The Evolving Role of Calcium Channel Blockers in Hypertension Management: Pharmacological and Clinical Considerations.

Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

Xylazine: A Drug Adulterant of Clinical Concern.

PURPOSE OF REVIEW: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. RECENT FINDINGS: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.

The Use of Oxytocin for the Treatment of Opioid Use Disorder.

Nearly 27 million people have an opioid use disorder (OUD) according to the 2016 Global Burden of Disease study, most of which occur in the US where opioids are a common class of medication used to treat acute and chronic pain. In 2016 alone, more than 60 million patients had at least one prescription for opioids filled or refilled. Over the past decade, prescription rates have risen astronomically and have created an epidemic in the US dubbed the "opioid crisis." In this regard, there has been an increase in overdoses and OUD diagnoses. Several studies have found dysregulation of balance between several neurotransmitters involved in the neural circuitry that subserves several behavioral domains, such as reward recognition, motivation, learning, and memory, affect, stress, and executive function, that contribute to the manifestation of craving. On the horizon is a new treatment approach consisting of the neuropeptide oxytocin, which may be involved in the overlapping mechanisms of stable attachment formation and coping with stress. Through this mechanism, it can shift processing from novelty and reward-seeking to an appreciation of familiarity and thus reduce stress and increase resilience in the face of addiction. It has been hypothesized that there is a connection between the glutaminergic and oxytocinergic systems, making oxytocin a possible therapeutic agent in reducing drug-induced actions seen in OUD patients. This manuscript will review the potential and feasible use of oxytocin in treating OUD.

Low-Dose Initiation of Buprenorphine: A Narrative Review.

PURPOSE OF REVIEW: Opioid use disorder (OUD) is a chronic disorder in which a person loses control over the use of opioids, develops a compulsive behavior, and defends the use despite knowing the negative consequences. There are numerous treatments for OUD, including buprenorphine. Since it is displacing a full agonist opioid, precipitated withdrawal can occur with standard inductions involving buprenorphine. RECENT FINDINGS: Case reports have noted success with a low-dose initiation of buprenorphine, which is different from typical protocols, relatively limited by adverse effects when patients were recently administered full agonists. A cohort investigation studied the use of a transdermal patch as part of the protocol, which was fairly well tolerated. While ongoing research is being conducted on this topic, recent case studies and smaller cohort studies have demonstrated the feasibility of a trial to treat OUD with low-dose initiation of buprenorphine.

The Emerging Role of Ketamine in Acute Postoperative Pain Management.

PURPOSE OF REVIEW: Postoperative pain (POP) is among the most unpleasant experiences that patients face after surgery. Interest in and use of N-methyl-D-aspartate (NMDA) receptor antagonists for the management of POP has increased over the years with ketamine being the most popular drug of this class. RECENT FINDINGS: Several randomized controlled trials found that the use of ketamine either alone or in combination with other medications leads to decreased postoperative pain and opioid consumption. However, there are other studies that have not found these benefits. The results as of now suggest that the role of intraoperative ketamine in postoperative pain control varies among different operative procedures. While some studies have shown promise in ketamine's potential use as a postoperative analgesic, there is still a great deal of proposed research and randomized controlled trials needed to deduce the most efficacious and tolerable form and dose of ketamine.

Cebranopadol for the Treatment of Chronic Pain.

PURPOSE OF REVIEW: Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. RECENT FINDINGS: In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

Treatment of Acute Pain in Patients on Naltrexone: A Narrative Review.

PURPOSE OF REVIEW: The tissue damage and trauma associated with surgery almost always result in acute postoperative pain. The intensity of postoperative pain can range from mild to severe. Naltrexone is suitable for patients who do not wish to be on an agonist treatment such as methadone or buprenorphine. However, naltrexone has been shown to complicate postoperative pain management. RECENT FINDINGS: Multiple studies have found that the use of naltrexone can increase the opioid requirement for postoperative pain control. Other modalities exist that can help outside of opioids such as ketamine, lidocaine/bupivacaine, duloxetine, and non-pharmacological management can help manage pain. Multimodal pain regiments should also be employed in patients. In addition to traditional methods for postoperative pain management, other methods of acute pain control exist that can help mitigate opioid dependence and help control pain in patients who use naltrexone for their substance use disorders.

Improved chest wall trauma taxonomy: an interdisciplinary CWIS and ASER collaboration.

