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Biomedical subjects

R H Shmerling

Publications and source records attributed to R H Shmerling.

13 recordsLinked to original sources

Antinuclear antibody testing. A study of clinical utility.

OBJECTIVE: To determine the clinical utility of the antinuclear antibody (ANA) test as ordered in a large teaching hospital. METHODS: Retrospective chart review in a 400-bed teaching hospital that provides care for hospital-based and community-based practices. PATIENTS: A consecutive sample of 1010 patients (including inpatients and outpatients) for whom ANA testing was ordered over 10 months; all patients with positive ANA test results and an equal number of randomly selected patients with negative test results were included. Clinical utility of the ANA in the identification of rheumatic disease was determined by its estimated sensitivity, specificity, and positive and negative predictive values. RESULTS: Of 1010 ANA test results reviewed, 153 were positive. The group with positive ANA test results included more patients aged 65 years or older than the group with negative ANA test results (30% vs 15%, P < .003). The diagnosis of systemic lupus erythematosus (SLE) was established in 17 patients, all of whom had positive ANA test results. Other rheumatic diseases were found in an additional 22 patients. The estimated sensitivity and specificity of the ANA test for SLE were 100% and 86%, respectively. For other rheumatic diseases, sensitivity and specificity were 42% and 85%, respectively. The positive predictive value of the ANA test was 11% for SLE and 11% for other rheumatic diseases. Specificity and positive predictive value for ANA testing in the elderly patients were lower than among younger patients. CONCLUSIONS: The sensitivity of the ANA test for SLE was high, but overall the positive predictive value was low for SLE or other rheumatic diseases. Sensitivity was low for ANA testing among patients with non-SLE rheumatic disease. More selective test ordering might improve the clinical utility of this test. Clinicians ordering the ANA test should be aware of the test's low-positive predictive value in settings with a low prevalence of rheumatic disease, particularly among older patients.

Aged

Rheumatic disease: choosing the most useful diagnostic tests.

Many tests are available for evaluating older patients with suspected rheumatic disease. Factors that help you determine which tests would be most helpful are the individual history and physical exam plus your knowledge of how likely a particular disease is in that population. The clinical utility of common tests such as the ESR, rheumatoid factor, and antinuclear antibody is quite limited. Other autoantibodies may be useful in well-defined contexts. Radiographic evaluation is useful when particular problems are suspected but is rarely helpful as a diagnostic test in older patients with recent onset of symptoms and no history of trauma. In select situations, other specific diagnostic testing (eg, for bony pain, neuropathies, and vasculitides) is indicated.

Aged

Interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid arthritis. A double-blind, placebo-controlled trial with open-label extension.

OBJECTIVE: This pilot phase II, double-blind, placebo-controlled trial of 1 month duration, with a 2-3-month open-label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid arthritis (RA). METHODS: Forty-five RA patients were enrolled in the trial, and were randomized, after a 3-4-week disease-modifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB486IL-2 or placebo (saline) for 5 days. A blinded, third-party observer evaluated arthritis activity. Clinical response was defined as > or = 25% improvement in swollen and tender joints and > or = 25% improvement in at least 2 of 6 additional parameters. The double-blind phase was 4 weeks; placebo patients could cross over to receive open-label treatment for a maximum of 3 monthly DAB486IL-2 cycles. RESULTS: In the double-blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open-label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB486IL-2, respectively. Adverse events included transient fever/chills (45%), nausea/vomiting (50%), elevated (< or = 3 x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB486IL-2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL-2-treated versus placebo-treated patients. CONCLUSION: Clinical responses were noted in patients treated with DAB486IL-2 (18%) compared with placebo (0%) in the double-blind phase. In the open-label phase, 33% of patients completing 3 monthly DAB486IL-2 cycles had improvement in arthritis activity. Further studies of IL-2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action.

Adolescent

Synovial fluid analysis. A critical reappraisal.

Analysis of synovial fluid (SF) is among the most useful means of evaluating patients with joint complaints. The best reasons to aspirate a joint include suspicion of infection or crystal-induced arthritis, and generally, the risks of the procedure are acceptably low. While there is no consensus regarding which tests should be considered routine for all SF obtained, data support the performance of a SF white blood cell count with differential, gram stain and culture, and examination for crystals by polarizing microscopy. The separation of SF into groups (noninflammatory, inflammatory, or purulent) should not be relied upon diagnostically. Care must be taken in obtaining and handling joint fluid, and caution applied to interpretation of test results, because over-reliance on any individual test may promote misdiagnosis.

