To determine the diagnostic accuracy and usefulness of sentinel lymph node biopsy (SLNB) and computed tomographic scans in the initial evaluation and treatment of patients with Merkel cell carcinoma (MCC).Design: Single-institution case series and literaturebased case-level meta-analysis.Setting: Academic cutaneous oncology clinic.Patients: Sixty-one adults with biopsy-proven MCC (30 who had undergone SLNB) plus 92 cases from the literature of patients who had undergone SLNB.Main Outcome Measures: Relapse-free survival. Results:In 122 patients with no nodal disease found by physical examination, SLNB findings revealed nodal involvement in 39 cases (32%). At 3 years, the recurrence rate for those with a positive SLNB was 3 times (60%) higher than for those with a negative SLNB (20%; P =.03). Patients with a positive SLNB who received adjuvant nodal therapy had a relapse-free survival rate of 51% at 3 years (n=26) compared with 0% for patients who did not re-

No abstract

Abstract. Objectives:To determine the frequency of potentially inappropriate medication selection for older persons presenting to the ED, the most common problematic drugs, risk factors for suboptimal medication selection, and whether use of these medications is associated with worse outcomes. Methods: The authors performed a prospective cohort study of 898 patients 65 years or older who presented to an urban academic ED in 1995 and 1996. Seventy-nine percent of the patients were African-American and 43% did not graduate from high school. Potentially inappropriate medications and adverse drug-disease interactions were identified using the 1997 Beers explicit criteria for elders. During the three months after the initial visit, revisits to the ED or hospital, death, and changes in health-related quality of life were analyzed as measured by validated questions adapted from the Medical Outcomes Study. Results: Upon presentation, 10.6% of the patients were taking a potentially inappropriate medication, 3.6% were given one in the ED, and 5.6% were prescribed one upon discharge from the ED. The most frequently prescribed potentially inappropriate medications in the ED were diphenhydramine, indomethacin, meperidine, and cyclobenzaprine. Emergency physicians added potentially inappropriate medications most often to patients with discharge diagnoses of musculoskeletal disorder, back pain, gout, and allergy or urticaria. Potentially adverse drug-disease interactions were relatively uncommon at presentation (5.2%), in the ED (0.6%), and on discharge from the ED (1.2%). Potentially inappropriate medications and adverse drug-disease interactions prescribed in the ED were not associated with higher rates of revisit to the ED, hospitalization, or death, but were correlated with worse physical function and pain. However, confidence intervals were wide for analyses of revisits and death. Conclusions: Suboptimal medication selection was fairly common and was associated with worse patient-reported health-related quality of life. Key words: emergency services; aging; drugs; pharmacology; outcomes; quality of care. ACADEMIC EMER-GENCY MEDICINE 1999; 6:1232-1242 A DVERSE drug reactions are common and expensive. For example, a recent meta-analysis estimated that 6.7% of hospitalized patients have serious adverse drug reactions.1 In the outpatient setting, rates of adverse drug reactions have ranged from 1.7% to 50.6%.2 Costs associated with adverse drug events in a typical tertiary care hospital have been approximated to be $1.1-5.6 million per year, 3,4 and drug-related morbidity and mortality have been estimated to cost $76.6 billion annually in the ambulatory setting.5 Therefore, clinicians, administrators, and policymakers have become interested in what system factors contribute to adverse drug reactions and how provider practices around medication prescribing can be improved. 6,7 Several factors place older persons at especially high risk for iatrogenic complications of medication use. The normal aging process is associated with ...

Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations.