Predicting the Collapse of Pain Medicine Using the Economic Recession of 2008 as a Comparator: Lessons Remain Unlearned.

The last decade has seen a boom in pain medicine, basic science and interventional pain management. Concomitantly, there is a need to educate trainees, young attendings, and seasoned attendings on these innovations. There has been a growth in the number of societies that represent pain medicine physicians, each with its own philosophy and guiding principles. The variety of thought within pain management, within the various groups that practice this field, and amongst the societies which protect those missions inherently creates divergence and isolation within these different communities. There is the enormous opportunity for our field to grow, but we need the voices of all different specialties and sub-specialties which practice pain medicine to collectively design the future of our emerging field. The explosion of revolutionary percutaneous surgeries, medications, psychotherapy, and research and development in our field has outpaced the ability of payers to fully embrace them. There is an increased number of pain practitioners using novel therapies, postgraduate training programs do not adequately train users in these techniques thereby creating a potential for sub-optimal outcomes. In part, this is a reason why payers for many of our more novel treatments have decreased patient access or eliminated remuneration for some of them. We believe that society-based collaborative regulation of education, research, and treatment guidelines is needed to improve visibility for payers and end users who provide these treatments. Furthermore, postgraduate chronic pain fellowship education has been deemed by many to be insufficient to educate on all of the necessary requirements needed for the independent practice of pain medicine, especially the consummation of newer technologies. Here, we draw comparison with this tenuous stage in pain management history with the last United States recession to remind us of how poor institutional regulation and neglect for long-term growth hampers a community.

Radiofrequency ablation of the hip: review.

Radiofrequency ablation (RFA) of the articular branches of the femoral and obturator nerves (the innervation of the anterior capsule of the hip) is an emerging treatment for chronic hip pain. Body mass index (BMI) greater than 30, older age, large acetabular/femoral head bone marrow lesions, chronic widespread pain, depression, and female sex increase the risk of developing hip pain. Chronic hip pain is a common condition with a wide range of etiologies, including hip osteoarthritis (OA), labral tears, osteonecrosis, post total hip arthroplasty (THA), post-operative dislocation/fracture, and cancer. The most common and well studied is hip OA. Management of chronic hip pain includes conservative measures (pharmacotherapy and exercise), surgery, and percutaneous procedures such as RFA. While surgery is effective, those whose medical comorbidities preclude surgery, those who do not wish to have surgery, and those whose pain persists after surgery (11-36% of patients) could benefit from RFA. Because of the aforementioned circumstances, hip RFA is often a palliative intervention. Hip RFA is an effective treatment, one recent retrospective study of 138 patients found 69% had >50% pain relief at 6 months. The most frequent adverse event reported for hip RFA is pain from needle placement. No serious bleeding events have been reported, despite the valid concern of the procedure's proximity to vasculature. This descriptive review details the pathophysiology of hip pain, its etiologies, its clinical presentation, conservative management, the anatomy/technique of hip RFA, hip RFA efficacy, and RFA adverse events.

Current Waveforms in Spinal Cord Stimulation and Their Impact on the Future of Neuromodulation: A Scoping Review.

BACKGROUND: Neuromodulation is a standard and well-accepted treatment for chronic refractory neuropathic pain. There has been progressive innovation in the field over the last decade, particularly in areas of spinal cord stimulation (SCS) and dorsal root ganglion stimulation. Improved outcomes using proprietary waveforms have become customary in the field, leading to an unprecedented expansion of these products and a plethora of options for the management of pain. Although advances in waveform technology have improved our fundamental understanding of neuromodulation, a scoping review describing new energy platforms and their associated clinical effects and outcomes is needed. The authors submit that understanding electrophysiological neuromodulation may be important for clinical decision-making and programming selection for personalized patient care. OBJECTIVE: This review aims to characterize ways differences in mechanism of action and clinical outcomes of current spinal neuromodulation products may affect contemporary clinical decision-making while outlining a possible path for the future SCS. STUDY DESIGN: The study is a scoping review of the literature about newer generation SCS waveforms. MATERIALS AND METHODS: A literature report was performed on PubMed and chapters to include articles on spine neuromodulation mechanism of action and efficacy. RESULTS: A total of 8469 studies were identified, 75 of which were included for the scoping review after keywords defining recent waveform technology were added. CONCLUSIONS: Clinical data suggest that neuromodulation remains a promising tool in the treatment of chronic pain. The evidence for SCS for treating chronic pain seems compelling; however, more long-term and comparative data are needed for a comparison of waveforms when it comes to the etiology of pain. In addition, an exploration into combination waveform therapy and waveform cycling may be paramount for future clinical studies and the development of new technologies.

Adipose Tissue Impacts Radiofrequency Ablation Lesion Size: Results of an Ex Vivo Poultry Model.

BACKGROUND: Radiofrequency ablation (RFA) is a common treatment in which radiofrequency (RF) is used to heat neural tissue and reduce pain. The impact of adipose content in tissue on the lesion size may impact efficacy, and to date, there is little, if any, data comparing its influence on RFA. OBJECTIVES: We evaluated the influence of adipose tissue on RF lesion size. STUDY DESIGN: Controlled, ex vivo study. SETTING: Academic institution in a procedural setting. METHODS: RF lesions were created using 20-G 10-mm protruding electrode (PE) needles inserted into unbrined chicken breasts and thighs at 21°C. RF current was applied for 90 seconds at 80°C. Chicken breasts were used as the control group and chicken thighs were used as the high adipose variant. Four different groups were examined: 1- Standard 20 g RFA needle, 2- 20 g RFA PE needle, 3- Standard RFA needle with lidocaine 2% injectate, and 4- Standard RFA needle with iohexol 240 mg injectate. There were 12 lesions performed in each group; length, width, and depth were measured. RESULTS: The control group had significantly deeper lesions in all 4 cohorts. Lesions' lengths were smaller in the fat-rich group. The control and PE cohorts showed a significant difference in width between the 2 fat-rich and nonfatty groups. LIMITATIONS: Radiofrequency ablation was performed at room temperature and not heated to physiological temperature. This was an ex vivo study, thus factors of human anatomy and physiology could not be evaluated. CONCLUSIONS: Adipose tissue content was inversely related to lesion size in all samples. This factor should be considered when assessing methods of enhancing lesion size in human models.

Percutaneous Ultrasound-Guided Coracohumeral Ligament Release for Refractory Adhesive Capsulitis: A Prospective, Randomized, Controlled, Crossover Trial Demonstrating One-Year Efficacy.

BACKGROUND: Adhesive capsulitis (AC) is a painful and disabling condition with restricted range of motion (ROM) that affects 2% to 3% of the population and up to 20% of patients with diabetes. AC can be idiopathic, iatrogenic, or secondary to shoulder injuries. Some associated conditions include diabetes mellitus, thyroid disorders, dyslipidemia, stroke, prolonged immobilization, and autoimmune conditions. Management ranges from analgesics to physical therapy, local injections, hydrodilatation, and advanced surgical interventions. This study examines percutaneous coracohumeral ligament (PCHL) sectioning with the hypothesis that interruption would improve pain and ROM in patients with AC refractory to conservative management. OBJECTIVES: To use sonographically guided percutaneous interruption of the CHL for the treatment of refractory AC. STUDY DESIGN: A prospective, randomized, controlled, cross-over trial. SETTING: Academic medical center. METHODS: Patients were identified based on inclusion and exclusion criteria under the supervision of the Principal Investigator. After primary screening, research staff explained the study, risks, and benefits to the patients, and consent was obtained. Patients' pain score and shoulder ROM were assessed before and after the procedure, at one month, and one year. The Oxford Shoulder Scoring (OSS) questionnaire was also completed before the procedure and in the one-year follow-up visit.Forty patients were enrolled with refractory AC. Forty-six shoulders were treated; 6 patients underwent a bilateral procedure. Block 2:1 randomization was performed for the 2 groups (PCHL release [PCHLR] and local anesthetic CHL [LACHL]). The LACHL group received a lidocaine injection at CHL, and the PCHLR group received the CHL using a Tenex® (Tenex Health, Lake Forest, CA) needle. ROM, Numeric Rating Scale (NRS-11), and OSS were evaluated at baseline, immediate postprocedure, and long term. RESULTS: Among 46 shoulders included in the study, 7 were excluded due to lost to follow-up, total shoulder replacement, and shoulder manipulation. Twenty-six were randomized to the PCHLR group and 13 to LACHL group. ROM (external rotation and abduction), pain, NRS-11 score, and OSS score were measured at baseline and long term, confirmed by a nonbiased health care personnel. There was no statistically significant difference in ROM, NRS-11, and OSS between the 2 cohorts at the baseline visit. Nine patients in LACHL group crossed over to the PCHLR arm at one month. Data analysis in the long term revealed durability of the PCHLR group with a statistically significant difference in ROM, NRS-11, and OSS. External rotation improved by double, and abduction improved by almost 30% (P value < .001). NRS-11 decreased from 8 (IQR 8, 9) at baseline to 3 (IQR 2, 7) at long term among those who received PCHLR. The baseline mean OSS in the PCHLR group increased from 7.44 to 31.86 at one-year follow-up and was statistically significant (P value < .001). LIMITATIONS: This study represents a small population of patients with a CHL-related ROM deficit. Patients were not excluded for osteoarthritis or other motion-disabling shoulder conditions. We submit that the strength of the study could have been improved if the physician performing the procedure was blinded and if the patient was blinded as well to minimize operator and patient bias. CONCLUSIONS: We demonstrate that our technique for PCHLR is a safe, effective, and durable procedure that improved ROM, pain, and shoulder function in our patient population when compared to the control. KEY WORDS: Tenex, frozen shoulder, pain, range of motion, function, shoulder, minimally invasive, durable.

Percutaneous Ultrasound-Guided Tenotomy of the Iliotibial Band for Trochanteric Pain Syndrome: A Longitudinal Observational Study With One-Year Durability Results.

BACKGROUND: Upper lateral hip pain is a common complaint in adults and is referred to as greater trochanteric pain syndrome (GTPS) and is more prevalent among older women. This is a debilitating condition that could result in lower physical activity and quality of life, and higher unemployment rate. GTPS is a clinical diagnosis, and many cases improve with conservative medical management (CMM). However, there is still a gap between patients not responding to CMM and those who are not good surgical candidates. Thus, percutaneous ultrasound tenotomy (PUT) may be a valuable treatment option to limit this gap. OBJECTIVES: Demonstration of the one-year pain and functional outcomes, including sit to stand. SETTING: Academic tertiary care medical center. METHODS: Forty-eight consecutive patients with refractory trochanteric pain due to iliotibial band (ITB) tendinopathy. Fifty-six hips were treated; 8 patients underwent bilateral procedures. Electronic medical record review of consecutive patients who underwent ITB TENEX® was performed at Montefiore Medical Center from December 2019 to December 2021. Institutional guidelines recommended TENEX® for greater trochanteric pain refractory to conservative treatment and ultrasound (US) confirmed ITB tendinopathy (hypoechogenicity or thickened tendon > 6 mm). Pain level, as well as sit-to-stand, side-lying, and walking tolerance levels were evaluated at baseline preprocedure visit and one-year visit. Follow-up was performed by independent practitioners and corroborated by chart review. RESULTS: Numeric Rating Scale (NRS-11) improved by 4 points across all patients. Seventy percent of patients endorsed pain relief at one-year visit. Median preprocedure NRS-11 was 9. The reported median NRS-11at one year was 5 (Wilcoxon signed rank NRS-11 demonstrated a Z score of -6.042 with P < 0.001). One-year analysis among all patients revealed 57%, 78%, and 66% improvement in side-lying, sit-to-stand, and walking tolerance levels, respectively. LIMITATIONS: We believe that our results must be confirmed with a randomized control trial with a control arm and more patients included. CONCLUSIONS: PUT of the ITB using the TENEX® tissue remodeling device could be a safe and effective treatment for ITB tendinopathy-associated GTPS.

Contrast Spread After Erector Spinae Plane Block at the Fourth Lumbar Vertebrae: A Cadaveric Study.

