Developing and assessing the measurement properties of an instrument to assess the impact of musculoskeletal pain in children aged 9 to 12-the pediatric musculoskeletal pain impact summary score.

BACKGROUND: Despite the high prevalence of musculoskeletal (MSK) pain in children, there is a lack of instruments to measure the impact of MSK pain on children's activity and participation. OBJECTIVE: To assess the reliability and construct validity of the Pediatric MSK Pain Impact summary score in school children (aged 9 to 12) with MSK pain. METHODS: We used a pragmatic approach in a reflective framework to assess internal consistency, structural validity, convergent validity, and discriminative validity in a sample of 615 children with MSK pain. RESULTS: The confirmatory factor analysis results indicate that the summary score has limited internal consistency and construct validity. The estimated Cronbach's alpha was 0.63, and most goodness of fit indices met the recommended thresholds (SRMR = 0.030; GFI = 0.993, CFI = 0.955, RMSEA 0.073), although they were close to the lower bounds of the thresholds. The convergent validity showed appropriate correlation of the summary score with quality of life (r = -0.33), care-seeking (r = 0.45), and medication intake (r = 0.37). Discriminative validity showed that the instrument can discriminate between the impact of pain on children with frequent and infrequent (2.93; 95% CI: 2.36 - 3.50) MSK pain. CONCLUSION: The Pediatric MSK Pain Impact summary showed limited internal consistency and construct validity; however, it can discriminate between children with frequent and infrequent pain. The results are promising for clinical and research practices as it is a short and convenient tool to be used in school-aged children.

It's OK to move! Effect of a brief video on community confidence in activity despite back pain: A randomised trial.

OBJECTIVE: To estimate the difference in confidence to become active despite low back pain in people who were exposed to one of two video interventions delivered on social media, compared to no intervention. DESIGN: A proof of concept three group randomised controlled trial, in a 1:1:1 ratio. METHODS: Participants aged 18 years and over, with and without low back pain, were recruited via the social media channel Facebook, to view either a humorous video, a neutral video or to no intervention. The videos were delivered online, explained evidence-based management for low back pain, and were designed to "go viral". The primary outcome was confidence in becoming active despite pain, measured using the Pain Self Efficacy Questionnaire(Item 10) [range from 0 (not at all confident) to 6 (completely confident)] immediately after watching the video. We aimed to capture the real-time impact and immediate reactions that contributed to the content's reach. RESULTS: Among 1933 randomized participants (mean [SD] age 58.9 [14.0] years, 1285 [75%] women) 1232 [70%] had low back pain and 88.8% completed the primary outcome. 1264 participants were randomised to receive a video intervention, and 633 participants did not receive a video. On a 6-point scale, individuals exposed to either video (n=1088) showed a mean confidence level 0.3 points higher (95% CI 0.1 to 0.6) compared with no video (n=630). CONCLUSION: Participants who viewed a brief video intervention reported a very small difference in confidence to become active despite low back pain, compared with no intervention. The difference may lack clinical relevance.

Overview of the economic burden of musculoskeletal pain in children and adolescents: a systematic review with meta-analysis.

ABSTRACT: Studies suggest a high economic burden among children and adolescents with musculoskeletal pain. There is no summary in the literature on the overall economic burden of musculoskeletal pain in children and adolescents. The aim of this systematic review of cost-of-illness studies was to synthesize the economic burden of musculoskeletal pain in children and adolescents. We conducted electronic searches on MEDLINE, EMBASE, CINAHL, EconLit, NHSEED, and HTA databases. We included cost-of-illness studies that estimated healthcare, patient/family, lost productivity, and/or societal costs in children and adolescents with musculoskeletal pain. The risk of bias was assessed with the Consolidated Health Economic Evaluation Reporting Standards checklist. All values were adjusted to the same reference year (2021) and converted to American Dollar. We included 45 cost-of-illness studies (n = 665,623). Twenty-two studies estimated the annual healthcare costs that ranged from $143 to $41,379 per patient. Nine studies estimated the annual patient/family costs that ranged from $287 to $27,972 per patient. Seven studies estimated the annual lost productivity costs that ranged from $124 to $4671 per patient. Nine studies estimated the annual societal costs that ranged from $1095 to $69,351 per patient. Children and adolescents with juvenile idiopathic arthritis and musculoskeletal pain had higher annual incremental healthcare costs than those without these conditions (mean difference: $3800 higher, 95% confidence interval [CI]: 50-7550; mean difference: $740 higher, 95% CI: 470-1,010, respectively). In conclusion, the estimated annual economic burden of children and adolescents with musculoskeletal pain ranged from $124 to $69,351.

Individuals with musculoskeletal conditions awaiting orthopaedic surgery consultation: an untapped opportunity for patient health management?

