Progress toward personalized treatment of rheumatoid arthritis.

Treatment of rheumatoid arthritis (RA) has advanced significantly over the past decade, in part because of the identification of key elements in the immunopathogenesis of the disease, leading to the development of targeted immune-based therapies. Despite the availability of many highly specific therapies, the process of selecting a treatment regimen for an individual patient remains empirical. Personalized treatment, focused on predicting efficacy, non-response, and toxicity to better guide medication selection, moves closer to realization as genomic methods continue to be extended and refined.

Broadening our understanding of clinical quality: from attribution error to situated cognition.

The tendency to overestimate the influence of personal characteristics on outcomes, and to underestimate the influence of situational factors, is known as the fundamental attribution error. We argue that medical-education researchers and policy makers may be guilty of this error in their quest to understand clinical quality. We suggest that to truly understand clinical quality, they must examine situational factors, which often have a strong influence on the quality of clinical encounters.

Improving the use of allopurinol in chronic gout: monitoring oxypurinol levels to guide therapy.

Urate-lowering therapy (ULT), adjusted to achieve and maintain a serum uric acid (SUA) of <6 mg/dl, remains the standard of care for the chronic management of gout. New urate-lowering medications are important options; however, these agents should be reserved for patients who do not tolerate or cannot achieve SUA <6 mg/dl on allopurinol. The result of oxypurinol monitoring to guide allopurinol therapy suggests that allopurinol should still be considered first-line ULT for gout.

A curricular divide: basic pharmacology vs. clinical pharmacology.

Two current surveys of graduating medical students and/or recently graduated physicians from the United Kingdom raise significant concerns about the quality and quantity of clinical pharmacology instruction. Compared with the relative abundance of information about the instruction of basic pharmacology in US medical schools, little information exists about similar curricular content of clinical pharmacology. Here, we highlight this lack of information and encourage clinical pharmacology educators to address this curricular divide.

Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis.

OBJECTIVES: To investigate factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the preclinical phase of rheumatoid arthritis (RA) development. METHODS: 243 serial prediagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies. RESULTS: Of the 83 cases, 47 (57%) and 51 (61%) subjects had at least one prediagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of preclinical antibody appearance. Preclinical anti-CCP positivity was strongly associated with the development of erosive RA (odds ratio = 4.64; 95% confidence interval 1.71 to 12.63; p<0.01), but RF was not (p = 0.60). Additionally, as age at the time of diagnosis of RA increased the duration of prediagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of preclinical antibody positivity seen in patients diagnosed with RA over the age of 40. In no subjects did symptom onset precede the appearance of RF or anti-CCP antibodies. CONCLUSIONS: The period of time that RF and anti-CCP are present before diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposure influencing the temporal relationship between the development of RA-related autoantibodies and clinically apparent disease onset may differ with age.

Emerging biological therapies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations such as glomerulonephritis or thrombosis. Virtually every organ system is subject to potential damage. Symptoms typically wax and wane over the course of the disease; yet unfortunately, many patients will experience a slow decline in their health because of the ongoing systemic inflammation. Effective treatment must be individualized and is often based on the specific manifestations that are seen in each patient. In a similar manner, prognosis is also dependent on the severity and the specific organ systems involved.

Non-local concepts and models in biology.

In this paper, we consider local and non-local spatially explicit mathematical models for biological phenomena. We show that, when rate differences between fast and slow local dynamics are great enough, non-local models are adequate simplifications of local models. Non-local models thus avoid describing fast processes in mechanistic detail, instead describing the effects of fast processes on slower ones. As a consequence, non-local models are helpful to biologists because they describe biological systems on scales that are convenient to observation, data collection, and insight. We illustrate these arguments by comparing local and non-local models for the aggregation of hypothetical organisms, and we support theoretical ideas with concrete examples from cell biology and animal behavior.

Osseous disease in patients with pulmonary sarcoidosis and musculoskeletal symptoms.

Little is known about the clinical manifestations and correlates of osseous sarcoidosis and few data exist to guide pulmonologists in their evaluation of patients for possible osseous involvement. To determine the relationship between pulmonary and osseous sarcoidosis, and to develop an algorithm for use by pulmonologists in assessing patients with suspected osseous sarcoidosis, we conducted a retrospective, case control study of patients with pulmonary sarcoidosis and musculoskeletal complaints who were evaluated for osseous disease. All patients underwent a standard evaluation to include physical examination, chest radiograph (CXR), spirometry (PFTs), bone scintigraphy and plain radiographs of the hands and feet. Patients completed a health assessment questionnaire and serum angiotenisin converting enzyme, erythrocyte sedimentation rate, and C-reactive protein were measured. Patients eventually diagnosed with osseous sarcoidosis were compared to those lacking osseous involvement. Osseous involvement in patients with pulmonary sarcoidosis and musculoskeletal symptoms was common and seen in 38.9% of subjects. Patients with osseous sarcoidosis were more likely to concomitantly suffer from cutaneous sarcoidosis and to have elevated ACE levels and ESRs. No measure of pulmonary involvement (CXR stage, PFTs or symptoms) differentiated patients with osseous sarcoidosis from those without this condition. In cases of osseous sarcoidosis, bone scintigraphy identified a mean of four sites of osseous involvement, some of which would have been missed with the use of plain radiographs limited to the hands and feet. We conclude that in patients with pulmonary sarcoidosis who have significant musculoskeletal complaints, osseous involvement is frequent. Pulmonary features of sarcoidosis do not differ between patients with and without osseous disease. Bone scintigraphy aids in the evaluation of these patients.

Ovarian cancer presenting as leukocytoclastic vasculitis.

We describe a 53-year-old woman with a 4-month history of palpable purpuric papules on the upper and lower extremities. Biopsy of the skin lesions revealed leukocytoclastic vasculitis. Although she denied any systemic symptoms, urinalysis demonstrated hematuria and proteinuria. Although the patient's skin lesions responded to prednisone, her urinalysis did not improve. A 10-cm complex mass involving the left ovary and adnexa was incidentally discovered on renal ultrasound. Serum CA-125, an ovarian cancer marker, was elevated. Laparotomy revealed ovarian carcinoma confined to the left ovary. After the cancer was resected, the patient's urinalysis slowly improved. Leukocytoclastic vasculitis (LCV) is infrequently associated with underlying malignancy and only rarely with solid tumors. We postulate that the patient's vasculitis represented a paraneoplastic phenomenon that allowed a diagnosis of asymptomatic ovarian carcinoma. To our knowledge, this is the first report of LCV occurring as the presenting sign of ovarian cancer.