Adverse outcomes in trials of graded exercise therapy for adult patients with chronic fatigue syndrome.

OBJECTIVES: Graded exercise therapy (GET) is an effective treatment for chronic fatigue syndrome (CFS), but concerns have been raised about its safety. Two randomised controlled trials have not supported these concerns. We further assessed safety outcomes in all ten published trials of GET for CFS. METHODS: We undertook meta-analyses of three outcomes: Self-ratings of Clinical Global Impression (CGI) change scores of 6 or 7 ("much worse" or "very much worse"), numbers of participants withdrawing from treatments, and numbers of participants dropping out of trial follow up. We provide risk ratios (95% confidence intervals (CI)), comparing GET with control interventions. RESULTS: The 10 trials involved 1279 participants. CGI scores of 6 or 7 were reported by 14/333 (4%) participants after GET and 26/334 (8%) participants after control interventions (RR (CI): 0.62 (0.32, 1.17)). Withdrawals from treatment occurred in 64/535 (12%) participants after GET and 53/534 (10%) participants after control interventions (RR (CI):1.21 (0.86, 1.69)). Drop-outs from trial follow up occurred in 74/679 (11%) participants after GET and 41/600 (7%) participants after control interventions (RR (CI): 1.51 (1.03, 2.22)). The certainty of this evidence was rated low by GRADE, due to imprecision. CONCLUSIONS: There was no evidence of excess harm with graded exercise therapy by either self-rated deterioration or by withdrawing from GET, in comparison to control interventions. More GET participants dropped out of trial follow up in comparison to control interventions. Future research should ascertain the most effective and safest form of graded exercise therapy.

Getting soldiers with brain injury back to work: the defence medical rehabilitation centre neurological vocational pathway.

The Neuro-Rehabilitation Group at the Defence Medical Rehabilitation Centre (DMRC) has developed an integrated vocational pathway to transition service personnel back into employment. This article describes how vocational rehabilitation at DMRC fits with the wider UK military, in comparison with civilian rehabilitation. It also describes the ongoing development of the vocational pathway, which contributes to improved outcomes from neurological disorders, including traumatic brain injury. We present two cases to highlight how the programme integrates with and influences patient care.

Injury severity at presentation is not associated with long-term vocational outcome in British Military brain injury.

INTRODUCTION: Injury Severity Score (ISS) and GCS can be retrospective markers of injury severity, but if used by clinicians to decide on the treatment of acutely brain-injured casualties at the point of injury may potentially limit interventions on people who may ultimately survive with good functional outcomes. METHODS: ISS/GCS and long-term outcomes were reviewed by assessing all UK military neurorehabilitation patients with an operational/combat brain injury treated over 4 years (February 2008-July 2012) at Defence Medical Rehabilitation Centre (Headley Court). RESULTS: 34 participants from 9 operational tours of Iraq and Afghanistan were analysed. Overall, 44% of injuries were due to improvised explosive devices (IEDs) and 41% from gunshot wounds; 70.9% of injuries were penetrating wounds with the remainder due to blast/blunt trauma or combined injury. The primary injury was head/neck in 76.5%, although eight patients (23.4%) requiring neurorehabilitation were initially 'non-head injury'. Eight patients (26.5%) sustained more than 10 injuries, and 18 had between three and nine injuries. Eleven patients (32%) had an initial GCS of 3, and 16 (47%) had ISS of 75 (deemed 'unsurvivable'). All patients with ISS of 75 were long-term survivors. At 4 months after discharge, 47% (16) were fully independent, and a further 41% (14) were independent in own homes, but needed assistance with some activities, such as paying bills. Over three-quarters (27 patients, 79%) returned to full/part-time work, 11 of whom returned to military duties; 93% of 'unsurvivable' ISS, and 91% of patients with GCS of 3 were capable of returning/returned to work. In total, 7/11 casualties returning to military duties had major trauma ISS, and two were 'unsurvivable'. All seven casualties with both GCS 3 and ISS 75 survived and returned to independence (help with some activities). CONCLUSIONS: ISS/GCS at the point of injury does not reflect eventual outcome. IEDs/gunshots cause the greatest number of injuries and the highest incidence of brain injury. Brain injury should be considered in every battlefield casualty, irrespective of whether the head/neck/spinal cord was avoided. ISS should not be considered indicative or predictive of long-term prognosis/quality of life/employability as brain injury in this small cohort is both survivable and recoverable. It should not be used as a retrospective guide to alter treatment pathways, as there is poor correlation with long-term outcome. Subsequent neurorehabilitation should always be considered because survival, return to independence and full employment are very likely.