OBJECTIVE: To describe the health characteristics, condition-specific measures, chronic disease risk factors, and healthcare and medication use over time of individuals with musculoskeletal conditions awaiting orthopaedic surgical consultation. Study importance: Musculoskeletal conditions are highly prevalent in the general population and often coexist with chronic diseases. However, little is documented about the overall health of this group. This study describes the health of these individuals, with particular emphasis on modifiable risk factors of chronic disease. STUDY TYPE: A repeated measures longitudinal cohort study of individuals referred for orthopaedic consultation across three time points (2014, 2015 and 2016). METHODS: This study was undertaken in the orthopaedic outpatient service of a public tertiary referral hospital in New South Wales, Australia. Participants were aged 18 years and older and were referred for and awaiting orthopaedic surgical consultation for a musculoskeletal condition (back, neck, hand or wrist pain, or hip or knee osteoarthritis). Measures included patient demographics, condition-specific indicators (e.g. pain, disability, quality of life [QoL]) and chronic disease risk factors (e.g., excess weight, smoking). RESULTS: The mean age of participants was 57.7 years, and 7.3% identified as Aboriginal and/or Torres Strait Islander. Back (43.1%) and knee (35.0%) pain were the most prevalent conditions. At baseline (N = 1052), participants reported moderate pain (mean numerical pain rating scale score of 6.4, standard deviation [SD] 2.4) and QoL (Physical Component Score of 32.7, SD 10.7; Mental Component Score of 46.6, SD 13.3). Chronic disease risk factors were highly prevalent, with 74.6% of participants having three or more. For most measures, there were only small changes over time. CONCLUSION: Individuals with musculoskeletal conditions who are awaiting orthopaedic surgical consultation have a complex clinical picture and numerous chronic disease risk factors. Given the modifiable nature of many of these risk factors, identifying and addressing them before or while awaiting consultation may improve the health of these individuals.

Red flags to screen for vertebral fracture in patients presenting with low-back pain.

EDITORIAL NOTE: See https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014461.pub2/full for a more recent review that covers this topic and has superseded this review. BACKGROUND: Low-back pain (LBP) is a common condition seen in primary care. A principal aim during a clinical examination is to identify patients with a higher likelihood of underlying serious pathology, such as vertebral fracture, who may require additional investigation and specific treatment. All 'evidence-based' clinical practice guidelines recommend the use of red flags to screen for serious causes of back pain. However, it remains unclear if the diagnostic accuracy of red flags is sufficient to support this recommendation. OBJECTIVES: To assess the diagnostic accuracy of red flags obtained in a clinical history or physical examination to screen for vertebral fracture in patients presenting with LBP. SEARCH METHODS: Electronic databases were searched for primary studies between the earliest date and 7 March 2012. Forward and backward citation searching of eligible studies was also conducted. SELECTION CRITERIA: Studies were considered if they compared the results of any aspect of the history or test conducted in the physical examination of patients presenting for LBP or examination of the lumbar spine, with a reference standard (diagnostic imaging). The selection criteria were independently applied by two review authors. DATA COLLECTION AND ANALYSIS: Three review authors independently conducted 'Risk of bias' assessment and data extraction. Risk of bias was assessed using the 11-item QUADAS tool. Characteristics of studies, patients, index tests and reference standards were extracted. Where available, raw data were used to calculate sensitivity and specificity with 95% confidence intervals (CI). Due to the heterogeneity of studies and tests, statistical pooling was not appropriate and the analysis for the review was descriptive only. Likelihood ratios for each test were calculated and used as an indication of clinical usefulness. MAIN RESULTS: Eight studies set in primary (four), secondary (one) and tertiary care (accident and emergency = three) were included in the review. Overall, the risk of bias of studies was moderate with high risk of selection and verification bias the predominant flaws. Reporting of index and reference tests was poor. The prevalence of vertebral fracture in accident and emergency settings ranged from 6.5% to 11% and in primary care from 0.7% to 4.5%. There were 29 groups of index tests investigated however, only two featured in more than two studies. Descriptive analyses revealed that three red flags in primary care were potentially useful with meaningful positive likelihood ratios (LR+) but mostly imprecise estimates (significant trauma, older age, corticosteroid use; LR+ point estimate ranging 3.42 to 12.85, 3.69 to 9.39, 3.97 to 48.50 respectively). One red flag in tertiary care appeared informative (contusion/abrasion; LR+ 31.09, 95% CI 18.25 to 52.96). The results of combined tests appeared more informative than individual red flags with LR+ estimates generally greater in magnitude and precision. AUTHORS' CONCLUSIONS: The available evidence does not support the use of many red flags to specifically screen for vertebral fracture in patients presenting for LBP. Based on evidence from single studies, few individual red flags appear informative as most have poor diagnostic accuracy as indicated by imprecise estimates of likelihood ratios. When combinations of red flags were used the performance appeared to improve. From the limited evidence, the findings give rise to a weak recommendation that a combination of a small subset of red flags may be useful to screen for vertebral fracture. It should also be noted that many red flags have high false positive rates; and if acted upon uncritically there would be consequences for the cost of management and outcomes of patients with LBP. Further research should focus on appropriate sets of red flags and adequate reporting of both index and reference tests.

Red flags to screen for vertebral fracture in people presenting with low back pain.

