Practical Tips on Epidermolysis Bullosa for Caregivers: Part 2.

The heritable condition epidermolysis bullosa (EB) is a rare but potentially devastating and life-threatening condition that is characterized primarily by cutaneous fragility, manifested when the dermis and epidermis fail to adhere properly. EB has no cure, and because of its rarity, few healthcare professionals have experience in treating it. Most families with an EB child are forced to rely on family caregiving which can be disruptive to family routines but, more importantly, place enormous time and emotional and financial burdens on the family. EB can be extremely painful, and families are often caught in the bind of trying to manage overwhelming financial burdens in an effort to help their children cope with excruciating pain. For many years, the nonprofit organization NoBabyBlisters.org has worked on five continents with families caring for EB children. Many of these families reside in under-developed nations with hot climates and limited healthcare resources. Over time, the healthcare professionals with NoBabyBlisters.org have worked with EB families both internationally and in the United States to develop a series of simple tips or "hacks" that may provide relief or great benefit to these children. The objective of this article is to share these field-tested tips with a wider audience. This is not a scientific study or a systematic review and is offered as a companion article to an earlier article on the same subject.

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 The drug was withdrawn from the United States market because of side effects that included hallucinations, visual distortions, and psychosis; it has also been linked to rare cases of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.

Epidermolysis Bullosa: Practical Clinical Tips From the Field.

Epidermolysis bullosa (EB) is a rare genetic condition characterized by fragile skin caused by impaired adhesion between the dermis and epidermis. EB is present at or near birth. There is no cure and treatments are supportive. Children with EB are at elevated risk of squamous cell cancer. Under ideal circumstances, EB patients benefit from interdisciplinary care teams who can offer state-of-the-art treatments. In reality and particularly in less-developed nations, care can be limited. In all cases, families dealing with a member with EB face great challenges in caregiving, much of which is managed at home, and incur great financial expenses for dressings, equipment, transportation, and out-of-pocket expenses. While research groups are working to find a cure for EB, clinicians working with EB patients around the world have found practical and relatively inexpensive tips to make life easier for people with EB. NoBabyBlisters.org, a nonprofit organization actively supplying monthly medical supplies for EB children on five continents and working on EB research, has innovated, developed, collected, and now offers here seven such practical and actionable items learned from its experience in the real world assisting children in less-developed nations, typically with hot climates. These are based on real-world clinical experience dealing with a complex disorder under challenging circumstances. The goal of this short paper is to provide advice to EB caregivers and their loved ones that may make things easier and enhance quality of life, including blister and pain reduction.

Pirates of Clinical Trials.

With the burgeoning numbers of clinical trials, the competition among sponsors for research subjects has grown intensely. Many clinical trials fail to meet their recruitment goals. Contract research organizations (CROs) that help conduct all or portions of a clinical study have transitioned from highly specialized niches, such as biostatistical analysis or regulatory compliance, to more overall functions to keep a trial moving forward. CROs establish agreements with sponsors, including how much a site will be paid per study subject. CROs are locked into that pricing, but over the course of a study's recruitment period, sponsors with deeper pockets may step in and offer more compensation per subject. The result is a competitive market place that favors big sponsors and puts smaller CROs and start-ups at a disadvantage.

Brave New Healthcare: A Narrative Review of Digital Healthcare in American Medicine.

The digital revolution has had a profound effect on American and global healthcare, which was accelerated by the pandemic and telehealth applications. Digital health also includes popular and more esoteric forms of wearable monitoring systems and interscatter and other wireless technologies that facilitate their telemetry. The rise in artificial intelligence (AI) and machine learning (ML) may serve to improve interpretation from imaging technologies to electrocardiography or electroencephalographic tracings, and new ML techniques may allow these systems to scan data to discern and contextualize patterns that may have evaded human physicians. The necessity of virtual care during the pandemic has morphed into new treatment paradigms, which have gained patient acceptance but still raise issues with respect to privacy laws and credentialing. Augmented and virtual reality tools can facilitate surgical planning and "hands-on" clinical training activities. Patients are working with new frontiers in digital health in the form of "Dr. Google" and patient support websites to learn or share medical information. Patient-facing digital health information is both a blessing and curse, in that it can be a boon to health-literate patients who seek to be more active in their own care. On the other hand, digital health information can lead to false conclusions, catastrophizing, misunderstandings, and "cyberchondria." The role of blockchain, familiar from cryptocurrency, may play a role in future healthcare information and would serve as a disruptive, decentralizing, and potentially beneficial change. These important changes are both exciting and perplexing as clinicians and their patients learn to navigate this new system and how we address the questions it raises, such as medical privacy in a digital age. The goal of this review is to explore the vast range of digital health and how it may impact the healthcare system.

