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Introduction The multifaceted clinical presentation of fibromyalgia (FM) supports the modern understanding of the disorder as a more global condition than one simply affecting pain sensation. The main pharmacologic therapies used clinically include anti-epileptics and anti-depressants. Conservative treatment options include exercise, myofascial release, psychotherapy, and nutrient supplementation. Methods Narrative review. Results Nutrient supplementation is a broadly investigated treatment modality as numerous deficiencies have been linked to FM. Additionally, a proposed link between gut microbiome patterns and chronic pain syndromes has led to studies investigating probiotics as a possible treatment. Despite positive results, much of the current evidence regarding this topic is of poor quality, with variable study designs, limited sample sizes, and lack of control groups. Conclusions The etiology of FM is complex, and has shown to be multi-factorial with genetics and environmental exposures lending influence into its development. Preliminary results are promising, however, much of the existing evidence regarding diet supplementation is of poor quality. Further, more robust studies are needed to fully elucidate the potential of this alternative therapeutic option.

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.

Background: Patients who are diagnosed with dextrocardia, a rare congenital heart condition in which the heart points toward the right side of the chest, need their specific situs classification (eg, solitus, inversus, ambiguus) ascertained to optimize their care and outcomes. In this report, we discuss the perioperative anesthetic management of a patient presenting with dextrocardia. Case Report: A 44-year-old African American female with a history of hypertension, hyperlipidemia, gastroesophageal reflux disease, and diabetes mellitus type 2 was admitted for shortness of breath, dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea. The patient had been diagnosed with dextrocardia in 2003 at an outside hospital and was asymptomatic prior to this presentation. Chest x-ray revealed bilateral perihilar vascular congestion with bibasilar atelectasis and suspected small bilateral pleural effusions consistent with new-onset congestive heart failure. Preoperative 2-dimensional transthoracic echocardiography revealed an ostium secundum–type atrial septal defect (ASD) with mild left-to-right atrial shunting. The patient's ASD was repaired using a pericardial patch. Conclusion: The anesthetic management of patients presenting with dextrocardia is complex. Preoperative cardiac transthoracic echocardiography can identify cardiac lesions or aberrant anatomy associated with dextrocardia. Proper placement of electrocardiogram electrodes is necessary to avoid false-positive results for perioperative ischemia. Central line access must be adjusted to anatomic variations. Clinicians should have high suspicion for associated pulmonary hypertension and should limit sedatives preoperatively to minimize the cardiovascular effects of hypoxia and/or hypercarbia on the pulmonary vasculature. Finally, high clinical suspicion for respiratory complications should be maintained, as dextrocardia has been associated with respiratory complications secondary to primary ciliary dyskinesia in approximately 25% of patients.

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.

Parkinson’s Disease (PD) is a common neurodegenerative disorder and the leading cause of disability. It causes significant morbidity and disability through a plethora of symptoms, including movement disorders, sleep disturbances, and cognitive and psychiatric symptoms. The traditional pathogenesis theory of PD involves the loss of dopaminergic neurons in the substantia nigra (SN). Classically, treatment is pursued with an assortment of medications that are directed at overcoming this deficiency with levodopa being central to most treatment plans. Patients taking levodopa tend to experience “off episodes” with decreasing medication levels, causing large fluctuations in their symptoms. These off episodes are disturbing and a source of morbidity for these patients. Opicapone is a novel, peripherally acting Catechol-O-methyl transferase (COMT) inhibitor that is used as adjunctive therapy to carbidopa/levodopa for treatment and prevention of “off episodes.” It has been approved for use as an adjunct to levodopa since 2016 in Europe and has recently (April 2020) gained FDA approval for use in the USA. By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Several clinical studies demonstrated significant improvement in treatment efficacy and reduction in duration of “off episodes.” The main side effect demonstrated was dyskinesia, mostly with the 100mg dose, which is higher than the approved, effective dose of 50mg. Post-marketing surveillance and analysis are required to further elucidate its safety profile and contribute to patient selection. This paper reviews the seminal and latest evidence in the treatment of PD “off episodes” with the novel drug Opicapone, including efficacy, safety, and clinical indications.

Background The Special Olympics Pennsylvania Summer Games attract over 2000 athletes each year. Volunteer medical staff ensures their safety throughout this period. However, few studies have examined the incidence of orthopedic injury and sickness in this group, especially with a large sample. Objective Identify the incidence of orthopedic injury and Illness at the Special Olympics Pennsylvania Summer Games based on demographic criteria and identify the incidence of transports required for advanced care. Methods Data was collected from logs provided by Special Olympics Pennsylvania. The data were analyzed and stratified by gender, age, sport, and type of encounter. We summarized the data and compared it to data from other years and the average. Results An average of 1971 athletes competed annually. On average, 10% (N=144) of competitors required medical care. Males comprised 58.2% (N = 837) of encounters, females 33.6% (N = 483), and in 8.1% (N = 117) of encounters gender was not identified/recorded. The mean age of participants was 29 years of age (range from 10 to 83). 56.6% (N= 813) of encounters required first aid management only. Injuries made up 31.7% (N = 455) of total encounters, and 11.8% (N=169) of encounters were classified as illnesses. Basketball was the sport with the most injuries, 49.5% (N = 711). An average of 9.8 transports was required annually. Conclusions Special Olympics athletes suffer the same injuries as regular athletes, but they are also prone to various medical disorders that regular athletes are not.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes significant functional impairment and is related to altered stress response and reinforced learned fear behavior. PTSD has been found to impact three functional networks in the brain: default mode, executive control, and salience. The executive control network includes the dorsolateral prefrontal cortex (DLPFC) and lateral PPC. The salience network involves the anterior cingulate cortex, anterior insula, and amygdala. This latter network has been found to have increased functional connectivity in PTSD. Transcranial Magnetic Stimulation (TMS) is a technique used in treating PTSD and involves stimulating specific portions of the brain through electromagnetic induction. Currently, high-frequency TMS applied to the left dorsolateral prefrontal cortex (DLPFC) is approved for use in treating major depressive disorder (MDD) in patients who have failed at least one medication trial. In current studies, high-frequency stimulation has been shown to be more effective in PTSD rating scales posttreatment than low-frequency stimulation. The most common side effect is headache and scalp pain treated by mild analgesics. Seizures are a rare side effect and are usually due to predisposing factors. Studies have been done to assess the overall efficacy of TMS. However, results have been conflicting, and sample sizes were small. More research should be done with larger sample sizes to test the efficacy of TMS in the treatment of PTSD. Overall, TMS is a relatively safe treatment. Currently, the only FDA- approved to treat refractory depression, but with the potential to treat many other conditions.

Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by strong emotions such as laughing. It is also associated with many other disorders, including psychiatric disorders, neurologic illnesses, and medication side effects. Common causes of delayed and incorrect diagnoses of these conditions include lack of physician familiarity with narcolepsy symptoms and comorbidities which mask narcolepsy signs and symptoms. Current pharmacologic therapies include Modafinil and Armodafinil for EDS and sodium oxybate for cataplexy. This review discusses the epidemiology, pathophysiology, risk factors, presentation, treatment of narcolepsy, and the role of a novel drug, Pitolisant, in the treatment of EDS in adults with narcolepsy. Pitolisant is a histamine-3 receptor (H3R), competitive antagonist, and inverse agonist, acting through the histamine system to regulate wakefulness. It is a novel drug approved in August 2019 by the FDA, is not classified as a controlled substance, and is approved for use in Europe and the United States to treat EDS and cataplexy in narcolepsy. Recent phase II and III trials have shown that Pitolisant helps reduce the ESS score and cataplexy. In summary, based on comparative studies, recent evidence has shown that Pitolisant is non-inferior to Modafinil in the treatment of EDS but superior to Modafinil in reducing cataplexy.

