Perivascular Macrophages Regulate Blood Flow Following Tissue Damage.

[Figure: see text].

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.

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.

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.

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.

Age and seasonal variation in testis and baculum morphology in East Greenland polar bears (Ursus maritimus) in relation to high concentrations of persistent organic pollutants.

Persistent organic pollutants (POPs) are found in high concentrations in the Artic. Polar bears (Ursus maritimus) are one of the most exposed mammals in the Arctic and are thereby vulnerable to reproductive disruption. The aim of this study was to investigate male polar bear reproduction based on a detailed evaluation of testis histology and to assess possible effects of environmental chemicals on male polar bear reproduction. Reproductive groups that were identified based on histology were as follows: actively reproductive (REP), non-reproductive either with degenerated testes (DEG), undeveloped seminiferous tubules (UND), or morphology in-transition (INT). Categorization into these groups was supported by significant differences in testis and baculum measurements among REP, DEG, and UND, as well as differences in the area and diameter of seminiferous tubules among REP, DEG, and UND. These results show that it is possible to identify the reproductive stage in polar bears even if capture date and or age is lacking. Based on testis morphology we suggest that adult male polar bears from East Greenland have active spermatogenesis in February to June, and inactive degenerated testes in August to January. January to February was the main period of reproductive transition, characterised by a shift between inactive and active spermatogenesis. Baculum and testis size measurements decreased significantly with increasing concentrations of the chlordane metabolite oxychlordane, suggesting a potential impact on male reproductive success. Half of the investigated polar bears in REP group displayed signs of disorganization of the spermatogenesis which might be a sign of disrupted reproduction. However, no correlations with levels of the investigated POPs were detected. Reproductive organ measurements in polar bears differed significantly between REP and DEG groups, which cannot be explained by age, and therefore should be considered when investigating the effect of POPs on male reproduction.

Risk factors for, and prevention of, shoulder injuries in overhead sports: a systematic review with best-evidence synthesis.

OBJECTIVE: To assess the evidence for risk factors and prevention measures for shoulder injuries in overhead sports. DESIGN: Systematic review with best-evidence synthesis. DATA SOURCES: Medline (Ovid), PubMed (complementary search), Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials, cohort studies and case-control studies on risk factors or prevention measures for shoulder injuries in overhead sports. The eligible studies were quality assessed using the Scottish Intercollegiate Guidelines Network criteria. RESULTS: Of 4778 studies identified, 38 were eligible for quality review and 17 met the quality criteria to be included in the evidence synthesis. One additional quality study presented a shoulder injury prevention programme. Most studies focused on baseball, lacrosse or volleyball (n=13). The risk factors examined included participation level (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external workload (n=2). The evidence for all risk factors was limited or conflicting. The effect of the prevention programme within the subgroup of uninjured players at baseline was modest and possibly lacked statistical power. CONCLUSIONS: All investigated potential risk factors for shoulder injury in overhead sports had limited evidence, and most were non-modifiable (eg, sex). There is also limited evidence for the effect of shoulder injury prevention measures in overhead sports. PROSPERO TRIAL REGISTRATION NUMBER: CRD42015026850.

Female adolescent elite handball players are more susceptible to shoulder problems than their male counterparts.

PURPOSE: Shoulder problems are frequent among senior elite handball players. The objective of this study was to assess the prevalence of shoulder problems among adolescent elite handball players and to investigate potential differences in gender, school grade, playing position and playing level. METHODS: During the 2014 and 2015 pre-season periods, 471 players (age 15-18 years, 54% female) completed a comprehensive baseline questionnaire regarding history of any shoulder pain and shoulder problems experienced during the past season. The players were monitored weekly for one competition season (September-April) regarding shoulder problems and the amount of match and training. Generalised linear models with a binomial link function were used to calculate a prevalence ratio (PR) with 95% confidence interval (CI) to compare the subgroups of players. RESULTS: In total, 110 players (23%) reported having substantial shoulder problems (defined as moderate/severe reduction in training volume, or moderate/severe reduction in performance, or complete inability to participate) at some point during the follow-up season, of which almost half reported complete inability to participate. Of those players reporting substantial problems, 43% (95% CI 39-48) did so for at least 3 consecutive weeks during the season. The prevalence was significantly higher in female players (PR 1.46, 95% 1.04-2.06) and in backcourt players (PR 1.58, 95% CI 1.08-2.32), but no differences were found for school grade (PR 1.21 95% CI 0.88-1.67) or playing level (PR 1.09 95% CI 0.76-1.56). CONCLUSIONS: The prevalence of substantial shoulder problems in adolescent elite handball players is high, especially among females, and this warrants further studies on risk factors for shoulder injury and the development of prevention strategies in handball players already before the age of 15. These findings also highlight the importance of introducing a clinical monitoring programme on a routine basis and improving the medical support, taking gender-related aspects into consideration, at handball-profiled secondary schools. LEVEL OF EVIDENCE: II.

