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To understand the flexible work practices during the COVID-19 pandemic and their impact on work-related musculoskeletal disorders (MSDs) and depression in frequent computer users.An e-survey determined the extent of workplace changes and MSD, and the relationships between them using descriptive-statistics and chi-squared tests.Of 700 who commenced the survey, 511 were analyzed. Since the pandemic commenced, 80% of respondents reported they were working more from home; and 89% reported some musculoskeletal pain. Compared with prepandemic, more people worked in nonergonomic environments, computer configurations and body postures. Work location was associated with upper back pain ( P = 0.011); body posture with headache ( P = 0.027) and low back pain ( P = 0.003).Nonergonomic work environments of frequent computer users during COVID-19 are related to having upper back pain, whereas nonergonomic postures are related to having headache and low back pain.

The Breast Reconstruction Risk Assessment (BRA) Score tool is a risk calculator developed to predict the risk of complications in individual patients undergoing breast reconstruction. It was developed in a North American population exclusively undergoing immediate breast reconstruction. This study sought to assess the predictions of the BRA Score tool against the measured outcomes of surgery for an Australian public hospital population, including both immediate and delayed reconstructions.This was a retrospective cohort study of data from women at a single Australian public teaching hospital unit. Data from the Flinders Breast Reconstruction Database was retrieved and compared to BRA Scores calculated for each patient. Receiver operating curve area under the curve analysis was performed as well as Brier scores to compare predicted versus observed complications.BRA Score predictions were reasonable or good (C-statistic0.7, Brier score0.09) for the complications of overall surgical complications, surgical site infection (SSI) and seroma at 30 days, and similarly accurate for prediction of the same complications for implant reconstructions at 12 months. There were similar findings between delayed and immediate reconstructions.The BRA Score risk calculator is valid to detect some risks in both patients undergoing immediate and delayed breast reconstruction in an Australian public hospital setting. SSI is the best predicted complication and is well-predicted across both autologous and prosthetic reconstruction types.

Objective To assess the cost-effectiveness of breast reduction surgery for women with symptomatic breast hypertrophy in Australia. Design Cost-utility analysis of data from a prospective cohort study. Setting, participants Adult women with symptomatic breast hypertrophy assessed for bilateral breast reduction at the Flinders Medical Centre, a public tertiary hospital in Adelaide, April 2007 - February 2018. The control group included women with breast hypertrophy who had not undergone surgery. Main outcome measures Health care costs (for the surgical admission and other related hospital costs within 12 months of surgery) and SF-6D utility scores (measure of health-related quality of life) were used to calculate incremental costs per quality-adjusted life-year (QALY) gained over 12 months, extrapolated to a 10-year time horizon. Results Of 251 women who underwent breast reduction, 209 completed the baseline and at least one post-operation assessment (83%; intervention group); 124 of 350 invited women waiting for breast reduction surgery completed the baseline and 12-month assessments (35%; control group). In the intervention group, the mean SF-6D utility score increased from 0.313 (SD, 0.263) at baseline to 0.626 (SD, 0.277) at 12 months; in the control group, it declined from 0.296 (SD, 0.267) to 0.270 (SD, 0.257). The mean QALY gain was consequently greater for the intervention group (adjusted difference, 1.519; 95% CI, 1.362-1.675). The mean hospital cost per patient was $11 857 (SD, $4322), and the incremental cost-effectiveness ratio (ICER) for the intervention was $7808 per QALY gained. The probability of breast reduction surgery being cost-effective was 100% at a willingness-to-pay threshold of $50 000 per QALY and 88% at $28 033 per QALY. Conclusions Breast reduction surgery for women with symptomatic breast hypertrophy is cost-effective and should be available to women through the Australian public healthcare system.

Background context Musculoskeletal (MSK) pain presents a global challenge. Individual and group pain management programmes (PMPs) are recommended approaches for patients with chronic MSK disorders. With advances in remote healthcare capability, telehealth, and the recent COVID-19 pandemic, the importance of telehealth PMPs has become even more evident. Nevertheless, it is not known how patients perceive PMPs for their MSK complaint when delivered via telehealth. Objective To synthesise the evidence of patients' experiences of group and individual telehealth PMPs for chronic MSK pain. Design A scoping review informed by the PRISMA extension for scoping reviews. Data sources Based on a planned search strategy, modified following initial searches, an electronic search was conducted of key databases: Cochrane Library, Medline, CINAHL, EMBASE, AMED, SportDiscus and APA PsychInfo from 2010 until 11 May 2021. Study selection Any qualitative or mixed methods study reporting patient experiences of telehealth PMPs for patients with MSK disorders. Data extraction and data synthesis Data were extracted and synthesised using thematic analysis. Results From 446 identified studies, 10 were included. Just two studies investigated group telehealth PMPs for patients with MSK disorders, with eight delivered individually. Four main themes emerged: (1) Usability of the technology, (2) Tailored care, (3) Therapeutic alliance and (4) Managing behaviour. The findings highlight patient acceptability of telehealth to support self-management for chronic MSK disorders, with appropriate clinical and technical support. Group telehealth has the potential to empower patients with peer support. Remote delivery of PMPs also impacts on how patients and providers interact, communicate and develop a therapeutic relationship. Conclusions and implications Barriers and enablers to engagement in telehealth PMPs for patients with chronic MSK disorders have been identified. Peer support and group cohesiveness can be achieved remotely to enhance the patient experience. There is a critical need for further research in this area.

Background Adult scoliosis represents a distinct subgroup of scoliosis patients for whom the diagnosis can have a large impact on their health-related quality of life (HR-QOL). Therefore, HR-QOL patient-reported outcome measures (PROMs) are essential to assess disease progression and the impact of interventions. The objective of this systematic review is to evaluate the measurement properties of HR-QOL PROMs in adult scoliosis patients. Methods We will conduct a literature search, from their inception onwards, of multiple electronic databases including AMED, CINAHL, EMBASE, Medline, PsychINFO and PubMed. The searches will be performed in two stages. For both stages of the search, participants will be aged 18 and over with a diagnosis of scoliosis. The primary outcome of interest in the stage one searches will be studies which use PROMs to investigate HR-QOL as defined by the Core Outcome Measures in Effectiveness Trials (COMET) taxonomy, the secondary outcome will be to assess the frequency of use of the various PROMs. In stage two, the primary outcome of interest will be studies which assess the measurement properties of the HR-QOL PROMs identified in stage one. No specific measurement property will be given priority. No planned secondary outcomes have been identified but will be reported if discovered. In stage one, the only restriction on study design will be the exclusion of systematic reviews. In Stage two the only restriction on study design will be the exclusion of full-text articles not available in the English language. Two reviewers will independently screen all citations and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or risk of bias) will be appraised using the Consensus-based Standards for the selection of Health Measurement Instruments (COSMIN) checklist. The overall strength of the body of evidence will then be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A narrative synthesis will be provided with information presented in the main text and tables to summarise and explain the characteristics and findings of the included studies. The narrative synthesis will explore the evidence for currently used PROMs in adult scoliosis patients and any areas that require further study. Discussion The review will help clinicians and researchers identify a HR-QOL PROM for use in patients with adult scoliosis. Findings from the review will be published and disseminated through a peer-reviewed journal and conference presentations. Systematic review registration This systematic review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), reference number: CRD42020219437

BACKGROUND: Establishing a set of uniform classification criteria (CC) for cervical radiculopathy (CR) is required to aid future recruitment of homogenous populations to clinical trials.OBJECTIVES: To establish expert informed consensus on CC for CR.DESIGN: A pre-defined four round e-Delphi study in accordance with the guidance on Conducting and Reporting Delphi Studies.METHODS: Individuals with a background in physiotherapy who had authored two or more peer-reviewed publications on CR were invited to participate. The initial round asked opinions on CC for CR. Content analysis was performed on round one output and a list of discrete items were generated forming the round two survey. In rounds two to four, participants were asked to rate the level of importance of each item on a six-point Likert scale. Data were analysed descriptively using median, interquartile range and percentage agreement. Items reaching pre-defined consensus criteria were carried forward to the next round. Items remaining after the fourth round constituted expert consensus on CC for CR.RESULTS: Twelve participants participated with one drop out. The final round identified one inclusion CC and 12 exclusion CC. The inclusion CC that remained achieved 82% agreement and was a cluster criterion consisting of radicular pain with arm pain worse than neck pain; paraesthesia or numbness and/or weakness and/or altered reflex; MRI confirmed nerve root compression compatible with clinical findings.CONCLUSIONS: The CC identified can be used to inform eligibility criteria for future CR trials although caution should be practiced as consensus on measurement tools requires further investigation.