Epilepsy is a complex neurological condition with numerous etiologies and treatment options. In a subset of these patients, sudden unexpected death can occur, and to date, there are numerous explanations as to the pathophysiological mechanisms and how to mitigate these catastrophic outcomes. Approximately 2.3 million Americans have epilepsy, and nearly 150,000 people develop the condition each year. Sudden unexpected death in epilepsy (SUDEP) accounts for 2–18% of all epilepsy-related deaths and this is equivalent to one death in 1000 person-years of diagnosed epilepsy. It is more common in young adults aged 20–45. Seizures in the past year; the absence of terminal remission in the last five years; increased seizure frequency, particularly GTCS; and nocturnal seizures are the most potent modifiable risk factors for SUDEP. Patients not receiving any antiepileptic drug therapy are at higher risk of SUDEP. Patient education on medication compliance; care plans for seizure clusters (rescue medicines); epilepsy self-management programs; and lifestyle changes to avoid seizure-triggering factors, including avoiding excessive alcohol use and sleep deprivation, should be provided by health care providers. Continued research into SUDEP will hopefully lead to effective interventions to minimize occurrences. At present, aggressive control of epilepsy and enhanced education for individuals and the public are the most effective weapons for combating SUDEP. This narrative review focuses on updated information related to SUDEP epidemiology; pathophysiology; risk factor treatment options; and finally, a discussion of important clinical studies. We seek to encourage clinicians who care for patients with epilepsy to be aggressive in controlling seizure activity and diligent in their review of risk factors and education of patients and their families about SUDEP.

Purpose The purpose of this study is to determine if using a combination of dexamethasone and dexmedetomidine (Dex-Dex) in a single-shot perineural local anesthestic provides an increased duration of pain relief and reduced consumption of opioids for patients undergoing shoulder surgery. Patients and methods This is a retrospective trial of adult patients without major comorbidities undergoing elective, upper arm orthopedic procedures with regional nerve block for post-operative analgesia. Patients underwent nerve block with either 0.5% ropivacaine or 0.2% ropivacaine with 5mg dexamethasone and 25mg dexmedetomidine (“dex-dex”). Patients were assessed in 1-week intervals for two weeks for duration of block analgesia, pain scores, and opioid use. Results 31 patients were included, 12 controls and 19 in the dex-dex group. These patients underwent one of arthroscopic rotator cuff repair, reverse total shoulder repair or repair of humerus fractures. Dex-dex blocks provided significantly longer analgesia (median block time 3.5 versus 1.5 days, p Conclusion Preoperative single-shot interscalene nerve blocks with preservative-free dexamethasone and dexmedetomidine added as adjuvants to ropivicaine provide approximately two additional days of benefit versus ropivicaine alone. Additionally, postoperative opioid consumption is reduced.

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.

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.

Hospitals face catastrophic financial challenges in light of the coronavirus disease 2019 (COVID-19) pandemic. Acute shortages in materials such as masks, ventilators, intensive care unit capacity, and personal protective equipment (PPE) are a significant concern. The future success of supply chain management involves increasing the transparency of where our raw materials are sourced, diversifying of our product resources, and improving our technology that is able to predict potential shortages. It is also important to develop a proactive budgeting strategy to meet supply demands through early designation of dependable roles to support organizations and through the education of healthcare staff. In this paper, we discuss supply chain management, governance and financing, emergency protocols, including emergency procurement and supply chain, supply chain gaps and how to address them, and the importance of communication in the times of crisis.

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. Summary 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.

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.

Myofascial Pain Syndrome (MPS) is a regional pain disorder that affects every age-group and is characterized by the presence of trigger points (TrPs) within muscles or fascia. MPS is typically diagnosed via physical exam, and the general agreement for diagnostic criteria includes the presence of TrPs, pain upon palpation, a referred pain pattern, and a local twitch response. The prevalence of MPS among patients presenting to medical clinics due to pain ranges anywhere from 30 to 93%. This may be due to the lack of clear criteria and guidelines in diagnosing MPS. Despite the prevalence of MPS, its pathophysiology remains incompletely understood. There are many different ways to manage and treat MPS. Some include exercise, TrP injections, medications, and other alternative therapies. More research is needed to form uniformly-accepted diagnostic criteria and treatments.

Pharmacogenomics is the study of how genetic differences between individuals affect pharmacokinetics and pharmacodynamics. These differences are apparent to clinicians when taking into account the wide range of responses to medications given in clinical practice. A review of literature involving pharmacogenomics and pain management was performed. The implementation of preoperative pharmacogenomics will allow us to better care for our patients by delivering personalized, safer medicine. This review describes the current state of pharmacogenomics as it relates to many aspects of clinical practice and how clinicians can use these tools to improve patient outcomes.

