The Emergence of the Old Drug Captagon as a New Illicit Drug: A Narrative Review.

First developed in the 1960s in Europe and approved briefly for use in the United States, fenethylline (sold as Captagon, one of its early trade names) is now a prominent drug of abuse in the Eastern Mediterranean Region. The drug was withdrawn from the United States market because of side effects that included hallucinations, visual distortions, and psychosis; it has also been linked to rare cases of myocardial infarction, seizures, and delusions. The chemical synthesis of fenethylline is straightforward and inexpensive. Manufactured in clandestine labs in Southern Europe and the Middle East, these amphetamines had been used by affluent Middle Eastern young people for recreation or study aids. Captagon has periodically emerged as a drug used in combat and conflict, and it was implicated in the 2015 riots in Paris. It has been described as "chemical courage" for combatants giving them focus, energy, and endurance in battle situations. Captagon is addictive but no cases of direct captagon-associated mortality have been reported. The use of drugs in war is nothing new, but captagon is also used heavily in the civilian population in war-torn areas to help them cope with food insecurity and maintain courage in dangerous situations. Captagon production and distribution drives the Syrian economy, but the drug's use is limited to certain regions and is rarely seen in North America. The drug is available online, but product may be contaminated with the inclusion of procaine, caffeine, or other substances.

To allow or avoid pain during shoulder rehabilitation exercises for patients with chronic rotator cuff tendinopathy-Study protocol for a randomized controlled trial (the PASE trial).

BACKGROUND: Rotator cuff (RC) tendinopathy is the most reported shoulder disorder in the general population with highest prevalence in overhead athletes and adult working-age population. A growing body of evidence support exercise therapy as an effective intervention, but to date there are no prospective randomized controlled trials addressing pain as an intervention variable. METHODS: A single-site, prospective, pragmatic, assessor-blinded randomized controlled superiority trial. Eighty-four patients aged 18-55 years with chronic (symptom duration over 3 months) RC tendinopathy are randomized 1:1 to receive shoulder exercise during which pain is either allowed or avoided. The intervention period lasts 26 weeks. During that period, participants in both groups are offered 8 individual on-site sessions with an assigned sports physiotherapist. Participants perform home exercises and are provided with a pain and exercise logbook and asked to report completed home-based exercise sessions and reasons for not completing sessions (pain or other reasons). Patients are also asked to report load and the number of sets and repetitions per sets for each exercise session. The logbooks are collected continuously throughout the intervention period. The primary and secondary outcomes are obtained at baseline, 6 weeks, 26 weeks, and 1 year after baseline. The primary outcome is patient-reported pain and disability using the Shoulder PAin and Disability Index (SPADI). Secondary outcomes are patient-reported pain and disability using Disability Arm Shoulder and Hand short-form (Quick DASH), and shoulder pain using Numeric Pain Rating Scale. Objective outcomes are shoulder range of motion, isometric shoulder muscle strength, pain sensitivity, working ability, and structural changes in the supraspinatus tendon and muscle using ultrasound. DISCUSSION: The results of this study will contribute knowledge about the treatment strategies for patients with RC tendinopathy and help physiotherapists in clinical decision-making. This is the first randomized controlled trial comparing the effects of allowing pain versus avoiding pain during shoulder exercises in patients with chronic RC tendinopathy. If tolerating pain during and after exercise proves to be effective, it will potentially expand our understanding of "exercising into pain" for this patient group, as there is currently no consensus. TRIAL REGISTRATION: ClinicalTrials.gov NCT05124769. Registered on August 11, 2021.

Randomised, siteless study to compare systematic atrial fibrillation screening using enrichment by a risk prediction model with standard care in a Swedish population aged ≥ 65 years: CONSIDERING-AF study design.

