Cyclosporin A-dependent downregulation of the Na+/Ca2+ exchanger expression.

Cyclosporin A (CsA) is an immunosuppressive drug commonly given to transplant patients. Its application is accompanied by severe side effects related to calcium, among them hypertension and nephrotoxicity. The Na+/Ca2+ exchanger (NCX) is a major calcium regulator expressed in the surface membrane of all excitable and many nonexcitable tissues. Three genes, NCX1, NCX2, and NCX3 code for Na+/Ca2+ exchange activity. NCX1 gene products are the most abundant. We have shown previously that exposure of NCX1-transfected HEK 293 cells to CsA, leads to concentration-dependent reduction of Na+/Ca2+ exchange activity and surface expression, without a reduction in total cell-expressed NCX1 protein. We show now that the effect of CsA on NCX1 protein expression is not restricted to transfected cells overexpressing the NCX1 protein but exhibited also in cells expressing endogenously the NCX1 protein (L6, H9c2, and primary smooth muscle cells). Exposure of NCX2- and NCX3-transfected cells to CsA results also in reduction of Na+/Ca2+ exchange activity and surface expression, though the sensitivity to the drug was lower than in NCX1-transfected cells. Studying the molecular mechanism of CsA-NCX interaction suggests that cyclophilin (Cyp) is involved in NCX1 protein expression and its modulation by CsA. Deletion of 426 amino acids from the large cytoplasmic loop of the protein retains the CsA-dependent downregulation of the truncated NCX1 suggesting that CsA-Cyp-NCX interaction involves the remaining protein domains.

Skin level division of percutaneous endoscopic gastrostomy without endoscopy retrieval: a hazardous procedure.

Percutaneous endoscopic gastrostomy (PEG) has become the method of choice for long-term enteral access in the pediatric population. Since its introduction, several common complications have been described. Less well known is the danger of removing or replacing a PEG by cutting the device at skin level without endoscopic assistance to ensure the complete removal of all parts. The aim of the present work is to describe a patient in whom gastrostomy parts were retained after PEG removal, causing bowel obstruction and perforation.

Factors affecting appropriateness of hospital utilization in two hospitals in Turkey.

To determine the extent of inappropriate hospital use, to investigate factors related to variations in appropriateness, and to identify reasons for inappropriateness, the Appropriateness Evaluation Protocol (AEP) was applied to 2,067 patient days in two hospitals between March 1997 and 1998 in Ankara, Turkey. A substantial amount of inappropriate utilization was found in both hospitals (34.2%, 24.6%). Factors affecting the appropriateness of hospital utilization and reasons for inappropriateness were varied and presented by internal medicine, general surgery, and gynecology services. In general, results of the logistic regression analysis indicated that inappropriateness was significantly associated with admission number (first admission/readmission), admission route (emergent/non-emergent), and day of the week. The most common reason for inappropriateness was diagnostic procedures and/or treatments that could have been carried out on an ambulatory basis. This study demonstrates that the AEP can be used as a tool to improve the efficiency of the Turkish hospitals.

Mammography use, breast cancer stage at diagnosis, and survival among older women.

