Low back pain (LBP) is both the single most common cause of disability and the leading cause of visits to primary care doctors. Not surprisingly, the direct and indirect costs of low back pain accounts for approximately $88 billion of health care expenditure—barely trailing the cost of care for diabetes and heart disease. In order to reduce the large financial and personal cost, clinical studies must be designed to treat LBP.

Peer-reviewed literature has shown that the incidence of lumbar facet mediated pain ranges from 15-45% among patients with LBP. Some of the challenge to diagnosing facet mediated pain is based on poor correlation of abnormal imaging findings to patient’s symptoms. Not only is there a high prevalence of abnormalities on magnetic resonance imaging (MRI) of asymptomatic population, advanced imaging such as computed tomography (CT) scans fail to show an association between facet joint pain and degenerative changes seen within CT. It is due to such poor correlation of image findings to patient’s symptoms that medial branch block (MBB) has become the standard to diagnose facet joint pain.

Once facet joint pain has been diagnosed clinically, the current interventional treatment options for prolonged relief includes corticosteroid (CSI) injection of the facet joint or radiofrequency ablation of the medial branch nerves. There are variable evidence to the effectiveness of the corticosteroid injection of the lumbar facet joints, with a systemic review showing Level III evidence of trials with short term effectiveness less than 6 months. The evidence for radiofrequency ablation is more robust with Level 1 evidence for effectiveness less than 6 month and Level 2 evidence for effectiveness greater than 6 months (Manchikanti L. et al., 2015; Rajni Vekaria et al., 2016). There are also studies that have suggested similar effectiveness of intra-articular facet joint injection and radiofrequency ablation. Other clinical providers have evaluated autologous use of biological material to treat facet mediated pain including platelet rich plasma (PRP), to accelerate healing of a degenerative tissue. (Wu J et al., 2016).

Novel treatment methods for treating facet pain are sorely needed since CSI treatments have reported risks associated with injection, osteoporosis, accelerated degeneration, avascular necrosis, and suppression of endogenous corticosteroid production. Further, the long-term consequence of ongoing radiofrequency ablation treatment has not been fully elucidated. While radiofrequency ablation (RFA) temporarily denervates the medial branch that provides the sensation to the facet joint, RFA also denervates parts of paraspinal muscles, which can potentially cause weakness and further slow rehabilitation.

The use of orthobiologics and concepts behind regenerative therapy has gained increased traction as a way to treat musculoskeletal issues. PRP is an autologous source of blood product that contains higher platelet concentration after being prepared in a centrifuge. It is thought that the higher level of growth factors (such as PDGF, TGF-B, VEGF< EGF, bFGF< IGF-1) and cytokines released by the platelets promote a healing cascade. Preclinical and clinical studies have investigated use of PRP on treating various structures including tendons, ligaments and joints. While these trials have shown promising results, there continues to be lack of high-quality studies.

In order to improve the rehabilitation of service members with LBP, novel trials that include PRP must be studied. Although early clinical evidence suggests that PRP therapy may improve outcomes without destruction of tissues, to date, no randomized single blinded placebo-controlled study to look at the effectiveness of PRP injection for lumbar facet mediated joint pain exists.

The study will provide evidence-based medicine on a new regenerative medicine treatment option that may affect significant military personnel with LBP. PRP may offer alternate treatment methods that may help preserve the facet joint structures, improve pain and function without causing destructive lesions or worsening degenerative joints. This healing process may favor improved participation with rehabilitation therapy and ultimately improve return to duty status. This study will also assess the effectiveness of point of care generated PRP, as a minimally invasive treatment option for treating lumbar facet pain. Specifically, PRP effectiveness will be compared to injecting placebo control when injected into facet joints.

