The impact of visuospatial and executive function on activity performance and outcome after robotic or conventional gait training, long-term after stroke-as part of a randomized controlled trial.

INTRODUCTION: Visuospatial and executive impairments have been associated with poor activity performance sub-acute after stroke. Potential associations long-term and in relation to outcome of rehabilitation interventions need further exploration. AIMS: To explore associations between visuospatial and executive function and 1) activity performance (mobility, self-care and domestic life) and 2) outcome after 6 weeks of conventional gait training and/or robotic gait training, long term (1-10 years) after stroke. METHODS: Participants (n = 45), living with stroke affecting walking ability and who could perform the items assessing visuospatial/executive function included in the Montreal Cognitive Assessment (MoCA Vis/Ex) were included as part of a randomized controlled trial. Executive function was evaluated using ratings by significant others according to the Dysexecutive Questionnaire (DEX); activity performance using 6-minute walk test (6MWT), 10-meter walk test (10MWT), Berg balance scale, Functional Ambulation Categories, Barthel Index and Stroke Impact Scale. RESULTS: MoCA Vis/Ex was significantly associated with baseline activity performance, long-term after stroke (r = .34-.69, p < .05). In the conventional gait training group, MoCA Vis/Ex explained 34% of the variance in 6MWT after the six-week intervention (p = 0.017) and 31% (p = 0.032) at the 6 month follow up, which indicate that a higher MoCA Vis/Ex score enhanced the improvement. The robotic gait training group presented no significant associations between MoCA Vis/Ex and 6MWT indicating that visuospatial/executive function did not affect outcome. Rated executive function (DEX) presented no significant associations to activity performance or outcome after gait training. CONCLUSION: Visuospatial/executive function may significantly affect activity performance and the outcome of rehabilitation interventions for impaired mobility long-term after stroke and should be considered in the planning of such interventions. Patients with severely impaired visuospatial/executive function may benefit from robotic gait training since improvement was seen irrespective of visuospatial/executive function. These results may guide future larger studies on interventions targeting long-term walking ability and activity performance. TRIAL REGISTRATION: clinicaltrials.gov (NCT02545088) August 24, 2015.

Learning from the past to plan for the future: A scoping review of musculoskeletal clinical research in Sweden 2010-2020.

Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors. Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14% of the publications, 84% from secondary health care, and 2% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34%) and rehabilitation (15%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25%), fractures (16%), and joint, tendon, and muscle injuries (13%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8%, respectively). Pain disorder-related publications (10%) as well as bone health and osteoporosis-related publications (4%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3%, respectively). Conclusions: Swedish-affiliated MSK disorder research 2010-2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.

Atherosclerosis Induced by Adeno-Associated Virus Encoding Gain-of-Function PCSK9.

Induction of atherosclerosis in mice with one or more genetic alterations (e.g., conditional deletion of a gene of interest) has traditionally required crossbreeding with Apoe or Ldlr deficient mice to achieve sufficient hypercholesterolemia. However, this procedure is time consuming and generates a surplus of mice with genotypes that are irrelevant for experiments. Several alternative methods exist that obviate the need to work in mice with germline-encoded hypercholesterolemia. In this chapter, we detail an efficient and increasingly used method to induce hypercholesterolemia in mice through adeno-associated virus-mediated transfer of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene.

Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype.

Endothelial-mesenchymal transition (EndMT) is associated with various cardiovascular diseases and in particular with atherosclerosis and plaque instability. However, the molecular pathways that govern EndMT are poorly defined. Specifically, the role of epigenetic factors and histone deacetylases (HDACs) in controlling EndMT and the atherosclerotic plaque phenotype remains unclear. Here, we identified histone deacetylation, specifically that mediated by HDAC9 (a class IIa HDAC), as playing an important role in both EndMT and atherosclerosis. Using in vitro models, we found class IIa HDAC inhibition sustained the expression of endothelial proteins and mitigated the increase in mesenchymal proteins, effectively blocking EndMT. Similarly, ex vivo genetic knockout of Hdac9 in endothelial cells prevented EndMT and preserved a more endothelial-like phenotype. In vivo, atherosclerosis-prone mice with endothelial-specific Hdac9 knockout showed reduced EndMT and significantly reduced plaque area. Furthermore, these mice displayed a more favorable plaque phenotype, with reduced plaque lipid content and increased fibrous cap thickness. Together, these findings indicate that HDAC9 contributes to vascular pathology by promoting EndMT. Our study provides evidence for a pathological link among EndMT, HDAC9, and atherosclerosis and suggests that targeting of HDAC9 may be beneficial for plaque stabilization or slowing the progression of atherosclerotic disease.

Unequal physical activity among children with cerebral palsy in Sweden-A national registry study.

AIM: To examine the extent to which sex, country of birth, and functional aspects influence participation in physical education and physical leisure activity among children with cerebral palsy (CP) in Sweden. METHODS: This national cross-sectional registry study included children with CP aged 6 to 18 years who participated in the Swedish national quality registry, the Cerebral Palsy Follow-up Program, CPUP, in 2015. Comparisons and associations between sex, country of birth, and functional aspects and physical leisure/physical education were examined using chi-squared and multivariable logistic regression analysis. RESULTS: The study included 1935 children. Of them, 1625 (87%) reported participating in physical education and 989 (53%) reported participating in physical leisure activity. Children born in Sweden had higher odds of participating in physical education (OR: 1.99; 95% CI: 1.20-3.28) and physical leisure activity (OR: 2.51; 95% CI: 1.70-3.72) compared with children born outside Europe. Greater impairment of gross motor function was associated with lower participation levels. Boys participated slightly more frequently in leisure activities than girls. CONCLUSION: Enhancing social inclusion with regard to disability, birth country, and sex are important and achievable goals for policymakers and practitioners for promoting participation in physical activity for children and adolescents with CP.

Effects of neuromuscular training on knee proprioception in individuals with anterior cruciate ligament injury: a systematic review and GRADE evidence synthesis.

OBJECTIVE: To systematically review and summarise the evidence for the effects of neuromuscular training compared with any other therapy (conventional training/sham) on knee proprioception following anterior cruciate ligament (ACL) injury. DESIGN: Systematic Review. DATA SOURCES: PubMed, CINAHL, SPORTDiscus, AMED, Scopus and Physical Education Index were searched from inception to February 2020. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials investigating the effects of neuromuscular training on knee-specific proprioception tests following a unilateral ACL injury were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted data and assessed risk of bias of the eligible studies using the Cochrane risk of bias 2 tool. Overall certainty in evidence was determined using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. RESULTS: Of 2706 articles retrieved, only 9 RCTs, comprising 327 individuals with an ACL reconstruction (ACLR), met the inclusion criteria. Neuromuscular training interventions varied across studies: whole body vibration therapy, Nintendo-Wii-Fit training, balance training, sport-specific exercises, backward walking, etc. Outcome measures included joint position sense (JPS; n=7), thresholds to detect passive motion (TTDPM; n=3) or quadriceps force control (QFC; n=1). Overall, between-group mean differences indicated inconsistent findings with an increase or decrease of errors associated with JPS by ≤2°, TTDPM by ≤1.5° and QFC by ≤6 Nm in the ACLR knee following neuromuscular training. Owing to serious concerns with three or more GRADE domains (risk of bias, inconsistency, indirectness or imprecision associated with the findings) for each outcome of interest across studies, the certainty of evidence was very low. CONCLUSIONS: The heterogeneity of interventions, methodological limitations, inconsistency of effects (on JPS/TTDPM/QFC) preclude recommendation of one optimal neuromuscular training intervention for improving proprioception following ACL injury in clinical practice. There is a need for methodologically robust RCTs with homogenous populations with ACL injury (managed conservatively or with reconstruction), novel/well-designed neuromuscular training and valid proprioception assessments, which also seem to be lacking. PROSPERO REGISTRATION NUMBER: CRD42018107349.

Inequity in physiotherapeutic interventions for children with Cerebral Palsy in Sweden-A national registry study.

AIM: The aim of this study was to investigate the distribution of physiotherapeutic interventions for children with Cerebral Palsy in Sweden from an equity perspective, considering sex, country of birth and geographical region. METHOD: This national cross-sectional registry study includes children with Cerebral Palsy aged 0-18 years who participated in 2015 in the Swedish national quality registry, the Cerebral Palsy follow-up programme, CPUP. Comparisons and associations between physiotherapeutic interventions and sex, country of birth and geographical regions were conducted using chi-square and logistic regression analysis, controlling for cognitive level, level of motor function, age group and dominating symptom. RESULTS: Of the 2855 participants, 2201 (79%) had received physiotherapy. Children born in Sweden had 1.60 times higher odds (95% CI 1.10-2.33) of receiving physiotherapy compared with children born in foreign countries. Distribution of physiotherapeutic interventions differed significantly between geographical regions. No associations between sex and physiotherapeutic interventions were observed. CONCLUSION: The results of this study indicate inequity in care in Sweden towards children with Cerebral Palsy born in other counties. Further, physiotherapeutic interventions were not equally distributed in different geographical regions of Sweden. Knowledge of inequity is crucial in order to address the problem.

18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis.

BACKGROUND: Arterial 18fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered a measure of atherosclerotic plaque macrophages and is used for quantification of disease activity in clinical trials, but the distribution profile of FDG across macrophages and other arterial cells has not been fully clarified. OBJECTIVES: The purpose of this study was to analyze FDG uptake in different arterial tissues and their contribution to PET signal in normal and atherosclerotic arteries. METHODS: Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, high-cholesterol diet to induce atherosclerosis and subjected to a clinical FDG-PET and computed tomography scan protocol. Volumes of arterial media, intima/lesion, macrophage-rich, and hypoxic tissues were measured in serial histological sections. Distributions of FDG in macrophages and other arterial tissues were quantified using modeling of the in vivo PET signal. In separate transgenic minipigs, the intra-arterial localization of FDG was determined directly by autoradiography. RESULTS: Arterial FDG-PET signal appearance and intensity were similar to human imaging. The modeling approach showed high accuracy in describing the FDG-PET signal and revealed comparable FDG accumulation in macrophages and other arterial tissues, including medial smooth muscle cells. These findings were verified directly by autoradiography of normal and atherosclerotic arteries. CONCLUSIONS: FDG is taken up comparably in macrophage-rich and -poor arterial tissues in minipigs. This offers a mechanistic explanation to a growing number of observations in clinical imaging studies that have been difficult to reconcile with macrophage-selective FDG uptake.

Sick leave due to musculoskeletal pain: determinants of distinct trajectories over 1 year.

PURPOSE: This study aimed to identify sub-groups of workers with different trajectories of sick leave due to musculoskeletal pain over 1 year, and to investigate the extent to which the identified trajectories are associated with personal, occupational, lifestyle, and pain-related factors at baseline. METHODS: Data on 981 blue- and white-collar workers were analyzed in the DPHACTO cohort (2012-2014). The number of days on sick leave due to pain was reported using text messages at 4-week intervals across 1 year. Latent class growth analysis was used to distinguish sub-groups with different trajectories of sick leave. A web-based questionnaire at baseline was used to assess personal, occupational (physical and psychosocial), lifestyle, and pain-related factors. Multinomial regression models were constructed to determine associations between baseline factors and trajectories of sick leave (referencing no sick leave), with adjustment for potential confounders. RESULTS: Four distinct sub-groups were identified, with trajectories of sick leave due to pain ranging from no sick leave (prevalence 76%; average 0.5 days/year) to some days and increasing sick leave due to pain over 1 year (2%; 89 days/year). The increasing trajectory of sick leave was associated with higher perceived physical exertion, more time in manual work, less social community and influence at work, less leisure-time physical activity, smoking, and more severe symptoms (e.g., multisite pain, low back pain intensity, and pain interference). CONCLUSIONS: We identified four distinct trajectories of sick leave due to musculoskeletal pain. The sub-group with increasing sick leave due to pain was associated with several modifiable physical and psychosocial factors at work and outside work, which may have implications for prevention.

Predictive models for short-term and long-term improvement in women under physiotherapy for chronic disabling neck pain: a longitudinal cohort study.

OBJECTIVES: To develop predictive models for short-term and long-term clinically important improvement in women with non-specific chronic disabling neck pain during the clinical course of physiotherapy. DESIGN: Longitudinal cohort study based on data from a randomised controlled trial evaluating short-term and long-term effects on sensorimotor function over 11 weeks of physiotherapy. PARTICIPANTS AND SETTINGS: Eighty-nine women aged 31-65 years with non-specific chronic disabling neck pain from Gävle, Sweden. MEASURES: The outcome, clinically important improvement, was measured with the Patient Global Impression of Change Scale (PGICS) and the Neck Disability Index (NDI), assessed by self-administered questionnaires at 3, 9 and 15 months from the start of the interventions (baseline). Twelve baseline prognostic factors were considered in the analyses. The predictive models were built using random-effects logistic regression. The predictive ability of the models was measured by the area under the receiver operating characteristic curve (AUC). Internal validity was assessed with cross-validation using the bootstrap resampling technique. RESULTS: Factors included in the final PGICS model were neck disability and age, and in the NDI model, neck disability, depression and catastrophising. In both models, the odds for short-term and long-term improvement increased with higher baseline neck disability, while the odds decreased with increasing age (PGICS model), and with increasing level of depression (NDI model). In the NDI model, higher baseline levels of catastrophising indicated increased odds for short-term improvement and decreased odds for long-term improvement. Both models showed acceptable predictive validity with an AUC of 0.64 (95% CI 0.55 to 0.73) and 0.67 (95% CI 0.59 to 0.75), respectively. CONCLUSION: Age, neck disability and psychological factors seem to be important predictors of improvement, and may inform clinical decisions about physiotherapy in women with chronic neck pain. Before using the developed predictive models in clinical practice, however, they should be validated in other populations and tested in clinical settings.

Office-Cycling: A Promising Way to Raise Pain Thresholds and Increase Metabolism with Minimal Compromising of Work Performance.

AIM: Establishing the effects of low intensity cycling (LC), moderate intensity cycling (MC), and standing at a simulated office workstation on pain modulation, work performance, and metabolic expenditure. METHODS: 36 healthy adults (21 females), mean age 26.8 (SD 7.6) years, partook in this randomized 3 × 3 crossover trial with 75 minutes of LC on 20% of maximum aerobic power (MAP) output, 30 minutes of MC on 50% of MAP, and standing 30 minutes with 48-hour wash-out periods. Outcome measures were pain modulation (pressure pain threshold (PPT) and thermal pain threshold)), work performance (transcription, mouse pointing, and cognitive performance), and metabolic expenditure. RESULTS: PPTs increased in all conditions. PPT trapezius showed the highest increase after LC, 39.3 kilopascals (kPa) (15.6; 78.6), compared to MC, 17.0 kPa (2.8; 49.9), and standing, 16.8 kPa (-5.6; 39.4), p = 0.015. Transcription was reduced during LC and MC. Mouse pointing precision was best during standing and worst and slowest during MC. Cognitive performance did not differ between conditions. Metabolic expenditure rates were 1.4 (1.3; 1.7), 3.3 (2.3; 3.7), and 7.5 (5.8; 8.7) kcal/minute during standing, LC, and MC, respectively (p < 0.001). CONCLUSIONS: LC seems to be the preferred option; it raised PPTs, more than doubled metabolic expenditure, whilst minimally influencing work performance.

Impact of Workplace Exposure and Stress on Neck Pain and Disabilities in Women-A Longitudinal Follow-up After a Rehabilitation Intervention.

Introduction: The aim was to evaluate if pain, disability, and work productivity are influenced by physical and psychosocial work exposures as well as by stress, up to 1 year after a randomized controlled trial treatment intervention, and to determine whether any such association differed between treatment and control groups. Methods: Ninety-seven working women suffering non-specific neck pain (n = 67 treatment group, n = 30 control group) were followed from end of treatment intervention and at 9- and 15-month follow-ups, respectively. Physical and psychosocial exposures, as well as perceived stress, were assessed after the treatment intervention. Pain, neck disability, and work productivity were assessed at baseline, after intervention 3 months later and at 9- and 15-month follow-ups. Longitudinal assessment was conducted using the exposure level at 3 months as predictor of pain, disability, and work productivity at 3, 9, and 15 months, respectively. Mixed models were used to estimate longitudinal associations, accounting for within-individual correlation of repeated outcome measures by incorporation of a random intercept. Age and duration of neck pain were adjusted for in all models. To evaluate group differences, interactions between exposures and treatment groups were estimated. Results: High perceived stress was associated with more neck pain, more neck disability, and decreased work productivity in both cross-sectional and longitudinal analyses. High 'control of decision' was associated with less neck pain, less neck disability, and higher work productivity in cross-sectional analyses but only to less disability and higher productivity in longitudinal analyses. Shoulder/arm load was the only physical exposure variable that was significantly associated with work productivity in the univariate analyses. Only small differences were observed between treatment and control groups. Conclusion: High perceived stress and low 'control of decision' were associated with more neck pain, increased neck disability, and decreased work productivity. Treatment interventions for individuals with neck pain should take into account psychosocial workplace exposures and stress to improve intermediate and long-term results.

Systematic review of quantitative imaging biomarkers for neck and shoulder musculoskeletal disorders.

BACKGROUND: This study systematically summarizes quantitative imaging biomarker research in non-traumatic neck and shoulder musculoskeletal disorders (MSDs). There were two research questions: 1) Are there quantitative imaging biomarkers associated with the presence of neck and shoulder MSDs?, 2) Are there quantitative imaging biomarkers associated with the severity of neck and shoulder MSDs? METHODS: PubMed and SCOPUS were used for the literature search. One hundred and twenty-five studies met primary inclusion criteria. Data were extracted from 49 sufficient quality studies. RESULTS: Most of the 125 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. Only half controlled for potential confounders via exclusion or in the analysis. Approximately one-third reported response rates. In sufficient quality articles, 82% demonstrated at least one statistically significant association between the MSD(s) and biomarker(s) studied. The literature synthesis suggested that neck muscle size may be decreased in neck pain, and trapezius myalgia and neck/shoulder pain may be associated with reduced vascularity in the trapezius and reduced trapezius oxygen saturation at rest and in response to upper extremity tasks. Reduced vascularity in the supraspinatus tendon may also be a feature in rotator cuff tears. Five of eight studies showed an association between a quantitative imaging marker and MSD severity. CONCLUSIONS: Although research on quantitative imaging biomarkers is still in a nascent stage, some MSD biomarkers were identified. There are limitations in the articles examined, including possible selection bias and inattention to potentially confounding factors. Recommendations for future studies are provided.

Cross-Cultural Adaptation of the Profile Fitness Mapping Neck Questionnaire to Brazilian Portuguese: Internal Consistency, Reliability, and Construct and Structural Validity.

OBJECTIVE: The purpose of this study was to adapt and evaluate the psychometric properties of the ProFitMap-neck to Brazilian Portuguese. METHODS: The cross-cultural adaptation consisted of 5 stages, and 180 female patients with chronic neck pain participated in the study. A subsample (n = 30) answered the pretest, and another subsample (n = 100) answered the questionnaire a second time. Internal consistency, test-retest reliability, and construct validity (hypothesis testing and structural validity) were estimated. For construct validity, the scores of the questionnaire were correlated with the Neck Disability Index (NDI), and the Hospital Anxiety and Depression Scale (HADS), the Tampa Scale of Kinesiophobia (TSK), and the 36-item Short-Form Health Survey (SF-36). RESULTS: Internal consistency was determined by adequate Cronbach's α values (α > 0.70). Strong reliability was identified by high intraclass correlation coefficients (ICC > 0.75). Construct validity was identified by moderate and strong correlations of the Br-ProFitMap-neck with total NDI score (-0.56 50%, Kaiser-Meyer-Olkin index > 0.50, eigenvalue > 1, and factor loadings > 0.2. CONCLUSION: Br-ProFitMap-neck had adequate psychometric properties and can be used in clinical settings, as well as research, in patients with chronic neck pain.

Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

BACKGROUND: Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine. METHODS: Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure. FINDINGS: Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour. INTERPRETATION: The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

Responsiveness and minimal important change for the ProFitMap-neck questionnaire and the Neck Disability Index in women with neck-shoulder pain.

PURPOSE: The aim was to determine the responsiveness and minimal important change (MIC) of the questionnaire ProFitMap-neck that measures symptoms and functional limitations in women with neck pain. The same measurement properties were determined for Neck Disability Index (NDI) for comparison purposes. METHODS: Longitudinal data were derived from two randomized controlled trials, including 103 and 120 women with non-specific neck pain, with questionnaire measurements performed before and after interventions. Sensitivity and specificity to discriminate between improved and not or little changed participants, based on categorization of a global rating of change scale (GRCS), were determined for the ProFitMap-neck indices and NDI by using area under receiver operating characteristic curves (AUC). Correlations between the GRCS anchor and change scores of the questionnaires were also used to assess responsiveness. The change score that showed the highest combination of sensitivity and specificity was set for MIC. RESULTS: The ProFitMap-neck indices showed similar responsiveness as NDI with AUC exceeding 0.70 (Range: ProFitMap-neck, 0.74-0.83; NDI, 0.75-0.86). The MIC in the two samples ranged between 6.6 and 13.6 % for ProFitMap-neck indices and 5.2 and 6.3 % for NDI. Both questionnaires had significant correlations with GRCS (Spearman's rho 0.47-0.72). CONCLUSIONS: Validity of change scores was endorsed for the ProFitMap-neck indices and NDI with adequate ability to discriminate between improved and not or little changed participants. Values of minimal important change were presented.

Is tailored treatment superior to non-tailored treatment for pain and disability in women with non-specific neck pain? A randomized controlled trial.

BACKGROUND: The evidence for the effect of treatments of neck pain is modest. In the absence of causal treatments, a possibility is to tailor the treatment to the individuals' functional limitations and symptoms. The aim was to evaluate treatment effects of a tailored treatment versus a non-tailored treatment. Our hypothesis was that tailored treatment (TT) would have better effect on pain intensity and disability than either non-tailored treatment (NTT) (same treatment components but applied quasi-randomly) or treatment-as-usual (TAU) (no treatment from the study, no restrictions). We further hypothesized that TT and NTT would both have better effect than TAU. METHOD: One hundred twenty working women with subacute and chronic non-specific neck pain were allocated to 11 weeks of either TT, NTT or TAU in a randomized controlled trial with follow-ups at 3, 9 and 15 months. The TT was designed from a decision model based on assessment of function and symptoms with defined cut-off levels for the following categories: reduced cervical mobility, impaired neck-shoulder strength and motor control, impaired eye-head-neck control, trapezius myalgia and cervicogenic headache. Primary outcomes were pain and disability. Secondary outcomes were symptoms, general improvement, work productivity, and pressure pain threshold of m. trapezius. RESULTS: Linear mixed models analysis showed no differences between TT and NTT besides work productivity favoring TT at 9- and 15-months follow-ups. TT and NTT improved significantly more than TAU on pain, disability and symptoms at 3-month follow-up. General improvement also favored TT and NTT over TAU at all follow-ups. CONCLUSION: Tailored treatment according to our proposed decision model was not more effective than non-tailored treatment in women with subacute and chronic neck pain. Both tailored and non-tailored treatments had better short-term effects than treatment-as-usual, supporting active and specific exercise therapy, although therapist-patient interaction was not controlled for. Better understanding of the importance of functional impairments for pain and disability, in combination with a more precise tailoring of specific treatment components, is needed to progress. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 49348025. Registered 2 August 2011.

Prior renovascular hypertension does not predispose to atherosclerosis in mice.

BACKGROUND: Hypertension is a major risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Although lowering blood pressure with antihypertensive drugs reduces the increased risk of ASCVD, residual increased risk still remains, suggesting that hypertension may cause chronic changes that promote atherosclerosis. Thus, we tested the hypothesis that hypertension increases the susceptibility to atherosclerosis in mice even after a period of re-established normotension. METHODS: We used the 2-kidney, 1-clip (2K1C) technique to induce angiotensin-driven renovascular hypertension, and overexpression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene to cause severe hypercholesterolemia and atherosclerosis. RESULTS: First, we performed 2K1C (n = 8) or sham surgery (n = 9) in PCSK9 transgenic mice before they were fed a high fat diet for 14 weeks. As expected, 2K1C did not affect cholesterol levels, but induced cardiac hypertrophy and significantly increased the atherosclerotic lesion area compared to sham mice (1.8 fold, p < 0.01). Next, we performed 2K1C (n = 13) or sham surgery (n = 14) in wild-type mice but removed the clipped/sham-operated kidney after 10 weeks to eliminate hypertension, and subsequently induced hypercholesterolemia by way of adeno-associated virus-mediated hepatic gene transfer of PCSK9 combined with high-fat diet. After 14 weeks of hypercholesterolemia, atherosclerotic lesion areas were not significantly different in mice with or without prior 2K1C hypertension (0.95 fold, p = 0.35). CONCLUSION: Renovascular hypertension in mice does not induce pro-atherogenic changes that persist beyond the hypertensive phase. These results indicate that hypertension only promotes atherogenesis when coinciding temporally with hypercholesterolemia.

Stanniocalcin-2 overexpression reduces atherosclerosis in hypercholesterolemic mice.

BACKGROUND AND AIM: The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been suggested as a proatherogenic molecule by its ability to locally increase insulin-like growth factor signaling. Stanniocalcin-2 (STC2) was recently discovered to be a potent inhibitor of PAPP-A activity, but has not previously been implicated in vascular disease. The aim of this study was to substantiate the interaction between PAPP-A and STC2 as a potential local regulatory mechanism in the artery wall. METHODS AND RESULTS: We found that PAPP-A is secreted from cultured primary smooth muscle cells obtained from human aortas as a covalent complex with STC2, devoid of proteolytic activity. Extracts of human carotid atherosclerotic plaques contain both complexed and uncomplexed PAPP-A, and we show by immunohistochemistry that PAPP-A and STC2 are present in the tissue throughout early human lesion development. We then used adeno-associated virus-mediated expression of STC2 to increase the fraction of PAPP-A present in the inhibited state and found that it decreased the development of atherosclerosis by 47% (P = 0.0005) in apolipoprotein E-deficient mice challenged with a Western type diet compared to controls. CONCLUSIONS: This study is the first to suggest the involvement of STC2 in regulating PAPP-A activity during the development of atherosclerosis. Furthermore, we demonstrate that lesion development can be inhibited in an experimental model by driving the balance towards inhibited PAPP-A.

Association between plasma concentrations of linoleic acid-derived oxylipins and the perceived pain scores in an exploratory study in women with chronic neck pain.

BACKGROUND: Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women. METHODS: Blood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using ultra performance liquid chromatography coupled to tandem mass spectrometry. Current pain ("NRSday") and the average pain during the last week ("NRSweek") were rated by the participants using a numerical rating scale. RESULTS: There were no significant differences in the plasma concentrations of the fifteen lipids investigated between the women with pain and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13-hydroxy-octadecadienoic acid (Spearman's rho values 0.51 [P = 0.0016]) and 0.53 [P = 0.0011], respectively). CONCLUSIONS: The data obtained in this exploratory study indicate that although no group differences are seen in plasma lipid concentrations, there is an association between the NRSday scores and the 9- and 13-hydroxy-octadecadienoic acid levels. Whether or not the association reflects a causality (i.e. that the circulating lipids contribute to the perceived pain of the pain participants), requires further investigation.