Lateral epicondylitis (LE), also known as tennis elbow, is the most common cause of elbow pain in adults, with approximately 1-3% of the general population being afflicted. Although the condition is usually self-limiting, pain can be a major hindrance, limiting daily activity and the work capacity of patients. As a result, many treatment options have become available with the aim to shorten the duration of the disease and increase the quality of life. Steroid injections, NSAIDs, topical creams, platelet-rich plasma, physical therapy, and kinesiotaping are considered conservative treatments, while surgical options are last-resort treatments reserved for refractory LE. In this review, we will provide a brief summary of LE and focus on addressing conservative and minimally invasive interventional options for the treatment of LE.

Introduction Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. Methods A literature review of folic acid supplementation for various disease states including cardiovascular disease was conducted. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Results In this review, we discuss the biochemistry of folic acid, Hcy biosynthesis, Hcy and hydrogen sulfide bioavailability, pathogenesis of hyperhomocysteinemia and its role as a risk factor for disease, and treatment studies with folic acid supplementation in disease states. Conclusion Folic acid supplementation should be recommended to any patient who has an elevated Hcy level, and this level should be measured and treated at an early age, since folic acid is easily obtained and may likely reduce vascular disease and other deleterious pathologic processes in high-risk populations.

Platelet diseases and dysfunction are taught early in medical school to all future physicians. Understanding of the coagulation cascade and hemostatic mechanisms has allowed for targeted pharmacological therapies that have been significantly impactful in clinical practice. Platelets are an early participant in hemostasis physiologically and under pathophysiological states. A review of literature involving platelet disfunction. Various presentations of platelet diseases and dysfunction challenge clinicians and require a firm understanding of normal platelet function, drugs that mediate or modulate platelet effectiveness, and nonpharmacologic etiologies of platelet diseases and dysfunction with corresponding best practice treatment approaches. This review summarizes normal and abnormal states associated with platelets and treatment strategies.

Important elements of the preoperative assessment that should be addressed for the older adult population include frailty, comorbidities, nutritional status, cognition, and medications. Frailty has emerged as a plausible predictor of adverse outcomes after surgery. It is present in older patients and is characterized by multisystem physiologic decline, increased vulnerability to stressors, and adverse clinical outcomes. Preoperative preparation may include a prehabilitation program, which aims to address nutritional insufficiencies, modify chronic polypharmacy, and enhance physical and respiratory conditions prior to hospital admission. Special considerations are taken for particularly high-risk patients, where the approach to prehabilitation can address specific, individual risk factors. Identifying patients who are nutritionally deficient allows practitioners to intervene preoperatively to optimize their nutritional status, and different strategies are available, such as immunonutrition. Previous studies have shown an association between increased frailty and the risk of postoperative complications, morbidity, hospital length of stay, and 30-day and long-term mortality following general surgical procedures. Evidence from numerous studies suggests a potential benefit of including a standard assessment of frailty as part of the preoperative workup of older adult patients. Studies addressing validated frailty assessments and the quantification of their predictive capabilities in various surgeries are warranted.

The management principles of non-obstetric surgery during pregnancy are important concepts for all health care providers to be cognizant of. The goals of non-obstetric surgery are to ensure maternal safety, maintain the pregnancy, and ensure fetal well-being. In this regard, organogenesis occurs roughly between days 7-57 and thus, certain medications have a higher incidence of fetal teratogenicity in this first trimester. Some examples of common surgeries performed urgently or emergently include appendectomies, ovarian detorsions, bowel obstruction, trauma, and cholecystectomies. The choice of anesthetic technique and the selection of appropriate anesthetic drugs should be guided by indication for surgery, the nature of the surgery, and the site of the surgical procedure. Many of the concerns for any patients undergoing urgent or emergent surgery must be considered by anesthesia providers along with steps to ensure the fetus has the best outcome.

Preoperative laboratory testing is often necessary and can be invaluable for diagnosis, assessment, and treatment. However, performing routine laboratory tests for patients who are considered otherwise healthy is not usually beneficial and is costly. It is estimated that $18 billion (U.S.) is spent annually on preoperative testing, although how much is wasteful remains unknown. Ideally, a targeted and comprehensive patient history and physical exam should largely determine whether preprocedure laboratory studies should be obtained. Healthcare providers, primarily anesthesiologists, should remain cost-conscious when ordering specific laboratory or imaging tests prior to surgery based on available literature. We review the overall evidence and key points from the Choosing Wisely guidelines, the identification of potential wasteful practices, possible harms of testing, and key clinical findings associated with preoperative laboratory testing.

