Association of serum biomarkers with radiographic knee osteoarthritis, knee pain and function in a young, male, trauma-exposed population - Findings from the ADVANCE study.

OBJECTIVE: The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA. DESIGN: ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported. The primary analysis, adjusted for age, body mass, socioeconomic status, and ethnicity, was to determine any differences in biomarkers between those with/without combat injury, rOA and pain. Secondary analyses were performed to compare post-traumatic/idiopathic OA, painful/painfree rOA and injury patterns. RESULTS: A total of 1145 male participants were recruited, aged 34.1 ± 5.4, 8.9 ± 2.2 years post-injury (n = 579 trauma-exposed, of which, traumatic-amputation n = 161) or deployment (n = 566 matched). Cartilage oligomeric matrix protein (COMP) was significantly higher in the combat-injured group compared to uninjured (p = 0.01). Notably, COMP was significantly lower in the traumatic-amputation group compared to non-amputees (p < 0.001), decreasing relative to number of amputations (p < 0.001). Leptin was higher (p = 0.005) and adiponectin lower (p = 0.017) in those with v without knee pain, associated with an increased risk of 22% and 17% for pain, and 46% and 34% for painful rOA, respectively. There were no significant differences between trauma-exposed and unexposed participants with rOA. CONCLUSIONS: The most notable findings of this large, unique study are the similarities between those with rOA regardless of trauma-exposure, the injury-pattern and traumatic-amputation-associated differences in COMP, and the relationship between adipokines and pain.

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

Post-traumatic growth amongst UK armed forces personnel who were deployed to Afghanistan and the role of combat injury, mental health and pain: the ADVANCE cohort study.

BACKGROUND: Post-traumatic growth (PTG) is a positive psychological consequence of trauma. The aims of this study were to investigate whether combat injury was associated with deployment-related PTG in a cohort of UK military personnel who were deployed to Afghanistan, and whether post-traumatic stress disorder (PTSD), depression and pain mediate this relationship. METHODS: 521 physically injured (n = 138 amputation; n = 383 non-amputation injury) and 514 frequency-matched uninjured personnel completed questionnaires including the deployment-related Post-Traumatic Growth Inventory (DPTGI). DPTGI scores were categorised into tertiles of: no/low (score 0-20), moderate (score 21-34) or a large (35-63) degree of deployment-related PTG. Analysis was completed using generalised structural equation modelling. RESULTS: A large degree of PTG was reported by 28.0% (n = 140) of the uninjured group, 36.9% (n = 196) of the overall injured group, 45.4% (n = 62) of amputee and 34.1% (n = 134) of the non-amputee injured subgroups. Combat injury had a direct effect on reporting a large degree of PTG [Relative risk ratio (RRR) 1.59 (95% confidence interval (CI) 1.17-2.17)] compared to sustaining no injury. Amputation injuries also had a significant direct effect [RRR 2.18 (95% CI 1.24-3.75)], but non-amputation injuries did not [RRR 1.35 (95% CI 0.92-1.93)]. PTSD, depression and pain partially mediate this relationship, though mediation differed depending on the injury subtype. PTSD had a curvilinear relationship with PTG, whilst depression had a negative association and pain had a positive association. CONCLUSIONS: Combat injury, in particular injury resulting in traumatic amputation, is associated with reporting a large degree of PTG.

Relationship between combat-related traumatic injury and its severity to predicted cardiovascular disease risk: ADVANCE cohort study.

BACKGROUND: This study investigated the relationship between combat-related traumatic injury (CRTI) and its severity and predicted cardiovascular disease (CVD) risk. MATERIAL AND METHODS: This was an analysis of comparative 10-year predicted CVD risk (myocardial infarction, stroke or CVD-death) using the QRISK®3 scoring-system among adults recruited into the Armed Services Trauma Rehabilitation Outcome (ADVANCE) cohort study. Participants with CRTI were compared to uninjured servicemen frequency-matched by age, sex, rank, deployment (Afghanistan 2003-2014) and role. Injury severity was quantified using the New Injury Severity Score (NISS). RESULTS: One thousand one hundred forty four adult combat veterans were recruited, consisting of 579 injured (161 amputees) and 565 uninjured men of similar age ethnicity and time from deployment/injury. Significant mental illness (8.5% vs 4.4%; p = 0.006) and erectile dysfunction (11.6% vs 5.8%; p < 0.001) was more common, body mass index (28.1 ± 3.9 vs 27.4 ± 3.4 kg/m2; p = 0.001) higher and systolic blood pressure variability (median [IQR]) (1.7 [1.2-3.0] vs 2.1 [1.2-3.5] mmHg; p = 0.008) lower among the injured versus uninjured respectively. The relative risk (RR) of predicted CVD (versus the population expected risk) was higher (RR:1.67 [IQR 1.16-2.48]) among the injured amputees versus the injured non-amputees (RR:1.60 [1.13-2.43]) and uninjured groups (RR:1.52 [1.12-2.34]; overall p = 0.015). After adjustment for confounders CRTI, worsening injury severity (higher NISS, blast and traumatic amputation) were independently associated with QRISK®3 scores. CONCLUSION: CRTI and its worsening severity were independently associated with increased predicted 10-year CVD risk.