BACKGROUND: Low back pain is a common presentation across different healthcare settings. Clinicians need to confidently be able to screen and identify people presenting with low back pain with a high suspicion of serious or specific pathology (e.g. vertebral fracture). Patients identified with an increased likelihood of having a serious pathology will likely require additional investigations and specific treatment. Guidelines recommend a thorough history and clinical assessment to screen for serious pathology as a cause of low back pain. However, the diagnostic accuracy of recommended red flags (e.g. older age, trauma, corticosteroid use) remains unclear, particularly those used to screen for vertebral fracture. OBJECTIVES: To assess the diagnostic accuracy of red flags used to screen for vertebral fracture in people presenting with low back pain. Where possible, we reported results of red flags separately for different types of vertebral fracture (i.e. acute osteoporotic vertebral compression fracture, vertebral traumatic fracture, vertebral stress fracture, unspecified vertebral fracture). SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 26 July 2022. SELECTION CRITERIA: We considered primary diagnostic studies if they compared results of history taking or physical examination (or both) findings (index test) with a reference standard test (e.g. X-ray, magnetic resonance imaging (MRI), computed tomography (CT), single-photon emission computerised tomography (SPECT)) for the identification of vertebral fracture in people presenting with low back pain. We included index tests that were presented individually or as part of a combination of tests. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data for diagnostic two-by-two tables from the publications or reconstructed them using information from relevant parameters to calculate sensitivity, specificity, and positive (+LR) and negative (-LR) likelihood ratios with 95% confidence intervals (CIs). We extracted aspects of study design, characteristics of the population, index test, reference standard, and type of vertebral fracture. Meta-analysis was not possible due to heterogeneity of studies and index tests, therefore the analysis was descriptive. We calculated sensitivity, specificity, and LRs for each test and used these as an indication of clinical usefulness. Two review authors independently conducted risk of bias and applicability assessment using the QUADAS-2 tool. MAIN RESULTS: This review is an update of a previous Cochrane Review of red flags to screen for vertebral fracture in people with low back pain. We included 14 studies in this review, six based in primary care, five in secondary care, and three in tertiary care. Four studies reported on 'osteoporotic vertebral fractures', two studies reported on 'vertebral compression fracture', one study reported on 'osteoporotic and traumatic vertebral fracture', two studies reported on 'vertebral stress fracture', and five studies reported on 'unspecified vertebral fracture'. Risk of bias was only rated as low in one study for the domains reference standard and flow and timing. The domain patient selection had three studies and the domain index test had six studies rated at low risk of bias. Meta-analysis was not possible due to heterogeneity of the data. Results from single studies suggest only a small number of the red flags investigated may be informative. In the primary healthcare setting, results from single studies suggest 'trauma' demonstrated informative +LRs (range: 1.93 to 12.85) for 'unspecified vertebral fracture' and 'osteoporotic vertebral fracture' (+LR: 6.42, 95% CI 2.94 to 14.02). Results from single studies suggest 'older age' demonstrated informative +LRs for studies in primary care for 'unspecified vertebral fracture' (older age greater than 70 years: 11.19, 95% CI 5.33 to 23.51). Results from single studies suggest 'corticosteroid use' may be an informative red flag in primary care for 'unspecified vertebral fracture' (+LR range: 3.97, 95% CI 0.20 to 79.15 to 48.50, 95% CI 11.48 to 204.98) and 'osteoporotic vertebral fracture' (+LR: 2.46, 95% CI 1.13 to 5.34); however, diagnostic values varied and CIs were imprecise. Results from a single study suggest red flags as part of a combination of index tests such as 'older age and female gender' in primary care demonstrated informative +LRs for 'unspecified vertebral fracture' (16.17, 95% CI 4.47 to 58.43). In the secondary healthcare setting, results from a single study suggest 'trauma' demonstrated informative +LRs for 'unspecified vertebral fracture' (+LR: 2.18, 95% CI 1.86 to 2.54) and 'older age' demonstrated informative +LRs for 'osteoporotic vertebral fracture' (older age greater than 75 years: 2.51, 95% CI 1.48 to 4.27). Results from a single study suggest red flags as part of a combination of index tests such as 'older age and trauma' in secondary care demonstrated informative +LRs for 'unspecified vertebral fracture' (+LR: 4.35, 95% CI 2.92 to 6.48). Results from a single study suggest when '4 of 5 tests' were positive in secondary care, they demonstrated informative +LRs for 'osteoporotic vertebral fracture' (+LR: 9.62, 95% CI 5.88 to 15.73). In the tertiary care setting, results from a single study suggest 'presence of contusion/abrasion' was informative for 'vertebral compression fracture' (+LR: 31.09, 95% CI 18.25 to 52.96). AUTHORS' CONCLUSIONS: The available evidence suggests that only a few red flags are potentially useful in guiding clinical decisions to further investigate people suspected to have a vertebral fracture. Most red flags were not useful as screening tools to identify vertebral fracture in people with low back pain. In primary care, 'older age' was informative for 'unspecified vertebral fracture', and 'trauma' and 'corticosteroid use' were both informative for 'unspecified vertebral fracture' and 'osteoporotic vertebral fracture'. In secondary care, 'older age' was informative for 'osteoporotic vertebral fracture' and 'trauma' was informative for 'unspecified vertebral fracture'. In tertiary care, 'presence of contusion/abrasion' was informative for 'vertebral compression fracture'. Combinations of red flags were also informative and may be more useful than individual tests alone. Unfortunately, the challenge to provide clear guidance on which red flags should be used routinely in clinical practice remains. Further research with primary studies is needed to improve and consolidate our current recommendations for screening for vertebral fractures to guide clinical care.

Physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents.

BACKGROUND: Chronic pain is a major health and socioeconomic burden, which is prevalent in children and adolescents. Among the most widely used interventions in children and adolescents are physical activity (including exercises) and education about physical activity. OBJECTIVES: To evaluate the effectiveness of physical activity, education about physical activity, or both, compared with usual care (including waiting-list, and minimal interventions, such as advice, relaxation classes, or social group meetings) or active medical care in children and adolescents with chronic musculoskeletal pain. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PEDro, and LILACS from the date of their inception to October 2022. We also searched the reference lists of eligible papers, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared physical activity or education about physical activity, or both, with usual care (including waiting-list and minimal interventions) or active medical care, in children and adolescents with chronic musculoskeletal pain. DATA COLLECTION AND ANALYSIS: Two review authors independently determined the eligibility of the included studies. Our primary outcomes were pain intensity, disability, and adverse events. Our secondary outcomes were depression, anxiety, fear avoidance, quality of life, physical activity level, and caregiver distress. We extracted data at postintervention assessment, and long-term follow-up. Two review authors independently assessed risk of bias for each study, using the RoB 1. We assessed the overall certainty of the evidence using the GRADE approach. We reported continuous outcomes as mean differences, and determined clinically important differences from the literature, or 10% of the scale. MAIN RESULTS: We included four studies (243 participants with juvenile idiopathic arthritis). We judged all included studies to be at unclear risk of selection bias, performance bias, and detection bias, and at high risk of attrition bias. We downgraded the certainty of the evidence for each outcome to very low due to serious or very serious study limitations, inconsistency, and imprecision. Physical activity compared with usual care Physical activity may slightly reduce pain intensity (0 to 100 scale; 0 = no pain) compared with usual care at postintervention (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -0.82 to -0.08; 2 studies, 118 participants; recalculated as a mean difference (MD) -12.19, 95% CI -21.99 to -2.38; I² = 0%; very low-certainty evidence). Physical activity may slightly improve disability (0 to 3 scale; 0 = no disability) compared with usual care at postintervention assessment (MD -0.37, 95% CI -0.56 to -0.19; I² = 0%; 3 studies, 170 participants; very low-certainty evidence). We found no clear evidence of a difference in quality of life (QoL; 0 to 100 scale; lower scores = better QoL) between physical activity and usual care at postintervention assessment (SMD -0.46, 95% CI -1.27 to 0.35; 4 studies, 201 participants; very low-certainty evidence; recalculated as MD -6.30, 95% CI -18.23 to 5.64; I² = 91%). None of the included studies measured adverse events, depression, or anxiety for this comparison. Physical activity compared with active medical care We found no studies that could be analysed in this comparison. Education about physical activity compared with usual care or active medical care We found no studies that could be analysed in this comparison. Physical activity and education about physical activity compared with usual care or active medical care We found no studies that could be analysed in this comparison. AUTHORS' CONCLUSIONS: We are unable to confidently state whether interventions based on physical activity and education about physical activity are more effective than usual care for children and adolescents with chronic musculoskeletal pain. We found very low-certainty evidence that physical activity may reduce pain intensity and improve disability postintervention compared with usual care, for children and adolescents with juvenile idiopathic arthritis. We did not find any studies reporting educational interventions; it remains unknown how these interventions influence the outcomes in children and adolescents with chronic musculoskeletal pain. Treatment decisions should consider the current best evidence, the professional's experience, and the young person's preferences. Further randomised controlled trials in other common chronic musculoskeletal pain conditions, with high methodological quality, large sample size, and long-term follow-up are urgently needed.

Highly efficient platelet generation in lung vasculature reproduced by microfluidics.

Platelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung are principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number of functional platelets is poor. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates substantial platelet numbers, up to 3000 per megakaryocyte. Despite their large size, megakaryocytes are able repeatedly to passage through the lung vasculature, leading to enucleation and subsequent platelet generation intravascularly. Using ex vivo lung and an in vitro microfluidic chamber we determine how oxygenation, ventilation, healthy pulmonary endothelium and the microvascular structure support thrombopoiesis. We also show a critical role for the actin regulator Tropomyosin 4 in the final steps of platelet formation in lung vasculature. This work reveals the mechanisms of thrombopoiesis in lung vasculature and informs approaches to large-scale generation of platelets.