Postoperative pulmonary complications (PPCs), estimated between 2.0% and 5.6% in the general surgical population and 20-70% for upper abdominal and thoracic surgeries, are a significant factor leading to poor patient outcomes. Efforts to decrease the incidence of PPCs such as bronchospasm, atelectasis, exacerbations of underlying chronic lung conditions, infections (bronchitis and pneumonia), prolonged mechanical ventilation, and respiratory failure, begins with a detailed preoperative risk evaluation. There are several available preoperative tests to estimate the risk of PPCs. However, the value of some of these studies to estimate PPCs remains controversial and is still debated. In this review, the preoperative risk assessment of PPCs is examined along with preoperative pulmonary tests to estimate risk, intraoperative, and procedure-associated risk factors for PPCs, and perioperative strategies to decrease PPCs. The importance of minimizing these events is reflected in the fact that nearly 25% of postoperative deaths occurring in the first week after surgery are associated with PPCs. This review provides important information to help clinical anesthesiologists to recognize potential risks for pulmonary complications and allows strategies to create an appropriate perioperative plan for patients.

Purpose of Review This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the background, biology, diagnosis and conventional treatment for PHN, and then introduces and compares the recent evidence for the use of topical bupivacaine. Recent Findings PHN is defined by pain lasting 90 days or more after the initial presentation of herpes zoster (“Shingles”, HZ) rash and is the most common complication of this disease. A product of re-activation of the Varicella-Zoster virus (VZV), HZ is diagnosed more than 1 million times annually in the United States. Approximately 20% of patients with HZ will experience PHN and will continue to suffer intermittent neuropathic symptoms, including itching and pain, that is sharp, stabbing, throbbing or burning, with the pain localized to the site of their original rash. This long-lasting pain compares with the severity of long-standing rheumatics and osteo-arthritis and is accompanied by severe allodynia causing significant suffering, and a financial burden that is manifested in both healthcare costs and loss of quality-adjusted life years. Prevention of PHN may be achieved with the Zoster vaccine, although there is still a large segment of unvaccinated population. Moreover, the Zoster vaccine is not always effective for prevention. Current treatment includes medical (systemic tricyclic antidepressants, anticonvulsants and opioids, topical lidocaine and capsaicin) and interventional (subcutaneous Botox injections, nerve blocks and nerve stimulation) therapies. These therapies are not always effective, and each carries their own profile of side effects and risks. Moreover, up to 50% of patients with PHN are refractory to management. Recent evidence is emerging to support the use of topical local anesthetics for the treatment of PHN. Two small studies recently found topical lidocaine spray to be effective in treating paroxysmal pain attacks associated with PHN. Bupivacaine is a longer-lasting local anesthetic, and a film-forming formulation allows easy and durable application to the affected skin. Recent studies show that topical film-forming bupivacaine is safe and as effective as lidocaine for the treatment of PHN. Summary PHN is an important though common complication of HZ and can cause long-lasting pain and disability. Current treatment for PNH is limited by efficacy and safety profiles of individual therapies. Recent evidence points to topical local anesthetics as an effective and safe alternative to conventional therapy. Film-forming bupivacaine may offer a durable and safe option for this otherwise difficult to treat syndrome.

Purpose This is a comprehensive review of the current literature on central neuropathic pain mechanisms that is secondary to spinal cord injury. It reviews recent and seminal findings on the pathophysiology, diagnosis, and treatment and compares treatment options and recommendations. Recent Findings Neuropathic pain (NP) is a common complication of spinal cord injury (SCI). Chronicity of NP is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve–glia cross talk have also been implicated. Conventional treatment is medical and has had limited success. Recent studies have made headway in identifying novel biomarkers, including microRNA and psychosocial attributes that can predict progress from SCI to chronic NP (CNP). Recent advances have provided evidence of efficacy for two promising drugs. Baclofen was able to provide good, long-lasting pain relief. Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase (CPK) elevations, and further studies are required to define its safety profile. Non-medical interventions include brain sensitization and biofeedback techniques. These methods have recently had encouraging results, albeit preliminary. Case reports of non-conventional techniques, such as hypnosis, were also reported. Summary CNP is a common complication of SCI and is a prevalent disorder with significant morbidity and disability. Conventional medical treatment is limited in efficacy. Recent studies identified baclofen and ziconotide as possible new therapies, alongside non-medical interventions. Further research into the pathophysiology is required to identify further therapy candidates. A multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve therapeutic effects in this difficult to treat syndrome.