ADAPTations to low load blood flow restriction exercise versus conventional heavier load resistance exercise in UK military personnel with persistent knee pain: protocol for the ADAPT study, a multi-centre randomized controlled trial.

BACKGROUND: Muscle atrophy, muscle weakness and localised pain are commonly reported following musculoskeletal injury (MSKI). To mitigate this risk and prepare individuals to return to sport or physically demanding occupations, resistance training (RT) is considered a vital component of rehabilitation. However, to elicit adaptations in muscle strength, exercise guidelines recommend lifting loads ≥ 70% of an individual's one repetition maximum (1-RM). Unfortunately, individuals with persistent knee pain are often unable to tolerate such high loads and this may negatively impact the duration and extent of their recovery. Low load blood flow restriction (LL-BFR) is an alternative RT technique that has demonstrated improvements in muscle strength, hypertrophy, and pain in the absence of high mechanical loading. However, the effectiveness of high-frequency LL-BFR in a residential rehabilitation environment remains unclear. This study will compare the efficacy of high frequency LL-BFR to 'conventional' heavier load resistance training (HL-RT) on measures of physical function and pain in adults with persistent knee pain. METHODS: This is a multicentre randomised controlled trial (RCT) of 150 UK service personnel (aged 18-55) admitted for a 3-week residential rehabilitation course with persistent knee pain. Participants will be randomised to receive: a) LL-BFR delivered twice daily at 20% 1-RM or b) HL-RT three-times per week at 70% 1-RM. Outcomes will be recorded at baseline (T1), course discharge (T2) and at three-months following course (T3). The primary outcome will be the lower extremity functional scale (LEFS) at T2. Secondary outcomes will include patient reported perceptions of pain, physical and occupational function and objective measures of muscle strength and neuromuscular performance. Additional biomechanical and physiological mechanisms underpinning both RT interventions will also be investigated as part of a nested mechanistic study. DISCUSSION: LL-BFR is a rehabilitation modality that has the potential to induce positive clinical adaptations in the absence of high mechanical loads and therefore could be considered a treatment option for patients suffering significant functional deficits who are unable to tolerate heavy load RT. Consequently, results from this study will have a direct clinical application to healthcare service providers and patients involved in the rehabilitation of physically active adults suffering MSKI. TRIAL REGISTRATION: ClinicalTrials.org reference number, NCT05719922.

Hip joint and muscle loading for persons with bilateral transfemoral/through-knee amputations: biomechanical differences between full-length articulated and foreshortened non-articulated prostheses.

BACKGROUND: Currently, there is little available in-depth analysis of the biomechanical effect of different prostheses on the musculoskeletal system function and residual limb internal loading for persons with bilateral transfemoral/through-knee amputations (BTF). Commercially available prostheses for BTF include full-length articulated prostheses (microprocessor-controlled prosthetic knees with dynamic response prosthetic feet) and foreshortened non-articulated stubby prostheses. This study aims to assess and compare the BTF musculoskeletal function and loading during gait with these two types of prostheses. METHODS: Gait data were collected from four male traumatic military BTF and four able-bodied (AB) matched controls using a 10-camera motion capture system with two force plates. BTF completed level-ground walking trials with full-length articulated and foreshortened non-articulated stubby prostheses. Inverse kinematics, inverse dynamics and musculoskeletal modelling simulations were conducted. RESULTS: Full-length articulated prostheses introduced larger stride length (by 0.5 m) and walking speed (by 0.3 m/s) than stubbies. BTF with articulated prostheses showed larger peak hip extension angles (by 10.1°), flexion moment (by 1.0 Nm/kg) and second peak hip contact force (by 3.8 bodyweight) than stubbies. There was no difference in the hip joint loading profile between BTF with stubbies and AB for one gait cycle. Full-length articulated prostheses introduced higher hip flexor muscle force impulse than stubbies. CONCLUSIONS: Compared to stubbies, BTF with full-length articulated prostheses can achieve similar activity levels to persons without limb loss, but this may introduce detrimental muscle and hip joint loading, which may lead to reduced muscular endurance and joint degeneration. This study provides beneficial guidance in making informed decisions for prosthesis choice.

