M Hakala

Kainuu Central Hospital, Kjana, Oulu, Finland

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Publications (138)623.53 Total impact

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    ABSTRACT: Objectives: Better treatment strategies and therapeutic options have changed the treatment of rheumatoid arthritis (RA) during the past decade. Our objective was to examine clinical and patient-reported outcomes in patients with RA treated in 1998-99 and 2011-12. Method: The cross-sectional observational study included 303 consecutive outpatients (n = 103 in 1998-99 and n = 200 in 2011-12) from the same outpatient clinic. Patient questionnaires included patients' sociodemographics, the Health Assessment Questionnaire (HAQ) for functional ability, the Nottingham Health Profile (NHP) for health-related quality of life (HRQoL), self-reported general health (GH), and operations performed due to RA. A clinical examination was conducted for all patients. Comorbidities according to the Charlson Comorbidity Index (CCI), anti-rheumatic drugs and medications were recorded and the HAQ and NHP dimensions calculated. The results from these two patient cohorts were compared. Results: The cohorts were comparable with regard to age, sex, and RA duration while the patients in the 2011-12 cohort were less often seropositive for rheumatoid factor (RF), had a better socioeconomic situation, better functional and working ability, and a decreased rate of RA surgery. The patients in 2011-12 had higher comorbidities and poorer GH while the HRQoL dimensions did not differ between the cohorts except for better mobility in 2011-12. Methotrexate (MTX) and combinations of conventional anti-rheumatic drugs were more frequently used in 2011-12. Biologicals were used only in 2011-12. Conclusions: According to our results, more active anti-rheumatic therapy coincides with better RA-related outcomes. However, the result was the opposite with regard to overall health and comorbidities. Is this a new challenge in the treatment RA?
    Scandinavian journal of rheumatology. 12/2014;
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    ABSTRACT: Objectives: To assess the impact of abdominal obesity (AO) on disease severity, cardiovascular risk factors, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA). Method: Two hundred and thirty consecutive outpatients were cross-sectionally assessed. Waist circumference (WC) with a cut-off point of ≥ 102 cm in men and ≥ 88 cm in women indicated AO. Clinical assessment included joint counts, radiographs of small joints, and laboratory tests. Comorbidities and medication were verified from the patients' database. Patient questionnaires included sociodemographics, pain intensity, global disease activity, the Beck Depression Inventory (BDI), the Health Assessment Questionnaire (HAQ), physical activity level, and the 36-item Short Form Health Survey (SF-36). Metabolic syndrome (MetS) was defined according to the criteria of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). The association of AO with the 28-joint count Disease Activity Score (DAS28) and mental (MCS) and physical component scores (PCS) of the SF-36 and the HAQ was assessed by using regression models with the propensity score as a covariate. Results: The AO prevalence was 52% in the 200 eligible patients. In a univariate analysis, AO was associated with cardiovascular risk factors, low HAQ score, physical inactivity, disease activity parameters, impaired MCS, higher pain, and increased use of biological drugs and antidepressants. In a multivariable model, only poorer DAS28 (p = 0.018) and poorer HAQ score (p = 0.004) remained significantly associated with AO. Conclusions: AO is highly prevalent in patients with RA. In addition to cardiovascular risk factors, AO is associated with higher disease activity, higher disability, physical inactivity, more patients' perception of pain, and poorer mental health. Multifaceted promotion of lifestyle habits would be beneficial for improving AO-related health outcomes in patients with RA.
    Scandinavian journal of rheumatology 01/2014; · 2.51 Impact Factor
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    ABSTRACT: Background and purpose Drug-based treatment of rheumatoid arthritis (RA) has evolved markedly over the past 2 decades. Using nationwide register data, we studied how this has affected the rates of hip, knee, shoulder, and elbow replacement from 1995 to 2010. Methods The number of primary joint replacements was obtained from the Finnish Arthroplasty Register. To test the hypothesis that improvements in medical treatment of RA reduce the need for joint replacements, we also collected data about purchases of different disease-modifying anti-rheumatic agents (DMARDs) and biological drugs from the nationwide drug registers. Results The annual incidence of primary joint replacements for RA declined from 19 per 10(5) in 1995 to 11 per 10(5) in 2010. The decline was greater for upper-limb operations than for lower-limb operations. At the same time, the numbers of individuals using methotrexate, hydroxychloroquine, and sulfasalazine (the most commonly used DMARDs) increased 2- to 4-fold. Interpretation Our results are in accordance with observations from other countries, and indicate that the use of joint replacements in RA has decreased dramatically. Our data suggest that effective medical therapy is the most likely explanation for this favorable development.