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study. METHODS AND ANALYSIS: CONSIDERING-AF is a randomised, controlled, siteless, non-blinded diagnostic superiority trial with four parallel groups and a primary endpoint of identifying AF during a 6-month study period set in Region Halland, Sweden. In each group, 740 individuals aged≥65 years will be included. The primary objective is to compare the intervention of AF screening enrichment using a risk prediction model (RPM), followed by 14 days of a continuous ECG patch, with no intervention (standard care). Primary outcome is defined as the incident AF recorded in the Region Halland Information Database after 6 months as compared with standard care. Secondary endpoints include the difference in incident AF between groups enriched or not by the RPM, with and without an invitation to 14 days of continuous ECG recording, and the proportions of oral anticoagulation treatment in the four groups. ETHICS AND DISSEMINATION: This study has ethical approval from the Swedish Ethical Review Authority. Results will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: NCT05838781.

Identifying risk factors for chronic postsurgical pain and preventive measures: a comprehensive update.

INTRODUCTION: Chronic postsurgical pain (CPSP) is a prevalent condition that can diminish health-related quality of life, cause functional deficits, and lead to patient distress. Rates of CPSP are higher for certain types of surgeries than others (thoracic, breast, or lower extremity amputations) but can occur after even uncomplicated minimally invasive procedures. CPSP has multiple mechanisms, but always starts as acute postsurgical pain, which involves inflammatory processes and may encompass direct or indirect neural injury. Risk factors for CPSP are largely known but many, such as female sex, younger age, or type of surgery, are not modifiable. The best strategy against CPSP is to quickly and effectively treat acute postoperative pain using a multimodal analgesic regimen that is safe, effective, and spares opioids. AREAS COVERED: This is a narrative review of the literature. EXPERT OPINION: Every surgical patient is at some risk for CPSP. Control of acute postoperative pain appears to be the most effective approach, but principles of good opioid stewardship should apply. The role of regional anesthetics as analgesics is gaining interest and may be appropriate for certain patients. Finally, patients should be better informed about their relative risk for CPSP.

The majority of surgery patients experience pain right after surgery that diminishes day by day as the tissue heals. Surgeons can usually advise patients how long their postsurgical pain will last, but in some cases, pain persists much longer and can even become chronic. Chronic postsurgical pain or CPSP is a condition that occurs most often in people who have open-chest surgery, breast surgery, or have a lower limb amputated. However, CPSP can occur after any type of surgery, even minimally invasive procedures with no complications.CPSP is a form of chronic pain and can be treated as chronic pain. CPSP can be mild or severe. In some patients, CPSP can include a form of numbness or 'pins and needles' around the affected area.There are certain things that can increase a person's risk for developing CPSP. Some of these things cannot be changed, like the higher risk for females, younger people, and for certain types of surgery. Pre-existing pain before surgery can increase the risk of CPSP and so can having a very negative attitude called 'catastrophizing.' People who 'catastrophize' tend to focus and think constantly about worst-case scenarios. Genetics may also play a role in CPSP, but less is known about what genes are involved and how to reduce the risk.Some CPSP is unavoidable, such as a surgery that might cut or compress a nerve. In other cases, the inflammation following surgery can set the stage for CPSP.The best strategy to prevent or minimize CPSP is for the clinical team to effectively treat the acute postsurgical pain.] The recommended approach is to use a multimodal pain therapy which is based on two or more agents and may also combine nonpharmacologic approaches as well. Multimodal pain care solves two pain problems. First, CPSP tends to be different types of pain that occur together in something called a 'mixed pain syndrome.' Multimodal pain treatment uses more than one agent with different mechanisms of action. Second, multimodal pain regimens reduce or may even eliminate the use of opioid pain relievers. By using the lowest effective amount of opioids, patients are spared opioid-associated side effects and fewer opioids are used. Opioids are associated with opioid use disorder and new policies about good opioid stewardship urge hospitals and prescribers to use opioids only to the extent appropriate.

The Sex Data Gap Within Implantable Cardioverter Defibrillator (ICD) Studies: A Retrospective Study of Literature From 1980 Until 2022.

Implantable cardioverter defibrillators (ICDs) are a form of cardiac therapy used to prevent death in patients at risk for sudden heart failure. Using 100 articles from the introduction of ICDs until now, a retrospective literature review was conducted. These studies were analyzed for sex disparity over the past 40 years. The difference in the number of male participants to female participants was statistically significant for both the earlier and later study groups (p = 0.0014 and p = 0.0004 respectively), indicating a significant and consistently lower number of females in ICD research over time. This review shows no significant difference in the sex disparity since the implementation of ICDs. Unfortunately, due to a gap in the literature, the reason for this disparity between the sexes in ICD literature can only be speculated. This disparity may be partly due to a lack of incentive and encouragement for women to participate in research.

The New Stealth Drug on the Street: A Narrative Review of Xylazine as a Street Drug.

Xylazine is an alpha-adrenergic receptor agonist approved for use only in animals with a prescription from a veterinarian. It is a powerful sedative that is slowly infiltrating the recreational street drug scene and is often used by polysubstance abusers. Known as "tranq," it can be fatal, and xylazine-induced toxicity cannot be reversed with naloxone or nalmefene. Due to its vasoconstrictive effects, chronic use of xylazine is associated with necrotic skin lesions and general deterioration of health. Since xylazine is not approved for human use and is not scheduled as a controlled substance, there are no human studies to provide evidence of drug-drug interactions, lethal doses, or reversal protocols. Xylazine is available online without a prescription. Street drug users may take xylazine knowingly or unknowingly, as it is often combined with other illicit substances such as fentanyl. There are no rapid tests for xylazine, although there are specialty tests that can be ordered. Xylazine represents a major threat to street drug users and another challenge to emergency healthcare workers, first responders, and others who care for those who have taken this "new" street drug.

Considerations for Pain Assessments in Cancer Patients: A Narrative Review of the Latin American Perspective.

Cancer incidence in Latin America is lower than in Europe or the United States but morbidity and mortality rates are disproportionately high. A barrier to adequate pain control is inadequate pain assessment, which is a relatively easy and inexpensive metric. The objective of this narrative review is to describe pain assessment for cancer patients in Latin America. Cultural factors may influence pain perception, including contextualizing pain as noble or natural suffering and aspects of what is now called "spiritual pain." Unlike other painful conditions, cancer pain may be strongly associated with existential fear, psychosocial distress, anxiety, and spiritual concerns. Pain assessment allows not just quantification of pain intensity but may elucidate pain mechanisms involved or psychosocial aspects that may color the pain. Many current pain assessment instruments capture only pain intensity, which is but one aspect of the pain experience; some have expanded to include functional assessments, mental health status evaluations, and quality of life metrics. A quality-of-life assessment may be appropriate for cancer patients since chronic pain can severely impact function, which can in turn create a vicious cycle by exacerbating pain. The incidence of cancer in Latin America is expected to increase in the ensuing years. Better pain assessment and clinician education are needed to help manage pain in this large and growing patient population.

Exploring the Implications of New-Onset Diabetes in COVID-19: A Narrative Review.

Post-viral new-onset diabetes has been an important feature of the COVID-19 pandemic. It is not always clear if new-onset diabetes is the unmasking of a previously undiagnosed condition, the acceleration of prediabetes, or new-onset diabetes that would not have otherwise occurred. Even asymptomatic cases of COVID-19 have been associated with new-onset diabetes. Diabetes that emerges during acute COVID-19 infection tends to have an atypical presentation, characterized by hyperglycemia and potentially life-threatening diabetic ketoacidosis. It is not always clear if new-onset diabetes is type 1 or type 2 diabetes mellitus. Many cases of COVID-associated diabetes appear to be type 1 diabetes, which is actually an autoimmune disorder. The clinical course varies temporally and with respect to outcomes; in some cases, diabetes resolves completely or improves incrementally after recovery from COVID-19. Disruptions in macrophagy caused by COVID-19 infection along with an exaggerated inflammatory response that can occur in COVID-19 also play a role. Those who survive COVID-19 remain at a 40% elevated risk for diabetes in the first year, even if their case of COVID-19 was not particularly severe. A subsequent post-pandemic wave of new diabetes patients may be expected.