The functional activity assessment: a validated PROM, unreliable in the hands of clinicians.

OBJECTIVES: To examine the validity of the clinician-assessed version of a military occupational outcome measure (the functional activity assessment; FAA) and to compare the validity with the self-assessed version. METHODS: The relationship between the clinician-assessed FAA and the SF-36 and Physical Workload Questionnaire was examined in 192 service personnel with musculoskeletal injuries. Concurrent validity was checked by comparing actual medical category with the FAA. RESULTS: Clinicians preferentially chose an FAA grade of 2 (56% of all grades). The clinician-assessed FAA was significantly correlated with all measured variables in the expected direction. The performance of the regression models did not fully support construct validity. The discriminative ability of the models was poor. CONCLUSIONS: The clinician-assessed FAA is a less valid measure than its self-assessed counterpart. Use of the patient-reported FAA outcome measure is recommended.

The safety and efficacy, and recommendations for the use of biologic drugs in the UK military rheumatology population.

Inflammatory arthritis is a significant cause of morbidity in the military. In particular the sero-negative spondyloarthritides, which include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease related arthritis and undifferentiated spondyloarthritis, are especially prevalent in the young male phenotype, which is common in the Armed Forces. It is estimated that there are more than 1500 patients in the Armed Forces with spondyloarthritis alone, based on the prevalence in the general population of approximately 1%. Inflammatory arthritides are eminently treatable, especially with the development and widespread use of biologic drugs such as anti-Tumour Necrosis Factor (TNF) therapy. The use of these drugs can deliver patients an exceptionally good outcome leading to symptom control and normal function in many cases. Initial concerns regarding safety and side effects of anti-TNF drugs have been allayed by the evidence provided from comprehensive national databases developed over the last 10 years. With early diagnosis and prompt treatment military patients can complete a full career including deployment with only minor limitations. This paper reviews the burden of inflammatory arthritis in the armed services, its management and outcome in this population, the evidence for the safety of anti-TNF treatments and the recommendations for employability and deployability for service personnel.

Dynamic pressure testing for chronic exertional compartment syndrome in the UK military population.

OBJECTIVES: Chronic exertional compartment syndrome is one of the main causes of exertional leg pain. Diagnosis is based on the history and intracompartmental muscle pressure testing during exercise prior to consideration of fasciotomy for treatment. We present the data gathered at Defence Medical Rehabilitation Centre Headley Court during the first year of a revised protocol on dynamic pressure testing from May 2007. METHODS: The exercise protocol involved exercising patients using a representative military task: the Combat Fitness Test with a 15 kg Bergen on a treadmill, set at 6.5 km/h with zero incline up to 15 min and if completed, a further 5 min at 7.5 km/h. Subjects informed us when the exertional leg pain was 7/10 on a visual analogue scale and were instructed to carry on till failure (pain 10/10) or till the test finished. Mean pressure during this time period (7/10 to 10/10) was calculated by computer. RESULTS: Over 1 year, we performed 151 intracompartmental pressure studies in 76 patients. 120 were successful in 68 patients, with 31 technical failures. All studies were performed in the anterior or deep posterior muscle compartments as these were the symptomatic compartments; no patients had symptoms in the lateral or superficial posterior compartments and these were not tested. There was only one complication with a posterior tibial artery puncture. In 119 compartment studies, the mean pressure was 97.8 mm Hg (SD 31.7). These data are normally distributed (Shapiro Wilk test, W=0.98 p=0.125). CONCLUSIONS: Our data based on this exercise protocol are comparable with the few studies that record dynamic pressure during running-based exercise. There is no accepted diagnostic pressure or exercise protocol. Due to the uncertainty of diagnostic criteria, it is necessary to perform a study measuring dynamic pressures in normal asymptomatic subjects.