INTRODUCTION: In recent years, the erector spinae plane block (ESPB) has seen widespread use to treat acute and chronic pain in the regions of the thoracic spine. While limited data suggest its increasing utilization for pain management distal to the thoracic, abdomen and trunk, the anesthetic spread and analgesic mechanism of ESPB at the level of the lumbar spine has not been fully described or understood. METHODS: This is an observational anatomic cadaveric study to assess the distribution of solution following an ESPB block performed at the fourth lumbar vertebrae (L4) using ultrasound guidance to evaluate the spread of a 20 ml solution consisting of local anesthetic and methylene blue. The study was performed in an anatomy lab in a large academic medical center. Following injection of local anesthetic with contrast dye, cadaveric dissection was performed to better understand the extent of contrast dye and to determine the degree of staining to further predict analgesic potential. We reviewed the findings of other ESPB cadaveric studies currently available for comparison. RESULTS: Following cadaveric dissection in an anatomy lab, the contrast dye was observed in the ESP space, and staining was found most cranially at L2 and extending caudally underneath the sacrum. Evaluating the depth of its spread, we found it to be confined to the posterior compartment of the spine sparing the nerve roots bilaterally, which is consistent with the only other cadaveric study of ESPB performed at L4. CONCLUSION: Our results demonstrate the clinical utility of lumbar ESPB where posterior confinement of local anesthesia is preferred. However, further investigation is needed to determine the efficacy of ESPB in lower extremity analgesia which is predicated on ventral nerve root involvement.

The Effect of Local Anesthetics and Contrast Agents on Radiofrequency Ablation Lesion Size.

BACKGROUND: Radiofrequency ablation (RFA) is a validated treatment option for the treatment of chronic pain in patients with lumbar spondylosis. Lesion size has been suggested to correlate with good clinical outcomes. This has created an abundance of scientific interest in the development of products with larger lesion characteristics. Needle characteristics, energy transfer, and heat rate are known to modify lesion size. Here, we demonstrate that common intraoperative solutions, such as lidocaine, iodine, and gadolinium-based products, can also affect lesion shape. OBJECTIVES: To determine whether lidocaine and contrast agents modify lesion characteristics during the performance of monopolar RFA. STUDY DESIGN: Controlled, ex vivo study using clinically relevant conditions and pre-injections. SETTING: Academic institution in a procedural setting. METHODS: RFA lesion size was compared among six cohorts: 1) lidocaine 1%, 2) lidocaine 2%, 3) iohexol 180, 4) iohexol 240, 5) gadodiamide, and 6) control (no fluid control). Radiofrequency (RF) current was applied for 90 seconds at 80°C via 20-gauge 100-mm standard RFA needles with 10-mm active tips in orgranic chicken breasts without preservative at room temperature (21°C). Twelve lesions were performed for each medication cohort. The length, width, and depth of each lesion were measured. The statistical significance between each medication group and the control group was evaluated by t test. RESULTS: The mean lesion surface area of monopolar RFA without any pre-injection used was 80.8 mm2. The mean surface area of the monopolar RF lesion with a pre-injection of 0.2 mL of 2% lidocaine was 114 mm2, and the mean surface area of the monopolar RF lesion with a pre-injection of 0.2 mL of iohexol 240 was 130.6 mm2. The statistical analysis demonstrated that the control group had significantly smaller lesion sizes than did the groups in which lidocaine 2% and iohexol 240 were used (P<0.01). There were no statistically significant differences among the groups in which lidocaine 1%, iohexol 180, and gadodiamide were used. A notable difference was a 20% longer lesion with iohexol 240 compared with the control group and a 20% wider lesion with lidocaine 2% compared with the control group. LIMITATIONS: In vivo anatomy within a human was not used in this study, nor were the chicken breasts heated to physiological temperature. Randomization of pieces of chicken breast did not occur, and thus intrinsic differences among the chicken breast pieces could play a confounding role. CONCLUSIONS: Lidocaine 2% and iohexol 240, when used as pre-injections in RFAs, were found to be associated with statistically significant increases in lesion surface area. However, RFAs with lidocaine 1%, iohexol 180, or gadodiamide were not found to produce a statistically significant difference in lesion size compared with monopolar RFA without the use of injectate.

Best Practices for Minimally Invasive Lumbar Spinal Stenosis Treatment 2.0 (MIST): Consensus Guidance from the American Society of Pain and Neuroscience (ASPN).