Carbonic anhydrase generates CO2 and H+ that drive spider silk formation via opposite effects on the terminal domains.

Spider silk fibers are produced from soluble proteins (spidroins) under ambient conditions in a complex but poorly understood process. Spidroins are highly repetitive in sequence but capped by nonrepetitive N- and C-terminal domains (NT and CT) that are suggested to regulate fiber conversion in similar manners. By using ion selective microelectrodes we found that the pH gradient in the silk gland is much broader than previously known. Surprisingly, the terminal domains respond in opposite ways when pH is decreased from 7 to 5: Urea denaturation and temperature stability assays show that NT dimers get significantly stabilized and then lock the spidroins into multimers, whereas CT on the other hand is destabilized and unfolds into ThT-positive ß-sheet amyloid fibrils, which can trigger fiber formation. There is a high carbon dioxide pressure (pCO2) in distal parts of the gland, and a CO2 analogue interacts with buried regions in CT as determined by nuclear magnetic resonance (NMR) spectroscopy. Activity staining of histological sections and inhibition experiments reveal that the pH gradient is created by carbonic anhydrase. Carbonic anhydrase activity emerges in the same region of the gland as the opposite effects on NT and CT stability occur. These synchronous events suggest a novel CO2 and proton-dependent lock and trigger mechanism of spider silk formation.

A prospective cohort study identifying risk factors for shoulder injuries in adolescent elite handball players: the Karolinska Handball Study (KHAST) study protocol.

BACKGROUND: Handball is a physical contact sport that includes frequent overhead throwing, and this combination leads to a high rate of shoulder injuries. Several factors have been associated with shoulder injuries in overhead athletes, but strong scientific evidence is lacking for most suggested risk factors. We therefore designed the Karolinska Handball Study (KHAST) with the aim to identify risk factors for shoulder injuries in adolescent male and female elite handball players studying at handball-profiled secondary schools in Sweden. Secondary objectives are to investigate whether shoulder function changes during the competition season and whether the physical profile of the players changes during their time in secondary school. METHODS: Players aged 15 to 19 years were included during the pre-season period of the 2014-2015 and the 2015-2016 seasons. At inclusion, players signed informed consent and filled in a questionnaire regarding playing position, playing level, previous handball experience, history of shoulder problems and athletic identity. Players also completed a detailed test battery at baseline evaluating the shoulder, neck and trunk. Players were then prospectively monitored weekly during the 2014-2015 and/or 2015-2016 competitive seasons regarding injuries and training/match workload. Results from the annual routine physical tests in the secondary school curriculum including bench press, deep squat, hand grip strength, clean lifts, squat jumps, counter movement jumps, <30 m sprints, chins, dips and Cooper's test will be collected until the end of the competitive season 2017-2018. The primary outcome is the incidence of shoulder injuries and shoulder problems. The secondary outcome is the prevalence of shoulder injuries and shoulder problems. DISCUSSION: Shoulder problems are frequent among handball players and a reduction of these injuries is therefore warranted. However, in order to introduce appropriate preventive measures, a detailed understanding of the underlying risk factors is needed. Our study has a high potential to identify important risk factors for shoulder injuries in adolescent elite handball players owing to a large study sample, a high response rate, data collection during consecutive seasons, and recording of potential confounding factors.

Effect of Early Intensive Care on Recovery From Whiplash-Associated Disorders: Results of a Population-Based Cohort Study.

