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In the US, an estimated 1 - 2% of chronic venous insufficiency (CVI) patients (of 6 - 7 million nationwide) develop at least one venous stasis ulcer (VSU) during their illness. Of these, approximately 40% develop subsequent ulcers, making VSU prognostically poor. Current management of VSU is costly, with poor prognosis, high recurrence rate, inadequate pain management, and significantly reduced quality of life (QoL). Topical volatile anesthetic agents, such as sevoflurane, offer improved pain relief and symptom control in patients suffering from chronic VSU. The immediate impact of topical sevoflurane in reducing pain associated with ulcer bed debridement has several implications in improving the quality of life in patients with CVI induced ulcers and in the prognosis and healing of the ulcers. This review summarizes a topical formulation of a volatile anesthetic and its implications for the management of VSUs., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2021, Author(s).)

Patient safety advocacy involves avoiding, preventing, and amelioration of adverse outcomes or injuries caused by the process of healthcare rather than a patient's underlying medical illness. Intraoperative hypotension (IOH), a common morbid event, reduces perfusion to critical organs and tissues and has a wide incidence, depending on how it is defined. IOH has adverse intraoperative and postoperative consequences, which make its prevention important to improve patient outcomes. Certain populations have even greater consequences related to IOH, and clinicians must understand these risks. In this narrative review, we examine the risk of intraoperative hypotension in the oncological patient population., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2021, Author(s).)

Background: Chronic back and neck pain affects 20% of Americans. Spinal cord stimulation (SCS) is an effective therapy for otherwise refractory chronic pain. Traditional SCS relies on low-frequency stimulus in the 40 - 60 Hz range causing robust paresthesia in regions overlapping with painful dermatomes., Objectives: This study aims to determine the effect of superimposing sub-perception stimulation in patients who previously had good long-term relief with paresthesia., Methods: This is a prospective observational trial examining patients who had previously been implanted with paresthesia based SCS for failed back surgery syndrome (FBSS) or complex regional pain syndrome (CRPS). These patients presented for implantable pulse generator (IPG) replacement based on battery depletion with an IPG capable of combined sub-perception and paresthesia based SCS therapy. Patients were assessed immediately following the exchange and four weeks later using a telephone survey. Their pain was assessed on each follow up using a Numerical Rating scale (NRS); the primary outcome was the change in NRS after four weeks from the exchange day. Secondary outcomes included paresthesia changes, which included the subjective quality of sensation generated, the overall subjective coverage of the painful region, subjective variation of coverage with positional changes, and global perception of the percentage improvement in pain., Results: Based on our clinic registry, 30 patients were eligible for IPG exchange, 16 were consented for follow up and underwent an exchange, and 15 were available for follow up four weeks following. The average NRS decreased from 7.47 with traditional SCS to 4.5 with combination therapy. 80% of patients reported an improvement in the quality of paresthesia over traditional SCS therapy, and in most patients, this translated to significantly improved pain control., Conclusions: Our findings suggest improved pain relief in patients who had previously had good results with paresthesia based therapy and subsequently underwent IPG exchange to a device capable of delivering combined sub-perception stimulation. The mechanism of action is unclear though there may be an additive and/or synergistic effect of the two waveforms delivered. Larger studies with long-term follow-up are needed to elucidate the durability of pain relief and the precise mechanism by which combined subperception and paresthesia based SCS may improve overall patient outcomes., Competing Interests: Conflict of Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021, Author(s).)

Valtoco ® is a new FDA-approved nasal spray version of diazepam indicated for the treatment of acute, intermittent, and stereotypic episodes of frequent seizure activity in epilepsy patients six years of age and older. Although IV and rectal diazepam are already used to treat seizure clusters, Valtoco ® has less variability in plasma concentration compared to rectal diazepam. Furthermore, the intranasal administration of Valtoco ® is more convenient and less invasive than rectal or IV diazepam, making it ideal for self-administration outside of a hospital setting. Multiple clinical trials have taken place comparing Valtoco ® to the oral, rectal, and IV forms of diazepam. Aside from mild nasal irritation and lacrimation, Valtoco ® was found to have no increased safety risk in comparison to traditional forms of diazepam. This review of Valtoco ® will include a history of diazepam prescribing and withdrawal treatment, Valtoco ® drug information, its mechanism of action, pharmacokinetics and pharmacodynamics, and a comprehensive review of clinical studies.

Context: Pelvic pain is described as pain originating from the visceral or somatic system localizing to the pelvis, the anterior abdominal wall at the level of or below the umbilicus, lumbosacral back in either men or women., Evidence Acquisition: Narrative review., Results: Chronic pelvic pain can be a complex disorder that may involve multiple systems such as urogynecological, gastrointestinal, neuromusculoskeletal, and psychosocial systems. The etiopathogenesis for chronic pain remains unknown for many patients. For achieving optimal patient management, a multimodal and individualized assessment of each patient is the best strategy., Conclusions: There are non-pharmacologic treatments as well as pharmacologic treatments. In addition to these treatment options, inferior hypogastric plexus block is a promising treatment modality., Competing Interests: Conflict of Interests: None., (Copyright © 2021, Author(s).)

