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Background Prognostic research has many important purposes, including (i) describing the natural history and clinical course of health conditions, (ii) investigating variables associated with health outcomes of interest, (iii) estimating an individual’s probability of developing different outcomes, (iv) investigating the clinical application of prediction models, and (v) investigating determinants of recovery that can inform the development of interventions to improve patient outcomes. But much prognostic research has been poorly conducted and interpreted, indicating that a number of conceptual areas are often misunderstood. Recent initiatives to improve this include the Prognosis Research Strategy (PROGRESS) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) Statement. In this paper, we aim to show how different categories of prognostic research relate to each other, to differentiate exploratory and confirmatory studies, discuss moderators and mediators, and to show how important it is to understand study designs and the differences between prediction and causation. Main text We propose that there are four main objectives of prognostic studies – description, association, prediction and causation. By causation, we mean the effect of prediction and decision rules on outcomes as determined by intervention studies and the investigation of whether a prognostic factor is a determinant of outcome (on the causal pathway). These either fall under the umbrella of exploratory (description, association, and prediction model development) or confirmatory (prediction model external validation and investigation of causation). Including considerations of causation within a prognostic framework provides a more comprehensive roadmap of how different types of studies conceptually relate to each other, and better clarity about appropriate model performance measures and the inferences that can be drawn from different types of prognostic studies. We also propose definitions of ‘candidate prognostic factors’, ‘prognostic factors’, ‘prognostic determinants (causal)’ and ‘prognostic markers (non-causal)’. Furthermore, we address common conceptual misunderstandings related to study design, analysis, and interpretation of multivariable models from the perspectives of association, prediction and causation. Conclusion This paper uses a framework to clarify some concepts in prognostic research that remain poorly understood and implemented, to stimulate discussion about how prognostic studies can be strengthened and appropriately interpreted.

Background Presenteeism is a growing problem in developed countries mostly due to an aging workforce. The economic costs related to presenteeism exceed those of absenteeism and employer health costs. Employers are implementing workplace health promotion and wellness programs to improve health among workers and reduce presenteeism. How best to design, integrate and deliver these programs are unknown. The main purpose of this study was to use an intervention mapping approach to develop a workplace health promotion and wellness program aimed at reducing presenteeism. Methods We partnered with a large international financial services company and used a qualitative synthesis based on an intervention mapping methodology. Evidence from systematic reviews and key articles on reducing presenteeism and implementing health promotion programs was combined with theoretical models for changing behavior and stakeholder experience. This was then systematically operationalized into a program using discussion groups and consensus among experts and stakeholders. Results The top health problem impacting our workplace partner was mental health. Depression and stress were the first and second highest cause of productivity loss respectively. A multi-pronged program with detailed action steps was developed and directed at key stakeholders and health conditions. For mental health, regular sharing focus groups, social networking, monthly personal stories from leadership using webinars and multi-media communications, expert-led workshops, lunch and learn sessions and manager and employee training were part of a comprehensive program. Comprehensive, specific and multi-pronged strategies were developed and aimed at encouraging healthy behaviours that impact presenteeism such as regular exercise, proper nutrition, adequate sleep, smoking cessation, socialization and work-life balance. Limitations of the intervention mapping process included high resource and time requirements, the lack of external input and viewpoints skewed towards middle and upper management, and using secondary workplace data of unknown validity and reliability. Conclusions In general, intervention mapping was a useful method to develop a workplace health promotion and wellness program aimed at reducing presenteeism. The methodology provided a step-by-step process to unravel a complex problem. The process compelled participants to think critically, collaboratively and in nontraditional ways.