    Acta Orthopaedica 08/2013; 84(4):331-7. · 2.74 Impact Factor
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    ABSTRACT: We describe the epidemiological and microbiological process in the clearing of a foodborne outbreak of Yersinia pseudotuberculosis O:1 linked to raw carrots and frequency of the associated reactive extra-gastrointestinal manifestations. The patient samples were investigated by routine culture or antibody testing methods. The real-time bacterial PCR was used to detect Y pseudotuberculosis in samples from the grated carrots and in those taken from the carrot storage. Genotype of bacterial isolates was determined by pulsed-field gel electrophoresis. For case identification, we retrospectively looked over the laboratory files of the central hospital focusing on the time period of the outbreak. Altogether 49 case patients were identified. Y pseudotuberculosis was detected by real-time PCR analysis in samples taken from grated carrots and from the carrot distributor. Bacterial isolates originating from the farm environment showed identical serotype (O:1) and genotype (S12) with the patients' isolates. Among 37 adults, reactive arthritis (ReA) was found in 8 (22%) and three adults had probable ReA. Six (67%) out of nine human leucocyte antigen (HLA) typed patients with ReA were HLA-B27 positive. Erythema nodosum was found in 42% of the 12 children, whereas none of them had definite ReA. In this outbreak, Y pseudotuberculosis was for the first time detected in both patient and food samples. ReA was more common than earlier reported in the outbreaks associated with this pathogen; the reason may be that the previous outbreaks have occurred among children. HLA-B27 frequency was higher than usually reported in single-source outbreaks of ReA.
    Annals of the rheumatic diseases 07/2013; · 8.11 Impact Factor
  • Annals of the rheumatic diseases 11/2012; · 8.11 Impact Factor
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    ABSTRACT: The first patient entered the Rheumatism Foundation Hospital, Heinola, Finland in July 1951. From that point on, the hospital helped patients suffering from rheumatic disorders. Specialists in the hospital actively developed treatments and published a large number of scientific articles in international journals. The hospital was well known internationally among people working in the field. Progress in the development of disease-modifying medication (biological agents in particular) has dramatically improved the life of patients with rheumatic diseases, but all effective treatments may also have adverse effects. In this article, we briefly review the history of the Rheumatism Foundation Hospital, which was closed permanently in March 2010 due to bankruptcy. The economical difficulties were caused primarily by the progress made in disease-modifying therapy, which decreased the need of rehabilitation and operative treatment of patients with rheumatic diseases. It seems that a great success in biological agents can carry "serious adverse effects", which may kill hospitals. This is an important primary observation, which should be noticed when the future of specialised institutes is planned.
    Clinical Rheumatology 05/2012; 31(8):1151-4. · 2.04 Impact Factor
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    ABSTRACT: To study the efficacy and safety of once-monthly oral ibandronate in the prevention of glucocorticoid (GC)-induced osteoporosis (GIOP) in postmenopausal women with inflammatory rheumatic diseases. A randomized, double-blind, placebo-controlled, parallel-group study of 140 postmenopausal women was conducted. At baseline, the mean lumbar spine (LS) (L1-L4) bone mineral density (BMD) was normal or osteopaenic (T-score ≥ -2.0) and the patients were receiving treatment with 5-15 mg/day of prednisone equivalent. Patients were randomized 1:1 to receive either monthly oral ibandronate 150 mg or placebo for 12 months. All patients received vitamin D and calcium supplements. The primary endpoint was the relative change in mean LS BMD from baseline to 12 months. Mean LS BMD increased significantly by 2.6% and 3.2% from baseline to 6 and 12 months with ibandronate compared to 0.3% and -0.1% with placebo, respectively (p < 0.001). Comparable significant mean increases were also found in trochanter, femoral neck and total hip BMDs at 12 months. Reductions in the serum levels of bone turnover markers C-terminal telopeptide of type I collagen (sCTX), N-terminal propeptide of type I procollagen (P1NP), and tartrate-resistant acid phosphatase (TRACP) were significantly more marked in the ibandronate group than in the placebo group at 1, 6, and 12 months. Adverse events (AEs) were reported at a similar frequency in both groups. A higher proportion of serious AEs (SAEs) were reported in the ibandronate group without emergence of any single SAE. Once-monthly oral ibandronate provides a significant increase in LS and total hip BMD with an acceptable safety profile in postmenopausal women treated with low-dose GCs for inflammatory rheumatic diseases.
