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1.  Effects of a progressive aquatic resistance exercise program on the biochemical composition and morphology of cartilage in women with mild knee osteoarthritis: protocol for a randomised controlled trial 
Background
Symptoms associated with osteoarthritis of the knee result in decreased function, loss of working capacity and extensive social and medical costs. There is a need to investigate and develop effective interventions to minimise the impact of and even prevent the progression of osteoarthritis. Aquatic exercise has been shown to be effective at reducing the impact of osteoarthritis. The purpose of this article is to describe the rationale, design and intervention of a study investigating the effect of an aquatic resistance exercise intervention on cartilage in postmenopausal women with mild knee osteoarthritis.
Methods
A minimum of 80 volunteers who meet the inclusion criteria will be recruited from the local population through newspaper advertisements. Following initial assessment volunteers will be randomised into two groups. The intervention group will participate in a progressive aquatic resistance exercise program of 1-hour duration 3 times a week for four months. The control group will be asked to maintain normal care during this period. Primary outcome measure for this study is the biochemical composition of knee cartilage measured using quantitative magnetic resonance imaging; T2 relaxation time and delayed gadolinium-enhanced magnetic resonance imaging techniques. In addition, knee cartilage morphology as regional cartilage thickness will be studied. Secondary outcomes include measures of body composition and bone traits using dual energy x-ray absorptiometry and peripheral quantitative computed tomography, pain, function using questionnaires and physical performance tests and quality of life. Measurements will be performed at baseline, after the 4-month intervention period and at one year follow up.
Discussion
This randomised controlled trial will investigate the effect a progressive aquatic resistance exercise program has on the biochemical composition of cartilage in post-menopausal women with mild knee osteoarthritis. This is the first study to investigate what impact aquatic exercise has on human articular cartilage. In addition it will investigate the effect aquatic exercise has on physical function, pain, bone and body composition and quality of life. The results of this study will help optimise the prescription of aquatic exercise to persons with mild knee osteoarthritis.
Trial Registration
ISRCTN65346593
doi:10.1186/1471-2474-14-82
PMCID: PMC3599473  PMID: 23497162
Osteoarthritis; Quantitative MRI; T2 relaxation time; dGEMRIC; Bone; Aquatic exercise
2.  Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study 
BMC Neurology  2013;13:21.
Backround
Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia.
Methods
158 patients with primary fibromyalgia underwent a neurological examination including bedside sensory testing. They also fulfilled four questionnaires: PainDETECT, Beck depression inventory IA (BDI IA), Fibromyalgia Impact Questionnaire (FIQ) and a self-made questionnaire regarding present pain and pain relieving methods of the patients. The results of the clinical evaluation and questionnaires were then compared.
Results
Clinically verified neuropathic pain was diagnosed in 53/158 [34% (95% Cl: 26 to 41)] patients. The ROC curve achieved a maximum Youden´s index at score of 17 when sensitivity was 0.79 (95% Cl: 0.66 to 0.89) and specificity 0.53 (95% Cl: 0.43 to 0.63). The PainDETECT total score (OR: 1.14 95% Cl: 1.06 to 1.22), FM as the worst current pain (OR: 0.31; 95% 0.16 to 0.62), body mass index (BMI) (OR: 1.05; 95% Cl: 1.00 to 1.11) and the intensity of current pain (OR: 1.20; 95% Cl: 1.01 to 1.41) were significantly associated with the presence of neuropathic pain in univariate analyses.
Conclusion
This study highlights the importance of thorough clinical examination. The Neuropathic pain screening tool PainDETECT is not as useful in patients with fibromyalgia as in patients with uncompromised central pain control.
doi:10.1186/1471-2377-13-21
PMCID: PMC3582578  PMID: 23409793
3.  Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study 
Background
Increased ferritin concentrations are associated with metabolic syndrome (MetS). The association between ferritin as well as hemoglobin level and individual MetS components is unclear. Erythropoietin levels in subjects with MetS have not been determined previously. The aim of this study was to compare serum erythropoietin, ferritin, haptoglobin, hemoglobin, and transferrin receptor (sTFR) levels between subjects with and without MetS and subjects with individual MetS components.