Introduction Adolescent idiopathic scoliosis (AIS) is a three-dimensional rotational change in the normal shape of the spine which affects children aged 10 to 18 years. Both the condition and its management can have significant impact on functional ability. Currently, expected restriction in spinal motion is experience based, rather than evidence based, and discussions to inform patient expectations pre-operatively can be difficult. The aim of this review is to evaluate the evidence pertaining to measurement of spinal motion and whether this is altered following surgery, dependent on the anatomical level of surgical fixation in AIS. Methods/analysis This protocol is reported in line with both PRISMA-P and informed by the COSMIN methodology. Electronic databases will be searched using a two-stage search strategy. The first stage will identify and evaluate the methods used to assess spinal motion. The second stage aims to evaluate the change in spinal motion using these methods based on anatomical level of fixation following surgery along with the measurement properties of those methods, to include the validity, reliability and responsiveness of the methods. Two reviewers will independently screen the search results against eligibility criteria, extract the data and assess the quality of the included studies. Any disputes between the reviewers will be resolved with a third independent reviewer. Data may be pooled where possible; however, this is not expected. The overall strength of the body of evidence will then be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Patient and public involvement Patients and members of the public will not be consulted in the production of this review, although the review was conceived based on the experiences of the authors when managing this patient population and a need to address patient expectations in pre-operative planning. Ethics, dissemination and data availability No ethical approval required. The final review will be submitted to peer-reviewed journals for publication and disseminated publicly. The datasets used and/or analysed in this review will be available from the corresponding author on reasonable request. Systematic review registration PROSPERO registration number. CRD42021282264.

Early-onset scoliosis (EOS) is a spinal deformity affecting children under the age of 10. Understanding the impact of EOS on quality of life can be achieved through appropriate patient/carer-reported outcome measures (PROMs). The aim of this systematic review was to identify, evaluate and summarize the evidence for the measurement properties of health-related quality of life (HR-QoL) outcome measures in the EOS population.A 2-stage search methodology was conducted across the PubMed, MEDLINE, EMBASE, EMCARE, PsychINFO, and CINAHL databases. Search 1 identified PROMs used to evaluate the quality of life in EOS, and search 2 identified studies of the measurement properties of these PROMs. Two reviewers performed searching, study screening and selection and assessed studies for risk of bias using the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. One reviewer performed data extraction. Evidence for each measurement property per PROM was summarized and evaluated using a modified GRADE approach.Search 1 identified 19 (10 disease-specific, 9 generic) PROMs that have been used to assess HR-QoL or a relevant domain in the EOS population. Search 2 identified only one PROM (the 24-item Early-Onset Scoliosis Questionnaire, EOSQ) with eligible studies (n=4) evaluating measurement properties. There is low-quality evidence for sufficient content validity, very low-quality evidence for sufficient reliability and low-quality evidence for sufficient criterion validity, specifically regarding the pulmonary function domain) of the EOSQ. Construct validity and responsiveness were rated as indeterminate. There were no studies on measurement error.Our search strategy found that measurement properties have only been evaluated for one PROM, the EOSQ. There is low-quality evidence for sufficient measurement properties for the EOSQ in patients under the age of 10 with EOS. Further research is needed to improve the quality of evidence for EOSQ measurement properties and investigate other PROMs in this population.Level II.

Objective Test whether a single e-learning session can improve empathy and communication across pre-registration and postgraduate physiotherapy students. Methods Design: Two-phase sequential mixed methods study. Phase 1: Pilot randomised control trial. Phase 2: Qualitative study using interpretive phenomenological analysis. Sampling: A purposive sample for both phases. Outcome measures: Phase 1: At baseline, post and 6-week follow up. Demographics. Primary outcome: Inter-personal Reactivity Index (IRI). Phase 2: Demographics and interview schedule. Intervention: An e-learning (E) narrative intervention group or active control condition. Analysis: Phase 1: Descriptive statistics and confidence intervals. Mann-Whitney U test to compare across group change. Phase 2: Thematic analysis. Results Thirty-nine participants took part in the mixed methods study (Phase 1 n = 25; Phase 2 n = 14). Phase 1: No significant differences between groups were identified. Potentially importance changes across time were found for the intervention group and control group. Phase 2 results identified 5 themes and 12 sub-themes. Conclusion The e-learning groups identified an increase in the perceived ability to handle distressing communication. Other important findings from the e-learning are discussed. Further research is warranted. Practical Implications Novel e-learning intervention may have an important role in curriculum development and clinical practice to promote therapeutic communication. Practical Implications Novel e-learning intervention may have an important role in curriculum development and clinical practice to promote therapeutic communication.

Objective To investigate the test-retest reliability and validity of the Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score (KJOC) in elite Canoe Slalom athletes and determine its ability to predict future shoulder pain. Design Observational study with embedded test-retest reliability study. Setting British Canoe Slalom National Training Centre. Participants Nineteen athletes from the British Canoe Slalom team for the 2019 season. Main outcome measures The KJOC was completed at the start of winter training and start of the 2019 competitive season. Current, historical (6-months pre-questionnaire) and prospective (4-months post-questionnaire) shoulder injuries were recorded. Results Test-retest reliability was found to be excellent (ICC3,1 = 0.97), with a minimal detectable change (MDC95%) of 6.7. Compared to uninjured athletes, currently injured and historically injured athletes scored significantly lower (p = 0.002 and p = 0.011, respectively), with the difference between means > MDC95%. A cut-off of 88 was found to be predictive of shoulder pain (AUC: 0.779; sensitivity: 0.60; specificity: 0.95; positive likelihood ratio: 11.4). Conclusion The KJOC demonstrated excellent reliability and can distinguish between athletes with and without current or historical shoulder pain. A KJOC score of

Background Chronic musculoskeletal disorders are the second largest contributor to disability globally. Exercise is typically recommended by physiotherapists to manage symptoms. However, adherence to the prescribed exercise programme is often poor. Adjunctive digital interventions offer potential to enhance exercise adherence. Objectives To review evidence on the effectiveness of digital interventions for improving exercise adherence in people with chronic musculoskeletal conditions. The study is reported in line with PRISMA guidance and was registered with PROSPERO (CRD42019124502). Data Sources MEDLINE, Embase and PsycInfo were searched using a comprehensive search strategy. The reference lists of all included papers and relevant systematic reviews identified during the search were scanned for relevant articles. Study appraisal and synthesis methods Two researchers independently checked articles for inclusion and extracted data. Results The search returned a total of 4257 results of which five trials were included in the review and two studies were included in a random effects meta-analysis. There was no statistically significant difference in exercise adherence (SMD: 0.23; 95% CI: −0.10, 0.57). Studies that were not suitable for inclusion in the meta-analysis reported similar results. Heterogeneity of effects was high and study quality ranged from low to moderate. All of the meta-analysed data related to osteoarthritis of the hip and/or knee. Conclusion We found no evidence that digital interventions enhance adherence to therapeutic exercise in patients with chronic musculoskeletal disorders. However, further, high quality research is required to draw definitive conclusions on their effectiveness and to identify key components that are associated with effectiveness. Systematic Review Registration Number PROSPERO CRD42019124502

Background The term temporomandibular disorder (TMD) includes disorders of the temporomandibular joints (TMJ), masticatory muscles and adjacent tissues. Several studies have examined the effectiveness of manual therapy (MT) for TMDs by evaluating changes in pain and maximum mouth opening (MMO). Nevertheless, the effectiveness of MT exclusively applied to the craniomandibular structures (craniomandibular manual therapy (CMMT)) on pain and TMJ range of motion remains unclear. This review aims to evaluate the effectiveness of CMMT on pain and TMJ range of motion in people with TMDs. Methods This protocol is reported in line with the preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P). Databases including MEDLINE, Embase, CINAHL, ZETOC, Web of Science, SCOPUS, PEDro, PubMed, Cochrane Library and Best Evidence, EBM reviews–Cochrane Central Register of Controlled Trials, Index to Chiropractic Literature ChiroAccess and Google Scholar will be searched from inception as well as key journals and grey literature. Randomised controlled trials involving adults with TMD that compare the effect of any type of CMMT (e.g. mobilisation) on pain and range of motion with a placebo intervention, controlled care intervention or other types of treatment will be included. Two reviewers will independently screen articles for inclusion, extract data, assess risk of bias (revised Cochrane risk of bias tool) for included studies and evaluate overall quality of evidence (Grading of Recommendations Assessment, Development and Evaluation). A meta-analysis will be conducted if possible. If not, a narrative synthesis will be conducted reporting the effectiveness of CMMT according to disorder type (TMJ disorders, masticatory muscle disorders and mixed disorders). Discussion In this review, the effectiveness of MT applied to craniomandibular structures for the treatment of TMD will be evaluated. Results will be submitted for publication in a peer-reviewed journal and presented at conferences. We expect our findings will facilitate treatment planning for manual therapists managing patients with TMD and provide future clinical research implications. Systematic review registration PROSPERO CRD42019160213

ObjectivesThere are critical periods of mortality risk at onset and cessation of opioid agonist treatment. We aim to determine whether non-fatal overdose followed the same pattern as fatal overdose, comparing the first 4 weeks of treatment and treatment cessation and the remainder time off treatment, with the remainder treatment time, to determine intervention markers. ApproachRetrospective cohort study of people with a history of opioid agonist treatment using linked New South Wales data. The incidence of non-fatal overdose hospitalization; emergency department presentation; and fatal overdose from national death records were compared. Rates were calculated using generalized estimating equations adjusting for demographics, year, and recent health and incarceration events. ResultsThe rate of an emergency department drug overdose presentation was highest. It was more than three-fold the rate of opioid non-fatal overdose hospitalisation and 14 times higher than fatal opioid overdose. It was also twice the rate of non-opioid non-fatal overdose hospitalisation. Fatal overdose was lowest while in treatment. This differed from the measures of non-fatal overdose, the overdose rate was elevated in the first four weeks in treatment as well as the first four weeks post treatment. ConclusionsRetention on opioid agonist treatment is protective against drug related overdose. There is elevated risk of non-fatal overdose at treatment initiation that is not evident for fatal overdose, however the first month of treatment cessation is a critical period for both non-fatal and fatal overdose. These findings emphasize the importance of treatment retention and interventions for polysubstance overdose at cessation.

