MRI changes. Twelve patients (46%) showed moderately high signal in the globus pallidus (score 1), and nine (35%) very high signal (score 2). Analysis of variance showed that age was the only significant variable (P = 0.038). Analysis of co-variance after adjustment for age showed that high pallidal signal was correlated only to ammonia level (P = 0.02) but not to any other clinical or biological parameter. We conclude that T1 high intensity pallidal signal is common in non-alcoholic cirrhosis even when neurological examination is normal, but its significance remains unclear.
Interferon-alpha has not been used previously in hemodialysis patients with chronic hepatitis B and C. This uncontrolled report evaluates the biochemical and/or histologic profile resulting from the administration of interferon-alpha in seven hemodialysis patients, two with chronic hepatitis B and five with hepatitis C. Biochemical improvement was noted in all patients. Histologic progression did not occur in the two cases in which such assessment was made, and five of them were subsequently transplanted without recurrence of disease.
To determine what patient characteristics are associated with prolonged emergency department (ED) length-of-stay (LOS) for surgical critical care patients, the charts of 169 patients admitted from the ED directly to the operating room (OR) or intensive care unit (ICU) during a 6-week period in 1993 were reviewed. The ED record was reviewed for documentation of factors that might be associated with prolonged ED LOS, such as use of computed tomographic (CT), radiology special procedures, and the number of plain radiographs and consultants. ED LOS was considered to be the time from triage until a decision was made to admit the patient. Using a Cox proportional hazards model, use of CT and special procedures were the strongest independent predictors of prolonged ED length-of-stay. The number of plain radiographs and consultants had only a minimal effect. Use of a protocol-driven trauma evaluation system was associated with a shorter ED LOS. In addition to external factors that affect ED overcrowding, ED patient management decisions may also be associated with prolonged ED length-of-stay. Such ED-based factors may be more important in surgical critical care patients, whose overall ED LOS is affected more by the length of the ED work-up rather than the time spent waiting for a ICU bed or operating suite.
Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy.
Functional p53 protein is essential for the cellular response to drug-induced DNA damage. We investigated p53 accumulation in tumour specimens from premenopausal breast cancer patients who were randomised to adjuvant chemotherapy (CMF) or postoperative radiotherapy. Of the tumours from 139 patients, 20 showed abnormal accumulation as judged with immunohistochemistry (> 10% positive tumour cells). The risk of distant recurrence was similar in the two treatment groups for patients whose primary tumours lacked p53 accumulation, whereas there was a significant benefit from CMF for patients showing abnormal accumulation (relative risk 0.18, 95% CI, 0.04-0.93). This result suggests that p53-dependent apoptosis is not a general mechanism by which breast cancer cells respond during CMF chemotherapy.
The use of a focus group as a research method has become increasingly common in general practice related studies. Although existing guidelines for planning focus groups are very useful, a review of these guidelines indicate that a few of them are vague and need further elaboration. The authors review five existing guidelines for planning focus groups. These are size, number, duration, format and composition of a focus group. Suggestions have been made to address the uncertainties in these areas when a focus group is used. This paper was a section of manuscript presented at the 2nd International Qualitative Health Research Conference on 11 June 1994, Hershey, Pennsylvania.
Phosphorothioate modification of internucleoside linkages is widely used to prevent degradation of oligodeoxynucleotide (ODN) therapeutic agents in serum and cells. This modification generally increases ODN potency, but in many instances it is associated with an increase of poorly understood nonspecific effects. In this study, we have found that both cellular retention and nonspecific protein binding are dependent upon the extent of the oligonucleotide's modification. Flow cytometry of cells treated with fluorescein-labeled single-stranded (ss) or double-stranded (ds) ODNs demonstrated that fully phosphorothioate-modified ODNs exhibit much greater cellular association than 3'-terminally modified ODNs (with three 3'-terminal phosphorothioate linkages). Additionally, gel shift assays with either ss- or ds-probes showed that fully phosphorothioate-modified ODNs also exhibit much greater cytoplasmic and nuclear protein binding than either 3'-terminally modified or unmodified ODNs. However, gel shift competition assays showed that transcription factor binding by fully phosphorothioate-modified ds-ODNs was completely nonspecific relative to 3'-terminally modified and unmodified ds-ODNs. These results suggest that the benefits derived from full phosphorothioate modification of ODNs may be negated by increases of nonspecific protein binding and associated sequence-independent effects.
We have compared the prediction of distant recurrence for S-phase fraction (SPF) and DNA-ploidy, as estimated by flow cytometry, on an epithelial cell population and an unselected cell population from 268 node-negative breast-cancer patients diagnosed between 1985 and 1988. The tumor tissue was mechanically disintegrated and divided for flow cytometric analysis using both gated cells containing cytokeratin 8 and 18 and ungated cells treated with a detergent-trypsin solution. The relationship to distant recurrence was investigated for flow cytometric data, tumor size and estrogen and progesterone receptor content in univariate and multivariate Cox's regression analysis. The regression analyses were performed on 209 cases with S-phase fractions estimated by both methods. In 11 cases, DNA-ploidy classification differed, reflecting increased sensitivity to minor aneuploid peaks but a decreased ability to separate peaks in the near-diploid region for the gated populations. When SPF were used in univariate analysis as a continuous parameter or the upper tertile was used as cut-off value, SPF from the cytokeratin-gated cell population were most closely associated with recurrence and contributed additional prognostic information to SPF from the unselected cell population in the multivariate analysis. Out of the following variables:tumor size, ER and PR status, SPF and DNA ploidy, only SPF from immunoselected cells contributed prognostic information in multivariate analysis. These results indicate that SPF from immunoselected cell populations improves the prediction of recurrence in node-negative breast cancer.