Fixed Dose Versus Loose Dose: Analgesic Combinations.

Combinations of drugs may be fixed (two or more entities in a single product) or loose (two or more agents taken together but as individual agents) to help address multimechanistic pain. The use of opioids plus nonopioids can result in lower opioid consumption without sacrificing analgesic benefits. Drug combinations may offer additive or synergistic benefits. A variety of fixed-dose combination products are available on the market such as diclofenac plus thiocolchicoside, acetaminophen and caffeine, acetaminophen and opioid, ibuprofen and acetaminophen, tramadol and acetaminophen, and others. Fixed-dose combination products offer predictable pharmacokinetics and pharmacodynamics, known adverse events, and can reduce the pill burden. However, they are limited to certain drug combinations and doses; loose dosing allows prescribers the versatility to meet individual patient requirements as well as the ability to titrate as needed. Not all drug combinations offer synergistic benefits, which depend on the drugs and their doses. Certain drugs offer dual mechanisms of action in a single molecule, such as tapentadol, and these may further be used in combination with other analgesics. New technology allows for co-crystal productions of analgesic agents which may further improve drug characteristics, such as bioavailability. Combination analgesics are important additions to the analgesic armamentarium and may offer important benefits at lower doses than monotherapy.

What Do We Need to Know About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative Review and Update.

The most common type of idiopathic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF), an irreversible, progressive disorder that has lately come into question for possible associations with COVID-19. With few geographical exceptions, IPF is a rare disease but its prevalence has been increasing markedly since before the pandemic. Environmental exposures are frequently implicated in IPF although genetic factors play a role as well. In IPF, healthy lung tissue is progressively replaced with an abnormal extracellular matrix that impedes normal alveolar function while, at the same time, natural repair mechanisms become dysregulated. While chronic viral infections are known risk factors for IPF, acute infections are not and the link to COVID-19 has not been established. Macrophagy may be a frontline defense against any number of inflammatory pulmonary diseases, and the inflammatory cascade that may occur in patients with COVID-19 may disrupt the activity of monocytes and macrophages in clearing up fibrosis and remodeling lung tissue. It is unclear if COVID-19 infection is a risk factor for IPF, but the two can occur in the same patient with complicating effects. In light of its increasing prevalence, further study of IPF and its diagnosis and treatment is warranted.

Current and emerging COX inhibitors for treating postoperative pain following oral surgery.

INTRODUCTION: The numerous drugs in the NSAID class are often used to treat acute postoperative pain associated with oral surgery such as impacted third-molar extractions. These drugs are effective in this setting and dental pain studies often serve as models for acute pain relief and for registration of analgesics. With numerous cyclooxygenase (COX) inhibitors available as monotherapy, for use in combination with analgesic regimens, and in different doses and formulations, it was our aim to determine if there were clear-cut distinctions among these products and dosing regimens. AREAS COVERED: This is a literature review of recent randomized controlled clinical trials evaluating NSAIDs for use in postoperative pain management following oral surgery. Of particular interest were head-to-head studies, which might offer some insight into comparative effectiveness. EXPERT OPINION: Postoperative oral surgery pain is largely managed in real-world clinical practice using NSAIDs, either alone or in combination, and there is good evidence supporting their use especially in multimodal therapy. Head-to-head and comparative studies do not show a clear-cut 'optimal NSAID' in this setting, although ibuprofen, ketoprofen, dexketoprofen, and naproxen have gained most acceptance. Combination therapy with other analgesics or adjuvants is largely accepted.