IntroductionThere is a high global prevalence of patients presenting with physical and mental health comorbidities. Physiotherapeutic interventions, such as exercise, can have positive benefits for physical and mental health. However, poor accessibility and negative experiences of healthcare services for those with mental illness (MI) have been consistently observed within literature with recent research identifying poor experiences of physiotherapeutic interactions and processes such as referrals and discharges. One way to help improve physiotherapy services for this population is to understand the personal experiences and perceptions of healthcare professionals (HCPs) toward physiotherapy for patients with MI. Qualitative-based evidence syntheses are suited to bring this data together with the aim of improving physiotherapy services for patients with MI. This review will systematically search and synthesise existing evidence around HCP experiences and perceptions of physiotherapy for people with MI.Methods and analysisA systematic search and seven-phase meta-ethnography will be undertaken. A comprehensive search of electronic databases (CINAHL plus, MEDLINE, Pubmed, Embase and Psycinfo) and search engines as well as grey literature (unpublished primary research such as theses) will be completed. Searches are planned to take place in July 2022. Eligibility criteria include: (a) qualitative data, (b) perceptions identified from HCP, including physiotherapists, assistants and HCP referring into physiotherapy, about physiotherapy for patients with MI and (c) are primary studies.Ethics and disseminationThis work is exempt from requiring ethical approval due to review methodology with data accessed from published works. This systematic review is expected to provide insight into experiences and perceptions of HCP around benefits and barriers to accessing physiotherapy for patients with mental health illness. Findings will be used to inform further research and co-develop recommendations to overcome barriers and optimise facilitators to care for this population. Findings will be disseminated via peer-reviewed journal, conference presentations and to key stakeholder groups.PROSPERO registration numberCRD42021293035.

Background SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. Results We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206+ regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal mucosa. Conclusions This study identifies SP140 as a druggable epigenetic therapeutic target for CD.

Introduction Spinal and peripheral joint manipulation and mobilization are interventions used by many healthcare providers to manage musculoskeletal conditions. Although there are many reports of adverse events (or undesirable outcomes) following such interventions, there is no common definition for an adverse event or clarity on any severity classification. This impedes advances of patient safety initiatives and practice. This scoping review mapped the evidence of adverse event definitions and classification systems following spinal and peripheral joint manipulation and mobilization for musculoskeletal conditions in adults. Methods An electronic search of the following databases was performed from inception to February 2021: MEDLINE, EMBASE, CINAHL, Scopus, AMED, ICL, PEDro, Cochrane Library, Open Grey and Open Theses and Dissertations. Studies including adults (18 to 65 years old) with a musculoskeletal condition receiving spinal or peripheral joint manipulation or mobilization and providing an adverse event definition and/or classification were included. All study designs of peer-reviewed publications were considered. Data from included studies were charted using a standardized data extraction form and synthesised using narrative analysis. Results From 8248 identified studies, 98 were included in the final synthesis. A direct definition for an adverse event and/or classification system was provided in 69 studies, while 29 provided an indirect definition and/or classification system. The most common descriptors to define an adverse event were causality, symptom severity, onset and duration. Twenty-three studies that provided a classification system described only the end anchors (e.g., mild/minor and/or serious) of the classification while 26 described multiple categories (e.g., moderate, severe). Conclusion A vast array of terms, definition and classification systems were identified. There is no one common definition or classification for adverse events following spinal and peripheral joint manipulation and mobilization. Findings support the urgent need for consensus on the terms, definition and classification system for adverse events related to these interventions.

IntroductionChronic pain conditions are a leading cause of disease and disability. They are associated with symptoms such as fatigue, sleep and mood disturbances. Minimal evidence is available to support effective treatments and alternatives treatment approaches are called for. Photobiomodulation therapy has been highlighted as one promising option. A whole-body therapy device (NovoTHOR) has recently been developed with a number of potential advantages for people with chronic pain. Research is needed to consider the feasibility of this device.Methods and analysisA single-centre single-armed (no placebo group) feasibility study with an embedded qualitative component will be conducted. The intervention will comprise 18 treatments over 6 weeks, with 6-month follow-up, in the whole-body photobiomodulation device. A non-probability sample of 20 adult participants with a clinician diagnosis of chronic axial pain, polyarthralgia, myofascial pain or widespread pain will be recruited (self-referral and clinician referral). Outcome measures will focus on acceptability of trial processes with a view to guiding a definitive randomised controlled trial. Analyses will use descriptive statistics for quantitative aspects. The qualitative element will be assessed by means of a participant-reported experience questionnaire postintervention and semistructured audio-recorded interviews at three stages; preintervention, midintervention and postintervention. The latter will be transcribed verbatim and a reflexive thematic analysis will be used to identify emerging themes. Exploratory outcomes (participant-reported and performance-based measures) will be analysed according to data distribution.Ethics and disseminationThe study has received ethical approval from the Leicester Central Research and Ethics Committee. Findings will be disseminated via local chronic pain groups, public register update, submission for presentation at scientific meetings and open-access peer-reviewed journals, and via academic social networks.Trial registration numberNCT05069363.

ObjectivesTo evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics.DesignIndividual patient level data meta-analysis and modelling study.SettingFourteen studies from 13 countries, including randomised controlled trials and prospective observational studies.ParticipantsIndividual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated.Main outcome measureAdjudicated diagnosis of acute heart failure.ResultsOverall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged 75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure.ConclusionsIn an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach.Study registrationPROSPERO CRD42019159407.

Objective Fluid resuscitation is a ubiquitous intervention in the management of patients treated in the intensive care unit, which has implications for intensive care unit resourcing and budgets. Our objective was to calculate the relative cost of resuscitation fluids in several countries to inform future economic evaluations. Methods We collected site-level data regarding the availability and cost of fluids as part of an international survey. We normalised costs to net present values using purchasing power parities and published inflation figures. Costs were also adjusted for equi-effective dosing based on intravascular volume expansion effectiveness and expressed as US dollars (USD) per 100 mL crystalloid equivalent. Results A total of 187 sites had access to cost data. Between countries, there was an approximate six fold variation in the cost of crystalloids and colloids overall. The average cost for crystalloids overall was less than 1 USD per 100 mL. In contrast, colloid fluids had higher average costs (59 USD per 100 mL). After adjusting for equi-effective dosing, saline was ∼27 times less costly than albumin (saline: 0.6 USD per 100 mL crystalloid equivalent; albumin 4–5%: 16.4 USD; albumin 20–25%: 15.8 USD) and ∼4 times less costly than hydroxyethyl starch solution (saline: 0.6 USD; hydroxyethyl starch solution: 2.5 USD). Buffered salt solutions, such as compound sodium acetate solutions (e.g., Plasmalyte®), had the highest average cost of crystalloid fluids, costing between 3 and 4 USD per 100 mL. Conclusion The cost of fluid varies substantially between fluid types and between countries, although normal (0.9%) saline is consistently less costly than colloid preparations and some buffered salt solutions. These data can be used to inform future economic evaluations of fluid preparations.

