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Background: Between 1988 and 1998, antibody-associated pure red-cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 such cases were reported from France — 12 in patients who had received the Eprex formulation of epoetin alfa and 1 in a patient who had received Neorecormon (a formulation of epoetin beta); both are products that are marketed outside the United States. Methods: We obtained reports of epoetin-associated pure red-cell aplasia from the Food and Drug Administration and from the manufacturers of Eprex, Epogen (another formulation of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of exposure-adjusted incidence were analyzed according to the product, the cause of anemia, the route of administration, the country in which pure red-cell aplasia was identified, and the date on which pure red-cell aplasia was reported. Results: Between January 1998 and April 2004, 175 cases of epoetin-associated pure red-cell aplasia were reported for Eprex, 11 cases for Neorecormon, and 5 cases for Epogen. Over half these cases had occurred in France, Canada, the United Kingdom, and Spain. Between 2001 and 2003, the estimated exposure-adjusted incidence was 18 cases per 100,000 patient-years for the Eprex formulation without human serum albumin, 6 per 100,000 patient-years for the Eprex formulation with human serum albumin, 1 case per 100,000 patient-years for Neorecormon, and 0.2 case per 100,000 patient-years for Epogen. After procedures were adopted to ensure appropriate storage, handling, and administration of Eprex to patients with chronic kidney disease, the exposure-adjusted incidence decreased by 83 percent worldwide. Conclusions: After the peak incidence of Eprex-associated pure red-cell aplasia was reached in 2001, interventions designed in response to drug-monitoring programs worldwide resulted in a reduction of more than 80 percent in the incidence of pure red-cell aplasia due to Eprex. N Engl J Med 2004;351:1403-8. [ABSTRACT FROM AUTHOR]

Background: Ambulatory training in internal medicine residency programs has historically been considered less robust than inpatient-focused training, which prompted a 2009 revision of the Accreditation Council for Graduate Medical Education (ACGME) Program Requirements in Internal Medicine. This revision was intended to create a balance between inpatient and outpatient training standards and to spur innovation in the ambulatory setting., Objective: We explored innovations in ambulatory education in internal medicine residency programs since the 2009 revision of the ACGME Program Requirements in Internal Medicine., Methods: The authors conducted a scoping review of the literature from 2008 to 2017, searching PubMed, ERIC, and Scopus databases. Articles related to improving educational quality of ambulatory components of US-based internal medicine residency programs were eligible for inclusion. Articles were screened for relevance and theme categorization and then divided into 6 themes: clinic redesign, curriculum development, evaluating resident practice/performance, teaching methods, program evaluation, and faculty development. Once a theme was assigned, data extraction and quality assessment using the Medical Education Research Study Quality Instrument (MERSQI) score were completed., Results: A total of 967 potentially relevant articles were discovered; of those, 182 were deemed relevant and underwent full review. Most articles fell into curriculum development and clinic redesign themes. The majority of included studies were from a single institution, used nonstandardized tools, and assessed outcomes at the satisfaction or knowledge/attitude/skills levels. Few studies showed behavioral changes or patient-level outcomes., Conclusions: While a rich diversity of educational innovations have occurred since the 2009 revision of the ACGME Program Requirements in Internal Medicine, there is a significant need for multi-institution studies and higher-level assessment., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Purpose: To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug-associated adverse drug reactions (ADRs) reported in the postmarketing setting., Methods: ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed., Results: Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period., Conclusion: Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.