Effect of Ultrasonography-Guided Corticosteroid Injection vs Placebo Added to Exercise Therapy for Achilles Tendinopathy: A Randomized Clinical Trial.

Importance: Corticosteroid injections and exercise therapy are commonly used to treat chronic midportion Achilles tendinopathy, but the evidence for this combination is limited. Objective: To investigate the effect of corticosteroid injection and exercise therapy compared with placebo injection and exercise therapy for patients with Achilles tendinopathy. Design, Setting, and Participants: This was a participant-blinded, physician-blinded, and assessor-blinded randomized clinical trial of patients with Achilles tendinopathy verified by ultrasonography. Assessment of pain and function were conducted at baseline and at 1, 2, 3, 6, 12, and 24 months. Patients were recruited from a university medical clinic and a private rheumatology clinic in Denmark between April 2016 and September 2018. Data analysis was performed from June to September 2021. Interventions: Corticosteroid injection and placebo injection were performed with ultrasonography guidance. Exercise therapy was based on previous trials and consisted of 3 exercises done every second day. Main Outcomes and Measures: The primary outcome was the Victorian Institute of Sports Assessment-Achilles (VISA-A) score (range, 1-100, with 100 representing no symptoms) at 6 months. Secondary outcomes included pain measured using a 100-mm Visual Analog Scale for morning pain and pain during exercise (with higher scores indicating worse pain), global assessment (Likert scale), and tendon thickness. Results: A total of 100 patients were included, with 52 randomized to placebo (mean age, 46 years [95% CI, 44-48 years]; 32 men [62%]) and 48 randomized to corticosteroid injection (mean age, 47 years [95% CI, 45-49 years]; 28 men [58%]). Patients in the 2 groups had similar height (mean [SD], 177 [8] cm), weight (mean [SD], 79 [12] kg), and VISA-A score (mean [SD], 46 [18]) at baseline. The group receiving exercise therapy combined with corticosteroid injections had a 17.7-point (95% CI, 8.4-27.0 points; P < .001) larger improvement in VISA-A score compared with patients receiving exercise therapy combined with placebo injections at 6 months. No severe adverse events were observed in either group, and there was no deterioration in the long term (2-year follow-up). Conclusions and Relevance: Corticosteroid injections combined with exercise therapy were associated with better outcomes in the treatment of Achilles tendinopathy compared with placebo injections and exercise therapy. A combination of exercise therapy and corticosteroid injection should be considered in the management of long-standing Achilles tendinopathy. Trial Registration: ClinicalTrials.gov Identifier: NCT02580630.

The Use of Monoclonal Antibody-Based Proprotein Convertase Subtilisin-Kexin Type 9 (PCSK9) Inhibitors in the Treatment of Hypercholesterolemia.

In this review, we evaluated several studies in the literature to analyze the benefits and deleterious effects of the use of monoclonal antibodies (MABs)-based proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in patients with hypercholesterolemia. Increased low-density lipoprotein cholesterol (LDL-C) levels lead to an increase in the risk of cardiovascular (CV) disease. Statins are the cornerstones of hypercholesterolemia treatment, but the patient response may often vary, and additional therapies may be needed to control the increased LDL-C levels. MABs bind to PCSK9 receptors, causing a reduction in LDL-C levels. MAB-based PCSK9 inhibitors such as alirocumab and evolocumab have been approved for use in hypercholesterolemia in combination with statins. Studies have suggested that both alirocumab and evolocumab are effective in lowering LDL-C levels, have favorable side effect profiles, and can be administered at convenient dosing intervals; however, further double-blind, randomized trials evaluating the long-term safety and efficacy of both the agents could assist with clinical decision-making.

Multimechanistic Single-Entity Combinations for Chronic Pain Control: A Narrative Review.