Astrocytes are thought to play a pivotal role in coupling neural activity and cerebral blood flow. However, it has been shown that astrocytes undergo morphologic changes in response to brain metastasis, switching to a reactive phenotype, which has the potential to significantly compromise cerebrovascular function and contribute to the neurological sequelae associated with brain metastasis. Given that STAT3 is a key regulator of astrocyte reactivity, we aimed here to determine the impact of STAT3-mediated astrocyte reactivity on neurovascular function in brain metastasis. Rat models of brain metastasis and ciliary neurotrophic factor were used to induce astrocyte reactivity. Multimodal imaging, electrophysiology, and IHC were performed to determine the relationship between reactive astrocytes and changes in the cerebrovascular response to electrical and physiological stimuli. Subsequently, the STAT3 pathway in astrocytes was inhibited with WP1066 to determine the role of STAT3-mediated astrocyte reactivity, specifically, in brain metastasis. Astrocyte reactivity associated with brain metastases impaired cerebrovascular responses to stimuli at both the cellular and functional level and disrupted astrocyte–endothelial interactions in both animal models and human brain metastasis samples. Inhibition of STAT3-mediated astrocyte reactivity in rats with brain metastases restored cerebrovascular function, as shown by in vivo imaging, and limited cerebrovascular changes associated with tumor growth. Together these findings suggest that inhibiting STAT3-mediated astrocyte reactivity may confer significant improvements in neurological outcome for patients with brain metastases and could potentially be tested in other brain tumors. Significance: These findings demonstrate that selectively targeting STAT3-mediated astrocyte reactivity ameliorates the cerebrovascular dysfunction associated with brain metastasis, providing a potential therapeutic avenue for improved patient outcome.

Molecular magnetic resonance imaging (MRI) allows visualization of biological processes at the molecular level. Upregulation of endothelial ALCAM (activated leukocyte cell adhesion molecule) is a key element for leukocyte recruitment in neurological disease. The aim of this study, therefore, was to develop a novel molecular MRI contrast agent, by conjugating anti-ALCAM antibodies to microparticles of iron oxide (MPIO), for detection of endothelial ALCAM expression in vivo. Binding specificity of ALCAM-MPIO was demonstrated in vitro under static and flow conditions. Subsequently, in a proof-of-concept study, mouse models of brain metastasis were induced by intracardial injection of brain-tropic human breast carcinoma, lung adenocarcinoma or melanoma cells to upregulate endothelial ALCAM. At selected time-points, mice were injected intravenously with ALCAM-MPIO, and ALCAM-MPIO induced hypointensities were observed on T2*-weighted images in all three models. Post-gadolinium MRI confirmed an intact blood-brain barrier, indicating endoluminal binding. Correlation between endothelial ALCAM expression and ALCAM-MPIO binding was confirmed histologically. Statistical analysis indicated high sensitivity (80–90%) and specificity (79–83%) for detection of endothelial ALCAM in vivo with ALCAM-MPIO. Given reports of endothelial ALCAM upregulation in numerous neurological diseases, this advance in our ability to image ALCAM in vivo may yield substantial improvements for both diagnosis and targeted therapy.

Background and objective Chronic pain following musculoskeletal trauma is common, which may partially be attributed to the early presence of central sensitisation (CS). Multiple measures are suggested to assess clinical features of CS, yet no systematic review has evaluated the measurement properties of these measures in a musculoskeletal trauma population. Databases and data treatment This systematic review, which followed a published and PROSPERO registered protocol (CRD42018091531), aimed to establish the scope of CS measures used within a musculoskeletal trauma population and evaluate their measurement properties. Searches were conducted in two stages by two independent reviewers. The Consensus-based Standards for the selection of Health Measurement instruments (COSMIN) checklist was used to evaluate risk of bias and overall quality was assessed using the modified Grading of Recommendations Assessment, Development and Evaluation. Results From 86 studies, 30 different CS outcome measures were identified. Nine studies evaluated measurement properties of nine outcome measures; eight evaluated reliability and one evaluated construct validity. Measures included seven quantitative sensory testing methods (pressure, cold and electrical pain thresholds; warm, cold and vibration detection thresholds; vibration perception thresholds), pain drawings and a pinwheel. Risk of bias was assessed as doubtful/inadequate for all but one study, overall quality of evidence was low/very low for all measures. Reliability of measures ranged from poor to excellent. Conclusions Many measures are used to evaluate CS but with limited established measurement properties in musculoskeletal trauma. High quality research to establish measurement properties of CS outcome measures is required.

Objectives To explore the multidisciplinary team experience of Low Back Pain (LBP) in elite gymnastics. Design A qualitative focus group. Setting British Gymnastics. Participants Ten coaching, sports science and medicine multidisciplinary team members working with British gymnasts. Main outcome measures A topic guide informed by literature/expert opinion enabled discussion that was recorded/transcribed verbatim. Initial inductive analytic process developed theoretical insights. Manual coding using constant comparative methods categorised meaningful themes and sub-themes. Results Two key aspects were identified. Emerging themes for LBP presentation included: early identification LBP and influence of multidisciplinary team members on outcomes; factors influencing LBP reporting e.g. coach-athlete relationship; frequent presentations of LBP and accepted norms; athlete history and physical examination e.g. training load. Emerging themes for causation of LBP included: intrinsic risk factors e.g. growth and maturation; extrinsic risk factors e.g. equipment. Conclusions Individual responses of a gymnast to experiencing LBP were important across all themes. Some LBP was perceived as normal. The coach-athlete relationship and support team are crucial decision-makers around training load and adaptation. Early detection will help minimise time loss from training/performance to expedite healing.

Objectives: Spinal manipulative therapy (SMT) is widely used by manual therapists to manage spinal complaints. Notwithstanding the perceived relative safety of SMT, instances of severe thoracic adverse events (AE) have been documented. An evidence synthesis is required to understand the nature, severity and characteristics of thoracic AE following all SMT. The primary objective of this study was to report thoracic AE following SMT and secondly to report patient characteristics to inform further research for safe practice. Methods: A systematic review and data synthesis were conducted according to a registered protocol (PROSPERO CRD42019123140). A sensitive topic-based search strategy for key databases, gray literature and registers used study population terms and keywords, to search to 12/6/19. Two reviewers were involved at each stage. Using the Oxford Center for Evidence-based Medicine (CEBM) the level evidence was evaluated with grade presented for each AE. Results were reported in the context of overall quality. Results: From 1013 studies identified from searches, 19 studies (15 single case studies and 4 case series) reporting 21 unique thoracic AE involving the spinal cord tissues [nonvascular (n = 7), vascular (n = 6)], pneumothorax or hemothorax (n = 3), fracture (n = 3), esophageal rupture (n = 1), rupture of thoracic aorta (n = 1), partial pancreatic transection (n = 1). Reported outcomes included fully recovery (n = 8), permanent neurological deficit (n = 5), and death (n = 4). Conclusion: Although causality cannot be confirmed, serious thoracic AE to include permanent neurological deficit and death have been reported following SMT. Findings highlight the importance of clinical reasoning, including pre-thrust examination, as part of best and safe practice for SMT.

Author(s): Chaillon, A; Bharat, C; Stone, J; Jones, N; Degenhardt, L; Larney, S; Farrell, M; Vickerman, P; Hickman, M; Martin, NK; Borquez, A | Abstract: BACKGROUND AND AIMS: The individual-level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established but there is less evidence on population-level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in community and prison on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation. DESIGN: Dynamic modeling. SETTING AND PARTICIPANTS: A cohort of 49,359 individuals who ever received OAT in NSW from 2001-2018. MEASUREMENTS: Receipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1-9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1-12 months ago. The model incorporated elevated mortality post-release from prison, and OAT impact on reducing mortality and incarceration. FINDINGS: Among the cohort, mortality was 0.9 per 100 person-years, OAT coverage and retention remained high (g50%, 1.74 years/episode). Over 2001-2020, we estimate OAT provision reduced overdose and other cause mortality among the cohort by 53% [95% credible interval: 49%-56%] and 27% [22%-30%], respectively. We estimate 1.2 deaths averted and 9.7 life-years gained per 100 person-years on OAT. Prison OAT with post-release OAT-linkage accounted for 12% [11%-13%] of all deaths averted by the OAT program, primarily through preventing deaths in the first month post-release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% [1%-2%] and 3% [2%-5%] of deaths, respectively. CONCLUSION: The community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population-level overdose and all-cause mortality in the past 20 years, partially due to high retention.

Abortion and contraception are essential components of reproductive healthcare. As 26 states are likely to severely restrict access to abortion following the Supreme Court decision in Dobbs v. Jackson Women's Health Organization, access to emergency contraception will be more important than ever. Existing barriers to emergency contraception - including cost, obstacles to over-the-counter purchase, low awareness and availability of the most effective options, myths about safety and mechanism of action - already substantially limit access. Proactive solutions include public information campaigns; healthcare provider education about all emergency contraceptive options, including IUDs and advance provision of emergency contraceptive pills; innovative service delivery options such as vending machines and community distribution programs; and policy initiatives to ensure insurance coverage, eliminate pharmacy refusals, and support all service delivery options. In addition, we urge the U.S. Food and Drug Administration to approve updated labeling to align with the best available evidence that oral contraceptive pills work before ovulation and do not prevent implantation of a fertilized egg, as this language contributes to public confusion and access barriers. In the face of extreme limits on reproductive healthcare, now is the time to expand and protect access to emergency contraception so that everyone has the possibility of preventing pregnancy after unprotected sex or sexual assault.

