Acting on imperfect evidence: How much regret are we ready to accept?
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Breast Neoplasms↗
Biomedical subjects
Charles L Bennett
Publications and source records attributed to Charles L Bennett.
Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project.
Since its introduction in 1988, recombinant human erythropoietin (epoetin) has been standard treatment for patients with anemia due to chronic kidney disease. From 1998 to 2004, nearly 200 epoetin-treated persons with chronic kidney disease developed antibodies to epoetin, resulting in pure red cell aplasia (PRCA). The majority of these patients received Eprex, an epoetin alfa product marketed exclusively outside the United States. Herein, we report on the long-term outcome of these individuals. For 170 chronic kidney disease patients who developed epoetin-associated PRCA and had 3 months or more follow-up information available, case reports from the Food and Drug Administration and epoetin manufacturers were reviewed for information on clinical characteristics of the patients, immunosuppressive treatments, epoetin responsiveness, and hematologic recovery. Overall, 64% of the PRCA patients received immunosuppressive therapy, including 19 who also underwent a renal transplantation. Thirty-seven percent experienced a hematologic recovery, with higher hematologic recovery rates among PRCA patients who received immunosuppressive therapy (57% vs 2%, P < .001). Among 34 patients who received epoetin after the onset of PRCA, 56% regained epoetin responsiveness. The highest rates of epoetin responsiveness were observed among persons whose antierythropoietin antibodies were undetectable when epoetin was administered (89%). Among chronic kidney disease patients with epoetin-associated PRCA, epoetin discontinuation and immunosuppressive therapy or renal transplantation is necessary for hematologic recovery. Reinitiation of epoetin therapy among individuals could be considered if antierythropoietin antibodies are undetectable.
Autoantibodies↗
High rates of adverse drug events in a highly computerized hospital.
BACKGROUND: Numerous studies have shown that specific computerized interventions may reduce medication errors, but few have examined adverse drug events (ADEs) across all stages of the computerized medication process. We describe the frequency and type of inpatient ADEs that occurred following the adoption of multiple computerized medication ordering and administration systems, including computerized physician order entry (CPOE). METHODS: Using explicit standardized criteria, pharmacists classified inpatient ADEs from prospective daily reviews of electronic medical records from a random sample of all admissions during a 20-week period at a Veterans Administration hospital. We analyzed ADEs that necessitated a changed treatment plan. RESULTS: Among 937 hospital admissions, 483 clinically significant inpatient ADEs were identified, accounting for 52 ADEs per 100 admissions and an incidence density of 70 ADEs per 1000 patient-days. One quarter of the hospitalizations had at least 1 ADE. Of all ADEs, 9% resulted in serious harm, 22% in additional monitoring and interventions, 32% in interventions alone, and 11% in monitoring alone; 27% should have resulted in additional interventions or monitoring. Medication errors contributed to 27% of these ADEs. Errors associated with ADEs occurred in the following stages: 61% ordering, 25% monitoring, 13% administration, 1% dispensing, and 0% transcription. The medical record reflected recognition of 76% of the ADEs. CONCLUSIONS: High rates of ADEs may continue to occur after implementation of CPOE and related computerized medication systems that lack decision support for drug selection, dosing, and monitoring.
Clinical Pharmacy Information Systems↗
The Research on Adverse Drug Events and Reports (RADAR) project.
CONTEXT: In 1998, a multidisciplinary team of investigators initiated RADAR (Research on Adverse Drug events And Reports), a clinically based postmarketing surveillance program that systematically investigates and disseminates information describing serious and previously unrecognized adverse drug and device reactions (ADRs). OBJECTIVE: To describe the structure, operations, and preliminary findings from the RADAR project and related dissemination efforts by pharmaceutical suppliers and the US Food and Drug Administration (FDA). DESIGN: After identifying a serious and unexpected clinical event suitable for further investigation, RADAR collaborators postulated clinical hypotheses and derived case series and incidence estimates from physician queries, published and unpublished clinical trials, published case reports, FDA databases, and manufacturer sales figures. RESULTS: RADAR investigators identified 16 types of serious ADRs among 1699 patients, of whom 169 (10%) died as a result of the reaction. Initial cases were identified by 7 RADAR investigators, 4 collaborating physicians, 2 attorneys, and by reviewing 3 published reports. Additional sources included queries of occupational health programs and medical directors of interventional cardiology laboratories (3 types of ADRs), published manuscripts and clinical trials (11 types of ADRs), review of medical records at a RADAR site (2 types of ADRs), unpublished clinical trial reports (3 types of ADRs), and reports from attorneys, family members, or patients (4 types of ADRs). Incidence estimates, ranging from 0.4% to 33%, were derived from 5 clinical trial reports, 2 physician queries, and 2 observational databases. Laboratory support for hypotheses included identification of 3 neutralizing antibodies and 3 histopathological findings. ADR reports were disseminated as 8 revised package inserts, 7 "dear doctor" letters, and 9 peer-reviewed articles. CONCLUSION: A new, clinically based, hypothesis-driven approach to postmarketing surveillance may supplement existing regulatory surveillance systems and improve patient safety.
