Needs-based novel digital curriculum for the neuromodulation training deficit: Pain Rounds.

This study reports the needs-based development, effectiveness and feasibility of a novel, comprehensive spinal cord stimulation (SCS) digital curriculum designed for pain medicine trainees. The curriculum aims to address the documented systematic variability in SCS education and empower physicians with SCS expertise, which has been linked to utilization patterns and patient outcomes. Following a needs assessment, the authors developed a three-part SCS e-learning video curriculum with baseline and postcourse knowledge tests. Best practices were used for educational video production and test-question development. The study period was from 1 February 2020 to 31 December 2020. A total of 202 US-based pain fellows across two cohorts (early-fellowship and late-fellowship) completed the baseline knowledge assessment, while 122, 96 and 88 participants completed all available post-tests for Part I (Fundamentals), Part II (Cadaver Lab) and Part III (Decision Making, The Literature and Critical Applications), respectively. Both cohorts significantly increased knowledge scores from baseline to immediate post-test in all curriculum parts (p<0.001). The early-fellowship cohort experienced a higher rate of knowledge gain for Parts I and II (p=0.045 and p=0.027, respectively). On average, participants viewed 6.4 out of 9.6 hours (67%) of video content. Self-reported prior SCS experience had low to moderate positive correlations with Part I and Part III pretest scores (r=0.25, p=0.006; r=0.37, p<0.001, respectively). Initial evidence suggests that Pain Rounds provides an innovative and effective solution to the SCS curriculum deficit. A future controlled study should examine this digital curriculum's long-term impact on SCS practice and treatment outcomes.

Epidural Blood Patch in a Patient with a Hematological Malignancy.

Postdural puncture headache is a frequently encountered complication following procedures such as lumbar puncture, neuraxial anesthesia, or intrathecal drug delivery device implantation. It classically presents as a painful orthostatic headache that is exacerbated when a patient is upright. For treatment, patients are often started on conservative options such as hydration, caffeine, bedrest, and NSAID analgesics; however, certain patients who fail these therapies may require intervention with an epidural blood patch. The epidural blood patch remains the gold standard for treating refractory postdural puncture headache. Contraindications to epidural blood patch include severe coagulopathy, patient refusal, or infection at the intended site of entry. There are no clear consensus recommendations regarding patients with a hematological malignancy and potential risk that autologous blood may seed malignant cells into the neuraxis. In this case report, we present a patient with acute myeloid leukemia who developed a postdural puncture headache after receiving subarachnoid administration of antineoplastics. The patient was refractory to conservative therapy, prompting multidisciplinary consultation and discussion with the patient about the risks and benefits of proceeding with an epidural blood patch. Ultimately, the patient elected to proceed with the offered epidural blood patch which led to complete resolution of his painful headaches and did not cause any spread of malignant cells into his neuraxis or cerebral spinal fluid.

Does Fibromyalgia Affect the Outcomes of Spinal Cord Stimulation: An 11-Year, Multicenter, Retrospective Matched Cohort Study.

BACKGROUND: Fibromyalgia is a prevalent disorder manifesting with widespread musculoskeletal pain and central sensitization, as well as fatigue, sleep issues, psychologic distress, and poor quality of life. Patients with fibromyalgia also may be diagnosed with other painful conditions amenable to treatment with spinal cord stimulation (SCS), although it is unclear how these patients respond to SCS compared with patients without fibromyalgia. MATERIALS AND METHODS: We performed an 11-year, multicenter, retrospective matched cohort study comparing SCS-treated patients with fibromyalgia and those without fibromyalgia. The primary outcome was comparison in mean calculated percentage pain relief between cohorts at six months after SCS implantation. Secondary outcomes included comparison of patient satisfaction between six and 12 months after SCS implantation, and percentage of patients reporting opioid intake and neuropathic medication intake at six months and 12 months after SCS implantation. Adjusted regression analysis was performed to make comparisons while adjusting for age, sex, body mass index, Charlson comorbidity index, preoperative opioid intake, and preoperative neuropathic medication intake. RESULTS: Of 90 patients with fibromyalgia who underwent SCS trial, 18 patients (20%) failed their SCS trial and did not proceed toward implantation. Sixty-eight patients with fibromyalgia were matched to 141 patients in the control cohort based on age, sex, Charlson comorbidity index, and the American Society of Anesthesiologists physical status score. At six months after SCS implantation, there was no statistical difference in calculated percentage change in pain intensity between the fibromyalgia cohort (46.6 ± 29.0) and the control cohort (50.9 ± 32.8; ß, -18.4; 95% CI, -44.3 to 7.6; p = 0.157). At baseline, a greater percentage of patients in the fibromyalgia cohort reported preoperative opioid intake (51.5% vs 22.7%, p < 0.001) and preoperative neuropathic medication intake (67.6% vs 15.6%, p < 0.001). However, there was no difference between cohorts in the percentage of patients taking opioid or neuropathic medications at six months and 12 months after SCS implantation. Similarly, there was no difference between cohorts in the percentage of patients reporting satisfaction between six and 12 months. CONCLUSION: Patients with fibromyalgia who received a diagnosis approved for treatment with SCS may expect similar post-SCS-implantation pain relief, overall satisfaction, and analgesic use rate to those of patients without fibromyalgia.

