Objective: The objective of this study was to evaluate an extended role for the physiotherapist in primary care in referring patients to plain X-ray. Methods: This prospective cohort study was set in a single region in Sweden. It included 20 physiotherapists who were educated in a 1-day training in performing referral to X-ray, along with 107 patients with musculoskeletal disorders who were referred to X-ray. We evaluated referral quality and patient and physiotherapist satisfaction and calculated healthcare and patient costs. Results: All referrals fulfilled the basic requirements of quality, and 78% were classified as good, fulfilling all criteria. Both patients and physiotherapists were satisfied with the extended role for the physiotherapist that decreased the waiting time to diagnosis and to adequate treatment. Costs were reduced for patients (by _53/patient) and healthcare (by _6286.2/107 patients). The cost to visit a physician was twice that of a physiotherapist visit. Conclusions: An extended role for physiotherapists in primary care in referring patients to X-ray was effective and safe for patients and reduced costs for patients and for healthcare. Physiotherapists in primary care were able to refer patients to X-ray after a 1 day of training, and the extended role freed up 45 min of physician time for each patient with a musculoskeletal disorder in need of an X-ray.
Objective: The objective of this study was to evaluate an extended role for the physiotherapist in primary care in referring patients to plain X-ray. Methods: This prospective cohort study was set in a single region in Sweden. It included 20 physiotherapists who were educated in a 1-day training in performing referral to X-ray, along with 107 patients with musculoskeletal disorders who were referred to X-ray. We evaluated referral quality and patient and physiotherapist satisfaction and calculated healthcare and patient costs. Results: All referrals fulfilled the basic requirements of quality, and 78% were classified as good, fulfilling all criteria. Both patients and physiotherapists were satisfied with the extended role for the physiotherapist that decreased the waiting time to diagnosis and to adequate treatment. Costs were reduced for patients (by _53/patient) and healthcare (by _6286.2/107 patients). The cost to visit a physician was twice that of a physiotherapist visit. Conclusions: An extended role for physiotherapists in primary care in referring patients to X-ray was effective and safe for patients and reduced costs for patients and for healthcare. Physiotherapists in primary care were able to refer patients to X-ray after a 1 day of training, and the extended role freed up 45 min of physician time for each patient with a musculoskeletal disorder in need of an X-ray.
Up to 90% of people with neurological deficits following whiplash injury report chronic symptoms. A recent unique study of neck-specific exercise showed positive results (post-intervention at 12 weeks), regarding arm pain and neurological deficits in people with chronic whiplash associated disorders (WAD). This 1-year follow-up of that randomised controlled study with assessor blinding aimed to examine whether neck-specific exercise with (NSEB) or without (NSE) a behavioural approach has long-term benefits over physical activity prescription (PPA) regarding arm pain and neurological deficits (n=171). Interventions were: NSE, NSEB, or PPA. Follow-up of arm pain, paraesthesia bothersomeness (questionnaires) and clinical neurological tests were performed after 3, 6 and 12 months and analysed with Linear Mixed Models and General Estimating Equations. The NSE and/or NSEB groups reported significantly less pain and paraesthesia bothersomeness as well as higher odds of normal key muscle arm strength and of normal upper limb neural tension over the year (all p<0.03), compared with PPA. In conclusion, results suggest that neck-specific exercise with or without a behavioural approach may have persisting long term benefits over PPA regarding arm pain and clinical signs associated with neurological deficits in chronic WAD. ; Funding Agencies|Swedish government through the REHSAM Foundation [RS2010/009]; Swedish Research CouncilSwedish Research Council [521-2014-2982]; County Council of ostergotland [LIO-533041, LIO-439541, LIO-197631, LIO-276151, LIO-354241]; Centre for Clinical Research Sormland at Uppsala University [DLL-553281, DLL-465071, DLL-221851, DLL-112241, DLL-376711]; Medical Research Council of Southeast Sweden [FORSS-472691, FORSS-302601, FORSS-384421]; Uppsala-orebro Regional Research Council [RFR-384651, RFR-150591, RFR-297301, RFR-215571]; Linkoping University, Sweden; Linkoping University; regional Centre for Clinical Research [LIO-533041, LIO-439541, LIO-197631, LIO-276151, LIO-354241]
PURPOSE: The aim was to evaluate whether neck-specific exercise, with (NSEB) or without (NSE) a behavioural approach, improves health-related quality of life (HRQoL) compared to physical activity prescription (PPA) in chronic whiplash-associated disorders (WAD) grades 2 and 3. A secondary aim was to identify factors associated with HRQoL and HRQoL improvement following exercise interventions. METHODS: This is a secondary analysis of a multicentre randomized clinical trial. Participants (n = 216) with chronic WAD grades 2 and 3 were randomized to 12 weeks of PPA or physiotherapist-led NSE or NSEB. The EQ-5D 3L/EQ-VAS and SF-36v2 physical (PCS) and mental (MCS) component summaries were collected together with several neck-related and psychosocial outcomes at baseline, after 3, 6 and 12 months, and were analysed with linear mixed models (all time points) and multivariate linear regressions (baseline, 6 months). RESULTS: NSE/NSEB resulted in better outcomes than PPA (EQ-VAS and SF-36 PCS, both groups, p < 0.01) but not in a higher EQ-5D score. Improvement over time was seen in EQ-5D/EQ-VAS for the NSEB group (p < 0.01), and for NSE/NSEB as measured with the PCS (p < 0.01). Factors associated with baseline HRQoL and change to 6 months in HRQoL (R2 = 0.38-0.59) were both neck-related and psychosocial (e.g. depression, work ability). CONCLUSION: Neck-specific exercise, particularly with a behavioural approach, may have a more positive impact on HRQoL than physical activity prescription in chronic WAD grades 2 and 3. HRQoL is however complex, and other factors also need to be considered. Factors associated with HRQL and improvements in HRQoL following exercise are multidimensional. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, No. NCT01528579. ; Funding agencies: Vetenskapsradet [521-2014-2982]; Swedish Government through the REHSAM Foundation [RS2010/009]; Swedish Research Council; County Council of Ostergotland [LIO-533041, LIO-439541, LIO-197631, IO-276151, LIO-354241]; Centre for Clinical Research Sormland at
Chronic pain and disability is common in whiplash-associated disorders (WAD), leading to personal suffering, sick leave, and social cost. The cervical spine is heavily dependent on muscular support and whiplash injury can cause damage to the neck muscles, but diagnostic tools to measure neck muscle impairment and evaluate exercise interventions are lacking. Therefore, the present study investigated ventral neck muscle interactions in 26 individuals with chronic WAD randomized to neck-specific exercise (NSE) or remaining on a waiting list (WL) in 3 months. We performed real-time, non-invasive ultrasound measurements with speckle tracking analysis and calculated the deformation area and deformation rate in three ventral neck muscles. Multivariate statistics were used to analyse interactions between the muscles. After 3 months of NSE, significant improvements were observed in neck muscle interactions and pain intensity in the NSE group compared to the WL group. Thus, this study demonstrates that non-invasive ultrasound can be a diagnostic tool for muscle impairment and used to evaluate exercise interventions in WAD and stands to make a breakthrough for better management in chronic WAD. ; Funding Agencies|Swedish government; Swedish Social Insurance Agency through the REHSAM foundation; Swedish Research Council; Centre for Clinical Research Sormland at Uppsala University Sweden; Uppsala-Orebro Regional Research Council Sweden
Background: Almost 40% of individuals with chronic whiplash-associated disorders (WAD) report headache after 5 years, making it one of the most common persistent symptoms besides neck pain, but randomized treatment studies are lacking. This study aimed to evaluate the effect of 3 different exercise approaches on headache in chronic WAD grades 2 and 3, and to identify potential factors associated with such headache, and whether they differ depending on 3 different aspects of such headache (current headache, maximum headache, or headache bothersomeness).Methods: This was an analysis of a randomized clinical trial of people with chronic WAD and headache (n = 188), who were randomized to either 12 weeks of neck-specific exercise without (NSE) or with a behavioral approach (NSEB) or physical activity prescription (PPA). Data were collected at baseline and at 3, 6, and 12 months. Physical and psychosocial factors were tested for association with headache. Multivariate regression models and linear mixed models were used.Results: The NSE/NSEB groups reported reduced headache both over time and compared to PPA. Up to 51% (NSE) and 61% (NSEB) reported at least 50% reduction in their headache at 12 months. The PPA group was not improved over time. Neck pain and dizziness were associated with headache regardless of aspect of headache. The only associated psychosocial factor was anxiety, which was associated with headache bothersomeness. Other factors were mainly physical, and up to 51% of the variance was explained.Conclusion: Headache in chronic WAD, may be reduced with neck-specific exercise with or without a behavioral approach. Chronic headache was associated with neck pain and dizziness regardless of aspect tested. Other factors associated with headache in chronic WAD were mainly physical rather than psychosocial.Trial registration number: Clinical Trials.gov, no: NCT015285 ; Funding Agencies|Swedish Government through the REHSAM Foundation; Swedish Research CouncilSwedish Research Council; Regional Centre for Clinical Research; Centre for Clinical Research Sormland at Uppsala University; Medical Research Council of Southeast Sweden; Uppsala-Orebro Regional Research Council; Ostergotland County Council
Objective: To explore whether neck-specific exercise, with or without a behavioural approach, has benefits after 1 and 2 years compared with prescribed physical activity regarding pain, self-rated functioning/disability, and self-efficacy in management of chronic whiplash. Design: Follow-up of a randomized, assessor blinded, clinical trial. Patients: A total of 216 volunteers with chronic whiplash associated disorders, grades 2 or 3. Methods: Participants were randomized to 1 of 3 exercise interventions: neck-specific exercise with or without a behavioural approach, or physical activity prescription. Self-rated pain (visual analogue scale), disability/functioning (Neck Disability Index/Patient Specific Functional Scale) and self-efficacy (Self-Efficacy Scale) were evaluated after 1 and 2 years. Results: Both neck-specific exercise groups maintained more improvement regarding disability/functioning than the prescribed physical activity group at both time-points (p <= 0.02). At 1 year, 61% of subjects in the neck-specific group reported at least 50% pain reduction, compared with 26% of those in the physical activity prescription group (p < 0.001), but at 2 years the difference was not significant. Conclusion: After 1-2 years, participants with chronic whiplash who were randomized to neck-specific exercise, with or without a behavioural approach, remained more improved than participants who were prescribed general physical activity. ; Funding Agencies|Swedish government through the REHSAM Foundation; Swedish Research Council; regional Center for Clinical Research; County Council of Ostergotland; Centre for Clinical Research Sormland at Uppsala University; Medical Research Council of Southeast Sweden; Uppsala-Orebro Regional Research Council, Sweden
Objective The aim of this study was to investigate and compare the mechanical responses of dorsal neck muscles in individuals with whiplash-associated disorders (WAD) versus healthy individuals. Design This study included 36 individuals with WAD (26 women and 10 men) and 36 healthy controls (26 women and 10 men). Ultrasound imaging with speckle tracking was used to measure deformation and deformation rate in five dorsal neck muscles during a neck extension task. Results Compared with controls, individuals with WAD showed higher deformations of the semispinalis cervicis (P = 0.02) and multifidus (P = 0.002) muscles and higher deformation rates (P = 0.03 and 0.0001, respectively). Among individuals with WAD, multifidus deformation and deformation rate were significantly associated with pain, disability, and fatigue (r = 0.31-0.46, P = 0.0001-0.01). Conclusions These findings indicate that the mechanical responses of the deep dorsal neck muscles differ between individuals with WAD and healthy controls, possibly reflecting that these muscles use altered strategies while performing a neck extension task. This finding provides new insight into neck muscles pathology in patients with chronic WAD and may help improve rehabilitation programs. To Claim CME Credits Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME Objectives Upon completion of this article, the reader should be able to: (1) Summarize the mechanical responses of dorsal neck muscles during loading of the neck muscles via an extension task in individuals with chronic whiplash associated disorders and healthy volunteers; (2) Differentiate mechanical responses between five dorsal neck muscles while loading the neck via an extension task; and (3) Describe the relationships between the mechanical responses of the dorsal neck muscles with the patients perception of neck pain, disability, and fatigue. Level Advanced Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. ; Funding Agencies|Swedish government; Swedish Social Insurance Agency through the REHSAM Foundation [RS2010/009]; Uppsala Orebro Regional Research Council Sweden; Swedish Research Council, Centre for Clinical Research Sormland at Uppsala University Sweden