    Scandinavian journal of rheumatology 01/2012; 41(4):260-6. · 2.51 Impact Factor
  • Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 06/2011; 18 Suppl 1:224-5. · 2.51 Impact Factor
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    ABSTRACT: To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis. Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls. The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP). The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.
    Scandinavian journal of rheumatology 04/2011; 40(4):256-62. · 2.51 Impact Factor
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    ABSTRACT: Risk for amyloidosis in rheumatic diseases is associated with a long-lasting inflammation. To assess possible changes in the incidence of terminal uraemia due to amyloidosis associated with rheumatic diseases on a nationwide basis, we scrutinised the files of the Finnish Registry for Kidney Diseases for patients suffering from amyloidosis associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) or juvenile idiopathic arthritis (JIA) over the period 1995-2008. The registry has an estimated 97-99% coverage of all patients accepted for renal replacement therapy (RRT) in the country. Data on the consumption of antirheumatic drugs were collected from two sources: the Social Insurance Institution's Drug Reimbursement Register, and the Sales Register of the National Agency for Medicines from the above period. Altogether 264 cases were identified. Two hundred twenty-nine of them had RA, 15 AS and 20 JIA. When the total annual number of new admissions to RRT varied between 20 and 37 at the end of 1990s, it was under half of that from 2002 onwards. Over this period, the number of users of low-dose methotrexate (MTX) has increased 3.6-fold, the drug being the most frequently used disease modifying anti-rheumatic drug in Finland. The present nationwide series is the first to show that the incidence of end-stage renal disease due to amyloidosis associated with rheumatic diseases is decreasing. An obvious reason for this is intensive anti-rheumatic drug therapy.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 03/2011; 18(1):25-8. · 2.51 Impact Factor
  • Scandinavian journal of rheumatology 03/2011; 40(2):152-3. · 2.51 Impact Factor
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    ABSTRACT: To assess long-term impact of RA on the HR-QoL in a cohort of working-age patients with early disease treated by a multidisciplinary team including early and active use of disease-modifying anti-rheumatic drugs (DMARDs). Fifty-five consecutive patients with RA who were naïve to DMARDs and glucocorticoids were assessed at baseline and at 6 months, 1, 2, 5 and 10 years. HR-QoL, disease activity, function, and joint destruction of hands and feet were assessed by using the Nottingham Health Profile (NHP) instrument, the 28-joint based Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and the Larsen scores, respectively. GEE (generalised estimation equations)-method was used to evaluate longitudinal relationships between the HR-QoL changes and other variables. All NHP dimensions except social isolation improved significantly during the first six months and remained favourable up to 10 years. The most prominent improvements were seen in the dimensions for pain and emotional reaction (p<0.001). In longitudinal evaluation statistically significant associations (p<0.001) were found between the DAS28 and the NHP dimensions for pain, energy and emotional reaction, and between the HAQ and the NHP dimensions for pain, energy and mobility. The extent of joint damage had no statistically significant associations to the six dimensions of the NHP instrument. Early improvements in HR-QoL carried over the ten-year follow-up in patients with recent-onset RA treated with a multidisciplinary strategy including early and active DMARD therapy. HR-QoL changes were longitudinally associated especially with disease activity and function.
    Clinical and experimental rheumatology 01/2011; 29(1):65-71. · 2.66 Impact Factor
  • K Immonen, M Kauppi, M Hakala
    Scandinavian journal of rheumatology 01/2011; 40(3):236-8. · 2.51 Impact Factor
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    ABSTRACT: To assess the incidence, prevalence, and outcome of amyloidosis associated with inflammatory rheumatic diseases. An observational study was performed in the outpatient department of Kainuu Central Hospital from 1993 to 2007. The following criteria were used for the performance of abdominal subcutaneous fat aspiration (ASFA) and/or rectal biopsies: erythrocyte sedimentation rate (ESR) > 40 mm/h at two consecutive visits; and proteinuria (> 0.5 g/day) or serum creatinine > 150 μmol/L. Renal biopsy was performed when there was a high suspicion of amyloidosis in cases with negative findings in the above-mentioned biopsies. In addition, amyloid staining was used routinely for mucosal specimens taken in gastroscopy and colonoscopy. The patients were followed until death or to the end of 2007. New diagnoses of amyloidosis in the consecutive 5-year periods from 1993 onwards numbered 11, 3, and 5, respectively. During the study period, there was a mean annual incidence of amyloidosis of 1.8 [95% confidence interval (CI) 1.1-2.8)/100,000]. At the end of 2007 there were eight subjects with amyloidosis, giving a point prevalence of 12.0/100,000 (95% CI 5.2-23.6). Five patients out of the 19 underwent haemodialysis because of terminal uraemia and three of them also had renal transplantation. Overall, 12 (63%) patients died after a median survival time of 6 (95% CI 4-8) years, one-third from amyloidosis. The 5-year survival rate of the series was 67% (95% CI 41-86). Amyloidosis is rarely encountered today. ASFA or rectal biopsy facilitates its early diagnosis.
    Scandinavian journal of rheumatology 11/2010; 39(6):461-5. · 2.51 Impact Factor
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    ABSTRACT: With the exception of a previous history of pulmonary sarcoidosis, a previously healthy 38-year old man developed a sudden unilateral metatarsal pain and gradually progressing osteoporotic, partly lytic metatarsal bone lesions. The patient received a bisphosphonate treatment. Clinical and radiological situation began to improve during the follow-up observation. The diagnosis was based on clinical picture.
    Duodecim; lääketieteellinen aikakauskirja 01/2010; 126(11):1317-21.
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    ABSTRACT: Infliximab is effective and well tolerated in the treatment of juvenile idiopathic arthritis (JIA). The aim of the present study was to measure circulating levels of inflammatory mediators in patients with JIA during treatment with infliximab. Eight patients with active JIA refractory to standard treatments were treated with infliximab (3-4 mg/kg) at weeks 0, 2 and 6 and thereafter at approximately 6-week intervals up to 24 weeks. All patients (n = 8) responded to the treatment. By 6 weeks of treatment the number of active joints had reduced from 16+/-4 (mean+/-SEM) to 4+/-1 (p<0.01) and C-reactive protein (CRP) levels had fallen from 31+/-8 to 8+/-3 (p<0.001). Infliximab treatment also reduced the serum concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO), and soluble adhesion molecules ICAM-1 (intercellular adhesion molecule-1), and E-selectin. Tumour necrosis factor-alpha (TNFalpha) levels tended to increase while the concentrations of endogenous TNF antagonists (sTNF-RI and sTNF-RII) reduced in most patients during treatment. Infliximab reduced serum levels of IL-6, MPO and soluble adhesion molecules in JIA patients, producing a good clinical response to the treatment.
    Scandinavian Journal of Rheumatology 07/2009; 36(3):189-93. · 2.22 Impact Factor
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    ABSTRACT: To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS). A 96-week open-label extension study, which followed a 12-week double-blind placebo-controlled trial, was designed to provide longterm efficacy and safety data, including radiographic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all, 81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20% (ASAS20) criteria, the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test within-group changes from baseline. The percentage of responders, by ASAS20 criteria, remained relatively constant in patients who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week 96 of the open-label extension); more patients from the placebo group became responders after being switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were injection site reactions (n=30; 37.0%) and headache (n=18; 22.2%), and the most frequent infections were upper respiratory tract infections (n=43; 53.1%) and flu syndrome (n=22; 27.2%). For 2 years, etanercept was clinically effective and well tolerated, with no unexpected safety findings.
    The Journal of Rheumatology 06/2009; 36(6):1256-64. · 3.26 Impact Factor
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    ABSTRACT: To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission. At 11 years, 138 patients were assessed (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/-SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination-DMARD group and the single-DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively. Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single-DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.
