Deaths caused by venomous snakes in the State of S?o Paulo: evaluation of 43 cases from 1988 to 1993]

PURPOSE: To examine rheumatology subspecialty practice patterns, determinants of referral to rheumatologists, and utilization of aspiration and injection procedures in a population-based sample of elderly individuals. SUBJECTS AND METHODS: We obtained Medicare physician claims for all visits to rheumatologists among beneficiaries aged 65 years and older in Colorado, Massachusetts, and Virginia in 1993, and for visits to all providers by patients with coded diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We examined variations in visit frequency and aspiration/injection procedures, and we analyzed determinants of referral to a rheumatologist for RA or SLE. RESULTS: In 1 year, 144,797 visits were made to rheumatologists by 38,443 patients in the three states. An inflammatory disorder was coded in 45% of visits and a noninflammatory disorder in 50%. Half of patients with RA were seen three or fewer times in the year. For RA and SLE, African Americans were about 60% as likely to be seen by a rheumatologist as whites. Utilization of rheumatologist services for rheumatoid arthritis and systemic lupus erythematosus was highest in the state (Virginia) with the lowest per capita supply of rheumatologists. Among patients with bursitis, tendinitis, and osteoarthritis, African-American women were more likely to receive an injection or aspiration procedure than whites or African-American men. CONCLUSION: Elderly patients with rheumatologic disorders were seen by specialists less frequently than recommended by a recent rheumatology manpower survey. African-Americans with RA and SLE had fewer rheumatology visits than whites.     

Referral and diagnosis of common rheumatic diseases by primary care physicians

OBJECTIVE: To describe primary care patterns of referral and diagnoses of patients with rheumatic diseases referred to rheumatologists. METHODS: The medical records of all consecutive patients referred in 1994 by >300 primary care physicians to two rheumatologists at an academic centre were reviewed. The referring physician diagnosis was compared with the rheumatologist's diagnosis. Sensitivity, specificity and predictive values of primary care diagnoses were estimated using the rheumatologist diagnosis as the 'gold standard'. SETTING: University-based rheumatology out-patient clinic. RESULTS: Over half of the patients referred had a rheumatologist diagnosis of soft-tissue rheumatism or a spinal pain syndrome. Three hundred and forty-seven patients (49%) had a primary care diagnosis of a defined rheumatic disease. Of these, 142 (41%) of the primary care diagnoses were subsequently modified by the rheumatologist. The highest agreement between primary care physician and rheumatologist was observed for crystal-induced arthritis (kappa = 0.86), and the lowest agreement for polymyalgia rheumatica (kappa = 0.39) and systemic lupus (kappa = 0.46). Sensitivity was lowest for a primary care diagnosis of fibromyalgia (48%) and highest for ankylosing spondylitis (94%). Positive predictive values were generally low, in particular for systemic lupus erythematosus (33%) and polymyalgia rheumatica (30%). CONCLUSION: Most patients referred to an academic rheumatology centre had soft-tissue rheumatism or other pain syndromes. In general, diagnostic agreement between rheumatologists and primary care physicians was low. Increased emphasis on musculoskeletal disorders should be encouraged in medical education to increase the efficiency of rheumatology referrals.     

Total hip arthroplasty with cement in patients who have rheumatoid arthritis. A minimum ten-year follow-up study

One hundred and six consecutive total hip arthroplasties with cement were performed by one surgeon, at least ten years before the time of the present clinical and radiographic review, in seventy-five patients who had adult-onset rheumatoid arthritis. Two patients (three hips) were lost to follow-up. Seven (7 per cent) of the remaining 103 hips were revised. The revisions were performed because of infection (three hips), dislocation (two hips), or aseptic loosening (two hips). Of the ninety-eight hips that were not lost to follow-up or revised because of infection or dislocation, eight (8 per cent) had radiographic loosening of the acetabular component and two (2 per cent) had radiographic loosening of the femoral component. Although the prevalence of radiographic loosening of the acetabular component was four times greater than the prevalence of radiographic loosening of the femoral component, the prevalence of revision because of aseptic loosening of the acetabular component was identical to that for the femoral component (one component each). These results compared favorably with those of total hip arthroplasty with cement, performed by the same surgeon, for the treatment of other diagnoses. Loosening of the acetabular component was significantly associated with a younger age at the time of the index operation (p = 0.03) and with acetabular osteolysis (p = 0.0006). Of forty-eight hips in thirty-two patients who survived for at least ten years, 96 per cent (forty-six hips) were considered by the patients to have a satisfactory result. At the time of the latest follow-up, twenty-four (75 per cent) of the patients had no pain in the hip. Although eighteen patients (56 per cent) could walk without support at a minimum of ten years after the operation, we found that the functional results for patients who had rheumatoid arthritis were inferior to those observed for patients who had had a total hip arthroplasty with cement, performed by the same surgeon, for the treatment of other diagnoses.     