BACKGROUND: Women age 65 years and older account for most newly diagnosed breast cancers and deaths from breast cancer. Yet, older women are least likely to undergo mammography, perhaps because mammography's value is less well demonstrated in older women. OBJECTIVE: To investigate the relationship between prior mammography use, cancer stage at diagnosis, and breast cancer mortality among older women with breast cancer. DESIGN: Retrospective cohort study using the Linked Medicare-Tumor Registry Database. SETTING: Population-based data from three geographic areas included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. PARTICIPANTS: Women aged 67 and older diagnosed with a first primary breast cancer, from 1987 to 1993, residing in Connecticut, metropolitan Atlanta, Georgia, or Seattle-Puget Sound, Washington. MEASUREMENTS: Medicare claims were reviewed and women were classified according to their mammography use during the 2 years before diagnosis: nonusers (no prior mammograms), regular users (at least two mammograms at least 10 months apart), or peri-diagnosis users (only mammogram(s) within 3 months before diagnosis). Mammography utilization was linked with SEER data to determine stage at diagnosis and cause of death. Our main outcome variables were (1) stage at diagnosis, classified as early (in situ/Stage I) or late (Stage II or greater), and (2) breast cancer mortality, measured from diagnosis until death from breast cancer or end of the follow-up period (December 31, 1994). RESULTS: Older women who were nonusers of mammography were diagnosed with breast cancer at Stage II or greater more often than regular users (adjusted odds ratio (OR), 3.12; 95% confidence interval (CI), 2.74-3.58). This association was present within each age group studied. Nonusers of mammography were at significantly greater risk of dying from their breast cancer than regular users for all women (adjusted hazard ratio (HR), 3.38; 95% CI, 2.65-4.32) and for women within each age group. Even assuming a lead time of 1.25 years, nonusers of mammography continued to be at increased risk of dying from breast cancer. Our findings remained significant for all women and for the two youngest age groups (67-74 years, 75-85 years), although the benefit was no longer statistically significant for the oldest women (85 years and older). CONCLUSIONS: Older women who undergo regular mammography are diagnosed with an earlier stage of disease and are less likely to die from their disease. These data support the use of regular mammography in older women and suggest that mammography can reduce breast cancer mortality in older women, even for women age 85 and older.

The Addiction Severity Index: a field study of internal consistency and validity.

This study investigated whether the use of the Addiction Severity Index (ASI) in a network of inner-city alcohol and drug abuse clinics under nonideal conditions would yield internally consistent and valid data. A sample of 8,984 ASI scores was collected over a 34-month period. Construct validity was examined by computing the internal consistency of all subscales. Convergent and divergent validity of composite scores and of severity ratings were evaluated using correlation matrices. Findings demonstrated that ASI scores were internally consistent and valid, even though the recommended administration protocol may not always have been followed as faithfully as might be desirable. This robustness bodes well for the use of the ASI in on-line clinical environments. Results should be viewed with caution until the reliability of ASI administration is tested under similar nonideal conditions and until permissible deviations from standard protocol can be quantified.

The value of case management in the publicly funded substance abuse treatment system. The perspective of program directors, case managers and clients.

The many purposes of this article is to understand the role and value of case management from the perspective of program directors, case managers and clients. A survey of program directors from publicly funded substance abuse treatment programs in Boston was administered, and in-depth interviews with a sample of program directors, case managers, and clients were conducted. Case management allowed programs to serve more complex clients and increased time available for counselors to focus on the clinical needs of clients. From the perspective of case managers and clients, much of the value of case management came from educating clients about steps they could take to meet their needs and then supporting them in their efforts as they took these steps. Successful steps taken to deal with these needs helped lay the foundation necessary to confront the challenges of treatment. Program directors, case managers, and clients considered case management a valuable enhancement to substance abuse treatment.

The value of acupuncture detoxification programs in a substance abuse treatment system.

Our purpose is to compare baseline characteristics and detoxification readmission rates of clients treated at outpatient acupuncture programs and at short-term residential programs, two options available to persons seeking substance abuse detoxification. This was a retrospective cohort study using data on clients discharged from publicly funded detoxification programs in Boston between January 1993 and September 1994. Multivariate models were used to examine the effect on 6-month detoxification readmission rates of treatment at residential detoxification programs (used by 6,907 clients) versus at outpatient acupuncture programs (used by 1,104 clients) after adjusting for baseline differences. Acupuncture clients were less likely to be readmitted for detoxification within 6 months (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.53-0.95). Similar results were found when the analysis was performed on a subsample of clients that were relatively similar in terms of baseline characteristics (OR 0.61, 95% CI 0.39-0.94). We determined that acupuncture detoxification programs are a useful component of a substance abuse treatment system.

Cigarettes, alcohol, marijuana, other risk behaviors, and American youth.