    Arthritis & Rheumatology 05/2009; 60(5):1222-31. · 7.48 Impact Factor
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    ABSTRACT: To evaluate the utility of the Stanford Health Assessment Questionnaire (HAQ) in the estimation of loss of productivity due to early rheumatoid arthritis (RA) and to develop a simple model for analysis of the cost-benefit of therapies. In the Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial, 162 patients with recent-onset RA who were available for the workforce were randomized to receive either a combination of three disease-modifying anti-rheumatic drugs (DMARDs) or a single DMARD for 2 years and were followed up for 5 years. No biological drugs were used. Data on sick leave and RA-related disability pensions came from official register records. Loss of productivity was computed by both the human capital approach (HCA) and the friction cost approach (FCA). Functional capacity was assessed by the HAQ at baseline and at 6 months. Over 5 years, mean loss of productivity per year was EUR 8344 by the HCA and EUR 1928 by the FCA. The level of the HAQ index at 6 months, but not the change in HAQ from baseline, determined productivity costs. With the HCA, a monotonous association between annual loss of productivity and the 6-month HAQ was found: EUR 2087 [95% confidence interval (CI) 1340-2903] per one step (0.13) on the HAQ scale from 0 to 1.88. With the FCA, the increase in loss of productivity was cut at the HAQ level of 0.5 to 0.75 (EUR 17 740 in 5 years). The HAQ index at 6 months may serve as a determinant of long-term RA-related indirect costs in economic analyses in early RA.
    Scandinavian journal of rheumatology 01/2009; 38(2):96-103. · 2.51 Impact Factor
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    ABSTRACT: To examine treatment induced changes in health-related quality of life (HR-QoL) in patients with early rheumatoid arthritis (RA). Changes in HR-QoL were assessed by the Nottingham Health Profile (NHP) instrument in 62 consecutive working age patients with recent onset RA with duration of symptoms of less than two years and naive with regard to disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. Treatment-response was assessed by the criteria of the European League against Rheumatism (EULAR; 28-joint score; DAS28) at 6 months. NHP mean scores for pain (p=0.029) and emotional reaction (p=0.035) at baseline were related to EULAR response at 6 months, i.e. non-responders had the poorest baseline HR-QoL scores. When the patients were grouped according to EULAR response at 6 months there was a statistically significant mean linear change to better HR-QoL in NHP energy (p=0.0023), pain (p<0.001) and mobility (p=0.0085) from baseline to 6 months from the lowest to highest treatment-response level. Our results show that good treatment-response as measured by the EULAR response criteria translates into improved HR-QoL dimensions for energy, pain and mobility.
    Clinical and experimental rheumatology 01/2009; 27(1):108-11. · 2.66 Impact Factor

Publication Stats

2k Citations
623.53 Total Impact Points

Institutions

  • 2013
    • Kainuu Central Hospital
      Kjana, Oulu, Finland
  • 2012
    • Päijät-Hämeen Central Hospital
      Lahti, Southern Finland Province, Finland
  • 2007–2012
    • University of Tampere
      • Medical School
      Tampere, Western Finland, Finland
  • 1998–2011
    • Pohjois-Karjalan Sairaanhoito
      Yoensu, Eastern Finland Province, Finland
  • 2004–2010
    • Central Hospital Central Finland
      Jyväskylä, Province of Western Finland, Finland
  • 2008–2009
    • Lapland Central Hospital
      Rovanieni, Lapponia, Finland
  • 1995–2009
    • Oulu University Hospital
      • Department of Physical Medicine and Rehabilitation
      Uleoborg, Oulu, Finland
  • 1986–2008
    • University of Oulu
      • • Department of Clinical Chemistry
      • • Department of Internal Medicine
      • • Department of Medical Microbiology
      Oulu, Oulu, Finland
  • 2006
    • Turku University Hospital
      Turku, Province of Western Finland, Finland
  • 2000–2006
    • University of Turku
      • • Department of Virology
      • • Department of Medical Biochemistry and Genetics
      Turku, Western Finland, Finland
  • 1998–2000
    • Kuopio University Hospital
      • • Department of Medicine
      • • Department of Internal Medicine
      Kuopio, Province of Eastern Finland, Finland
  • 1996
    • Kansai Medical University
      • Department of Orthopaedic Surgery
      Moriguchi, Ōsaka, Japan