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Biomedical subjects

J H Silber

Publications and source records attributed to J H Silber.

At least 37 records · Page 2Linked to original sources

Evaluation of the complication rate as a measure of quality of care in coronary artery bypass graft surgery.

OBJECTIVE: To determine whether hospital rankings based on complication rates provide the same information as hospital rankings based on mortality rates. DESIGN: A retrospective study of in-hospital death, complication, and death following complication (failure to rescue). Hospitals were ranked using residuals based on the difference between the observed and the expected number of events (from logistic regression models); rankings were compared using Spearman rank correlations. SETTING: Hospitals performing coronary artery bypass graft (CABG) surgery in the 1991 and 1992 MedisGroups National Comparative Data Bases. PATIENTS AND DATA SETS: Record abstraction data for 16,673 patients who underwent CABG procedures at 57 hospitals, linked with data from the 1991 American Hospital Association Annual Survey. RESULTS: After adjusting for patient admission severity of illness, there were low correlations between hospital rankings based on death or failure to rescue and those rankings based on complication (death vs complication, r = 0.07, P = .58; failure to rescue vs complication, r = -0.22, P = .11). In addition, many hospital characteristics that are generally associated with a higher quality of care were associated with higher complication rates but with expected or lower-than-expected mortality rates. CONCLUSIONS: Hospital rankings based on complication rates provide different information than those based on mortality rates. Until more is known about these differences, complication rates should not be used to judge hospital quality of care in CABG surgery.

Coronary Artery Bypass↗

Surveillance scanning of children with medulloblastoma.

BACKGROUND: The standard follow-up care for children with medulloblastoma includes regular clinical evaluations and surveillance scanning of the central nervous system with computed tomography or magnetic resonance imaging. The evaluations and scanning assess the response of the tumor to treatment, detect any recurrence of disease, and monitor any complications of treatment. We compared the effectiveness of a periodic history taking and physical examination with that of surveillance scanning in detecting recurrent tumors. METHODS: We reviewed the medical records, including 794 scanning reports or scans, of 86 children with posterior fossa medulloblastoma who were followed regularly between 1980 and 1991. Recurrent tumors were classified as symptomatic if neuroimaging studies had been prompted by clinical symptoms or signs and as radiographic if the tumor had been detected by imaging in an asymptomatic patient. RESULTS: Twenty-three of the 86 children (27 percent) had a recurrence of tumor. Four recurrences (17 percent) were detected on scanning only, and 19 (83 percent) were associated with symptoms arising a median of four months after the previous scan. The median and range of survival after a recurrence of the tumor were 5 months and < 1 to 38 months, respectively, for a symptomatic recurrence and 20 months and 10 to 32 months, respectively, for a radiographic recurrence (P = 0.03). No patient survived after a recurrence. The longer survival of patients with recurrent tumors detected by scanning most likely reflects the small number of patients and lead-time and length biases associated with screening. CONCLUSIONS: Among children with medulloblastoma, surveillance scanning is of little clinical value. Scanning detected a minority of recurrences, and no patient who had a recurrence survived.

Adolescent↗

Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease.

Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

Adolescent↗

Comparison of cardiac function tests after anthracycline therapy in childhood. Implications for screening.

BACKGROUND: Numerous methods for evaluating cardiac function after cardiotoxic therapy have been suggested. A practical algorithm for screening a large patient population is needed. METHODS: Seventy-three patients (median age, 15.3 years [range, 9-29 years) who received anthracyclines (median dose, 300 mg/m2 [range, 50-750 mg/m2) for a childhood malignancy underwent a battery of commonly used tests of cardiac function: (1) echocardiographic shortening fraction (ESF); (2) resting and exercise radionuclide scan (multiple gaited acquisition [MUGA]); (3) electrocardiogram (ECG); (4) 24-hour Holter monitor, and (5) questionnaire concerning exercise tolerance. RESULTS: Patients with an abnormal resting ejection fraction on MUGA were more likely to have an abnormal ESF (P = 0.023), prolongation of the QTc interval (P = 0.014), and complaints of "difficulty" with exercise (P = 0.04). An abnormal results for a resting study was not predictive of an abnormal MUGA exercise response. There was no association between the presence of significant dysrhythmia on Holter monitor and any resting test. An algorithm was developed using a normal ESF and QTc interval, and a negative history of exercise intolerance to identify patients who need not undergo a MUGA. With the use of such an algorithm, 29 of the 73 patients would not have undergone the MUGA, only 2 of whom had an abnormal resting ejection fraction. CONCLUSION: Patients at risk for cardiac damage after cancer therapy who have normal ESF and QTc interval results and no history of exercise intolerance are unlikely to have abnormal MUGA results. Significant dysrhythmia may be present in the absence of other abnormalities.