Arthritis

Case report 705. Osteosclerotic sarcoidosis.

In summary, Sarcoidosis is a rare but well-recognized cause of diffuse osteosclerosis. The differential diagnosis of osteosclerosis is limited and includes osteoblastic metastases, sclerotic myeloma, myelofibrosis, and less common infiltrative bone marrow processes such as mastocytosis and sarcoidosis. In all of these entities the sclerosis is found most often in the axial (red marrow) skeleton. In this regard, it is interesting that cases of osseous sarcoid are usually lytic and located in the peripheral skeleton. In patients with osteosclerotic sarcoidosis, the diagnosis may be suggested by a past history of the disease or ancillary signs such as hilar node enlargement and subtle skin involvement. However, the specific diagnosis usually requires bone marrow biopsy with the demonstration of extensive, noncaseating granulomas.

Bone Diseases

How useful is the rheumatoid factor? An analysis of sensitivity, specificity, and predictive value.

BACKGROUND: The rheumatoid factor (RF) is frequently ordered in an effort to detect disease, yet its diagnostic utility has not been thoroughly examined. To determine the test's sensitivity, specificity, positive predictive value, and negative predictive value, we analyzed tests ordered in our institution. METHODS: We performed a retrospective analysis of all 86 patients with a positive RF over a 6-month period identified consecutively soon after the test was ordered. A similar analysis was applied to 86 seronegative patients selected at random from a total seronegative population of 477 during the same period. The patients represented the primary care and subspecialty practices and inpatient wards of a 504-bed university teaching hospital. RESULTS: A positive RF result was strongly associated with rheumatoid arthritis or another rheumatic disease. For rheumatoid arthritis, sensitivity = 0.28 and specificity = 0.87, while for any rheumatic disease, sensitivity = 0.29 and specificity = 0.88. The positive predictive values for rheumatoid arthritis and any rheumatic disease were 0.24 and 0.34, respectively, and the negative predictive values were 0.89 and 0.85, respectively. Seropositive patients were slightly older (55 vs 49 years old), but the incidence of false-positive RFs among the elderly (69%) was not significantly higher than among younger patients (65%). The cost per true-positive RF result was $563. CONCLUSIONS: In this study, most positive RF results were not helpful since the majority represented false-positive results. The low positive predictive value of the RF casts doubt on the utility of the RF in the diagnostic evaluation of patients. Contrary to traditional clinical expectations, the diagnostic utility of the RF may be greatest when it is negative. However, the subset of patients with seronegative rheumatic disease reduces the test's power to exclude such disorders even when the RF is negative. Given the test's limitations, clinicians should reconsider their expectations when ordering an RF. The utility of the RF may improve if it is ordered more selectively.

Aged

The rheumatoid factor: an analysis of clinical utility.

The rheumatoid factor (RF) is a frequently ordered diagnostic test, yet it possesses significant limitations in sensitivity, specificity, and predictive value. Recognition of these limitations could improve the test's utility by encouraging more selective test ordering and more circumspect interpretation of test results. An analysis of 563 requests for RF from a teaching hospital revealed a positive predictive value of only 24% to 34%. The RF performs best under conditions of moderate pretest likelihood of rheumatoid arthritis, and otherwise has rather limited clinical utility.

Biomarkers

Measurement of joint inflammation in rheumatoid arthritis with indium-111 chloride.

Studies in the collagen and rabbit models of arthritis have indicated that indium-111 chloride (111InCl3) scintigraphy objectively measures synovial inflammation. Indium-111 chloride scans, with imaging three days after 19 MBq intravenous injection, were performed on 21 patients with definite or classical rheumatoid arthritis (RA), all of whom were functional class II. Standard clinical indices of disease activity were recorded at the time of imaging by the same investigator, who was unaware of the results of joint scans. In addition, eight patients with severe osteoarthritis, four of whom were considered to need hip or knee joint replacement, were similarly scanned. In each patient 16 joints were graded as 0 to 5, based on increasing degrees of 111InCl3 uptake, by a single investigator blinded to the patient's diagnosis and clinical status. In the group with RA significant correlations were observed between individual joint uptake on scan and peripheral joints with swelling, joints reported to be painful, and joints with any abnormality on physical examination. In the group with osteoarthritis joints positive on scan correlated with the presence of pain. A total scan score (sum of individual joint scores) was calculated for each patient. In the patients with RA values ranged from 0 to 42 with a mean (SEM) of 20.7 (2.7) and correlated with the number of swollen joints and decreasing grip strength. In the group with osteoarthritis the mean total scan score (9.2 (1.5), range 3-14) was significantly lower than in the patients with RA. These data show that 111InCl3 scanning can measure joint involvement by RA.