PURPOSE: Chest wall injury taxonomy and nomenclature are important components of chest wall injury classification and can be helpful in communicating between providers for treatment planning. Despite the common nature of these injuries, there remains a lack of consensus regarding injury description. The Chest Wall Injury Society (CWIS) developed a taxonomy among surgeons in the field; however, it lacked consensus and clarity in critical areas and collaboration with multidisciplinary partners. We believe an interdisciplinary collaboration between CWIS and American Society of Emergency Radiology (ASER) will improve existing chest wall injury nomenclature and help further research on this topic. METHODS: A collaboration between CWIS and ASER gathered feedback on the consensus recommendations. The workgroup held a series of meetings reviewing each consensus statement, refining the terminology, and contributing additional clarifications from a multidisciplinary lens. RESULTS: After identifying incomplete definitions in the CWIS survey, the workgroup expanded on and clarified the language proposed by the survey. More precise definitions related to rib and costal cartilage fracture quality and location were developed. Proposed changes include more accurate characterization of rib fracture displacement and consistent description of costal cartilage fractures. CONCLUSIONS: The 2019 consensus survey from CWIS provides a framework to discuss chest wall injuries, but several concepts remained unclear. Creating a universally accepted taxonomy and nomenclature, utilizing the CWIS survey and this article as a scaffolding, may help providers communicate the severity of chest wall injury accurately, allow for better operative planning, and provide a common language for researchers in the future.

Critical Care Transport of Patients With COVID-19.

PURPOSE: Critical care transport is associated with a high rate of adverse events, and the risks and outcomes of transporting critically ill patients during the COVID-19 pandemic have not been previously described. MATERIALS AND METHODS: We performed a retrospective review of transports of subjects with suspected or confirmed COVID-19 from sending hospitals to tertiary care hospitals in Boston. Follow-up data were obtained for patients transported between March 1st and April 20th, 2020. RESULTS: Of 254 charts identified, 250 patients were transported. Nine patients (3.5%) had cardiac arrest prior to transport. Twenty-nine (11.6%) had hypotension, 22 (8.8%) had a critical desaturation, and 4 (1.6%) had both en route. Hospital follow-up data were available for 189 patients. Of those intubated during their hospitalization, 44 (25.0%) had died, 59 (33.5%) had been extubated, and 13 (17.6%) had been discharged alive. For the subgroup with prior cardiac arrest, follow-up data available for 6. Of these 6, 2 died and 4 (66.7%) have been discharged alive. CONCLUSIONS: Few patients with COVID-19 had an adverse event in transport. The in-hospital mortality rate was 25%, with a 33.5% extubation rate. Patients resuscitated from cardiac arrest prior to transport had a 66.7% discharge rate among those transported to consortium hospitals.

Recent Advances in the Treatment of Opioid Use Disorder.

PURPOSE OF REVIEW: Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States' healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy. RECENT FINDINGS: Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments' market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment.

Willingness to Pay for CT Colonography: A Survey of Patient Preferences.

OBJECTIVE: CT colonography (CTC) has received mixed reviews both in the radiology literature and in clinical practice. CTC is less invasive than optical colonoscopy (OC), is better for identifying polyps, and does not require sedation. However, its cost-effectiveness has been called into question, and there is a residual need for OC if the CTC findings are positive. Some radiologists are hesitant to perform CTC because of the time-intensive nature of its interpretation. Results of willingness-to-pay surveys can be informative about preferences and value placed on intangibles. The purpose of this study was to use such a survey to elicit the preferences of radiologists about CTC versus OC. SUBJECTS AND METHODS: A vignette was presented in which the insurer covered OC at no charge but required out-of-pocket payment for CTC. The strengths and weaknesses of OC and CTC were listed. The respondents were asked how much they would be willing to pay for CTC; for CTC with perfect sensitivity, specificity, and accuracy; and for CTC that required no bowel preparation. RESULTS: Twenty-eight of 42 radiologists preferred OC to CTC. One radiologist was indifferent. Four radiologists would reverse their preference and choose CTC if it had 100% sensitivity. Sixteen radiologists said they would prefer CTC if it had 100% specificity. If CTC eliminated the need for bowel preparation, 57% would prefer it to OC. Thirty-one (74%) radiologists preferred perfect sensitivity to perfect specificity. CONCLUSION: Despite the less invasive nature of CTC, most radiologists who responded to the survey preferred OC for colorectal cancer screening, mostly because of the definitive nature of OC due to the capability of immediate biopsy of suspicious lesions and the lack of requirement for a second round of bowel preparation.

Current State of Opioid Therapy and Abuse.