Adolescent↗

Pulse oximetry and factors associated with hemoglobin oxygen desaturation in children with sickle cell disease.

The observation of low transcutaneous arterial oxygen saturation (SaO2) in otherwise well sickle cell patients has lead to questions about the interpretation of pulse oximetry values in these patients. We undertook a prospective study of children with sickle cell disease to (1) determine the prevalence of, and factors associated with, low transcutaneous SaO2 in clinically well patients, (2) develop an algorithm for the use of pulse oximetry in acutely ill patients, and (3) assess the accuracy of pulse oximetry in these patients. Eighty-six clinically well children with hemoglobin (Hb) SS had a lower mean transcutaneous SaO2 than 22 Hb SC patients and 10 control subjects (95.6% v 99.1% v 99.0%, respectively; p < .001). In Hb SS patients, a history of acute chest syndrome and age greater than 5 years were associated with lower transcutaneous SaO2 (mean 93.8% for those with a history of acute chest syndrome v 97.8% for those without a history of acute chest syndrome, and 94.0% for patients > 5 years old v 97.2% for those < or = 5 years old; P < .001). These associations were not seen in Hb SC patients. During acute illness, Hb SS patients with acute chest syndrome had transcutaneous SaO2 values that were less than 96% and at least 3 points lower than measurements made when they were well. A nomogram was designed to aid in the interpretation of transcutaneous SaO2 in acutely ill Hb SS patients when a comparison value is not available. The accuracy of pulse oximetry was shown by the correlation between SaO2 measured by pulse oximetry and calculated by using the patient's oxygen dissociation curve and PaO2 (r = .97). This study provides evidence that Hb oxygen desaturation is not a universal finding among children with sickle cell disease and identifies factors associated with Hb oxygen desaturation. We conclude that pulse oximetry may be useful to assess whether progressive pulmonary dysfunction begins at an early age in Hb SS patients, and to assess acutely ill patients for the presence of hypoxemia associated with acute chest syndrome.

Anemia, Sickle Cell↗

Cardiac dysfunction following spinal irradiation during childhood.

PURPOSE: Although spinal irradiation used in the treatment of CNS malignancies includes a portion of the heart in the radiation field, cardiac effects have not been previously reported. PATIENTS AND METHODS: We compared patients treated for malignancy in childhood with spinal irradiation (n = 26) with patients treated with mediastinal/flank irradiation (n = 47) that included the heart in the radiation field. All patients were more than 1 year from completion of radiation therapy. Patients underwent at least two of the following cardiac evaluations: (1) ECG; (2) 24-hour ambulatory ECG; (3) echocardiogram; and (4) exercise-testing using cycle ergometry. RESULTS: Twelve of 16 patients (75%) in the spinal irradiation group with an assessable exercise test achieved a maximal cardiac index (MCI) below the fifth percentile as compared with 13 of 40 patients (32%) who had received mediastinal/flank irradiation (P = .007). Furthermore, after adjusting for normal heart growth, radiation and anthracycline doses, and follow-up time, the group of patients who received spinal irradiation had significantly higher estimated posterior wall stress (P = .002), expressed as the natural logarithm of the ratio of end-diastolic left ventricular internal diameter (LVID) to left ventricular posterior wall thickness (LVPWT), than the group who had received mediastinal/flank irradiation. Finally, eight of 26 patients (31%) in the spinal group had pathologic Q-waves in the inferior leads versus three of 47 (6.4%) in the mediastinal/flank group (P = .001). CONCLUSION: Patients who have received spinal irradiation for pediatric malignancies appear to be at risk for significant cardiac dysfunction. The asymmetric distribution of radiation to a growing heart, as given with spinal irradiation, may be the cause of these findings.