Clinical results of the Mayo total ankle arthroplasty

Two hundred and four primary Mayo total ankle arthroplasties were performed in 179 patients at the Mayo Clinic from 1974 through 1988. We evaluated the clinical result after 160 arthroplasties in 143 patients who had been followed for two years or more (mean, nine years; range, two to seventeen years). The result was good for thirty-one ankles (19 per cent), fair for fifty-five (34 per cent), and poor for seventeen (11 per cent); fifty-seven arthroplasties (36 per cent) were considered to be a failure (defined as removal of the implant). Adequate preoperative and follow-up radiographs were available for 101 ankles (eighty-nine patients). There was radiographic evidence of loosening of eight tibial components (8 per cent) and fifty-eight talar components (57 per cent), but we found no association between the clinical and radiographic results. Complications occurred after nineteen (12 per cent) of the 160 arthroplasties, and ninety-four additional reoperations were necessary after sixty-six (41 per cent). On the basis of these findings, we do not recommend ankle arthroplasty with a constrained Mayo implant for rheumatoid arthritis or osteoarthrosis of the ankle.     

Differences in the use of second-line agents and prednisone for treatment of rheumatoid arthritis by rheumatologists and non-rheumatologists

OBJECTIVE: To compare the use of methotrexate (MTX), intramuscular (i.m.) gold, hydroxychloroquine, and prednisone for rheumatoid arthritis (RA) treatment among patients managed by rheumatologists and nonrheumatologists. METHODS: Multiple regression analysis to estimate the likelihood of starting treatment and response to treatment for patients managed by rheumatologists and nonrheumatologists. All regression analyses were adjusted for patient demographic and clinical characteristics. RESULTS: Therapy with all agents studied was initiated more frequently for patients with RA with at least some contact with rheumatologists during the year than for those managed strictly by nonrheumatologists. The adjusted odds ratios for starts on these medications ranged from 1.14 for im gold to 15.11 for MTX for patients managed by rheumatologists compared to those managed by nonrheumatologists. However, due to the low frequency of initiation of treatment with most of these drugs for patients managed strictly by nonrheumatologists, only the odds ratio for prednisone reached statistical significance (OR = 2.94, p = 0.0082). In the year after initiation of therapy with these agents, patients managed by rheumatologists experienced better response to treatment than those managed by nonrheumatologists. These differences were statistically significant for MTX (p = 0.0447) and nearly significant for im gold (p = 0.0597). CONCLUSION: These results provide evidence of systematic differences in the propensity of rheumatologists and nonrheumatologists to initiate therapy with these antirheumatic drugs. If the observed differences in initial response to treatment translate into substantial differences in longterm outcomes, then these results suggest that the welfare of patients with RA may be jeopardized by the current trend toward primary care and restricted access to rheumatologists.     

Methotrexate in juvenile rheumatoid arthritis. Do the benefits outweigh the risks?

Juvenile rheumatoid arthritis (JRA) is a heterogeneous group of autoimmune diseases resulting in chronic idiopathic peripheral arthritis. The aetiology of JRA is unclear, and current pharmacotherapy is ameliorative rather than curative. Nonsteroidal anti-inflammatory drugs are given initially, but only one-third to one-fourth of patients are managed adequately with these agents. Advanced therapeutic drugs, frequently referred to as disease-modifying antirheumatic drugs or second-line agents, are given to the child with aggressive or resistant disease. Among these, the antimetabolite methotrexate has proven to be the most effective in alleviating articular disease manifestations and reducing laboratory parameters of inflammation. When given orally in low dosages (10 to 15 mg/m2/week), methotrexate is well tolerated, without evidence of substantial bone marrow suppression or severe hepatotoxicity. Extensive long term tolerability data are not yet available for children, but longitudinal studies in adult patients with rheumatoid arthritis suggest that the drug may be given safely for extended periods in many patients. Paediatric rheumatologists are beginning to give higher dosages of methotrexate (up to 1 mg/kg/week) parenterally with some success. The long term consequences of higher dose methotrexate in children are unknown. Methotrexate has now become, and will probably remain for some time, the drug of first choice for children with recalcitrant JRA.     

