Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
Paul R Yarnold
Publications and source records attributed to Paul R Yarnold.
Clinical features and correlates of gemcitabine-associated lung injury: findings from the RADAR project.
BACKGROUND: Gemcitabine is a commonly used chemotherapeutic agent structurally and pharmacologically similar to cytarabine. Recently, instances of severe gemcitabine-associated lung injury have been reported. Herein, investigators affiliated with the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program evaluated clinical characteristics of gemcitabine-associated severe acute lung injury from clinical trial reports, medical literature case reports, and spontaneous reports to the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). METHODS: Clinical data were obtained by reviewing adverse event case reports for gemcitabine-associated lung injury as reported in the medical literature and in the FDA AERS database. Upper limit estimates of ADE rate were derived from review of published clinical trials reporting gemcitabine-associated lung injury rates of 10% or higher. RESULTS: A total of 178 reports of gencitabine-associated lung injury were identified; in AERS, there were 55 cases from clinical trials and 92 spontaneous reports. A comprehensive search revealed 31 medical literature reports. Clinical features of gemcitabine-associated lung injury included dyspnea, fever, pulmonary infiltrate, and cough with recognition of toxicity occurring after a median duration of 48 (range, 1-529) days after initiation of gemcitabine. The taxanes, docetaxel and paclitaxel, were frequently reported as coadministered therapies. Eleven Phase II or Phase III clinical trials with 317 patients identified gemcitabine-associated lung injury rates of greater than 10%, with the highest rates (22% and 42%) being observed in Phase III clinical trials where Hodgkin disease patients were treated with a regimen that included gemcitabine and bleomycin. CONCLUSIONS: High rates of gemcitabine-associated severe lung injury were observed when gemcitabine was combined with other therapies known to also cause lung injury. Physicians should have a high index of suspicion for this toxicity and report the relevant clinical findings to the FDA's AERS.
Antimetabolites, Antineoplastic↗
Risk factors and outcomes associated with non-Enterococcus faecalis, non-Enterococcus faecium enterococcal bacteremia.
OBJECTIVES: To compare risk factors, clinical features, and outcomes in patients with Enterococcus avium, Enterococcus casseliflavus, Enterococcus durans, Enterococcus gallinarum, and Enterococcus mundtii bacteremia (cases) with those in patients with Enterococcus faecalis bacteremia (controls). DESIGN: A retrospective case-control study. SETTING: A 725-bed, university-affiliated, academic medical center. PATIENTS: The clinical microbiology database at Northwestern Memorial Hospital from January 1994 to May 2003 was searched to identify cases; each case was matched to one control on the basis of date of admission. RESULTS: Thirty-three cases were identified and matched with 33 controls. The mean duration of hospital stay was longer (29.7 vs 17.2 days; P = .03) and the mean time to acquisition of bacteremia was greater (16.5 vs 6.3 days; P = .003) for cases than controls. Cases were more likely to have underlying hematologic malignancies (P < .001), to have been treated with corticosteroids (P = .02), and to be neutropenic (P = .003). Controls were more likely to have an indwelling bladder catheter (P = .01), and cases were more likely to have the gastrointestinal tract as a source of infection (P = .007) and to have concurrent cholangitis (P = .002). There were no differences in severity of illness or in mortality rates. CONCLUSIONS: Compared with patients with E. faecalis bacteremia, patients with non-E. faecalis, non-Enterococcus faecium enterococcal bacteremia were more likely to have a hematologic malignancy, prior treatment with corticosteroids, neutropenia, and cholangitis; longer duration of hospital stay was also identified as a clinical feature. However, non-E. faecalis, non-E. faecium species are not associated with any differences in mortality.
Bacteremia↗
The roles of low literacy and social support in predicting the preventability of hospital admission.