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

The objectives of this review are to describe the acquired and hereditary causes of methemoglobinemia, to recommend the most sensitive diagnostic tests, and to enable critical care clinicians to rapidly detect and treat methemoglobinemia. To meet these objectives, Internet search engines were queried with the keywords to select articles for review that included case reports, case series, observational, longitudinal, and surveillance studies. The most common causes of methemoglobinemia include oxidizing reactions to cocaine-derived anesthetics, such as benzocaine and lidocaine, to antibiotics, such as dapsone and other sulfonamides, and to gases, such as nitric oxide. Additionally, CO-oximetry is superior to standard pulse oximetry in detecting methemoglobinemia. Finally, effective treatments for methemoglobinemia include intravenous administration of methylene blue, ascorbic acid, and riboflavin. In this manuscript we will discuss methemoglobinemia, how it occurs, and how to treat it.

Surgeries and chronic pain states of the upper extremity are quite common and pose unique challenges for the clinical anesthesiology and pain specialists. Most innervation of the upper extremity involves the brachial plexus. The four most common brachial plexus blocks performed in clinical setting include the interscalene, supraclavicular, infraclavicular, and axillary brachial plexus blocks. These blocks are most commonly performed with the use of ultrasound-guided techniques, whereby analgesia is achieved by anesthetizing the brachial plexus at different levels such as the roots, divisions, cords, and branches. Additional regional anesthetic techniques for upper extremity surgery include wrist, intercostobrachial, and digital nerve blocks, which are most frequently performed using landmark anatomical techniques. This review provides a comprehensive summary of each of these blocks including anatomy, best practice techniques, and potential complications.

Kratom, or Mitragyna, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties. It is commonly consumed by preparing the leaves into decoction or tea, or by grinding them into a powder. Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant properties, which together raise potential concern for dependence and addiction. Moreover, growing evidence suggests that the prevalence of kratom use is increasing in many parts of the world, raising important considerations for healthcare providers. This manuscript will discuss the most current epidemiology, pharmacology, toxicity, and management related to kratom, while seeking to provide a contemporary perspective on the issue and its role in the greater context of the opioid epidemic.

When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.

The potential for cancer cells to grow and to metastasize depends on complex interactions between inflammatory signals and pathways, immune cells, and elements of the stromal tissue in which they invade. Related to the nature of many cancers, the probability of recurrence can potentially be quite high for some patients. Immunology, lifestyle modifications, timing of disease, genetics, age, gender, and race are only a handful of ways the likelihood of cancer recurrence can be influenced. The quantity, or density, of certain immunological cells or factors, plays a role in the propagation of cancer cells. Opioids are often used in cancer patients for acute postoperative and chronic pain management. While they can produce significant pain relief, the type of analgesic utilized is important, as it may influence cancer propagation. In this regard, certain opioids have been found to increase T regulatory cells while suppressing NK cell function. Morphine may promote tumor neovascularization and expansion. Fentanyl administration significantly diminishes NK-cells and CD8+ cytotoxic T-cells. In a recent meta-analysis, propofol-based anesthesia improved both cancer-free survival and overall survival. COX inhibitors have also shown promise in persevering cancer immune function, as in literature involving ketorolac and celecoxib. In summary, inhaled anesthesia and opioids may contribute to a pro-tumor metastasis environment also known as cancer propagation; whereas propofol and COX inhibitors may provide a better alternative to reduce cancer recurrence and propagation.

Depression is a leading cause of disability globally, with a prevalence of 3.8% among the whole population, 5% of the adult population, and 5.7% of the elderly population over 60 years of age. There is evidence that depression is linked to certain neurodegenerative diseases, one being Alzheimer’s disease (AD). The efficacy of conventional antidepressants to treat depression in AD is conflicting, especially regarding selective serotonin reuptake inhibitors (SSRIs). A recent systemic review and meta-analysis of 25 randomized controlled trials including fourteen antidepressant medications showed no high efficacy in treating AD patients’ symptoms. However, ketamine, a nonselective N-methyl-D-aspartate (NMDA) receptor antagonist, can mediate a wide range of pharmacological effects, including neuroprotection, anti-inflammatory and anticancer properties, multimodal analgesia, and treatment of depression, suicidal attempts, and status epilepticus. Esketamine, which is ketamine formulated as a nasal spray, was approved by the Federal Drug Administration (FDA) in March 2019 as an adjuvant drug to treat treatment-resistant depression. NMDA receptor antagonists treat AD through offsetting AD-related pathological stimulation of subtypes of glutamate receptors in the central nervous system. Recent clinical findings suggest that ketamine may provide neuroprotection and reduce neuropsychiatric symptoms associated with AD. In the present investigation, we evaluate the potential role of ketamine and its postulated mechanism in AD management.