From Antidepressant Tianeptine to Street Drug ZaZa: A Narrative Review.

Tianeptine is often incorrectly described as a selective serotonin reuptake inhibitor, but it actually is a µ-opioid receptor agonist with anxiolytic effects. It has been approved since the last 1980s in about 24 countries as a treatment for depression, but it was never cleared to market in the United States for this purpose. Nevertheless, tianeptine joined the billion-dollar US market of nootropics as ZaZa or Tianna Red and is widely available online and in small shops without a prescription, to the point that it has been nicknamed "gas station heroin." While the therapeutic dose range is about 25 to 50 mg/day, tianeptine abusers may take 100 times that amount. Tolerance occurs rapidly and users who seek to recapture the short-lived euphoric effects of the drug have to take more and more. Social media has peer-support sites for those trying to discontinue tianeptine. Tianeptine is associated with multiple side effects at high doses along with dependence, withdrawal symptoms, toxicity, respiratory depression, and even mortality. Agitation is more often a presenting symptom of withdrawal than toxicity. Tianeptine is often used by polysubstance drug abusers who may be unaware of the drug's dangers. Few clinicians are aware of tianeptine and most urine assays do not screen for it. Greater awareness is needed for this drug and steps must be taken as tianeptine or "gas station heroin" is emerging as a new public health threat.

Old Drugs and New Challenges: A Narrative Review of Nitazenes.

Nitazenes are a group of compounds developed in the 1950s as opioid analgesics, but they were never approved to market. As such, they are not well known outside of academic research laboratories. A characteristic of nitazenes is their high potency (e.g., hundreds to thousands fold more potent than morphine and other opioids and tenfold more potent than fentanyl). In the past few years, several nitazenes, including "designer analogs," have been detected in the illicit drug supply and have been implicated in overdose mortality, primarily due to their exceptionally high potency. In the street drug supply, nitazenes are often found mixed with fentanyl or other agents but their presence is not always disclosed to drug buyers, who may not even be familiar with nitazenes. These drugs pose a particular challenge since there is little experience in how to reverse a nitazene overdose or potential drug-drug or drug-alcohol interactions. Public health efforts are needed to better inform street drug consumers, first responders, healthcare professionals, and the general public about these "new old drugs" that are infiltrating the recreational drug supply.

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.

How Opioids Changed What We Thought About Addiction and the Implications for Public Health: An Editorial.

Dealing with substance use disorder is moving out of the realm of criminality, morality, and law enforcement toward a more medically grounded approach. This was particularly evident when opioid use disorder, which started roughly around 1999 and has continued to increase over the decades, was observed to affect mainly White people. This has driven a re-assessment of the nature of addiction. The previous big drug epidemic involved crack cocaine which was criminalized to the point that many users drew harsh prison sentences. Crack addiction was seen as a crime. Of course, crack was a drug predominantly used by Black people. The emergence of a White drug addict prompted a re-evaluation of what addiction meant and how it might be treated. This has led to neuropsychiatric evaluations of substance use disorder and the notion that opioid use disorder is a disease rather than a moral failure. Treating opioid use disorder as a physiological disorder caused by prolonged exposure to a drug that has the ability to rewire a healthy brain to drive it to compulsively seek more drugs appears to be a reasonable, compassionate, and scientifically sound approach to substance use disorder. This may lead to effective ways to treat or manage opioid use disorder. While this is a good thing, it is regrettable that such measures were not considered when the drug epidemic affected racial or ethnic minorities with less political influence and social clout. In other words, seeing opioid use disorder as, first and foremost, a disease rather than a crime is enlightened, even if we did not take the most enlightened path to get there.

A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review.

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy.

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.

Treating Geriatric Sports Injury Among Pickleball Players: A Narrative Review of an Exercise Craze Among Seniors.

