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Biomedical subjects

S Lemeshow

Publications and source records attributed to S Lemeshow.

At least 19 recordsLinked to original sources

Therapy-related myelodysplasia and leukemia occur infrequently following VP-16 priming and autotransplantation without total body irradiation.

The use of VP-16 for stem cell mobilization has been cited as a significant risk factor for the development of therapy-related myelodysplasia/leukemia (tMDS/tAML) following autologous transplantation. The present study analyzed a large cohort of patients who underwent autotransplantation following stem cell mobilization with VP-16 and radiation-free preparation in order to determine the risk of tMDS/tAML. The estimated incidence of 9.9% at 7 years suggests that in the absence of TBI, VP-16 priming is not associated with an increased incidence of tMDS/tAML.

Adolescent↗

Demographic and phenotypic features of 70 families segregating Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Based on reported familial patterns, inheritance of a predisposition of developing Barrett's oesesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. oesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. AIMS: We analysed the phenotypic features of 70 familial BO/OAC families accrued for the purpose of initiating a linkage study to search for genes that contribute to susceptibility for BO/OAC. METHODS: Families with young or familial BO/OAC were recruited from participating institutions and self-referral from advertisement. RESULTS: A total of 70 families (173 affected and 784 unaffected individuals) were recruited into this study. Mean ages of diagnosis of BO and OAC among males were 50.6 and 57.4 years, respectively; among females, 52.1 and 63.5 years, respectively. The standardised incidence ratio (SIR) of cancers other than OAC or oesophagogastric junctional adenocarcinoma (OGJAC), among probands was 0.71. Seventy one percent of the pedigrees have "typical" structures with less than three affected individuals. Power calculations under realistic model assumptions suggest that if genetic heterogeneity is absent or limited, then DNA collection from members of these pedigrees could enable the identification of a novel candidate susceptibility gene for BO/OAC in a genome scan. CONCLUSIONS: This is the largest series of families with BO/OAC yet reported, features of which are consistent with inherited germline predisposition. Further, the SIR of cancers other than OAC/OGJAC was 0.71 among 70 probands, indicating these individuals were not more likely to develop non-OAC cancers.

Adenocarcinoma↗

Genetic model of multi-step breast carcinogenesis involving the epithelium and stroma: clues to tumour-microenvironment interactions.

Although numerous studies have reported that high frequencies of loss of heterozygosity (LOH) at various chromosomal arms have been identified in breast cancer, differential LOH in the neoplastic epithelial and surrounding stromal compartments has not been well examined. Using laser capture microdissection, which enables separation of neoplastic epithelium from surrounding stroma, we microdissected each compartment of 41 sporadic invasive adenocarcinomas of the breast. Frequent LOH was identified in both neoplastic epithelial and/or stromal compartments, ranging from 25 to 69% in the neoplastic epithelial cells, and from 17 to 61% in the surrounding stromal cells, respectively. The great majority of markers showed a higher frequency of LOH in the neoplastic epithelial compartment than in the stroma, suggesting that LOH in neoplastic epithelial cells might precede LOH in surrounding stromal cells. Furthermore, we sought to examine pair-wise associations of particular genetic alterations in either epithelial or stromal compartments. Seventeen pairs of markers showed statistically significant associations. We also propose a genetic model of multi-step carcinogenesis for the breast involving the epithelial and stromal compartments and note that genetic alterations occur in the epithelial compartments as the earlier steps followed by LOH in the stromal compartments. Our study strongly suggests that interactions between breast epithelial and stromal compartments might play a critical role in breast carcinogenesis and several genetic alterations in both epithelial and stromal compartments are required for breast tumour growth and progression.

Adenocarcinoma↗

Delays in receipt of immunizations in low-birth-weight children: a nationally representative sample.