The treatment of pain, both acute and chronic, has been a focus of medicine for generations. Physicians have tried to develop novel ways to effectively manage pain in surgical and post-surgical settings. One intervention demonstrating efficacy is nerve blocks. Single-injection peripheral nerve blocks (PNBs) are usually preferred over continuous PNBs, since they are not associated with longer lengths of stay. The challenge of single injection PNBs is their length of duration, which at present is a major limitation. Novel preparations of local anesthetics have also been studied, and these new preparations could allow for extended duration of action of anesthetics. An emerging preparation of bupivacaine, exparel, uses a multivesicular liposomal delivery system which releases medication in a steady, controlled manner. Another extended-release local anesthetic, HTX-011, consists of a combination of bupivacaine and low-dose meloxicam. Tetrodotoxin, a naturally occurring reversible site 1 sodium channel toxin derived from pufferfish and shellfish, has shown the potential to block conduction of isolated nerves. Neosaxitoxin is a more potent reversible site 1 sodium channel toxin also found in shellfish that can also block nerve conduction. These novel formulations show great promise in terms of the ability to prolong the duration of single injection PNBs. This field is still currently in development, and more researchers will need to be done to ensure the efficacy and safety of these novel formulations. These formulations could be the future of pain management if ongoing research continues to prove positive effects and low side effect profiles.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Over the past twenty years, research on the disease and its characteristics and treatment options has grown exponentially. The first-line pharmacologic treatment of ADHD is stimulants, which have a response rate of ~70%. With the support of four phase 3 studies involving more than 1,000 pediatric patients 6–17 years old, the FDA has approved the non-stimulant, serotonin-norepinephrine modulating agent (SNMA) viloxazine in an extended-release capsule (viloxazine ER) for treatment of ADHD in children aged 6–17. Viloxazine modulates serotonergic activity as a selective 5-HT22B receptor antagonist and 5-HT2C receptor agonist and moderately inhibits norepinephrine transporter (NET), thus blocking the reuptake of norepinephrine. A phase 2 study by Johnson et al. found that once-daily dosing of viloxazine ER in 200, 300, or 400 mg dosages in children with ADHD for eight weeks resulted in a statistically significant reduction of ADHD-RS-IV total score. A post hoc analysis of data from four phase 3, randomized, placebo-controlled, double-blind, three-arm, clinical trials by Faraone et al. found that early response to viloxazine treatment, defined as a change in ADHD-RS-5 total score at week 2, best predicted the treatment response at week 6 [75% positive predictive power (PPP), 75% sensitivity]. Proper treatment of the symptoms and comorbidities associated with ADHD is crucial in improving a patient's quality of life, cognitive function, and overall therapeutic outcomes. Viloxazine's mechanism of action, clinical effects, and limited side effect profile point toward the drug's relevance in the treatment of ADHD.

The treatment of substance abuse with oxytocin is a novel approach to a challenging public health issue that continues to contribute to a growing economic cost for societies worldwide. Methamphetamine addiction is one of the leading causes of mortality worldwide, and despite advances in understanding the neurobiology of methamphetamine addiction, treatment options are limited. There are no medications that the Food and Drug Administration currently approves for stimulant use disorder. Off-label use of therapies for stimulant misuse include antidepressants, anxiolytics, and milder stimulants as replacement agents. Due to the shortcomings of these attempts to treat a complicated psychiatric disorder, recent attention to oxytocin therapy (OT) has gained momentum in clinical studies as a possible therapy in the context of social stress, social anxiety, social cognition, and psychosis. Oxytocin produces enhanced connectivity between cortical regions. The results from studies in rodents with OT suggest that central neuromodulation of oxytocin may be beneficial across transition states of stimulant dependence and may alleviate intense withdrawal symptoms. Studies of oxytocin in the context of other drugs of abuse, including cocaine, cannabis, and alcohol, also support the potential of oxytocin to treat stimulant use disorder, methamphetamine type. Methamphetamine abuse continues to be a significant cause of distress and dysfunction throughout the world. The effects of oxytocin on methamphetamine use outlined in this review should act as a catalyst for further investigation into the efficacy of treating stimulant use disorder, methamphetamine type with oxytocin in humans. More human-based research should initiate studies involving the long-term efficacy, side effects, and patient selection.