Exercise Increases Pain Self-efficacy in Adults With Nonspecific Chronic Low Back Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the effect of exercise on pain self-efficacy in adults with nonspecific chronic low back pain (NSCLBP). DESIGN: Intervention systematic review with meta-analysis LITERATURE SEARCH: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, PsycINFO, and CINAHL databases from October 20, 2018, to March 23, 2022. SELECTION CRITERIA: We included randomized controlled trials that compared the effect of exercise on pain self-efficacy to control, in adults with NSCLBP. DATA SYNTHESIS: We conducted a meta-analysis using a random-effects model. We evaluated the risk of bias using the Cochrane risk-of-bias tool (RoB 2) and judged the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. RESULTS: Seventeen trials were included, of which eight (n = 1121 participants; 60.6% female; mean age: 49.6 years) were included in the meta-analysis. Exercise increased pain self-efficacy by 3.02 points (95% confidence interval: 1.72, 4.32) on the 60-point Pain Self-Efficacy Questionnaire. The certainty of evidence was moderate; all trials were at high risk of bias. CONCLUSION: There was moderate-certainty evidence that exercise increased pain self-efficacy in adults with NSCLBP. Future research should investigate if this effect is meaningful, whether it increases with more targeted treatments to enhance pain self-efficacy, and the effects on outcomes for adults with NSCLBP. J Orthop Sports Phys Ther 2023;53(6):1-8. Epub: 10 May 2023. doi:10.2519/jospt.2023.11622.

Meaningful coproduction with clinicians: establishing a practice-based research network with physiotherapists in regional Australia.

BACKGROUND: The disconnect between research and clinical practice leads to research evidence that is often not useful for clinical practice. Practice-based research networks are collaborations between researchers and clinicians aimed at coproducing more useful research. Such networks are rare in the physiotherapy field. We aimed to describe (i) clinicians' motivations behind, and enablers to, participating in a network, (ii) the process of network establishment and (iii) research priorities for a practice-based network of physiotherapists in the Hunter Region of New South Wales (NSW), Australia that supports research coproduction. METHODS: We describe the methods and outcomes of the three steps we used to establish the network. Step 1 involved consultation with local opinion leaders and a formative evaluation to understand clinicians' motivations behind, and enablers to, participating in a network. Step 2 involved establishment activities to generate a founding membership group and codesign a governance model. Step 3 involved mapping clinical problems through a workshop guided by systems thinking theory with local stakeholders and prioritizing research areas. RESULTS: Through formative evaluation focus groups, we generated five key motivating themes and three key enablers for physiotherapists' involvement in the network. Establishment activities led to a founding membership group (n = 29, 67% from private practice clinics), a network vision and mission statement, and a joint governance group (9/13 [70%] are private practice clinicians). Our problem-mapping and prioritization process led to three clinically relevant priority research areas with the potential for significant change in practice and patient outcomes. CONCLUSIONS: Clinicians are motivated to break down traditional siloed research generation and collaborate with researchers to solve a wide array of issues with the delivery of care. Practice-based research networks have promise for both researchers and clinicians in the common goal of improving patient outcomes.

Mixed messages: most spinal pain and osteoarthritis observational research is unclear or misaligned.

OBJECTIVES: We assessed authors' language and methods to determine alignment between reported aims, methods, intent, and interpretations in observational studies in spinal pain or osteoarthritis. STUDY DESIGN AND SETTING: We searched five databases for observational studies that included people with spinal pain or osteoarthritis published in the last 5 years. We randomized 100 eligible studies, and classified study intent (aims and methods) and interpretations as causal, non-causal, unclear, or misaligned. RESULTS: Overall, 38% of studies were aligned regarding their intent and interpretation (either causally (22%) or non-causally (16%)). 29% of studies' aims and 29% of study methods were unclear. Intent was misaligned in 16% of studies (where aim differed to method) and 23% of studies had misaligned interpretations (where there were multiple conflicting claims). The most common kind of aim was non-causal (38%), and the most common type of method (39%), intent (38%), and interpretations (35%) was causal. CONCLUSIONS: Misalignment and mixed messages are common in observational research of spinal pain and osteoarthritis. More than 6 in 10 observational studies may be uninterpretable, because study intent and interpretations do not align. While causal methods and intent are most common in observational research, authors commonly shroud causal intent in non-causal terminology.

Alterations in platelet proteome signature and impaired platelet integrin αIIbß3 activation in patients with COVID-19.

BACKGROUND: Patients with COVID-19 are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality. OBJECTIVES: To characterize the mechanism of altered platelet function in COVID-19 patients. METHODS: The platelet proteome, platelet functional responses, and platelet-neutrophil aggregates were compared between patients hospitalized with COVID-19 and healthy control subjects using tandem mass tag proteomic analysis, Western blotting, and flow cytometry. RESULTS: COVID-19 patients showed a different profile of platelet protein expression (858 altered of the 5773 quantified). Levels of COVID-19 plasma markers were enhanced in the platelets of COVID-19 patients. Gene ontology pathway analysis demonstrated that the levels of granule secretory proteins were raised, whereas those of platelet activation proteins, such as the thrombopoietin receptor and protein kinase Cα, were lowered. Basally, platelets of COVID-19 patients showed enhanced phosphatidylserine exposure, with unaltered integrin αIIbß3 activation and P-selectin expression. Agonist-stimulated integrin αIIbß3 activation and phosphatidylserine exposure, but not P-selectin expression, were decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This association was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction. CONCLUSIONS: Overall, our data suggest the presence of 2 platelet populations in patients with COVID-19: one of circulating platelets with an altered proteome and reduced functional responses and another of P-selectin-expressing neutrophil-associated platelets. Platelet-driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients.

Physiotherapists' opinions, barriers, and enablers to providing evidence-based care: a mixed-methods study.

BACKGROUND: Physiotherapists deliver evidence-based guideline recommended treatments only half of the time to patients with musculoskeletal conditions. Physiotherapists' behaviour in clinical practice are influenced by many cognitive, social, and environmental factors including time and financial pressures. Many initiatives aimed at improving physiotherapists' uptake of evidence-based care have failed to appreciate the context involved in clinical decisions and clinical practice. Therefore, we aimed to describe: i) opinions toward evidence; ii) how evidence is accessed; iii) factors influencing evidence access; iv) factors influencing evidence application, for physiotherapists working in regional areas. METHODS: We used a mixed-methods study with online survey and focus groups. We included registered physiotherapists in the survey and physiotherapists practising in regional New South Wales in the focus groups. Quantitative and qualitative data were used to inform all research objectives. We used eight domains of the Transtheoretical Domains Framework to design survey questions. We analysed quantitative and qualitative data in parallel, then integrated both sources through by developing a matrix while considering the Transtheoretical Domains Framework domains to generate themes. RESULTS: Fifty-seven physiotherapists participated in the study (survey only n = 41; focus group only n = 8; both survey and focus group n = 8). Participants reported that evidence was important, but they also considered patient expectations, colleagues' treatment choices, and business demands in clinical decision making. Physiotherapists reported they access evidence on average 30 minutes or less per week. Competing demands like business administration tasks are barriers to accessing evidence. Participants reported that patient expectations were a major barrier to applying evidence in practice. Environmental and systemic factors, like funding structures or incentives for evidence-based care, and social factors, like lacking or having a culture of accountability and mentorship, were reported as both barriers and enablers to evidence application. CONCLUSIONS: This study provides context to physiotherapists' opinion, access, and application of evidence in clinical practice. Physiotherapists' provision of evidence-based care may be improved by enhancing structural support from workplaces to access and apply evidence and exploring discrepancies between physiotherapists' perceptions of patient expectations and actual patient expectations.

Strategies for enhancing the implementation of school-based policies or practices targeting diet, physical activity, obesity, tobacco or alcohol use.

BACKGROUND: Several school-based interventions are effective in improving child diet and physical activity, and preventing excessive weight gain, and tobacco or harmful alcohol use. However, schools are frequently unsuccessful in implementing such evidence-based interventions. OBJECTIVES: 1. To evaluate the benefits and harms of strategies aiming to improve school implementation of interventions to address student diet, physical activity, tobacco or alcohol use, and obesity. 2. To evaluate the benefits and harms of strategies to improve intervention implementation on measures of student diet, physical activity, obesity, tobacco use or alcohol use; describe their cost or cost-effectiveness; and any harms of strategies on schools, school staff or students. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was between 1 September 2016 and 30 April 2021 to identify any relevant trials published since the last published review. SELECTION CRITERIA: We defined 'Implementation' as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised controlled trial (RCT) or non-randomised controlled trial (non-RCT)) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by students to 'no intervention', 'usual' practice or a different implementation strategy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Given the large number of outcomes reported, we selected and included the effects of a single outcome measure for each trial for the primary (implementation) and secondary (student health behaviour and obesity) outcomes using a decision hierarchy. Where possible, we calculated standardised mean differences (SMDs) to account for variable outcome measures with 95% confidence intervals (CI). For RCTs, we conducted meta-analyses of primary and secondary outcomes using a random-effects model, or in instances where there were between two and five studies, a fixed-effect model. The synthesis of the effects for non-randomised studies followed the 'Synthesis without meta-analysis' (SWiM) guidelines. MAIN RESULTS: We included an additional 11 trials in this update bringing the total number of included studies in the review to 38. Of these, 22 were conducted in the USA. Twenty-six studies used RCT designs. Seventeen trials tested strategies to implement healthy eating, 12 physical activity and six a combination of risk factors. Just one trial sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials used multiple implementation strategies, the most common being educational materials, educational outreach and educational meetings. The overall certainty of evidence was low and ranged from very low to moderate for secondary review outcomes. Pooled analyses of RCTs found, relative to a control, the use of implementation strategies may result in a large increase in the implementation of interventions in schools (SMD 1.04, 95% CI 0.74 to 1.34; 22 RCTs, 1917 participants; low-certainty evidence). For secondary outcomes we found, relative to control, the use of implementation strategies to support intervention implementation may result in a slight improvement on measures of student diet (SMD 0.08, 95% CI 0.02 to 0.15; 11 RCTs, 16,649 participants; low-certainty evidence) and physical activity (SMD 0.09, 95% CI -0.02 to 0.19; 9 RCTs, 16,389 participants; low-certainty evidence). The effects on obesity probably suggest little to no difference (SMD -0.02, 95% CI -0.05 to 0.02; 8 RCTs, 18,618 participants; moderate-certainty evidence). The effects on tobacco use are very uncertain (SMD -0.03, 95% CIs -0.23 to 0.18; 3 RCTs, 3635 participants; very low-certainty evidence). One RCT assessed measures of student alcohol use and found strategies to support implementation may result in a slight increase in use (odds ratio 1.10, 95% CI 0.77 to 1.56; P = 0.60; 2105 participants). Few trials reported the economic evaluations of implementation strategies, the methods of which were heterogeneous and evidence graded as very uncertain. A lack of consistent terminology describing implementation strategies was an important limitation of the review. AUTHORS' CONCLUSIONS: The use of implementation strategies may result in large increases in implementation of interventions, and slight improvements in measures of student diet, and physical activity. Further research is required to assess the impact of implementation strategies on such behavioural- and obesity-related outcomes, including on measures of alcohol use, where the findings of one trial suggest it may slightly increase student risk. Given the low certainty of the available evidence for most measures further research is required to guide efforts to facilitate the translation of evidence into practice in this setting.