The Stanford Hall consensus statement for post-COVID-19 rehabilitation.

The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0-10. Substantial agreement (range 7.5-10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post COVID-19 illness, for a target population of active individuals, including military personnel and athletes.

MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group.

OBJECTIVES: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation. METHODS: The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC). RESULTS: No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97). CONCLUSION: The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.

Recommendations for acquisition and interpretation of MRI of the spine and sacroiliac joints in the diagnosis of axial spondyloarthritis in the UK.

OBJECTIVES: To develop evidence-based recommendations on the use of MRI in the diagnosis of axial SpA (axSpA). METHODS: A working group comprising nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA was established, with support from the British Society of Spondyloarthritis (BRITSpA). Two meetings were held. In the first meeting, research questions were formulated. In the second meeting, the results of a systematic literature review designed to inform the recommendations were reviewed. An anonymized Delphi process was used to formulate the final set of recommendations. For each recommendation, the level of evidence and strength of recommendation was determined. The level of agreement was assessed using a 0-10 numerical rating scale. RESULTS: Two overarching principles were formulated, as follows: The diagnosis of axSpA is based on clinical, laboratory and imaging features (overarching principle 1), and patients with axSpA can have isolated inflammation of either the sacroiliac joints or the spine (overarching principle 2). Seven recommendations addressing the use of MRI in the assessment of patients with suspected axSpA were formulated, covering topics including recommended sequences, anatomical coverage, acquisition parameters and interpretation of active and structural MRI lesions. The level of agreement for each recommendation was very high (range 8.8-9.8). CONCLUSION: A joint rheumatology and radiology consensus on the acquisition and interpretation of MRI in axSpA diagnosis was achieved, and a research agenda formulated. This consensus should help standardize practice around MRI and ensure a more informed, consistent approach to the diagnosis of axSpA.

Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents?

A spectrum of disease extends beyond the rigid confines of ankylosing spondylitis (AS). Axial spondyloarthritis (axSpA) encompasses non-radiographic axSpA (nr-axSpA) in individuals without established radiographic changes but with other clinical/imaging axSpA features and AS in those with definite sacroiliac joint changes on pelvic X-rays. A broad consensus about the management of nr-axSpA is emerging among clinicians, but the evidence base remains open to question. To explore whether nr-axSpA and AS should be treated similarly, we examined the literature on their prevalence, natural history, disease burden, and treatment. There is strong evidence that nr-axSpA and AS are expressions of the same disease. Approximately 10% of patients with nr-axSpA will develop radiographic disease over 2 years; after >20 years, the figure may exceed 80%. Nr-axSpA patients have lower CRP and less spinal inflammation on MRI than AS patients but similar disease activity, pain, and quality-of-life impairment. Most patients with nr-axSpA manage well with conservative treatment, but a minority has severe disabling symptoms. Anti-TNF therapy has demonstrated similar efficacy and safety in nr-axSpA and AS. Current evidence does not clearly indicate that anti-TNF treatment can inhibit or limit bony progression of AS, the basis of conservative and anti-TNF treatment is control of symptoms and function. For some patients with nr-axSpA, the need for powerful treatments is as great as in some with AS; thus, treatment of axSpA should be consistent across the axSpA spectrum with anti-TNF agents being available, irrespective of radiographic change, according to the same criteria as those applied to AS.

Study protocol: a double blind randomised control trial of high volume image guided injections in Achilles and patellar tendinopathy in a young active population.