Purpose In chemical exchange saturation transfer imaging, saturation effects between − 2 to − 5 ppm (nuclear Overhauser effects, NOEs) have been shown to exhibit contrast in preclinical stroke models. Our previous work on NOEs in human stroke used an analysis model that combined NOEs and semisolid MT; however their combination might feasibly have reduced sensitivity to changes in NOEs. The aim of this study was to explore the information a 4-pool Bloch–McConnell model provides about the NOE contribution in ischemic stroke, contrasting that with an intentionally approximate 3-pool model. Methods MRI data from 12 patients presenting with ischemic stroke were retrospectively analyzed, as well as from six animals induced with an ischemic lesion. Two Bloch–McConnell models (4 pools, and a 3-pool approximation) were compared for their ability to distinguish pathological tissue in acute stroke. The association of NOEs with pH was also explored, using pH phantoms that mimic the intracellular environment of naïve mouse brain. Results The 4-pool measure of NOEs exhibited a different association with tissue outcome compared to 3-pool approximation in the ischemic core and in tissue that underwent delayed infarction. In the ischemic core, the 4-pool measure was elevated in patient white matter ( 1.20±0.20 ) and in animals ( 1.27±0.20 ). In the naïve brain pH phantoms, significant positive correlation between the NOE and pH was observed. Conclusion Associations of NOEs with tissue pathology were found using the 4-pool metric that were not observed using the 3-pool approximation. The 4-pool model more adequately captured in vivo changes in NOEs and revealed trends depending on tissue pathology in stroke.

Introduction The evaluation of muscle strength is frequently used as part of the physical examination process, with decreased trunk muscle strength reported in individuals with spinal disorders (e.g., low back pain). Access to practicable performance-based outcome measures (PBOM) to monitor patients’ progress in spinal rehabilitation is essential. Knowledge of the psychometric properties of the available practicable PBOM for trunk strength evaluation is therefore needed to inform practitioners and further research. Objective To synthesise evidence on the measurement properties of practicable measures of trunk muscle strength in adults with and without musculoskeletal pain. Methods Following a published and registered protocol [PROSPERO CRD42020167464], databases were searched from the database inception date up to 30th of June 2021. Citations and grey literature were also searched. Eligibility criteria comprised: 1) studies which examined the psychometric properties of the trunk strength outcome measures, 2) included adults ≥ 18 years, either asymptomatic or with spinal musculoskeletal pain. Non-English language studies were excluded. Two independent reviewers evaluated the quality and synthesized the data from included studies according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. The overall quality of evidence was evaluated using a modified Grading of Recommendations Assessment Development and Evaluation (GRADE). Results From 34 included studies, 15 different PBOMs were identified that have been investigated for reliability and validity, none evaluated responsiveness. In asymptomatic individuals, high quality evidence supports intra-rater reliability of digital-loading cells and moderate quality evidence supports the criterion validity of the hand-held dynamometer. Very low quality evidence exists for the reliability and validity estimates of testing tools among individuals with spinal pain. Conclusions Findings underpin a cautious recommendation for the use of practicable PROMs to evaluate muscle strength in individuals with spinal pain in clinical practice due to the level of evidence and the heterogeneity of the protocols used. Further high quality research to explore the psychometric properties of the practicable PBOMs with detailed methodology is now needed.

To systematically review and synthesise the evidence on the measurement properties of patient-reported outcome measure (PROMs) used to assess the quality of life in patients with adult scoliosis.Based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines and a published protocol, a two-stage search was conducted and reported in line with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA). Stage one identified all studies of patients with adult scoliosis which included PROMs of health-related quality of life (HR-QOL). Databases including AMED, CINAHL, EMBASE, Medline, PsychINFO and Pubmed were searched from inception until 31st December 2020. This derived list of PROMs, was then utilised for a stage 2 search to identify studies which evaluated the measurement properties of the PROMs. Two reviewers independently performed the searches, study screening, selection and risk of bias assessment using the COSMIN tool. The overall quality of the evidence was assessed using a modified Grading of Recommendations Assessment, Development and Evaluation approach.Stage one yielded 16 PROMs of HR-QOL with the Oswestry Disability Index (ODI) and Scoliosis Research Society-22 (SRS-22) the most used. Stage two identified three stage one PROMs that fulfilled eligibility criteria: SRS-22, ODI and SRS-22r; with five studies investigating measurement properties in an adult scoliosis population. The SRS-22 was the most comprehensively evaluated PROM in this cohort with very low-quality evidence indicating indeterminate reliability, sufficient construct validity and sufficient responsiveness of the SRS-22. There is very low-quality evidence indicating sufficient responsiveness of the ODI. There is very low-quality evidence indicating indeterminate cross-cultural validity for the SRS-22r. All other measurement properties in the SRS-22, ODI and SRS-22r have not been evaluated.A large number of PROMs are being utilised in the adult scoliosis population and of these, the most commonly utilised are the ODI and SRS-22. The SRS-22, ODI and SRS-22r are the only PROMs to have had their measurement properties evaluated in the adult scoliosis population. The findings of this systematic review are that there currently is not sufficient evidence on the measurement properties of any PROMs in adult scoliosis. Further research is now urgently required to assess the measurement properties of these PROMs.

Purpose: Despite optimal local therapy, tumor cell invasion into normal brain parenchyma frequently results in recurrence in patients with solid tumors. The aim of this study was to determine whether microvascular inflammation can be targeted to better delineate the tumor-brain interface through vascular cell adhesion molecule-1 (VCAM-1)-targeted MRI. Experimental Design: Intracerebral xenograft rat models of MDA231Br-GFP (breast cancer) brain metastasis and U87MG (glioblastoma) were used to histologically examine the tumor-brain interface and to test the efficacy of VCAM-1–targeted MRI in detecting this region. Human biopsy samples of the brain metastasis and glioblastoma margins were examined for endothelial VCAM-1 expression. Results: The interface between tumor and surrounding normal brain tissue exhibited elevated endothelial VCAM-1 expression and increased microvessel density. Tumor proliferation and stemness markers were also significantly upregulated at the tumor rim in the brain metastasis model. T2*-weighted MRI, following intravenous administration of VCAM-MPIO, highlighted the tumor-brain interface of both tumor models more extensively than gadolinium-DTPA–enhanced T1-weighted MRI. Sites of VCAM-MPIO binding, evident as hypointense signals on MR images, correlated spatially with endothelial VCAM-1 upregulation and bound VCAM-MPIO beads detected histologically. These findings were further validated in an orthotopic medulloblastoma model. Finally, the tumor-brain interface in human brain metastasis and glioblastoma samples was similarly characterized by microvascular inflammation, extending beyond the region detectable using conventional MRI. Conclusions: This work illustrates the potential of VCAM-1–targeted MRI for improved delineation of the tumor-brain interface in both primary and secondary brain tumors.

Introduction: The impact of conservative interventions on lymphatic function and the relationship to clinical outcomes is currently unknown. A systematic review was undertaken to evaluate studies that used lymphoscintigraphy to measure outcomes from conservative intervention for secondary arm lymphedema and to explore the relationship between changes in the lymphoscintigraphy and clinical outcomes. Methods and Results: Five databases were systematically searched using the selection criteria: randomized controlled trials (RCTs); quasi-RCTs; pre/post and cohort studies; upper limb secondary lymphedema; use of lymphoscintigraphy as an outcome measure; and conservative intervention. Seven articles met the inclusion criteria. Compression, exercise, hyperbaric oxygen therapy, and pharmacological interventions were evaluated using lymphoscintigraphy. There was heterogeneity with all aspects of the lymphoscintigraphy techniques, including radioisotope used, injection location, use of exercise, and imaging sequence between the studies as well as the outcome analysis. Also most studies did not show a relationship between the clinical and lymphoscintigraphy outcomes measured. Conclusions: Lymphoscintigraphy has not been used regularly or recently to evaluate conservative upper limb lymphedema treatment outcomes. Lack of standardization of lymphoscintigraphy protocols and lack of consensus and understanding of the lymphoscintigraphy analyses used to measure the outcomes of diverse conservative lymphedema interventions currently limit the use of lymphoscintigraphy as an outcome measure. Further research adopting recent guidelines to standardize lymphoscintigraphy and use of reliable analysis techniques that measure the physiological impact of the chosen conservative lymphedema intervention is recommended to evaluate the impact of conservative interventions on lymphatic function.