Increases in adolescent marijuana and other drug use have created widespread concern. One theory argues that increased use of cigarettes and alcohol among younger adolescents leads to greater use of marijuana which, in turn, leads to subsequent use of other drugs (e.g. cocaine, heroin, hallucinogens). Detractors of this theory claim that use of these substances is a symptom of a larger set of destructive behaviors (e.g. violence, suicide, promiscuous sex), and marijuana has no independent effect on the use of other more serious drugs. The authors examined whether, for high school seniors, early use of cigarettes, alcohol and marijuana has an independent effect on more serious drug use even when other behaviors are considered. Using the 1995 Youth Risk Behavior Survey (n = 2871) and logistic analysis, after accounting for selected other behaviors, seniors using cigarettes before age 13 were 3.3 (95% C.I. 2.3,4.6) times likelier to have used marijuana than ones who never smoked; for alcohol, the odds ratio was 4.5 (2.6,7.7). Seniors using marijuana before the age of 14 were 7.4 times (4.0,13.6) likelier to have used other drugs. Though no causal effect is demonstrated, cigarette and alcohol use was associated with the likelihood of marijuana use; marijuana use was associated with the likelihood of other drug use, even after selected other risk and protective behaviors were considered.

R2: a useful measure of model performance when predicting a dichotomous outcome.

R2 has been criticized as a measure of model performance when predicting a dichotomous outcome, both because its value is often low and because it is sensitive to the prevalence of the event of interest. The C statistic is more widely used to measure model performance in a 0/1 setting. We use a simple parametric family of models to illustrate the potential usefulness of models with low R2 values, to clarify the effect of prevalence on both C and R2, and to demonstrate how R2 captures information not picked up by C. We also show that C is subject to a 'random mixing' problem that does not affect R2. Finally, we report both R2 and C values for different risk-adjustment models in situations with different prevalences and show the relationship between the measures and decile death rates, thereby providing a context for interpreting R2 values in a 0/1 setting.

Mammography use helps to explain differences in breast cancer stage at diagnosis between older black and white women.

BACKGROUND: Older black women are less likely to undergo mammography and are more often given a diagnosis of advanced-stage breast cancer than older white women. OBJECTIVE: To investigate the extent to which previous mammography explains observed differences in cancer stage at diagnosis between older black and white women with breast cancer. DESIGN: Retrospective cohort study using the Linked Medicare-Tumor Registry Database. SETTING: Population-based data from three geographic areas of the United States included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (Connecticut; metropolitan Atlanta, Georgia; and Seattle-Puget Sound, Washington). PARTICIPANTS: Black and white women 67 years of age and older in whom breast cancer was diagnosed between 1987 and 1989. MEASUREMENTS: Medicare claims were used to classify women according to mammography use in the 2 years before diagnosis as nonusers (no previous mammography), regular users (> or =2 mammographies done at least 10 months apart), or peri-diagnosis users (mammography done only within 3 months before diagnosis). Information on mammography use was linked with SEER data to determine cancer stage at diagnosis. Stage was classified as early (in situ or local) or late (regional or distant). RESULTS: Black women were more likely to not undergo mammography (odds ratio [OR], 3.00 [95% CI, 2.41 to 3.75]) and to be given a diagnosis of late-stage disease (OR, 2.49 [CI, 1.59 to 3.92]) than white women. When women were stratified by previous mammography use, the black-white difference in cancer stage occurred only among nonusers (adjusted OR, 2.54 [CI, 1.37 to 4.71]). Among regular users, cancer was diagnosed in black and white women at similar stages (adjusted OR, 1.34 [CI, 0.40 to 4.51]). In logistic modeling, previous mammography alone explained about 30% of the excess late-stage disease in black women. In a separate model, previous mammography explained 12% of the excess late-stage disease among black women after adjustment for sociodemographic and comorbidity information. CONCLUSION: Differences in breast cancer stage at diagnosis between older black and white women are related to previous mammography use. Increased regular use of mammography may result in a shift toward earlier-stage disease at diagnosis and narrow the observed differences in stage at diagnosis between older black and white women.

Predicting in-hospital deaths from coronary artery bypass graft surgery. Do different severity measures give different predictions?