Nerve injuries sustained during warfare: part I--Epidemiology.

We describe 261 peripheral nerve injuries sustained in war by 100 consecutive service men and women injured in Iraq and Afghanistan. Their mean age was 26.5 years (18.1 to 42.6), the median interval between injury and first review was 4.2 months (mean 8.4 months (0.36 to 48.49)) and median follow-up was 28.4 months (mean 20.5 months (1.3 to 64.2)). The nerve lesions were predominantly focal prolonged conduction block/neurapraxia in 116 (45%), axonotmesis in 92 (35%) and neurotmesis in 53 (20%) and were evenly distributed between the upper and the lower limbs. Explosions accounted for 164 (63%): 213 (82%) nerve injuries were associated with open wounds. Two or more main nerves were injured in 70 patients. The ulnar, common peroneal and tibial nerves were most commonly injured. In 69 patients there was a vascular injury, fracture, or both at the level of the nerve lesion. Major tissue loss was present in 50 patients: amputation of at least one limb was needed in 18. A total of 36 patients continued in severe neuropathic pain. This paper outlines the methods used in the assessment of these injuries and provides information about the depth and distribution of the nerve lesions, their associated injuries and neuropathic pain syndromes.

Nerve injuries sustained during warfare: part II: Outcomes.

The outcomes of 261 nerve injuries in 100 patients were graded good in 173 cases (66%), fair in 70 (26.8%) and poor in 18 (6.9%) at the final review (median 28.4 months (1.3 to 64.2)). The initial grades for the 42 sutures and graft were 11 good, 14 fair and 17 poor. After subsequent revision repairs in seven, neurolyses in 11 and free vascularised fasciocutaneous flaps in 11, the final grades were 15 good, 18 fair and nine poor. Pain was relieved in 30 of 36 patients by nerve repair, revision of repair or neurolysis, and flaps when indicated. The difference in outcome between penetrating missile wounds and those caused by explosions was not statistically significant; in the latter group the onset of recovery from focal conduction block was delayed (mean 4.7 months (2.5 to 10.2) vs 3.8 months (0.6 to 6); p = 0.0001). A total of 42 patients (47 lower limbs) presented with an insensate foot. By final review (mean 27.4 months (20 to 36)) plantar sensation was good in 26 limbs (55%), fair in 16 (34%) and poor in five (11%). Nine patients returned to full military duties, 18 to restricted duties, 30 to sedentary work, and 43 were discharged from military service. Effective rehabilitation must be early, integrated and vigorous. The responsible surgeons must be firmly embedded in the process, at times exerting leadership.

Use of ultrasound to identify chronic Achilles tendinosis in an active asymptomatic population.

OBJECTIVES: The aim of the study was to identify the prevalence of degenerative change in the Achilles tendons of currently asymptomatic individuals and correlate it with their degree of physical activity. METHODS: We recruited 126 healthy subjects, mean age 33.1, range 20 - 50 (78 males and 48 females). Their levels of physical activity were assessed by a questionnaire and scored using the Allied Dunbar Fitness Survey criteria, modified to exclude non-weight bearing activity. One investigator, who was blinded to the activity levels, ultrasound scanned all 252 tendons. Tendons were examined for evidence of hypoechoic regions, localised fusiform thickening, and the cross-sectional diameter of each was measured. RESULTS: Overall 59% (149) of tendons had ultrasound evidence of hypoechoic regions. In 50 tendons (in 31 patients) there was a history of previous Achilles pain and 84% of these had hypoechoic regions. Thirty three percent of subjects in the lowest quartile of activity had evidence of hypoechoic regions compared to 72.6% in the most active quartile (Pearson Chi2 p < 0.01). Only 5.6% of all Achilles tendons had ultrasound evidence of localised fusiform thickening, with none in the inactive group compared to 6.4% in the very active group (Pearson Chi2 p = 0.03). CONCLUSIONS: Degenerative changes, identified by ultrasound, are common in the Achilles tendon and are often asymptomatic. There is a direct relationship between these changes and levels of current and lifetime activity. The natural history of asymptomatic chronic Achilles tendinosis and their relationship to future pain or tendon pathology is unknown.