Context: The anatomy of the radial nerve is prone to entrapment, each with different symptomology. Compression of entrapment of the radial nerve can occur near the radiocapitellar joint, the spiral groove, the arcade of Frohse, the tendon of the extensor carpi radialis brevis (ECRB), and at the radial tunnel. Those who require repetitive motions are at increased risk of peripheral neuropathy syndromes, including repetitive pronation and supination, trauma, or systemic disease; however, t the influence of all risk factors is not well understood. Depending on the location of entrapment, radial nerve entrapment syndrome presents different symptoms. It may include both a motor component and a sensory component. The motor component includes a dropped arm, and the sensory component can include pain and paresthesia in the distribution of the radial nerve that resolves with rest and exacerbates by repetitive pronation and supination., Evidence Acquisition: Diagnostic evaluation for radial nerve entrapment, apart from clinical symptoms and physical exam, includes electromyography, nerve conduction studies, ultrasonography, and magnetic resonance imaging. Conservative management for radial nerve entrapment includes oral anti-inflammatory medications, activity modification, and splinting. Some recently performed studies mentioned promising minimally invasive techniques, including corticosteroid injections, peripheral nerve stimulation, and pulsed radiofrequency., Results: When minimally invasive techniques fail, open or endoscopic surgery can be performed to release the nerve., Conclusions: Endoscopic surgery has the benefit of decreasing incision size and reducing time to functional recovery., Competing Interests: Conflict of Interests: The authors declare no conflict of interest., (Copyright © 2021, Author(s).)

Context: The International Association for the Study of Pain (IASP) defines chronic pain as pain that persists or recurs for longer than 3 months. Chronic pain has a significant global disease burden with profound effects on health, quality of life, and socioeconomic costs., Evidence Acquisition: Narrative review., Results: There are several treatment options, including pharmacological therapy, physical rehabilitation, psychological therapies, and surgical interventions, for chronic pain management. Magnesium has been FDA-approved for several indications including hypomagnesemia, arrhythmia, prevention of seizures in eclampsia/preeclampsia, and constipation. Magnesium has been used for numerous off-label uses, notably for acute and chronic pain management. The mechanism of magnesium in pain management is primarily through its action as a voltage-gated antagonist of NMDA receptors, which are involved in pain transduction., Conclusions: This narrative review will focus on the current evidence and data surrounding the utilization of magnesium as a treatment option for chronic pain., Competing Interests: Conflict of Interests: None., (Copyright © 2021, Author(s).)

Purpose of Review: This is a comprehensive review of the literature regarding post-surgical cutaneous nerve entrapment, epidemiology, pathophysiology, and clinical presentation. It focuses mainly on nerve entrapment leading to chronic pain and the available therapies., Recent Findings: Cutaneous nerve entrapment is not an uncommon result (up to 30% of patients) of surgery and could lead to significant, difficult to treat chronic pain. Untreated, entrapment can lead to neuropathy and damage to enervated structures and musculature, and significant morbidity and financial loss. Nerve entrapment is defined as pressure neuropathy from chronic compression. It causes changes to all layers of the nerve tissue. It is most significantly associated with hernia repair and other procedures employing a Pfannenstiel incision. The initial insult is usually incising of the nerve, followed by formation of a neuroma, incorporation of the nerve during closing, or constriction from adhesions. The three most commonly involved nerves are the iliohypogastric, ilioinguinal, and genitofemoral nerves. Cutaneous abdominal nerve entrapment could occur during thoracoabdominal surgery. The presentation of nerve entrapment usually involved post-surgical pain in the territory innervated by the trapped nerve, possibly with radiation that tracks the nerve course. Once a suspected neuropathy is identified, it can be diagnosed with relief in pain after a nerve block has been instilled. Treatment is usually started with pharmaceutical solutions, topical first and oral if those fail. Most patients require escalation to a second line of treatment and see good result with injection therapy. Those that require further escalation can choose between ablation and surgical therapies. Post-surgical nerve entrapment is not uncommon and causes serious morbidity and financial loss. It is underdiagnosed and thus undertreated. Preventing nerve entrapment is the best treatment; when it does occur, options include topical and oral analgesics, nerve blocks, ablation therapy, and repeat surgery.

Background Midazolam is commonly used preoperatively for anxiety. Adverse effects data in pediatric patients with obstructive sleep apnea (OSA) undergoing tonsillectomy and adenoidectomy (T&A) is limited. Aims We hypothesized that preoperative midazolam increases the time to emergence from anesthesia and postoperative discharge. Secondary objectives assessed if patients receiving midazolam experienced increased side effects or complications from treatment. Methods This study was a retrospective chart review of patients undergoing T&A from July 2014 to December 2015. Midazolam receiving patients (midazolam group: MG) were compared to patients who did not (non-midazolam group: NMG). Multivariable analyses were performed and adjusted for predefined potential cofounder variables. Results Emergence and discharge times were 5.2 minutes (95% CI [-7.1, 17.4]; p=0.41) and 10.1 minutes (95% CI [-6.7, 26.8]; p=0.24) longer in MG. These results were not statistically significant. Comparing by OSA status, there was no statistical difference in emergence and discharge times between mild, moderate and severe OSA groups or between MG and NMG within each OSA group. Emergence and discharge times in moderate OSA was 6.1 minutes (95% CI [-17.6, 29.8]; p=0.61) and 18.8 minutes (95% CI [-16.4, 53.9]; p=0.29) longer than mild OSA, and in the severe OSA group, 2.6 minutes (95% CI [-19.9, 25.1]; p=0.82) shorter and 2.8 minutes (95% CI [-30.3, 35.9]; p=0.87) longer. The incidence of postoperative complications was comparable between MG and NMG groups. Conclusions Premedication with midazolam was not associated with prolonged emergence or discharge time or higher incidence of complications after anesthesia for T&A in patients with OSA., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Garcia et al.)

Context: Piriformis syndrome is a solely clinical diagnosis that often eludes the practitioner and goes underdiagnosed. PS is a pain syndrome and for those it affects, causes persistent pain and limits daily activity and work capacity. It is a form of deep gluteal syndrome that needs to be considered on the differential of low back pain as it comprises between 0.3% - 6% of all low back pain cases and is frequently underdiagnosed. Piriformis syndrome may be primary due anatomic anomalies or secondary, though the majority of cases are secondary to some insult. The objective of this manuscript is to provide a description of the epidemiology and presentation of piriformis as well as both non-operative and operative treatment options. We review all of the recent clinical evidence regarding the aforementioned therapies., Evidence Acquisition: Literature searches were performed using the below MeSH Terms using Mendeley version 1.19.4. Search fields were varied until further searches revealed no new articles. All articles were screened by title and abstract. Decision was made to include an article based on its relevance and the list of final articles was approved three of the authors. This included reading the entirety of the article. Any question regarding the inclusion of an article was discussed by all authors until an agreement was reached., Results: Medical management and physical therapy show some promise; however, when conservative treatment fails minimally invasive methods such as steroid injections, botulinum toxin injections, dry needling are all efficacious and there is substantial clinical evidence regarding these therapies. In those patients in which minimally invasive techniques do not result in an adequate relief of pain and return of function, endoscopic release can be considered. Endoscopic release is far superior to open release of the piriformis syndrome given the higher success and lower rate of complications., Conclusions: Piriformis syndrome is an important differential diagnosis in the work up of lower back pain and should not be ruled out with proper examination and testing. Clinicians should consider medical management and conservative management in the initial treatment plan for piriformis syndrome. There are many options within the conservative management and the literature shows much promise regarding these. Physical therapy, steroid injections, botulinum toxin injections, and dry needling are all potentially effective therapies with few adverse effects. Surgical options remain as gold standard, but only when conservative management has failed and the symptoms are significant to affect daily living activities. Endoscopic decompression of the sciatic nerve with or without release of the piriformis muscle has a reported high likelihood of success and a low complication rate. Current literature supports the preference of the endoscopic approach over the open approach due to improved outcomes and decreased complications. Further research is to well define the metrics for the diagnosis of piriformis syndrome and may include a need to develop diagnostic criteria., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2021, Author(s).)

Spinal cord stimulation is an effective treatment modality for patients with numerous pain conditions. Although proven to be highly successful, device implantation does come with some inherent risks. One of the most challenging complications is perioperative infection. For most patients, a simple trial of oral antibiotics and in-office drainage of any superficial infectious material may be sufficient. Deeper infections with wound dehiscence necessitate device removal and intravenous antibiotic therapy. The question remains, if the device was previously providing pain relief for the patient, when is the appropriate time to reimplant the device after the infection has cleared? We describe the case of explantation of an infected device and successful reimplantation after 1 year., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Migraine is a neurobiological headache disorder that affects around 16% of adults in the United States. Medical treatment of mild to moderate migraines include non-prescription non-steroidal anti-inflammatory drugs, acetaminophen, or aspirin and caffeine-containing combination analgesics. Additionally, moderate to severe migraines and those that are mild to moderate that have not responded to analgesics can be treated with triptans, which are drugs specific for migraine treatment. Non-pharmacological treatments include cognitive behavioral therapy and relaxation training. Medications for the prevention of migraines have also been developed since they are more affective in offsetting the symptoms. Ubrogepant's high specificity and selectivity for calcitonin gene-related peptide (CGRP) sets it apart from certain other drugs, which previously limited the treatment of migraines with or without aura due to their decreased selectivity. The most frequently reported side effects are oropharyngeal pain, nasopharyngitis, and headache. Most studies found that participants receiving Ubrogepant were free from pain within 2 h when compared to placebo. Patients taking Ubrogepant should avoid taking it when pregnant or with end stage renal disease. In summary, Ubrogepant has good tolerability and an overall favorable safety profile. It appears to hold promise for the acute treatment of migraines with or without aura in adults.

Purpose of Review: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available., Recent Findings: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.

Purpose of Review: This evidence-based systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. It will cover the background and the burden of low back pain and present the current options for treatment and weigh the evidence that is available to support acupuncture as a treatment modality for low back pain., Recent Findings: Low back pain (LBP), defined as a disorder of the lumbosacral spine and categorized as acute, subacute, or chronic, can be a debilitating condition for many patients. Chronic LBP is more typically defined by its chronicity with pain persisting > 12 weeks in duration. Conventional treatment for chronic LBP includes both pharmacologic and non-pharmacologic options. First-line pharmacologic therapy involves the use of NSAIDs, then SNRI/TCA/skeletal muscle relaxants, and antiepileptics. Surgery is usually not recommended for chronic non-specific LBP patients. According to the 2016 CDC Guidelines for Prescribing Opioids for Chronic Pain and the 2017 American College of Physicians (ACP) clinical practice guidelines for chronic pain, non-pharmacologic interventions, acupuncture can be a first-line treatment for patients suffering from chronic low back pain. Many studies have been done, and most show promising results for acupuncture as an alternative treatment for low back pain. Due to non-standardized methods for acupuncture with many variations, standardization remains a challenge.

Postmastectomy pain syndrome (PMPS) is a common complication after breast cancer surgery and is often challenging to manage. Treatment options include medication management, physical therapy, and interventional procedures. The erector spinae plane block (ESPB) is a regional technique proven to help both acute postoperative analgesia and chronic neuropathic pain conditions. This block is becoming more popular in the chronic pain setting for neuropathic thoracic pain conditions. We describe the utilization of the ESP block for significant neuropathic breast pain after total mastectomy. Our case demonstrates the utility of this block for women suffering from severe PMPS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Hasoon et al.)