OBJECTIVES: Severity-adjusted death rates for coronary artery bypass graft (CABG) surgery by provider are published throughout the country. Whether five severity measures rated severity differently for identical patients was examined in this study. METHODS: Two severity measures rate patients using clinical data taken from the first two hospital days (MedisGroups, physiology scores); three use diagnoses and other information coded on standard, computerized hospital discharge abstracts (Disease Staging, Patient Management Categories, all patient refined diagnosis related groups). The database contained 7,764 coronary artery bypass graft patients from 38 hospitals with 3.2% in-hospital deaths. Logistic regression was performed to predict deaths from age, age squared, sex, and severity scores, and c statistics from these regressions were used to indicate model discrimination. Odds ratios of death predicted by different severity measures were compared. RESULTS: Code-based measures had better c statistics than clinical measures: all patient refined diagnosis related groups, c = 0.83 (95% C.I. 0.81, 0.86) versus MedisGroups, c = 0.73 (95% C.I. 0.70, 0.76). Code-based measures predicted very different odds of dying than clinical measures for more than 30% of patients. Diagnosis codes indicting postoperative, life-threatening conditions may contribute to the superior predictive power of code-based measures. CONCLUSIONS: Clinical and code-based severity measures predicted different odds of dying for many coronary artery bypass graft patients. Although code-based measures had better statistical performance, this may reflect their reliance on diagnosis codes for life-threatening conditions occurring late in the hospitalization, possibly as complications of care. This compromises their utility for drawing inferences about quality of care based on severity-adjusted coronary artery bypass graft death rates.

Improving publicly funded substance abuse treatment: the value of case management.

OBJECTIVES: This study evaluated the impact of case management on client retention in treatment and short-term relapse for clients in the publicly funded substance abuse treatment system. METHODS: A retrospective cohort design was used to study clients discharged from the following four modalities in 1993 and 1994: short-term residential (3112 clients), long-term residential (2888 clients), outpatient (7431 clients), and residential detox (7776 clients). Logistic regression models were used to analyze the impact of case management after controlling for baseline characteristics. RESULTS: The odds that case-managed clients reached a length of stay previously identified as associated with more successful treatment were 1.6 (outpatient programs) to 3.6 (short-term residential programs) times higher than the odds for non-case-managed clients. With the exception of outpatient clients, the odds of case-managed clients' being admitted to detox within 90 days after discharge (suggesting relapse) were about two thirds those of non-case-managed clients. The odds of case-managed detox clients' transitioning to post-detox treatment (a good outcome) were 1.7 times higher than the odds for non-case-managed clients. CONCLUSIONS: Case management is a low-cost enhancement that improves short-term outcomes of substance abuse treatment programs.

Differences in procedure use, in-hospital mortality, and illness severity by gender for acute myocardial infarction patients: are answers affected by data source and severity measure?

OBJECTIVES: According to some studies, women with heart disease receive fewer procedures and have higher in-hospital death rates than men. These studies vary by data source (hospital discharge abstract versus detailed clinical information) and severity measurement methods. The authors examined whether evaluations of gender differences for acute myocardial infarction patients vary by data source and severity measure. METHODS: The authors considered 10 severity measures: four using clinical medical record data and six using discharge abstracts (diagnosis and procedure codes). The authors studied all 14,083 patients admitted in 1991 for acute myocardial infarction to 100 hospitals nationwide, examining in-hospital death and use of coronary angiography, coronary artery bypass graft surgery (CABG), and percutaneous transluminal coronary angioplasty (PTCA). Logistic regression was used to calculate odds ratios for death and procedure use for women compared with men, controlling for age and each of the severity scores. RESULTS: After adjusting only for age, women were significantly more likely than men to die and less likely to receive CABG and coronary angiography. Severity measures provided different assessments of whether women were sicker than men; for all cases, clinical data-based MedisGroups rated women's severity compared with men's, whereas four code-based severity measures viewed women as sicker. After adjusting for severity and age, women were significantly more likely than men to die in-hospital and less likely to receive coronary angiography and CABG; women and men had relatively equal adjusted odds ratios of receiving PTCA. Odds ratios reflecting gender differences in procedure use and death rates were similar across severity measures. CONCLUSIONS: Comparisons of severity-adjusted in-hospital death rates and invasive procedure use between men and women yielded similar findings regardless of data source and severity measure.

Length of stay as an outcome in an era of managed care. An empirical study.