BACKGROUND: Prior studies found higher hospitalization rates among patients with low literacy, but did not determine the preventability of these admissions or consider other determinants of hospitalization, such as social support. This study evaluated whether low literacy was a predictor for preventability of hospitalization when considered in the context of social support, sociodemographics, health status, and risk behaviors. METHODS: A convenience sample of 400 patients, admitted to general medicine wards in a university-affiliated Veterans Affairs hospital between August 1, 2001 and April 1, 2003, completed a face-to-face interview to assess literacy, sociodemographics, social support, health status, and risk behaviors. Two Board-certified Internists independently assessed preventability of hospitalization and determined the primary preventable cause through blinded medical chart reviews. RESULTS: Neither low literacy ( or =12 people talked to weekly (P<.023). Among nonbinge drinkers with lower social support for medical care, larger social networks were predictive of preventability of hospitalization. Among nonbinge drinkers with higher support for medical care, lower outpatient utilization was predictive of the preventability of hospitalization. CONCLUSIONS: While low literacy was not predictive of admission preventability, the formal assessment of alcohol binge drinking, social support for medical care, social network size, and prior outpatient utilization may enhance our ability to predict the preventability of hospitalizations and develop targeted interventions.
Aged↗
Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project.
OBJECTIVES: We undertook the review of all available cases of hypersensitivity reactions after placement of a drug-eluting stent (DES) and classified potential causes. BACKGROUND: Six months after the approval of the first DES, the Food and Drug Administration (FDA) reported 50 hypersensitivity reactions after stent placement but later concluded these were due to concomitantly prescribed medications such as clopidogrel. Nevertheless, the FDA continued to receive reports of hypersensitivity. METHODS: Reports available from April 2003 through December 2004 for hypersensitivity-like reactions associated with the sirolimus-eluting stent (CYPHER, Cordis Corp., Miami Lakes, Florida) and paclitaxel-eluting stent (TAXUS, Boston Scientific Corp., Natick, Massachusetts) were reviewed. Sources of reports included the FDA's adverse-device-event database, the published literature, and investigators from the Research on Adverse Drug/Device events And Reports (RADAR) project. Causality was assessed using standardized World Health Organization criteria. RESULTS: Of 5,783 reports identified for the DES in the FDA database, 262 unique events included hypersensitivity symptoms. Of these reports, 2 were certainly and 39 unlikely caused by clopidogrel and 1 was certainly, 9 probably, and 13 unlikely caused by the DES. From all sources, we identified 17 distinct cases that were probably or certainly caused by the stent, of which 9 had symptoms that lasted longer than four weeks. Four autopsies confirmed intrastent eosinophilic inflammation, thrombosis, and lack of intimal healing. CONCLUSIONS: The FDA reports and autopsy findings suggest that DES may be a cause of systemic and intrastent hypersensitivity reactions that, in some cases, have been associated with late thrombosis and death.
Coronary Vessels↗
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↗
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↗
Evolving risk for thromboembolism in spinal cord injury (SPIRATE Study).
OBJECTIVE: To compare the frequency of venous thromboembolism (VTE) in patients examined during 1992-1995 with those examined during 1999-2003. DESIGN: A comprehensive review of the charts of all patients admitted between late 1999 and early 2003 for rehabilitation after spinal cord injury. Only records, including evidence for objective testing for VTE (ultrasound, venography, lung scanning) were included, and patients having inferior vena cava filter placement or previous VTE were excluded. Analysis variables included type and location of spinal cord injury, American Spinal Injury Association classification, concomitant injuries, surgical procedures, complications, preexisting illnesses, and use of antithrombotic prophylaxis. Using univariate optimal discriminant analysis, data from the current group of patients were compared with a previous study of 243 subjects examined between 1992 and 1995. RESULTS: The current sample consisted of 76 persons with acute spinal cord injury, of whom six had VTE (7.9%). As compared with the frequency of VTE in the previous patient sample (21%), this represented a significant decrease (P<0.01). The major differences between the current and previous patient samples were a decrease in the use of unfractionated heparin (15.8% vs. 56.8%, P<0.0001) and an increase in the use of low molecular weight heparin (81.6% vs. 59.7%, P<0.0001). CONCLUSIONS: VTE has been a common and occasionally lethal complication in persons with spinal cord injury. The recent switch from unfractionated heparin to low molecular weight heparin for the prevention of VTE has coincided with a decrease in the frequency of this complication in patients with spinal cord injury.