Introduction: Lumbar spinal stenosis (LSS) is a common spinal disease of aging with a growing patient population, paralleling population growth. Minimally invasive treatments are evolving, and the use of these techniques needs guidance to provide the optimal patient safety and efficacy outcomes. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for guidance on the prudent use of the innovative minimally invasive surgical therapies for the treatment of symptomatic LSS. The executive board nominated experts spanning anesthesiology, physiatry, orthopedic surgery, and neurosurgery based on expertise, publications, research, diversity and field of practice. Evidence was reviewed, graded using the United States Preventive Services Task Force (USPSTF) criteria for evidence and recommendation strength and grade, and expert opinion was added to make consensus points for best practice. Results: The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for LSS-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using USPSTF criteria and consensus points are presented. Discussion: The algorithm for patient selection in the management of symptomatic spinal stenosis is evolving. Careful consideration of patient selection and anatomic architecture variance is critical for improved outcomes and patient safety. Conclusion: ASPN created a guidance for best practice for minimally invasive surgical treatment of symptomatic spinal stenosis.

MRI and Anatomical Determinants Affecting Neuroforaminal Stenosis Evaluation: A Descriptive Observational Study.

Purpose: Neuroforaminal stenosis (NFS), a narrowing of the intervertebral foramen, is a cause of disability in the aging population. Formal magnetic resonance imaging (MRI) classification of NSF has been developed recently and contradictory findings have been reported. This study aims to assess whether in-plane, anatomically conformed two-dimensional (2D) views of the neuroforamen characterize NFS more accurately than traditional axial, coronal, and sagittal views in healthy individuals with and without simulated scoliosis. Patients and methods: This observational study was approved by the designated institutional review board at our academic tertiary care center. Four volunteers underwent lumbar spine MRI twice, once in the supine position and once with intentionally introduced hip tilt. The latter resulted in lumbar curvature mimicking positioning errors approximating degenerative lumbar scoliosis. Anatomically oriented cuts such as axial with endplate correction and coronally obliqued parasagittals, also called coronal obliques, were performed. Standard sagittal and axial views were also performed in both the supine and rotated groups. Results: Coronal oblique and anatomically oriented axial views demonstrated the highest correlation with true neuroforaminal caliber. Deviation from anatomical congruence resulted in false measurements of neuroforaminal size. The hip-tilt studies produced MR that were less favorable to characterization of the caliber of neuroforamina. Coronal sections demonstrated reliability only when performed at the mid-pedicular lines. Standard axial views were reliable only when taken at the upper one-third of the neuroforamen. Coronal oblique views demonstrated superiority when evaluating consecutive neuroforamen on one image compared to non-obliqued parasagittal slices. Conclusion: To minimize error in neuroforaminal analysis, imaging specialists should perform anatomically oriented cuts to conform to individual patient anatomy. When this cannot be performed due to a patient's spine rotation or position, the MRI reader should view oblique, axial, and coronal images simultaneously and dynamically for proper foraminal characterization.

The MOTION Study: A Randomized Controlled Trial with Objective Real-World Outcomes for Lumbar Spinal Stenosis Patients Treated with the mild® Procedure: One-Year Results.

OBJECTIVE: The purpose of this study is to provide Level-1 objective, real-world outcome data for patients with lumbar spinal stenosis suffering from neurogenic claudication secondary to hypertrophic ligamentum flavum. DESIGN: The MOTION Study is a prospective, multicenter, randomized controlled trial comparing the mild® Procedure (minimally invasive lumbar decompression; Vertos Medical, Aliso Viejo, CA, USA) as a first-line therapy in combination with nonsurgical conventional medical management (CMM) vs CMM alone as the active control. METHODS: Patients in the test group received the mild Procedure at baseline. Both the mild+CMM group and the control group were allowed unrestricted access to conventional real-world therapies. Patient-reported outcomes included the Oswestry Disability Index, the Zurich Claudication Questionnaire, and the Numeric Pain Rating Scale. A validated Walking Tolerance Test, the incidence of subsequent lumbar spine interventions, and the occurrence of adverse events were used to measure objective outcomes. RESULTS: Sixty-nine patients in each group were analyzed at 1-year follow-up. No device- or procedure-related adverse events were reported in either group. Results from all primary and secondary outcome measures showed statistical significance in favor of mild+CMM. CONCLUSIONS: One-year results of this Level-1 study demonstrated superiority of mild+CMM over CMM alone for patients with lumbar spinal stenosis who were suffering from neurogenic claudication secondary to hypertrophic ligamentum flavum. Use of the validated Walking Tolerance Test to objectively measure increased ability to walk without severe symptoms provided evidence of statistically significantly better outcomes for mild+CMM than for CMM alone. With no reported device or procedure-related adverse events, the long-standing safety profile of the mild Procedure was reaffirmed. mild is a safe, durable, minimally invasive procedure that has been shown to be effective as an early interventional therapy for patients suffering from symptomatic lumbar spinal stenosis.

An Algorithmic Approach to the Physical Exam for the Pain Medicine Practitioner: A Review of the Literature with Multidisciplinary Consensus.

BACKGROUND: Increased utilization of telemedicine has created a need for supplemental pain medicine education, especially for the virtual physical assessment of the pain patient. Traditional clinical training utilizes manual and tactile approaches to the physical examination. Telemedicine limits this approach and thus alternative adaptations are necessary to acquire information needed for sound clinical judgement and development of a treatment plan. Clinical assessment of pain is often challenging given the myriad of underlying etiologies contributing to the sensory experience. The COVID-19 pandemic has led to a dramatic increase in the use of virtual and telemedicine visits, further complicating the ease of assessing patients in pain. The increased reliance on telemedicine visits requires clinicians to develop skills to obtain objective information from afar. While eliciting a comprehensive history and medication assessment are performed in a standard fashion via telemedicine, a virtual targeted physical examination is a new endeavor in our current times. In order to appropriately diagnose and treat patients not directly in front of you, a pivot in education adaptations are necessary. OBJECTIVE: To summarize best care practices in the telemedicine physical exam while presenting an algorithmic approach towards virtual assessment for the pain practitioner. DESIGN: Review of the literature and expert multidisciplinary panel opinion. SETTING: Nationally recognized academic tertiary care centers. SUBJECTS: Multidisciplinary academic experts in pain medicine. METHODS: Expert consensus opinion from the literature review. RESULTS: An algorithm for the virtual physical exam for pain physicians was created using literature review and multidisciplinary expert opinion. CONCLUSIONS: The authors here present simple, comprehensive algorithms for physical exam evaluations for the pain physician stemming from a review of the literature.

Guidelines for composing and assessing a paper on the treatment of pain: A practical application of evidence-based medicine principles to a cost-effectiveness analysis of the MINT randomized clinical trials.

Objective: Apply established principles of evidence-based medicine to the interpretation of the cost-effectiveness analysis related to the MINT Randomized Clinical Trials (RCTs). Design: Editorial. Methods: Spine Intervention Society's guidelines for assessing studies on the treatment of pain were applied to a published cost-effectiveness analysis of radiofrequency denervation data from the MINT RCTs. Results: Application of evidence-based medicine principles reveals the MINT RCTs' major deficiencies in patient selection, diagnostic paradigm, radiofrequency neurotomy technique, co-interventions, outcome measurement, power analysis study sample characteristics, data analysis, and loss to follow-up; which marginalizes the generalizability and conclusions of the cost-effectiveness analysis. Conclusions: The cost analysis performed in "Cost-Effectiveness of Radiofrequency Denervation for Patients With Chronic Low Back Pain: The MINT Randomized Clinical Trials" is based on the MINT RCTs results. The MINT RCTs significant metholodological design flaws, lead to issues in validty for the subsequent cost-effectiveness analysis. Application of the cost-effective analysis to patient care paradigms should be limited given the concerns with validity.

Telemedicine and current clinical practice trends in the COVID-19 pandemic.

Telemedicine is the medical practice of caring for and treating patients remotely. With the spread of the coronavirus disease-2019 (COVID-19) pandemic, telemedicine has become increasingly prevalent. Although telemedicine was already in practice before the 2020 pandemic, the internet, smartphones, computers, and video-conferencing tools have made telemedicine easily accessible and available to almost everyone. However, there are also new challenges that health care providers may not be prepared for, including treating and diagnosing patients without physical contact. Physician adoption also depends upon reimbursement and education to improve the telemedicine visits. We review current trends involving telemedicine, how pandemics such as COVID-19 affect the remote treatment of patients, and key concepts important to healthcare providers who practice telemedicine.