Methods
A population based cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) from five age groups born in Pieksämäki, Finland who were invited to a health check-up in 2004 with no exclusion criteria. Laboratory analyzes of blood samples collected in 2004 were done during year 2010. MetS was defined by National Cholesterol Education Program criteria.
Results
159 (53%) men and 170 (40%) women of study population met MetS criteria. Hemoglobin and ferritin levels as well as erythropoietin and haptoglobin levels were higher in subjects with MetS (p < 0.001, p = 0.018). sTFR level did not differ significantly between subjects with or without MetS. Hemoglobin level was significantly higher in subjects with any of the MetS components (p < 0.001, p = 0.002). Ferritin level was significantly higher in subjects with abdominal obesity or high TG or elevated glucose or low high density cholesterol component (p < 0.001, p = 0.002, p = 0.02). Erythropoietin level was significantly higher in subjects with abdominal obesity component (p = 0.015) but did not differ significantly between subjects with or without other MetS components. Haptoglobin level was significantly higher in subjects with blood pressure or elevated glucose component o MetS (p = 0.028, p = 0.025).
Conclusion
Subjects with MetS have elevated hemoglobin, ferritin, erythropoietin and haptoglobin concentrations. Higher hemoglobin levels are related to all components of MetS. Higher ferritin levels associate with TG, abdominal obesity, elevated glucose or low high density cholesterol. Haptoglobin levels associate with blood pressure or elevated glucose. However, erythropoietin levels are related only with abdominal obesity. Higher serum erythropoietin concentrations may suggest underlying adipose tissue hypoxemia in MetS.
doi:10.1186/1475-2840-11-116
PMCID: PMC3471017  PMID: 23016887
Erythropoietin; Ferritin; Hemoglobin; Metabolic syndrome
4.  Relationships between depressive symptoms and self-reported unintentional injuries: the cross-sectional population–based FIN-D2D survey 
BMC Public Health  2012;12:516.
Background
There is a lack of knowledge on the influence of different levels of physical activity (PA) on unintentional injuries among those with depressive symptoms (DS). The aim of this study was to evaluate the relationship between PA categories and unintentional injuries among participants with and without DS based on a cross-sectional population–based FIN-D2D survey conducted in 2007.
Methods
Out of 4500, 2682 participants (60%) aged 45–74 years attended in this study. The unintentional injuries over the past year were captured in a questionnaire. DS were determined with the Beck Depression Inventory (≥ 10 points) and PA with the International Physical Activity Questionnaire. The statistical significance between DS and unintentional injury categories was evaluated by using t-test, chi-square test, or permutation test, analysis of covariance, or regression models. The factors related to unintentional injuries were estimated by univariate and multivariate logistic regression models.
Results
The proportion of subjects with unintentional injuries was higher among those with DS (17%) compared to those without DS (10%) (age- and gender-adjusted p = 0.023). The median (range) number of activity-loss days after injury was 22 (0–365) in participants with DS and 7 (0–120) in participants without DS ( p = 0.009). The percentage of subjects with unintentional injuries was not significantly different between PA categories in participants with DS and without DS. A stepwise multivariate logistic regression analysis showed that DS, functional ability, and musculoskeletal diseases were related to unintentional injuries.
Conclusions
PA level was not related to unintentional injuries, whereas those with DS had a higher prevalence of unintentional injuries and prolonged activity-loss after injury. These results underline the importance of injury prevention, especially among those who have DS and additional risk factors.
doi:10.1186/1471-2458-12-516
PMCID: PMC3506522  PMID: 22781103
Beck depression inventory; Depressive symptoms; Injury; Physical activity
5.  Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial 
Trials  2012;13:85.
Background
Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people’s drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents’ quality of life and use of health services.
Methods and design
During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months.
The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations.
Discussion
To our knowledge, this is the first large-scale randomized trial exploring whether relatively light intervention, that is, staff training, will have an effect on reducing harmful drugs and improving QOL among institutionalized older people.
