Implementation of a hospitalist system in a large health maintenance organization: the Kaiser Permanente experience.

This paper presents preliminary quality and utilization data from a hospitalist system that is being implemented at Kaiser Permanente, a large health maintenance organization with 16 hospitals in northern California. Hospitalist programs, which are staffed by clinicians highly skilled in caring for inpatients, are being launched with the aim of delivering high-quality, efficient medical care in an increasingly competitive health care delivery environment. This paper also describes, in some detail, the process of implementation at one hospital. Challenges to implementation included 1) overcoming the reluctance of clinic physicians to relinquish inpatient care responsibilities, 2) developing sustainable work schedules, 3) creating effective channels of communication between staff in inpatient and outpatient settings, and 4) designing appropriate compensation scales for hospitalists. Mean length of stay, patient-day rates, admission rates, consultation request rates, costs, and readmission rates were examined for patients discharged from adult medicine services at all 16 hospitals between 1 January 1994 and 30 June 1997. These preliminary resource utilization data seem promising, but further analysis is needed to assess how hospitalist programs may affect clinical quality of care, costs, and patient and provider satisfaction.

Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study.

The value of a short course of intensive immunosuppression with cyclophosphamide in stabilising chronic progressive multiple sclerosis (MS) was examined in a randomised single-blinded, placebo-controlled clinical trial. Forty two patients, from the Kaiser Permanente Medical Care Program, Northern California, were studied. Twenty two patients received a short course of cyclophosphamide in an outpatient neurology clinic until their leucocyte counts fell below 4000/mm3, and 20 patients received folic acid. Level of disability, impairment of functional systems, and performance of social roles were assessed before randomisation and reassessed 12, 18, and 24 months after therapy. In both the cyclophosphamide and folic acid groups, the mean level of disability increased from the baseline examination to the 12 month follow up examination (the primary endpoint) by 0.5 on Kurtzke's Expanded Disability Status Scale, indicating similar disease progression in the two groups. Although immunosuppression therapy can be safely administered to MS patients in an outpatient clinic, evidence of substantial benefits was not found.

Experience with cyclophosphamide in multiple sclerosis: the cons.

Neurologists in the Kaiser-Permanente Medical Care Program recently designed a study to evaluate the utility of intensive immunosuppression with cyclophosphamide compared with folic acid in 44 patients with chronic progressive multiple sclerosis (MS). Although preliminary results based on incomplete data suggest cyclophosphamide may be safely administered in an outpatient clinic setting and modest benefits cannot be ruled out, it is doubtful that there are very substantial benefits to that therapy. Although several other studies have been cited as evidence of cyclophosphamide's favorable effect on the clinical course of patients with MS, many of these studies have had design shortcomings. If these flaws are considered, the hypothesis that cyclophosphamide has a favorable effect on the course of MS must be considered weak.

Comprehensive viral immunology of multiple sclerosis. II. Analysis of serum and CSF antibodies by standard serologic methods.

Sera and CSFs of 85 patients with multiple sclerosis (MS), 49 patients with probable MS, and 165 control patients with other neurologic diseases were assayed for antibodies to rubella, mumps, measles, parainfluenza I (strain 6/94), herpes simplex, cytomegalovirus, varicella-zoster, and vaccinia viruses. Methods included complement fixation (CF), hemagglutination inhibition (HI), and complement-dependent plaque reduction (CPR). Significant differences between the groups with MS and the control groups were higher serum antibody titers to measles virus in the groups with MS, higher proportion of patients with MS with CSF antibodies to measles, rubella, and vaccinia viruses, and greater percentage of patients with MS with more than one CSF viral antibody. Duration and severity of disease in the patients with MS were associated with presence of multiple CSF antibodies. Presence of CSF antibody was positively correlated with the height of the correspnding serum titer, yet a high serum titer did not ensure the presence of CSF antibody. Oligoclonal bands were present in the CSFs of equal proportions of patients with MS with and without CSF viral antibody. Our data support the hypothesis of local antibody synthesis within the CNS. However, we favor the view that preprogrammed antibody-forming lymphocytes enter the CNS and then produce antibody either because of nonspecific polyclonal activation in situ or because of failure of normal regulation.

