Matthew J. Fisher

Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: Report from the Research on Adverse Drug Events and Reports (RADAR) project

Pegylated recombinant human megakaryocyte growth and development factor (PEG‐rHuMGDF) and granulocyte colony‐stimulating factor (G‐CSF) promote haematopoietic progenitor cell maturation. We reviewed the findings for healthy volunteers/donors who developed haematological malignancies following PEG‐rHuMGDF or G‐CSF administration. Information was reviewed for three of 538 volunteers who received PEG‐rHuMGDF in clinical trials and two of 200 donors who underwent G‐CSF mobilised stem cell harvesting procedures for sibling stem cell transplants. Mantle cell, diffuse large B‐cell lymphoma and chronic lymphocytic leukaemia were diagnosed 1–5 years after PEG‐rHuMGDF exposure among three volunteers. For one patient, thrombocytopenia due to autoantibodies to PEG‐rHuMGDF developed shortly after PEG‐rHuMGDF administration and persisted until chemotherapy was administered. All three achieved complete remission, although one patient relapsed. Acute myeloid leukaemia was diagnosed 4 and 5 years after G‐CSF mobilisation in two donors who underwent peripheral blood stem cell donation for sibling allogeneic haematopoietic stem cell transplantation. Following intensive chemotherapy, one died from acute leukaemia and the second is in complete remission. Controversy exists over the appropriateness of administering haematopoietic growth factors to healthy individuals. While a causal relationship with haematological malignancies cannot be demonstrated, long‐term follow‐up among healthy individuals who receive haematopoietic growth factors is needed.

Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008)

Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions.

Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project.

BACKGROUND In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. METHODS We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). RESULTS The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. CONCLUSIONS Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing.

Economics of Malignant Gliomas: A Critical Review

PURPOSE Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society. METHODS A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the studys publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another. RESULTS Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from

Results from the First Decade of Research Conducted by the Research on Adverse Drug Events and Reports (RADAR) Project

50,600 to

Legal, financial, and public health consequences of transfusion-transmitted hepatitis C virus in persons with haemophilia

92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of

Defining a Mismatch: Differences in Usage of Social Networking Sites Between Medical Students and the Faculty Who Teach Them

50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial. CONCLUSION With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively.

Is Illinois heeding the call to regionalize pancreatic surgery

IntroductionIn 1998, a multidisciplinary team of investigators initiated the Research on Adverse Drug events And Reports (RADAR) project, a post-marketing surveillance effort that systematically investigates and disseminates information describing serious and previously unrecognized serious adverse drug and device reactions (sADRs).ObjectiveHerein, we describe the findings, dissemination efforts, and lessons learned from the first decade of the RADAR project.MethodsAfter identifying serious and unexpected clinical events suitable for further investigation, RADAR collaborators derived case information from physician queries, published and unpublished clinical trials, case reports, US FDA databases and manufacturer sales figures.Study selectionAll major RADAR publications from 1998 to the present are included in this analysis.Data extractionFor each RADAR publication, data were abstracted on data source, correlative basic science findings, dissemination and resultant safety information.ResultsRADAR investigators reported 43 serious ADRs. Data sources included case reports (17 sADRs), registries (5 sADRs), referral centers (8 sADRs) and clinical trial reports (13 sADRs). Correlative basic science findings were reported for ten sADRs. Thirty-seven sADRS were described as published case reports (5 sADRs) or published case-series (32 sADRs). Related safety information was disseminated as warnings or boxed warnings in the package insert (17 sADRs) and/or ‘Dear Healthcare Professional’ letters (14 sADRs).ConclusionAn independent National Institutes of Health-funded post-marketing surveillance programme can supplement existing regulatory and pharmaceutical manufacturer-supported drug safety initiatives.

Colonoscopy is high yield in spinal cord injury

Background  Since the first cases of acquired immunodeficiency syndrome in persons with haemophilia were reported in 1982, much has been written about the consequences of human immunodeficiency virus (HIV) contamination of the blood supply. Relatively little attention has been paid to similar hepatitis C virus (HCV) concerns since the first cases of HCV‐infected persons with haemophilia were identified in 1989.

Cremophor EL-containing paclitaxel-induced anaphylaxis: A call to action

Background: Use of social networking sites (SNS) by medical students is increasing, and some students lack awareness of pitfalls arising from the intersection of social networking and medicine. Many institutions have developed guidelines on using SNS, but they are insufficient for students. Educators need new methods to train students on the appropriate use of this technology, but more information is needed before implementing change. Purposes: Differences in SNS usage between students and faculty were examined. The goal was to evaluate four content areas: SNS usage patterns, attitudes regarding activity on SNS, experience with patient interactions online, and awareness of institutional guidelines on use of SNS. Methods: A cross-sectional survey took place at Feinberg School of Medicine, Northwestern University, in 2012. Participants included all students and a cohort of faculty who teach them in a class on professionalism. Results: The response rate was 42% by students (300/711) and 78% by faculty (31/40). Of the students, 94% use SNS, compared to 48% of faculty. Students were more likely than faculty to display content they would not want patients to see (57% vs. 27%), report seeing inappropriate content on colleagues’ SNS profiles (64% vs. 42%), and ignore harmful postings by colleagues (25% vs. 7%). Faculty were more likely than students to have been approached by patients on SNS (53% vs. 3%). Most participants were unlikely to conduct Internet searches on patients. Conclusions: Students are more likely than faculty to use SNS and use it very differently than faculty. Students would benefit from training on appropriate use of SNS. Topics that should be addressed include editing ones online presence, managing friend requests from patients, dealing with colleagues who post harmful content, conducting Internet searches on patients, and discussion of boundaries to identify potential harms associated with SNS usage. Differences in usage between students and faculty raise questions if faculty are well suited to provide this training.