Employment retention after moderate-severe traumatic brain injury (TBI) in the British Army 1989-98.

AIMS: To examine retention in employment of subjects with moderate-severe traumatic brain injury (TBI) in the British Army. METHODS: Comparative groups study of retention in Army employment after TBI using 564 TBI, 368 lower limb fracture, and 25 575 healthy subjects. Kaplan-Meier survival analysis was used to examine, stratifying for age, continuation in Army employment for six years after TBI. RESULTS: Subjects in the younger groups (mean ages 23 years and 27 years respectively) with either TBI or lower limb fracture remained in employment longer than healthy peers (median time for TBI, 3.91 years, lower limb fracture, 4.39 years, and healthy, 1.74 years). This trend changed through age stratification and for older subjects the reverse pattern was seen. In group 4 (mean age 41 years), median retention time for TBI was 3.33 years, for lower limb fracture, 3.75 years, healthy 5.55 years. Older subjects also showed a marked drop out rate at one year after injury; 32.7% of those with TBI in group 3 (mean age 31 years) had left Army employment at the end of year one compared with 19% in age group 1 (mean age 23 years). CONCLUSIONS: Younger soldiers with either TBI or lower limb fracture are retained in Army employment longer than their healthy peers. This may be due to sheltered employment, the availability of ongoing support, or transience of the healthy population. Since these results were drawn from incidence data on moderate and severe TBI it may be that those who serve on after TBI will do so with some degree of disability which affects occupational performance. There may be a significant unmet rehabilitation need for this group which is the focus of ongoing research.

The incidence and occupational outcome of overuse anterior knee pain during army recruit training.

OBJECTIVES: To determine the incidence and occupational outcome of overuse anterior knee pain (AKP) in Army recruits undergoing basic training. METHODS: A prospective cohort study of 1008 Army recruits. Recruits underwent the 12-week phase 1 training program. Cases of AKP were captured through self-presentation of pain at a primary care medical centre. All recruits medical records were reviewed on leaving training and any other lower limb injuries were recorded for comparison with the AKP group. Training outcomes in terms of medical discharges (MD) and discharges as of right (DAOR) i.e, voluntary discharge, were recorded along with training days lost (TDL) and whether a recruit had been held back in training (BS). RESULTS: 8.75% (95% CI: 6.93-10.57) of recruits reported to the medical centre with AKP. Of these more than half were referred to see a GP and the majority were from patients with no previous history of AKP (91%, 95% CI: 85.2-97.5). The median TDL per AKP case was 3 days (IQR: 3-5 days). The AKP group had a significantly higher (p < 0.01) MD rate (12.5%) than the lower limb injury group (3.3%; 95% CI diff: 1.1-17.2%) and the baseline rate of all other recruits (2.5%; 95% CI diff: 2.3-17.7%). The majority of AKP cases occurred by week 4 (median) of training (IQR: 2.2-64). CONCLUSIONS: There was a high incidence of AKP, and while the short term prognosis appears relatively good in the majority of cases as reflected in the median TDL, a large minority were medically discharged and held back in training. Further work should examine methods of reducing the disease burden of AKP in the Army, addressing areas such as aetiology, prevention and treatment.

Early discharge of patients with presumed opioid overdose: development of a clinical prediction rule.

