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Markku Hakala

Publications and source records attributed to Markku Hakala.

At least 19 recordsLinked to original sources

Bone oedema predicts erosive progression on wrist MRI in early RA--a 2-yr observational MRI and NC scintigraphy study.

OBJECTIVES: To investigate if disease assessment by contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative nanocolloid (NC) scintigraphy gives useful additional information in early rheumatoid arthritis (RA). METHODS: Twenty-seven patients with early RA (disease duration < or =12 months) were followed up for 1 yr and 24 of them for 2 yrs with contrast-enhanced MRI and NC scintigraphy of the wrist joint. Synovial inflammation was assessed by measuring time-dependent enhancement rates (E-rate) from dynamic MRI scans and technetium(99m)-labelled nanocolloid ((99m)Tc-NC) uptake from scintigraphy scans. Synovial membrane hypertrophy, bone oedema and erosions were semiquantitatively scored according to the Outcome Measures in Rheumatology Clinical Trials RA-MRI scoring system from static MR images. Response to the treatment was evaluated based on whether or not > or = 50% improvement was achieved in the tender and swollen joint scores and the Health Assessment Questionnaire score, with normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) levels. Progression of the erosion score on wrist MRI was evaluated as the outcome. RESULTS: The baseline MRI bone oedema score (rho= 0.67), MRI synovitis score (rho= 0.57), ESR (rho= 0.56), CRP (rho= 0.48), E-rate (rho= 0.47) and (99m)Tc-NC uptake (rho= 0.45) were related with the change in the MRI erosion score from baseline to 2 yrs (rho= Spearman's correlation). In the multivariate logistic regression model, the bone marrow oedema score was the only baseline variable that predicted erosive progression at 2 yrs' follow-up (OR 4.2, 95% CI 1.3-13.8). The median (interquartile range) change in the erosion score from baseline to 2 yrs was 0 (0, 0) and 4 (2, 5) in the patients with (n= 9) and without (n= 15) a persistent clinical response over the 2 yrs, respectively (P= 0.001). The non-responders who presented with erosive progression from 1 yr to 2 yrs had higher MRI synovitis scores, bone oedema scores, E-rate and (99m)Tc-NC uptake at 1-yr follow-up than the non-responders without progressive bone damage. CONCLUSION: The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.

Adult↗

Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or previously on TNF blocking drugs: an observational study.

The aim of this study was to evaluate the effectiveness of IL-1 inhibition in rheumatic disease using real-life, observational methods. We analyzed data from 47 patients collected from the national ROB-FIN for rheumatic disease. Commonly used, validated measures of efficacy and adverse effects were documented and analyzed. The series contains 47/1,135 patients (mean age 47+/-11 years, range 25-73, females 83%) on anakinra of whom 39 patients suffered from rheumatoid arthritis (RA), two presented with psoriatic arthritis, and four with juvenile RA. At 3 months (26/40), 46% reached American College of Rheumatology (ACR) 20 and 27% ACR 50. In patients naive to biological drugs, the response rate at 3 months was 60% for ACR 20 and 20% for ACR 50. At follow-up of the total series, ACR responses at 6 and 12 months were 69/56% for ACR 20 and 23/22% for ACR 50. These data give room for IL-1 suppression when treating patient with rheumatic disease. Careful selection of patients, together with combining anakinra with disease-modifying antirheumatic drugs, perhaps adds effectiveness. For treating clinicians in Finland, these results are encouraging, as reimbursed treatment alternatives for patients refractory to all other therapies are still few.

Adult↗

Survival and complications are similar after Swanson and Sutter implant replacement of metacarpophalangeal joints in patients with rheumatoid arthritis.

We compared the survival, fracture, and deformation rates of Swanson and Sutter implants in a prospective series of 53 patients with rheumatoid arthritis (RA). Fifty-eight hands were operated on with 215 silastic implants. The Swanson group comprised 25 hands and 89 implants, and the Sutter group 33 and 126, respectively. Follow up was 58 (37-80) months. During a period of 48 months the survival of Swanson and Sutter prostheses did not differ significantly: 92% (95% CI 84% to 96%) and 97% (95% CI 92% to 99%), respectively. The fracture rate was high in both groups: 26 (34%) in the Swanson and 25 (26%) in the Sutter group. There was no significant difference between the groups in definite fracture rates of implants. The Sutter prosthesis appears to be at least as durable an implant in rheumatoid patients' metacarpophalangeal arthroplasty as the Swanson.