BACKGROUND: Studies of very low-birth-weight (VLBW) children discharged from neonatal intensive care units have shown delays in receipt of routine childhood immunizations. However, a recent study of VLBW children in 3 health maintenance organizations found no significant delays in immunizations. OBJECTIVE: To assess the risk of immunization delays for moderately low-birth-weight (MLBW; 1500 g-2499 g) and VLBW (<1500 g) children compared with normal-birth-weight children in a nationally representative birth sample. DESIGN: Logistic regression analysis using the 1988 National Maternal and Infant Health Survey and the 1991 Longitudinal Follow-up Survey. SETTING: Nationally representative sample of children born in 1988 in the United States. PARTICIPANTS: A total of 8285 children whose mothers completed both surveys. MAIN OUTCOME MEASURES: Age at receipt of each of the first 4 doses of diphtheria and tetanus toxoids and pertussis vaccine, the first 3 doses of polio vaccine, and the first dose of measles-mumps-rubella vaccine for MLBW and VLBW children, and normal-birth-weight children. We also examined whether children were up-to-date for all immunizations at ages 12, 24, and 36 months based on birth-weight groups. RESULTS: Very low-birth-weight children received their first 3 doses of diphtheria and tetanus toxoids and pertussis vaccine and their first 2 doses of polio vaccine significantly later than normal-birth-weight children (P <.001). Very low-birth-weight children were significantly less likely to be up to date for all immunizations at ages 12 months (odds ratio [OR] =.556; P =.001), 24 months (OR =.439; P <.001), and 36 months (OR =.446; P <.001) compared with normal-birth-weight children. CONCLUSION: Very low-birth-weight children are at risk for immunization delays compared with normal-birth-weight children.

Age Distribution↗

Elevated blood pressure predicts the risk of acute rejection in renal allograft recipients.

BACKGROUND: Acute rejection (AR) is a strong predictor of renal allograft survival. Recent advances in immunosuppression have reduced considerably the incidence of AR. Still, approximately 25% of patients have AR early post-transplant, and the factors that predispose to AR have not been fully clarified. METHODS: The study includes 1641 adults, recipients of first cadaveric (CAD, N = 1195) or living related renal grafts (LRD, N = 446), transplanted in one institution. The variables associated with the occurrence of AR during the first year post-transplant were identified. RESULTS: By univariate analyses, AR was associated with the following variables: younger (P < 0.001); heavier (P = 0.003); and African American recipients (P = 0.002); CAD transplants (P = 0.001); higher number of HLA mismatches (P = 0.001); delayed graft function (DGF, P = 0.001); higher levels of serum creatinine post-transplant (P = 0.003); and higher levels of systolic and/or diastolic blood pressure (BP) post-transplant (P < 0.001). Higher BP levels were also associated with earlier AR episodes (P < 0.0001). By multivariable analysis AR was significantly associated with recipient age, number of HLA mismatches, DGF, pre-PRA and systolic BP. Analysis of BP measured weekly post-transplant indicated that elevated BP levels, even three weeks prior to the AR episode, were significantly associated with AR. For every level of BP, the use of BP medications was associated with a lower incidence of AR (P < 0.0001). Furthermore, the use of calcium channel blockers was also associated with lower incidence of AR (P = 0.001). Of note, 81% of recipients whose BP increased after the transplant had AR. In contrast, 22% of patients whose BP declined post-transplant had AR. CONCLUSIONS: Elevated BP levels post-transplant identify patients at high risk of AR independently of graft function. Treatment of BP and reduction of BP levels appears to be associated with a decreased risk of AR. We hypothesize that high BP may be an indicator of a particular type of allograft damage, perhaps ischemic, that may predispose to AR.

Acute Disease↗

Does cardioplegia type affect outcome and survival in patients with advanced left ventricular dysfunction? Results from the CABG Patch Trial.