OBJECTIVE: To develop a clinical prediction rule to identify patients who can be safely discharged one hour after the administration of naloxone for presumed opioid overdose. METHODS: Patients who received naloxone for known or presumed opioid overdose were formally evaluated one hour later for multiple potential predictor variables. Patients were classified into two groups: those with adverse events within 24 hours and those without. Using classification and regression tree methodology, a decision rule was developed to predict safe discharge. RESULTS: Clinical findings from 573 patients allowed us to develop a clinical prediction rule with a sensitivity of 99% (95% CI = 96% to 100%) and a specificity of 40% (95% CI = 36% to 45%). Patients with presumed opioid overdose can be safely discharged one hour after naloxone administration if they: 1) can mobilize as usual; 2) have oxygen saturation on room air of >92%; 3) have a respiratory rate >10 breaths/min and <20 breaths/min; 4) have a temperature of >35.0 degrees C and <37.5 degrees C; 5) have a heart rate >50 beats/min and <100 beats/min; and 6) have a Glasgow Coma Scale score of 15. CONCLUSIONS: This prediction rule for safe early discharge of patients with presumed opioid overdose performs well in this derivation set but requires validation followed by confirmation of safe implementation.

Frequent users of the emergency department: a program to improve care and reduce visits.

The authors describe a case-management program for frequent users of the emergency department. The study had a single-subject design, with evaluation for each patient of the number of visits to the emergency department for a 12-month period before referral to the program and a similar period after implementation of an individualized care plan. Referrals were made on the basis of 2 or more of the following criteria: chronic medical condition, complex medical condition, drug-seeking behaviour, violent behaviour and abusive behaviour. A multidisciplinary team developed the individualized care plans. Twenty-four patients agreed to participate. For the 12-month period before their referral, these patients accounted for a total of 616 (median 26.5) visits to the emergency department; for a similar period after implementation of the care plans, they accounted for 175 (median 6.5) visits. The difficult-case management program appeared to be effective in reducing the total number of visits to the emergency department during the study period and in improving the care for these patients.

Development, implementation and reliability assessment of an emergency physician performance evaluation tool.

UNLABELLED: Evaluation of physician practice is necessary, both to provide feedback for self-improvement and to guide department heads during yearly evaluations. OBJECTIVE: To develop and implement a peer-based performance evaluation tool and to measure reliability and physician satisfaction. METHODS: Each emergency physician in an urban emergency department evaluated their peers by completing a survey consisting of 21 questions on effectiveness in 4 categories: clinical practice, interaction with coworkers and the public, nonclinical departmental responsibilities, and academic activities. A sample of emergency nurses evaluated each emergency physician on a subset of 5 of the questions. Factor analysis was used to assess the reliability of the questions and categories. Intra-class correlation coefficients were calculated to determine inter-rater reliability. After receiving their peer evaluations, each physician rated the process's usefulness to the individual and the department. RESULTS: 225 surveys were completed on 16 physicians. Factor analysis did not distinguish the nonclinical and academic categories as distinct; therefore, the survey questions fell into 3 domains, rather than the 4 hypothesized. The overall intra-class correlation coefficient was 0.43 for emergency physicians, indicating moderate, but far from perfect, agreement. This suggests that variability exists between physician evaluators, and that multiple reviewers are probably required to provide a balanced physician evaluation. The intra-class correlation coefficient for emergency nurses was 0.11, suggesting poor reliability. Overall, 11 of 15 physicians reported the process valuable or mostly valuable, 3 of 15 were unsure and 1 of 15 reported that the process was definitely not valuable. CONCLUSION: Physician evaluation by a single individual is probably unreliable. A useful physician peer evaluation tool can be developed. Most physicians view a personalized, broad-based, confidential peer review as valuable.

Is early discharge safe after naloxone reversal of presumed opioid overdose?

