Regionalization of cell types in silk glands of Larinioides sclopetarius suggest that spider silk fibers are complex layered structures.

In order to produce artificial silk fibers with properties that match the native spider silk we likely need to closely mimic the spinning process as well as fiber architecture and composition. To increase our understanding of the structure and function of the different silk glands of the orb weaver Larinioides sclopetarius, we used resin sections for detailed morphology, paraffin embedded sections for a variety of different histological stainings, and a histochemical method for localization of carbonic anhydrase activity. Our results show that all silk glands, except the tubuliform glands, are composed of two or more columnar epithelial cell types, some of which have not been described previously. We observed distinct regionalization of the cell types indicating sequential addition of secretory products during silk formation. This means that the major ampullate, minor ampullate, aciniform type II, and piriform silk fibers most likely are layered and that each layer has a specific composition. Furthermore, a substance that stains positive for polysaccharides may be added to the silk in all glands except in the type I aciniform glands. Active carbonic anhydrase was found in all silk glands and/or ducts except in the type I aciniform and tubuliform glands, with the strongest staining in aggregate glands and their ductal nodules. Carbonic anhydrase plays an important role in the generation of a pH gradient in the major ampullate glands, and our results suggest that some other glands may also harbor pH gradients.

Deep learning-based method for segmenting epithelial layer of tubules in histopathological images of testicular tissue.

Purpose: There is growing concern that male reproduction is affected by environmental chemicals. One way to determine the adverse effect of environmental pollutants is to use wild animals as monitors and evaluate testicular toxicity using histopathology. We propose an automated method to process histology images of testicular tissue. Approach: Testicular tissue consists of seminiferous tubules. Segmenting the epithelial layer of the seminiferous tubule is a prerequisite for developing automated methods to detect abnormalities in tissue. We suggest an encoder-decoder fully connected convolutional neural network model to segment the epithelial layer of the seminiferous tubules in histological images. The ResNet-34 is used in the feature encoder module, and the squeeze and excitation attention block is integrated into the encoding module improving the segmentation and localization of epithelium. Results: We applied the proposed method for the two-class problem, where the epithelial layer of the tubule is the target class. The F -score and Intersection over Union of the proposed method are 0.85 and 0.92. Although the proposed method is trained on a limited training set, it performs well on an independent dataset and outperforms other state-of-the-art methods. Conclusion: The pretrained ResNet-34 in the encoder and attention block suggested in the decoder result in better segmentation and generalization. The proposed method can be applied to testicular tissue images from any mammalian species and can be used as the first part of a fully automated testicular tissue processing pipeline. The dataset and codes are publicly available on GitHub.

Deep learning-based method for segmenting epithelial layer of tubules in histopathological images of testicular tissue.

Purpose: There is growing concern that male reproduction is affected by environmental chemicals. One way to determine the adverse effect of environmental pollutants is to use wild animals as monitors and evaluate testicular toxicity using histopathology. We propose an automated method to process histology images of testicular tissue. Approach: Testicular tissue consists of seminiferous tubules. Segmenting the epithelial layer of the seminiferous tubule is a prerequisite for developing automated methods to detect abnormalities in tissue. We suggest an encoder-decoder fully connected convolutional neural network model to segment the epithelial layer of the seminiferous tubules in histological images. The ResNet-34 is used in the feature encoder module, and the squeeze and excitation attention block is integrated into the encoding module improving the segmentation and localization of epithelium. Results: We applied the proposed method for the two-class problem, where the epithelial layer of the tubule is the target class. The F-score and Intersection over Union of the proposed method are 0.85 and 0.92. Although the proposed method is trained on a limited training set, it performs well on an independent dataset and outperforms other state-of-the-art methods. Conclusion: The pretrained ResNet-34 in the encoder and attention block suggested in the decoder result in better segmentation and generalization. The proposed method can be applied to testicular tissue images from any mammalian species and can be used as the first part of a fully automated testicular tissue processing pipeline. The dataset and codes are publicly available on GitHub.

