The unsolved case of “bone-impairing analgesics”. The endocrine effects of opioids on bone metabolism

The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density

Prophylaxis of Postoperative Nausea and Vomiting in Adolescent Patients: A Review with Emphasis on Combination of Fixed-Dose Ondansetron and Transdermal Scopolamine

Postoperative nausea and vomiting (PONV) is a relatively common occurrence (20–30%) that delays discharge and, if persistent, can lead to serious complications. The incidence of PONV is a function of patient characteristics, the type and duration of surgery, the type of anesthesia, and the choice of pre-, intra-, and postoperative pharmacotherapy. There are no completely effective antiemetic agents for this condition, but recommendations for treatment strategies are separately available for pediatric and adult patients. Left unclear is whether adolescents should be guided by the pediatric or the adult recommendations. We review the developmental physiology of the relevant physiological factors (absorption, distribution, metabolism, and elimination). We also review the clinical evidence regarding the safety and efficacy of a fixed-dose combination of ondansetron (4 mg, i.v.) and transdermal scopolamine (1.5 mg)

The Subcutaneous Implantable Cardioverter-Defibrillator

The subcutaneous ICD (S-ICD) represents an important advancement in defibrillation therapy that obviates the need for a transvenous lead, the most frequent complication with transvenous devices. The S-ICD has been shown similarly safe and effective as transvenous ICD therapy, but the two devices are not interchangeable. The S-ICD is only suitable for patients who do not require bradycardia or antitachycardia pacing functionality. In patients with underlying diseases associated with polymorphic ventricular tachycardia and a long life expectancy, an S-ICD may be the preferred choice. Moreover, it is advantageous in the situation of increased risk of endocarditis, i.e., previous device system infection and immunosuppression, including hemodialysis. In patients with abnormal vascular access and/or right-sided heart structural abnormalities, it may be the only option. The S-ICD is bulkier, the battery longevity is shorter, and the device cost is higher, even though remote follow-up is possible. A two- or three-incision implant procedure has been described with a lateral placement of the device and a single subcutaneous lead. The rate of inappropriate therapy for both S-ICD and transvenous systems is similar, but S-ICD inappropriate shocks are more frequently attributable to oversensing, which can often be resolved with sensing adjustments

Gabapentinoid use disorder. Update for clinicians

Gabapentinoids (gabapentin and pregabalin) are versatile drugs, indicated mainly for epilepsy and neuropathic pain, and have long been viewed as agents with little potential for abuse. Burgeoning prescribing patterns and studies indicate that these drugs are increasingly being abused, particularly by polydrug abusers who also abuse opioids. Gabapentinoid abuse is found in less 2% of the general population but may be as high as 15% to 22% among opioid abusers. Other risk factors for gabapentinoid abuse are less clear-cut but include mental health disorders. Gabapentinoids are relatively easy for drug abusers to obtain and many clinicians are not fully aware of their abuse potential. It is thought that gabapentinoids may offer psychoactive effects or enhance the effects of other drugs of abuse. Those who discontinue gabapentinoids abruptly may suffer withdrawal symptoms, but gabapentinoid overdose fatality is rare. Since gabapentinoids are often prescribed off-label to treat psychiatric disorders, these drugs may be dispensed to a particularly vulnerable population. Clinicians must be aware of the potential for Gabapentinoid Use Disorder: Update for Clinicians

The Wearable Cardioverter-Defibrillator

The wearable cardioverter-defibrillator (WCD) is a rechargeable external device that can be worn under the clothing all day long and protects the wearer from potentially life-threatening ventricular tachyarrhythmias. When a dangerous arrhythmia is detected, the WCD can deliver high-energy shocks. The WCD has been shown to be effective in accurately detecting and appropriately treating ventricular tachycardia (VT) and ventricular fibrillation (VF). It is intended for temporary use as a bridge to an implantable cardioverter-defibrillator (ICD), heart transplantation, or left ventricular assist device; patients with heart failure with reduced ejection fraction may benefit from the WCD while their condition improves. It can be used temporarily after explant of an ICD until reimplantation is deemed possible. In select patients with myocardial infarction, a WCD may be useful during the immediate period after infarction. It is indicated for use when a permanently implanted ICD must be explanted because of infection; the patient can use the WCD until the infection resolves, and a new ICD can be implanted. The role of the WCD is emerging as an important therapeutic option to protect patients at elevated risk of sudden cardiac death (SCD)