Adverse Drug Reaction Reporting Systems↗
Low-molecular-weight heparins: do we have the GUSTO to identify differences between alternative formulations?
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Chemistry, Pharmaceutical↗
Development of a brief survey on colon cancer screening knowledge and attitudes among veterans.
INTRODUCTION: Poor knowledge of and negative attitudes toward available screening tests may account in part for colorectal cancer screening rates being the lowest among 17 quality measures reported for the Department of Veterans Affairs health care system, the largest integrated health system in the United States. The purpose of this study was to develop a brief assessment tool to evaluate knowledge and attitudes among veterans toward colorectal cancer screening options. METHODS: A 44-item questionnaire was developed to assess knowledge, attitudes, and beliefs about colorectal cancer and screening and was then administered as part of an ongoing randomized controlled trial among 388 veterans receiving care in a general medicine clinic. Sixteen candidate items on colorectal cancer knowledge, attitudes, and beliefs were selected for further evaluation using principal components analysis. Two sets of items were then further analyzed. RESULTS: Because the Cronbach alpha for beliefs was low (alpha = 0.06), the beliefs subscale was deleted from further consideration. The final scale consisted of seven items: a four-item attitude subscale (alpha = 0.73) and a three-item knowledge subscale (alpha = 0.59). Twelve-month follow-up data were used to evaluate predictive validity; improved knowledge and attitudes were significantly associated with completion of flexible sigmoidoscopy (P = .004) and completion of either flexible sigmoidoscopy or colonoscopy (P = .02). CONCLUSION: The two-factor scale offers a parsimonious and reliable measure of colorectal cancer screening knowledge and attitudes among veterans. This colorectal Cancer Screening Survey (CSS) may especially be useful as an evaluative tool in developing and testing of interventions designed to improve screening rates within this population.
Aged↗
Health care provider-directed intervention to increase colorectal cancer screening among veterans: results of a randomized controlled trial.
PURPOSE: Colorectal cancer screening is the most underused cancer screening tool in the United States. The purpose of this study was to test whether a health care provider-directed intervention increased colorectal cancer screening rates. PATIENTS AND METHODS: The study was a randomized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center. The records of 5,711 patients were reviewed; 1,978 patients were eligible. Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps, had not received colorectal cancer screening, and had at least one visit to the clinic during the study period. Health care providers in the intervention firm attended a workshop on colorectal cancer screening. Every 4 to 6 months, they attended quality improvement workshops where they received group screening rates, individualized confidential feedback, and training on improving communication with patients with limited literacy skills. Medical records were reviewed for colorectal cancer screening recommendations and completion. Literacy level was assessed in a subset of patients. RESULTS: Colorectal cancer screening was recommended for 76.0% of patients in the intervention firm and for 69.4% of controls (P = .02). Screening tests were completed by 41.3% of patients in the intervention group versus 32.4% of controls (P = .003). Among patients with health literacy skills less than ninth grade, screening was completed by 55.7% of patients in the intervention group versus 30% of controls (P < .01). CONCLUSION: A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans.
Colorectal Neoplasms↗
Astrophysical observations: lensing and eclipsing Einstein's theories.
Albert Einstein postulated the equivalence of energy and mass, developed the theory of special relativity, explained the photoelectric effect, and described Brownian motion in five papers, all published in 1905, 100 years ago. With these papers, Einstein provided the framework for understanding modern astrophysical phenomena. Conversely, astrophysical observations provide one of the most effective means for testing Einstein's theories. Here, I review astrophysical advances precipitated by Einstein's insights, including gravitational redshifts, gravitational lensing, gravitational waves, the Lense-Thirring effect, and modern cosmology. A complete understanding of cosmology, from the earliest moments to the ultimate fate of the universe, will require developments in physics beyond Einstein, to a unified theory of gravity and quantum physics.
Journal Article↗
Colorectal cancer screening among African-American and white male veterans.