Adult↗

Osteolysis after Sutter metacarpophalangeal arthroplasty: a prospective study of 282 implants followed up for 5.7 years.

Our aim was to evaluate the incidence and degree of osteolysis in a prospective series of patients with rheumatoid arthritis operated on with Sutter implants. Eighty-seven of the 110 operated hands (104 patients) with 282 implants were evaluated after a mean of 5.7 years (2.1-7.4). Osteolytic changes were present in 142 (50%) of the metacarpal and 152 (54%) of the phalangeal bones. Twenty-six of the metacarpal (9%) and 36 of the proximal phalangeal (13%) bones had osteolytic changes that did not affect the cortical bone. Cortical invasion was recorded in 100 (35%) of the metacarpal and 103 (37%) of the proximal phalangeal bones. The cortex was perforated in both bones in 14 (5%). Osteolytic changes were related to fractures of implants and to the dominant hand, but not to pain. Surgeons who operate on patients with rheumatoid diseases should note that silicone rubber implants often cause osteolytic changes.

Arthritis, Rheumatoid↗

[Not Available].

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Journal Article↗

Aortic valve insufficiency in patients with chronic rheumatic diseases.

Aortic valve lesions are often found in patients with rheumatic diseases, but their clinical significance has not been properly evaluated. In the present study, the echocardiographic files of the cardiology unit of the Oulu University Hospital were screened for a diagnosis of aortic insufficiency (AI). The aetiology of the valve disease and specific details of the rheumatic disease were evaluated in 160 patients. Twenty-eight patients (18%) had a history of rheumatic fever. Rheumatic disease was found in 14 patients (8.8%) with AI, which is significantly more than the prevalence of rheumatic diseases (1.8%) in the corresponding age group (35-100 years) in Finland. Rheumatoid arthritis or juvenile rheumatoid arthritis was found in seven patients (4.4%), whereas ankylosing spondylitis or seronegative spondylarthropathy were found in four patients (2.5%). Other rheumatic diseases included Takayasu's arteritis (two patients) and scleroderma (one patient). When 38 patients with pure AI without other possible aetiology were analysed, rheumatic disease was found in five patients (13%). Patients with rheumatic disease as a potential aetiology of AI often had symptomatic valve disease, which required surgical treatment, although great differences between different aetiologies were not found.

Adult↗

Early suppression of disease activity is essential for maintenance of work capacity in patients with recent-onset rheumatoid arthritis: five-year experience from the FIN-RACo trial.

OBJECTIVE: To explore the impact of an early treatment response on maintenance of work capacity in patients with early, active rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomized to receive either a combination of disease-modifying antirheumatic drugs (DMARDs) with prednisolone or a single DMARD with or without prednisolone for 2 years. Treatment responses were evaluated according to the American College of Rheumatology (ACR) criteria. After a 5-year followup, the cumulative number of days of sick leave and RA-related permanent work disability was calculated for each of the 162 patients who were available for the active work force at baseline. RESULTS: Of the 159 patients assessed at 6 months, 29 were in clinical remission, 66 achieved an ACR50 response but not remission, 29 achieved an ACR20 response but not an ACR50 response, and 35 failed to achieve an ACR20 response. In these 4 groups, the median numbers of work disability days per patient-year from 6 months through 60 months of followup were 0 (interquartile range [IQR] 0-3), 4 (IQR 0-131), 16 (IQR 0-170), and 352 (16-365), respectively (P < 0.001). Pairwise multiple comparisons showed a statistically significant difference between all groups except the ACR50 and ACR20 groups. At 12 months, 30 patients were in remission. None of the 44 patients in remission at 6 or 12 months became permanently work disabled over the 5-year followup, as compared with 15 patients in the ACR50 group (23%), 6 in the ACR20 group (21%), and 19 without an ACR20 response at 6 months (56%). CONCLUSION: Prompt induction of remission translates into maintenance of work capacity. At 6 months, an ACR50 response is no better than an ACR20 response with regard to future productivity, while failure to achieve an ACR20 response carries a high risk for work disability.