Purpose of Review: This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the treatment of chronic pain, cognitive and neurological adverse effects, special cases and addiction., Recent Findings: Cannabinoids work through the endocannabinoids system and inhibit the release of GABA and glutamate in the brain, impact neuromodulation, as well as dopamine, acetylcholine and norepinephrine release. They affect reward, learning and pain. The use of cannabis is increasing nationally and world-wide for both recreational and medicinal purposes, however, there is relatively only low quality evidence to the efficacy and adverse effects of this. Cannabis and its derivatives may be used for treatment of chronic pain. They are via CB1 receptors that are thought to modulate nociceptive signals in the brain. CB2 receptors in the DRG likely affect pain integration in the afferent pathways, and peripherally CB2 also affects noradrenergic pathways influencing pain. A large proportion of users may see more than 50% of chronic pain alleviation compared with placebo. Cannabis affects cognition, most notably executive function, memory and attention, and may deteriorate the boundary between emotional and executive processing. Cannabis impairs memory in the short run, which become more significant with chronic use, and may also be accompanied by poorer effort, slower processing and impacted attention. It is generally believed that long-term use and earlier age are risk factor for neurocognitive deficits; neuroimaging studies have shown reduced hippocampal volume and density. Executive functions and memory are worse in adolescent users versus adults. Cannabis addiction is different and likely less common than other addictive substances, but up to 10% of users meet criteria for lifetime cannabis dependence. Addiction patterns may be linked to genetic and epigenetic differences. It is still unclear whether abstinence reverses patterns of addiction, and more research is required into this topic., Summary: Cannabis use has become more abundant for both medical and recreational use. It carries likely benefits in the form of analgesia, anti-emesis and improved appetite in chronic patients. The evidence reviewing adverse effects of this use are still limited, however, exiting data points to a clear link with neurocognitive deterioration, backed by loss of brain volume and density. Addiction is likely complex and variable, and no good data exists to support treatment at this point. It is becoming clear that use in earlier ages carries a higher risk for long-term deficits. As with any other drug, these risks should be considered alongside benefits prior to a decision on cannabis use., (Copyright © 1964–2019 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Opiates are routinely used for chronic pain patients, and up to 44% of them will have a prescription for an opiate medication for pain alleviation. However, of the 76 million adults prescribed opiates for pain management, about 12% report misuse, and a large number of these may find themselves addicted to opioid medications. Opioid addiction is an ongoing epidemic, costing many lives. Withdrawal is very difficult. This requires providers to consider alternative analgesic plans and minimize opiate use. Here we report the use of a dexamethasone-dexmedetomidine combination for a regional nerve block in an elderly woman chronically treated with opiate medications who had previously failed opiate weaning. Following her nerve block, she was able to completely wean off of opioids and continues having good pain control with an opioid-free regimen., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Context: Chronic pain accounts for one of the most common reasons patients seek medical care. The financial burden of chronic pain on health care is seen by direct financial cost and resource utilization. Many risk factors may contribute to chronic pain, but there is no definite risk. Managing chronic pain is a balance between maximally alleviating symptoms by utilizing a therapeutic regimen that is safe for long-term use. Currently, non-opioid analgesics, NSAIDs, and opioids are some of the medical treatment options, but these have numerous adverse effects and may not be the best option for long-term use. However, Lidocaine can achieve both central and peripheral analgesic effects with relatively few side effects, which may be an ideal compound for managing chronic pain., Evidence Acquisition: This is a Narrative Review., Results: Infusion of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide), an amino-amide compound, is emerging as a promising option to fill the therapeutic void for treatment of chronic pain. Numerous studies have outlined dosing protocols for lidocaine infusion for the management of perioperative pain, outlined below. While there are slight variations in these different protocols, they all center around a similar dosing regimen to administer a bolus to reach a rapid steady state, followed by infusion for up to 72 hours to maintain the therapeutic analgesic effects., Conclusions: Lidocaine may be a promising pharmacologic solution with a low side effect profile that provides central and peripheral analgesia. Even though the multifaceted mechanism is not entirely understood yet, lidocaine may be a promising novel remedy in treating chronic pain in various conditions., Competing Interests: Conflict of Interests: None declared., (Copyright © 2020, Author(s).)

Background: Twelfth rib syndrome, or slipping of the 12th rib, is an often overlooked cause for chronic chest, back, flank, and abdominal pain from irritation of the 12th intercostal nerve. Diagnosis is clinical and follows the exclusion of other causes of pain. This syndrome is usually accompanied by long-suffering, consequent psychiatric comorbidities, and increased health care costs, which are secondary to the delayed diagnosis., Objectives: This manuscript is a review of twelfth rib syndrome and its management options. The review provides etiology, pathophysiology, and epidemiology of twelfth rib syndrome. Additionally, diagnosis and current options for treatment and management are presented., Study Design: This is a narrative review of twelfth rib syndrome., Setting: A database review., Methods: A PubMed search was conducted to ascertain seminal literature regarding twelfth rib syndrome., Results: Conservative treatment is usually the first line, including local heat or ice packs, rest, and oral over-the-counter analgesics. Transcutaneous stimulation and 12th intercostal nerve cryotherapy have also been described with some success. Nerve blocks can additionally be tried and are usually effective in the immediate term; there is a paucity of evidence to suggest long-term efficacy. Surgical removal of all or part of the 12th rib and possibly the 11th rib, as well as the next line of therapy, may provide long-lasting relief of pain., Limitations: Further large scale clinical studies are needed to assess the most effective management of twelfth rib syndrome., Conclusions: Twelfth rib syndrome is usually diagnosed late and causes significant morbidity and suffering. The actual epidemiology is unclear given the difficulty of diagnosis. Nerve blocks and surgical rib resection appear to be effective in treating this syndrome, however, further evidence is required to properly evaluate them. Familiarity with this syndrome is crucial in reaching a prompter diagnosis.

Objectives: Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS., Methods: Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy., Results: Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P < 0.001)., Conclusions: Our study suggests that socioeconomic disparities may exist in the utilization of SCS among hospitalized patients with CRPS I and FBSS the United States. However, confirming these data from other administrative databases, in the outpatient setting, may shed more insight., (© 2020 World Institute of Pain.)