Longer length of stay (LOS) in substance abuse treatment, a standard measure of treatment success, conflicts with pressures from managed care. To maintain LOS as an outcome, we identified, for four modalities, LOS categories such that program completion rates were relatively constant within category and differed among categories. We validated the cutoffs by showing that future utilization over a 2-year period by clients differed by category. Clients in the long-LOS category used the system in a way consistent with more successful treatment. Thus, rather than using increase in LOS as an outcome, one can use increase in the percentage of clients reaching the long-LOS category. Categories were developed and utilization analyzed for discharges from publicly funded Boston treatment programs between 1/92 and 12/94 from the following modalities: short-term residential (5,462 discharges), long-term residential (5,086 discharges), outpatient (13,656 discharges), and detox (19,965 discharges).

Predicting in-hospital mortality for stroke patients: results differ across severity-measurement methods.

OBJECTIVE: To see whether severity-adjusted predictions of likelihoods of in-hospital death for stroke patients differed among severity measures. METHODS: The study sample was 9,407 stroke patients from 94 hospitals, with 916 (9.7%) in-hospital deaths. Probability of death was calculated for each patient using logistic regression with age-sex and each of five severity measures as the independent variables: admission MedisGroups probability-of-death scores; scores based on 17 physiologic variables on admission; Disease Staging's probability-of-mortality model; the Seventy Score of Patient Management Categories (PMCs); and the All Patient-Refined Diagnosis Groups (APR-DRGs). For each patient, the odds of death predicted by the severity measures were compared. The frequencies of seven clinical indicators of poor prognosis in stroke were examined for patients with very different odds of death predicted by different severity measures. Odds ratios were considered very different when the odds of death predicted by one severity measure was less than 0.5 or greater than 2.0 of that predicted by a second measure. RESULTS: MedisGroups and the physiology scores predicted similar odds of death for 82.2% of the patients. MedisGroups and PMCs disagreed the most, with very different odds predicted for 61.6% of patients. Patients viewed as more severely III by MedisGroups and the physiology score were more likely to have the clinical stroke findings than were patients seen as sicker by the other severity measures. This suggests that MedisGroups and the physiology score are more clinically credible. CONCLUSIONS: Some pairs of severity measures ranked over 60% of patients very differently by predicted probability of death. Studies of severity-adjusted stroke outcomes may produce different results depending on which severity measure is used for risk adjustment.

Judging hospitals by severity-adjusted mortality rates: the influence of the severity-adjustment method.

OBJECTIVES: This research examined whether judgments about a hospital's risk-adjusted mortality performance are affected by the severity-adjustment method. METHODS: Data came from 100 acute care hospitals nationwide and 11880 adults admitted in 1991 for acute myocardial infarction. Ten severity measures were used in separate multivariable logistic models predicting in-hospital death. Observed-to-expected death rates and z scores were calculated with each severity measure for each hospital. RESULTS: Unadjusted mortality rates for the 100 hospitals ranged from 4.8% to 26.4%. For 32 hospitals, observed mortality rates differed significantly from expected rates for 1 or more, but not for all 10, severity measures. Agreement between pairs of severity measures on whether hospitals were flagged as statistical mortality outliers ranged from fair to good. Severity measures based on medical records frequently disagreed with measures based on discharge abstracts. CONCLUSIONS: Although the 10 severity measures agreed about relative hospital performance more often than would be expected by chance, assessments of individual hospital mortality rates varied by different severity-adjustment methods.

Do severity measures explain differences in length of hospital stay? The case of hip fracture.

OBJECTIVE: To examine whether judgments about hospital length of stay (LOS) vary depending on the measure used to adjust for severity differences. DATA SOURCES/STUDY SETTING: Data on admissions to 80 hospitals nationwide in the 1992 MedisGroups Comparative Database. STUDY DESIGN: For each of 14 severity measures, LOS was regressed on patient age/sex, DRG, and severity score. Regressions were performed on trimmed and untrimmed data. R-squared was used to evaluate model performance. For each severity measure for each hospital, we calculated the expected LOS and the z-score, a measure of the deviation of observed from expected LOS. We ranked hospitals by z-scores. DATA EXTRACTION: All patients admitted for initial surgical repair of a hip fracture, defined by DRG, diagnosis, and procedure codes. PRINCIPAL FINDINGS: The 5,664 patients had a mean (s.d.) LOS of 11.9 (8.9) days. Cross-validated R-squared values from the multivariable regressions (trimmed data) ranged from 0.041 (Comorbidity Index) to 0.165 (APR-DRGs). Using untrimmed data, observed average LOS for hospitals ranged from 7.6 to 23.9 days. The 14 severity measures showed excellent agreement in ranking hospitals based on z-scores. No severity measure explained the differences between hospitals with the shortest and longest LOS. CONCLUSIONS: Hospitals differed widely in their mean LOS for hip fracture patients, and severity adjustment did little to explain these differences.