Adult↗

Comparison of Swanson and Sutter metacarpophalangeal arthroplasties in patients with rheumatoid arthritis: a prospective and randomized trial.

PURPOSE: To perform a prospective and randomized comparison of the clinical outcome of patients with rheumatoid arthritis who had Swanson or Sutter implant replacement arthroplasty of the metacarpophalangeal joints. METHODS: There were 45 patients (3 men, 42 women) and 49 hands; a total of 75 Swanson and 99 Sutter implants were inserted. The mean time between surgery and the final follow-up control visit was 58 months (range, 37-80 mo). Preoperative and postoperative measurements were performed including active extension and flexion, correction of ulnar deviation, and strength. RESULTS: There was no statistically significant difference between groups with regard to active extension deficit correction. Mean active flexion decreased less in the Sutter group than in the Swanson group but difference between the groups was statistically significant in only the index finger. At the final follow-up examination no significant differences existed between the groups in the correction of ulnar deviation or arc of motion. Grip strengths, chuck pinch, and thump-to-fingertip grip strengths did not improve in either of the groups. CONCLUSIONS: In this study clinical results showed no significant difference between the groups with the single exception of the amount of index finger metacarpophalangeal joint flexion.

Arthritis, Rheumatoid↗

Sensitive immunoassays for the autoantibodies reacting against citrullinated carboxy-terminal telopeptides of type I and type II collagens in patients with rheumatoid arthritis.

We developed sensitive assay methods for autoantibodies recognizing the citrullinated synthetic peptides derived from type I and type II collagens in patients with rheumatoid arthritis (RA). These peptides were tested with the chemiluminescence method (Nichols Advantage System). In 44 RA patients out of 120, the sera showed increased binding of citrullinated synthetic C-telopeptide derived from the alpha1 chain of type I collagen (p=0.003 compared to controls). For a corresponding C-telopeptide pair from the alpha1 chain of type II collagen, 35 patient sera bound the citrullinated peptide more strongly than the arginine peptide, but the difference compared to the controls was not significant (p=0.074). Correlation between the two carboxy-telopeptides was r=0.473 (p<0.001). The anti-CCP assay (antibodies against citrullinated filaggrin sequence-derived peptides) was positive in 59% of our RA patients. There was no relationship between the anti-CCP results and the antibodies against collagen C-telopeptides, but both are increased in RA patients. We demonstrated autoantibodies in RA patients that bound citrullinated C-telopeptides derived from type I and type II collagen antigens. The peptide sequences detected (-YYXA and -YMXA) were different from that based on the cyclic filaggrin antigen (-STXG-, where X represents citrulline).

Adult↗

Evaluation of the MDHAQ in Finnish patients with RA [corrected].

OBJECTIVE: To study the characteristics of the Multidimensional Health Assessment Questionnaire (MDHAQ) in Finnish patients with rheumatoid arthritis. METHODS: The reliability of the questionnaire was tested by test-retest procedure. Construct validity was studied by factor analysis and convergent validity by calculating correlations between the Finnish MDHAQ (Finn-MDHAQ) scales and the Finnish Health Assessment Questionnaire (HAQ) and the Finnish Arthritis Impact Measurement Scales (Finn-AIMS2). Correlations between Finn-MDHAQ and measures of clinical characteristics, disease activity, and functional class were also measured. An item analysis was made of the Finn-MDHAQ scales Function (FN) and Psychological (PS). RESULTS: Internal consistency on the FN scale was 0.92 (95% lower limit 0.89) and 0.66 (0.56) on the PS scale. Reproducibility (95% CI) on FN was 0.93 (0.82 to 0.97) and on PS 0.84 (0.70 to 0.92). Factor analysis identified 2 factors, mobility of upper extremities and trunk, and mobility of lower extremities. Strong correlations were found between the FN scale and HAQ and physical subscales of Finn-AIMS2 and between PS and the psychological subscales of Finn-AIMS2. In item analysis corrected item correlation was high on the Finn-MDHAQ scales, except in one item on the PS scale. CONCLUSION: The Finn-MDHAQ is an applicable, reliable, and valid instrument for the part of the FN scale measuring functional ability in Finnish rheumatic patients. The incongruity in the PS scale structure that produced moderate internal consistency can be overcome with minor modifications.

Activities of Daily Living↗

Impact of initial aggressive drug treatment with a combination of disease-modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: a five-year randomized followup trial.

OBJECTIVE: To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age. RESULTS: The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods </=300 days): median 11.7 days (IQR 0-44) per patient-observation year in those treated with combination therapy and 30.0 days (IQR 6-68) in those treated with single therapy (P = 0.002). No statistically significant difference was seen in RA-related disability pensions. CONCLUSION: Aggressive initial treatment of RA with a combination of DMARDs improves 5-year outcome in terms of lost productivity in patients with RA of recent onset.

Adult↗

Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study.

OBJECTIVE: To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score. RESULTS: A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively. CONCLUSION: Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.

Adult↗

Etanercept does not essentially increase the total costs of the treatment of refractory juvenile idiopathic arthritis.

OBJECTIVE: To assess the costs of adding etanercept to the prevailing drug therapy for a one-year period in a group of 31 children with juvenile idiopathic arthritis (JIA) whose disease was refractory to conventional disease modifying antirheumatic drugs. METHODS: The changes in total costs were retrospectively collected from medical records and by interviewing parents 6 months before the initiation of etanercept treatment and during a 12-month followup divided into 3-month periods. RESULTS: Direct median costs increased during the first 3 months after the introduction of etanercept, but decreased later during the followup. The estimated median direct costs per patient increased by 4200 US dollars per year, and the indirect costs were reduced by 50%, i.e., 1700 US dollars . The estimated median total cost per patient was increased by about 2700 US dollars per year (10%). CONCLUSION: After combining etanercept with the prevailing treatment, the total costs of refractory JIA calculated per year were only slightly higher than those of traditional therapy. This finding must be evaluated in light of the reduced inflammatory activity of the joint disease and the probable reduction of lifetime pain and disability produced by the disease.

Adolescent↗

Assay for cross-linked carboxyterminal telopeptide of type I collagen (ICTP) unlike CrossLaps assay reflects increased pathological degradation of type I collagen in rheumatoid arthritis.

We compared the ability of assay for cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and CrossLaps assay to reflect increased pathological degradation of type I collagen in serum and synovial fluid samples of patients with rheumatoid arthritis (RA; n = 40). ICTP and CrossLaps concentrations were correlated with each other and with markers of collagen synthesis (PINP and PIIINP, amino terminal propeptides of type I and type III procollagens, respectively) and with markers of inflammation, i.e., C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum ICTP was increased in half of the RA patients, whereas CrossLaps assays were increased only occasionally. Serum ICTP correlated with the other markers of collagen metabolism as well as with CRP and ESR. Serum CrossLaps correlated only with PINP and ICTP, but not with serum PIIINP, CRP or ESR. Two patients had false-positive reactions in the CrossLaps assay due to the rheumatoid factor. The ICTP and CrossLaps antigens were clearly separate peaks in gel filtration analysis. The CrossLaps assay is able to detect the same ICTP antigen, but not vice versa. The ICTP assay reflects increased matrix metalloproteinase-mediated collagen degradation in joints in RA. In contrast, the physiological cathepsin K-mediated bone resorption measured by the CrossLaps assay was only occasionally increased.

Adult↗

Comprehensive study of autonomic function in a population with primary Sjögren's syndrome. No evidence of autonomic involvement.

OBJECTIVE: Autonomic neuropathy is associated with increased mortality. Autonomic nervous system disorders have been described in patients with primary Sjögren's syndrome (SS), but the results in controlled studies have been contradictory, varying from normal to sympathetic or parasympathetic dysfunction. Since the earlier studies employed varying methodologies, which may have led to the discrepancy, we conducted a comprehensive study on autonomic function in patients with primary SS and compared our findings to healthy, carefully matched population based controls. METHODS: A conventional cardiovascular reflex test battery (Valsalva maneuver, deep breathing test, active orthostatic test) and measurements of baroreflex sensitivity with phenylephrine and 24 hour heart rate variability were performed on 30 patients with primary SS and 30 healthy age and sex matched population based controls. RESULTS: There were no significant differences between the SS patients and the healthy controls in any of the tests. CONCLUSIONS: The prevalence of autonomic dysfunction is not increased in patients with primary SS compared to the general population.

Adrenal Cortex Hormones↗