Adult

Finger pain.

The local, systemic, and referred causes of finger pain are generally recognizable by historical features and physical examination findings, although radiographs and laboratory evaluation are often required to support the diagnostic impression. Most minor traumatic causes of finger pain require only conservative management, including immobilization followed by exercise. Infectious causes of finger pain include cellulitis, tendinitis, paronychia, felon, and infectious emboli, which generally require antibiotics with or without drainage. Certain patients with finger pain resulting from infection should be referred to a hand surgeon. Vascular and ischemic causes of finger pain represent true emergencies, because tissue viability is dependent on prompt intervention. Whereas any sensory neuropathy may present with finger pain, carpal tunnel syndrome is among the most common. Systemic rheumatic disease, such as rheumatoid arthritis or vasculitis, may begin with finger pain. In addition, such pain may be the first manifestation of a serious systemic illness, as in hypertrophic pulmonary osteoarthropathy. Reflex sympathetic dystrophy is an example of referred pain, presumably by way of neural mechanisms. Certain infectious, traumatic, and ischemic causes of finger pain must be diagnosed promptly to avoid significant morbidity; depending upon the cause of the symptoms, referral to a hand surgeon, rheumatologist, or neurologist may be appropriate. Symptomatic and functional improvement may also be hastened by the input of an occupational therapist.

Diagnosis, Differential

Tophaceous deposition in the finger pads without gouty arthritis.

Tophi are rarely observed in patients without a prior history of gouty arthritis. We describe four patients whose initial manifestation of gout was tophaceous deposition in an unusual location, the finger pad. None of these patients had a history of acute gouty arthritis and none had tophi elsewhere. All four patients were postmenopausal women with decreased renal function; all were taking diuretics. We conclude that tophaceous gout without arthritis may be more common than previously recognized and that tophi may deposit in the finger pad. We recommend prompt aspiration and crystal analysis of white subcutaneous finger pad deposits in hyperuricemic patients even without a history of gouty arthritis.

Aged

Discussing cardiopulmonary resuscitation: a study of elderly outpatients.

Decisions about when to perform cardiopulmonary resuscitation (CPR) are frequently made without knowing the wishes of the patient. To evaluate the feasibility of outpatient discussions about CPR, the authors surveyed 22 male and 53 female, mentally competent, ambulatory patients 65 years of age and older. Only 7% of those interviewed had an accurate understanding of what CPR meant before hearing a standardized description. Eighty-seven per cent thought discussions about CPR should take place routinely, but only 3% had previously discussed this issue with their physicians. Seventy per cent felt such discussions should take place during periods of health, and 84% felt their views should be part of the medical record. When asked about three terminal illnesses, a minority of patients wanted CPR: 25% felt CPR was indicated in the presence of irreversible coma, 28% for terminal cancer, and 41% for irreversible heart failure. More patients felt they would request CPR if they had irreversible heart failure than if in a coma (p less than 0.002) or for terminal cancer (p = 0.002). The majority of elderly outpatients have clearly defined opinions about the application of CPR and wish to discuss them with their physicians.

Aged

Synovial fluid tests. What should be ordered?

To determine which synovial fluid tests are most useful, we prospectively analyzed the synovial fluid test results of 100 consecutive patients undergoing diagnostic arthrocentesis. Each patient's diagnosis was established independently of synovial fluid laboratory test results; in 69 patients a definite inflammatory or noninflammatory categorization could be made. Sensitivity and specificity were estimated for synovial fluid white blood cell count (sensitivity, 0.84; specificity, 0.84), percentage of polymorphonuclear cells (sensitivity, 0.75; specificity, 0.92), glucose (sensitivity, 0.20; specificity, 0.84), protein (sensitivity, 0.52; specificity, 0.56), and lactate dehydrogenase (sensitivity, 0.83; specificity 0.71). Receiver operating characteristic regression analysis indicated that both white blood cell count and percentage of polymorphonuclear cells were found to contribute independent diagnostic information but lactate dehydrogenase did not. In a separate, retrospective analysis of 19 patients with definite septic arthritis, similar results were observed. We conclude that synovial fluid white blood cell count and percentage of polymorphonuclear cells perform well as discriminators between inflammatory and noninflammatory disease. Ordering chemistry studies of synovial fluid should be discouraged because they are likely to provide misleading or redundant information.

Arthritis, Infectious