Introduction: Non-pharmacologic alternative therapies for pain have been around for a long time, some for hundreds of years. They have been used throughout history to treat many issues., Recent Findings: Currently, alternative medicine is most frequently used to treat musculoskeletal pain, and between 59 and 90% of patients utilizing alternative therapies for chronic pain claimed they were helpful and can serve as an effective adjunctive for the treatment of chronic pain. Some examples of alternative therapies that will be discussed in this review include acupuncture, tai chi, osteopathic manipulation, and chiropractic care. Acupuncture, traditionally a Chinese practice, is becoming more popular across the world to attempt to relieve pain. It involves the placement of thin needles at various points in the body. The efficacy of acupuncture for pain is heavily debated. More research and discussion are necessary to determine the exact role it plays in the treatment of chronic pain. Tai chi is also a traditional Chinese practice that is often used as a form of meditation and for potential health benefits. Tai chi involves a series of complex movements such as squatting combined with deep breathing to achieve relaxation and pain reduction. Osteopathic manipulative treatment (OMT) is a technique used by both osteopathic physicians (DO) as well as other health professionals to manage a wide range of conditions in any given patient. The technique involves utilization and manipulation of the musculoskeletal system to achieve potential health benefits. OMT has been used as therapy for many issues but is commonly used for pain conditions. Alternative therapies may serve as an effective adjunctive treatment modality for the management of chronic pain conditions. There has been a tremendous amount of research dictating the effectiveness of alternative therapies for chronic pain management. The purpose of this review is to provide a comprehensive evidence-based update of alternative therapy used for the management of chronic pain conditions.

Ganglioneuromas (GNs) are benign, differentiated tumors that are derived from neural crest sympathogonia. They can be found anywhere in the body along autonomic ganglia. These tumors are seen most often in individuals over 10 years of age and are usually asymptomatic. However, GNs can grow large and cause symptoms due to mass effect. GNs are rarely located within the suprarenal gland and are benign tumors that are often diagnosed late in their course due to mass effect or found incidentally on imaging studies. We describe a case of a 22-year-old female who presented to clinic with vague abdominal pain. She underwent an extensive workup which ultimately revealed a rare presentation of a left suprarenal GN that required surgical removal. She underwent an extensive workup which ultimately revealed a left suprarenal GN that required surgical removal. The patient underwent laparotomy and surgical excision of the mass and made a full recovery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Burroughs et al.)

Context: Carpal tunnel syndrome (CTS) is the most frequent peripheral compression-induced neuropathy observed in patients worldwide. Surgery is necessary when conservative treatments fail and severe symptoms persist. Traditional Open carpal tunnel release (OCTR) with visualization of carpal tunnel is considered the gold standard for decompression. However, Endoscopic carpal tunnel release (ECTR), a less invasive technique than OCTR is emerging as a standard of care in recent years., Evidence Acquisition: Criteria for this systematic review were derived from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two review authors searched PubMed, MEDLINE, and the Cochrane Database in May 2018 using the following MeSH terms from 1993-2016: 'carpal tunnel syndrome,' 'median nerve neuropathy,' 'endoscopic carpal tunnel release,' 'endoscopic surgery,' 'open carpal tunnel release,' 'open surgery,' and 'carpal tunnel surgery.' Additional sources, including Google Scholar, were added. Also, based on bibliographies and consultation with experts, appropriate publications were identified. The primary outcome measure was pain relief., Results: For this analysis, 27 studies met inclusion criteria. Results indicate that ECTR produced superior post-operative pain outcomes during short-term follow-up. Of the studies meeting inclusion criteria for this analysis, 17 studies evaluated pain as a primary or secondary outcome, and 15 studies evaluated pain, pillar tenderness, or incision tenderness at short-term follow-up. Most studies employed a VAS for assessment, and the majority reported superior short-term pain outcomes following ECTR at intervals ranging from one hour up to 12 weeks. Several additional studies reported equivalent pain outcomes at short-term follow-up as early as one week. No study reported inferior short-term pain outcomes following ECTR., Conclusions: ECTR and OCTR produce satisfactory results in pain relief, symptom resolution, patient satisfaction, time to return to work, and adverse events. There is a growing body of evidence favoring the endoscopic technique for pain relief, functional outcomes, and satisfaction, at least in the early post-operative period, even if this difference disappears over time. Several studies have demonstrated a quicker return to work and activities of daily living with the endoscopic technique., Competing Interests: Conflict of Interests: Alan Kaye is on the Speakers Bureau for Merck Pharmaceuticals., (Copyright © 2020, Author(s).)

Context: Ulnar nerve entrapment is a relatively common entrapment syndrome second only in prevalence to carpal tunnel syndrome. The potential anatomic locations for entrapment include the brachial plexus, cubital tunnel, and Guyon's canal. Ulnar nerve entrapment is more so prevalent in pregnancy, diabetes, rheumatoid arthritis, and patients with occupations involving periods of prolonged elbow flexion and/or wrist dorsiflexion. Cyclists are particularly at risk of Guyon's canal neuropathy. Patients typically present with sensory deficits of the palmar aspect of the fourth and fifth digits, followed by motor symptoms, including decreased pinch strength and difficulty fastening shirt buttons or opening bottles., Evidence Acquisition: Literature searches were performed using the below MeSH Terms using Mendeley version 1.19.4. Search fields were varied until further searches revealed no new articles. All articles were screened by title and abstract. Decision was made to include an article based on its relevance and the list of final articles was approved three of the authors. This included reading the entirety of the artice. Any question regarding the inclusion of an article was discussed by all authors until an agreement was reached., Results: X-ray and CT play a role in diagnosis when a bony injury is thought to be related to the pathogenesis (i.e., fracture of the hook of the hamate.) MRI plays a role where soft tissue is thought to be related to the pathogenesis (i.e., tumor or swelling.) Electromyography and nerve conduction also play a role in diagnosis. Medical management, in conjunction with physical therapy, shows limited promise. However, minimally invasive techniques, including peripheral percutaneous electrode placement and ultrasound-guided electrode placement, have all been recently studied and show great promise. When these techniques fail, clinicians should resort to decompression, which can be done endoscopically or through an open incision. Endoscopic ulnar decompression shows great promise as a surgical option with minimal incisions., Conclusions: Clinical diagnosis of ulnar nerve entrapment can often be delayed and requires the suspicion as well as a thorough neurological exam. Early recognition and diagnois are important for early institution of treatment. A wide array of diagnostic imaging can be useful in ruling out bony, soft tissue, or vascular etiologies, respectively. However, clinicians should resort to electrodiagnostic testing when a definitive diagnois is needed. Many new minimally invasive techniques are in the literature and show great promise; however, further large scale trials are needed to validate these techniques. Surgical options remains as a gold standard when adequate symptom relief is not achieved through minimally invasive means., Competing Interests: Conflict of Interests: We have no conflicts of interest., (Copyright © 2020, Author(s).)

Gastrointestinal cancers, such as malignant carcinoid tumor and pancreatic cancer, are responsible for excruciating and debilitating abdominal pain. Too often, patients are placed on chronic high-dose opioids, but the pain remains poorly controlled. It is incumbent on the medical team to approach the patient's debilitating pain in a thorough multi-modal fashion. Opioids may play an important role, but they make up only a portion of available invasive and noninvasive management. We present a case of a patient who was serendipitously diagnosed with malignant carcinoid tumor after endoscopic polypectomy and Whipple procedure for pancreatic cancer. Her abdominal pain was refractory to opioid and non-opioid medications, and therefore we proposed radiofrequency ablation (RFA) of the splanchnic nerve and superior hypogastric plexus. This technique was preceded by a diagnostic block of these nerves. She experienced significant pain relief and an improved quality of life, and was able to stop all opioid medications. The preferred approach to pain management is a multi-modal one. This includes physical therapy, pharmacological management, and minimally invasive procedures such as RFA. The medical team must consider all available pain management modalities to provide the patient with proper care of such debilitating pain as that described in our case presentation. A systematic approach is important, as demonstrated by our team by first performing diagnostic blocks of the superior hypogastric plexus and splanchnic nerve to test the likelihood of a successful RFA. Only after achieving favorable results, we decided to proceed with RFA treatment of those same nerves. Ultimately, our RFA technique provided significant pain relief for our patient and she did not require any opioid medications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Noor et al.)

Charcot spine arthropathy (CSA), a result of reduced afferent innervation, is an occurrence of Charcot joint, a progressive, degenerative disorder in vertebral joints, related mostly to spinal cord injury. The repeated microtrauma is a result of a lack of muscle protection and destroys cartilage, ligaments, and disc spaces, leading to vertebrae destruction, joint instability, subluxation, and dislocation. Joint destruction compresses nerve roots, resulting in pain, paresthesia, sensory loss, dysautonomia, and spasticity. CSA presents with back pain, spinal deformity and instability, and audible spine noises during movement. Autonomic dysfunction includes bowel and bladder dysfunction. It is slowly progressive and usually diagnosed at a late stage, usually, on average, 20 years after the first initial insult. Diagnosis is rarely clinical related to the nature of nonspecific symptoms and requires imaging with computed tomography (CT) and magnetic resonance imaging (MRI). Conservative management focuses on the prevention of fractures and the progression of deformities. This includes bed rest, orthoses, and braces. These could be useful in elderly or frail patients who are not candidates for surgical treatment, or in minimally symptomatic patients, such as patients with spontaneous fusion leading to a stable spine. Symptomatic treatment is offered for autonomic dysfunction, such as anticholinergics for bladder control. Most patients require surgical treatment. Spinal fusion is achieved with open, minimally-open (MOA) or minimally-invasive (MIS) approaches. The gold standard is open circumferential fusion; data is lacking to determine the superiority of open or MIS approaches. Patients usually improve after surgery; however, the rarity of the condition makes it difficult to estimate outcomes. This is a review of the latest and seminal literature about the treatment and chronic management of Charcot spine. The review includes the background of the syndrome, clinical presentation, and diagnosis, and compares the different treatment options that are currently available., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

BACKGROUND Icosapent ethyl, a form of eicosapentaenoic acid with anti-inflammatory activity, has been approved as an adjunctive treatment with statins in patients with hypertriglyceridemia. Icosapent ethyl is currently undergoing clinical trials to determine its anti-inflammatory effects in patients with coronavirus disease 2019 (COVID-19). This report describes 3 intensive care unit (ICU) patients with moderate to severe COVID-19 pneumonia treated with icosapent ethyl as part of their supportive care who had favorable outcomes. CASE REPORT Case 1 was a 75-year-old man with a past medical history of hyperlipidemia, hypertension, type 2 diabetes mellitus, obesity, and benign prostatic hyperplasia. Case 2 was a 23-year old man with a past medical history of type 2 diabetes mellitus and obesity. Case 3 was a 24-year old man with a history of autism. All cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were confirmed from a nasopharyngeal swab using the Becton Dickinson nasopharyngeal reverse-transcription polymerase chain reaction. All patients in these cases were treated with a course of 2 g of icosapent ethyl twice a day by nasogastric tube. CONCLUSIONS This report of 3 cases describes the use of icosapent ethyl as a component of supportive treatments in ICU patients with moderate to severe COVID-19 pneumonia. However, as of yet there are no evidence-based treatments for SARS-CoV-2 infection from controlled clinical trials. The outcomes of ongoing clinical trials are awaited to determine whether icosapent ethyl has anti-inflammatory effects in patients with SARS-CoV-2 infection and which patients might benefit from the use of this adjunctive treatment.

Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as "off episodes", are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing "off episodes". It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.

The use of regional anesthetic techniques in the peri-operative period has increased as a means to improve analgesia and patient outcomes. Traditionally, various local anesthetics are used and addition of adjuncts such as epinephrine, clonidine, and dexamethasone has shown to prolong the block effect. There has been ongoing research to support the prolongation of a regional block with the addition of dexamethasone and dexmedetomidine (Dex-Dex), providing analgesia for multiple days. We present a case of a 35-year-old female who underwent an Achilles tendon repair with an adductor/popliteal nerve block. Both dexmedetomidine and dexamethasone were added to the local anesthetic mixture with substantial postoperative analgesic control. The patient also did not require any supplemental opioid medication. This case emphasizes the proposed synergistic effect of dexmedetomidine and dexamethasone when added to the local anesthesia injectate for lower extremity peripheral nerve blocks., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Kassem et al.)

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing-remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

Occipital neuralgia (ON) is unilateral or bilateral neuralgia in the dermatomal nerve distribution of the greater, lesser or third occipital nerves and is a very common presentation of neuropathic pain. ON, although common and well defined, is still a poorly understood pain syndrome. It often requires invasive treatment for long term and significant pain alleviation; however, the evidence supporting different options is still limited. Several minimally invasive techniques have proven to be efficacious and safe, and the selection depends mostly on response to nerve blocks, patient choice and provider preference. This is a comprehensive review of the latest and seminal literature available about occipital neuralgia and currently available minimally invasive treatment options. It covers the anatomical and physiologic biology at the base of neuralgia, the presentation and diagnostic process. It then reviews the available literature to provide description and comparison of the available methods for alleviation.

Postoperative nausea and vomiting (PONV) is an undesirable outcome that occurs in up to 30% of patients. Over the years, the cost of treating PONV has decreased due to the availability of cheaper yet effective antiemetics. Limiting PONV development benefits the hospital system as studies have shown that prevention is associated with shorter post-anesthesia care unit (PACU) stays as well as decreased supply costs and staffing burden. The financial burden for prophylaxis against PONV has been shown to be less than what patients are willing to pay to prevent the development of PONV. Studies have also shown that prevention of initial development of PONV limits readmission rates, which is beneficial to both the patient and the hospital. Owing to recent economic analysis and reductions in antiemetic prices, the patient's preference for comfort, the hospital's commitment to providing the best care, and the system's desire for fiscal prudence are aligned. This culminates in recommending PONV prophylaxis for all patients undergoing anesthesia., Competing Interests: Declaration of Competing Interest Dr. Urman received consulting fees from Heron and Takeda pharma and research funding from Acacia pharmaceuticals, Medtronic and Merck. Other authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose of Review: The number and the complexity of procedures taking place at ambulatory surgery centers is steadily increasing. The rate at which medically complex patients, including those with baseline neurocognitive disorders, are undergoing ambulatory procedures is seeing a concurrent rise. Given the significant physical and psychological stress associated with surgery even in the ambulatory setting, it is essential to evaluate the ability of a patient to acclimate to stressful triggers in order to assess risk of subpar medical outcomes and increased mortality. In this review, we discuss recent advances in the assessment of both cognition and frailty and describe the implementation of these tools in the ambulatory surgery setting., Recent Findings: Recent Society for Perioperative Assessment and Quality Improvement (SPAQI) recommendations for evaluating at-risk patients focus on a two-pronged approach that encompasses screening for both impaired cognition and frailty. Screening should ideally occur as early as possible, but tools such as the Mini-Cog examination and FRAIL Questionnaire are efficient and effective even when used the day of surgery in high-risk patients., Summary: The recognition of at-risk patients using standardized screening and the use of this assessment to guide perioperative monitoring and interventions is essential for optimizing outcomes for the complex ambulatory surgery patient.

Acupuncture is a form of traditional Chinese medicine that is performed by placing needles or pressure in specific locations on a patient's skin to achieve a therapeutic effect. Although used to treat a variety of disorders, one of the most common applications of acupuncture is to treat chronic pain, especially headache and migraine pain. Migraines are difficult to treat, and pharmacotherapies are often the first line of treatment, although these options have many unwanted side effects, such as exacerbation of headache pain in those with chronic migraine. Many complimentary and integrative therapies are available to treat migraine (including nutraceuticals, yoga, tai chi, and biofeedback), among which acupuncture as a treatment is gaining increasing attention. In this review, we provide an overview of the current understanding of both acupuncture and migraine and of current research investigating the effectiveness of acupuncture in treating migraine and chronic migraine.

It is estimated that one-third of oncologic patients in the USA do not receive analgesia proportional to or adequate for the intensity of their pain. A mechanism-based approach to oncologic pain therapy is critical to ensure that analgesia regimens are individualized and effective. Since the mechanisms that lead to cancer pain are complex, healthcare providers must be willing to elicit and recognize the symptoms of each individual patient since these factors influence both the experience of pain and response to treatment. This process is centered on the use of detailed history in order to understand symptom expression in the context of primary tumor diagnosis and progression, history of cancer pain, psychological distress, sleep disturbances, cognitive function, and addictive behavior. Incorporating all of these factors into the assessment of a patient's pain condition can facilitate management decisions and help predict patient response to treatment.

Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000-10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.