Variability in mammography use among older women.

OBJECTIVE: To determine rates of and explore factors associated with mammography use among older women. DESIGN: Retrospective review of part B (physician) bills submitted to Medicare during 1990. SETTING: Health Care Financing Administration (HCFA) data, including sociodemographic information and part B physician bills for all services delivered to Medicare-eligible women in 1990. PATIENTS/PARTICIPANTS: Women age 65 or older as of January 1, 1990, residing in one of 10 states with part B coverage through December 31, 1990. MEASUREMENTS AND MAIN RESULTS: The outcome was receipt of a mammogram (yes/no). We explored factors associated with mammography use within three age groups: 65 to 74, 75 to 84, and 85+. The factors considered were race, state, median income of ZIP Code of residence (from the 1990 US Census, and used to divide the population into quintiles within each state), and number of primary care visits (0, 1, 2, and 3+). Overall, 15% of women had a mammogram: 20% of women age 65 to 74, 12% of women age 75 to 84, and 4% of women age 85 and older. Mammography use was lowest in Oklahoma and highest in Washington. However, in each state the older the age category, the less the mammography use (e.g., 9% vs 5% vs 2% in Oklahoma and 25% vs 16% vs 5% in Washington for women 65-74, 75-84, and 85+, respectively). Mammography use was lower for black than for white women age 65 to 74 (14% vs 21%, P < .001) and 75 to 84 (9% vs 12%, P < .001). Women in each of these two age groups had lower mammography use if they resided in the lowest income quintile and highest if they resided in the highest income quintile (17% vs 23% 65-74, and 10% vs 13% 75-84, P values < .001). Among the oldest women (those 85+), mammography use was low (4%) and varied minimally by race and income (P = .907 and .003, respectively). In all age groups, mammography use was lowest among women who did not have a primary care visit, was greater among women who had at least one visit, and continued to rise with increasing numbers of visits (all P values < .001). For example, among women age 75 to 84, mammography use increased from 5% to 10%, 14%, and 17% for those with 0, 1, 2, and 3+ visits. CONCLUSIONS: We found that mammography use was less for women who were older, of black race, who did not visit a primary care provider, and who lived in areas with lower median income and certain geographic locations (states). Similar factors influenced mammography use in women age 65 to 74, where there is greater consensus as to who should receive a mammogram, and women age 75 to 84, where there is neither consensus nor data. Surprisingly, neither race nor income had much influence on mammography use among women age 85 or older.

The importance of comorbidities in explaining differences in patient costs.

OBJECTIVES: The authors examine to what extent comorbidities contribute to differences in patient hospital costs. METHODS: The medical record data for this study were collected from 15 metropolitan Boston hospital for 4,439 patients admitted mostly in 1985 for one of eight common conditions. Massachusetts hospital discharge abstract data for 1985 and 1993 also were used. Comorbidities were identified from the medical record for the 15-hospital data set and from discharge abstracts for all cases. Stepwise regression models were used to develop comorbidity scores. RESULTS: Across all conditions, the medical record-based comorbidity score increased the R2 value from .42 in a model with diagnosis-related groups alone to .50. In condition-specific analyses, including the comorbidity score increased the R2 by more than 50% in six of eight conditions, and was more important than several other dimensions of severity in explaining condition-specific costs. When comorbidities were determined from discharge abstract data rather than medical records, only approximately half as much comorbidity was found. Also, there was much less explanatory power: the all-condition R2 only went from .42 to .44. However, a comorbidity score developed from statewide hospital discharge abstract data was more useful in explaining variations in charges in the eight condition-specific analyses conducted on patients 65 years and older. CONCLUSIONS: Comorbidities, particularly when determined from the medical record, are important determinants of patient costs.