BACKGROUND: Chronic tendinopathy is a significant problem particularly in active populations limiting sporting and occupational performance. The prevalence of patellar tendinopathy in some sports is near 50% and the incidence of lower limb tendinopathy is 1.4% p.a. in the UK Military. Management includes isometric, eccentric, heavy slow resistance exercises and extracorporeal shockwave therapy (ESWT). Often these treatments are inadequate yet there is no good evidence for injection therapies and success rates from surgery can be as low as 50%. High Volume Image Guided Injection (HVIGI) proposes to strip away the neovascularity and disrupt the nerve ingrowth seen in chronic cases and has shown promising results in case series. This study aims to investigate the efficacy of HVIGI in a randomised controlled trial (RCT). METHODS: RCT comparing 40ml HVIGI, with or without corticosteroid, with a 3ml local anaesthetic sham-control injection. Ninety-six participants will be recruited. INCLUSION CRITERIA: male, 18-55 years old, chronic Achilles or patellar tendinopathy of at least 6 months, failed conservative management including ESWT, and Ultrasound (US) evidence of neovascularisation, tendon thickening and echogenic changes. Outcome measures will be recorded at baseline, 6 weeks, 3, 6 and 12 months. Primary outcome measures include The Victoria Institute of Sport Assessments for Achilles and patellar tendinopathy (VISA-A and VISA-P) and VAS pain. Secondary outcome measures include Modified Ohberg score, maximum tendon diameter and assessment of hypoechoic appearance on US, and Functional Activity Assessment. DISCUSSION: Despite previous interventional trials and reviews there is still insufficient evidence to guide injectable therapy for chronic tendinopathy that has failed conservative treatment. The scant evidence available suggests HVIGI has the greatest potential however there is no level one RCT evidence to support this. Investigating the efficacy of HVIGI against control in a RCT and separating the effect of HVIGI and corticosteroid will add high level evidence to the management of chronic tendinopathy resistant to conservative treatment. TRIAL REGISTRATION: EudraCT: 2015-003587-36 3 Dec 2015.

A comparison of multidisciplinary team residential rehabilitation with conventional outpatient care for the treatment of non-arthritic intra-articular hip pain in UK Military personnel - a protocol for a randomised controlled trial.

BACKGROUND: Non-arthritic hip disorders are defined as abnormalities of the articulating surfaces of the acetabulum and femur before the onset of osteoarthritis, including intra-articular structures such as the acetabular labrum and chondral surfaces. Abnormal femoroacetabular morphology is commonly seen in young men who constitute much of the UK military population. Residential multidisciplinary team (MDT) rehabilitation for patients with musculoskeletal injuries has a long tradition in the UK military, however, there are no studies presenting empirical data on the efficacy of a residential MDT approach compared with individualised conventional outpatient treatment. With no available data, the sustainability of this care pathway has been questioned. The purpose of this randomised controlled trial is to compare the effects of a residential multidisciplinary intervention, to usual outpatient care, on the clinical outcomes of young active adults undergoing treatment for non-arthritic intra-articular hip pain. METHODS/DESIGN: The trial will be conducted at the Defence Medical Rehabilitation Centre, Headley Court, UK. One hundred military male participants with clinical indicators of non-arthritic intra-articular hip pain will be randomly allocated to either: (1) 7-day residential multidisciplinary team intervention, n = 50; (2) 6-week physiotherapist-led outpatient intervention (conventional care), n = 50. Measurements will be taken at baseline, post-treatment (1-week MDT group; 6-weeks physiotherapy group), and 12-weeks. The primary outcome measures are the function in daily living sub-scale of the Copenhagen Hip and Groin Outcome Score (HAGOS), the physical function subscale of the Non-arthritic Hip Score (NAHS), and VAS pain scale. Secondary outcomes include objective measures of physical capacity and general health. An intention-to-treat analysis will be performed using linear and mixed models. DISCUSSION: This study will be the first to assess the efficacy of intensive MDT rehabilitation, versus conventional outpatient care, for the management of non-arthritic hip pain. The results from this study will add to the evidence-base and inform clinical practice for the management of intra-articular non-arthritic hip pain and femoroacetabular impingement in young active adults. TRIAL REGISTRATION: ISRCTN Reference: ISRCTN 59255714 dated 11-Nov-2015.

Functional and Mental Health Status of United Kingdom Military Amputees Postrehabilitation.