Background Taking the natural course of recurrent and fluctuating low back pain (LBP) seen in longitudinal studies of adults into consideration, the aetiology and development of LBP in children and adolescents also needs to be reflected in a long-term course. Therefore, a systematic critical literature review was undertaken to assess the natural course of LBP in the general population from childhood through adolescence to young adulthood. Methods A systematic literature search was conducted in MEDLINE, EMBASE, CINAHL and PsycINFO with synonyms of search terms for 1) low back pain; 2) natural course; 3) cohort study and 4) children. Records in English, German, French, Danish, Swedish, and Norwegian were included. To assess the methodological quality of the studies, the NIH quality assessment checklist for cohort studies was adapted and risk of bias was assessed on a study level. Two authors independently reviewed selected studies, assessed quality, and extracted data. A synthesis of results in relation to the natural course of LBP was created. Results Totally, 3373 records were identified, eight articles were included for quality assessment, and finally, four studies of good to fair quality were included for synthesis of results. Indication of three common patterns of LBP were identified across studies and labelled as 1) ´children and adolescents with no LBP or low probability of LBP´ (49 to 53%), 2) ´children and adolescents with fluctuation of LBP´ (16 to 37%) and 3) ´children and adolescents with repeated reporting of LBP´ (< 1 to 10%). Conclusion Although methodological heterogeneity, mainly due to different age ranges, an indication of a natural course of LBP was seen across studies. The majority of children and adolescents repeatedly reporting no or low probability of LBP. With recall periods between one week to three months and sampling rates ranging from one to four years, a very low rate repeatedly reported LBP, and approximately one-fifth to one-third of children and adolescents had fluctuating reports of LBP. A need of future research of LBP trajectories with short reporting period lengths and narrower sampling windows in a long-term perspective is emphasized in order to study childhood influences on the development of LBP throughout life.

Background Wireless, wearable, inertial motion sensor technology introduces new possibilities for monitoring spinal motion and pain in people during their daily activities of work, rest and play. There are many types of these wireless devices currently available but the precision in measurement and the magnitude of measurement error from such devices is often unknown. This study investigated the concurrent validity of one inertial motion sensor system (ViMove) for its ability to measure lumbar inclination motion, compared with the Vicon motion capture system. Methods To mimic the variability of movement patterns in a clinical population, a sample of 34 people were included – 18 with low back pain and 16 without low back pain. ViMove sensors were attached to each participant’s skin at spinal levels T12 and S2, and Vicon surface markers were attached to the ViMove sensors. Three repetitions of end-range flexion inclination, extension inclination and lateral flexion inclination to both sides while standing were measured by both systems concurrently with short rest periods in between. Measurement agreement through the whole movement range was analysed using a multilevel mixed-effects regression model to calculate the root mean squared errors and the limits of agreement were calculated using the Bland Altman method. Results We calculated root mean squared errors (standard deviation) of 1.82° (±1.00°) in flexion inclination, 0.71° (±0.34°) in extension inclination, 0.77° (±0.24°) in right lateral flexion inclination and 0.98° (±0.69°) in left lateral flexion inclination. 95% limits of agreement ranged between -3.86° and 4.69° in flexion inclination, -2.15° and 1.91° in extension inclination, -2.37° and 2.05° in right lateral flexion inclination and -3.11° and 2.96° in left lateral flexion inclination. Conclusions We found a clinically acceptable level of agreement between these two methods for measuring standing lumbar inclination motion in these two cardinal movement planes. Further research should investigate the ViMove system’s ability to measure lumbar motion in more complex 3D functional movements and to measure changes of movement patterns related to treatment effects.

Background Investigations into the possible associations between early in life motor function and later in life musculoskeletal health, will require easily obtainable, valid, and reliable measures of gross motor function and kinematics. Marker-based motion capture systems provide reasonably valid and reliable measures, but recordings are restricted to expensive lab environments. Markerless motion capture systems can provide measures of gross motor function and kinematics outside of lab environments and with minimal interference to the subjects being investigated. It is, however, unknown if these measures are sufficiently valid and reliable in young children to warrant further use. This study aims to document the concurrent validity of a markerless motion capture system: “The Captury.” Method Measures of gross motor function and lower extremity kinematics from 14 preschool children (age between three and 6 years) performing a series of squats and standing broad jumps were recorded by a marker-based (Vicon) and a markerless (The Captury) motion capture system simultaneously, in December 2015. Measurement differences between the two systems were examined for the following variables: jump length, jump height, hip flexion, knee flexion, ankle dorsi flexion, knee varus, knee to hip separation distance ratio (KHR), ankle to hip separation distance ratio (AHR), frontal plane projection angle, frontal plane knee angle (FPKA), and frontal plane knee deviation (FPKD). Measurement differences between the systems were expressed in terms of root mean square errors, mean differences, limits of agreement (LOA), and intraclass correlations of absolute agreement (ICC (2,1) A) and consistency of agreement. Results Measurement differences between the two systems varied depending on the variables. Agreement and reliability ranged from acceptable for e.g. jump height [LOA: − 3.8 cm to 2.2 cm; ICC (2,1) A: 0.91] to unacceptable for knee varus [LOA: − 33° to 19°; ICC (2,1) A: 0.29]. Conclusions The measurements by the markerless motion capture system “The Captury” cannot be considered interchangeable with the Vicon measures, but our results suggest that this system can produce estimates of jump length, jump height, KHR, AHR, knee flexion, FPKA, and FPKD, with acceptable levels of agreement and reliability. These variables are promising for use in future research but require further investigation of their clinimetric properties.

Background Spinal pain in children and adolescents is a common condition, usually transitory, but the picture of spinal pain still needs elucidation, mainly due to variation in measurement methods. The aim of this study was to describe the occurrence of spinal pain in 8–15 year-old Danish school children, over a 3-year period. Specifically determining the characteristics of spinal pain in terms of frequency and duration. Methods The study was a 3-year prospective longitudinal cohort study including 1400 school children. The outcomes were based on weekly text messages (SMS) to the parents inquiring about the child’s musculoskeletal pain, and on clinical data from examinations of the children. Results The 3-year prevalence was 55%. The prevalence was 29%, 33% and 31% for each of the three study years respectively, and increased statistically significantly with age, especially for lumbopelvic pain. Most children had few and short-lasting episodes with spinal pain, but more than one out of five children had three or more episodes during a study year and 17% of all episodes lasted for more than 4 weeks. Conclusion This study demonstrates that spinal pain is a substantial problem. Most episodes are brief, but there are a vast number of children with frequent and long-lasting episodes of spinal pain indicating a need for action regarding evidence-based prevention and management.

Background Evidence on prognostic factors associated with progression to total hip replacement (THR) in hip osteoarthritis (OA) is for the most patient- and disease-specific characteristics either conflicting or inconclusive. Therefore, the objectives of this study of participants with hip OA enrolled in a structured program of supervised education and exercise therapy were to describe the rate of THR and to identify prognostic factors for receiving THR within the following 2 years. Methods Participants aged ≥ 45 years with hip OA enrolled in Good Life with osteoArthritis in Denmark (GLA:D®) from July 2014 to March 2017 were included. Potential prognostic factors included demographic and disease-specific baseline characteristics and measures of physical activity and quality of life (QoL). Information on THR was retrieved from The Danish National Patient Registry. A multivariable Cox proportional hazards model was developed. Results Of 3657 included participants, 30% received a THR within 2 years. Of the 100 participants already wait-listed for THR, 60% had the procedure. Of 22 candidate prognostic factors, 14 were statistically significant for receiving THR. Factors associated with a faster rate of THR included being “male” (HR 1.43), having “self-reported radiographic hip OA” (HR 2.32), being “wait-listed for THR” (HR 2.17), and having a higher “pain intensity” (HR 1.01). In contrast, faster “walking speed” (HR 0.64), better “hip-related QoL” (HR 0.98), and having “three or more comorbidities” (HR 0.62) were predictive of a slower rate of THR. Conclusion During the 2-year follow-up period, 30% of the cohort received a THR. Notably, 40% of those wait-listed for THR when entering the program did not receive THR within 2 years. A number of baseline prognostic factors for receiving THR were identified.