The sudden and enormous popularity of pickleball has included a surprising and large contingent of geriatric players. Similar to tennis and badminton, pickleball is a game with a short learning curve that offers low-impact cardiovascular benefits. Unlike tennis, most injuries in pickleball are sustained by older rather than younger players. In fact, pickleball-related injuries increase with increasing age. Such injuries include strains, sprains, joint pain, falls, and fractures. The most affected joints are the wrists, shoulders, knees, and ankles. Clinicians can advise their older pickleball patients on strategies and tips to minimize the risk of injury. This may be particularly important because many older individuals playing pickleball today were previously sedentary. Older people may be attracted to pickleball because it is an inclusive sport with a high socialization factor. Nevertheless, pickleball can deliver an excellent cardiovascular workout and it may be an example of a successful way to promote exercise among older people and those who resist exercise.

The Challenges of Pain Assessment in Geriatric Patients With Dementia: A Review.

Pain in dementia patients is common, poorly measured, and undertreated. It is important to discuss the challenges in the pain assessment and management to find a possible solution for adequate pain management. The aim of this article is to discuss the challenges in the assessment of pain in geriatric patients with dementia. An extensive online database search was conducted via multiple websites using the following keywords: "dementia," "pain assessments," "pain assessment with dementia," "causes of pain with dementia," "pain assessments using recent technology," "geriatric," and "old age" to identify the relevant articles. Our inclusion criteria were articles that focused on pain in geriatric patients diagnosed with dementia, in English, published between January 2018 and January 2023, and available as free full text and those which were clinical trials, observational studies, review articles, systemic reviews, meta-analysis, or case series. The exclusion criteria were articles that did not have pain in geriatric patients diagnosed with dementia as their primary focus, involving geriatric or non-geriatric patients with major psychological distress, not in the English language, not published between January 2018 and January 2023, and not available as free full-text and those which were case reports and editorial articles. After manually excluding the articles that did not meet our inclusion criteria, we ended up with 38 articles. In conclusion, any instruments have been made for the pain assessment in patients with dementia. The two most common tools used to assess pain in this vulnerable population are the Pain Assessment in Advanced Dementia (PAINAD) and Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC) scales. The utilization of new technology may offer promising solutions for the pain assessment in patients with dementia.

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.

Mobile Narcotic Treatment Programs: On the Road Again?

Many Americans with opioid use disorder (OUD), do not have access to treatment. Mobile narcotic treatment programs are now under new regulations that may make treatment more accessible to more people. These mobile programs can help expand the reach of opioid agonist treatment for OUD, help reduce human immunodeficiency viruses (HIV) and hepatitis C in the OUD population, and have retention rates that are often better than those at fixed-site clinics. Mobile services can also help reach marginalized individuals, the homeless, rural communities, and other underserved communities. They may offer methadone or buprenorphine treatment. Such mobile services have been used inside and outside the United States with promising results. In particular, mobile programs can make treatment available to people who do not have insurance, who lack reliable transportation, live in chaotic situations, or may be undomiciled. The potential pairing of mobile programs together with technology, such as smartphone apps or online resources, may allow mobile patients to benefit from counseling as well. Mobile clinics must be attached to a fixed-site narcotic treatment program and may have limitations with respect to the geographic area served. Mobile programs must have policies and procedures to store, transport, deliver, account for, reconcile, and dispose of opioid waste and would be subject to audit. Mobile opioid agonist therapy is an important and innovative service of particular value to underserved communities.

Controlled Substance Waste: Concerns, Controversies, Solutions.

Hospitals, clinics, and organizations using controlled substances must have policies and procedures in place for disposing of these substances and to avoid potential drug diversion as well as environmental pollution. Challenging, particularly to hospitals, is the ability to dispose of the waste of any number of hundreds of products every day, some of which require specific handling and protocols for safety. Incineration might be appropriate but many hospitals and certainly smaller clinics lack the appropriate facilities. Clinics and facilities that use controlled substances must maintain adequate and detailed records, but individual healthcare systems impose their own specific requirements. Some, for example, require drug disposal to be witnessed. However, recordkeeping systems must be robust and frequently audited to prevent diversion. Most healthcare systems want to dispose of controlled substances in an environmentally responsible way but in addition to federal laws in the United States, most states have their own environmental agencies and may have local regulations. Navigating this system can be complex, and since all regulations are subject to change, it requires vigilance and expertise.

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.