Adult↗
Emerging incidence of Enterococcus faecium among hospital isolates (1993 to 2002).
Historically, most clinical microbiology laboratories report that 80 to 90% of enterococci are Enterococcus faecalis, whereas E. faecium accounts for 5 to 10% of isolates. At our medical center from 1993 to 2002, we evaluated the percentages of E. faecium among all enterococcal isolates and the percentages of E. faecium isolates that were vancomycin resistant. Over this 10-year period, the percentage of enterococci that were identified as E. faecium increased from 12.7 to 22.2% (P < 0.001) and the proportion of E. faecium that was vancomycin resistant increased from 28.9 to 72.4% (P < 0.001). Both the percentage of E. faecium among the enterococci and the proportion of vancomycin-resistant E. faecium increased significantly over this 10-year period.
Chicago↗
Pharmacist interventions to improve the management of coronary artery disease.
Explore the source record for details and available documents.
Academic Medical Centers↗
The epidemiology of prescribing errors: the potential impact of computerized prescriber order entry.
BACKGROUND: Adverse drug events (ADEs) are the most common cause of injury to hospitalized patients and are often preventable. Medication errors resulting in preventable ADEs most commonly occur at the prescribing stage. OBJECTIVES: To describe the epidemiology of medication prescribing errors averted by pharmacists and to assess the likelihood that these errors would be prevented by implementing computerized prescriber order entry (CPOE). METHODS: At a 700-bed academic medical center in Chicago, Ill, clinical staff pharmacists saved all orders that contained a prescribing error for a week in early 2002. Pharmacist investigators subsequently classified drug class, error type, proximal cause, phase of hospitalization, and potential for patient harm and rated the likelihood that CPOE would have prevented the prescribing error. RESULTS: A total of 1111 prescribing errors were identified (62.4 errors per 1000 medication orders), most occurring on admission (64%). Of these, 30.8% were rated clinically significant and were most frequently related to anti-infective medication orders, incorrect dose, and medication knowledge deficiency. Of all verified prescribing errors, 64.4% were rated as likely to be prevented with CPOE (including 43% of the potentially harmful errors), 13.2% unlikely to be prevented with CPOE, and 22.4% possibly prevented with CPOE depending on specific CPOE system characteristics. CONCLUSIONS: Prescribing errors are common in the hospital setting. While CPOE systems could improve practitioner prescribing, design and implementation of a CPOE system should focus on errors with the greatest potential for patient harm. Pharmacist involvement, in addition to a CPOE system with advanced clinical decision support, is vital for achieving maximum medication safety.
Clinical Pharmacy Information Systems↗
Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration.
BACKGROUND AND PURPOSE: Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)-and identified prognostic factors associated with mortality. METHODS: This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis. RESULTS: Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for </=2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival (100% versus 27.3%, P<0.001). CONCLUSIONS: Compared with reports submitted by suppliers or the FDA, reports obtained through active surveillance provided timelier and more complete information. Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly.
Adult↗
The Emergency Severity Index (version 3) 5-level triage system scores predict ED resource consumption.
OBJECTIVES: The Emergency Severity Index (ESI) version 3 is a valid and reliable 5-level triage instrument that is gaining in popularity. A unique component of the ESI algorithm is prediction of resource consumption. Our objective was to validate the ESI version 3 triage algorithm in a clinical setting for the following outcome measures: actual resource consumption and patient length of stay in the emergency department and hospital. METHODS: We conducted a retrospective, descriptive study of 403 ED patients who presented to a large academic medical center. The following dependent variables were abstracted from the ED record: number of ED resources used and emergency department and hospital length of stay. The relationship between ESI level and each of the dependent variables was determined. RESULTS: Mean resource use decreased monotonically as a function of ESI level 1 (5), 2 (3.89), 3 (3.3), 4 (1.2) and 5 (0.2). The ED average length of stay (minutes) per ESI level was as follows: 1 (195), 2 (255), 3 (304), 4 (193), and 5 (98). ESI triage level did not predict hospital length of stay. CONCLUSIONS: The ESI algorithm accurately predicted ED resource intensity and gives administrators the opportunity to benchmark ED length of stay according to triage acuity level.