Atypical opioids such as tramadol, tapentadol, and cebranopadol combine two complementary mechanisms of action into a single molecule, creating novel analgesic agents. These are synthetic small molecules: cebranopadol is not yet market released; tramadol and tapentadol are commercially available and have immediate-release (IR) and extended-release (ER) formulations. Tramadol has been widely used in the United States in recent years and works as a prodrug in that its metabolites are active in inhibiting serotonin and norepinephrine reuptake. Tapentadol is a direct-acting agent with a faster onset of action and is a mu-opioid-receptor agonist and also inhibits noradrenaline reuptake. Cebranopadol is the newest of these drugs, a first-in-class atypical analgesic that combines mu-opioid receptor (MOR) agonism with activity at the nociception/orphanin (NOP) FQ petide receptors. Cebranopadol may be considered a partial kappa-opioid receptor agonist as well. The pharmacology of these unique single-entity agents allows them to offer analgesic benefit with fewer side effects and risks. Clinical studies have demonstrated the safety and efficacy of tramadol and tapentadol, and promising but limited studies for cebranopadol show good analgesic effect and safety. Serotonin toxicity or 'serotonin syndrome' may occur with accumulation of serotonin with tramadol. While the misuse of these agents is limited in the United States, tramadol misuse is prevalent in Iran and parts of Africa. Patients have been successfully rotated from one of these agents to another. All three agents show promise in the treatment of cancer and non-cancer pain and their unique formulation in a single molecule reduces the pill burden.

Pharmacotherapeutic management of trigeminal neuropathic pain: an update.

INTRODUCTION: Guidelines recommend a number of pharmacotherapeutic options used as monotherapy or in combination with others for treating the pain of trigeminal neuropathy. AREAS COVERED: The authors examine the pharmacotherapeutic options for treating trigeminal neuralgia and supporting evidence in the literature. Guidelines reported the most effective treatment for trigeminal neuropathy, in particular trigeminal neuralgia, appears to be carbamazepine or oxcabazepine, but side effects can be treatment limiting. Lamotrigine and gabapentin are also recommended in guidance. In real-world clinical practice, baclofen, cannabinoids, eslicarbazepine, levetiracetam, brivaracetam, lidocaine, misoprostol, opioids, phenytoin, fosphenytoin, pimozide, sodium valproate, sumatriptan, tizanidine, tocainide, tricyclic antidepressants, and vixotrigine are sometimes used, either as monotherapy or in combination. The relatively small patient population has limited the number of large-scale studies and there is limited evidence on which to base prescribing choices. EXPERT OPINION: While there is no optimal pharmacotherapy for treating trigeminal neuropathy, advancements in our understanding of the underlying mechanisms of this condition and drug development indicate promise for NaV inhibitors, despite the fact that not all patients respond to them and they may have potentially treatment-limiting side effects. Nevertheless, better understanding of NaV channels may be important avenues for future drug development for trigeminal neuropathy.

The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs).

Interleukins (ILs)-which are important members of cytokines-consist of a vast group of molecules, including a wide range of immune mediators that contribute to the immunological responses of many cells and tissues. ILs are immune-glycoproteins, which directly contribute to the growth, activation, adhesion, differentiation, migration, proliferation, and maturation of immune cells; and subsequently, they are involved in the pro and anti-inflammatory responses of the body, by their interaction with a wide range of receptors. Due to the importance of immune system in different organisms, the genes belonging to immune elements, such as ILs, have been studied vigorously. The results of recent investigations showed that the genes pertaining to the immune system undergo progressive evolution with a constant rate. The occurrence of any mutation or polymorphism in IL genes may result in substantial changes in their biology and function and may be associated with a wide range of diseases and disorders. Among these abnormalities, single nucleotide polymorphisms (SNPs) can represent as important disruptive factors. The present review aims at concisely summarizing the current knowledge available on the occurrence, properties, role, and biological consequences of SNPs within the IL-1 family members.

Effects of Digoxin in Heart Failure (HF) With Reduced Ejection Fraction (EF).