Dorsal Root Ganglion Stimulation for Lower Extremity Neuropathic Pain Syndromes: An Evidence-Based Literature Review.

Dorsal root ganglion stimulation (DRG-S) is a form of selective neuromodulation therapy that targets the dorsal root ganglion. DRG-S offers analgesia in a variety of chronic pain conditions and is approved for treatment of complex regional pain syndrome (CRPS) by the US Food and Drug Administration (FDA). There has been increasing utilization of DRG-S to treat various neuropathic pain syndromes of the lower extremity, although evidence remains limited to one randomized controlled trial and 39 observational studies. In this review, we appraised the current evidence for DRG-S in the treatment of lower extremity neuropathic pain using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The primary outcome was change in pain intensity after DRG-S compared to baseline. We stratified presentation of results based of type of neuropathy (CRPS, painful diabetic neuropathy, mononeuropathy, polyneuropathy) as well as location of neuropathy (hip, knee, foot). Future powered randomized controlled trials with homogeneous participants are warranted.

Sex Disparity Persists in Pain Medicine: A Cross-Sectional Study of Chairpersons Within ACGME-Accredited Chronic Pain Fellowship Programs in the United States.

Objective: To compare the representation of female and male chairpersons and evaluate their respective demographic, academic, and program-related characteristics in academic chronic pain institutions. Methods: We identified all chronic pain fellowship programs that are accredited by the Accreditation Council for Graduate Medical Education (ACGME) on April 19, 2021. We queried institutional websites or contacted programs directly to identify the respective departmental/divisional program chairperson. We abstracted data on program chairpersons from public databases and performed statistical comparisons of demographic, academic, and program-related characteristics between female and male program chairpersons. Results: Of the 111 ACGME-accredited chronic pain fellowship programs, we identified the current chairperson at 87 programs (78.4%). There were 17 female chairpersons (19.5%) and 70 male chairpersons (80.5%). A higher proportion of female chairpersons reported an academic rank of assistant professor compared with male chairpersons (35.3% vs 11.4%, P = .027). Male chairpersons published more peer-reviewed articles compared with female chairpersons (median 32.0 vs 10.0 publications, P = .001). Concordantly, male chairpersons achieved a higher H-index score compared with female chairpersons (median 10.0 vs 3.0, P = .001). No differences were identified in other academic or program-related characteristics. Conclusion: This cross-sectional study illuminates important details on sex-related differences in the chronic pain program chair role. Women chairpersons are underrepresented, have fewer peer-reviewed publications, and achieved a lower H-index score compared with male chairpersons. Establishing these baseline associations provides a reference for future studies to evaluate changes over time.

Evidence-Based Treatment of Painful Diabetic Neuropathy: a Systematic Review.

PURPOSE OF REVIEW: Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for evidence on conservative, pharmacological, and neuromodulation treatment options for PDN. RECENT FINDINGS: Intensive glycemic control with insulin in patients with type 1 diabetes may be associated with lower odds of distal symmetric polyneuropathy compared to patients who receive conventional insulin therapy. First-line pharmacologic therapy for PDN includes gabapentinoids (pregabalin and gabapentin) and duloxetine. Additional pharmacologic modalities that are approved by the Food and Drug Administration (FDA) but are considered second-line agents include tapentadol and 8% capsaicin patch, although studies have revealed modest treatment effects from these modalities. There is level I evidence on the use of dorsal column spinal cord stimulation (SCS) for treatment of PDN, delivering either a 10-kHz waveform or tonic waveform. In summary, this review provides an overview of treatment options for PDN. Furthermore, it provides updates on the level of evidence for SCS therapy in cases of PDN refractory to conventional medical therapy.