Background and Aims: There is limited evidence on the relationship between retention in opioid agonist treatment for opioid dependence and characteristics of treatment prescribers. This study estimated retention in buprenorphine and methadone treatment and its relationship with person, treatment, and prescriber characteristics. Design: Retrospective longitudinal study.Setting: New South Wales, Australia.Participants: People entering the opioid agonist treatment program for the first time between August 2001 and December 2015.Measurements: Time in opioid agonist treatment (primary outcome) was modelled using a generalised estimating equation model to estimate associations with person, treatment, and prescriber characteristics. Findings: The impact of medication type on opioid agonist treatment retention reduced over time; risk of leaving treatment when on buprenorphine compared with methadone was higher among those that entered treatment earlier (e.g. 2001-2003: OR 1.59, 95% CI 1.44-1.74) and lowest among those that entered most recently (2013-2015: OR 1.24, 95% CI 1.12-1.37). In adjusted analyses, risk of leaving was reduced among people whose prescriber had longer tenure of prescribing (e.g. 3 versus 8 years: OR 0.94, 95% CI 0.93-0.95) compared with prescribers with shorter tenure. Aboriginal and Torres Strait Islander people, being of younger age, past-year psychosis disorder, and having been convicted of more criminal charges in the year prior to treatment entry were associated with increased risk of leaving treatment. Conclusion: In New South Wales, Australia, retention in buprenorphine treatment for opioid dependence, compared with methadone, has improved over time since its introduction in 2001. Opioid agonist treatment (OAT) retention is affected not only by characteristics of the person and his or her treatment, but also of the prescriber, with those of longer prescribing tenure associated with increased retention of people in OAT.

IntroductionRecent systematic reviews have identified many biopsychosocial factors associated with the development of chronic musculoskeletal pain (CMP). Despite often being specific to a particular musculoskeletal condition, findings are similar across systematic reviews. Research is needed to aggregate these findings to identify consistent factors across musculoskeletal disorders that are associated with the development of CMP. The objective of this study is to provide a meta-level synthesis of all biopsychosocial factors associated with the development of CMP.Methods and analysisAn umbrella review and meta-level narrative synthesis±meta-analysis has been designed informed by Joanna Briggs Institute and Cochrane guidance. This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P. Sources will include Ovid Medline, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO, CINAHL, PEDro, PROSPERO, Google Scholar and grey literature. Inclusion criteria: any systematic review which investigates biopsychosocial factors which may be associated with the development of CMP through prospective longitudinal methods. The outcome is musculoskeletal pain lasting beyond 3 months. Two independent reviewers will be involved in all stages; screening, selection, data extraction and risk of bias evaluation using the Assessing the Methodological Quality of Systematic Reviews-2 guidelines. A meta-level narrative synthesis will be conducted based on (a) factors associated with development of CMP, (b) the range of musculoskeletal disorders for which the same/similar findings have been established and (c) the quality of studies informing these findings. Where possible, meta-analysis will be performed. The Grading of Recommendations, Assessment, Development and Evaluation guidelines will be followed to determine the level of evidence for each biopsychosocial factor.Ethics and disseminationThis umbrella review does not require ethical approval. Findings will be presented at conferences and published in a peer reviewed journal.PROSPERO registration numberCRD42020193081.

IntroductionEarly-onset scoliosis (EOS) is a rare spinal deformity affecting children under the age of 10. Both the condition and its treatment have associated morbidity and can impact quality of life. Understanding this impact can be achieved by using appropriate patient-reported and/or carer-reported outcome measures. The aim of the review described in this protocol is to evaluate the evidence on measurement properties relevant to health-related quality of life outcomes in the EOS population. The focus will be on outcome measures relevant to patients undergoing treatment of EOS under the age of 10.Methods/analysisThis protocol is reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol and COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology. The MEDLINE, EMBASE, EMCARE, PubMed, PsychINFO and CINAHL databases will be searched using a two-stage search strategy. The first stage will identify measures of HRQoL used in EOS through screening of titles and abstracts. The second stage will assess the measurement properties of those measures identified through screening of full-text articles. The measurement properties of interest are the ‘reliability’, ‘validity’ and ‘responsiveness’ of the instrument. Only English language articles will be considered. Two reviewers will independently review the search results against the eligibility criteria, perform data extraction and assess for risk of bias, with disputes handled by a third reviewer. Data will be quantitatively pooled where possible or reported as a narrative synthesis. The summarised results for each measurement property will be rated against the criteria for good measurement properties following the COSMIN methodology. Two reviewers will assess the body of evidence for each measurement property using modified Grading of Recommendations, Assessment, Development and Evaluation guidelines.Ethics and disseminationNo ethical approval is required for this review and the results will be submitted for publication in peer-reviewed publications.PROSPERO registration numberCRD42020219721.

Background Previous findings reported that people with chronic neck pain walk with reduced range trunk rotation, especially when walking in more challenging conditions. Quantification of the quality of neck and trunk movement during gait could provide further insight into biomechanical changes that occur in people with neck pain. This study uniquely compared the variability of trunk and neck rotation during single-task and dual-task gait in people with chronic neck pain and asymptomatic individuals. Methods An observational case-control study was conducted on 20 asymptomatic individuals and 24 people with chronic neck pain of idiopathic or traumatic origin. Participants performed rectilinear walking whilst keeping the head in a neutral position (single-task) and whilst rotating the head at a natural speed (dual-task). Trunk and head rotation angles were averaged across gait cycles for the task trials. The data were normalised in time, and the average variability of angular distribution along the normalised cycle was extracted. The Tampa Scale for Kinesiophobia was used to assess fear of movement. Findings During single-task gait, there were no group differences for the variability of trunk (p = 0.862) or neck (p = 0.427) rotation. For dual-task gait, there was no difference between groups for the variability of neck rotation (p = 0.636), however, the participants with neck pain displayed reduced variability of trunk rotation (p = 0.021). The neck pain group also walked at a significantly slower speed during dual-task gait (p = 0.043) compared to asymptomatic individuals and the speed of their gait was associated with the extent of fear of movement. Interpretation The strategy observed in participants with chronic neck pain likely reflects adaptive behaviour when faced with more challenging conditions for postural control.

Background Masters-level education is a key pathway of professional development for healthcare practitioners. Whilst there is evidence that Masters-level education leads to career enhancement, it is unclear how the programme pedagogy contributes to this. The objective was to: (1) examine the programme pedagogies and context that supports learning, and (2) synthesise the outputs, outcomes and impact of Masters-level healthcare programmes. Methods A systematic review was conducted according to the Cochrane Collaboration handbook and is reported in line with PRISMA. Using pre-defined key terms and eligibility criteria, two reviewers independently searched Medline, ERIC, Web of Science, ProQuest, and CINAHL Plus databases from inception to 14th November 2016, reference lists of retrieved articles and selected websites. Data were extracted independently. The Mixed Methods Appraisal Tool was used to assess methodological quality. A Weight of Evidence Framework enabled evaluation of the overall quality of evidence. Data were synthesised using thematic qualitative analysis. Results Thirty-five studies were included. All studies were retrospective, evaluated programmes in nursing (n = 19), physiotherapy (n = 6), general and family medicine (n = 4), public health (n = 3), dentistry (n = 1), interdisciplinary (n = 1), and occupational therapy (n = 1). Most studies were rated low in methodological quality, with an overall low to moderate weight of evidence for programmes’ outcomes and impact. Pedagogies that promote social participation and knowledge co-construction, reflection, learner-centred approach, relevance and authenticity influenced outcomes and impact. Conclusion(s) Notwithstanding the low to moderate weight of evidence, the review identified multiple positive outcomes of Master-level education for healthcare practitioners. Whilst the pedagogies that contributed to such positive outcomes were examined in some studies, there is a need to further explore links between programme pedagogy, outputs, outcomes and impact. A cultural approach to evaluation may capture how M-level education drives changes. Electronic supplementary material The online version of this article (10.1186/s12909-019-1768-7) contains supplementary material, which is available to authorized users.

Purpose Multi-phase PCASL has been proposed as a means to achieve accurate perfusion quantification that is robust to imperfect shim in the labelling plane. However, there exists a bias in the estimation process that is a function of noise in the data. In this work, this bias is characterised and then addressed in animal and human data. Methods The proposed algorithm to overcome bias uses the initial biased voxel-wise estimate of phase tracking error to cluster regions with different off-resonance phase shifts, from which a high-SNR estimate of regional phase offset is derived. Simulations were used to predict the bias expected at typical SNR. Multi-phase PCASL in three rat strains (n = 21) at 9.4 T was considered, along with 20 human subjects previously imaged using ASL at 3 T. The algorithm was extended to include estimation of arterial blood flow velocity. Results Based on simulations, a perfusion estimation bias of 6–8% was expected using 8-phase data at typical SNR. This bias was eliminated when a high-precision estimate of phase error was available. In the preclinical data, the bias-corrected measure of perfusion (107±14 mL/100g/min) was lower than the standard analysis (116±14 mL/100g/min), corresponding to a mean observed bias across strains of 8.0%. In the human data, bias correction resulted in a 15% decrease in the estimate of perfusion. Conclusion Using a retrospective algorithmic approach, it was possible to exploit common information found in multiple voxels within a whole region of the brain, offering superior SNR and thus overcoming the bias in perfusion quantification from multi-phase PCASL.