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

Pain, the most common symptom reported among patients in the primary care setting, is complex to manage. Opioids are among the most potent analgesics agents for managing pain. Since the mid-1990s, the number of opioid prescriptions for the management of chronic non-cancer pain (CNCP) has increased by more than 400%, and this increased availability has significantly contributed to opioid diversion, overdose, tolerance, dependence, and addiction. Despite the questionable effectiveness of opioids in managing CNCP and their high rates of side effects, the absence of available alternative medications and their clinical limitations and slower onset of action has led to an overreliance on opioids. Conolidine is an indole alkaloid derived from the bark of the tropical flowering shrub Tabernaemontana divaricate used in traditional Chinese, Ayurvedic, and Thai medicine. Conolidine could represent the beginning of a new era of chronic pain management. It is now being investigated for its effects on the atypical chemokine receptor (ACK3). In a rat model, it was found that a competitor molecule binding to ACKR3 resulted in inhibition of ACKR3’s inhibitory activity, causing an overall increase in opiate receptor activity. Although the identification of conolidine as a potential novel analgesic agent provides an additional avenue to address the opioid crisis and manage CNCP, further studies are necessary to understand its mechanism of action and utility and efficacy in managing CNCP.

Neuropathic pain is a challenge for physicians to treat and often requires a multimodal approach with both pharmacologic and lifestyle interventions. Mirogabalin, a potent, selective ligand of the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs), provides analgesia by inhibiting neurotransmitter release at the presynaptic end of the neuron. Mirogabalin offers more sustained analgesia than its gabapentinoid counterparts in addition to a wider safety margin for adverse events. Recent clinical trials of mirogabalin have demonstrated both efficacy and tolerability of the drug for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia, leading to its approval in Japan. While still not yet FDA approved, mirogabalin is still in its infancy and offers potential into the treatment of neuropathic pain and its associated comorbidities.

Peripheral nerve blocks (PNB) have become standard of care for enhanced recovery pathways after surgery. For brachial plexus delivery of anesthesia, both supraclavicular (SC) and infraclavicular (IC) approaches have been shown to require less supplemental anesthesia, are performed more rapidly, have quicker onset time, and have lower rates of complications than other approaches (axillary, interscalene, etc.). Ultrasound-guidance is commonly utilized to improve outcomes, limit the need for deep sedation or general anesthesia, and reduce procedural complications. Given the SC and IC approaches are the most common approaches for brachial plexus blocks, the differences between the two have been critically evaluated in the present manuscript. Various studies have demonstrated slight favorability towards the IC approach from the standpoint of complications and safety. Two prospective RCTs found a higher incidence of complications in the SC approach – particularly Horner syndrome. The IC method appears to support a greater block distribution as well. Overall, both SC and IC brachial plexus nerve block approaches are the most effective and safe approaches, particularly under ultrasound-guidance. Given the success of the supraclavicular and infraclavicular blocks, these techniques are an important skill set for the anesthesiologist for intraoperative anesthesia and postoperative analgesia.

Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.

Patients diagnosed with cancer often experience pain during their treatment course, making it difficult to care for themselves and continue with their activities of daily living. When cancer is found at later stages, the pain can become severe and constant; reducing their quality of life and significantly affecting mental and physical well-being. Despite opioids being known to provide adequate analgesia for higher pain levels, they are often the reason for under-dosing because of their adverse effects and concern for addiction. There are also patients who do not respond well to opioids because of genetic anomalies or personal preference. Therefore, there is a need for novel non-opioid cancer pain treatments. There are many new cancer pain treatments that are emerging. This manuscript discusses cancer pain, risk factors, epidemiology, guidelines for the treatment of cancer pain, personalization of cancer pain therapy, breakthrough pain, cancer-induced peripheral neuropathy, established cancer pain treatment options, and novel emerging cancer pain treatment options.