Currently, there is growing tension between the twin challenges of opioid therapy for chronic pain and adverse consequences of abuse, leading to multiple complications including respiratory failure and death. The recent data from Centers for Disease Control and Prevention (CDC) have shown continued escalation of prescription opioid use with opioid overdose deaths topping all previous estimations. Numerous policy initiatives, advisories, and guidelines have been advanced through the years to control the opioid epidemic. The strategies to prevent opioid abuse and to maintain opioid therapy when medically necessary fall into primary and secondary prevention categories. The primary prevention category is extremely crucial, since it involves education of primary care providers and patients at the starting point of opioid therapy. The education of surgeons and other prescribers is as crucial as the education of primary care physicians.

Improving Radiologist-IT Staff Communications and Collaboration Through a Shadowing Project.

It is important for radiology practices to have efficient and skillful IT staff to provide support for issues that arise during patient care. However, an anecdotal barrier exists between radiologists and IT staff that can hinder the delivery of this care, either by lengthening the time required to solve problems with the IT infrastructure or not bringing critical issues to the IT staff's attention. We first created a survey of the radiologists and IT staff in our department to investigate this barrier, and found that there was, at baseline, a significant difference in how one group viewed the other, and, at times, there were irrational expectations from either party of what their counterparts were responsible for or capable of. We then instituted a shadowing project, whereby radiologists shadowed IT staff and vice versa, in order to give each group a better understanding of the others' daily workflows. We gave the participants a post-intervention survey to assess their experiences, which were markedly positive. In one case, an IT issue regarding pre-fetching of cardiovascular studies was, in fact, solved during the shadowing session.

Hyponatremia With Anticonvulsant Medications: A Narrative Review.

Hyponatremia is an adverse effect of many antiseizure medications (ASMs). It occurs with interference with the normal balance of electrolytes within the body. Various risk factors associated with the development of hyponatremia in patients taking these medications include age, gender, dosage, and combinations with other drugs. ASMs such as carbamazepine (CBZ), oxcarbazepine (OXC), and valproic acid have a higher risk of hyponatremia. Hyponatremia induced by an antiseizure medication can occur through various mechanisms depending on the drug's specific mechanism of action. Hyponatremia can be a potentially fatal side effect. Patients taking these medications need to be monitored closely for the signs and symptoms of hyponatremia. Acute hyponatremia, defined as developing in <48 hours, is more likely to show symptoms than chronic hyponatremia. Signs of acute hyponatremia include delirium, seizures, decerebrate posturing, and cerebral edema with uncal herniation. Chronic hyponatremia, defined as developing in >48 hours, can cause lethargy, dizziness, weakness, headache, nausea, and confusion. Hyponatremia is associated with longer hospital stays and increased mortality. Treatment varies based on the degree of severity of hyponatremia. Choosing a treatment option should include consideration of the drug causing the electrolyte disturbance, the patient's risk factor profile, and the severity of symptoms as they present in the individual patient. Healthcare providers should be aware of hyponatremia as a potential side effect of ASMs, the signs and symptoms of hyponatremia, the different treatment options available, and the potential complications associated with rapid correction of hyponatremia.

Rabies Vaccine for Prophylaxis and Treatment of Rabies: A Narrative Review.

Rabies, a millennia-old viral infection transmitted through animal bites, poses a lethal threat to humans, with a historic fatality rate of 100% if left untreated. Louis Pasteur's introduction of the rabies vaccine in 1885 marked a turning point in the battle against rabies, preventing numerous cases. The purpose of this paper is to review the historical development, current challenges, and future prospects of rabies vaccination and treatment, with emphasis on the importance of continued research and collaborative efforts in the quest to eradicate this deadly infection. Historical vaccine development progressed from inactivated to live-attenuated forms, with modern recombinant techniques showing promise. The preventive measures at present primarily involve vaccination, but challenges persist, such as differing safety profiles and immunogenicity among vaccine types. Pre-exposure prophylaxis with a three-dose vaccine series is crucial, especially in high-risk scenarios. Post-exposure prophylaxis combines human rabies immunoglobulin and inactivated rabies virus vaccine. The quest for the next generation of vaccines explores genetically modified and viral vector-based approaches; emerging treatments include gene therapy, virus-like particles, and monoclonal antibodies, offering hope for improved outcomes. Economic barriers to post-exposure prophylaxis, limited education, and awareness challenge rabies control. Cost-effective solutions and comprehensive awareness campaigns are vital for the successful eradication of rabies. More research and collaborative endeavors remain pivotal in the ongoing journey to eradicate rabies, one of the deadliest infectious diseases known to humans, if not met with prophylactic measures.

Treatment and Toxicity Considerations in Tuberculosis: A Narrative Review.

Tuberculosis remains one of the most significant bacterial infections plaguing the medical community worldwide. The bacteria Mycobacterium tuberculosis retains the ability to manifest as an active infection, latent infection, miliary infection, or reactivation of latent infections in times of immunosuppression. Therefore, the medication regimen to treat the condition revolves around four medications, each with a mechanism that targets a different part of the bacteria. Isoniazid weakens the cell wall but produces neuropathy and hepatotoxicity as side effects. Rifampin interrupts protein synthesis but creates the opportunity for many drug-to-drug interactions and red-orange discolorations as side effects. Pyrazinamide is poorly understood, but it is believed to acidify the internal environment of the bacteria, with gout exacerbations and arthralgias as major side effects. Ethambutol also works as a bacteriostatic medication to interrupt the cell membrane; however, its mechanism is poorly understood. The most concerning side effect is optic neuropathy. The unfavorable side effect profile for tuberculosis treatment may contribute to the higher rates of medication noncompliance with therapy and needs to be addressed in the future.

Delirium Tremens: A Review of Clinical Studies.

Delirium tremens (DT) is a severe condition resulting from alcohol withdrawal. This review highlights the challenges in diagnosing and managing DT and emphasizes the importance of early recognition and intervention to prevent complications and ensure optimal patient outcomes. The discussion of the pathophysiology of DT, focusing on the neurochemical imbalances involving the neurotransmitters gamma-aminobutyric acid and glutamate, explains how chronic alcohol dependence leads to these imbalances and contributes to the hyperexcitability seen in DT. The management of DT involves ensuring patient safety and alleviating symptoms, primarily through pharmacological approaches, such as benzodiazepines. Closely monitoring vital signs and electrolyte imbalances is necessary due to autonomic dysregulation associated with DT. The mention of the potential complexity of DT when coexisting with other conditions emphasizes the need for additional research to advance comprehension, identify predictive factors, and enhance its management.

The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade. Despite the approval of many new pharmaceutical therapies in the past 20 years, there remains a growing need for alternative therapies to manage the course of this disease. Treatments are separated into two main categories: management of acute flare versus long-term prevention of flares via disease-modifying therapy. Primary drug therapies for acute flare include corticosteroids to limit inflammation and symptomatic management, depending on symptoms. Several different drugs have been recently approved for use in modifying the course of the disease, including a group of medications known as fumarates (e.g., dimethyl fumarate, diroximel fumarate, monomethyl fumarate) that have been shown to be efficacious and relatively safe. In the present investigation, we review available evidence focused on monomethyl fumarate, also known as Bafiertam®, along with bioequivalent fumarates for the long-term treatment of relapsing-remitting multiple sclerosis.

Odevixibat: A Novel Bile Salt Inhibitor Treatment for Pruritus in Progressive Familial Intrahepatic Cholestasis.

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. One such disease that results from chronic pruritus is progressive familial intrahepatic cholestasis (PFIC), a group of uncommon hereditary disorders that affects the formation of bile and its outflow from the liver. Previously, the drug ursodeoxycholic acid was used to help manage pruritus or surgical procedures, e.g., partial external biliary diversion or partial internal biliary diversion, to help control complications of the disease. This literature review will discuss three clinical studies covering the effectiveness of odevixibat in treating pruritus in patients with PFIC. Odevixibat (Bylvay) is an oral drug that has been FDA-approved to treat pruritus in patients three months of age and older with PFIC. Odevixibat prevents the reabsorption of bile salts in the intestines, resulting in decreased levels of bile salts via their excretion in stool. Several studies have determined that the drug is well tolerated and provides a nonsurgical, pharmacological treatment alternative for those with PFIC.

Fluoroquinolones: Neurological Complications and Side Effects in Clinical Practice.

Fluoroquinolones, a popular antibiotic class that inhibits nucleic acid synthesis of bacteria by disrupting the activity of the enzyme's topoisomerase IV and DNA gyrase, are used to treat bacterial infections. However, the widespread use of these drugs has allowed for the development of microbial resistance in recent years. Quinolones also have many clinically relevant side effects, including psychosis, confusion, seizures, headaches, dizziness, and nausea. Common side effects include tendinitis, myopathy, depression, and fatigue. Cardiovascular side effects include increased risk of aortic aneurysm, aortic dissection, and QT interval prolongation. Overall, quinolones can be an effective choice for treating bacterial infections. Still, the side effect profile and decreased efficacy secondary to microbial resistance no longer make the quinolone class an ideal choice for many types of infection. A better understanding of the role of quinolone-mediated or neurological damage, cardiovascular impairment, and musculoskeletal involvement is imperative to determine the risks/benefits for the clinician.