Trial registration
ACTRN12611001078943
doi:10.1186/1745-6215-13-85
PMCID: PMC3541247  PMID: 22709731
Inappropriate drugs; Psychotropic drugs; Anticholinergic drugs; Drug-drug interactions; Polypharmacy; Assisted living; Serviced housing; Randomized controlled trial
6.  Assessment of cardiovascular risk in primary health care 
Objective
This study aimed at investigating whether cardiovascular risk factors and their impact on total risk estimation differ between men and women.
Design
Cross-sectional cohort study.
Subjects
Finnish cardiovascular risk subjects (n = 904) without established cardiovascular disease, renal disease, or known diabetes.
Main outcome measures
Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), oral glucose tolerance test, and total cardiovascular risk using SCORE risk charts.
Results
According to the SCORE risk charts, 27.0% (95% CI 23.1–31.2) of the women and 63.1% (95% CI 58.3–67.7) of the men (p < 0.001) were classified as high-risk subjects. Of the women classified as low-risk subjects according to SCORE, 25% had either subclinical peripheral arterial disease or renal insufficiency.
Conclusions
The SCORE system does not take into account cardiovascular risk factors typical in women, and thus underestimates their total cardiovascular risk. Measurement of ABI and eGFR in primary care might improve cardiovascular risk assessment. especially in women.
doi:10.3109/02813432.2012.675564
PMCID: PMC3377999  PMID: 22643155
Ankle-brachial index; cardiovascular risk estimation; gender difference; glucose disorders; renal function
7.  Chronic Gastritis in Dermatitis Herpetiformis: A Controlled Study 
Background and Objective. Previous small studies suggest that chronic atrophic gastritis is common in dermatitis herpetiformis (DH). We here examined the frequency and topography of chronic gastritis in 93 untreated DH subjects and in 186 controls with dyspepsia. Methods. Specimens were drawn from the gastric corpus and antrum and examined for atrophy, intestinal metaplasia, and Helicobacter pylori. Duodenal biopsies were taken. Results. Atrophic corpus gastritis was more frequent in DH than in controls (16.0% and 2.7%, resp., P < 0.001); atrophy in the antrum was rare in both groups (3.2% and 1.1%, P = 0.34). Intestinal metaplasia was present in 13 (14.0%) DH and 12 (6.5%) control patients (P = 0.038) and H. pylori in 17 (18.3%) and 17 (9.3%) (P = 0.028), respectively. Small-bowel villous atrophy was seen in 76% of the DH patients, equally in patients with and without chronic gastritis. One DH patient with atrophic gastritis developed gastric cancer. Conclusion. In DH, chronic atrophic gastritis was common in the corpus, but not in the antrum. H. pylori will partly explain this, but corpus atrophy is suggestive of an autoimmune etiology. Atrophic gastritis may increase the risk of gastric cancer. We advocate performing upper endoscopy with sufficient histologic samples in DH.
doi:10.1155/2012/640630
PMCID: PMC3351085  PMID: 22611420
8.  Association of Depressive Symptoms With Impaired Glucose Regulation, Screen-Detected, and Previously Known Type 2 Diabetes 
Diabetes Care  2010;34(1):71-76.
OBJECTIVE
To study the association between impaired glucose regulation (IGR), screen-detected type 2 diabetes, and previously known diabetes and depressive symptoms.
RESEARCH DESIGN AND METHODS
Altogether, 2,712 participants from three hospital districts in Finland attended a health examination. Cutoff scores ≥10 and ≥16 in the 21-item Beck Depression Inventory (BDI-21) were used for depressive symptoms. The participants were defined as having known diabetes if they reported diabetes. An oral glucose tolerance test was used to detect normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and screen-detected diabetes. The participants were defined as having IGR if they had IFG or IGT.
RESULTS
Prevalence of depressive symptoms, defined as a BDI-21 cutoff score ≥10, was 14.4% for those with NGR, 13.7% for those with IGR, 14.8% for those with screen-detected diabetes, and 26.4% for those with previously known diabetes. The corresponding prevalences for a cutoff score ≥16 were 3.4, 3.4, 4.2, and 7.5%, respectively. Compared with NGR and adjusted for demographic, lifestyle, and biological factors, the odds ratios for IGR, screen-detected diabetes, and previously known diabetes were 0.91 (95% CI 0.69–1.20), 0.70 (0.45–1.08), and 1.35 (0.84–2.15), respectively, for a cutoff score ≥10. For a cutoff score ≥16, the corresponding odds ratios were 1.05 (0.62–1.76), 0.87 (0.40–1.90), and 1.56 (0.69–3.50), respectively.