BACKGROUND: Population-based studies from Medicare and privately insured individuals have consistently identified lower rates of colorectal cancer-screening tests among African-American versus white individuals. The purpose of this study was to evaluate whether, at a Veterans Affairs (VA) medical center, similar racial/ethnic differences in colorectal cancer screening could be identified. METHODS: Study participants were male veterans, aged > or =50, attending a general medicine clinic in a VA hospital, who had not had either a fecal occult blood test (FOBT) within the past year or a flexible sigmoidoscopy/colonoscopy within the past 5 years. Based on review of electronic medical records, rates of physician recommendation for FOBT, flexible sigmoidoscopy, or colonoscopy, and patient completion of these tests were obtained and compared by race/ethnicity. RESULTS: Sixty percent of 1599 veterans had not undergone recent colorectal cancer screening. Physicians recommended colorectal screening tests equally among African-American and white patients (71.0% vs 68.2%, p=0.44). African-American patients were 1.3 times more likely than white patients to receive colorectal screening procedures (36.3% vs 28.9%, p=0.03). CONCLUSIONS: In contrast to other settings, in a general medicine clinic at a VA hospital, rates of colorectal cancer-screening tests were not lower for African-American patients compared to white patients.
Black or African American↗
Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
BACKGROUND: Atrial fibrillation (AF) is a common complication after major noncardiac thoracic surgery and increases the cost and morbidity of these operations. We sought to derive and validate a clinical prediction rule to risk-stratify patients for postoperative AF. METHODS: For a cohort of cancer patients who underwent noncardiac thoracic surgery, we examined the association of preoperative clinical variables with development of postoperative AF. Logistic regression identified multivariable predictors of AF and a clinical risk score was developed by assigning weighted point scores for the presence of each significant covariate. An independent data set was used for validation purposes. RESULTS: Of the 856 patients, 147 (17.2%) developed postoperative AF. Male gender (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1 to 2.4), advanced age (55 to 74 years OR 4.4, 95% CI 2.0 to 9.8; > or =75 years OR 9.2, 95% CI 3.9 to 21.5), and preoperative heart rate greater than or equal to 72 beats per minute (OR 1.7, 95% CI 1.2 to 2.5) were independent predictors of postoperative AF. A risk score was assigned with male gender and heart rate greater than or equal to 72 beats per minute each receiving 1 point, and age 55 to 74 and greater than or equal to 75 years receiving 3 and 4 points, respectively. The risk of postoperative AF ranged from 0% (0 points) to 54.6% (6 points) (p < 0.001). The score-based risk in both derivation and validation sets was similar (p = 0.66). CONCLUSIONS: A prediction rule using clinical variables can be used to predict the risk of postoperative AF after noncardiac thoracic surgery. This information can be used to guide prophylactic therapy.
Aged↗
Clinical characteristics of erythropoietin-associated pure red cell aplasia.
Recombinant human erythropoietin (epoetin) was first used for the treatment of anemia resulting from renal disease in 1986. During the first 10 years of its use, there were only three cases of epoetin-induced antibodies reported, which resulted in pure red cell aplasia (PRCA). Between 1998 and 2002, 191 chronic kidney disease patients developed PRCA during the course of epoetin treatment. Clinical characteristics of patients with PRCA include an absolute resistance to epoetin therapy, with a rapid development of severe anemia and very low reticulocyte count. In addition, patients developed high titre, high affinity neutralizing antibodies, which are detectable by immunoassays. The diagnosis of PRCA requires the onset of severe anemia, erythropoietin neutralizing antibodies in circulation, the lack of red cell precursors in the bone marrow aspirate, and normal to elevated transferrin saturation. Patients require blood transfusions to maintain an acceptable level of hemoglobin. Cessation of epoetin treatment alone does not improve PRCA. Patients have required immunosuppressive treatment. However, the most efficacious treatment has been kidney transplantation accompanied by immunosuppressive agents that prevent organ rejection. Evaluating patients receiving recombinant epeoetin therapy who experience a sudden loss of epoetin efficacy for the possibility of antibody-mediated PRCA is crucial. Timely identification and treatment of this rare syndrome can prevent the development of severe red blood cell transfusion requirements and the potential complications of iron overload, which results from these transfusions.
Anemia↗
Epoetin-induced pure red-cell aplasia (PRCA): preliminary results from the research on adverse drug events and reports (RADAR) group.