INTRODUCTION: Patients with suspected opioid overdose frequently require naloxone treatment. Despite recommendations to observe such patients for 4 to 24 hours after naloxone, earlier discharge is becoming more common. This prospective, observational study of patients with presumed opioid overdose examines the safety of early disposition decisions and the accuracy of outcome prediction by physicians 1 hour after the administration of naloxone. METHODS: The study was carried out at St. Paul's Hospital, an inner city teaching centre that cares for most of the injection drug users in Vancouver, BC. Patients were formally assessed 1 hour after receiving naloxone for presumed opioid overdose. Demographics, medical history and physical examination were documented on specific data forms, and physicians recorded their comfort with early discharge. Patients were followed up, and those who required a critical intervention or suffered a pre-defined adverse event (AE) within 24 hours of their 1-hour assessment were identified. RESULTS: Of 573 patients, 48% were discharged in less than 2 hours, 23% in 2-4 hours and 29% in >4 hours. 94 patients who were held in the emergency department (ED) or admitted required a critical intervention, including supplemental oxygen for hypoxia (74), repeat naloxone (52), antibiotics administered intravenously (IV) (14), assisted ventilations (13), fluid bolus for hypotension (12), charcoal for associated life-threatening overdose (6), IV inotropic agents (2), antiarrhythmics for sustained tachycardia >130 beats/min (1), and administration of bicarbonate for arterial [HCO3] <5 or venous CO2 <5 (1). Physicians predicted adverse events with 94% sensitivity and 59% specificity. No discharged patients suffered a serious AE within 24 hours of ED discharge. CONCLUSIONS: Emergency physicians can clinically identify patients at risk of deterioration after naloxone reversal of suspected opioid overdose. Prolonged observation or hospital admission is not usually required. Selective early discharge of patients with presumed opioid overdose is feasible and appears safe. A clinical prediction rule may be useful in identifying patients eligible for early discharge.

The effects of 10 weeks military training on heel ultrasound and bone turnover.

To measure the physiological changes in bone in response to strenuous exercise we performed a prospective study of male army recruits over 10 weeks of basic training. Measurements performed at the start and completion of training consisted of ultrasound (US) measurements of the heel: velocity of sound (VOS in m/seconds) and broadband ultrasound attenuation (BUA in dB/MHz) and bone turnover markers; osteocalcin (OC), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP). Forty subjects were recruited for the study and 26 completed training. Over the 10-week study period there was a significant 1.7% fall in mean VOS [mean paired difference (mpd) 27.2 m/second, SEM 9.5 (95% CI 7.5-46.8) P = 0.009] and a nonsignificant 3.4% increase in BUA (P = 0.159). There were significant falls in markers of bone formation OC [11.6%, mpd 0. 11 microg/liter (95% CI 0.07-0.14) P < 0.001] and BALP [13.3%, mpd 3. 49 U/liter (CI 0.80-6.18) P = 0.013] and a nonsignificant 9.5% fall in TRAP a marker of bone resorption. The 10 recruits subsequently injured had a significantly lower VOS on entry [mean difference 24.2 m/seconds (95% CI 4.6-43.7) P = 0.017] and nonsignificantly raised BUA and baseline levels of all bone markers. The ultrasound changes may be accounted for by increase in trabecular separation and a fall in trabecular connectivity due to microfracture. The decrease in bone markers implies a fall in bone turnover.

Rubella virus and chronic joint disease: is there an association?

Synovial fluid samples and/or biopsies from 79 patients with various chronic inflammatory joint diseases or traumatic joint injury were tested for rubella virus (RV) in order to confirm or refute results from other studies that suggested RV as a cause of chronic inflammatory joint disease. Sixty-eight of the 72 patients tested had RV antibodies. RV RNA was detected by reverse transcription-PCR in the synovial fluid cells from two patients. RV was also isolated by cell culture from the synovial fluid of one of these two patients. This patient was a 42-year-old female with common variable immune deficiency and Mycoplasma hominis arthritis, while the other was a 68-year-old female with rheumatoid arthritis. While these results fail to confirm that RV is associated with chronic inflammatory joint disease, they suggest that RV may persist within a joint and be reactivated when cell-mediated immunity is suppressed.