The Ramifications of Opioid Utilization and Outcomes of Alternative Pain Control Strategies for Total Knee Arthroplasties.

Morbidity and mortality related to opioid use has generated a public health crisis in the United States. Total knee arthroplasty (TKA) is an increasingly common procedure and is often accompanied by post-operative opioid utilization. Unfortunately, post-operative opioid usage after TKA has been shown to lead to higher rates of complications, longer hospital stays, increased costs, and more frequent need for revision surgery. Pre-operative opioid utilization has been shown to be one of the most important predictors of post-operative opioid usage. Additional risk factors for continued post-operative opioid utilization after TKA include pre-operative substance and tobacco use as well as higher post-operative prescription dosages, younger age, female gender, and Medicaid insurance. One method for mitigating excessive post-operative opioid utilization are Enhanced Recovery After Surgery (ERAS) protocols, which include a multidisciplinary approach that focuses on perioperative factors to optimize patient recovery and function after surgery. Additional strategies include multimodal pain regimens with epidural anesthetics, extended duration local anesthetics and adjuvants, and ultrasound guided peripheral nerve blocks. In recent years, opioid prescribing duration limitations have also been put into place by state and federal government, hospital systems, and ambulatory surgery centers making effective acute pain management imperative for all stakeholders. In this regard, as rates of TKA continue to increase across the United States, multidisciplinary efforts by all stakeholders are needed to ensure adequate pain control while preventing the negative sequalae of opioid medications.

Opioid Use Consequences, Governmental Strategies, and Alternative Pain Control Techniques Following Total Hip Arthroplasties.

Over the last several decades, rates of opioid use and associated problems have dramatically increased in the United States leading to laws limiting prescription duration for acute pain management. As a result, orthopedic surgeons who perform total hip arthroplasty (THA), a procedure that often leads to significant postoperative pain, have been faced with substantial challenges to adequately mitigate patient pain while also reducing opioid intake. Current strategies include identifying and correcting modifiable risk factors associated with postoperative opioid use such as preoperative opioid use, alcohol and tobacco abuse, and untreated psychiatric illness. Additionally, recent evidence has emerged in the form of Enhanced Recovery After Surgery (ERAS) protocols suggesting that a multidisciplinary focus on patient factors perioperatively can lead to reduced postoperative opioid administration and decreased hospital stays. A cornerstone of ERAS protocols includes multimodal pain regimens with opioid rescue only as needed, which often includes multiple systemic pain therapies such as acetaminophen, gabapentin, non-steroidal anti-inflammatory drugs, as well as targeted pain therapies that include epidural catheters and ultrasound-guided nerve blocks. Many hospital systems and states have also implemented opioid prescribing limitations with mixed success. As the opioid epidemic continues in the United States, while contributing to poor outcomes following elective surgeries, further research is warranted to identify multidisciplinary strategies that mitigate opioid use while also allowing for adequate pain control and rehabilitation.

Calcitonin (FORTICAL, MIACALCIN) for the treatment of vertebral compression fractures.

PURPOSE OF REVIEW: Osteoporosis is a common condition affecting the musculoskeletal system. It carries with it increased risks of fracture in many areas of the body, leading to reduced quality of life, limited mobility, and other long-term implications such as chronic pain. Vertebral compression fractures are a common development in patients with osteoporosis. Current treatment options focus on reducing pain; preventative methods are somewhat limited and focus on minimizing risk factors for the development of osteoporosis. In this review, we explore the use of calcitonin (FORTICAL, MIACALCIN) to treat vertebral compression fractures (VCFs). RECENT FINDINGS: Osteoporosis had a prevalence of more than 10% in the United States in 2010. The CDC estimates that nearly 25% of women over age 65 have findings of osteoporosis, which include low spinal bone mass. The condition is highly prevalent and, in an aging U.S. population, quite clinically relevant. Risk factors for development include advanced age, cigarette smoking, medications, reduced physical activity, and low calcium and vitamin D intake. Family history may also play a role. Diagnosis is made based on bone mineral density.Standard therapy for VCFs in osteoporosis includes analgesic medications, such as NSAIDs and biphosphonates, and surgical intervention. NSAIDs address the chronic pain that is a common long-term effect of VCFs. Biphosphonates have recently been used to attempt to halt the progression and provide prevention. Surgical interventions such as balloon kyphoplasty and vertebroplasty are typically reserved for patients who have failed other methods.Calcitonin is a peptide naturally produced by the human body, released from the parathyroid gland. It binds to osteoclasts, inhibiting them from inducing bone resorption. By relatively unknown mechanisms, it also appears to cause endorphin release and mitigate pain. Clinical data has shown safety and efficacy for exogenous calcitonin in reducing bone turnover and reducing VCF-induced pain. SUMMARY: Osteoporosis is a common condition that can lead to complications such as vertebral compression fractures. It can significantly impact the quality of life in many elderly Americans. There is currently no singular treatment, but calcitonin has recently been explored as a possible option for minimizing pain and reducing disease progression. Further studies are needed to understand its preventative benefits fully.

An Update on Postoperative Opioid Use and Alternative Pain Control Following Spine Surgery.

Opioids are commonly prescribed postoperatively for pain control, especially in spine surgery. Not only does this pose concerns for potential abuse, but it also has been shown to worsen certain outcomes. Risk factors for increased use include preoperative opioid use, female sex, psychiatric diagnoses, and drug and alcohol use. Over the past few decades, there have been increasing efforts mostly spearheaded by governmental agencies to decrease postoperative opioid use via opioid prescription limitation laws regulating the number of days and amounts of analgesics prescribed and promotion of the use of enhanced recovery after surgery (ERAS) protocols, multimodal pain regimens, epidural catheters, and ultrasound-guided peripheral nerve blocks. These strategies collectively have been efficacious in decreasing overall opioid use and better controlling patients' postoperative pain while simultaneously improving other outcomes such as postoperative nausea, vomiting, and length of stay. With an aging population undergoing an increasing number of spinal surgeries each year, it is now more important than ever to continue these efforts to improve the quality and safety of pain control methods after spinal surgery and limit the transition of acute management to the development of opioid dependence and addiction long-term.

Monomethyl Fumarate (MMF, Bafiertam) for the Treatment of Relapsing Forms of Multiple Sclerosis (MS).

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies-including antibody therapy and oral agents-were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

Postoperative Rehabilitation of Multidirectional Instability Surgery: A Systematic Review.

Multidirectional instability (MDI) of the shoulder is managed with surgery when conservative rehabilitation fails. The optimal postsurgical management of MDI is not well understood. The purpose of this study is to create a systematic review evaluating postsurgical rehabilitation protocols treating MDI. Articles were included if a postsurgical rehabilitation protocol was described following surgical treatment for MDI. Identified articles underwent 2 phases of screening by blinded team members. Remaining articles had their level of evidence determined by a predefined grading system, ranging from levels I to V. Articles with evidence levels I to IV were included in analysis. Of the 163 articles identified in the literature, 9 were included in this study. Surgical techniques examined in these articles include capsular plication, rotator interval closure, and capsular shift. Rehabilitation protocols were evaluated for duration of treatment and physical therapy modalities. Article results were evaluated for subjective and objective measures of protocol success. Overall, there is a lack of evidence to indicate the optimal rehabilitation protocol post-MDI surgery. Further research is needed to compare rehabilitation protocols following specific surgical procedures to determine their effect on postsurgical patient outcomes.

Istradefylline to Treat Patients with Parkinson's Disease Experiencing "Off" Episodes: A Comprehensive Review.

Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as "off episodes", are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing "off episodes". It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.

The utilization of buprenorphine in chronic pain.

Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis. This can help address critical factors including suffering, quality of life, participation, and with family and social life, which continue to become more important in evaluating the quality of the health care we give our patients today. During the past decade of the opioid epidemic, methadone was the primary treatment for opioid addiction until buprenorphine was approved. Buprenorphine's high-affinity partial agonist properties make it a good alternative to methadone due to lower abuse potential and safer adverse effect profile while maintaining significant efficacy. Expanded out-patient prescribing options have allowed physician and physician extenders such as physician assistants and nurse practitioners to treat these patients that otherwise would have been required to utilize methadone. With unique pharmacological properties, buprenorphine is a safe and effective analgesic for chronic pain. The literature for buprenorphine shows great potential for its utilization in the treatment of chronic pain.

The use of antineuropathic medications for the treatment of chronic pain.

Chronic pain syndromes cost the US healthcare system over $600 billion per year. A subtype of chronic pain is neuropathic pain (NP), which is defined as "pain caused by a lesion or disease of the somatosensory system," according to the International Association for the Study of Pain (IASP). The pathophysiology of neuropathic pain is very complex, and more research needs to be done to find the exact mechanism. Patients that have preexisting conditions such as cancer and diabetes are at high-risk of developing NP. Many NP patients are misdiagnosed and receive delayed treatment due to a lack of a standardized classification system that allows clinicians to identify, understand, and utilize pain management in these patients. Medications like tricyclic antidepressants, serotonin-norepinephrine reuptake Inhibitor (SNRIs), and gabapentinoids are first-line treatments followed by opioids, cannabinoids, and other drugs. There are limited studies on the treatment of NP.

A Review of Patisiran (ONPATTRO®) for the Treatment of Polyneuropathy in People with Hereditary Transthyretin Amyloidosis.

Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000-10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.

Lasmiditan for the Treatment of Migraines With or Without Aura in Adults.

Migraines are a common form of primary headache, affecting women more than men (17.4% and 5.7% of US population, respectively, a total of 12%) that carry significant morbidity and disability, as well as a hefty healthcare price tag. They are most prevalent in women of reproductive ages and are estimated to be the 6th disease in order of causing global burden. They are estimated to cause 45.1 million years lived with disability, or 2.9% of global years lost to disability. Migraine treatment divides into acute, abortive treatment for relief of an ongoing migraine attack, and prophylactic therapy to reduce the occurrence of migraines, specifically for patients suffering from chronic and frequent episodic migraines. Traditional abortive treatment usually begins with NSAID and non-specific analgesics that are effective in curbing mild to moderate attacks. 5HT1-agonists, such as triptans, are often used for second-line and for severe attacks. Triptans are generally better tolerated in the longterm than NSAIDs and other analgesics, though they carry a significant side-effect profile and are contraindicated in large parts of the population. Prophylactic therapy is usually reserved for patients with frequent recurrence owing to medication side effects and overall poor adherence to the medication schedule. Importantly, medication overuse may actually lead to the development of chronic migraines from previously episodic attacks. Recent research has shed more light on the pathophysiology of migraine and the role of CGRP in the trigeminovascular system. Recent pharmacological advances were made in developing more specific drugs based on this knowledge, including CGRP neutralizing antibodies, receptor antagonists, and the development of ditans. These novel drugs are highly specific to peripheral and central 5-HT1F receptors and effective in the treatment of acute migraine attacks. Binding these receptors reduces the production of CGRP and Glutamate, two important ligands in the nociceptive stimulus involved with the generation and propagation of migraines. Several large clinical studies showed Lasmiditan to be effective in the treatment of acute migraine attacks. Importantly, due to its receptor specificity, it lacks the vasoconstriction that is associated with triptans and is thus safer is larger parts of the population, specifically in patients with cardiac and vascular disease. Though more research is required, specifically with aftermarket surveillance to elucidate rare potential side effects, Lasmiditan is a targeted anti-migraine drug that is both safe and effective, and carries an overall superior therapeutic profile to its predecessors. It joins the array of medications that target CGRP signaling, such as gepants and CGRP-antibodies, to establish a new line of care for this common disabling condition.