JAAD ONLINE RESEARCH Assessing the evidence: Clinical research trends in dermatology over a 10-year period To the Editor: The availability of high-quality evidence impacts clinical practice, making it useful to evaluate trends in research methodology to assess clinician access to information that influences patient care. Our objective was to investigate how research methods reported in two American dermatology journals have changed over a 10-year period. A simple random sample was generated from all research articles published between 1998 and 2007 in Archives of Dermatology and Journal of the American Academy of Dermatology using statistical software (SPSS 17.0). The sample size (701) was chosen to produce estimates within 5% of the population percentage with 95% probability. From this sample, 598 articles presented original research. Each article was examined and coded into one of 5 categories: randomized controlled trials (RCTs) and meta-analyses, uncontrolled or nonrandomized trials, observational studies, case reports and case series, and review articles. Articles presenting non-clinical research were categorized separately. Presented in Fig 1, a decreasing trend was observed for both RCTs and meta-analyses ( 11.3%) and uncontrolled or nonrandomized trials ( 9.7%). LETTERS For both categories, the linear trend line ( produced using least squares method) was negative with a slope of 273 (P ¼ .648) and 1.290 (P ¼ .05), respectively. A concurrent increase in case reports and case series (112.9%) with a positive linear trend line (slope .974, P ¼.007) was demonstrated. Findings suggest the evidence available to inform clinical decision-making is increasingly based on less rigorous research designs. Utilization of rigorous methodologies is at best stagnant (in the case of RCTs) and, at worst, declining (in uncontrolled or non-randomized trials) while these methods constitute a small fraction of research publications. Several factors may contribute to these findings, including funding and time constraints which limit the design of research protocols, requirements for publication among researchers which incentivize rapid publication, thereby lessening the likelihood of using stronger methodology, and the declining number of dermatology residents entering academia.1 The smaller proportion of articles citing rigorous methodology may also reflect to some degree the clinical utility of such studies to dermatologic practice. For example, the rarity of many diseases may prohibit the undertaking of large-scale studies, and case reports may provide invaluable information Fig 1. Publication rate of case report or case series, noncontrolled or nonrandomized trials, and randomized controlled trials or meta-analyses. J AM ACAD DERMATOL FEBRUARY 2011 e15 e16 Letters J AM ACAD DERMATOL FEBRUARY 2011 regarding novel treatments and adverse events, thereby contributing substantially to education.2 While this study suggests a decreasing trend in rigorous research designs, its limitations should be acknowledged. Use of a single coder limited checks on coding reliability and, while two widely read clinical journals were included in this study, further exploration of the quality of evidence in additional journals is warranted. We found the results of this analysis to be of interest to clinicians and the academic community and hope these data will encourage and facilitate dialogue and research within the field of dermatology. Further research investigating trends in study design are likely to be useful in assessing the state of dermatology in the context of increasing recognition of evidence-based practice. Rachel Farley-Loftus, MD,a Elizabeth Nash FarleyRipple, PhD,b and Roopal V. Kundu, MDc,d Department of Dermatology, New York University Langone Medical Center,a New York City; School of Education, University of Delaware, Newark, CASE Nicolau syndrome following subcutaneous glatiramer-acetate injection To the Editor: A 39-year-old woman with a 2-year history of multiple sclerosis presented with a palmsized, indurated, erythematous plaque with a purpuric center and bizarrely configured extensions on the left lower abdomen (Fig 1). In addition, the patient experienced a local sensation of heat and intense pressure pain. However, no general symptoms were reported. Pain occurred immediately after the patient had injected glatiramer acetate, a drug used in the treatment of multiple sclerosis, subcutaneously in the lower left abdomen 2 days before presentation. This therapy was given once daily and had been well tolerated since its beginning 2 years previously. Histopathologic examination showed thrombotic occlusion of vessels in the dermis and subcutis with rare signs of inflammation. On the basis of the typical clinical and histopathological picture, the diagnosis of Nicolau syndrome (NS) was made. Although glatiramer acetate may also induce skin necrosis as a side effect, NS can be easily distinguished by its typical clinical features. Continuation of treatment with glatiramer acetate at other injection sites Delawareb; Department of Dermatology, New York University Langone Medical Center,c and Northwestern University Feinberg School of Medicine,d Chicago, Illinois Funding sources: None. Conflicts of interest: None declared. Correspondence to: Rachel Farley-Loftus, MD, Natow, Rosenberg, and Pion, MD, PC, 949 Central Ave, Woodmere, NY 11598 E-mail: farleyrl@gmail.com REFERENCES 1. Wu JJ, Ramirez CC, Alonso CA, Mendoza N, Berman B, Tyring SK. Dermatology residency program characteristics that correlate with graduates selecting an academic dermatology career. Arch Dermatol 2006;142:845-50. 2. Albrecht J, Werth VP, Bigby M. The role of case reports in evidence-based practice, with suggestions for improving their reporting. J Am Acad Dermatol 2009;60:412-8. doi:10.1016/j.jaad.2010.10.004 LETTERS was recommended and further injections were tolerated without any complications. The recovery of the patient was uneventful, and the lesion healed within 10 weeks without any residual effects. NS, also known as embolia cutis medicamentosa, is a rare but serious adverse reaction, which in most cases occurs after intramuscular injection of various drugs. However, it has also been rarely observed after subcutaneous injection. NS was first described by Nicolau1 and Freudenthal2 after intramuscular injections of bismuth suspensions used for the treatment of syphilis. NS is characterized by sudden intense pain, followed by swelling and erythema at the injection site, leading to cutaneous, subcutaneous, or even muscular necrosis. The pathogenesis of NS has not been totally determined. Unintentional intra-arterial or perinervous injections, causing an acute vasospasm of the vessel, or periarterial injection with direct trauma and/or inflammation of vessel structures followed by thrombosis and necrosis are considered to be the underlying pathogenic mechanisms. It is noteworthy that in a relevant proportion of intramuscular injections the drug is not administered properly.3 However, in NS