Effects of Slow Deep Breathing on Acute Clinical Pain in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Slow deep breathing (SDB) may help patients with acute pain. The primary aim of this systematic review and meta-analysis is to investigate the effects of SDB on acute pain. Secondary aims include investigating the effects of SDB on acute pain-related physical and emotional functioning. An a priori protocol was registered and a database search was conducted by a reference librarian. Randomized controlled trials (RCT) were eligible for inclusion and exclusion criteria included studies of SDB for non-pain indications and studies that applied SDB as a component of an encompassing intervention. The risk or bias was assessed using the Cochrane Collaboration's revised tool for assessing risk of bias in randomized trials. Meta-analysis was conducted using the random effects model. A total of 11 968 studies were screened and seven RCTs met inclusion criteria; five were judged to have low risk of bias. Meta-analysis of post-intervention pain scores demonstrated that SDB was associated with significantly lower pain scores compared with a control group, but with high levels of heterogeneity. Subgroup analyzes demonstrated that trials of burn pain were associated with a larger reduction in pain which partially explains the heterogeneity. Very low certainty evidence suggests that SDB may reduce acute pain intensity. Further research is needed to identify patients who are candidates for SDB and determine the best approach to deliver this therapy.

Adverse Events Associated With 10-kHz Dorsal Column Spinal Cord Stimulation: A 5-Year Analysis of the Manufacturer and User Facility Device Experience (MAUDE) Database.

BACKGROUND: High-frequency (10-kHz) spinal cord stimulation (SCS) continues to be an emerging therapy in chronic pain management. The same complications that plagued earlier SCS systems may affect newer stimulation technologies, although there is limited data on the type of complications and surgical management of these complications. OBJECTIVE: The aim of this study was to systematically examine real-world complications associated with 10-kHz SCS reported on the Manufacturer and User Facility Device Experience (MAUDE) database. MATERIALS AND METHODS: The MAUDE database was queried for entries reported between January 1, 2016 and December 31, 2020. Entries were classified into procedural complications, device-related complications, patient complaints, surgically managed complications, serious adverse events, and/or other complications. Primary outcomes included type and frequency of complications, and surgical management of complications. RESULTS: A total of 1651 entries were analyzed. Most entries were categorized as procedural complications (72.6%), followed by serious adverse events (10.5%), device-related complications (10.5%), and patient complaints (9.9%). Most complications were managed surgically with explant (50.9%) rather than revision (5.0%) or incision/drainage (6.6%). Of procedural complications, the most common entries included non-neuraxial infection (52.9%), new neurological symptoms (14.7%), and dural puncture (9.5%). Of device-related complications, the most common entries included lead damage (41.6%), erosion (18.5%), and difficult insertion (11.5%). CONCLUSION: This retrospective 5-year analysis of complications from10-kHz SCS provides a real-world assessment of safety data unique for this stimulation modality. This analysis may help inform future clinical decisions, lead to device enhancement and optimization, and improve mitigation of risks to provide safe and efficacious use of 10-kHz SCS.

Dorsal Root Ganglion Stimulation for Chronic Groin Pain: A Review.

INTRODUCTION: Chronic neuropathic groin pain develops in a significant number of postsurgical patients; however, multiple etiologies have been identified, and this makes it a challenging condition to treat. While treatment often involves a multimodal approach, advancements in neuromodulation technology, particularly dorsal root ganglion (DRG) stimulation, have benefited patients plagued by chronic pain refractory to standard treatment modalities. Our goal was to provide a definitive source of information for interventional pain physicians regarding groin pain and the use of DRG stimulation for its treatment. MATERIALS AND METHODS: In this narrative review, we provide an overview of groin pain and discuss potential pain generators. We also outline appropriate treatment options with particular interest on DRG stimulation. Lastly, we provide a narrative review of the published literature regarding DRG stimulation for chronic groin pain from a variety of etiologies. CONCLUSION: DRG stimulation has emerged as an alternative neuromodulatory technique for patients with chronic groin pain. While previous studies suggest substantial sustained pain relief with DRG stimulation in this patient population, prospective randomized controlled studies are necessary before formal recommendations can be made.