CONCLUSIONS
Participants with diagnosed diabetes had a higher prevalence of depressive symptoms than participants with NGR, IGR, and previously unknown diabetes. When potential confounding factors were included in the analysis, previously known diabetes was not significantly associated with depressive symptoms.
doi:10.2337/dc10-1044
PMCID: PMC3005462  PMID: 20929992
9.  Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis 
Background
The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis.
Methods
Adalimumab was initiated in 94 patients with juvenile idiopathic arthritis to treat active arthritis and/or active associated uveitis. In 18 patients, therapy was discontinued after a short period because of inefficacy or side effects. The activity of uveitis (using Standardized Uveitis Nomenclature [SUN] criteria and clinical examination) and arthritis (number of swollen or active joints) was evaluated at the start and at end of the study.
Results
At the end of the study, uveitis was under good clinical control in two thirds of 54 patients (31% did not need any local treatment and 35% used only 1–2 corticosteroid drops a day), and one third had active uveitis (at least three corticosteroid drops a day). According to SUN criteria, adalimumab treatment for uveitis showed improved activity (a two-fold decrease in uveitis activity) in 28% of patients, with a moderate response in 16 patients, no change in a further 16 patients, and worsening activity (a two-fold increase in uveitis activity) in 13% of patients. The overall proportion of patients with active arthritis decreased. At the beginning of the study, 69% of patients with uveitis had more than two active joints, and at the end of the study only 27% had active joint disease. In 27 patients with juvenile idiopathic arthritis without uveitis on adalimumab, the number of active joints decreased from 93% to 59%. Systemic corticosteroid treatment could be stopped in 22% of patients with uveitis and in 11% of those without uveitis. Most of the patients had received methotrexate, other immunosuppressive therapy, or other biological drugs before initiating adalimumab.
Conclusion
Adalimumab is a valuable option in the treatment of uveitis associated with active juvenile idiopathic arthritis.
doi:10.2147/OPTH.S23646
PMCID: PMC3198418  PMID: 22034564
adalimumab; juvenile idiopathic arthritis; uveitis
10.  QUEST‐RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries 
Annals of the Rheumatic Diseases  2007;66(11):1491-1496.
Objective
To conduct a cross‐sectional review of non‐selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA.
Methods
The review included current disease activity using data from clinical assessment and a patient self‐report questionnaire, which was translated into each language. Data on demographic, disease and treatment‐related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28‐joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries.
Results
Between January 2005 and October 2006, the QUEST‐RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 ⩽3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1.
Conclusions
This international multicentre cross‐sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005–6 including countries that are infrequently involved in clinical research projects.
doi:10.1136/ard.2006.069252
PMCID: PMC2111618  PMID: 17412740
11.  Exercise rehabilitation on home-dwelling patients with Alzheimer's disease - a randomized, controlled trial. Study protocol 
Trials  2010;11:92.
Background
Besides cognitive decline, Alzheimer's disease (AD) leads to physical disability, need for help and permanent institutional care. The trials investigating effects of exercise rehabilitation on physical functioning of home-dwelling older dementia patients are still scarce. The aim of this study is to investigate the effectiveness of intensive exercise rehabilitation lasting for one year on mobility and physical functioning of home-dwelling patients with AD.
Methods
During years 2008-2010, patients with AD (n = 210) living with their spousal caregiver in community are recruited using central AD registers in Finland, and they are offered exercise rehabilitation lasting for one year. The patients are randomized into three arms: 1) tailored home-based exercise twice weekly 2) group-based exercise twice weekly in rehabilitation center 3) control group with usual care and information of exercise and nutrition. Main outcome measures will be Guralnik's mobility and balance tests and FIM-test to assess physical functioning. Secondary measures will be cognition, neuropsychiatric symptoms according to the Neuropsychiatric Inventory, caregivers' burden, depression and health-related quality of life (RAND-36). Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two year follow-up.
Discussion
To our knowledge this is the first large scale trial exploring whether home-dwelling patients with AD will benefit from intense and long-lasting exercise rehabilitation in respect to their mobility and physical functioning. It will also provide data on cost-effectiveness of the intervention.
Trial registration
ACTRN12608000037303
doi:10.1186/1745-6215-11-92
PMCID: PMC2978202  PMID: 20925948
13.  Prevalence of neck pain in subjects with metabolic syndrome - a cross-sectional population-based study 
Background
Metabolic syndrome (MetS) is increasingly common. Obesity has been suggested to associate with neck pain but prevalence of neck pain in subjects with MetS has not been studied. Aim of this study was to analyse the association between MetS and neck pain.
Methods
The study population consisted of 1294 middle-aged subjects in Pieksämäki, Finland. A total of 399 males and 500 females participated (69%). The mean age of both males and females was 46 years. Clinical and biochemical measurements were taken. The participants filled out a standard questionnaire. Psychological distress was assessed with the 12-item General Health Questionnaire (GHQ-12). Neck pain was defined as neck pain perceived daily. MetS was defined using National Cholesterol Education Program (NCEP) criteria. Statistical comparisons between the groups were performed using a bootstrap-type t-test or Chi-Square test. Risk ratios of having neck pain were calculated using generalised linear models with age, smoking, alcohol use, exercise and GHQ-12 score as covariates.
Results
The prevalence of MetS was 33% in males and 29% in females. Neck pain was present in 11% (N = 42) of males and 19% (N = 93) of females (P < 0.001). The prevalence of neck pain was 7.9% (95% CI, 4.9% to 12%) among male subjects without MetS and 16% (95% CI, 10% to 23%) among those with MetS. The respective proportions among females were 16% (95% CI, 12% to 20%) and 25% (95% CI, 18% to 33%). The multivariate analysis showed an increased risk of neck pain in males with MetS (RR 2.1, 95% CI, 1.2 to 3.7, P = 0.010) and in females with MetS (RR 1.5, 95% CI, 1.0 to 2.1, P = 0.040).
Conclusions
MetS was associated with neck pain. This association was stronger in males, but the prevalence of neck pain was higher in females. Prospective studies should explore the potential causal association between neck pain and MetS and the potential common background factors of neck pain and MetS.
doi:10.1186/1471-2474-11-171
PMCID: PMC2918543  PMID: 20670458
14.  Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial 
Arthritis Research & Therapy  2010;12(3):R122.
Introduction
Early treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs (DMARDs) or a single DMARD.
Methods
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 (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug-treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years.
Results
Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P = 0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years.
Conclusions
Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy.
Trial registration
Current Controlled Trials ISRCTN18445519.
doi:10.1186/ar3060
PMCID: PMC2911916  PMID: 20576092
15.  Effect of neck strength training on health-related quality of life in females with chronic neck pain: a randomized controlled 1-year follow-up study 
Background
Chronic neck pain is a common condition associated not only with a decrease in neck muscle strength, but also with decrease in health-related quality of life (HRQoL). While neck strength training has been shown to be effective in improving neck muscle strength and reducing neck pain, HRQoL among patients with neck pain has been reported as an outcome in only two short-term exercise intervention studies. Thus, reports on the influence of a long-term neck strength training intervention on HRQoL among patients with chronic neck pain have been lacking. This study reports the effect of one-year neck strength training on HRQoL in females with chronic neck pain.
Methods
One hundred eighty female office workers, 25 to 53 years of age, with chronic neck pain were randomized to a strength training group (STG, n = 60), endurance training group (ETG, n = 60) or control group (CG, n = 60). The STG performed high-intensity isometric neck strengthening exercises with an elastic band while the ETG performed lighter dynamic neck muscle training. The CG received a single session of guidance on stretching exercises. HRQoL was assessed using the generic 15D questionnaire at baseline and after 12 months. Statistical comparisons among the groups were performed using bootstrap-type analysis of covariance (ANCOVA) with baseline values as covariates. Effect sizes were calculated using the Cohen method for paired samples.