A clinical study of Thai patients with spondyloarthropathy

Eighty-eight Thai patients (61 males and 27 females) with spondyloarthropathy (SpA) were studied. Their mean age and mean duration of the disease were 25.97 and 3.34 years respectively. In 16 cases the disease first appeared before the age of 16 or had juvenile onset. Eleven cases were ankylosing spondylitis (AS), 9 were juvenile AS (JAS), 20 were Reiter's syndrome (RS), 4 were juvenile RS, 14 were psoriatic arthritis (PsA), 27 were undifferentiated SpA (uSpA), and 3 were juvenile uSpA. Peripheral arthritis, especially oligoarthritis of the lower extremity joints, was the most common form of arthritis in all groups, except for PsA, where polyarthritis was common. Back pain and bilateral sacroiliitis were commonly seen in JAS and AS. Enthesopathy was not uncommon. Extra-articular manifestations were more common in RS patients. Acute inflammatory eye diseases were seen in 45 per cent of AS and 66 per cent of RS cases. In general, the clinical features of Thai patients with SpA were similar to those reported in other countries in Asia and the west.     

How Canadian and US rheumatologists treat moderate or aggressive rheumatoid arthritis: a survey

OBJECTIVE: To determine which second line agents Canadian and US rheumatologists use to treat patients with active rheumatoid arthritis (RA). METHODS: A one page survey was sent by fax or mail to all 263 members of the Canadian Rheumatology Association and 320 members of the American College of Rheumatology (10% random sample weighted by region) known to practice adult rheumatology. The survey asked for first and second treatment preferences in patients with (1) aggressive RA; (2) moderate RA; and (3) aggressive RA failing a trial of methotrexate (MTX) 25 mg. RESULTS: Altogether 231 (87.8%) Canadian and 230 (71.7%) US rheumatologists responded, and 214 responses in each survey were analyzable. In aggressive RA. MTX was the drug of first choice of most Canadian (68.7%) and US (78.5%) rheumatologists. Intramuscular gold was a drug of first choice for 14.5 and 1.9% of Canadians and Americans, respectively. 93.9% of Canadian and 90.2% of US respondents preferred single agents for the treatment of moderate RA. Among US rheumatologists. no clear leader emerged as a single agent alternative for the management of aggressive RA unresponsive to MTX. Most said they would use combination (38.3%) or triple (23.8%) therapy involving MTX plus sulfasalazine and/or hydroxychloroquine. 52.3% of Canadians preferred single agent therapy, with 34.6% choosing gold as an alternative to MTX. CONCLUSION: Canadian and US rheumatologists preferred MTX for the treatment of aggressive RA. Canadian rheumatologists saw a small but significant role for intramuscular gold. No single agent emerged as a clear alternative to MTX among US rheumatologists.     

Clinical course and remission rate in patients with early rheumatoid arthritis: relationship to outcome after 5 years

OBJECTIVE: To investigate the clinical course in early rheumatoid arthritis (RA) patients followed prospectively, to relate course to outcome after 5 yr, and to try to identify prognostic features. METHODS: A total of 183 patients with definite RA and a mean disease duration of 11 months were included. Of these, 75% were rheumatoid factor (RF) positive; 85% carried the shared epitope, 32% on both alleles. Most patients were assessed every 6 months. Disability was evaluated with the Health Assessment Questionnaire (HAQ) and radiographic findings according to Larsen. Remission was defined in two ways: with the American Rheumatism Association (ARA) criteria and as 'no arthritis at least at one follow-up visit'. RESULTS: Twenty per cent achieved ARA-defined remission periods of at least 6 months duration; 21 were spontaneous and 18 drug induced. Average length of remission was 20.5 months. The remission periods constituted 7% of follow-up for all patients. Another 36% achieved remission according to the second definition. All 56% were considered to have a relapsing-remitting disease pattern, in contrast to the remaining 44% with a persistent disease pattern. More patients with persistent disease were treated with disease-modifying anti-rheumatic drugs (DMARDs) and had also received a larger number of different drugs. Outcome after 5 yr regarding disability, joint inflammation and joint damage was worse for patients with persistent disease. Neither ARA-defined remission nor disease pattern could be accurately predicted. CONCLUSIONS: Long-term ARA-defined remission was rare, constituting 7% of follow-up for the entire cohort. For those 20% achieving remission, this period represented 34% of their follow-up. A total of 56% had a relapsing-remitting disease pattern and 44% had a persistent disease pattern. This classification had prognostic implications with persistency being a bad prognostic sign.     