Defining Growing Pains: A Scoping Review.

BACKGROUND AND OBJECTIVES: Up to one third of children may be diagnosed with growing pains, but considerable uncertainty surrounds how to make this diagnosis. The objective of this study was to detail the definitions of growing pains in the medical literature. METHODS: Scoping review with 8 electronic databases and 6 diagnostic classification systems searched from their inception to January 2021. The study selection included peer-reviewed articles or theses referring to "growing pain(s)" or "growth pain(s)" in relation to children or adolescents. Data extraction was performed independently by 2 reviewers. RESULTS: We included 145 studies and 2 diagnostic systems (ICD-10 and SNOMED). Definition characteristics were grouped into 8 categories: pain location, age of onset, pain pattern, pain trajectory, pain types and risk factors, relationship to activity, severity and functional impact, and physical examination and investigations. There was extremely poor consensus between studies as to the basis for a diagnosis of growing pains. The most consistent component was lower limb pain, which was mentioned in 50% of sources. Pain in the evening or night (48%), episodic or recurrent course (42%), normal physical assessment (35%), and bilateral pain (31%) were the only other components to be mentioned in more than 30% of articles. Notably, more than 80% of studies made no reference to age of onset in their definition, and 93% did not refer to growth. Limitations of this study are that the included studies were not specifically designed to define growing pains. CONCLUSIONS: There is no clarity in the medical research literature regarding what defines growing pain. Clinicians should be wary of relying on the diagnosis to direct treatment decisions.

Low back pain presentations to rural, regional, and metropolitan emergency departments.

OBJECTIVE: To describe the context of low back pain (LBP) presentations to emergency departments (EDs) by remoteness areas, hospital delineation level and staffing portfolios. DESIGN: A retrospective observational study using routinely captured ED and admission data over a 5-year period (July 2014-June 2019). SETTINGS: Thirty seven EDs across a large health district in NSW, Australia, covering major cities, inner regional areas and outer regional areas. PARTICIPANTS: Emergency department (ED) presentations with a principal or secondary diagnosis of LBP based on ICD-10 code (M54.5). MAIN OUTCOME MEASURES: ED presentation and associated admission measures, including presentation rate, referral source, time in ED, re-presentation rate, admission details and cost to the health system. RESULTS: There were 26 509 ED presentations for LBP across the 5 years. Time spent in ED was 206 min for EDs in major cities, 146 min for inner regional EDs and 89 min for outer regional EDs. Re-presentation rates were 6% in major cities, 8.8% in inner regional EDs and 11.8% in outer regional EDs. Admission rates were 20.4%, 15.8% and 18.8%, respectively. CONCLUSIONS: This study describes LBP presentations across 37 EDs, highlighting the potential burden these presentations place on hospitals. LBP presentations appear to follow different pathways depending on the ED remoteness area, delineation level and staff portfolio.

Epigenetic Regulation of F2RL3 Associates With Myocardial Infarction and Platelet Function.

BACKGROUND: DNA hypomethylation at the F2RL3 (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. F2RL3 encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease. METHODS: We conducted multiple independent experiments to assess whether DNA hypomethylation at F2RL3 in response to smoking is associated with risk of myocardial infarction via changes to platelet reactivity. Using cohort data (N=3205), we explored the relationship between smoking, DNA hypomethylation at F2RL3, and myocardial infarction. We compared platelet reactivity in individuals with low versus high DNA methylation at F2RL3 (N=41). We used an in vitro model to explore the biological response of F2RL3 to cigarette smoke extract. Finally, a series of reporter constructs were used to investigate how differential methylation could impact F2RL3 gene expression. RESULTS: Observationally, DNA methylation at F2RL3 mediated an estimated 34% of the smoking effect on increased risk of myocardial infarction. An association between methylation group (low/high) and platelet reactivity was observed in response to PAR4 (protease-activated receptor 4) stimulation. In cells, cigarette smoke extract exposure was associated with a 4.9% to 9.3% reduction in DNA methylation at F2RL3 and a corresponding 1.7-(95% CI, 1.2-2.4, P=0.04) fold increase in F2RL3 mRNA. Results from reporter assays suggest the exon 2 region of F2RL3 may help control gene expression. CONCLUSIONS: Smoking-induced epigenetic DNA hypomethylation at F2RL3 appears to increase PAR4 expression with potential downstream consequences for platelet reactivity. Combined evidence here not only identifies F2RL3 DNA methylation as a possible contributory pathway from smoking to cardiovascular disease risk but from any feature potentially influencing F2RL3 regulation in a similar manner.