OBJECTIVE: To determine whether the results from previous research suggesting that early intensive health care delays recovery from whiplash-associated disorders (WADs) were confounded by expectations of recovery and whether the association between early health care intensity and time to recovery varies across patterns of health care. DESIGN: Population-based inception cohort. SETTING: All adults (≥18y) injured in motor vehicle collisions who received treatment from a regulated health professional or reported their injuries to the single provincially administered motor vehicle insurer. PARTICIPANTS: Participants with WAD (N=5204). Self-report visits to physicians, chiropractors, physiotherapists, massage therapists, and other professionals during the first 42 days postcollision were used to define health care intensity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Self-perceived recovery. RESULTS: Individuals with high utilization health care had slower recovery independent of expectation of recovery and other confounders. Compared with individuals who reported low utilization of physician services, recovery was slower for those with high health care utilization, regardless of the type of profession. For instance, those with high physician (hazard rate ratio [HRR]=.56; 95% confidence interval [CI], .42-.75), physician and high physiotherapy utilization (HRR=.68; 95% CI, .61-.77), physician and high chiropractor utilization (HRR=.74; 95% CI, .64-.85), and physician and high massage therapy utilization (HRR=.78; 95% CI, .68-.90) had significantly slower recovery. CONCLUSIONS: Our study adds to the existing evidence that early intensive care is associated with slower recovery from WAD, independent of expectation of recovery. The results have policy implications and suggest that the optimal management of WADs focuses on reassurance and education instead of intensive care.

Spinal pain--good sleep matters: a secondary analysis of a randomized controlled trial.

PURPOSE: The estimated prevalence of poor sleep in patients with non-specific chronic low back pain is estimated to 64% in the adult population. The annual cost for musculoskeletal pain and reported poor sleep is estimated to be billions of dollars annually in the US. The aim of this cohort study with one-year follow-up was to explore the role of impaired sleep with daytime consequence on the prognosis of non-specific neck and/or back pain. METHODS: Secondary analysis of a randomized controlled trial, including 409 patients. RESULTS: Patients with good sleep at baseline were more likely to experience a minimal clinically important difference in pain [OR 2.03 (95% CI 1.22-3.38)] and disability [OR 1.85 (95% CI 1.04-3.30)] compared to patients with impaired sleep at one-year follow-up. CONCLUSION: Patients with non-specific neck and/or back pain and self-reported good sleep are more likely to experience a minimal clinically important difference in pain and disability compared to patients with impaired sleep with daytime consequence.

The impact of work related physical activity and leisure physical activity on the risk and prognosis of neck pain - a population based cohort study on workers.

BACKGROUND: The effect of physical activity on risk and prognosis for neck pain has been studied earlier with inconclusive results. There is a need for large prospective studies on the subject. The aim of this study was to investigate if work related physical activity and physical activity during leisure time are of importance for the risk and prognosis of neck pain in men and women. METHODS: We used the Stockholm Public Health Cohort and formed two sub-cohorts of the working population based on data from 2002. Cohort I (risk cohort) included persons without neck pain (n = 4681), and cohort II (prognostic cohort) included persons with occasional neck pain (n = 6820) during the previous six months. Both cohorts were assessed for the outcome long duration troublesome neck pain (LDNP) in 2007. The exposures and potential confounders were assessed through a questionnaire in 2002. The question regarding work related physical activity over the past 12 months had five answering categories ranging from "sedentary" to"heavy". The question regarding leisure physical activity for the past 12 months had five answering categories ranging from "sedentary" to "regular physical activity". LDNP in 2007 was defined as having had troublesome neck pain lasting ≥ 3 consecutive months during the previous five years. Associations between work related physical activity and LDNP, as well as leisure physical activity and LDNP, were investigated by multivariable logistic regression, considering potential confounding factors. RESULTS: In cohort I (risk cohort) we found an association between leisure physical activity and LDNP. In cohort II (prognostic cohort) we found no association between the exposures and the outcome. CONCLUSION: The results suggest that leisure physical activity has a protective effect on the risk of developing LDNP in a population free from neck pain. It did not, however, affect the prognosis of occasional neck pain. Neither the risk nor the prognosis of neck pain was affected by work related physical activity in this study.

Three combinations of manual therapy techniques within naprapathy in the treatment of neck and/or back pain: a randomized controlled trial.