BackgroundSome studies support the prescription of exercise for people with whiplash-associated disorders (WAD); however, the response is highly variable. Further research is necessary to identify factors which predict response. MethodsThis is a secondary analysis of a randomized, multicentre controlled clinical trial of 202 volunteers with chronic WAD (grades 2 and 3). They received either neck-specific exercise with, or without a behavioural approach, or prescription of physical activity for 12weeks. Treatment response, defined as a clinical important reduction in pain or disability, was registered after 3 and 12months, and factors associated with treatment response were explored using logistic regression. ResultsParticipation in the neck-specific exercise group was the only significant factor associated with both neck pain and neck disability reduction both at 3 and 12months. Patients in this group had up to 5.3 times higher odds of disability reduction and 3.9 times higher odds of pain reduction compared to those in the physical activity group. Different baseline features were identified as predictors of response depending on the time point examined and the outcome measure selected (pain vs. disability). ConclusionFactors associated with treatment response after exercise interventions differ in the short and long term and differ depending on whether neck pain or disability is considered as the primary outcome. Participation in a neck-specific exercise intervention, in contrast to general physical activity, was the only factor that consistently indicated higher odds of treatment success. These results support the prescription of neck-specific exercise for individuals with chronic WAD. ; Funding Agencies|Swedish government through the REH-SAM Foundation; Clinical Research of Ostergotland Council; Clinical Research of Sormland County Council; Medical Research Council of Southeast Sweden; Uppsala-O rebro Regional Research Council Sweden; Swedish Research Council
Objectives: The aim of this study was to compare the effect on self-rated pain, disability, and self-efficacy of 3 interventions for the management of chronic whiplash-associated disorders: physiotherapist-led neck-specific exercise (NSE), physiotherapist-led NSE with the addition of a behavioral approach, or Prescription of Physical Activity (PPA). Materials and Methods: A total of 216 volunteers with chronic whiplash-associated disorders participated in this randomized, assessor blinded, clinical trial of 3 exercise interventions. Self-rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck Disability Index), and self-efficacy (Self-Efficacy Scale) were evaluated at baseline and at 3 and 6 months. Results: The proportion of patients reaching substantial reduction in pain bothersomness (at least 50% reduction) was more evident (P less than 0.01) in the 2 NSE groups (29% to 48%) compared with the PPA group (5%) at 3 months. At 6 months 39% to 44% of the patients in the 2 neck-specific groups and 28% in the PPA group reported substantial pain reduction. Reduction of disability was also larger in the 2 neck-specific exercise groups at both 3 and 6 months (P less than 0.02). Self-efficacy was only improved in the NSE group without a behavioral approach (P = 0.02). However, there were no significant differences in any outcomes between the 2 physiotherapist-led NSE groups. Discussion: NSE resulted in superior outcomes compared with PPA in this study, but the observed benefits of adding a behavioral approach to the implementation of exercise in this study were inconclusive. ; Funding Agencies|Swedish government through the Swedish Research Council; Swedish Social Insurance Agency through the REHSAM foundation Stockholm, Sweden; Sormland, Sweden County Council; Uppsala, Sweden County Council; Swedish Research Council, Stockholm, Sweden; Health Practitioner Research Fellowship (Queensland Health); Health Practitioner Research Fellowship (University of Queensland, Brisbane, Australia [NHMRC CCRE Spinal Pain, Injury and Health])
Background: Dizziness and unsteadiness are common symptoms following a whiplash injury. Objective: To compare the effect of 3 exercise programs on balance, dizziness, proprioception and pain in patients with chronic whiplash complaining of dizziness. Design: A sub-analysis of a randomized study. Methods: One hundred and forty subjects were randomized to either a physiotherapist-guided neck-specific exercise (NSE), physiotherapist-guided neck-specific exercise, with a behavioural approach (NSEB) or prescription of general physical activity (PPA) group. Pre intervention, 3, 6 and 12 months post baseline they completed the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ), Visual Analogue Scales (VAS) for, dizziness at rest and during activity and physical measures (static and dynamic clinical balance tests and head repositioning accuracy (HRA)). Results: There were significant time by group differences with respect to dizziness during activity and UCLA-Q favouring the physiotherapy led neck specific exercise group with a behavioural approach. Within group analysis of changes over time also revealed significant changes in most variables apart from static balance. Conclusion: Between and within group comparisons suggest that physiotherapist led neck exercise groups including a behavioural approach had advantages in improving measures of dizziness compared with the general physical activity group, although many still complained of dizziness and balance impairment. Future studies should consider exercises specifically designed to address balance, dizziness and cervical proprioception in those with persistent whiplash. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved. ; Funding Agencies|Swedish government through the REHSAM foundation; regional Centres for Clinical Research of Ostergotland and Sormland County Councils; Medical Research Council of Southeast Sweden; Swedish government; Swedish Social Insurance Agency through the REHSAM foundation; Centre for Clinical Research Sormland at Uppsala University Sweden; Uppsala-Orebro Regional Research Council Sweden; Swedish Research Council; County Council of Ostergotland; County Council of Jonkoping
Introduction Patients suffering from remaining disability after anterior cervical decompression and fusion (ACDF) surgery for cervical disc disease may be prescribed physical activity (PPA) or neck-specific exercises (NSEs). Currently, we lack data for the success of either approach. There is also a knowledge gap concerning the use of internet-based care for cervical disc disease. The scarcity of these data, and the high proportion of patients with various degrees of incapacity following ACDF, warrant increased efforts to investigate and improve cost-effective rehabilitation. The objective is to compare the effectiveness of a structured, internet-based NSE programme, versus PPA following ACDF surgery. Methods and analysis This is a prospective, randomised, multicentre study that includes 140 patients with remaining disability (amp;gt;= 30% on the Neck Disability Index, NDI) following ACDF for radiculopathy due to cervical disc disease. Patient recruitment occurs following attendance at routine clinical appointments, scheduled at 3 months postsurgery. Patients are then randomised to one of two groups (70 patients/group) for a 3-month treatment programme/period of either internet-based NSE or PPA. Questionnaires on background data, pain and discomfort, physical and mental capacity, satisfaction with care, and health and workplace factors are completed, along with physical measures of neck-related function conducted by independent test leaders blinded to randomisation. Measures are collected at inclusion, after the 3-month treatments (end of treatment) and at a 2-year follow-up. Radiography will be completed at the 2-year follow-up. Preoperative data will be collected from the Swedish Spine Registry. Data on healthcare consumption, drug use and sick leave will be requested from the relevant national registers. Ethical considerations This study was approved by the Regional Ethical Review Board in Linkoping Ref. 2016/283-31 and 2017/91-32. The scientists are independent with no commercial ties. Patients are recruited after providing written informed consent. Patient data are presented at group level such that no connection to any individual can be made. All data are anonymised when reported, and subject to the Swedish Official Secrets Health Acts. The test leaders are independent and blinded for randomisation. Exercises, both general and neck-specific, have been used extensively in clinical practice and we anticipate no harm from their implementation other than a risk of muscle soreness. Both randomisation groups will receive care that is expected to relieve pain, although the group receiving NSE is expected to demonstrate a greater and more cost-effective improvement versu s the PPA group. Any significant harm or unintended effects in each group will be collected by the test leaders. All questionnaires and test materials are coded by the research group, with code lists stored in locked, fireproof file cabinets, housed at the university in a room with controlled (card-based) access. Only individuals in receipt of a unique website address posted by the researchers can access the programme; patients can neither communicate with each other nor with caregivers via the programme. Study participation might lead to improved rehabilitation versus non-participation, and might therefore be of benefit. The results of this study should also contribute to more effective and flexible rehabilitation, shorter waiting times, lower costs and the possibility to implement our findings on a wider level. Dissemination If effective, the protocols used in this study can be implemented in existing healthcare structures. The results of the study will be presented in scientific journals and popular science magazines of relevance to health. The findings will also be presented at local, regional, national and international conferences and meetings, as well as in the education of university students and at public lectures. Information about the results will be communicated to the general population in cooperation with patient organisations and the media. ; Funding Agencies|regional Center for Clinical Research; Region Council of Ostergotland County