Discogenic pain accounts for 20-45% of cases of mechanical low back pain and is more common in younger and middle-aged adults (Manchikanti, 2000). Diagnosis can be made on the basis of a combination of symptoms and exam findings, imaging, lack of improvement with facet injections sacroiliac injections and epidural steroid injections, and concordant pain relief with provocative discography. Surgical treatments may include spinal fusion or artificial disc replacement. A systematic review of fusion to non-surgical treatment in patients with more than one year of moderate to serve low back pain found only a 35% improvement in the surgical group and 20% improvement in the non-surgical group. Various injectables, including corticosteroids and tumor necrosis factor, have been investigated for the treatment of discogenic low back pain. In a study of 120 patients randomized to receive intradiscal corticosteroid or saline, Cao et al found a significant improvement in pain and function at 3 and 6 months in the corticosteroid group. In Cohen’s placebo-controlled study of 36 patients, intradiscal etanercept did not seem to improve outcomes. There is growing interest in the use of cell therapy, primarily mesenchymal stem cells, for the regeneration of intervertebral disc cells thought to contribute to disc degeneration and discogenic pain. Pettine treated 26 patients with intradiscal autologous mesenchymal stem cells and reported an average percentage of visual analog score reduction of 64%, 64%, and 57% and Oswestry Disability Index (ODI) reduction of 58%, 55%, and 57% at 3, 6, and 12 months respectively. There are other published case series showing similar benefit, but there are no controlled trials evaluating stem cells for discogenic pain. It is not clear whether the stem cells, extracellular matrix, or other factors contribute to the improvement observed in these cases.

Chronic exertional compartment syndrome (CECS) is a debilitating disorder affecting mostly an active population. The proposed pathophysiology is increased pressure in muscle compartments causing pain, paresthesia, and inability to tolerate exercise in the affected fascial compartment. CECS involves the lower extremities, primarily affects young active adults, and limits running and/or endurance activities. While the incidence of CECS in the general population is unknown, the prevalence in the military population has been found to be 0.49 cases per 1000 patient-years.

The current standard for definitive treatment of CECS is surgical fasciotomy of the involved compartments. According to a 2016 systematic review, surgical intervention for CECS is successful in only 66% of those affected, with 13% of patients reporting complications from surgery, and 6% needing a repeat procedure. A 2014 retrospective review of military members showed that only 59% of patients who underwent elective fasciotomy for CECS were able to return to full duty while 22% of the patients that were treated with fasciotomy were eventually medically discharged. One of the reasons for the limited success rate, is an incomplete understanding of the pathophysiology coupled with proper patient selection.

Gait retraining is an attractive alternative to fasciotomy. It aims to influence the effect of foot contact and running kinematics to reduce leg compartment pressures which relieves pain. Diebal et al. published a case series of 10 military members with CECS who underwent a gait retraining program that emphasized forefoot running. At six-weeks and one-year post-intervention, running distance, pain, and performance all significantly improved. Despite high rates of success in limited case studies, real world application of gait retraining has limitations. Many patients struggle to make and/or sustain adaptations in their running style. Some patients have severe pain with exercise which limits efforts at effective gait re-training.

A newer proposed treatment is the intramuscular administration of onabotulinumtoxin A, also known as botulinum toxin A or BoNT-A into the muscles of the involved compartment(s). One case series studying botulinum toxin injections for CECS demonstrated normalized intramuscular pressure up to nine months post-injection in 87.5% (14/16) of patients, and exertional pain was completely eliminated in 94% (15/16) of patients. Eleven patients experienced reduced muscle strength that was without functional consequences and transient, with only 1 of the 16 patients who complained of new posterior leg pain that did not appear to be related to BoNT-A injections. There were no other adverse effects reported.

Military sports medicine clinics at Fort Belvoir Community Hospital (FBCH) and USU have been utilizing BoNT-A injections for the non-surgical treatment of CECS. A retrospective review of patients with CECS treated with BoNT-A at FBCH Sports Medicine Clinic from 2014 to 2017 provided data on twenty-nine patients who were treated with BoNT-A for CECS. Prior to treatment, none of the 29 patients were able to perform their desired activity and 24% were unable to run one mile without severe leg pain. After botulinum injections, these numbers improved to 66% and 72% respectively. Sixty-nine percent of patients reported that they were satisfied or somewhat satisfied with their treatment, twelve patients continued to have sustained relief by the time they were contacted, and seven patients experienced a recurrence of symptoms. In those with recurrence, the mean duration of improvement was 7.8 months. Of note,11 patients received both BoNT-A and fasciotomy during their treatment course. Only one patient reported a favorable response to fasciotomy and failure with BoNT-A, suggesting that BoNT-A injections might be predictive of success with fasciotomy.