BACKGROUND: Manual therapy as spinal manipulation, spinal mobilization, stretching and massage are common treatment methods for neck and back pain. The objective was to compare the treatment effect on pain intensity, pain related disability and perceived recovery from a) naprapathic manual therapy (spinal manipulation, spinal mobilization, stretching and massage) to b) naprapathic manual therapy without spinal manipulation and to c) naprapathic manual therapy without stretching for male and female patients seeking care for back and/or neck pain. METHOD: Participants were recruited among patients, ages 18-65, seeking care at the educational clinic of Naprapathögskolan - the Scandinavian College of Naprapathic Manual Medicine in Stockholm. The patients (n = 1057) were randomized to one of three treatment arms a) manual therapy (i.e. spinal manipulation, spinal mobilization, stretching and massage), b) manual therapy excluding spinal manipulation and c) manual therapy excluding stretching. The primary outcomes were minimal clinically important improvement in pain intensity and pain related disability. Treatments were provided by naprapath students in the seventh semester of eight total semesters. Generalized estimating equations and logistic regression were used to examine the association between the treatments and the outcomes. RESULTS: At 12 weeks follow-up, 64% had a minimal clinically important improvement in pain intensity and 42% in pain related disability. The corresponding chances to be improved at the 52 weeks follow-up were 58% and 40% respectively. No systematic differences in effect when excluding spinal manipulation and stretching respectively from the treatment were found over 1 year follow-up, concerning minimal clinically important improvement in pain intensity (p = 0.41) and pain related disability (p = 0.85) and perceived recovery (p = 0.98). Neither were there disparities in effect when male and female patients were analyzed separately. CONCLUSION: The effect of manual therapy for male and female patients seeking care for neck and/or back pain at an educational clinic is similar regardless if spinal manipulation or if stretching is excluded from the treatment option. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92249294.

γδ T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer.

Intestinal homeostasis is maintained by a hierarchy of immune defenses acting in concert to minimize contact between luminal microorganisms and the intestinal epithelial cell surface. The intestinal mucus layer, covering the gastrointestinal tract epithelial cells, contributes to mucosal homeostasis by limiting bacterial invasion. In this study, we used γδ T-cell-deficient (TCRδ(-/-)) mice to examine whether and how γδ T-cells modulate the properties of the intestinal mucus layer. Increased susceptibility of TCRδ(-/-) mice to dextran sodium sulfate (DSS)-induced colitis is associated with a reduced number of goblet cells. Alterations in the number of goblet cells and crypt lengths were observed in the small intestine and colon of TCRδ(-/-) mice compared with C57BL/6 wild-type (WT) mice. Addition of keratinocyte growth factor to small intestinal organoid cultures from TCRδ(-/-) mice showed a marked increase in crypt growth and in both goblet cell number and redistribution along the crypts. There was no apparent difference in the thickness or organization of the mucus layer between TCRδ(-/-) and WT mice, as measured in vivo. However, γδ T-cell deficiency led to reduced sialylated mucins in association with increased gene expression of gel-secreting Muc2 and membrane-bound mucins, including Muc13 and Muc17. Collectively, these data provide evidence that γδ T cells play an important role in the maintenance of mucosal homeostasis by regulating mucin expression and promoting goblet cell function in the small intestine.

Introduction to the findings of the International Collaboration on Mild Traumatic Brain Injury Prognosis: what is a prognostic study?

Prognostic studies of mild traumatic brain injury (MTBI) can serve many purposes. First, they are used to describe paths and outcomes of patients with MTBI. Second, they provide information on which characteristics are associated with the occurrence of outcomes. Third, they provide insight into the causation of poor or favorable course of the disease. Finally, they can assess how differences in the probability of outcomes can help predict the course of patients. In this article, we summarize methodologic principles used by the International Collaboration on MTBI Prognosis to appraise the prognostic literature. Differentiating prognostic factors (causally linked with outcome), prognostic markers (associated but not causally), and predictors is important to guide interventions, public health policy, and research. Ideally, prognostic studies need a clear statement of the type of question (hypothesis-generating descriptive, exploration of possible prognostic variables, confirmatory modeling of prognosis); a cohort study design with standardized follow-up of a representative population of patients with MTBI; a standardized data collection using reliable and accurate tools to capture clinically, biologically, psychologically, or socially relevant variables and outcomes; and an analysis of data based on survival methods. Interpretation of prognostic studies should consider biases related to differential inclusion of nonrepresentative samples of patients, poor measurements of outcomes, and poor control for confounders. Transferring prognostic results into clinical practice should be based on estimates of the predictive performance of models and on a demonstration that patient outcomes can be improved by the use of prediction rules.

Systematic review of prognosis after mild traumatic brain injury in the military: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: The World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury (MTBI) published its findings on the prognosis of MTBI in 2004. This is an update of that review with a focus on deployed military personnel. DATA SOURCES: Relevant literature published between January 2001 and February 2012 listed in MEDLINE and 4 other databases. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. After 77,914 titles and abstracts were screened, 13 articles were rated eligible for this review and 3 (23%) with a low risk of bias were accepted. Two independent reviewers critically appraised eligible studies using a modification of the Scottish Intercollegiate Guidelines Network criteria. DATA EXTRACTION: The reviewers independently extracted data from eligible studies and produced evidence tables. DATA SYNTHESIS: The evidence was synthesized qualitatively and presented in evidence tables. Our findings are based on 3 studies of U.S. military personnel who were deployed in Iraq or Afghanistan. We found that military personnel with MTBI report posttraumatic stress disorder and postconcussive symptoms. In addition, reporting of postconcussive symptoms differed on the basis of levels of combat stress the individuals experienced. The evidence suggests a slight decline in neurocognitive function after MTBI, but this decline was in the normal range of brain functioning. CONCLUSIONS: We found limited evidence that combat stress, posttraumatic stress disorder, and postconcussive symptoms affect recovery and prognosis of MTBI in military personnel. Additional high-quality research is needed to fully assess the prognosis of MTBI in military personnel.

Nonsurgical interventions after mild traumatic brain injury: a systematic review. Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence regarding the impact of nonsurgical interventions on persistent symptoms after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) with terms including "rehabilitation." Inclusion criteria were original, peer-reviewed research published in English and other languages. References were also identified from the bibliographies of eligible articles. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI cases and assess nonsurgical interventions using clinically relevant outcomes such as self-rated recovery. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from the admissible studies into evidence tables. DATA SYNTHESIS: The evidence was synthesized qualitatively according to the modified SIGN criteria. Recommendations were linked to the evidence tables using a best-evidence synthesis. After 77,914 records were screened, only 2 of 7 studies related to nonsurgical interventions were found to have a low risk of bias. One studied the effect of a scheduled telephone intervention offering counseling and education on outcome and found a significantly better outcome for symptoms (6.6 difference in adjusted mean symptom score; 95% confidence interval, 1.2-12.0), but no difference in general health outcome at 6 months after MTBI. The other was a randomized controlled trial of the effectiveness of 6 days of bed rest on posttraumatic complaints 6 months postinjury, compared with no bed rest, and found no effect. CONCLUSIONS: Some evidence suggests that early, reassuring educational information is beneficial after MTBI. Well-designed intervention studies are required to develop effective treatments and improve outcomes for adults and children at risk for persistent symptoms after MTBI.

Methodological issues and research recommendations for prognosis after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

The International Collaboration on Mild Traumatic Brain Injury (MTBI) Prognosis performed a comprehensive search and critical review of the literature from 2001 to 2012 to update the 2002 best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force on the prognosis of MTBI. Of 299 relevant studies, 101 were accepted as scientifically admissible. The methodological quality of the research literature on MTBI prognosis has not improved since the 2002 Task Force report. There are still many methodological concerns and knowledge gaps in the literature. Here we report and make recommendations on how to avoid methodological flaws found in prognostic studies of MTBI. Additionally, we discuss issues of MTBI definition and identify topic areas in need of further research to advance the understanding of prognosis after MTBI. Priority research areas include but are not limited to the use of confirmatory designs, studies of measurement validity, focus on the elderly, attention to litigation/compensation issues, the development of validated clinical prediction rules, the use of MTBI populations other than hospital admissions, continued research on the effects of repeated concussions, longer follow-up times with more measurement periods in longitudinal studies, an assessment of the differences between adults and children, and an account for reverse causality and differential recall bias. Well-conducted studies in these areas will aid our understanding of MTBI prognosis and assist clinicians in educating and treating their patients with MTBI.