OBJECTIVES: To evaluate the functional and mental health status of severely injured traumatic amputees from the United Kingdom military at the completion of their rehabilitation pathway and to compare these data with the published normative data. DESIGN: Retrospective independent group comparison of descriptive rehabilitation data recorded postrehabilitation. SETTING: A military complex trauma rehabilitation center. PARTICIPANTS: Amputees (N=65; mean age, 29±6 y) were evaluated at the completion of their rehabilitation pathway; of these, 54 were operationally (combat) injured (23 unilateral, 23 bilateral, 8 triple) and 11 nonoperationally injured (all unilateral). INTERVENTIONS: Continuous ∼4-week inpatient, physician-led, interdisciplinary rehabilitation followed by ∼4-weeks of patient-led, home-based rehabilitation. MAIN OUTCOME MEASURES: The New Injury Severity Score at the point of injury was used as the baseline reference. The 6-minute walk test, Amputee Mobility Predictor with Prosthesis, Special Interest Group in Amputee Medicine, Defence Medical Rehabilitation Centre mobility and activity of daily living scores as well as depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder Scale-7), mental health support, and pain scores were recorded at discharge and compared with the published normative data. RESULTS: The mean New Injury Severity Score was 40±15. After 34±14 months of rehabilitation, amputees achieved a mean 6-minute walk distance of 489±117 m compared with age-matched normative distances of 459 to 738 m. The 2 unilateral groups walked (544 m) significantly further (P>.05) than did the bilateral amputee (445±104 m) and triple amputee (387±99 m) groups. All groups demonstrated mean functional mobility scores consistent with scores of either active adults or community ambulators with limb loss. In total, 85% could walk/run independently and 95% could walk and perform activities of daily living independently with an aid/adaptation. No significant difference in mental health outcome was reported between the groups (P>.05). At discharge, 98% of patients were able to control their pain. CONCLUSIONS: Severely injured military amputees who completed intensive interdisciplinary rehabilitation achieved levels of physical function comparable with those in age-matched healthy adults. Mental health outcomes were indicative of preparedness for full integration back into society.

Musculoskeletal injuries in British Army recruits: a prospective study of diagnosis-specific incidence and rehabilitation times.

BACKGROUND: Musculoskeletal injuries during initial military training are a significant medical problem facing military organisations globally. In order to develop an injury management programme, this study aims to quantify the incidence and rehabilitation times for injury specific diagnoses. METHODS: This was a prospective follow-up study of musculoskeletal injuries in 6608 British Army recruits during a 26-week initial military training programme over a 2-year period. Incidence and rehabilitation times for injury specific diagnoses were recorded and analysed. RESULTS: During the study period the overall incidence of musculoskeletal injuries was 48.6%, and the most common diagnosis was iliotibial band syndrome (6.2%). A significant proportion of the injuries occurred during the first 11 weeks of the programme. The longest rehabilitation times were for stress fractures of the femur, calcaneus and tibia (116 ± 17 days, 92 ± 12 days, and 85 ± 11 days, respectively). The combination of high incidence and lengthy rehabilitation indicates that medial tibial stress syndrome had the greatest impact on training, accounting for almost 20% of all days spent in rehabilitation. CONCLUSION: When setting prevention priorities consideration should be given to both the incidence of specific injury diagnoses and their associated time to recovery.

Pituitary dysfunction after blast traumatic brain injury: The UK BIOSAP study.

OBJECTIVE: Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. METHODS: Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. RESULTS: Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. INTERPRETATION: We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function.

The Influence of Physical and Mental Health Mediators on the Relationship Between Combat-Related Traumatic Injury and Ultra-Short-Term Heart Rate Variability in a U.K. Military Cohort: A Structural Equation Modeling Approach.

INTRODUCTION: Combat-related traumatic injury (CRTI) adversely affects heart rate variability (HRV). The mediating effect of mental and physical health factors on the relationship between CRTI, its severity and HRV has not been previously studied and investigated. MATERIALS AND METHODS: A cross-sectional mediation analysis of the ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) prospective cohort study was performed. The sample consisted of injured and uninjured British male servicemen who were frequency-matched based on their age, rank, role-in-theater, and deployment to Afghanistan (2003-2014). CRTI and injury severity (the New Injury Severity Scores [NISS] [NISS < 25 and NISS ≥ 25]) were included as exposure variables. HRV was quantified using the root mean square of successive differences (RMSSD) obtained using pulse waveform analysis. Depression and anxiety mediators were quantified using the Patient Health Questionnaire and Generalized Anxiety Disorder, respectively. Body mass index and the 6-minute walk test (6MWT) represented physical health measures. Two mediation pathways between exposure and outcome variables were examined in comparison with the uninjured group using structural equation modeling. RESULTS: Of 862 servicemen, 428 were injured and 434 were uninjured with the mean age at assessment of 33.9 ± 5.4 (range 23-59) years. Structural equation modeling revealed that depression, anxiety, and body mass index did not significantly mediate the relationship between injury/injury severity and RMSSD. However, the 6MWT significantly mediated the relationship between CRTI and RMSSD (27% mediation). The indirect effect of 6MWT on the relationship between injury severity (NISS ≥ 25 vs. uninjured) and RMSSD was -0.06 (95% CI: -0.12, -0.00, P < .05). CONCLUSIONS: The findings suggest that greater physical function may improve HRV following CRTI. Longitudinal studies are warranted to further validate these findings.

