Novel Orthobiologic Preparation and Regenerative Rehabilitation of a Complex Shoulder Injury in a Competitive Adolescent Female Athlete.

Background: Platelet-rich plasma (PRP) and prolotherapy have resulted in promising outcomes in patients with various types of shoulder injuries. However, there is a lack of preliminary evidence supporting preparation of PRP production, timely application of these therapies and regenerative rehabilitation protocols. The purpose of this case report is to describe the distinct method including orthobiologic preparation, tissue-specific treatment and regenerative rehabilitation of an athlete with a complex shoulder injury. Case Presentation: A 15y/o competitive female wrestler with a complex shoulder injury presented to the clinic after unsuccessful conservative rehabilitation. Unique methods were incorporated to optimize PRP production, specific tissue healing and regenerative rehabilitation. Multiple injuries required different orthobiologic interventions at different time frames, in order to promote optimal healing and stability of the shoulder. Outcomes: The described interventions resulted in successful outcomes including pain, disability, full return to sport, and regenerative tissue healing confirmed with diagnostic imaging. Level of Evidence: 5.

Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a systematic review and a meta-analysis.

BACKGROUND: Low back pain with or without radiculopathy is an important cause of disability and economic expenditure. However, many patients are not meeting optimal pain control through existing treatments. Recent studies have linked nerve growth factor (NGF) and the pathophysiology of persistent pain. Anti-NGF could be an alternative drug treatment for low back pain. OBJECTIVE: Systematically review the efficacy and safety of anti-NGF in the treatment of low back pain. METHODS: A systematic review of the literature with no language, date or publication status restriction, using Medline, EMBASE, Cochrane Library, and the clinicaltrials.gov database. Additional literature was retrieved by conferring with experts in the field or reviewing bibliographies and annals of meetings and congresses. Search terms included "monoclonal antibodies," "nerve growth factor," "anti-ngf," "fulranumab," "tanezumab," "sciatica," "back pain," and "spine." STUDY DESIGN: Inclusion criteria were observational studies with safety as an outcome and randomized or nonrandomized controlled trials studying the efficacy and/or the safety of anti-NGF drugs on low back pain. Exclusion criteria included patients with autoimmune conditions or osteoporosis. Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, and quality of evidence (GRADE approach). RESULTS: 1,168 studies were retrieved. After excluding duplicates and applying the inclusion/exclusion criteria, 4 RCTs remained (n = 2,109): 2 for tanezumab, one for REGN475, and one for fulranumab. Only the tanezumab studies showed any significant difference over placebo (n = 1,563) for both pain relief and functional improvement. CONCLUSIONS: There is very low evidence that systemically administered anti-NGF therapy has a small positive effect compared to placebo for both pain relief (standarized mean difference [SMD] = -0.29, 95% confidence interval [CI] -0.58 to 0.00) and functional improvement (SMD = -0.21, 95%CI -0.37 to -0.05 ) of low back pain. There was low evidence of adverse effects (AEs) compared to placebo and low evidence of neurological AEs than placebo (relative risk = 1.93, 95%CI 1.41 to 2.64).Tanezumab, as a specific anti-NGF treatment, showed low evidence of a small to moderate effect for pain relief of low back pain (SMD = -0.44, 95%CI -0.81 to -0.07); and low evidence of a small effect for functional improvement (SMD = -0.26, 95%CI -0.40 to -0.12) with systemic administration, although not clinically significant. Tanezumab and anti-NGFs overall had, respectively, moderate and low evidence of overall AEs and serious AEs and a higher risk of developing neurological AEs when compared with placebo. Although anti-NGF, specifically tanezumab, showed a low-to-moderate effect on pain relief and functional improvement, it cannot be recommended for low back pain treatment. Without more research on the pathophysiology of anti-NGFs and adverse effects, its use is not safe in the overall population. However, as corroborated by the US Food and Drug Administration, this meta-analysis underscores a role for greater insight into anti-NGF therapy for painful conditions that are refractory to current drugs, such as oncologic pain, chronic pancreatitis, and phantom-limb pain. Given the pathophysiology of axial pain involving inflammatory mediators and the adverse effects of systemic anti-NGF use, consideration of local therapies may warrant further exploration.

Anti-tumor necrosis factor antagonists in the treatment of low back pain and radiculopathy: a systematic review and meta-analysis.

BACKGROUND: Low back pain, with or without radiculopathy, is an important cause of disability and economic expenditure. However, many patients are not achieving optimal pain control with existing medications. Tumor necrosis factor antagonists (anti-TNFα) could be an alternative drug treatment. OBJECTIVES: Systematic review the efficacy and safety of anti-TNFα in the treatment of low back pain with or without radiculopathy. STUDY DESIGN: Inclusion criteria were observational studies with safety as an outcome, and randomized or nonrandomized controlled trial (RCT) studies on efficacy and/or safety of anti-TNFα drugs on low back pain. Exclusion criteria included patients with auto-immune conditions or osteoporosis. RESULTS: Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, quality, and strength of evidence (GRADE approach). Of the 1,179 studies retrieved, all duplicates were excluded and then the inclusion/exclusion criteria was applied. One observational study (n = 143) and 11 RCTs remained (n = 539): 8 for etanercept (n = 304), one for adalimumab (n = 61), one for adalimumab and etanercept (n = 60), one for infliximab (n = 40) and one for REN-1654 (n = 74). Only 3 etanercept and 2 adalimumab studies showed statistically significant pain relief when compared to placebo. There was no difference in the overall incidence of adverse effects when comparing anti-TNF-α and placebo. LIMITATIONS: Despite the statistically significant effect, this meta-analysis has important limitations, such as high heterogeneity and high use of outcome imputation. CONCLUSIONS: There is low evidence that epidural etanercept has a low-to-moderate effect size when compared to placebo for pain due to discogenic lumbar radiculopathy (5 studies, n=185), with a standardized mean difference = -0.43 (95% confidence interval [CI] -0.84 to -0.02).There is moderate evidence that epidural etanercept does not have a higher adverse effects incidence rate when compared to placebo for discogenic lumbar radiculopathy (5 studies, n = 185) with a relative risk (RR) = 0.84 (95% CI 0.53 to 1.34).There is moderate evidence that anti-TNFα does not have a higher adverse effects incidence rate when compared to placebo for low back pain (10 studies, n= 343) with an RR = 0.93 (95% CI 0.56 to 1.55).We strongly suggest that anti-TNFα continue to be studied in experimental settings for the treatment of low back pain. We cannot currently recommend this therapy in clinical practice. New research could shed some light on the efficacy of anti-TNFα and change this recommendation in the future.