Objective: Patient enablement reflects patients understanding of and coping with illness. The aim of this study was to investigate the content validity, construct validity, internal consistency and selfrated change (SRC) of the Patient Enablement Instrument (PEI) in patients with whiplash-associated disorders, cervical radiculopathy and mixed chronic pain treated in different settings. Design: Psychometric analyses. Participants: Patients with disabling non-malignant chronic musculoskeletal pain. Methods: Participants answered questionnaires on disability (Neck Disability Index (NDI) or Functional Rating Index (FRI)), anxiety/depression (Hospital Anxiety and Depression Scale; HADS) and general health (EuroQol; EQ-5D). Content validity, construct validity (confirmatory factor analysis), internal consistency and cut-off for SRC were investigated for the PEI after treatment. The SRC value was the receiver operating characteristic (ROC) curve optimal cut-off point. Results: After treatment all items were completed by 516 patients (mean standard deviation (SD) age 45.1 years (SD 10.1), women 75% (n=385)). The 1-factor PEI model had approximate fit to the data. The internal consistency Cronbachs alpha was between 0.878 and 0.929 for the 3 groups. Correlations between the PEI and the NDI/FRI, HADS and EQ-5D were fair to good. The SRCROC for whiplash-associated disorders, cervical radiculopathy and mixed chronic pain groups was 5, 6 and 4 points in the PEI, respectively. Conclusion: The PEI showed fair content validity, construct validity and internal consistency. However, the scale needs further development to improve measurement of change. ; Funding Agencies|Swedish government; Swedish Social Insurance Agency through the REHSAM foundation; Research Council of Southeast Sweden; Uppsala-Orebro Regional Research Council, Sweden; County Council of Ostergotland, Sweden; Swedish Research Council; Swedish Society of Medicine; Futurum, the Academy for Healthcare, Jonkoping County Council, Sweden; Centre for Clinical Research Sormland: Uppsala University, Sweden
Background: Fifty percent of people injured by whiplash still report neck pain after 1 year and costs associated with whiplash associated disorders (WAD) are mostly attributed to health service and sick-leave costs in chronic conditions. With increasing health care expenditures the economic impact of interventions needs to be considered. Objective: To analyze the cost-effectiveness of physiotherapist-led neck-specific exercise without (NSE) or with a behavioral approach (NSEB), or prescription of physical activity (PPA) in chronic WAD, grade 2 to 3. Methods: This is a secondary cost-effectiveness analysis of a multicenter randomized clinical trial of 216 participants with chronic WAD grade 2 to 3. The interventions were physiotherapist-led neck-specific exercise without or with a behavioral approach, or prescription of physical activity for 12 weeks. Incremental cost-effectiveness ratios (ICERs) were determined after 1 year and bootstrapped cost-effectiveness planes and sensitivity analyses of physiotherapy visits were performed. Health care and production loss costs were included and quality-adjusted life years (QALYs) were estimated, using the Euroqol-5D questionnaire. Comparisons with the Short Form-6D, and neck disability index (NDI) were also made. Results: The 1-year follow-up was completed by 170 participants (79%). Both physiotherapist-led groups improved in health related quality of life. The intervention cost alone, per quality-adjusted life year (QALY) gain in the NSE group was US$12,067. A trend for higher QALY gains were observed in the NSEB group but the costs were also higher. The ICERs varied depending on questionnaire used, but the addition of a behavioral approach to neck-specific exercise alone was not cost-effective from a societal perspective (ICER primary outcome $127,800 [95% confidence interval [CI], 37,816-711,302]). The sensitivity analyses confirmed the results. The prescription of physical activity did not result in any QALY gain and the societal costs were not lower. Conclusion: Neck-specific exercise was cost-effective from a societal perspective in the treatment of chronic WAD compared with the other exercise interventions. ICERS varied depending on health-related quality of life questionnaires used, but the addition of a behavioral approach was not cost-effective from a societal perspective. The prescription of physical activity did not result in any QALY gain and was thus not considered a relevant option. ; Funding Agencies|Swedish Research Council; Swedish government through the REHSAM foundation; Medical Research Council of Southeast Sweden; County Council of Ostergotland; regional Center for Clinical Research; Centre for Clinical Research Sormland at Uppsala University; Uppsala-Orebro Regional Research Council, Sweden
