Quinn E. Whiting-O'Keefe

Methotrexate and histologic hepatic abnormalities: A meta-analysis

STUDY OBJECTIVE To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS A total of 636 patients from 15 studies. RESULTS The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity.

Fatal Infections in Systemic Lupus Erythematosus: The Role of Opportunistic Organisms

The causes of death were examined in patients with systemic lupus erythematosus (SLE) who were cared for at the University of California, San Francisco and who died after 1969. Of the 44 deaths analyzed, 33 patients had autopsies. Infections were common and often determined to be the cause of death. Overall, infections were present in 55 percent (22/44), and judged to be a cause of death in 30 percent (13/44) of all deaths. The infections could be divided into 2 groups: those due to common bacterial organisms and those due to opportunistic infections. These two types of infections occurred with similar frequency. When compared to common bacterial infections, however, the opportunistic infections were more likely to be first diagnosed at autopsy (p = .001). In only 3 of the 15 patients with an opportunistic infection was the diagnosis made antemortem. Failure to diagnose an opportunistic infection early occurred when the infection simulated active SLE, and when the possibility of an opportunistic infection was not aggressively investigated. The most common opportunistic infections were Candida albicans and Pneumocystis carinii. The most common site of opportunistic infection was the lung. Seventeen patients had 27 common bacterial infections, chiefly sepsis from Staphylococcus aureus and aerobic gram-negative organisms. Eight patients had both a common bacterial and an opportunistic infection. Stepwise linear regression analysis showed that death from infection correlated most strongly with prednisone and cytotoxic drug use in the 3 months before final admission. No measure of lupus activity was found to correlate with death from infection, except that hypocomplementemia correlated with death from bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS)

The Frequency of Lupus Anticoagulant in Systemic Lupus Erythematosus: A Study of Sixty Consecutive Patients by Activated Partial Thromboplastin Time, Russell Viper Venom Time, and Anticardiolipin Antibody Level

Recent reviews have suggested a higher frequency of the lupus anticoagulant or related antiphospholipid antibodies in patients with systemic lupus erythematosus (21% to 65%) than was found in earlier studies (6% to 18%). In our study of 60 consecutive patients, we found the frequency of the lupus anticoagulant by Russell viper venom time was 6.7% (95% confidence interval, 16.2 to 1.8) and by anticardiolipin antibody assay was 25% (95% Cl, 37.0 to 15.7), compared with 0% (p = not significant) and 2.5% (p = 0.002), respectively, in the normal control population. The Russell viper venom time (p = 0.0001 by t-test) and anticardiolipin antibody levels (p = 0.01) were significantly associated with presumed thrombotic events (stroke, deep venous thrombosis, and digital gangrene). No association with miscarriage or pulmonary hypertension was detected. The Russell viper venom time was more specific than the anticardiolipin antibody level in the prediction of past presumed thrombotic events, miscarriage, or pulmonary hypertension (100% compared with 84%, p = 0.01).

Mononeuritis multiplex: The yield of evaluations for occult rheumatic diseases

We identified 35 patients who had electrodiagnostic evidence of mononeuritis multiplex and did not have diabetes or multiple nerve compressions. Their charts were reviewed to determine the etiologies of the mononeuritis multiplex and to determine how often the laboratory examination revealed a rheumatic disease in patients whose initial history and physical examination did not suggest that a rheumatic disease was present. In 11/35 (31%; CI = 17-49) a disorder capable of causing mononeuritis multiplex was diagnosed before the symptoms of mononeuritis multiplex began. Ten had a rheumatic disease; 1 had lymphoma. Nine of the other patients were suspected, on the basis of the history and physical examination, of having new onset of a rheumatic disease. Subsequent laboratory evaluation showed that 5/9 (56%; CI = 21-86) had a rheumatic disease, and 4/9 (44%; CI = 14-79) were unknowns. In 15/35 (43%; CI = 26-61) patients with mononeuritis multiplex, no rheumatic disease was suspected on the basis of the initial history and physical examination. The subsequent laboratory examination revealed an underlying rheumatic disease in 0/15 (0%; CI = 0-18). Mean clinical follow-up of 16 +/- 16 months in the patients with mononeuritis multiplex of unknown cause also failed to identify a rheumatic disease. Overall 19/35 (54%; CI = 37-71) did not have a rheumatic disease or any other known cause. Of the 14 patients with mononeuritis multiplex associated with a rheumatic disease, 5/14 (36%; CI = 13-15) had systemic lupus erythematosus; an additional patient had both lupus and the CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

A Controlled Experiment to Evaluate the Use of a Time-Oriented Summary Medical Record

A randomized single-blind experiment was done in a medical subspecialty clinic in order to determine whether a flow-sheet type of summary medical record could validly serve as a means to communicate clinical information in the absence of the traditional medical record. Two groups of outpatient physician-patient encounters were compared: In the 68 study encounters (Group S), physicians were given a flow-sheet summary record with the option to receive the standard medical record if they desired; in the 27 control encounters (Group C), physicians were given the standard medical record plus the flow-sheet summary record. Fifty-nine per cent of study-group physicians did not choose to receive the full medical record. The study group was found not to differ (p = 0.013) from controls significantly with regard to the follow-up of clinical information as measured by pre- and post-encounter chart review. Physician providers in the study group were unable to detect by retrospective chart review overlooked clinical information with greater frequency than control group providers. We conclude that a flow-sheet type of summary medical record can serve as the sole source of clinical information in a substantial number of outpatient follow-up encounters in a medical subspecialty clinic without deterioration in the communication of clinical information.

Local area networks and the hospital

Hospital information systems are characterized by their complexity of individual functions, heterogeneity of functions, and dependence upon integration. A distributed computerized information system is well suited to meeting the needs of hospitals. A local area communications network (LACN) removes a major impediment to the use of distributed systems. An advanced microprocessor-based LACN using fiberoptic communications has been developed by the Applied Physics Laboratory of The Johns Hopkins University and has been implemented at the University of California, San Francisco Hospital.

Summary time oriented record (stor) -- a node in a local area network

The STOR ambulatory record system remains committed to its original principles of prioritization of information, time orientation, and inter-physician communication. It has been expanded to provide a sophisticated user help system, to provide extensive interactive access to its database to augment its hardcopy output, and to function as an interface to the UCSF distributed hospital information system. The complex and difficult application level issues of effectively using a distributed database accessed through a local area network are being dealt with. In a limited context, the major question of whether physicians would accept the change STOR imposes on the way they record and display clinical data has been answered.

An automated system for coding data from summary time oriented record (stor)

A system to automatically encode a portion of the patient specific data of an ambulatory record system has been developed and implemented. The first use of the system that passes the clinical data of 224 patients to the ARAMIS research databank is described. Issues concerning the capture and use of naturally occurring patient data for clinical research are discussed.