Diagnosis and course of early-onset arthritis: results of a special early arthritis clinic compared to routine patient care

OBJECTIVE: Early arthritis patients referred to an Early Arthritis Clinic (EAC) (n = 233) were compared to 241 patients from the routine out-patient clinic with respect to lag time between the onset of symptoms and the visit to the rheumatologist, clinical presentation and the consistency of the diagnosis after 1 yr. RESULTS: The reduction in median lag time for the EAC patients was at least 3 months. An insidious onset of symptoms was found more often in the rheumatoid arthritis (RA) patients in the routine clinic. In 70% of all cases, a diagnosis could be made after 2 weeks and, if the clinical diagnosis was definite RA, this hardly changed during the following year. Early erosions were seen in 25% of RA patients and were associated with a positive rheumatoid factor (OR 2.08, 95% CI 0.95 4.59). CONCLUSION: An early diagnosis of RA at the EAC is possible and reliable; the high frequency of erosions illustrates the need for early treatment.     

Utilization and predictive value of laboratory tests in patients referred to rheumatologists by primary care physicians

OBJECTIVE: Antinuclear antibodies (ANA), rheumatoid factors (RF), and erythrocyte sedimentation rate (ESR) are among the most frequently requested tests in the diagnosis and investigation of connective tissue diseases (CTD). We evaluate the utilization patterns and predictive value of these tests in patients referred to rheumatologists by primary care physicians. METHODS: We reviewed the records of all new patients referred by primary care physicians in 1994 to 2 rheumatologists practicing at the University of Alberta. Data extracted from the records included diagnostic tests requested by referring primary care physicians, signs and symptoms at the initial rheumatology consult, and followup diagnoses. RESULTS: Seven hundred eleven new patients had been referred by over 300 primary care physicians: RF had been requested in 25%, ANA in 21%, and ESR in 29%. One hundred nine (15%) of the 711 patients had a CTD, 45 (6%) had rheumatoid arthritis (RA), and 8 (1%) systemic lupus erythematosus (SLE). The predictive values of positive tests for the diagnosis of CTD were low: 49% for RF, 29% for ANA, and 35% for ESR. For RA, the positive predictive values were 44% for RF, 8% for ANA, 17% for ESR; for SLE, 2, 12, and 3%, respectively. Diffuse musculoskeletal pain and fatigue were significantly associated with test utilization, although most patients with these symptoms had fibromyalgia or localized soft tissue rheumatism. CONCLUSION: Primary care physicians frequently requested autoantibodies in patients referred to rheumatologists. Most tests were negative, and were often requested in patients without CTD, resulting in low positive predictive values and questionable clinical utility. These findings suggest inappropriate overuse and lack of understanding of the use of autoantibody tests in diagnosing rheumatic diseases. A decrease in inappropriate use could be achieved by emphasizing that fatigue and diffuse musculoskeletal pain are not indicative of CTD in the absence of other features such as joint swelling, typical rash, or organ involvement.     

Muramic acid in human peripheral blood leucocytes in different age groups

Presence of muramic acid (as a marker for bacterial cell wall peptidoglycan) was analysed by gas chromatography and mass spectrometry in the peripheral blood leucocytes of subjects from a range of ages (9-80 years) and groups (healthy individuals, patients with rheumatoid arthritis, osteoarthrosis, essential hypertension or multiple sclerosis). Sixty per cent of the sample from the youngest subjects contained detectable muramic acid. The percentage of people with circulating leucocytes containing muramic acid decreased gradually with age, being less than 5% in all groups over 40 years. No clear correlation between the presence of muramic acid and the disease was observed.     