Adolescent↗
Identifying three types of violent offenders and predicting violent recidivism while on probation: a classification tree analysis.
This study employs classification tree analysis (CTA) to address whether 3 groups of violent offenders have similar or different risk factors for violent recidivism while on probation. A sample of 1344 violent offenders on probation was classified as generalized aggressors (N = 302), family only aggressors (N = 321), or nonfamily only aggressors (N = 717). The strongest predictor of violent recidivism while on probation was whether the offender was a generalized aggressor or not, with generalized aggressors more likely to be arrested for new violent crimes. Prior arrests for violent crimes predicted violent recidivism of generalized aggressors, but did not significantly predict violent recidivism of family only and nonfamily only aggressors. For generalized aggressors and family only batterers, treatment noncompliance was an important risk predictor of violent recidivism. CTA compared to logistic regression classified a higher percentage of cases into low-risk and high-risk groups, provided higher improvement in classification accuracy of violent recidivists beyond chance performance, and provided a better balance of false positives and false negatives. The implications for the risk assessment and domestic violence literature are discussed.
Adult↗
Multidrug-resistant Pseudomonas aeruginosa cholangitis after endoscopic retrograde cholangiopancreatography: failure of routine endoscope cultures to prevent an outbreak.
BACKGROUND: Nosocomial infections due to medical devices are of increasing concern to infection control practitioners. Attempts to prevent such infections have included surveillance cultures of endoscopes and bronchoscopes. In July 2002, the infectious disease consultation service was asked to see three patients with sepsis due to multidrug-resistant Pseudomonas aeruginosa after endoscopic retrograde cholangiopancreatography (ERCP). OBJECTIVE: To describe an outbreak of multidrug-resistant P. aeruginosa sepsis after ERCP at an institution that performs routine surveillance cultures of endoscopes. DESIGN: A traditional outbreak investigation supplemented by pulsed-field gel electrophoresis (PFGE) was undertaken, including a case-control analysis based on the hypothesis that all infected individuals had their ERCP performed with the same endoscope. SETTING: A tertiary-care academic medical center. RESULTS: The case-control analysis confirmed the hypothesis that undergoing ERCP with the implicated endoscope was associated with a culture positive for Pseudomonas (P = .01). The available strains were identical by PFGE. This outbreak occurred despite a negative surveillance culture of the implicated endoscope 1 month earlier. CONCLUSIONS: Infectious morbidity can occur after endoscopy despite negative surveillance cultures. The practice of routine endoscope cultures does not prevent device-related infectious morbidity.
Aged↗
HIV-related pneumonia care in older patients hospitalized in the early HAART era.
Age-related variations in care have been identified for HIV-associated Pneumocystis carinii pneumonia (PCP) in both the 1980s and 1990s. We evaluated if age-related variations affected all aspects of HIV-specific and non-HIV-specific care for HIV-infected individuals with PCP or community-acquired pneumonia (CAP), or whether age-related variations were primarily limited to HIV-specific aspects of care. Subjects were HIV-infected persons with PCP (n = 1855) or CAP (n = 1415) hospitalized in 8 cities from 1995 to 1997. Nine percent of our study patients had received protease inhibitors and 39% had received any type of antiretroviral therapy prior to hospitalization. Data were abstracted from medical records and included severity of illness, HIV-specific aspects of care (initiation of PCP medications), general measures of care [initiation of CAP medications, intubation, and intensive care units (ICU)], and inpatient mortality. Compared to younger patients, pneumonia patients 50 years of age or older were significantly more likely to: be severely ill (PCP, 20.4% vs. 10.4%; CAP, 27.5% vs. 14.9%; each p = 0.001), receive ICU care (PCP, 22.0% vs. 12.8%, p = 0.002; CAP: 15.1% vs. 9.4%; p = 0.02), and be intubated (PCP, 14.6% vs. 8.4%, p = 0.01; CAP, 9.9% vs. 5.6%, p = 0.03). Compared to younger patients, older patients (>/=50 years) had similar rates of timely medications for CAP (48.5% vs. 50.8%) but had lower rates of receiving anti-PCP medications (85.8% vs. 92.9%, p = 0.002). Differences by age in timely initiation of PCP medications, ICU use, and intubation were limited to the nonseverely ill patients. Older hospitalized patients were more likely to die (PCP, 18.3% vs. 10.4%; CAP, 13.4% vs. 8.5%; each p < 0.05). After adjustment for disease severity and timeliness of antibiotic use, mortality rates were similar for both age groups. Physicians should develop strategies that increase awareness of the possibility of HIV infection in older individuals.