A 16-Year-Old Male with Thoracic Compression following Posterior Spinal Instrumentation and Fusion for Marfan-Associated Syndromic Scoliosis.

INTRODUCTION: Marfan syndrome is an autosomal dominant disorder caused by a mutation in the FBN1 gene which affects connective tissue. The features of Marfan syndrome include many musculoskeletal abnormalities which require orthopaedic surgical intervention. Given the expansive phenotypic variations and comorbidities associated with Marfan syndrome, knowledge of perioperative risk factors and potential complications is essential. CASE: In this case report, the authors describe a patient with Marfan syndrome who underwent spinal instrumentation and fusion from T3 to L4 for correction of syndromic scoliosis. The patient had a complicated perioperative course requiring significant fluid resuscitation and vasoactive medications to support blood pressure. He required intensive care unit level care for continued hemodynamic instability despite resuscitation in the postoperative period. Common causes of postoperative hypotension such as hypovolemic shock, sepsis, ongoing hemorrhage, and prolonged effects of anesthesia were diagnostically ruled out. Ultimately, the patient's refractory hypotension was determined to be from mechanical compression, both from prolonged intraoperative prone positioning exacerbated by pectus excavatum and from the surgically corrected spine decreasing the diameter of his thoracic cavity (as referenced by his postoperative Haller index). CONCLUSION: Mechanical compression of thoracic contents as a result of a worsening chest wall deformity can be a complication of spinal deformity correction.

Postoperative outcomes in patients with treatment-emergent central sleep apnea: a case series.

PURPOSE: Treatment-emergent central sleep apnea (TECSA) is a central sleep-related breathing disorder, characterized by either the persistence or emergence of central sleep apnea during the initiation of positive airway pressure therapy for obstructive sleep apnea. The purpose of this study was to review the perioperative course of patients diagnosed with TECSA. METHODS: We reviewed medical records of patients with TECSA who had a procedure or surgery with general anesthesia between January 1, 2009 and May 1, 2018. We describe postoperative outcomes including respiratory complications, unplanned intensive care unit (ICU) admissions, and other postoperative outcomes. RESULTS: We identified 150 (116 male, 34 female) patients with TECSA. Of these, 39 (26%) had their anesthesia recovery associated with moderate to profound sedation, 22 (14.7%) required unplanned transfer to ICU (8 for hypoxemia). Compared to patients without ICU admissions, patients with unplanned ICU admissions had higher rates of cardiovascular disease, Charlson comorbid scores, and perioperative benzodiazepines. Within the first 30 postoperative days there were 23 (16%) hospital re-admissions, and 7 (4.6%) deaths. CONCLUSION: Patients with TECSA have high rates of postoperative complications, characterized by an increased rate of unplanned intensive care admissions and both high 30-day readmission and mortality rates. When dealing with these patients perioperative physicians should implement an increased level of respiratory monitoring, and early postoperative use of their home prescribed non-invasive ventilation devices.

Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals.

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

Ultrasound-mediated gastrointestinal drug delivery.

There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

A pH-responsive supramolecular polymer gel as an enteric elastomer for use in gastric devices.

Devices resident in the stomach-used for a variety of clinical applications including nutritional modulation for bariatrics, ingestible electronics for diagnosis and monitoring, and gastric-retentive dosage forms for prolonged drug delivery-typically incorporate elastic polymers to compress the devices during delivery through the oesophagus and other narrow orifices in the digestive system. However, in the event of accidental device fracture or migration, the non-degradable nature of these materials risks intestinal obstruction. Here, we show that an elastic, pH-responsive supramolecular gel remains stable and elastic in the acidic environment of the stomach but can be dissolved in the neutral-pH environment of the small and large intestines. In a large animal model, prototype devices with these materials as the key component demonstrated prolonged gastric retention and safe passage. These enteric elastomers should increase the safety profile for a wide range of gastric-retentive devices.

Ultrahigh speed en face OCT capsule for endoscopic imaging.

Depth resolved and en face OCT visualization in vivo may have important clinical applications in endoscopy. We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs.

Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet non-specific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20kHz and 1MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20kHz alone. Additionally, LTRs generated by treatment with 20kHz+1MHz were found to be more permeable than those generated with 20kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20kHz+1MHz were calculated to be significantly larger than the pores in skin treated with 20kHz alone. This demonstrates for the first time that LTRs generated with 20kHz+1MHz are also more permeable than those generated with 20kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20kHz+1MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo.