Mechanisms and Preventative Strategies for Persistent Pain following Knee and Hip Joint Replacement Surgery: A Narrative Review.

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.

Perioperative cognition in association with malnutrition and frailty: a narrative review.

Postoperative delirium (POD) is a prevalent clinical entity characterized by reversible fluctuating altered mental status and cognitive impairment with acute and rapid onset a few days after major surgery. Postoperative cognitive decline (POCD) is a more permanent extension of POD characterized by prolonged global cognitive impairment for several months to years after surgery and anesthesia. Both syndromes have been shown to increase morbidity and mortality in postoperative patients making their multiple risk factors targets for optimization. In particular, nutrition imparts a significant and potentially reversible risk factor. Malnutrition and frailty have been linked as risk factors and predictive indicators for POD and less so for POCD. This review aims to outline the association between nutrition and perioperative cognitive outcomes as well as potential interventions such as prehabilitation.

Novel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review.

Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects. In this review, we discuss the mechanisms of action, findings from preclinical studies and clinical trials, and potential advantages of several novel opioids. The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)-all of which have demonstrated success in the clinical setting when compared to traditional opioids. On the other hand, dinalbuphine sebacate (DNS; semi-synthetic mu partial antagonist and kappa agonist), dual enkephalinase inhibitors (STR-324, PL37, and PL265), and endomorphin-1 analog (CYT-1010) have shown good efficacy in preclinical studies with future plans for clinical trials. Rather than relying solely on mu-opioid receptor agonism to relieve pain and risk opioid-related adverse events (ORAEs), novel opioids make use of alternative mechanisms of action to treat pain while maintaining a safer side-effect profile, such as lower incidence of nausea, vomiting, sedation, and respiratory depression as well as reduced abuse potential.

Anesthesia, the developing brain, and dexmedetomidine for neuroprotection.

Anesthesia-induced neurotoxicity is a set of unfavorable adverse effects on central or peripheral nervous systems associated with administration of anesthesia. Several animal model studies from the early 2000's, from rodents to non-human primates, have shown that general anesthetics cause neuroapoptosis and impairment in neurodevelopment. It has been difficult to translate this evidence to clinical practice. However, some studies suggest lasting behavioral effects in humans due to early anesthesia exposure. Dexmedetomidine is a sedative and analgesic with agonist activities on the alpha-2 (ɑ2) adrenoceptors as well as imidazoline type 2 (I2) receptors, allowing it to affect intracellular signaling and modulate cellular processes. In addition to being easily delivered, distributed, and eliminated from the body, dexmedetomidine stands out for its ability to offer neuroprotection against apoptosis, ischemia, and inflammation while preserving neuroplasticity, as demonstrated through many animal studies. This property puts dexmedetomidine in the unique position as an anesthetic that may circumvent the neurotoxicity potentially associated with anesthesia.

Extending the Population Health Workforce Through Service Learning Internships During COVID: A Community Case Study.

This report arises from the intersection of service learning and population health at an academic medical center. At the University of California, San Francisco (UCSF), the Office of Population Health and Accountable Care (OPHAC) employs health care navigators to help patients access and benefit from high-value care. In early 2020, facing COVID-19, UCSF leaders asked OPHAC to help patients and employees navigate testing, treatment, tracing, and returning to work protocols. OPHAC established a COVID hotline to route callers to the appropriate resources, but needed to increase the capacity of the navigator workforce. To address this need, OPHAC turned to UCSF's service learning program for undergraduates, the Patient Support Corps (PSC). In this program, UC Berkeley undergraduates earn academic credit in exchange for serving as unpaid patient navigators. In July 2020, OPHAC provided administrative funding for the PSC to recruit and deploy students as COVID hotline navigators. In September 2020, the PSC deployed 20 students collectively representing 2.0 full-time equivalent navigators. After training and observation, and with supervision and escalation pathways, students were able to fill half-day shifts and perform near the level of staff navigators. Key facilitators relevant to success reflected both PSC and OPHAC strengths. The PSC onboards student interns as institutional affiliates, giving them access to key information technology systems, and trains them in privacy and other regulatory requirements so they can work directly with patients. OPHAC strengths included a learning health systems culture that fosters peer mentoring and collaboration. A key challenge was that, even after training, students required around 10 h of supervised practice before being able to take calls independently. As a result, students rolled on to the hotline in waves rather than all at once. Post-COVID, OPHAC is planning to use student navigators for outreach. Meanwhile, the PSC is collaborating with pipeline programs in hopes of offering this internship experience to more students from backgrounds that are under-represented in healthcare. Other campuses in the University of California system are interested in replicating this program. Adopters see the opportunity to increase capacity and diversity while developing the next generation of health and allied health professionals.