In this review, we evaluated the literature on the benefits and deleterious effects of digoxin in heart failure (HF) with reduced ejection fraction (EF). Although digoxin was considered an effective treatment for HF, the supporting evidence is conflicting. Before the conventional use of modern HF therapies, digoxin was widely used for symptomatic relief on these patients. Further randomized trials are required to reach a definite conclusion about its efficacy and safety in patients experiencing HF with a reduced EF (HFrEF).

Treating Apnea of Prematurity.

Premature babies often suffer apnea of prematurity as a physiological consequence of an immature respiratory system. Hypercapnia may develop, and neonates with apnea of prematurity are at an increased risk of morbidity and mortality. The long-term effects of apnea of prematurity or their treatments are less clear. While a number of treatment options exist for apnea of prematurity, there is no clear-cut "first-line" approach or gold standard of care. Effective treatments, such as caffeine citrate, carbon dioxide inhalation, nasal continuous positive airway pressure, nasal intermittent positive pressure ventilation, and others, may be associated with safety concerns. More conservative treatments are available, such as kangaroo care, postural changes, and sensory stimulation, but they may not be effective. While apnea of prematurity resolves spontaneously as the respiratory system matures, it can complicate neonatal care and may have both short-term and long-term consequences. The role, if any, that apnea of prematurity may play in mortality of preterm neonates is not clear.

Cocaethylene: When Cocaine and Alcohol Are Taken Together.

Cocaine is taken frequently together with ethanol and this combination produces a psychoactive metabolite called cocaethylene which has similar properties to the parent drug and may be more cardiotoxic. Cocaethylene has a longer half-life than cocaine, so that people who combine cocaine and ethanol may experience a longer-lasting, as well as more intense, psychoactive effect. Cocaethylene is the only known instance where a new psychoactive substance is formed entirely within the body. Although known to science for decades, cocaethylene has not been extensively studied and even its metabolic pathways are not entirely elucidated. Like its parent drug, cocaethylene blocks the reuptake of dopamine and increases post-synaptic neuronal activity; the parent drug may also block reuptake of serotonin as well. Cocaethylene has been studied in animal models in terms of its pharmacology and its potential neurological effects. Since the combination of cocaine and alcohol is commonly used, it is important for clinicians to be aware of cocaethylene, its role in prolonging or intensifying cocaine intoxication, and how it may exacerbate cocaine-induced cardiovascular disorders. Most cardiac-related risk assessment tools do not ask about cocaine use, which can prevent clinicians from making optimal therapeutic choices. Greater awareness of cocaethylene is needed for clinicians, and those who use cocaine should also be aware of the potential for polysubstance use of cocaine and ethanol to produce a potentially potent and long-lasting psychoactive metabolite.

Potential neurological manifestations of COVID-19: a narrative review.

Neurological manifestations are increasingly reported in a subset of COVID-19 patients. Previous infections related to coronaviruses, namely Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) also appeared to have neurological effects on some patients. The viruses associated with COVID-19 like that of SARS enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells. A few rare cases of neurological sequelae of SARS and MERS have been reported. A growing body of evidence is accumulating that COVID-19, particularly in severe cases, may have neurological consequences although respiratory symptoms nearly always develop prior to neurological ones. Patients with preexisting neurological conditions may be at elevated risk for COVID-19-associated neurological symptoms. Neurological reports in COVID-19 patients have described encephalopathy, Guillain-Barré syndrome, myopathy, neuromuscular disorders, encephalitis, cephalgia, delirium, critical illness polyneuropathy, and others. Treating neurological symptoms can pose clinical challenges as drugs that suppress immune response may be contraindicated in COVID-19 patients. It is possible that in some COVID-19 patients, neurological symptoms are being overlooked or misinterpreted. To date, neurological manifestations of COVID-19 have been described largely within the disease trajectory and the long-term effects of such manifestations remain unknown.