BACKGROUND: There is controversy regarding which cardioplegic solution, temperature, and route of administration provides superior protection. The CABG Patch Trial enrolled a high-risk group of coronary artery disease patients with an ejection fraction of <36%. Thus, they constitute an ideal group to benefit most from optimal cardioplegic protection. METHODS AND RESULTS: All patients randomized into the trial were compared with respect to the use of blood and crystalloid cardioplegia. In addition, a questionnaire was sent to surgeons requesting blood cardioplegic temperature and route. Patients receiving crystalloid cardioplegia versus those receiving blood cardioplegia were found to have significantly more operative deaths (2% versus 0.3%, P:=0.02), postoperative myocardial infarctions (10% versus 2%, P:<0.001), shock (13% versus 7%, P:=0. 013), and postoperative conduction defects (21.6% versus 12.4%, P:=0. 001). Despite this, early death (6% crystalloid versus 4% blood cardioplegia) and late death (24% crystalloid versus 21% blood cardioplegia) statistics were not significantly different. Patients receiving normothermic blood had less postoperative right ventricular dysfunction (10%) than did patients receiving cold blood (25%) or cold blood with warm reperfusion (30%) (P:=0.004). There was no significant difference in early or late death. Finally, patients who received combined antegrade and retrograde cardioplegia had significantly less inotrope use (71% versus 84%, P:=0.002), right ventricular dysfunction (23% versus 41%, P:=0.001), and postoperative balloon pump use (12% versus 19%, P:=0.02) than did those who received antegrade cardioplegia. There was no difference in survival. CONCLUSIONS: Blood cardioplegia and combined antegrade and retrograde cardioplegia are superior to crystalloid and antegrade cardioplegia alone for postoperative morbidity. Despite this, there is no significant difference in early or late survival.

Cardioplegic Solutions↗

Patient characteristics and ICU organizational factors that influence frequency of pulmonary artery catheterization.

CONTEXT: Hemodynamic monitoring of patients with a pulmonary artery catheter is controversial because there are few data confirming its effectiveness, and patient and intensive care unit (ICU) organizational factors associated with its use are unknown. OBJECTIVE: To determine pulmonary artery catheter use in relationship to type of ICU organization and staffing, and patient characteristics, including severity of illness and insurance coverage. DESIGN, SETTING, AND PATIENTS: Retrospective database study of 10,217 nonoperative patients who received treatment at 34 medical, mixed medical and surgical, and surgical ICUs at 27 hospitals during 1998 (patients were enrolled in Project IMPACT). MAIN OUTCOME MEASURES: Pulmonary artery catheter use based on severity of illness measured by the Simplified Acute Physiology Score, resuscitation status at ICU admission, and ICU organizational variables, including type, size, and model. RESULTS: A pulmonary artery catheter was used for 831 patients (8.1%) in the ICU. In multivariate analysis adjusted for severity of illness, age, diagnosis, and do-not-resuscitate status, full-time ICU physician staffing was associated with a two-thirds reduction in the probability of catheter use (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.28-0.45). Higher catheter use was associated with white race (OR, 1.38; 95% CI, 1.10-1.72) and private insurance coverage (OR, 1.33; 95% CI, 1.10-1.60). Admission to a surgical ICU was associated with a 2-fold increase in probability of catheter use (OR, 2.17; 95% CI, 1.70-2.76) compared with either medical or mixed medical and surgical ICUs. CONCLUSION: Organizational characteristics of ICUs, insurance reimbursement, and race, as well as clinical variables, are associated with variation in practice patterns regarding pulmonary artery catheter use. Understanding such influences, combined with studies measuring clinical and economic outcomes, can contribute to the development of policies for the rational use of pulmonary artery catheters. JAMA. 2000;283:2559-2567

Adult↗

European system for cardiac operative risk evaluation (EuroSCORE).