AIMS: This paper reports on the preparedness of pathological gamblers to seek help through a new national toll-free telephone hotline and compares these callers, on some key dimensions, with a representative sample of pathological gamblers living in the community. METHODS: Callers were assessed using standard diagnostic screens. Sociodemographic data and reported symptoms of stress and depression were also recorded. Callers identified as pathological gamblers were compared with their counterparts in a recent nationwide epidemiological survey. RESULTS: During the first 3 months of operation, 1506 calls were received from 329 callers. Of these 167 were pathological gamblers, 117 were partners or family members and 45 were from various agencies. Pathological gamblers contacting the hotline resembled those from the community survey with respect to gender and age. Maori and Pacific Islanders were underrepresented. Suicidal ideation was reported by over 90% of pathological gambler callers. CONCLUSIONS: The new service provides a means to reach people with serious gambling-related problems and provides information to family members and helping agencies. High reported suicidal ideation was consistent with previous studies showing elevated rates of stress and depression among pathological gamblers. Underutilization by Maori, Pacific Islanders and people with less severe gambling disorders indicates the need to find better ways to engage these groups.
The c-erbB-2 oncogene is frequently amplified and overexpressed in human breast cancer. We have studied the c-erbB-2 protein in conjunction with DNA content in frozen samples from breast cancers using flow cytometry. The cell suspensions were obtained by mechanical disaggregation followed by a short fixation in 1% paraformaldehyde. The level of c-erbB-2 expression was calculated as a fluorescence index, taking into account the relative amount of total cellular fluorescence compared to nonspecific fluorescence. The flow cytometric value correlated with immunohistochemical results obtained with the same monoclonal antibody (c-neu, clone 9G6). Overexpression of c-erbB-2 was significantly more frequent in DNA aneuploid tumors than in DNA diploid ones and correlated with increasing S-phase fraction and estrogen receptor negativity. In 10 DNA multiploid tumors, the different aneuploid stemlines uniformly expressed c-erbB-2, supporting the hypothesis that overexpression is an early event in breast cancer. Of the 172 tumors, the 37 (22%) judged as positive with immunohistochemistry showed a somewhat higher rate of distant recurrence than others (P = 0.14). The fluorescence index was significantly associated with prognosis (P = 0.0012), as it was also among the immunohistochemically positive cases. If the degree of overexpression is important, then flow cytometry could be a feasible technique for classification.
The p53 gene product is a tumour suppressor protein, and alterations of the protein are common in human cancer. Previous studies have focused on nuclear accumulation of p53. To investigate if cytoplasmic accumulation of p53 strengthens the relationships to different pathobiological variables and distant recurrence-free survival in breast cancer, tumours from 164 stage II patients were examined with the monoclonal antibody PAb1801. Nine per cent of the tumours were nuclear positive and 21% were cytoplasmic positive. Cellular p53 accumulation, related to the nucleus or the cytoplasm or both, showed stronger associations with pathobiological variables than nuclear accumulation alone. Accumulation of p53 was significantly correlated to tumour size over 20 mm, negative oestrogen receptor (ER) status, DNA aneuploidy, high S-phase fraction and positive erbB-2 status. Cytoplasmic p53 was significantly correlated to distance recurrence-free survival in patients negative for nuclear p53 (P < 0.0001). Cellular p53 accumulation was an independent prognostic factor, in addition to lymph node status and ER content. We conclude that consideration of cytoplasmic staining enhances the clinical importance of p53.
Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post-operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07-0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours.
The majority of antineutrophil cytoplasmic antibodies (ANCA) in patients with systemic vasculitis (a subset of whom exhibit eosinophilia associated with systemic vasculitis) recognize two neutrophil primary cytoplasmic granule constituents, namely myeloperoxidase (MPO) and proteinase-3. As eosinophil peroxidase (EPO) shares 68% amino acid identity with neutrophil MPO, we have investigated whether serum ANCA reactive with MPO (P-ANCA) also reacts with EPO. In this study we demonstrate that P-ANCA-reactive serum binds to ethanol-fixed neutrophils but not to eosinophils in a perinuclear pattern as assessed by indirect immunofluorescence. In addition, P-ANCA reactive serum did not bind to purified EPO or alter purified EPO function as assessed in a guaiacol assay of EPO activity. These studies suggest that the antigenic epitope recognized by P-ANCA-reactive serum is not determined by the homologous 68% peroxidase sequence shared by neutrophil MPO and EPO.
Chloride channels were previously purified from bovine kidney cortex membranes using a drug affinity column. Reconstitution of the purified proteins into artificial liposomes and planar bilayers yielded chloride channels. A 64-kDa protein, p64, identified as a component of this chloride channel was used to generate antibodies which depleted solubilized kidney membranes of all chloride channel activity. This antibody has now been used to identify a clone, H2B, from a kidney cDNA library. Antibodies, affinity-purified against the fusion protein of H2B also depleted solubilized kidney cortex from all chloride channel activity. The predicted amino acid sequence of p64 shows that it contains two and possibly four putative transmembrane domains and potential phosphorylation sites by protein kinase A, protein kinase C, and casein kinase II. There was no significant homology to other protein (or DNA) sequences in the data base. The protein is expressed in all cells tested. Expression of its mRNA in Xenopus laevis oocytes led to the insertion of a protein with the appropriate molecular mass in microsomes but not in the plasma membrane. It is likely that p64 represents the chloride channel of intracellular organelles.