Background Sporadic inclusion body myositis (sIBM) is clinically characterised by progressive proximal and distal muscle weakness and impaired physical function while skeletal muscle tissue displays abnormal cellular infiltration of T cells, macrophages, and dendritic cells. Only limited knowledge exists about the effects of low-load blood flow restriction exercise in sIBM patients, and its effect on the immunological responses at the myocellular level remains unknown. The present study is the first to investigate the longitudinal effects of low-load blood flow restriction exercise on innate and adaptive immune markers in skeletal muscle from sIBM patients. Methods Twenty-two biopsy-validated sIBM patients were randomised into either 12 weeks of low-load blood flow restriction exercise (BFRE) or no exercise (CON). Five patients from the control group completed 12 weeks of BFRE immediately following participation in the 12-week control period leading to an intervention group of 16 patients. Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis for evaluation of CD3-, CD8-, CD68-, CD206-, CD244- and FOXP3-positive cells by three-colour immunofluorescence microscopy and Visiopharm-based image analysis quantification. A linear mixed model was used for the statistical analysis. Results Myocellular infiltration of CD3 − /CD8 + expressing natural killer cells increased following BFRE ( P  < 0.05) with no changes in CON. No changes were observed for CD3 + /CD8 − or CD3 + /CD8 + T cells in BFRE or CON. CD3 + /CD244 + T cells decreased in CON, while no changes were observed in BFRE. Pronounced infiltration of M1 pro-inflammatory (CD68 + /CD206 − ) and M2 anti-inflammatory (CD68 + /CD206 + ) macrophages were observed at baseline; however, no longitudinal changes in macrophage content were observed for both groups. Conclusions Low-load blood flow restriction exercise elicited an upregulation in CD3 − /CD8 + expressing natural killer cell content, which suggests that 12 weeks of BFRE training evokes an amplified immune response in sIBM muscle. However, the observation of no changes in macrophage or T cell infiltration in the BFRE-trained patients indicates that patients with sIBM may engage in this type of exercise with no risk of intensified inflammatory activity.

BACKGROUND: Accelerometry is increasingly being recognized as an accurate and reliable method to assess free-living physical activity (PA) in children and adolescents. However, accelerometer data reduction criteria remain inconsistent, and the consequences of excluding participants in for example intervention studies are not well described. In this study, we investigated how different data reduction criteria changed the composition of the adolescent population retained in accelerometer data analysis. METHODS: Accelerometer data (Actigraph GT3X), anthropometric measures and survey data were obtained from 1348 adolescents aged 11–14 years enrolled in the Danish SPACE for physical activity study. Accelerometer data were analysed using different settings for each of the three key data reduction criteria: (1) number of valid days; (2) daily wear time; and (3) non-wear time. The effects of the selected setting on sample retention and PA counts were investigated and compared. Ordinal logistic regression and multilevel mixed-effect linear regression models were used to analyse the impact of differing non-wear time definitions in different subgroups defined by body mass index, age, sex, and self-reported PA and sedentary levels. RESULTS: Increasing the minimum requirements for daily wear time and the number of valid days and applying shorter non-wear definitions, resulted in fewer adolescents retained in the dataset. Moreover, the different settings for non-wear time significantly influenced which participants would be retained in the accelerometer data analyses. Adolescents with a higher BMI (OR:0.93, CI:0.87-0.98, p=0.015) and older adolescents (OR:0.68, CI:0.49-0.95, p=0.025) were more likely to be excluded from analysis using 10 minutes of non-wear compared to longer non-wear time periods. Overweight and older adolescents accumulated more daily non-wear time if the non-wear time setting was short, and the relative difference between groups changed depending on the non-wear setting. Overweight and older adolescents did also accumulate more sedentary time, but this was not significant correlated to the non-wear setting used. CONCLUSIONS: Even small differences in accelerometer data reduction criteria can have substantial impact on sample size and PA and sedentary outcomes. This study highlighted the risk of introducing bias with more overweight and older adolescents excluded from the analysis when using short non-wear time definitions.