Perspectives of emergency department clinicians on the challenges of addressing low back pain in the emergency setting: A qualitative study.

OBJECTIVE: To identify and explore ED clinician perspectives on: (i) why patients with low back pain (LBP) present to the ED and are admitted into hospital from ED; (ii) barriers and enablers they face when providing care to patients with LBP; and (iii) strategies to improve the care of patients with LBP, and associated care processes, in the ED. METHODS: We undertook a qualitative exploratory study with ED clinicians (medical officers, nurses and physiotherapists) at a tertiary-level public hospital in New South Wales, Australia, using focus groups and individual interviews. We used thematic analysis to synthesise participant responses to answer the predefined research questions. RESULTS: Twenty-one clinicians participated (two individual interviews, 19 focus groups). Perceptions about better access to the ED and advanced care within ED were thought to drive presentations to the ED for LBP. Barriers and enablers to optimal patient care included patient-, clinician- and service-level factors. The main strategies to improve care included a department LBP pathway, modernised patient and clinician resources, better follow-up options post-discharge and improved communication between ED and primary care. CONCLUSION: We identified a range of targets to improve LBP management in ED. Clinicians perceived internal and external factors to the ED as influences of ED presentation and hospital admission. Clinicians also reported that patient-, clinician- and service-level barriers and enablers influenced patient management in ED. Strategies suggested by clinicians included improved follow-up options, access to resources and an 'LBP pathway' to support decision making.

At my own pace, space, and place: a systematic review of qualitative studies of enablers and barriers to telehealth interventions for people with chronic pain.

ABSTRACT: Telehealth is a promising approach to support self-management with the potential to overcome geographical barriers. Understanding patient perspectives will identify practical challenges to delivering self-management strategies by telehealth. The aim of this study was to synthesize the perceptions of people with chronic musculoskeletal pain for engaging in interventions delivered using telehealth. We searched MEDLINE, Embase, CINAHL, LILACS, and PsycINFO databases. We included qualitative studies that explored perceptions or experiences or attitudes of people with chronic musculoskeletal pain engaging with telehealth. We assessed the methodological quality using the Critical Appraisal Skills Programme checklist. Meta-synthesis was guided by a thematic synthesis approach. The level of confidence of review findings was assessed using the Confidence in the Evidence from Reviews of Qualitative Studies (GRADE-CERQual). Twenty-one studies were included (n = 429). Telehealth comprised web-based, videoconference-based, telephone-based, video-based, and smartphone app-based programs delivered solely or combined. Chronic musculoskeletal conditions included people with knee or hip osteoarthritis, chronic low back pain, persistent pain (chronic joint pain or nonspecific chronic musculoskeletal pain), rheumatoid arthritis, and functional fatigue syndrome. The enablers for engaging in telehealth interventions were as follows: (1) "at my own pace, space, and place" and (2) empowered patient. Barriers to engaging in telehealth interventions were as follows: (1) impersonal, (2) technological challenges, (3) irrelevant content, and (4) limited digital (health) literacy. Telehealth interventions with well-designed interactive platforms, flexibility to fit patients' routine, and the broad availability of material may favor better engagement. Encouragement of self-efficacy is linked to successful telehealth-delivered self-management programs.

Compliance with telephone-based lifestyle weight loss programs improves low back pain but not knee pain outcomes: complier average causal effects analyses of 2 randomised trials.

ABSTRACT: We conducted a complier average causal effect (CACE) analyses for 2 pragmatic randomised controlled trials. We aimed to assess the effectiveness of telephone-based lifestyle weight loss interventions compared with usual care among compliers. Participants from 2 trials with low back pain (n = 160) and knee osteoarthritis (n = 120) with a body mass index ≥27 kg/m2 were included. We defined adherence to the telephone-based lifestyle weight loss program as completing 60% (6 from 10) of telephone health coaching calls. The primary outcomes for CACE analyses were pain intensity (0-10 Numerical Rating Scale) and disability (Roland Morris Disability Questionnaire for low back pain and Western Ontario and McMaster Universities Osteoarthritis Index for knee osteoarthritis). Secondary outcomes were weight, physical activity, and diet. We used an instrumental variable approach to estimate CACE in compliers. From the intervention groups of the trials, 29% of those with low back pain (n = 23/80) and 34% of those with knee osteoarthritis (n = 20/60) complied. Complier average causal effect estimates showed potentially clinically meaningful effects, but with low certainty because of wide confidence intervals, for pain intensity (-1.4; 95% confidence interval, -3.1, 0.4) and small but also uncertain effects for disability (-2.1; 95% confidence interval, -8.6, 4.5) among compliers in the low back pain trial intervention compared with control but not in the knee osteoarthritis trial. Our findings showed that compliers of a telephone-based weight loss intervention in the low back pain trial generally had improved outcomes; however, there were inconsistent effects in compliers from the knee osteoarthritis trial. Complier average causal effect estimates were larger than intention-to-treat results but must be considered with caution.