Erratum: Publisher's note: Deep learning-based method for segmenting epithelial layer of tubules in histopathological images of testicular tissue.

[This corrects the article DOI: 10.1117/1.JMI.10.3.037501.].

Work ability and psychological distress in a working population: results from the Stockholm Public Health Cohort.

AIMS: Psychological distress is a global public health concern with individual and societal implications causing work-related disability and loss of productivity. It is less known how much work ability contributes to the development of psychological distress. This study aimed to assess the association between self-perceived physical and mental work ability in relation to job demands, and the incidence of psychological distress in a Swedish working population. METHODS: Data were obtained from three subsamples of the Stockholm Public Health Cohort with baseline in 2010 and follow-up in 2014, based on a working population in Stockholm County aged 18-60 years, with no or mild psychological distress at baseline (n=29,882). Self-perceived physical and mental work ability in relation to job demands were assessed at baseline with a subscale from the Work Ability Index. Study participants scoring 4 or more on the General Health Questionnaire 12 at follow-up were classified as having developed psychological distress during the study period. Poisson log linear regression was used to calculate crude and adjusted rate ratios with 95% confidence intervals. RESULTS: At follow-up, 2543 participants (12%) had developed psychological distress. Reporting poor physical and/or poor mental work ability in relation to job demands at baseline was associated with an almost doubled rate ratio of psychological distress at follow-up, compared to reporting good work ability (rate ratio 1.8; 95% confidence interval 1.6-2.0). CONCLUSIONS: Poor work ability is associated with a higher incidence of future psychological distress compared to good work ability.

Lifestyle behaviors in Swedish university students before and during the first six months of the COVID-19 pandemic: a cohort study.

BACKGROUND: Changes in Swedish university students' lifestyle behaviors during the COVID-19 pandemic are unknown. This study aimed to assess physical activity, sitting time, meal frequency and risk substance use (alcohol, tobacco, and illicit use of drugs) in Swedish university students before and during the first six months of the COVID-19 pandemic, for all and stratified by age and sex. METHODS: Data were obtained from the Sustainable University Life cohort study in which web-based surveys were sent to university students repeatedly for one year. Baseline assessment (before the pandemic) was between August 2019-March 2020, follow-up 1 (FU1) between March-June 2020, and follow-up 2 (FU2) between June-September 2020. Participants reported weekly minutes of physical activity, daily sitting hours, meal frequency by weekly intake of different meals, and motivation for eating irregularly, if so. Also, harmful use of alcohol, tobacco and illicit drugs was assessed. Population means and differences with 95% confidence intervals (95% CI) in lifestyle behaviors between time points were calculated with Generalized Estimating Equations. RESULTS: 1877 students (73% women, mean age 26.5 years) answered the baseline survey. Weekly exercise decreased by -5.7 min (95% CI: -10.0, -1.5) and -7.7 min (95% CI: -12.6, -2.8) between baseline and FU1 and FU2, respectively. Weekly daily activities increased by 5.6 min (95% CI: 0.3, 11.7) and 14.2 min (95% CI: 7.9, 20.5) between baseline and FU1 and FU2. Daily sitting time decreased by -1.4 h (95% CI: -1.7, -1.2) between baseline and FU2. Breakfast intake increased by 0.2 days per week (95% CI: 0.1, 0.3) between baseline and FU2. Lunch intake decreased by -0.2 days per week (95% CI: -0.2, -0.1) between baseline and FU1 and by -0.2 days per week (95% CI: -0.3, -0.0) between baseline and FU2. Dinner intake decreased by -0.1 days per week (95% CI: -0.2, -0.0) between baseline and both FU1 and FU2. Only minor differences in risk substance use were observed. Similar changes were observed in analyses stratified by age and sex. CONCLUSIONS: Lifestyle behaviors in Swedish university students slightly improved during the first six months of the COVID-19 pandemic compared to before. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04465435 . 10/07/2020.

Influence of work ability and smoking on the prognosis of long-duration activity-limiting neck/back pain: a cohort study of a Swedish working population.

OBJECTIVES: Long-duration activity-limiting neck/back pain is common, but the knowledge of what work and lifestyle factors that influence the prognosis is sparse. The objective was therefore to evaluate if two factors, good self-perceived work ability and no daily smoking, are associated with a favourable prognosis of long-duration activity-limiting neck/back pain in a working population, and if these exposures have a synergistic prognostic effect. DESIGN: A prospective cohort study based on three subsamples from the Stockholm Public Health Cohort. SETTINGS: A working population in Stockholm County, Sweden. PARTICIPANTS: Individuals, 18-61 years old, reporting long-duration activity-limiting neck/back pain the previous 6 months at baseline in 2010 (n=5177). MEASURES: The exposures were: self-perceived work ability (categorised into good, moderate and poor) and daily smoking (no/yes). The outcome in 2014 was 'absence of long-duration activity-limiting neck/back pain' the previous 6 months representing a favourable prognosis of reported problems at baseline in 2010. Risk ratios (RRs) and risk differences (RDs) with 95% CI was estimated by general linear regressions, and the synergistic effect was estimated by the synergy index (SI) with 95% CI. RESULTS: Participants with moderate or good work ability, respectively, had an adjusted RR for a favourable prognosis of 1.37 (95% CI 1.11 to 1.69), and 1.80 (1.49 to 2.17) in comparison with participants with poor work ability. The corresponding adjusted RD were 0.07 (0.02 to 0.11) and 0.17 (0.12 to 0.22). Participants not smoking on daily basis had an adjusted RR of 1.21 (1.02 to 1.42), and an adjusted RD of 0.05 (0.01 to 0.10) for a favourable outcome compared with daily smokers. The adjusted SI was 0.92 (0.60 to 1.43). CONCLUSION: For participants with long-duration activity-limiting neck/back pain, moderate or good self-perceived work ability and not being a daily smoker were associated with a favourable prognosis but having both exposures seemed to have no synergistic prognostic effect.

Sustainable UNiversity Life (SUN) study: protocol for a prospective cohort study of modifiable risk and prognostic factors for mental health problems and musculoskeletal pain among university students.

INTRODUCTION: Mental health problems and musculoskeletal pain are common health problems among young adults including students. Little is known about the aetiology and prognosis of these problems in university students. We aim to determine the role of personal, sociodemographic, academic and environmental factors for risk and prognosis of symptoms of depression, anxiety and stress as well as musculoskeletal pain in university students. The constructs that will be studied are based on the biopsychosocial model and psychopathology associated with disabling pain. This model acknowledges illness to consist of interrelated mechanisms categorised into biological, psychological, environmental and social cues. METHODS AND ANALYSIS: This cohort study aims to recruit around 5000 Swedish full-time students. Data will be collected using five online surveys during one academic year. A subgroup (n=1851) of the cohort, recruited before the COVID-19 pandemic, receive weekly text messages with three short questions assessing mood, worry and pain, sent through the web-based platform SMS-track . Statistical analyses will include Kaplan-Meier estimates, Cox regression analyses, multinomial logistic regression analyses and generalised estimating equations. We will assess effect measure modification when relevant and conduct sensitivity analyses to assess the impact of lost to follow-up. PROTOCOL AMENDMENTS: Due to opportunity and timing of the study, with relevance to the outbreak of the COVID-19 pandemic, this study further aims to address mental health problems, musculoskeletal pain and lifestyle in university students before and during the pandemic. ETHICS AND DISSEMINATION: The Sustainable UNiversity Life study was approved by the Swedish ethics authority (2019-03276; 2020-01449). Results will be disseminated through peer-reviewed research papers, reports, research conferences, student theses and stakeholder communications. TRIAL REGISTRATION NUMBER: NCT04465435.

Non-Preferred Work and the Incidence of Spinal Pain and Psychological Distress-A Prospective Cohort Study.

Mental illness and psychological distress are global concerns. This study aimed to investigate the association between having non-preferred work and the incidence of spinal pain, psychological distress, and spinal pain with concurrent psychological distress, and if associations are modified by sleep disturbance. A prospective study of 4285 participants 23-62 years old was conducted, from years 2007 to 2010. Participants reported their work situation as preferred/non-preferred regarding profession/workplace with a high/low possibility to change. Psychological distress was measured with the General Health Questionnaire 12 and spinal pain with questions about neck/back pain. Binominal regression analyses calculated relative risk (RR) with 95% confidence interval (CI). Non-preferred work with a low possibility to change was associated with a higher incidence of spinal pain (RR 1.8; 95% CI 1.2-2.6) and psychological distress (RR 1.8; 95% CI 1.4-2.4) compared to preferred work. The RR was 1.4 (95% CI 0.9-2.1) for spinal pain and 1.3 (95% CI 1.0-1.7) for psychological distress among those with a high possibility to change. Non-preferred work yielded a higher incidence of spinal pain with concurrent psychological distress (RR 1.9; 95% CI 1.0-3.7). Sleep disturbance did not modify associations. A replication based on newer data is needed to confirm the results. In conclusion, non-preferred work is associated with a higher incidence of spinal pain and psychological distress, especially if the possibility to change job is low.

Distinct B cell subsets in Peyer's patches convey probiotic effects by Limosilactobacillus reuteri.

BACKGROUND: Intestinal Peyer's patches (PPs) form unique niches for bacteria-immune cell interactions that direct host immunity and shape the microbiome. Here we investigate how peroral administration of probiotic bacterium Limosilactobacillus reuteri R2LC affects B lymphocytes and IgA induction in the PPs, as well as the downstream consequences on intestinal microbiota and susceptibility to inflammation. RESULTS: The B cells of PPs were separated by size to circumvent activation-dependent cell identification biases due to dynamic expression of markers, which resulted in two phenotypically, transcriptionally, and spatially distinct subsets: small IgD+/GL7-/S1PR1+/Bcl6, CCR6-expressing pre-germinal center (GC)-like B cells with innate-like functions located subepithelially, and large GL7+/S1PR1-/Ki67+/Bcl6, CD69-expressing B cells with strong metabolic activity found in the GC. Peroral L. reuteri administration expanded both B cell subsets and enhanced the innate-like properties of pre-GC-like B cells while retaining them in the sub-epithelial compartment by increased sphingosine-1-phosphate/S1PR1 signaling. Furthermore, L. reuteri promoted GC-like B cell differentiation, which involved expansion of the GC area and autocrine TGFß-1 activation. Consequently, PD-1-T follicular helper cell-dependent IgA induction and production was increased by L. reuteri, which shifted the intestinal microbiome and protected against dextran-sulfate-sodium induced colitis and dysbiosis. CONCLUSIONS: The Peyer's patches sense, enhance and transmit probiotic signals by increasing the numbers and effector functions of distinct B cell subsets, resulting in increased IgA production, altered intestinal microbiota, and protection against inflammation. Video abstract.

Vigorous regular leisure-time physical activity is associated with a clinically important improvement in back pain - a secondary analysis of randomized controlled trials.

BACKGROUND: Neck and back pain are musculoskeletal conditions with serious individual and societal consequences. Current evidence about the prognostic value for neck and back pain is limited and conflicting. This prospective cohort study aimed to assess the association between leisure-time physical activity (LPA) and improvement of neck and/or back pain in a working population receiving manual therapy or general care in one of two randomized controlled trials (RCTs). METHODS: Analyses of data from two RCTs evaluating the effect of manual therapies for neck and/or back pain was conducted. Participants (n = 1 464) answered questionnaires about frequency and effort level of LPA at baseline. LPA on moderate or vigorous levels was compared to no or low/irregular moderate and vigorous levels. Pain intensity was assessed with numerical scales at baseline and 3-, 6-, and 12-month follow-up. The outcome was minimal clinically important improvement in pain intensity, defined as ≥2 points improvement in mean pain intensity at follow-up. Crude- and adjusted risk ratios (RR) with 95% confidence intervals (CI) were calculated with Poisson regression analysis and stratified by pain location. RESULTS: Participants with neck and/or back pain performing vigorous LPA showed a minimal clinically important improvement after 12 months compared to the control group; RR 1.35 (95% CI; 1.06-1.73). No effect was observed at 3 or 6 months. Moderate LPA did not improve pain intensity in any follow-up. Stratified analyses revealed that the effect of vigorous LPA at 12 months in back pain was RR 1.83 (95% CI; 1.26-2.66) and neck pain RR 1.06 (95% CI; 0.75-1.49). CONCLUSIONS: Persons with neck and/or back pain receiving manual therapy or general evidence-based care have greater chance of improvement after 12 months if they prior to treatment frequently practice vigorous LPA. When analyzed separately, the effect was only present for back pain. TRIAL REGISTRATION: Registration in Current Controlled Trials (ISRCTN), Stockholm Manual Intervention Trial (MINT), ISRCTN92249294 BJORN-trial, ISRCTN56954776.

Predicting nonrecovery in adults with incident traffic injuries including post-traumatic headache.

IMPORTANCE: The management of traffic injuries is challenging for clinicians. Knowledge about predictors of nonrecovery from traffic injuries may help to improve patient care. OBJECTIVE: To develop a prediction model for self-reported overall nonrecovery from traffic injuries six months post-collision in adults with incident traffic injuries including post-traumatic headache (PTH). DESIGN: Inception cohort studies of adults with incident traffic injuries (including PTH) injured in traffic collisions between November 1997 and December 1999 in Saskatchewan, Canada; and between January 2004 and January 2005 in Sweden. METHODS: Prediction model development and geographical external validation. SETTING: The Saskatchewan cohort (development) was population-based (N = 4,162). The Swedish cohort (validation) (N = 379) were claimants from two insurance companies covering 20% of cars driven in Sweden in 2004. PARTICIPANTS: All adults injured in traffic collisions who completed a baseline questionnaire within 30 days of collision. Excluded were those hospitalized > 2 days, lost consciousness > 30 min, or reported headache < 3/10 on the numerical rating scale. Follow-up rates for both cohorts were approximately 80%. PREDICTORS: Baseline sociodemographic, pre-injury, and injury factors. OUTCOME: Self-reported nonrecovery from all injuries (not "all better (cured)" on the self-perceived recovery scale) six months after traffic collision. RESULTS: Both cohorts were predominantly female (69.8% in Saskatchewan, 65.2% in Sweden), with median ages 35.9 years (Saskatchewan), and 38.0 years (Sweden). Predictors were age, low back pain, symptoms in arms or hands, hearing problems, sleeping problems, pre-existing headache, and lower recovery expectations. With a positive score (i.e., ≥0.85 probability), the model can rule in the presence of self-reported nonrecovery from all injuries at six months (development: specificity = 91.3%, 95% CI 89.2%-93.0%; sensitivity = 27.8%, 95% CI 26.0%-29.7%; positive likelihood ratio (LR + ) = 3.2, 95% CI 2.5-4.0; negative likelihood ratio (LR-) = 0.79, 95% CI 0.76-0.82; validation: specificity = 72.6%, 95% CI 61.4%-81.5%; sensitivity = 60.5%, 95% CI 53.9%-66.7%); LR+ = 2.2, 95% CI 1.5-3.3; LR- = 0.5, 95% CI 0.4-0.7). CONCLUSIONS AND RELEVANCE: In adults with incident traffic injuries including PTH, predictors other than those related to baseline head and neck pain drive overall nonrecovery. Developing and testing interventions targeted at the modifiable predictors may help to improve outcomes for adults after traffic collision.

Depression, anxiety and stress among Swedish university students before and during six months of the COVID-19 pandemic: A cohort study.

AIMS: The COVID-19 pandemic has had a profound effect on societies and citizens worldwide, raising concerns about potential mental health impacts. We aimed to describe trajectories of depression, anxiety and stress symptoms during the COVID-19 outbreak compared to before the outbreak, and to determine if trajectories were modified by pre-pandemic loneliness, poor sleep quality and mental health problems. METHODS: We conducted a cohort study with 1836 Swedish university students entering the study before 13 March 2020, the onset of the pandemic, with follow-ups within three (FU1) and six months (FU2) of the outbreak. Generalized Estimating Equations were used to estimate mean differences in symptom levels over time-periods, and to estimate potential effect modifications. RESULTS: We found small differences in mean levels of the depression, anxiety and stress scale (DASS-21) over time. Compared to before the pandemic, depression increased by 0.25 points of 21 (95% CI: 0.04 to 0.45) at FU1 and decreased by 0.75/21 (95% CI:-0.97 to -0.53) at FU2. Anxiety decreased from baseline to FU1 by 0.09/21 (95% CI: -0.24 to 0.07) and by 0.77/21 (95% CI: -0.93 to -0.61) to FU2. Stress decreased from baseline to FU1 by 0.30/21 (95% CI: -0.52 to -0.09) and by 1.32/21 (95% CI: -1.55 to -1.09) to FU2. Students with pre-pandemic loneliness, poor sleep quality or pre-pandemic mental health problems did not have worse trajectories of mean mental health symptoms. CONCLUSIONS: Symptom levels were relatively stable during the first three months of the pandemic, while there was a slight decrease during the summer months, probably due to seasonality effects.

Perivascular Macrophages Regulate Blood Flow Following Tissue Damage.

[Figure: see text].

Co-option of PPARα in the regulation of lipogenesis and fatty acid oxidation in CLA-induced hepatic steatosis.

Nonalcoholic-fatty-liver-disease (NAFLD) is the result of imbalances in hepatic lipid partitioning and is linked to dietary factors. We demonstrate that conjugated linoleic acid (CLA) when given to mice as a dietary supplement, induced an enlarged liver, hepatic steatosis, and increased plasma levels of fatty acid (FA), alanine transaminase, and triglycerides. The progression of NAFLD and insulin resistance was reversed by GW6471 a small-molecule antagonist of peroxisome proliferator-activated receptor α (PPARα). Transcriptional profiling of livers revealed that the genes involved in FA oxidation and lipogenesis as two core gene programs controlled by PPARα in response to CLA and GW6471 including Acaca and Acads. Bioinformatic analysis of PPARα ChIP-seq data set and ChIP-qPCR showed that GW6471 blocks PPARα binding to Acaca and Acads and abolishes the PPARα-mediated local histone modifications of H3K27ac and H3K4me1 in CLA-treated hepatocytes. Thus, our findings reveal a dual role of PPARα in the regulation of lipid homeostasis and highlight its druggable nature in NAFLD.

[Differential diagnosis in obsessive-compulsive disorder].

Obsessive-compulsive-like symptomatology may be present in various psychiatric disorders including schizophrenia. This has been described since Kraepelin and Bleuler. In this review, we draw attention to the often ignored notion of pseudo-obsession. The concept can add to the distinction between true obsession in OCD and related psychopathological phenomena in the schizophrenia spectrum disorders and improve diagnostic practice. The recent changes in the diagnostic manuals have made this distinction more difficult by allowing a lack of insight and delusional beliefs in the diagnostic criteria for OCD.

Risk of transition from occasional neck/back pain to long-duration activity limiting neck/back pain: a cohort study on the influence of poor work ability and sleep disturbances in the working population in Stockholm County.

OBJECTIVES: The prevalence of neck/back pain (NBP) is high worldwide. Limited number of studies have investigated workers with occasional NBP regarding the risk of developing long-duration activity limiting NBP (LNBP). The objectives were to assess (1) the effect of poor work ability and sleep disturbances in persons with occasional NBP on the risk of LNBP, and (2) the interaction effect of these exposures. DESIGN: Cohort study based on three subsamples from the Stockholm Public Health Cohort. SETTINGS: The working population in Stockholm County. PARTICIPANTS: Persons aged 18-60 years, reporting occasional NBP the past 6 months at baseline year 2010 (n=16 460). MEASURES: Work ability was assessed with items from the Work Ability Index, perceived mental and/or physical work ability. Sleep disturbances were self-reported current mild/severe disturbances. The outcome in year 2014 was reporting NBP the previous 6 months, occurring ≥couple of days per week and resulting in decreased work ability/restricted other daily activities. The additive effect of having both poor work ability and sleep disturbances was modelled with a dummy variable, including both exposures. Poisson log-linear regression was used to calculate risk ratios (RRs) and 95% CIs. RESULTS: At follow-up, 9% had developed LNBP. Poor work ability and sleep disturbances were independent risk factors for LNBP; adjusted RR 1.7 (95% CI: 1.4 to 2.0) and 1.4 (95% CI: 1.2 to 1.5), respectively. No additive interaction was observed. CONCLUSION: Workers with occasional NBP who have poor work ability and/or sleep disturbances are at risk of developing LNBP. Having both conditions does not exceed additive risk.

Development and validation of a model predicting post-traumatic headache six months after a motor vehicle collision in adults.

IMPORTANCE: The prognosis of post-traumatic headache is poorly understood. OBJECTIVE: To develop and validate a prognostic model to predict the presence of post-traumatic headache six months after a traffic collision in adults with incident post-traumatic headache. DESIGN: Secondary analyses of adults with incident post-traumatic headache injured in traffic collisions between November 1997 and December 1999 in Saskatchewan, Canada (development cohort); and between January 2004 and January 2005 in Sweden (validation cohort). SETTING: The Saskatchewan cohort (development) was population-based (N = 4162). The Swedish cohort (validation) (N = 379) were claimants from two insurance companies covering 20 % of cars driven in Sweden in 2004. PARTICIPANTS: All adults injured in traffic collisions who completed a baseline questionnaire within 30 days of collision. Excluded were those hospitalized >2 days, lost consciousness >30 min, or reported headache <3/10 on the numerical rating scale. Follow-up rates for both cohorts were approximately 80 %. PREDICTORS: Baseline sociodemographic, pre-injury, and injury factors. OUTCOME: Self-reported headache pain intensity ≥3 (numerical rating scale) six months after injury. RESULTS: Both cohorts were predominantly female (69.7 % in Saskatchewan, 65.2 % in Sweden), with median ages 35.9 years (Saskatchewan), and 38.0 years (Sweden). Predictors were age, work status, headache pain intensity, symptoms in arms or hands, dizziness or unsteadiness, stiffness in neck, pre-existing headache, and lower recovery expectations. With a positive score (i.e., ≥0.75 probability), the model can rule in the presence of post-traumatic headache at six months (development: specificity = 99.8 %, 95 % CI 99.5 %-99.9 %; sensitivity = 1.6 %, 95 % CI 1.0 %-2.6 %; positive likelihood ratio (LR+) = 8.0, 95 % CI 2.7-24.1; negative likelihood ratio (LR-) = 1.0, 95 % CI 1.0-1.0; validation: specificity = 95.5 %, 95 % CI 91.1 %-97.8 %; sensitivity = 27.2 %, 95 % CI 20.4 %-35.2 %); LR+ = 6.0, 95 % CI 2.8-13.2; LR- = 0.8, 95 % CI 0.7-0.8). CONCLUSIONS AND RELEVANCE: Clinicians can collect patient information on the eight predictors of our model to identify patients that will report ongoing post-traumatic headache six months after a traffic collision. Future research should focus on selecting patients at high risk of poor outcomes (using our model) for inclusion in intervention studies, and determining effective interventions for these patients.