Cancer pain and analgesia.

Pain ranges in prevalence from 14-100% among cancer patients and occurs in 50-70% of those in active treatment. Cancer pain may result from direct invasion of tumor into nerves, bones, soft tissue, ligaments, and fascia, and may induce visceral pain through distension and obstruction. Cancer pain is multifaceted. Clinicians may describe cancer pain as acute, chronic, nociceptive (somatic), visceral, or neuropathic. Despite implementation of the WHO guidelines, reports of undertreatment of cancer pain persist in various clinical settings and in spite of decades of work to reduce unnecessary discomfort. Substantial obstacles to adequate pain relief with opioids include specific concerns of patients themselves, their family members, physicians, nurses, and the healthcare system. The WHO analgesic ladder serves as the mainstay of treatment for the relief of cancer pain in concert with tumoricidal, surgical, interventional, radiotherapeutic, psychological, and rehabilitative modalities. This multidimensional approach offers the greatest potential for maximizing analgesia and minimizing adverse effects. Primary therapies are directed at the source of the cancer pain and may enhance a patient's function, longevity, and comfort. Adjuvant therapies include nonopioids that confer analgesic effects in certain medical conditions but primarily treat conditions that do not involve pain. Nonopioid medications (over-the-counter agents) are useful in the management of mild to moderate pain, and their continuation through step 3 of the WHO ladder is an option after weighing a drug's risks and benefits in individual patients. Symptomatic treatment of severe cancer pain should begin with an opioid, regardless of the mechanism of the pain. They are very effective analgesics, titrate easily, and offer a favorable risk/benefit ratio. Cancer pain remains inadequately controlled despite the diagnostic and therapeutic means of ensuring that patients feel comfortable during their illness. Therefore, all practitioners need to make control of cancer pain a professional duty, even if they can only use the most basic and least expensive analgesic medications, such as morphine, codeine, and acetaminophen, to reduce human suffering.

Interventional pain treatments for cancer pain.

Cancer pain is prevalent and often multifactorial. For a segment of the cancer pain population, pain control remains inadequate despite full compliance with the WHO analgesic guidelines including use of co-analgesics. The failure to obtain acceptable pain or symptom relief prompted the inclusion of a fourth step to the WHO analgesic ladder, which includes advanced interventional approaches. Interventional pain-relieving therapies can be indispensable allies in the quest for pain reduction among cancer patients suffering from refractory pain. There are a variety of techniques used by interventional pain physicians, which may be grossly divided into modalities affecting the spinal canal (e.g., intrathecal or epidural space), called neuraxial techniques and those that target individual nerves or nerve bundles, termed neurolytic techniques. An array of intrathecal medications are infused into the cerebrospinal fluid in an attempt to relieve refractory cancer pain, reduce disabling adverse effects of systemic analgesics, and promote a higher quality of life. These intrathecal medications include opioids, local anesthetics, clonidine, and ziconotide. Intrathecal and epidural infusions can serve as useful methods of delivering analgesics quickly and safely. Spinal delivery of drugs for the treatment of chronic pain by means of an implantable drug delivery system (IDDS) began in the 1980s. Both intrathecal and epidural neurolysis can be effective in managing intractable cancer-related pain. There are several sites for neurolytic blockade of the sympathetic nervous system for the treatment of cancer pain. The more common sites include the celiac plexus, superior hypogastric plexus, and ganglion impar. Today, interventional pain-relieving approaches should be considered a critical component of a multifaceted therapeutic program of cancer pain relief.

Perceived barriers to information access among medical residents in Iran: obstacles to answering clinical queries in settings with limited Internet accessibility.

Studies performed in the US and other Western countries have documented that physicians generate many clinical questions during a typical day and rely on various information sources for answers. Little is known about the information seeking behaviors of physicians practicing in other countries, particularly those with limited Internet connectivity. We conducted this study to document the perceived barriers to information resources used by medical residents in Iran. Our findings reveal that different perceived barriers exist for electronic versus paper-based resources. Notably, paper-based resources are perceived to be limited by resident time-constraints and availability of resources, whereas electronic resources are limited by cost decentralized resources (such as PDAs) and accessibility of centralized, Internet access. These findings add to the limited literature regarding health information-seeking activities in international healthcare settings, particularly those with limited Internet connectivity, and will supplement future studies of and interventions in such settings.

Impacts of PDA-based access to clinical data in a teaching hospital: perceptions of housestaff physicians.

Personal digital assistants (PDAs) are commonly used to access medical information at the point of care. Systems that allow point-of-care access to hospital HIS data are currently in use or being implemented, but little has been reported about the clinical or educational impacts of such systems. We conducted group interviews with medical housestaff to ascertain their perceptions of such impacts. These findings add to the limited literature regarding the use of such systems.