Inherited deficiency of the second component of complement. Rheumatic disease associations

The prevalence of homozygous and heterozygous deficiency of the second component of complement (C2) was determined in patients with rheumatic disease including 137 with systemic lupus erythematosus (SLE), 274 with juvenile rheumatoid arthritis, and 134 with rheumatoid arthritis. 1 C2 homozygous deficient and 19 possible heterozygous deficient individuals were identified by using both immunochemical and functional assays to determine C2 levels. Of the 20, 8 had SLE (5.9%), 10 had juvenile rheumatoid arthritis (3.7%), and 2 had rheumatoid arthritis (1.4%), the homozygous deficient individual having SLE. The prevalence of C2 deficiency in the SLE and juvenile rheumatoid arthritis patients was significantly increased (P = 0.0009 and P = 0.02, respectively) when compared with controls, 6 (1.2%) of 509 blood donors having C2 levels consistent with heterozygous deficiency. 15 of the 20 C2 deficient patients were HLA typed and found to have antigens A10(Aw25), B18, or both. The patients with C2 deficiency and SLE had earlier age of onset of disease and less antinuclear antibody when compared with the C2 normal SLE patients. 11 families of the propositi were studied and found to have one or more C2 heterozygous deficient individuals. The family members had an equal distribution of rheumatic disease and antinuclear antibody in the C2 deficient and C2 normal groups. C2 deficient individuals were found to have significantly lower levels of properdin Factor B (242 mug/ml+/-54) when compared with the non-C2 deficient family members (282 mug/ml+/-73). These data support the concept that inherited deficiency of C2 is significantly associated with both SLE and juvenile rheumatoid arthritis.     

Residual effects of septic arthritis in infancy and childhood

Septic arthritis affects weight-bearing joints in three fourths of cases. When the disease occurs in infancy, joint dysfunction may not be apparent until many months later. We located 49 children who had had 50 episodes of septic arthritis from 1 1/2 to 12 years earlier (mean, 4.3 years). Thirteen patients (27%) had sequelae, and in eight (16%), there was impairment of ambulation. Residual damage was more common with hip and ankle involvement than with knee joint disease. Sequelae were equally common after Haemophilus influenzae and Staphylococcus aureus infection. Evaluation at the time of hosiptal discharge correctly identified only four of the 13 children with sequelae, and four others who were normal at follow-up had been thought to have permanent damage at discharge. Children with sequelae tended to have been sick longer before diagnosis, and drainage of pus was delayed.     

Clinical review of 74 cases with miliary tuberculosis

Seventy-four cases of miliary tuberculosis were studied retrospectively. The mean age of the patients was 45.3 years. Twenty-two patients suffered from another underlying diseases. Six were infected with human immunodeficiency virus. Twelve had been treated with corticosteroids. Fever was present in 97.3 per cent of patients. Elevation of serum alkaline phosphatase was found in 67.6 per cent of cases. The skin reaction to tuberculin was positive in 61.2 per cent. Nodular shadows were found in the chest X-ray in 98.6 per cent of cases. The nodules were smaller than 2 mm in diameter in 52.7 per cent of cases. Other findings were enlargement of mediastinal lymph node (17.6%), cavities (23.0%), pleural effusion (27.0%), and consolidation (35.1%). Sputum cultures and urine cultures were positive for Mycobacterium tuberculosis in 76.8 per cent and 58.6 per cent of cases respectively. The diagnosis was confirmed by histopathological findings in some cases. The rate of positive biopsies was 61.5 per cent by bone marrow aspiration, 83.3 per cent by lymph node biopsy, 100 per cent by liver and lung biopsy. Antituberculosis therapy was successful in most of the patients. Seven patients died of miliary tuberculosis, 4 of them had adult respiratory distress syndrome.     

Complications and long-term results of ankle arthrodeses following trauma

A review of sixty patients who had undergone ankle fusion for post-traumatic arthritis revealed that thirty-five (58 per cent) had the procedure performed within the first year after injury. A total of forty-eight complications occurred in twenty-nine (48 per cent) of the patients. Frequent complication were infection (23 per cent), non-union (23 per cent), inadequate surgical alignment or early loss of position (15 per cent), malunion (12 per cent), and delayed union (7 per cent). The lateral transfibular approach had the highest incidence of complications, and a two-incision approach using the Charnley compression apparatus was the procedure with the fewest complications. Forty-one patients were followed for an average of 7.5 years after operation. Of these, thirty-four (83 per cent) were satisfied with the procedure. Examination of thirty of the forty-one patients at an average of 7.3 years after surgery revealed virtually no subtalar motion but motion of 13 degrees at Chopart's joint. With shoes, patients had a near-normal gait. The roentgenograms revealed a minimum amount of degenerative arthritis at Chopart's joint, which may worsen with time. Varus or valgus angulation of the hind part of the foot was associated with a greater degree of symptoms in the subtalar area as well as the middle of the foot. The neutral position in varus-valgus angulation as well as dorsiflexion-plantar flexion was the optimum position for both men and women. The results of the procedure did not deteriorate with time.     