BoNT-A is FDA approved for intramuscular, intradetrusor, or intradermal use for muscle spasticity, migraine headaches, detrusor instability and severe forehead lines, lateral canthal lines, and glabellar lines in adults. To avoid side effects and predict treatment success, a recently published case review of pre-treatment with xylocaine injections prior to proposed BoNT-A injection for frontalis and glabellar rhytides was issued. Further, a yet unpublished case using the pre-treatment xylocaine protocol was conducted at FBCH. The subject improved her running symptoms with the xylocaine injection and subsequently underwent BoNT-A treatment. One month after the BoNT-A she is able to now walk/run up to 1 mile with no exertional symptoms.

The purpose of this grant application is to create a registry across all MTFs for CECS to compare diagnostic and therapeutic data. We will simultaneously assess the effectiveness of non-surgical treatments options for chronic exertional compartment syndrome as well as test the use of xylocaine injections to predict success for non-surgical or surgical options at selected sites. This study will also determine if successful gait retraining, either home based or supervised, is essential to positive results Furthermore this study will also determine if BoNT-A injections plus gait retraining is better than either treatment alone. Finally, this study would determine if xylocaine injections could predict who will benefit from BoNT-A injections or fasciotomy.

Military service members are the most at-risk population for shoulder instability and 80% of these individuals have a re-injury (recurrent instability). Of particular concern are military trainees who are 40X more likely to have a shoulder instability event than their civilian counterparts. The spectrum of shoulder instability includes shoulder subluxations (transient instability that maintains glenohumeral continuity) and frank dislocations (complete glenohumeral disassociation requiring reduction). Following a first-time shoulder instability event, both operative and non-operative management are routinely employed. Both treatment approaches yield outcomes that span the spectrum from complete success (no future instability events) to complete failure (recurrent instability events). Furthermore, there is no evidence to guide the optimal rehabilitation strategy (supervised versus self-managed rehabilitation). Thus, there is no clear indication for what treatment approach is superior and should be employed across the military. The ramifications of incorrect acute management of shoulder instability, will likely have long-term consequences for the individual. Improperly managed shoulders may lead to progressive articular cartilage damage, loss of humeral head or glenoid osseous support and labral-ligamentous injury. Collectively, these progressive sequelae increase the risk for recurrent shoulder instability events. Chronic recurrent instability results in increasing bone loss, higher surgical failure rates, and post-traumatic osteoarthritis. Conversely, immediate surgical stabilization following a single instability event may result in unnecessary surgery that could have been successfully managed with non-operative treatment. Due to the dearth of definitive evidence for the optimal initial method of treatment (operative versus non-operative), a large-scale trial is needed to optimize the outcomes for these most readiness-impairing and burdensome injuries. The findings of this study will inform military specific clinical practice guidelines (CPGs) that will lead to optimized management of shoulder instability in a young, physically active military population. Optimal management of shoulder instability will result in improved patient outcomes, maximize warfighter return to duty/activity (RTD/A) and mitigate re-injury in Service Members with shoulder instability. Collectively, the results of this study will result in improved Force medical readiness. This proposal also directly responds to the surgical and rehabilitation techniques and outcomes for soft tissue trauma of common musculoskeletal injuries for enhanced RTD/A techniques and outcomes for soft tissue trauma of common musculoskeletal injuries for enhanced RTD/A.

Chronic exertional compartment syndrome (CECS) is a condition provoked by exercise that is caused by a marked increase in tissue pressure within a closed fascial plane. It is most commonly seen in athletes who participate in ball and puck sports, military recruits, and long distance/high mileage runners. The incidence in the military has been shown to be .49 cases per 1000 patient years. Patients typically present with complaints of pain, recurrent leg cramping, and pressure, that is often identified at a specific point during training. Neurological symptoms may also occur, and include paresthesias or weakness in the distribution of a peripheral nerve.

Current gold standard for diagnosis of CECS is intramuscular compartment pressure measurement. Other methods of diagnosis have been proposed and include magnetic resonance imaging and near infrared spectroscopy (NIRS). However, MRI has been stated to be less reliable than compartment pressure and infrared spectroscopy. The cost, practicality, and availability of MRI or NIRS is a confounding factor in using these technologies for diagnostic decision making.  There remains a need for a reliable, non-invasive, accessible, and cost-effective tool to confirm clinical diagnosis. We hypothesize that this can be done with ultrasound shear wave muscle elastography. Shear wave elastography is an ultrasound-based technique that can characterize tissue mechanical properties.