© 2019 World Institute of Pain Purpose: To investigate whether people with chronic low back pain (LBP) show dysfunctional exercise-induced hypoalgesia (EIH) in response to repeated contractions of their back muscles during a lifting task. Methods: In this cross-sectional observational study conducted on asymptomatic participants (n = 18) and participants with chronic LBP (n = 21), quantitative sensory testing (QST) was applied extensively over the lumbar region and a remote area before and after a repeated task that involved lifting a 5-kg box for ~7 minutes. QST included pressure pain thresholds (PPTs), thermal detection, pain thresholds, and measures of temporal summation. Topographical maps of the percentage change in PPT detected at 16 locations over the lumbar region were generated to explore regional differences and compared between groups. Results: Mean (standard deviation) PPTs measured from 16 sites over the lower back changed significantly in asymptomatic participants (+29.78 kPa [41.4]) following task completion, indicative of EIH, whereas no significant change was observed for the low back pain (LBP) group (−14.87 kPa [61.2]). No changes were detected at the remote site for either group. No changes were revealed for the thermal tests. Temporal summation data revealed decreasing pain sensitivity as the test progressed, but the test response did not change after the exercise for either group. Conclusion(s): Unlike asymptomatic individuals, participants with LBP lacked EIH over the lumbar erector spinae muscles following repeated lifting. Although these results should be considered in relation to the study limitations, particularly the absence of a control group, the findings support impaired EIH in patients with LBP.

Background Upper limb neurodynamic tests (ULNTs) are used to identify a neuropathic pain component in patients' presenting with arm and/or neck pain. Clinical tests with established diagnostic accuracy are required to not only to inform clinical management but also minimise costs associated with expensive medical investigations. Objective To evaluate the role of ULNTs in assessment of peripheral neuropathic pain and to inform their value in clinical practice when assessing patients with arm and/or neck symptoms. Design Systematic review was undertaken according to published guidelines, and reported in line with PRISMA-DTA. Method Key databases were searched up to 21/11/2017. Inclusion criteria: Patient population experiencing arm and/or neck symptoms with suspected peripheral neuropathic involvement, studies that compared ULNT to a reference standard, any study design using primary diagnostic accuracy data. Two reviewers independently assessed risk of bias (ROB) using QUADAS-2. The overall quality of evidence was evaluated using GRADE. Results Of eight included studies (n = 579), four were assessed as low ROB, although all had concerns regarding applicability. For carpal tunnel syndrome, ULNT1 sensitivity values ranged 0.4–0.93, specificity 0.13–0.93, positive likelihood ratio 0.86–3.67 and negative likelihood ratio 0.5–1.9. For cervical radiculopathy ULNT1 and the combined use of four ULNTs had sensitivity of 0.97 (95%CI 0.85–1.00) whereas the ULNT3 was the most specific (0.87, 95%CI 0.62–0.98). Positive likelihood ratio ranged 0.58–5.68 and negative likelihood ratio 0.12–1.62. Conclusion Based on the available evidence ULNTs cannot be utilised as a stand-alone test for the diagnosis of CTS. Limited evidence suggests that ULNTs may be clinically relevant for the diagnosis of CR, but only as a “ruling out” strategy. However, the overall quality of the body of evidence after applying the GRADE approach was low to very low across studies. Further higher quality research is needed to establish firm conclusions.

Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors. Combining in vivo APT MRI measurements with ex vivo histological measurements of protein concentration in a rat model of brain metastasis, we determined that the proportion of APT MRI signal originating from changes in protein concentration was approximately 66%, with the remaining 34% originating from changes in tumor pH. In a mouse model of hypopharyngeal squamous cell carcinoma (FaDu), APT MRI showed that a reduction in tumor hypoxia was associated with a shift in tumor pH. The results of this study extend our understanding of APT MRI data and may enable the use of APT MRI to infer the pH of individual patients' tumors as either a biomarker for therapy stratification or as a measure of therapeutic response in clinical settings. Significance: These findings advance our understanding of amide proton transfer magnetic resonance imaging (APT MRI) of tumors and may improve the interpretation of APT MRI in clinical settings.

Exercise prescription is a central tenet of physiotherapy. One of the numerous benefits of exercise is its influence on endogenous pain modulation. Exercise-induced hypoalgesia (EIH) refers to a short-term change in pain sensitivity following an acute bout of exercise. Interest in this phenomenon has grown considerably with over 150 articles published, including four systematic reviews in 2020 alone.This narrative review provides an overview of EIH including a definition and summary of the underlying mechanisms and mediating factors. Recent systematic reviews assessing EIH in people with and without musculoskeletal complaints were evaluated using AMSTAR2. Review findings confirm the presence of EIH. For asymptomatic people, confidence in the evidence was low to very low due to high heterogeneity of included studies, risk of bias, and study eligibility. For people with pain, there is very low confidence, at best, that subgroups or isometric exercise show altered EIH. Despite the growing body of evidence, challenges within the available evidence due to its complex nature are highlighted. Recommendations regarding outcome measures and exercise parameters are required, and further understanding of reliability and validity of EIH is needed. There is a demand to further elucidate these parameters and contextual factors to advance our understanding of EIH. Additional clinical research, especially in patient populations, is required to then provide implications for rehabilitation.Übungen sind ein Kernbestandteil von Physiotherapie. Eine der vielen positiven Wirkungen von Übungsprogrammen ist der Effekt auf die endogene Schmerzmodellierung. Bewegungsinduzierte Hypoalgesie (BIH) ist definiert als eine kurzzeitige Erhöhung der Schmerzschwelle als direkte Antwort auf eine Bewegungsübung. Das Phänomen BIH hat in den letzten Jahren große Aufmerksamkeit in der Forschung bekommen mit über 150 publizierten Studien. Vier systematische Übersichtsarbeiten wurden allein im Jahr 2020 veröffentlicht.Dieses narrative Review liefert einen Überblick über das Phänomen BIH und fasst die zugrunde liegenden Mechanismen und Einflussfaktoren zusammen. Aktuelle systematische Übersichtsarbeiten bei gesunden Teilnehmern und Patienten wurden anhand von AMSTAR2 bewertet. Das Phänomen BIH ist wissenschaftlich fundiert, aber es besteht niedrige bis sehr niedrige Konfidenz, dass BIH bei Gesunden auftritt. Große Heterogenität, hohes Verzerrungsrisiko und das Nichterfüllen der Einschlusskriterien für die systematischen Übersichtsarbeiten beeinträchtigen die Auswertung. Für Menschen mit Erkrankungen besteht sehr niedrige Konfidenz, bestenfalls zeigen Subgruppen oder isometrische Übungen geänderte BIH. Trotz des großen Interesses an der Thematik konnten Probleme mit der aktuellen Studienlage durch die Komplexität von BIH aufgezeigt werden. Es fehlen Empfehlungen für Messinstrumente und Übungsparameter, zudem wurden Reliabilität und Validität bisher wenig erforscht.Weitere Grundlagenforschung zu BIH-Parametern und Kontextfaktoren wird benötigt und kann zum Verständnis von BIH beitragen, um dann in klinische Forschung, insbesondere bei Patientengruppen, und anschließend die Rehabilitation übertragen werden zu können.

Background Thoracic kyphosis is reported to increase with ageing. However, this relationship has not been systematically investigated. Peoples’ kyphosis often exceeds 40°, but 40° is the widely accepted cut-off and threshold for normality. Consequently, patients may be misclassified. Accurate restoration of kyphosis is important to avoid complications following spinal surgery. Therefore, specific reference values are needed. The objective of the review is to explore the relationship between thoracic kyphosis and age, provide normative values of kyphosis for different age groups and investigate the influence of gender and ethnicity. Methods Two reviewers independently conducted a literature search, including seven databases and the Spine Journal, from inception to April 2020. Quantitative observational studies on healthy adults (18 years of age or older) with no known pathologies, and measuring kyphosis with Cobb’s method, a flexicurve, or a kyphometer, were included. Study selection, data extraction, and study quality assessment (AQUA tool) were performed independently by two reviewers. The authors were contacted if clarifications were necessary. Correlation analysis and inferential statistics were performed (Microsoft Excel). The results are presented narratively. A modified GRADE was used for evidence quality assessment. Results Thirty-four studies (24 moderate-quality, 10 high-quality) were included (n = 7633). A positive moderate correlation between kyphosis and age was found (Spearman 0.52, p < 0.05, T5-T12). Peoples’ kyphosis resulted greater than 40° in 65% of the cases, and it was significantly smaller in individuals younger than 40 years old (x < 40) than in those older than 60 years old (x > 60) 75% of the time (p < 0.05). No differences between genders were found, although a greater kyphosis angle was observed in North Americans and Europeans. Conclusion Kyphosis increases with ageing, varying significantly between x < 40 and x > 60. Furthermore, kyphosis appears to be influenced by ethnicity, but not gender. Peoples’ thoracic sagittal curvature frequently exceeds 40°. Trial registration The review protocol was devised following the PRISMA-P Guidelines, and it was registered on PROSPERO (CRD42020175058) before study commencement.