Purpose of Review: This is a comprehensive review of the current literature on the usage of galcanezumab for migraine treatment. It reviews the biology, pathophysiology, epidemiology, diagnosis, and conventional treatment of migraines, then compares the literature available for galcanezumab with historical treatment options., Recent Findings: Migraine is a common headache disorder and constitutes a significant source of distress from both a personal and societal perspective. Conventional treatment includes abortive and preventive treatment. Treatment options are limited and may be only partially or minimally effective in some of the population. Recent evidence points to metabolic changes in the brain as possible causes of migraine, via reduced available energy or a spiking need for it, resulting in a relative insufficiency. This leads to trigeminocervical complex (TCC) activation and a headache episode, modulated by calcitonin gene-related peptide (CGRP). Galcanezumab (Emgality) is a monoclonal antibody targeting CGRP that is given in a monthly injection for the prevention of migraines. Its safety was previously shown in phase 1 and 2 trials, and recent phase 3 trials showed efficacy, with up to 50% reduction in monthly migraine days and improved functional capacity in migraineurs. Studies show that the drug is well tolerated and safe. Migraine headache is a common neurological syndrome that causes great pain and suffering. Treatment options today are limited. Galcanezumab does not prevent migraines, but it is effective in decreasing their frequency and length. It is also much better tolerated than the currently existing therapies. While it is unlikely to provide monotherapy for migraines, it is a novel therapy that may be added for cases of severe or frequent migraines.

Context: Neuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system that are commonly involved in headache pathophysiology, such as the vagus nerve (VNS), occipital nerves, or sphenopalatine ganglion (SPG) for stimulation. Pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, NSAIDs, beta-blockers, TCAs, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. Peripheral neuromodulation has gained popularity and FDA approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. Early trials found FDA approved neurostimulatory implant devices, including Cephaly and SpringTMS , improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity., Evidence Acquisition: This was a narrative review. The sources for this review are as follows: Searching on PubMed, Google Scholar, Medline, and ScienceDirect from 1990 - 2019 using keywords: Peripheral Neuromodulation, Headache, vagus nerve, occipital nerves, sphenopalatine ganglion., Results: The first noninvasive neurostimulator device approved for migraine treatment was the Cefaly device, an external trigeminal nerve stimulation device (e-TNS) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. The second noninvasive neurostimulation device receiving FDA approval was the single-pulse transcranial magnetic stimulator, SpringTMS , positioned at the occiput to treat migraine with aura. GammaCore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (CH) and migraine. Several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. The Scion device is a caloric vestibular stimulator (CVS) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. The pulsante SPG Microstimulator is a patient-controlled device implanted in the patient's upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. The occipital nerve stimulator (ONS) is an invasive neuromodulation device for headache treatment that consists of an implanted pulse generator on the chest wall connected to a subcutaneous lead with 4 - 8 electrodes that is tunneled the occiput., Conclusions: The aim of this review is to provide a comprehensive overview of the efficacy, preliminary outcomes, and limitations of neurostimulatory implants available for use in the US and those pending further development., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2020, Author(s).)

Neurological disorders, including Parkinson's disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson's patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients. A treatment plan can be devised that may include dopaminergic agents, acetaminophen, NSAIDs, opioids, antidepressants, physical therapies, DBS and other options discussed in this review. A thorough assessment of patient history and physical examination should be made in patients with PD so chronic pain may be managed effectively.

Acute pancreatitis is the most common gastrointestinal pathology that warrants hospital admission, with an estimated incidence of 13-45/100,000 annually in the US. The overall mortality is low but is significantly increased in 15-25% of patients that develop severe disease, likely secondary to an increase in inflammation and an exaggerated response, sometimes referred to as a cytokine storm. Management is largely supportive, and no specific cure exists to hasten recovery. Icosapent Ethyl (IPE, Vascepa®) is an omega-3 fatty acid derivative that is indicated for the treatment of hypertriglyceridemia and has been shown to improve mortality from cardiovascular causes, likely through an anti-inflammatory mechanism. We report here a case of very severe, abrupt acute alcoholic pancreatitis in a 31-year-old male, requiring intensive care unit admission, ventilation, and support with multiple vasoactive medications. Shortly after the initiation of IPE, the patient started to improve and ultimately made a complete recovery. His initially greatly elevated inflammatory markers downtrended quickly under IPE treatment and he followed with a remarkable clinical recovery. Several previous studies, such as the Patients With Persistent High Triglyceride Levels (≥ 200 mg/dL and < 500 mg/dL) Despite Statin Therapy (ANCHOR; NCT01047501) and the Multi-Center, PlAcebo-Controlled, Randomized, Double-BlINd, 12-week study with an open-label Extension (MARINE; NCT01047683), provided evidence of the anti-inflammatory activity of IPE. In our case, we provide the first evidence to support its use as a direct anti-inflammatory in severe disease. With the absence of direct therapy and the significant mortality from severe acute pancreatitis, IPE can be a breakthrough therapy. Its treatment is not limited to pancreatitis only, and it may also be beneficial in other cases of severe inflammation. Though anecdotal, this case provides evidence to support further study of IPE in states of exaggerated inflammation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Berger et al.)

Objective: Multiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices., Design: Cross-sectional analysis of the effect of MVM consumption on self-reported overall health and clinically measurable health outcomes., Participants: Adult MVM users and non-users from the 2012 National Health Interview Survey (n=21 603)., Primary and Secondary Outcome Measures: Five psychological, physical, and functional health outcomes: (1) self-rated health status, (2) needing help with routine needs, (3) history of 10 chronic diseases, (4) presence of 19 health conditions in the past 12 months, and (5) Kessler 6-Item (K6) Psychological Distress Scale to measure non-specific psychological distress in the past month., Results: Among 4933 adult MVM users and 16 670 adult non-users, MVM users self-reported 30% better overall health than non-users (adjusted OR 1.31; 95% CI 1.17 to 1.46; false discovery rate adjusted p<0.001). There were no differences between MVM users and non-users in history of 10 chronic diseases, number of present health conditions, severity of current psychological distress on the K6 Scale and rates of needing help with daily activities. No effect modification was observed after stratification by sex, education, and race., Conclusions: MVM users self-reported better overall health despite no apparent differences in clinically measurable health outcomes. These results suggest that widespread use of multivitamins in adults may be a result of individuals' positive expectation that multivitamin use leads to better health outcomes or a self-selection bias in which MVM users intrinsically harbour more positive views regarding their health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)