Results
Training led to statistically significant improvement in the 15D total scores for both training groups, whereas no changes occurred for the control group (P = 0.012, between groups). The STG improved significantly in five of 15 dimensions, while the ETG improved significantly in two dimensions. Effect size (and 95% confidence intervals) for the 15D total score was 0.39 (0.13 to 0.72) for the STG, 0.37 (0.08 to 0.67) for the ETG, and -0.06 (-0.25 to 0.15) for the CG.
Conclusions
One year of either strength or endurance training seemed to moderately enhance the HRQoL. Neck and upper body training can be recommended to improve HRQoL of females with neck pain if they are motivated for long-term regular exercise.
Trial Registration
ClinicalTrials.gov NCT01057836
doi:10.1186/1477-7525-8-48
PMCID: PMC2877013  PMID: 20465854
16.  Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study 
Introduction
Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries.
Methods
The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses.
Results
At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score.
Conclusions
Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.
doi:10.1186/ar2951
PMCID: PMC2888189  PMID: 20226018
17.  Stable occurrence of knee and hip total joint replacement in Central Finland between 1986 and 2003: an indication of improved long‐term outcomes of rheumatoid arthritis 
Annals of the Rheumatic Diseases  2006;66(3):341-344.
Background
Total joint replacement (TJR) surgery is an important severe long‐term outcome of rheumatoid arthritis, but relatively little is known about changes of its incidence in patients with rheumatoid arthritis over the past two decades.
Methods
A population‐based, retrospective, incidence case review was conducted to analyse the frequency of primary TJR surgery of the knee and hip in all patients, and specifically in patients with rheumatoid arthritis in Central Finland between 1986 and 2003. Patients with TJR surgery of the knee and hip were identified in hospital databases over the 18‐year period. Age‐standardised incidence rate ratios for the primary TJR of the knee and hip were calculated, stratified to sex and diagnosis, with 1986 as the reference value.
Results
In patients without rheumatoid arthritis the age‐adjusted incidence rate ratios (with 95% CI) for TJR of the knee increased 9.8‐fold from 1986 to 2003 in women and men, and for TJR of the hip 1.8‐fold in women and 2‐fold in men. By contrast, no meaningful change was seen over this period, in age‐adjusted incidence rate ratios for TJR of the knee or hip in patients with rheumatoid arthritis, ranging from 0.7 to 1.2 in 2003 compared with 1986.
Conclusion
The prevalence of TJR surgery has increased 2–10‐fold in patients without rheumatoid arthritis patients, associated with an ageing population, but has not increased in patients with rheumatoid arthritis between 1986 and 2003. These data are consistent with emerging evidence that long‐term outcomes of rheumatoid arthritis have improved substantially, even before the availability of biological agents.
doi:10.1136/ard.2006.057067
PMCID: PMC1855996  PMID: 17068067
18.  Gender-specific association of psychological distress with cardiovascular risk scores 
Objective
To examine the gender differences in the association of psychological distress with cardiovascular disease (CVD) risk scores using two different CVD risk assessment models.
Design and setting
A cross-sectional, population-based study from 1997 to 1998 in Pieksämäki, Finland.
Subjects
A population sample of 899 (399 male and 500 female) middle-aged subjects.
Main outcome measures
The 10-year risk for CVD events was calculated using the European SCORE model and the Framingham CVD risk prediction model. Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12). Study subjects were allocated into three groups according to their global GHQ-12 -scores: 0 points, 1–2 points, and 3–12 points.
Results
Psychological distress was associated with higher mean CVD risk scores in men. Men in the highest GHQ group (3–12 points) had significantly higher mean European CVD risk score (3.6 [SD 3.3]) compared with men in the lowest group (0 points) (2.5 [SD 2.6]), the difference being 1.1 (95% CI 0.4 to 1.9). The p-value for linearity between the three GHQ groups was 0.003. The Framingham CVD risk prediction model yielded similar results: 15.7 (SD 10.2) vs. 12.3 (SD 9.6), the difference 3.4 (95% CI 1.0 to 6.0) and p-value for linearity 0.008. No significant association was observed in women.
Conclusion
A gender-specific association was found betwen psychological distress and cardiovascular risk scores. These results highlight the importance of identifying men with psychological distress when assessing CVD risk.
doi:10.3109/02813431003648131
PMCID: PMC3440612  PMID: 20331387
Cardiovascular disease; Framingham; gender difference; general health questionnaire; psychological distress; SCORE
19.  Milk Products Containing Bioactive Tripeptides Have an Antihypertensive Effect in Double Transgenic Rats (dTGR) Harbouring Human Renin and Human Angiotensinogen Genes 
Tripeptides isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) act as ACE inhibitors in vitro. Double transgenic rats (dTGR) harbouring human renin and human angiotensinogen genes develop malignant hypertension due to increased angiotensin II formation. The present study was aimed to evaluate possible antihypertensive effect of IPP and VPP in this severe model. Four-week-old dTGR were randomized in three groups to receive: (1) water (control), (2) fermented milk containing IPP and VPP, and (3) IPP and VPP dissolved in water for three weeks. Fermented milk, but not peptides in water, attenuated the development of hypertension in dTGR by 19 mmHg versus the control group (P = .023). In vitro vascular function tests showed that high concentrations of the peptides evinced ACE inhibitory properties. In other hypertension related variables, no significant differences between the treatment groups were found. In conclusion, fermented milk product containing IPP and VPP prevents development of malignant hypertension in an animal model.
doi:10.1155/2010/287030
PMCID: PMC2915664  PMID: 20721338
20.  Gender Differences Relating to Metabolic Syndrome and Proinflammation in Finnish Subjects with Elevated Blood Pressure 
Mediators of Inflammation  2009;2009:959281.
Fasting insulin, adiponectin, high-sensitivity C-reactive protein (hs-CRP), and interleukin-1 receptor antagonist (IL-1Ra) were determined in 278 men and 273 women with blood pressure ≥130 and/or ≥85 mmHg and/or with antihypertensive medication. Metabolic syndrome (MetS) with the National Cholesterol Education Program (NCEP) criteria was observed in 35% of men and 34% of women. Men with MetS had lower hs-CRP and IL-1Ra than women. The absolute gender difference in adiponectin was smaller and those in IL-1Ra and hs-CRP were greater in subjects with MetS compared to those without. After adjustment with body mass index the association between insulin and the odd's ratio (OR) for MetS remained significant in both genders, in females also the association between the OR for MetS and adiponectin. There are gender differences in subjects with elevated blood pressure and MetS with respect to inflammatory markers and the relationship between adiponectin levels and MetS.
doi:10.1155/2009/959281
PMCID: PMC2730476  PMID: 19707530
21.  Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2 
Emerging Infectious Diseases  2009;15(7):1119-1122.
We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996–2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2–5 days after symptom onset.
doi:10.3201/eid1507.080716
PMCID: PMC2744243  PMID: 19624935
Meningitis; aseptic; herpes simplex virus type 2; prevalence; neurologic manifestations; viruses; Finland; dispatch
22.  Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study 
Introduction
Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA).
Methods
The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents.
Results
Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies.
Conclusions
In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.
doi:10.1186/ar2591
PMCID: PMC2688237  PMID: 19144159
23.  Proinflammation and Hypertension: A Population-Based Study 
Mediators of Inflammation  2008;2008:619704.
There is evidence that proinflammation may be linked to the development of hypertension (HT). We examined the association of both the interleukin-1 beta (IL-1β) and the interleukin 1-receptor antagonist (IL-1ra) with future blood pressure (BP) and HT occurrence (BP ≥ 140/90 mmHg, or antihypertensive drug) in a population-based prospective study. Our study consisted of 396 (147 men and 249 women) middle-aged, baseline apparently healthy, normotensive subjects participating in a 6.5-year follow-up study. Subjects with high-sensitivity CRP (hs-CRP) < 10 mg/L were excluded at the initial visit. At follow-up, the occurrence of HT was 32%. The levels of baseline IL-1β and IL-1ra were significantly higher for subjects who developed HT during the follow-up than for those who did not (IL-1β; 0.67 ± 0.62 pg/mL versus 0.56 ± 0.32 pg/mL, P = .020 and IL-1ra; 184 ± 132 pg/mL versus 154 ± 89 pg/mL, P = .007). After adjustments for age, follow-up time, sex, baseline systolic BP, and BMI, our results confirm a statistically significant (P = .036) linear association between the quartiles of IL-1β and change of systolic BP during the study. After adjustments for age, follow-up time, sex, and BMI, our results also show a linear association between incident HT and the quartiles of IL-1ra. (P = .026). These results provide evidence that proinflammation may precede BP elevation and HT.