Deep tissue massage, strengthening and stretching exercises, and a combination of both compared with advice to stay active for subacute or persistent non-specific neck pain: A cost-effectiveness analysis of the Stockholm Neck trial (STONE).

OBJECTIVE: To evaluate the cost-effectiveness of deep tissue massage ('massage'), strengthening and stretching exercises ('exercises') or a combination of both ('combined therapy') in comparison with advice to stay active ('advice') for subacute and persistent neck pain, from a societal perspective. METHODS: We conducted a cost-effectiveness analysis alongside a four-arm randomized controlled trial of 619 participants followed-up for one year. Health-related quality of life was measured using EQ-5D-3L and costs were calculated from baseline to one year. The interventions were ranked according to quality adjusted life years (QALYs) in a cost-consequence analysis. Thereafter, an incremental cost per QALY was calculated. RESULTS: In the cost-consequence analysis, in comparison with advice, exercises resulted in higher QALY gains, and massage and the combined therapy were more costly and less beneficial. Exercises may be a cost-effective treatment compared with advice to stay active if society is willing to pay 17 640 EUR per QALY. However, differences in QALY gains were minimal; on average, participants in the massage group, spent a year in a state of health valued at 0.88, exercises: 0.89, combined therapy: 0.88 and, advice: 0.88. CONCLUSIONS: Exercises are cost-effective compared to advice given that the societal willingness to pay is above 17 640 EUR per year in full health gained. Massage and a combined therapy are not cost-effective. While exercise appeared to have the best cost/benefit profile, even this treatment had only a modest benefit and treatment innovation is needed. Advice to stay active remains as a good therapeutic alternative from an economical perspective.

Effectiveness of deep tissue massage therapy, and supervised strengthening and stretching exercises for subacute or persistent disabling neck pain. The Stockholm Neck (STONE) randomized controlled trial.

OBJECTIVE: To compare the effectiveness of deep tissue massage, supervised strengthening and stretching exercises, and a combined therapy (exercise followed by massage) (index groups), with advice to stay active (control group). METHODS: Randomized controlled trial of 619 adults with subacute or persistent neck pain allocated to massage (n = 145), exercise (n = 160), combined therapy (n = 169) or advice (n = 147). Primary outcomes were minimal clinically important improvements in neck pain intensity and pain-related disability based on adapted questions from the Chronic Pain Questionnaire. Secondary outcomes were perceived recovery and sickness absence. Outcomes were measured at seven, 12, 26 and 52 weeks. RESULTS: We found improvement in pain intensity favouring massage and combined therapy compared to advice; at seven weeks (RR = 1.36; 95%CI:1.04-1.77) and 26 weeks (RR = 1.23; 95%CI:0.97-1.56); and seven (RR = 1.39; 95%CI:1.08-1.81) and 12 weeks (RR = 1.28; 95%CI:1.02-1.60) respectively, but not at later follow-ups. Exercise showed higher improvement of pain intensity at 26 weeks (RR = 1.31; 95%CI:1.04-1.65). Perceived recovery was higher in the index groups than in the advice group at all follow-ups. We found no consistent differences in pain related disability or sickness absence. CONCLUSIONS: In this study, at 12-months follow-up, none of the index therapies were more effective than advice in terms of pain intensity in the long term or in terms of pain-related disability in the short or long term. However, the index therapies led to higher incidence of improvement in pain intensity in the short term, and higher incidence of favorable perceived recovery in the short and in the long term than advice. TRIAL REGISTRATION: ISRCTN01453590. Registered 3 July 2014.