The long-term objective of this project is to develop a sensitive and non-invasive method of diagnosing CECS using shear wave muscle elastography (SWE) and to compare non-invasive shear wave muscle elastography to invasive pressure monitoring. After intervention, we will assess for objective changes within the symptomatic compartment using ultrasound shear wave elastography.

Shoulder pain is in the top five reasons related to musculoskeletal disorders that care is sought within the Military Health System. While acromioclavicular joint (ACJ) disorders, a subset of all shoulder pain disorders, are a high-volume condition seen in primary clinics, very little is known about the epidemiology in the military. At the United States Military Academy in West Point, 162 new cases were identified over a four-year period, which equaled an incidence rate of 9.2 per 1000 person-years. 

Onset of pain in athletes is most commonly related to activities which strain the ACJ, to include push-ups, military press, overhead press, as well as any forceful contact to the shoulder which provides a shear on the ACJ (falling on outstretched hand, direct blow to the elbow, landing forcefully on the side of the shoulder). These are all very common activities and often part of the daily routine for service members, as part of their physical and readiness training. Consequently, pain and inability to absorb normal stress in this joint after injury creates tremendous disability and greatly limits service members from being able to complete many of their daily duties. Ultimately, this affects military readiness substantially. Recovery is often slow and depends on the severity of the injury, but usually taking a minimum of six weeks and in many cases with recalcitrant symptoms lasting out to a year or more. Interventions that can speed up recovery and maximize pain-free function on return to duty are in high demand for service members, as they have the potential to directly impact the state of medical readiness for our service members.

Platelet-Rich Plasma (PRP) is a new treatment that shows promise for treating musculoskeletal disorders. The driving therapeutic mechanism is to leverage the restorative biological mechanisms in red blood cells using the patient’s own red blood cells to accelerate and promote healing. PRP is currently utilized in the clinic, but its cost can be prohibitive. Corticosteroid injections may be as clinically effective as PRP for managing acromioclavicular pain, but at a fraction of the price. This study aims to assess whether corticosteroid injections are non-inferior to PRP.

As of September 1, 2014, 1,573 US Military servicemembers have sustained a major limb amputation since 2001. In addition to the inherent mobility challenges posed by amputation, this population suffers from a variety of comorbidities, including osteoarthritis (OA). Osteoarthritis is the primary source of long-term disability in wounded servicemembers and the inability to return to active duty following traumatic injury. Osteoarthritis of the knee specifically is among the most prevalent and costly chronic diseases in the USA. The estimated lifetime incidence rate of knee OA among all American adults ages 25+ is at least 14%. Knee OA, particularly on the medial knee joint, is the most common form of OA and the leading cause of mobility impairment in older adults.

The risk of knee OA in the intact limb is especially concerning for young service members with amputations. At Walter Reed National Military Medical Center (WRNMMC), service members with amputations are treated by a large multidisciplinary team through physical and occupational therapy, prosthesis fitting and training, and gait and motion analysis, with generally successful outcomes, and advances in prosthesis technology have greatly improved the mobility of amputees and their ability to engage in physical activity. However, very little is currently done towards the objective of preventing knee OA, and the incidence and prevalence of chronic comorbidities in amputees remain high. Most servicemembers with amputations are relatively young when they receive their injuries and will live with any associated disabilities for many years. The incidence of knee OA increases with age and typically peaks at around 60 years old. Service members with amputations will thus live with a substantial and progressive risk of knee OA for many years.

In order to ultimately reduce the prevalence and healthcare burden of knee OA among servicemembers with amputations and salvaged limbs, we must first gain a better understanding of the mechanisms that increase knee OA risk in this population. This knowledge will facilitate development and evaluation of more effective preventive therapies for avoiding detrimental knee joint loading while maintaining a high level of mobility in service members with amputations.

The objective of this study is to develop clinical guidelines for using instrumented gait analysis and biomechanical modeling as a diagnostic tool for assessing knee OA risk in service members with unilateral amputation or limb salvage.