Adolescent↗

Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults.

Transient electrocardiographic changes and arrhythmias are known to be acute manifestations of cardiotoxicity secondary to cancer therapy with anthracyclines or cardiac irradiation. However, despite the known risk of late cardiac dysfunction in survivors of childhood cancer therapy, the risk of clinically important electrocardiographic abnormalities and arrhythmias after treatment is unknown. Standard 12-lead and 24-hour ambulatory electrocardiograms were recorded in 73 patients who received anthracyclines alone, 24 who received cardiac irradiation alone, and 27 who received both anthracyclines and cardiac irradiation. The mean age of the patients was 15 years. Mean cumulative anthracycline dose was 282 mg/m2 in patients who received anthracyclines alone and 244 mg/m2 in patients who received both anthracyclines and cardiac irradiation. Analysis of the 12-lead and 24-hour electrocardiograms demonstrated increased frequency of QTc prolongation, supraventricular premature complexes, supraventricular tachycardia, ventricular premature complexes, couplets and ventricular tachycardia (all p less than 0.001) when compared with an age-matched healthy population. Most patients had abnormalities limited to single supraventricular or ventricular premature complexes; however, potentially serious ventricular ectopy, including ventricular pairs and ventricular tachycardia, were noted in patients with cumulative doses greater than 200 mg/m2. Electrocardiographic abnormalities and arrhythmias are not limited to the acute phase of treatment with anthracyclines and cardiac irradiation. Survivors of childhood malignancy who received anthracyclines or cardiac irradiation, or both, probably should undergo ambulatory electrocardiographic monitoring as part of their follow-up to detect potentially life-threatening arrhythmias.

Adolescent↗

A modified transfusion program for prevention of stroke in sickle cell disease.

Regular red blood cell transfusions reduce the rate of recurrent cerebral infarction in sickle cell disease but lead to accumulation of excessive iron. We studied the effect on the prevention of recurrent stroke and the volume of blood transfused of a modified transfusion program in which the pretransfusion percentage of hemoglobin S (HbS) was maintained at 50%, rather than the conventional 30%. Fifteen patients with sickle cell disease and cerebral infarction who had been free of recurrent stroke for at least 4 years during which the pretransfusion HbS was maintained below 30% were assigned to a transfusion program in which the HbS was allowed to increase to 50%. Transfusion regimens included simple transfusion and manual and automated partial exchange transfusion. The duration of follow-up was 14 to 130 months with a median duration of 84 months. None of the 15 patients had a recurrent cerebral infarction during 1,023 patient-months in which the target pretransfusion HbS was 50%. Analysis of this finding, using a binomial distribution, indicates that there is less than a 5% chance that the risk per patient of recurrent stroke in the first year of the modified transfusion program is greater than 18%. One 23-year-old patient had a fatal intraventricular hemorrhage when the HbS was 30% and a 21-year-old patient had a fatal subarachnoid hemorrhage in the 40th week of pregnancy when the HbS was 29%. Blood requirements with simple transfusions decreased by 17% to 48% (mean 31%) when the target pretransfusion HbS level was increased from 30% to 50% (P less than .001). Manual or automated partial exchange transfusions and a target HbS level of 50% in eight patients reduced blood requirements by 33% to 99% (mean 67%) in comparison with simple transfusion and a target HbS level of 30% (P less than .001). This study offers evidence that a target pretransfusion HbS level of 50% affords a continuing high rate of protection against recurrent cerebral infarction in sickle cell disease after 4 years of a conventional transfusion program. Increasing the target HbS level from 30% to 50% provides a major reduction in blood requirements and lowers the rate of iron accumulation.

Adolescent↗

Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue.