Exploratory analysis of spontaneous versus paced breathing on heart rate variability in veterans with combat-related traumatic injury.

BACKGROUND: Respiration is a crucial determinant of autonomic balance and heart rate variability (HRV). The comparative effect of spontaneous versus paced breathing on HRV has been almost exclusively explored in healthy adults and never been investigated in an injured military cohort. OBJECTIVE: To examine the effect of spontaneous versus paced breathing on HRV in veterans with combat-related traumatic injury (CRTI). DESIGN: Observational cohort study. SETTING: ArmeD serVices trAuma rehabilitatioN outComE (ADVANCE) study, Stanford Hall, UK. PARTICIPANTS: The sample consisted of 100 randomly selected participants who sustained CRTI (eg, amputation) during their deployment (Afghanistan 2003-2014) and were recruited into the ongoing ADVANCE prospective cohort study. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: HRV was recorded using a single-lead ECG. HRV data were acquired during a sequential protocol of 5-minute spontaneous breathing followed immediately by 5 minutes of paced breathing (six cycles/minute) among fully rested and supine participants. HRV was reported using time domain (root mean square of successive differences), frequency domain (low frequency and high frequency) and nonlinear (sample entropy) measures. The agreement between HRV during spontaneous versus paced breathing was examined using the Bland-Altman analysis. RESULTS: The mean age of participants was 36.5 ± 4.6 years. Resting respiratory rate was significantly higher with spontaneous versus paced breathing (13.4 ± 3.4 vs. 7.6 ± 2.0 breaths/minute; p < .001), respectively. Resting mean heart rate and root mean square of successive differences were significantly higher with paced breathing than spontaneous breathing (p < .001). Paced breathing significantly increased median low frequency power than spontaneous breathing (p < .001). No significant difference was found in the absolute power of high frequency between the two breathing protocols. The Bland-Altman analysis revealed poor agreement between HRV values during spontaneous and paced breathing conditions with wide limits of agreement. CONCLUSION: Slow-paced breathing leads to higher HRV than spontaneous breathing and could overestimate resting "natural-state" HRV.

Upper Limb Function in People With Upper and Lower Limb Loss 8 Years Postinjury: The Armed Services Trauma Outcome Study (ADVANCE) Cohort Study.

OBJECTIVE: Upper limb (UL) disability in people with UL amputation/s is well reported in the literature, less so for people with lower limb amputation/s. This study aimed to compare UL disability in injured (major trauma) and uninjured UK military personnel, with particular focus on people with upper and lower limb amputation/s. METHODS: A volunteer sample of injured (n = 579) and uninjured (n = 566) UK military personnel who served in a combat role in the Afghanistan war were frequency matched on age, sex, service, rank, regiment, role, and deployment period and recruited to the Armed Services Trauma Rehabilitation Outcome (ADVANCE) longitudinal cohort study. Participants completed the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire, scored from 0 (no disability) to 100 (maximum disability) 8 years postinjury. Mann-Whitney U and Kruskal Wallis tests were used to compared DASH scores between groups. An ordinal model was used to assess the effect of injury and amputation on DASH scores. RESULTS: DASH scores were higher in the group with injuries compared to the group without injuries (3.33 vs 0.00) and higher in people with lower limb loss compared to the group without injuries (0.83 vs 0.00), although this was not statistically significant. In the adjusted ordinal model, the odds of having a higher DASH score was 1.70 (95% CI = 1.18-2.47) times higher for people with lower limb loss compared to the group without injuries. DASH score was not significantly different between people with major and partial UL loss (15.42 vs 12.92). The odds of having a higher DASH score was 8.30 (95% CI = 5.07-13.60) times higher for people with UL loss compared to the uninjured group. CONCLUSION: People with lower limb loss have increased odds of having more UL disability than the uninjured population 8 years postinjury. People with major and partial UL loss have similar UL disability. The ADVANCE study will continue to follow this population for the next 20 years. IMPACT: For the first time, potential for greater upper limb disability has been shown in people with lower limb loss long-term, likely resulting from daily biomechanical compensations such as weight-bearing, balance, and power generation. This population may benefit from prophylactic upper limb rehabilitation, strength, and technique.