In 2002, investigators from France reported 13 patients in whom pure red cell aplasia developed during treatment with recombinant human erythropoietin (epoetin). We reviewed 208 cases of this syndrome reported worldwide. Adverse event reports describing suspected and confirmed cases of epoetin-associated PRCA in websites maintained by the manufacturers and distributors of epoetin products and other publicly available sources were reviewed. Cases were reported from countries in Europe, North America, Asia, Australia and the United States (US). For >95% of the cases, EPREX had been administered subcutaneous to persons with chronic kidney disease (CKD) and anemia for a mean of nine months prior to diagnosis of PRCA. For 80% of persons with the syndrome, reversal of antibody production and recovery of reticulocytes occurred with discontinuation of epoetin and treatment with immunosuppressive agents. Patients with anemia of CKD who developed neutralizing anti-erythropoietin antibodies and pure red cell aplasia during treatment with epoetin have been identified in a number of countries. In non-US countries, switching renal dialysis patients from subcutaneous to intravenous administration of epoetin alpha and improved handling of the drug appear to have been successful strategies for reducing the occurrence of this toxicity. The decrease in cases occurred coincident with these varied changes, although it is difficult to prove causality. PRCA is a rare, but important side effect of epoetin therapy.
Adverse Drug Reaction Reporting Systems↗
The blue cross blue shield assessment technology review: summary of findings.
Epoetin (EPO; erythropoietin) treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this paper is to review the findings of the 2001 Blue Cross/Blue Shield Association Technology Evaluation Center overview on EPO use in oncology, which served the foundation for the 2002 ASH/ASCO clinical guideline on this subject. The BC/BS review had two major aims: (1) to quantify the effects of EPO on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia, and (2) to evaluate whether outcomes are superior when EPO treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying relevant studies published between 1985 and 1998. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized, but unblinded trials and trials with excessive exclusions were included in the meta-analysis, but were defined as lower quality. Twenty-two trials (n=1927) met inclusion criteria, and 12 (n=1390) could be combined for estimation of odds of transfusion. EPO decreased the percentage of patients transfused by 9-45% in adults with mean baseline hemoglobin concentrations of 10g/dL or less (7 trials; n=1080), by 7-47% in those with hemoglobin concentrations greater than 10g/dL, but less than 12g/dL (7 trials; n=431), and by 7-39% in those with hemoglobin concentrations of 12g/dL or higher (5 trials; n=308). In a sensitivity analysis, the combined odds ratio for transfusion in EPO-treated patients as compared with controls was 0.45 (95% confidence interval [CI]=0.33-0.62) in higher quality studies and 0.14 (95% CI=0.06-0.31) in lower quality studies. The number of treated patients needed to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10g/dL or less reported statistically significant effects of EPO treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed the effects of EPO on anemia-related symptoms. The review concluded that EPO reduced the odds of transfusion for cancer patients undergoing therapy. Evidence was insufficient to determine whether initiating EPO earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10g/dL. An update of this review, which includes information on quality of life, transfusion requirment, survival and tumor response, for first and second-generation epoetin products is ongoing.
Anemia↗
Effectiveness of erythropoietin in the treatment of patients with malignancies: methods and preliminary results of a Cochrane review.
Cancer and cancer therapy-associated anemia may have an impact on tumor response and overall survival. Additionally, anemia represents an important economic factor. Therefore, therapeutic alternatives such as erythropoietin (EPO) and red blood cell transfusions have to be evaluated systematically. The effectiveness of recombinant human EPO to prevent or alleviate anemia in patients with malignant disease was determined. Randomized controlled trials comparing prophylaxis or treatment of anemia with EPO plus red blood cell transfusion (RBCT) or RBCT only in patients with malignant disease undergoing antineoplastic therapy were included. The endpoints needed for RBCT were hematological response (hemoglobin increase of 2g/dL or hematocrit increase of 6%), tumor response, and overall survival. Medical databases (Cochrane Library, MEDLINE, EMBASE) and conference proceedings were searched (1985-2001). Full-text and abstract publications were included as well as unpublished data. Data extraction and quality assessment were done in duplicate. All authors were contacted to obtain missing data. Out of 33 eligible studies, 27 trials with 3,287 randomized patients were included.
Anemia↗
Thrombotic thrombocytopenic purpura-2005.
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ADAM Proteins↗
A qualitative study of literacy and patient response to HIV medication adherence questionnaires.