A mode of selective action of thiadiazolyl urea herbicides

A group education program was developed for clinic patients with rheumatoid arthritis. Teaching methods used included the Arthritis Foundation's handbook, Rheumatoid Arthritis, and a lecture by a rheumatologist. The 20 patients in the study were given a multiple choice test before and after the teaching program to determine their knowledge of arthritis. Results showed group education to be an effective teaching device. It was demonstrated that patients learned from reading the handbook alone, but the combination of reading and lecture was found to be a more effective method. Correlation studies showed that prior to group education, patients had a significant knowledge of their disease which was related to native intelligence, formal education, and socio-economic status, but not to duration of disease or length of clinic attendance. This suggests that future patient education experiments should include a pre-instruction test to document prior knowledge.     

Hand flexor tenosynovitis in rheumatoid arthritis. Prevalence, distribution, and associated rheumatic features

Tenosynovitis of one or more flexor tendons of the hand (mean 3.1 tendons per patient) was noted in 55% of 100 patients with rheumatoid arthritis (RA) examined periodically during a mean period of 5 years. The third flexor tendon was involved most frequently (71% of patients), followed by the second (62%), fourth (53%), fifth (27%), and first (13%). Patients with flexor tendonitis (FT) had a significantly higher prevalence of rheumatoid nodules (56% vs 33%), carpal tunnel syndrome (47% vs 13%), wrist extensor tenosynovitis (47% vs 9%), and elbow epicondylitis (22% vs 7%) than patients without FT. Dupuytren's contracture, DeQuervain's tenovaginitis, flexor carpi radialis and ulnaris tendonitis, and Achilles tendonitis were found exclusively in patients with FT. A control group of 50 non-RA patients with FT had statistically fewer diseased tendons per patient (mean 1.5) and a different digital distribution, the thumb being affected more frequently (P less than 0.05) than in RA patients.     

Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats

OBJECTIVE: To determine the reliability of some commonly used outcome measures in patients with rheumatoid arthritis. METHODS: We studied 22 consecutive patients with rheumatoid arthritis enrolled in a clinical trial in a tertiary care center. The study design consisted of a test-retest, in which the same rheumatologist evaluated all of the patients twice, with an interval between evaluations of 90 to 120 minutes. Statistical analysis of the data consisted of calculation of the weighted Kappa (kw) and the intraclass correlation coefficient (ICC). RESULTS: For the Ritchie articular index, kappa w = 0.83, ICC = 0.49, p < 0.0001; tender joint count, kappa w = 0.82, ICC = 0.49, p < 0.0001; physician's global assessment, kappa w = 0.79, ICC = 0.48, p < 0.0001; disease activity score, kappa w = 0.79, ICC = 0.49, p < 0.0001; utilities, kappa w = 0.71, ICC = 0.48, p < 0.0001; swollen joint count, kappa w = 0.7, ICC = 0.47, p < 0.0001; patient's global assessment, kappa w = 0.58, ICC = 0.44, p < 0.0001; pain kappa w = 0.45, ICC = 0.41, p < 0.0001. CONCLUSIONS: The reliability of most of the outcome measures was good. It was higher for those measurements evaluated by a rheumatologist and for the composite indexes. Those requiring patient participation need to be improved.     

Population based case-control study of sick leave in postmenopausal women before diagnosis of hyperparathyroidism

OBJECTIVE: To analyse sick leave in women at risk of primary hyperparathyroidism before its diagnosis. DESIGN: Case-control study nested within a screened cohort of postmenopausal women. Cases were women with hyperparathyroidism without prior knowledge of their disease and no traditional symptoms or complications. Controls were women from the screened population without hyperparathyroidism. SETTING: Population based screening within a Swedish community. SUBJECT: 48 case-control pairs of women aged 55-70 years. MAIN OUTCOME MEASURE: Sick leave during the 5 years before diagnosis. RESULTS: Total duration of sickness benefits was longer in the cases than controls, and this discrepancy included sick leave on full time or half time and for periods of longer than a week. Cases had an increased risk of sick leave more than half of the investigated time compared with controls (odds ratio 12). Doctors' certificates showed that the overrepresented sick leave in the cases related mainly to cardiovascular diseases. CONCLUSION: Asymptomatic mild primary hyperparathyroidism in postmenopausal women is accompanied by a previously unrecognised morbidity, which has consequences for clinical management of the disorder and its impact on the health economy.