AIDS-Related Opportunistic Infections↗
Reliability and validity of scores on The Emergency Severity Index version 3.
OBJECTIVES: No widely used triage instrument accurately assesses patient acuity. The Emergency Severity Index (ESI) promises to facilitate reliable acuity assessment and possibly predict patient disposition. However, reliability and validity of ESI scores have not been established in emergency departments (EDs) outside the original research sites, and version 3 (v.3) of the ESI has not been evaluated. The study hypothesis was that scores on the ESI v.3 show good interrater reliability and predict hospital admission, admission site, and death. METHODS: The authors conducted an ED-based cross-sectional retrospective study of 403 systematically selected ED records of patients who presented to an academic medical center. Twenty-seven variables were abstracted, including triage level assigned, admission status, site, and death. Using a standard process, the researchers determined the true triage level. Weighted kappa and Pearson correlation were used to calculate interrater reliability between true triage level and triage score assigned by the registered nurse (RN). The relationships between the true ESI level and admission, admission site, and death were assessed. RESULTS: Interrater reliability between RN ESI level and the true ESI level was kappa = 0.89; Pearson r = 0.83 (p < 0.001). Hospital admission by ESI level was as follows: 1 (80%), 2 (73%), 3 (51%), 4 (6%), and 5 (5%). A higher percentage of ESI level-1 and level-2 patients (40%, 12%) were admitted to the intensive care unit than ESI levels 3-5 (2%, 0%, 0%). Admission to telemetry for ESI levels 1-5 was 20%, 19%, 7%, 1%, and 0%, respectively. Three of four patients who died were ESI level 1 or 2. CONCLUSIONS: Scores on the ESI assigned by nurses have excellent interrater reliability and predict hospital admission and location of admission.
Adult↗
Assessment of resident professionalism using high-fidelity simulation of ethical dilemmas.
OBJECTIVES: To examine the responses of emergency medicine residents (EMRs) to ethical dilemmas in high-fidelity patient simulations as a means of assessing resident professionalism. METHODS: This cross-sectional observational study included all EMRs at a three-year training program. Subjects were excluded if they were unable or unwilling to participate. Each resident subject participated in a simulated critical patient encounter during an Emergency Medicine Crisis Resource Management course. An ethical dilemma was introduced before the end of each simulated encounter. Resident responses to that dilemma were compared with a professional performance checklist evaluation. Multi-response permutation procedure analysis was used to compare performance measures between resident classes, with the a priori hypothesis that mean performance should increase as experience increases. RESULTS: Of the 30 potential subjects, 90% (27) participated. The remaining three residents were unavailable due to scheduling conflicts. It was observed that senior residents (second and third year) performed more checklist items than did first-year residents (p < 0.028 for each senior class). Omnibus comparison of mean critical actions completed across all three years was not statistically significant (p < 0.13). Residents performed a critical action with 100% uniformity across training years in only one ethical scenario ("Practicing Procedures on the Recently Dead"). Residents performed the fewest critical actions and overall checklist items for the "Patient Confidentiality" case. CONCLUSIONS: Senior residents had better overall performance than incoming interns, suggesting that professional behaviors are learned through some facet of residency training. Although limited by small sample size, the application of this performance-assessment tool showed the ability to discriminate between experienced and inexperienced EMRs with respect to a variety of aspects of professional competency. These findings suggest a need for improved resident education in areas of professionalism and ethics.
Accreditation↗