OBJECTIVE: To construct a scoring system for the prediction of early mortality in cardiac surgical patients in Europe on the basis of objective risk factors. METHODS: The EuroSCORE database was divided into developmental and validation subsets. In the former, risk factors deemed to be objective, credible, obtainable and difficult to falsify were weighted on the basis of regression analysis. An additive score of predicted mortality was constructed. Its calibration and discrimination characteristics were assessed in the validation dataset. Thresholds were defined to distinguish low, moderate and high risk groups. RESULTS: The developmental dataset had 13,302 patients, calibration by Hosmer Lemeshow Chi square was (8) = 8.26 (P < 0.40) and discrimination by area under ROC curve was 0.79. The validation dataset had 1479 patients, calibration Chi square (10) = 7.5, P < 0.68 and the area under the ROC curve was 0.76. The scoring system identified three groups of risk factors with their weights (additive % predicted mortality) in brackets. Patient-related factors were age over 60 (one per 5 years or part thereof), female (1), chronic pulmonary disease (1), extracardiac arteriopathy (2), neurological dysfunction (2), previous cardiac surgery (3), serum creatinine >200 micromol/l (2), active endocarditis (3) and critical preoperative state (3). Cardiac factors were unstable angina on intravenous nitrates (2), reduced left ventricular ejection fraction (30-50%: 1, <30%: 3), recent (<90 days) myocardial infarction (2) and pulmonary systolic pressure >60 mmHg (2). Operation-related factors were emergency (2), other than isolated coronary surgery (2), thoracic aorta surgery (3) and surgery for postinfarct septal rupture (4). The scoring system was then applied to three risk groups. The low risk group (EuroSCORE 1-2) had 4529 patients with 36 deaths (0.8%), 95% confidence limits for observed mortality (0.56-1.10) and for expected mortality (1.27-1.29). The medium risk group (EuroSCORE 3-5) had 5977 patients with 182 deaths (3%), observed mortality (2.62-3.51), predicted (2.90-2.94). The high risk group (EuroSCORE 6 plus) had 4293 patients with 480 deaths (11.2%) observed mortality (10.25-12.16), predicted (10.93-11.54). Overall, there were 698 deaths in 14,799 patients (4.7%), observed mortality (4.37-5.06), predicted (4.72-4.95). CONCLUSION: EuroSCORE is a simple, objective and up-to-date system for assessing heart surgery, soundly based on one of the largest, most complete and accurate databases in European cardiac surgical history. We recommend its widespread use.

Cardiac Surgical Procedures↗

Practical considerations in the analysis of complex sample survey data.

Large scale sample surveys often provide fertile ground for analyses by epidemiologists. Recently, survey organizations such as the National Center for Health Statistics and the United States Bureau of the Census have distributed data from large surveys to interested investigators via CD-ROM. Confronted by the richness of such databases and the historic relative lack of availability of suitable software to appropriately account for the survey design, researchers have often simply ignored the complexities of the survey and analyzed the data as if they resulted from a simple random sample. The availability of modern programs such as STATA and SUDAAN provides data analysts with the new analytical capabilities to perform design-based analyses whenever appropriate. We used data from the NHANES III and the PAQUID study to illustrate the ease of performing design-based analyses. We also compared results of analyses under both model-based and design-based scenarios. When data from complex sample surveys were analyzed using both model-based and design-based strategies, differences in point estimates and standard errors of means, regression coefficients and odds ratios were found. The differences in regression coefficients and odds ratios between the two strategies were not as great as the differences in means. The potential for differences and the availability of survey analysis software should encourage researchers to use design-based techniques to analyze data from complex sample surveys more appropriately.

Adolescent↗

Illustration of analysis taking into account complex survey considerations: the association between wine consumption and dementia in the PAQUID study. Personnes Ages Quid.

Epidemiologists are increasingly looking to large-scale sample surveys to provide data for studies of the associations between known or suspected risk factors and disease. More often than not, widely available statistical software packages have been used to analyze such data, particularly when multivariable modeling is involved. Such packages assume that the data have resulted from simple random samples. However, when the survey design incorporates such features as clustering and stratification, the results of statistical analyses based on this assumption can be incorrect. The authors utilized data from the PAQUID (Personnes Agees Quid) study, collected periodically from 1988 to 1996, to illustrate the ease of performing a "design-based" (vs. a "model-based") analysis of complex survey data, and they compared the results obtained using both approaches. The PAQUID study is a stratified cluster sample of elderly community residents in the southwestern departments of Gironde and Dordogne, France. In the illustration presented-in which 3,777 community residents aged 65 years or older were selected to permit identification of baseline and lifetime factors that might be related to cognitive loss, dementia, and Alzheimer's disease--measures of association (such as odds ratios and their associated standard errors) were comparable for both analytical strategies. However, this may not be the case for other examples. Descriptive measures (such as estimates of means and proportions) may be more seriously compromised by the decision to ignore the sampling design. The availability of modern statistical packages with survey analysis capabilities should encourage data analysts to perform design-based analyses whenever possible.