The purpose of this study was to elicit patient feedback regarding the perceived clarity and level of difficulty associated with self-report human immunodeficiency virus (HIV) medication adherence measurement tools. HIV-infected patients from clinics in Shreveport, Louisiana, and Chicago, Illinois, were recruited to participate in four focus group discussions. Three groups consisted of patients with limited literacy skills (< ninth-grade reading ability), and one group contained patients with adequate literacy skills (> or = ninth-grade reading ability). Five themes emerged: (1) respondent understanding of the term "adherence," (2) recall, (3) question format, (4) visual aids, and (5) instrument administration. Participants struggled to define adherence, relied on visual cues to identify medications, and had a short recall time frame for missed doses (< or =3 days). Most preferred simple question formats and for their physician to assess adherence orally. Patients receiving treatment for HIV infection, especially those with limited literacy skills, may find it difficult to respond to existing HIV medication adherence questionnaires.
Adult↗
Opportunities for disease state management in prostate cancer.
In this paper, we examine how the management of prostate cancer lends itself to a disease state management (DSM)-based approach, and propose a framework that emphasizes the patient-provider-caregiver triad in managing the long-term implications of the condition. There is often no clearly superior approach to the management of patients with prostate cancer (eg, watchful waiting and hormonal therapy), and each option entails different trade-offs in quality of life. Ideally, the physician and patient discuss the options, issues, and patient preferences for treatment through the shared decision-making process. A family caregiver such as the spouse of the patient is often involved in the treatment decision and in the long-term management of the cancer experience. In order to develop a DSM program supporting both patient and caregiver, educational, psychosocial, and health care system support needs should be tailored to each phase of cancer treatment/management. To embrace the unique aspects of prostate cancer management, the proposed framework emphasizes communication among the patient-caregiver-provider triad, inclusion of family caregivers in the program, cancer phase-specific support, and psychosocial services as a basis for implementation and evaluation of a DSM program in prostate cancer.
Delivery of Health Care↗
Delays in suspicion and isolation among hospitalized persons with pulmonary tuberculosis at public and private US hospitals during 1996 to 1999.
BACKGROUND: While prior studies have shown that public and private hospitals differ in their rates of suspicion and isolation of patients who are at risk for tuberculosis (TB), no study has investigated whether this variation is due to differences in the impact of patient case-mix on hospitals or to variations attributable to specific hospital practice patterns. OBJECTIVE: To investigate patient-level and hospital-level factors associated with delays in TB suspicion and isolation among inpatients with pulmonary TB disease. DESIGN: Retrospective cohort study of patients hospitalized with culture-positive pulmonary TB during 1996 to 1999. SETTING: Patients with culture-proven pulmonary TB treated at three public hospitals (765 patients) and seven not-for-profit private hospitals (172 patients) in Chicago, Los Angeles, and southern Florida that provided care for five or more patients with TB per year during the study period. MEASUREMENTS: Two-day rates (within 48 h from admission) of acid-fast bacilli (AFB) smear orders and 1-day rates (within 24 h from admission) of TB isolation. RESULTS: Two-day rates of ordering AFB smears were > 80% at three public and two private hospitals vs 65 to 75% at five private hospitals. One-day rates of TB isolation at the three public hospitals were 64%, 79%, and 86%, respectively, vs 39 to 58% at the seven private hospitals. Delays of > 2 days in ordering AFB smears were associated with patient-level factors: absence of cough (adjusted odds ratio [AOR], 6.02; 95% confidence interval [CI], 3.82 to 9.52), cavitary lung lesion (AOR, 5.17; 95% CI, 1.98 to 13.50), night sweats (AOR, 3.38; 95% CI, 1.90 to 5.99), chills (AOR, 1.70; 95% CI, 1.01 to 2.88), and female gender (AOR, 1.66; 95% CI, 1.06 to 2.60). Delays of > 1 day in ordering pulmonary isolation were associated with patient-level factors: absence of cough (AOR, 3.40; 95% CI, 2.31 to 5.03), cavitary lung lesion (AOR, 2.66; 95% CI, 1.57 to 4.50), night sweats (AOR, 1.98; 95% CI, 1.35 to 2.92), and history of noninjecting drug use (AOR, 1.86; 95% CI, 1.16 to 2.99) and one hospital-level factor: receiving care at a nonpublic hospital. Even after adjustment for patient-level factors, TB patients at private hospitals were half as likely as those at public hospitals to be placed in pulmonary isolation (AOR, 0.47; 95% CI, 0.30 to 0.72), while odds of suspecting TB in these same patients were similar at both hospitals. CONCLUSION: Private hospitals should order TB isolation for all patients for whom AFB smears are ordered, a policy that has been instituted previously at public hospitals in our study.
Adult↗