To investigate whether upright magnetic resonance imaging (MRI) has a role in defining thoracolumbar spine pathology in elite gymnastics.A prospective cross-sectional observational study of National Senior and Junior Artistic gymnasts in three MRI positions (standard supine, upright flexed and extended positions). Two specialist musculoskeletal radiologists independently analysed images with neutral as a baseline with the effects of flexion and extension reported in line with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.Forty (18 males) gymnasts aged 13-24 years with a mean (SD) of 32 (5.3) training hours per week consented with 75% showing MRI abnormalities. Degenerative disc disease (DDD) was evident in 55% participants with vertebral end plate (VEP) changes in 42.5%. Spondylolysis was present in 40% with an additional 17% showing chronic bilateral complete L5 pars defects. 23% participants demonstrated different MRI findings in upright flexion compared to neutral.Findings suggest a high levels of MRI abnormalities in elite gymnastics including altered disc morphology and posterior element abnormalities. High prevalence of T11/12 DDD and VEP changes reflects the thoracolumbar junction being a transition zone. Upright MRI and varying spine position offer promise for enhanced visualisation of posterior element abnormalities.

Background Non-melanoma skin cancers (NMSC) are the most common skin cancers worldwide with research establishing that ultraviolet (UV) radiation influences occurrence. However, recent studies about NMSC tumour frequencies suggested high NMSC predilections in low UV-exposed skin regions. Methods The 'Human Surface Anatomy Labeling System' was used to define 100 skin regions to map NMSC locations excised at Flinders Medical Centre (FMC) between 1 January 2012 and 31 December 2017. Data were retrieved from the FMC histopathology database. A customised phrase algorithm was used to run a systematic word search on the dataset to quantify NMSC locations. Results A total of 22 303 NMSC excisions were identified; 80% were head and neck excisions. Scalp, periocular and nasal regions showed a significantly greater predilection for basal cell carcinomas (BCC). Squamous cell carcinomas (SCC) had significantly more excisions in lip, neck and scalp regions. Regarding gender-related variations, more males had BCC excisions in ear regions and more females had nasal, lip, and ankle excisions. In SCC excisions, more males had scalp excisions and more females had leg and lip excisions. Considering age-related variation, significantly higher proportions of BCC were found with forehead excisions compared to scalp, neck and lower limb regions for SCC, all being highest for 60-79-year age groups. Conclusion The relationship between NMSC type and anatomical distribution may be partially explained by gender and age affecting NMSC predilections particularly in the head and neck. However, other skin regions could not be explained solely by these factors.

BACKGROUND The current study assessed the level of reliability of ultrasound to assess dermal thickness, a clinical feature of breast lymphedema. Additionally, the relationship of dermal thickness to patient-reported outcomes was investigated. METHODS Women (n = 82) with unilateral breast edema secondary to treatment of breast cancer were randomized to an exercise or control group. Ultrasound measurements of the unaffected and affected breasts were taken at baseline and 12 weeks later at 3-4 cm superior, medial, inferior, and lateral to the nipple. Additionally, women completed breast-related questions from the European Organization Research and Treatment Committee Quality of Life breast cancer module (EORTC-BR23) and Lymphedema Symptom Intensity and Distress Questionnaire (LSIDS). Reliability of ultrasound measurements was determined on the unaffected breast. RESULTS Intraclass correlation coefficients (2,1) ranged from 0.66 (95% CI: 0.52-0.77) for the lateral location to 0.84 (0.77-0.90) for the superior location. Percent close agreement (80%) on the unaffected breast ranged from 0.20 to 0.27 mm compared to 0.57 to 0.93 mm on the affected breast. The standard error of measurement (%) on the unaffected breast varied from 9% to 13% with smallest real difference 0.34-0.41 mm. Dermal thickness of the affected breast was not-to-poorly associated with EORTC BR23 and LSIDS scores. CONCLUSION Reliability of dermal thickness measurements of the breast was excellent for the superior, medial, and inferior locations, and fair to good for the lateral location. However, these measurements were not related to the symptom's women perceive and measured with the EORTC BR23 or LSIDS.

To determine whether differences in landing force and asymmetry of landing force exist between gymnasts at the time of data collection versus those that subsequently experienced an ankle injury 12-months later. Prospective longitudinal observational design with baseline measures and 12 month follow up. British Gymnastics National Training Centre. Thirty-two asymptomatic elite level gymnasts from three artistic gymnastic squads (n = 15 senior female, n = 10 junior female and n = 7 senior male). A modified drop land task was used to quantify measures of landing performance. Peak Vertical Ground Reaction Force (PVGRF) was used to measure landing force. The level of inter-limb asymmetry of landing force was calculated using the Limb Symmetry index (LSI). Other measures included injury incidence and percentage coefficient of variation (% CV). There was no statistical difference for landing force (p = 0.481) and asymmetry of landing force (p = 0.698) when comparing injured and non-injured gymnasts. Most participants (69%) demonstrated inter-limb asymmetry of landing forces. Our findings observed inter-limb asymmetry of landing force in injured gymnasts, although uninjured gymnasts also exhibited asymmetry of landing force. Both magnitude of landing force and inter-limb asymmetries of landing force failed to identify the risk of ankle injury. [Abstract copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.]

Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth.

Background Chronic low back pain (CLBP) prevalence has steadily increased over the last two decades. Manual therapy (MT) is recommended within a multimodal management approach to improve pain and disability although evidence investigating the patients’ experience of MT is scarce. Objective To explore expectations and perceptions of MT techniques in people with CLBP. Methods A qualitative study embedded sequential to an experimental trial using semi-structured interviews (SSI) explored participants’ experiences of thrust, non-thrust and sham technique. Purposive sampling enabled variance in age and CLBP duration. An evidence informed topic guide was used. Data were analysed using thematic analysis (TA). Respondent validation and peer debriefing enhanced trustworthiness. The Consolidating Criteria for Reporting Qualitative Studies (COREQ) reported methodological rigour. Findings Ten participants (50% male) with a mean age of 29.1 years (Standard Deviation (SD): 7.9, range: 19–43), a mean pain intensity of 4.5 on a Numeric Rating Scale (NRS) 0–10 (SD: 1.5, range: 2–7), a mean Oswestry Disability Score (ODI) of 9 (SD: 4.6, range: 2–17) and a mean Tampa Scale of Kinesiophobia (TSK) score of 38.6 (SD: 4.8, range: 30–45) participated. Four themes were identified: understanding of pain; forming expectations; perception of care; re-evaluation of body awareness and management. Understanding of CLBP is formed by an individuals’ pain perception and exchange with social environment. This, combined with communication with physiotherapist influenced expectations regarding the MT technique. Conclusion Expectations for MT were formed by an individual’s social environment and previous experience. A treatment technique is perceived as positive if its characteristics are aligned with the individual’s understanding of pain and if care is delivered in an informative and reassuring manner.

A plethora of evidence supports the existence of neuromuscular changes in people with chronic spinal pain (neck and low back pain), yet it is unclear whether neuromuscular adaptations persist for people with recurrent spinal pain when in a period of remission. This systematic review aimed to synthesise the evidence on neuromuscular adaptations in people with recurrent spinal pain during a period of remission. Electronic databases, grey literature, and key journals were searched from inception up to the 4th of September 2020. Eligibility criteria included observational studies investigating muscle activity, spine kinematics, muscle properties, sensorimotor control, and neuromuscular performance in adults (≥ 18 years) with recurrent spinal pain during a period of remission. Screening, data extraction, and quality assessment (Newcastle-Ottawa Scale) were conducted independently by two reviewers. Data synthesis was conducted per outcome domain. A meta-analysis with a random-effects model was performed where possible. The overall strength of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation guidelines (GRADE). From 8292 records, 27 and five studies were included in a qualitative and quantitative synthesis, respectively. Very low level of evidence supports muscle activity changes in people with recurrent low back pain, especially greater co-contraction, redistribution of muscle activity, and delayed postural control of deeper trunk muscles. Reduced range of motion of the lumbar spine was also found. Meaningful conclusions regarding other outcome domains or people with recurrent neck pain could not be drawn. In conclusion, people with recurrent low back pain during a period of remission show muscle activity and spine kinematics adaptations. Future research should investigate the long-term impact of these changes, as well as adaptations in people with recurrent neck pain.