doi:10.1155/2008/619704
PMCID: PMC2612739  PMID: 19125204
24.  Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults 
AIM: To evaluate the effects of three potentially anti-inflammatory probiotic bacteria from three different genera on immune variables in healthy adults in a clinical setting based on previous in vitro characterization of cytokine responses.
METHODS: A total of 62 volunteers participated in this randomized, double-blind and placebo-controlled parallel group intervention study. The volunteers were randomized to receive a milk-based drink containing either Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis ssp. lactis Bb12 (Bb12), or Propionibacterium freudenreichii ssp. shermanii JS (PJS) or a placebo drink for 3 wk. Venous blood and saliva samples were taken at baseline and on d 1, 7 and 21. Fecal samples were collected at baseline and at the end of intervention.
RESULTS: The serum hsCRP expressed as the median AUC0-21 (minus baseline) was 0.018 mg/L in the placebo group, -0.240 mg/L in the LGG group, 0.090 mg/L in the Bb12 group and -0.085 mg/L in the PJS group (P = 0.014). In vitro production of TNF-α from in vitro cultured peripheral blood mononuclear cells (PBMC) was significantly lower in subjects receiving LGG vs placebo. IL-2 production from PBMC in the Bb12 group was significantly lower compared with the other groups.
CONCLUSION: In conclusion, probiotic bacteria have strain-specific anti-inflammatory effects in healthy adults.
doi:10.3748/wjg.14.2029
PMCID: PMC2701523  PMID: 18395902
Probiotic; Highly sensitive C-reactive protein; Cytokine; Inflammation; Immune response; Mononuclear cells
25.  Changes in the total Oswestry Index and its ten items in females and males pre- and post-surgery for lumbar disc herniation: a 1-year follow-up 
European Spine Journal  2006;16(3):347-352.
To study the characteristics and changes in the total Oswestry Disability Index (ODI) and in its ten component items in female and male patients pre- and post-surgery for lumbar disc herniation. Ninety-eight patients [mean (SD) age 43 (13), 61% males] undergoing lumbar disc herniation surgery were selected for this clinical 12-month follow-up. Subjective disability and back and leg pain were assessed by ODI version 1.0 and the visual analog scale. Pre-operatively females had a significantly higher mean (SD) total ODI [59(3)] than males [51(2)] (P = 0.030). Females were more disabled in the walking, sex life, social life and travelling items of the ODI compared to males. The total Oswestry decreased by 38 (95% CI − 44 to − 31) in females and by 34 (− 39 to − 30) in males at the 1-year follow-up. Most of the improvement (88% in females and 80% in males) occurred during the first 6 weeks; thereafter the changes were minor. In males the changes were greatest in pain, social life and travelling and in females in walking, social life and travelling. Internal consistency value of ODI was 0.88 (95% CI 0.82–0.91). Item analysis of the ODI showed that all the items except pain had high corrected item correlation. As recovery following lumbar disc surgery occurred to a great extent during the first 6 weeks, the early post-operative outcome appears to be quite a reliable indicator of the overall post-operative outcome over the 1-year follow-up. The ODI proved to capture a wide range of disability in these lumbar disc surgery patients, thereby supporting the future use of the index. The “pain intensity” component, which collects data on the use of painkillers in version 1.0 of the ODI did not support the item structure of the index in this study. The use of ODI version 2.0 might remove this problem.
doi:10.1007/s00586-006-0187-8
PMCID: PMC2200704  PMID: 16912888
Disability; Lumbar disc herniation; Surgery; Pain

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