We asked if the factors that predict overall mortality following two common surgical procedures are different from those that predict adverse occurrences (complications) during the hospitalization or death after an adverse occurrence, which we refer to as "failure to rescue." We examined 5,972 Medicare patients undergoing elective cholecystectomy or transurethral prostatectomy using three outcome measures: 1) the death rate (number of deaths/number of patients); 2) the adverse occurrence rate (number of patients who developed an adverse occurrence/number of patients); and 3) the failure rate (number of deaths in patients who developed an adverse occurrence/number of patients with an adverse occurrence). The death rate was associated with both hospital and patient characteristics. The adverse occurrence rate was associated primarily with patient characteristics. In contrast, failure to rescue was associated more with hospital characteristics, and was less influenced by patient admission severity of illness as measured by the MedisGroups score. We concluded that factors associated with hospital failure to rescue are different from factors associated with adverse occurrences or death. Understanding the reasons behind variation in mortality rates across hospitals should improve our ability to use mortality statistics to help hospitals upgrade the quality of care.

Age Factors↗

Residual disease at the end of induction therapy as a predictor of relapse during therapy in childhood B-lineage acute lymphoblastic leukemia.

PURPOSE: More than 95% of children with B-lineage acute lymphoblastic leukemia (ALL) achieve a clinical remission after the induction phase of chemotherapy (first 28 days) as evaluated by morphologic criteria. However, relapse occurs in approximately 30% of these children. The objective of this study was to determine whether the outcome of patients in clinical remission at the end of induction therapy could be predicted using a highly sensitive method to detect residual disease. PATIENTS AND METHODS: All children diagnosed with B-lineage ALL at the Children's Hospital of Philadelphia during a 2-year period were eligible. The extent of residual leukemia was quantitated in remission marrow samples obtained at the end of induction therapy in 44 children using a phage clonogenic assay in association with complementarity-determining-region 3 (CDR3)-polymerase chain reaction (PCR). RESULTS: Residual disease was a significant predictor of outcome independent of WBC count, age, or sex. The estimated relapse-free survival (RFS) during therapy was 50.4% (+/- 12.6%) for patients with high residual disease (> or = 0.6% leukemia cells among total marrow B cells) versus 91.9% (+/- 5.5%) for those with lower levels (P < .002). There were no significant differences in off-treatment RFS between patients with high or low residual disease who completed therapy in continuous remission (P = .82). The overall estimated RFS was 32.3% (+/- 11.6%) for patients with high residual disease versus 62.6% (+/- 10.7%) for patients with lower levels of residual leukemia cells, with a median follow-up of 5.3 years for patients in continuous remission (P < .008). CONCLUSION: PCR detection of high residual disease at the end of induction therapy identifies patients at increased risk for relapse during therapy.

Adolescent↗

Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.

PURPOSE: Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS: A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS: Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS: One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.

Adolescent↗

Models to predict outcome from childhood neuroblastoma: the role of serum ferritin and tumor histology.

We report on the development of three multiple logistic regression models to predict death from childhood neuroblastoma in patients treated without bone marrow transplantation. The models have been developed using a data set of 125 patients for whom age, stage, serum ferritin, and/or histology were available from diagnosis. Seventy-seven patients had all four variables recorded at diagnosis, 34 had age, stage, and serum ferritin, and 14 had age, stage, and histology. Minimum time from diagnosis for all patients was 3 years. The four-variable (full) model showed a predictive value positive rate (or 1 - the false positive rate) of 91.3% and a predictive value negative rate (or 1 - the false negative rate) of 94.4%. Survival curves, based on derived "good" and "poor" prognosis, were constructed for the full model of 77 patients and for the same patients using subset models either without ferritin or without histology. Correcting for prognostic factors noted at diagnosis, no time trend could be identified over the study period. Point estimates for the probability of death in all three models are displayed in graphical form. The results suggest that serum ferritin and tumor histology at diagnosis have independent prognostic significance and that patient outcome in neuroblastoma can be very accurately predicted with a four-variable model. Such information will help sort patients into good and poor prognosis for bone marrow transplant and intensive chemotherapy protocol triage and will help evaluate the efficacy of future therapeutic innovations.

Bone Marrow Transplantation↗