Comprehensive viral immunology of multiple sclerosis. III. Analysis of CSF antibodies by radioimmunoassay.

The CSF from 279 patients with multiple sclerosis (MS), probable MS, or controls was examined by radioimmunoassay (RIA) for antibodies to measles, rubella, mumps, parainfluenza 1 (Sendai) (strain 6/94), herpes simplex (HSV), varicella, and vaccinia viruses. Significantly more patients with MS than noninflammatory control patients had antibody to measles, rubella and varicella viruses, of which antibody to measles was the most prevalent. The percentage of patients with MS with two or more CSF antibodies was significantly greater than that in the controls. There was no tendency for certain antibodies to be associated. There was a general relationship between presence of CSF antibodies and severity of MS. The data support the hypothesis of local CNS antibody synthesis of several viral antibodies; however, such local synthesis may be a random event, possibly dependent on the number and specificity of peripheral virus antibody-forming lymphocytes available for ingress into the CNS.

Comprehensive viral immunology of multiple sclerosis. I. Clinical, epidemiological, and CSF studies.

Epidemiological, clinical, and CSF data were collected on 87 patients with clinically definite multiple sclerosis (MS) and 50 with probable MS. As part of a study of immunologic reactivity to viral antigens, a control group separated into 26 patients with probable inflammatory neural disease and 140 with noninflammatory neural disease was similarly studied. Among the groups with MS, females predominated and both Oriental and Spanish surnamed patients were under-represented. The spinal cord, optic nerves, and brainstem were the most common sites of initial disease and more than 20% of the patients had only cord symptoms after several years of disease activity. Of several CSF assays used, determination of oligoclonal IgG bands by agarose electrophoresis was most useful diagnostically.

Cytotoxic antibody to cells infected with measles virus in serum and cerebrospinal fluid of multiple sclerosis and control patients.

Sera and cerebrospinal fluids (CSFs) from 66 patients selected from a larger sample of multiple sclerosis (MS) and control patients were studied for presence of complement-dependent cytotoxic (CT) antibody against baby hamster kidney cells infected with measles virus, strain Lec. The MS group contained 26 patients with clinically definite disease and 7 with probable MS. Seventeen of the 33 patients selected from the MS group had hemagglutination-inhibiting (HI) antibody to measles virus in their CSFs. Specimens from 33 control patients with other identifiable neurological disorders were matched according to the time of specimen sampling and with the age of the donors. Seven of the controls had HI CSF antibody. The serum CT geometric mean antibody titer of the MS group was approximately twofold higher than that of the control group. Forty-two percent of the MS group and 18% of the control group had CT antibody in the CSF. With the exception of the ratio of one control patient, the serum/CSF ratios of CT antibody from all patients were 128 or less. Nine CSFs (six MS and three control specimens) had CT antibody but no detectable HI antibody. Conversely, 12 CSFs (eight MS and four control specimens) had HI antibody but no detectable CT antibody. Five patients in the MS group with both kinds of CSF antibodies had reduced CT ratios but normal HI ratios. The results suggest that the two tests detect CSF antibodies reactive with different antigens. In this study, where less than half of the MS patients displayed CSF CT antibody, it is unlikely that such antibodies play an active role in the pathogenetic mechanism operative in the disease.

Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques.

Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid.

Organic mercury identified as the cause of poisoning in humans and hogs.

Atomic absorption spectrophotometry and neutron activation analysis showed the presence of mercury in organic extracts of seed grain and in tissues of hogs fed the contaminated grain. Mercury was also found in the urine, serum, and cerebrospinal fluid of humans who ate the contaminated pork. Mass spectral analysis confirmed the presence of organic mercury. This paper reports the first documented episode of indirect mercury poisoning in humans in the United States caused by the ingestion of contaminated meat from animals that had consumed mercury in their food supply.