Ibuprofen Safety at the Golden Anniversary: Are all NSAIDs the Same? A Narrative Review

Ibuprofen first came to market about 50 years ago and rapidly moved to over-the-counter (OTC) sales. In April 2019, the National Agency for the Safety of Medicines and Health Products (ANSM) of France issued a warning for NSAID uses by patients with infectious diseases based on an analysis of 20 years of real-world safety data on ibuprofen and ketoprofen. Nevertheless, ibuprofen remains a mainstay in the analgesic armamentarium and with numerous randomized clinical trials, head-to-head studies, and decades of clinical experience. The authors offer a review of the safety of ibuprofen and how it may differ from other NSAIDs. Ibuprofen is associated with certain well-known gastrointestinal adverse effects that are related to dose and patient population. Among nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen has a comparatively low risk of cardiovascular adverse effects. It has been associated with renal and hepatic adverse effects, which appear to depend on dose, concomitant medications, and patient population. The association of ibuprofen with infections is more complex in that it confers risk in some situations but benefits in others, the latter in cystic fibrosis. Emerging interest in the literature is providing evidence of the role of ibuprofen as a possible endocrine disrupter as well as its potential antiproliferative effects for cancer cells. Taken altogether, ibuprofen has a favorable safety profile and is an effective analgesic for many acute and chronic pain conditions, although it—like other NSAIDs—is not without risk. After 50 years, evidence is still emerging about ibuprofen and its unique safety profile among NSAIDs. The Rapid Service Fee was funded by Abbott Established Pharmaceuticals Division (EPD)

Pain Management in the Elderly: An FDA Safe Use Initiative Expert Panel's View on Preventable Harm Associated with NSAID Therapy

Optimization of current pain management strategies is necessary in order to reduce medication risks. Promoting patient and healthcare provider education on pain and pain medications is an essential step in reducing inadequate prescribing behaviors and adverse events. In an effort to raise awareness on medication safety, the FDA has launched the Safe Use Initiative program. The program seeks to identify areas with the greatest amount of preventable harm and help promote new methods and practices to reduce medication risks. Since the establishment of the program, FDA's Safe Use initiative staff convened a panel of key opinion leaders throughout the medical community to address pain management in older adults (≥65 years of age). The aim of the expert panel was to focus on areas where significant risk occurs and where potential interventions will be feasible, implementable, and lead to substantial impact. The panel suggested one focus could be the use of NSAIDs for pain management in the elderly

Leadless Pacemakers

Leadless or transcatheter pacemakers have recently been introduced to market with important benefits and some limitations. Implanted entirely within the right ventricle, these devices eliminate the need for transvenous pacing leads and pacemaker pockets and thus reduce the risk of infections and lead-related problems. Currently, they offer only VVI/R pacing and they cannot provide atrial sensing, antitachycardia pacing, or AV synchrony. They offer a number of features (such as rate response) and electrogram storage, albeit more limited than in a transvenous system. Real-world clinical data are needed to better comment on projected battery life, which manufacturers suggest will be at least equivalent to transvenous devices. Extracting an implanted leadless pacemaker remains a challenge, although proprietary snare and removal systems are available. However, a leadless pacemaker at end of service may be programmed to OOO and left in place; a revised device may be implanted adjacent. These innovative new devices may have important uses in special populations. Initial data on implant success and adverse events are favorable. Currently, there are two leadless pacemakers available: the Micra™ device by Medtronic and the Nanostim™ device by Abbott (formerly St. Jude Medical)

Sudden Cardiac Death in Hereditary Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is characterized by the phenotype of a dilated left ventricle with systolic dysfunction. It is classified as hereditary when it is deemed of genetic origin; more than 50 genes are reported to be related to the condition. Symptoms include, among others, dyspnea, fatigue, arrhythmias, and syncope. Unfortunately, sudden cardiac death may be the first manifestation of the disease. Risk stratification regarding sudden death in hereditary DCM as well as preventive management poses a challenge due to the heterogeneity of the disease. The purpose of this chapter is to present the epidemiology, risk stratification, and preventive strategies of sudden cardiac death in hereditary DCM