Aged↗

Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model.

PURPOSE: To develop prospectively and validate a model for probability of hospital survival at admission to the intensive care unit (ICU) of patients with malignancy. PATIENTS AND METHODS: This was an inception cohort study in the setting of four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 1,483 patients and then validated on an additional 230 patients. Multiple logistic regression modeling was used to develop the models and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analysis. The main outcome measure was hospital survival after ICU admission. RESULTS: The observed hospital mortality rate was 42%. Continuous variables used in the ICU admission model are PaO2/FiO2 ratio, platelet count, respiratory rate, systolic blood pressure, and days of hospitalization pre-ICU. Categorical entries include presence of intracranial mass effect, allogeneic bone marrow transplantation, recurrent or progressive cancer, albumin less than 2.5 g/dL, bilirubin > or = 2 mg/dL, Glasgow Coma Score less than 6, prothrombin time greater than 15 seconds, blood urea nitrogen (BUN) greater than 50 mg/dL, intubation, performance status before hospitalization, and cardiopulmonary resuscitation (CPR). The P values for the fit of the preliminary and validation models are .939 and .314, respectively, and the areas under the ROC curves are .812 and .802. CONCLUSION: We report a disease-specific multivariable logistic regression model to estimate the probability of hospital mortality in a cohort of critically ill cancer patients admitted to the ICU. The model consists of 16 unambiguous and readily available variables. This model should move the discussion regarding appropriate use of ICU resources forward. Additional validation in a community hospital setting is warranted.

Academic Medical Centers↗

A comparison of goodness-of-fit tests for the logistic regression model.

Recent work has shown that there may be disadvantages in the use of the chi-square-like goodness-of-fit tests for the logistic regression model proposed by Hosmer and Lemeshow that use fixed groups of the estimated probabilities. A particular concern with these grouping strategies based on estimated probabilities, fitted values, is that groups may contain subjects with widely different values of the covariates. It is possible to demonstrate situations where one set of fixed groups shows the model fits while the test rejects fit using a different set of fixed groups. We compare the performance by simulation of these tests to tests based on smoothed residuals proposed by le Cessie and Van Houwelingen and Royston, a score test for an extended logistic regression model proposed by Stukel, the Pearson chi-square and the unweighted residual sum-of-squares. These simulations demonstrate that all but one of Royston's tests have the correct size. An examination of the performance of the tests when the correct model has a quadratic term but a model containing only the linear term has been fit shows that the Pearson chi-square, the unweighted sum-of-squares, the Hosmer-Lemeshow decile of risk, the smoothed residual sum-of-squares and Stukel's score test, have power exceeding 50 per cent to detect moderate departures from linearity when the sample size is 100 and have power over 90 per cent for these same alternatives for samples of size 500. All tests had no power when the correct model had an interaction between a dichotomous and continuous covariate but only the continuous covariate model was fit. Power to detect an incorrectly specified link was poor for samples of size 100. For samples of size 500 Stukel's score test had the best power but it only exceeded 50 per cent to detect an asymmetric link function. The power of the unweighted sum-of-squares test to detect an incorrectly specified link function was slightly less than Stukel's score test. We illustrate the tests within the context of a model for factors associated with low birth weight.

Humans↗

The Logistic Organ Dysfunction system. A new way to assess organ dysfunction in the intensive care unit. ICU Scoring Group.

OBJECTIVE: To develop an objective method for assessing organ dysfunction among intensive care unit (ICU) patients on the first day of the ICU stay. DESIGN AND SETTING: Physiological variables defined dysfunction in 6 organ systems. Logistic regression techniques were used to determine severity levels and relative weights for the Logistic Organ Dysfunction (LOD) score and for conversion of the LOD score to a probability of mortality. PATIENTS: A total of 13 152 consecutive admission to 137 adult medical/surgical ICUs in 12 countries from the European/North American Study of Severity Systems. OUTCOME MEASURES: Patient vital status at hospital discharge. RESULTS: The LOD System identified from 1 to 3 levels of organ dysfunction for 6 organ systems: neurologic, cardiovascular, renal, pulmonary, hematologic, and hepatic. From 1 to 5 LOD points were assigned to the levels of severity, and the resulting LOD scores ranged from 0 to 22 points. Model calibration was very good in the developmental and validation samples (P=.21 and P=.50, respectively), as was model discrimination (area under the receiver operating characteristic curves of 0.843 and 0.850, respectively). CONCLUSION: The LOD System provides an objective tool for assessing severity levels for organ dysfunction in the ICU, a critical component in the conduct of clinical trials. Neurologic, cardiovascular, and renal dysfunction were the most severe organ dysfunctions, followed by pulmonary and hematologic dysfunction, with hepatic dysfunction the least severe. The LOD System takes into account both the relative severity among organ systems and the degree of severity within an organ system.

Adult↗

The relationship between age and the use of DNR orders in critical care patients. Evidence for age discrimination.

OBJECTIVE: To determine whether a relationship exists between the use of do-not-resuscitate (DNR) orders in the intensive care unit and the age of the patient after controlling for the severity of illness. METHODS: Patients from the Mortality Probability Model database, which includes 6103 patients in 4 large hospitals, and from a second database, which includes 3226 additional patients in 25 hospitals, were analyzed through logistic regression seeking a relationship between age and DNR use. Adult medical and surgical intensive care units from 27 hospitals in the United States were included. RESULTS: In the Mortality Probability Model database, 11.4% of the patients had DNR orders written. In the group of patients younger than 65 years, 8% had DNR orders. This percentage climbed rapidly with age. For age ranges of 65 to younger than 75 years, 75 to younger than 85 years, and 85 years or older, the percentage of patients who had a DNR order was 11.2%, 18.9%, and 32.6%, respectively. Similar results were found in the second database: 5.4% of patients had DNR orders and, again, the rise in the use of DNR orders was associated with increased age. For patients younger than 75 years, 4.2% had DNR orders. For the older groups, 75 to younger than 85 years and 85 years and older, the rates were 8.8% and 15.4%, respectively. Logistic regression was used to control for severity of illness; when compared with patients younger than 65 years, patients 75 to younger than 85 years were 50% more likely to have DNR orders written and patients 85 years or older were 140% more likely to have DNR orders written. CONCLUSIONS: Older patients (> or = 75 years old) are significantly more likely than younger patients to have DNR orders written even after the severity of illness is controlled as a confounding variable. This association suggests age discrimination and becomes stronger as patient age increases.

Adult↗

[Use of mortality probability models (MPM II) in the evaluation of the effectiveness of care of critically ill patients. European and North American Study of Severity Systems].

BACKGROUND: The performance of the Mortality Probability Models (MPM II) has been assessed in Intensive Care Units (ICUs) in Catalonia and the Balearic Islands. The MPM II system has been customized to that geographic area and quality performance has been evaluated in each ICU. METHODS: 1,270 adult critical patients, consecutively admitted in 16 ICUs from Catalonia and 1 from the Balearic Islands have been included. Probability of dying in the hospital has been calculated at admission in the ICU and at 24 hours using the models MPM II0 and MPM II24. Goodness-of-fit of the MPM II system in the overall group of 17 ICUs has been analyzed. Logistic regression has been used to customize the MPM II system to all the ICUs together. A Quality Performance Index (QPI) for each ICU has been obtained by dividing the number of the observed deaths by the number of deaths expected by the MPM II system. RESULTS: The overall QPI was 1.15 when using the MPM II0 and 1.17 when using the MPM II24. The QPI in the 17 ICUs ranged from 0.58 to 2.05. Three ICUs showed excess of mortality and 2 ICUs had less deaths than expected. The process of customization of MPM II to the 17 ICUs as a group improved the estimation of expected mortality. CONCLUSIONS: The use of severity indexes allows to compare the outcome of patients in the ICU and provides an indicator of quality of care. The excess of mortality observed in some ICU should produce a watchful follow-up of outcome. Risk factors for excess of mortality should be studied.

Adult↗