Category: Pain Management

Categories : Pain ManagementTags :

New Monoclonal Antibody Eptinezumab Success in Hard-to-treat Migraine

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A trial for a new monoclonal antibody, eptinezumab, in the treatment of resistant migraine has demonstrated that it significantly reduced migraine days with acceptable safety and tolerability. The findings were published in The Lancet.

Eptinezumab, which targets calcitonin gene-related peptide, has shown migraine preventive effects starting the day following infusion and acceptable safety and tolerability in phase 3 trials, but benefits in the subpopulations of patients with previous preventive treatment failures were not examined.

In the 24-week double-blind placebo-controlled DELIVER phase 3b trial, the researchers recruited adults with episodic or chronic migraine with at least four monthly migraine days and two-to-four previous preventive treatment failures within the past 10 years. Patients were randomised to either eptinezumab 100mg, eptinezumab 300mg, or placebo. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (captured using a daily electronic diary) in weeks 1–12, assessed in the full analysis set. All participants and study personnel were masked to study drug assignments. A 48-week dose-blinded extension period is ongoing.

In all, 865 patients completed the placebo-controlled period. Compared to baseline, weeks 1–12 saw reductions of 4.8 mean monthly migraine days with eptinezumab 100mg and 5.3 days at 300mg, which was a significantly less than the reduction of 2.1 days with placebo.

Adverse events were reported in 42% of patients in the eptinezumab 100mg group, 41% in the 300mg group, and in 40% in the placebo group. COVID was the most common treatment-emergent adverse event. Serious adverse events were uncommon (five [2%] of 299 in the 100mg group, seven [2%] of 294 in the 300mg group, four [1%] of 298 in the placebo group) and included anaphylactic reaction (eptinezumab 300 mg n=2) and COVID-19 (eptinezumab 100 mg n=1 and eptinezumab 300 mg n=1).

In adults with migraine and two-to-four previous preventive treatment failures, eptinezumab provided significant migraine preventive effects compared with placebo, with acceptable safety and tolerability, indicating that eptinezumab might be an effective treatment option for this patient population. The trial has a dose-blinded extension period which will provide additional long-term safety data in patients with migraine and previous preventive treatment failures.

Categories : Pain ManagementTags :

Cannabis is Moderately Effective for Chronic Pain, Review Finds

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Cannabis’s pain reduction effects appear to be less effective than previously though. Photo by Kindel Media

Cannabis product use provides modest, short-term improvements in chronic pain, albeit with some side effects, according to a large review of research on cannabis pain management. The review also revealed a general lack of high quality evidence such as randomised controlled trials (RCTs). The data will be uploaded to a web app made by Oregon Health & Science University to inform clinicians on cannabis medications.

Reporting in Annals of Internal Medicine, researchers found evidence to support a short-term benefit in treating neuropathic pain with two synthetic products with 100% tetrahydrocannabinol (THC): dronabinol (under the trade name Marinol) and nabilone (Cesamet). Another product, a sublingual spray of equal parts THC and cannabidiol (CBD), known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain. All of the products had side effects, such as nausea, sedation and dizziness.

From 3000 studies, the researchers selected RCTs or comparative observational studies of patients with chronic pain that compared cannabis products with a placebo or no treatment (that is, usual care) for at least 4 weeks of treatment or follow-up.

They ended up with a total of 25 with scientifically valid evidence – 18 RCTs and seven observational studies. Cannabinoids were categorised as high, comparable, or low THC-to-CBD ratio. The researchers found:

  • Synthetic products with high THC (> 98%) and little or no CBD: moderate improvement in pain, but greater sedation risk and possible increase in dizziness
  • Extracted products with majority THC (THC:CBD ratio ranging from 3:1 to 47:1): no significant improvement in pain, but greater study withdrawal because of adverse events and dizziness
  • Sublingual sprays with comparable THC and CBD levels: small improvement in pain but a much greater increased risk of dizziness and sedation and a moderate increase in nausea

Besides these findings, there was little evidence to support any other conclusions.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, PharmD, emeritus professor at OHSU. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

“Unfortunately, there is very little scientifically valid research into most these products. We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”

“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors noted.

This situation makes it difficult to guide patients.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, MD. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes ‘clinician briefs’ to help health care workers translate the clinical implications.

“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, MD, MCR, professor of medicine at OHSU.

Source: Oregon Health & Science University

Categories : Pain ManagementTags :

Opioid Misuse in Young Sarcoma Patients

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Depression, young man
Source: Andrew Neel on Unsplash

Nearly a quarter of young patients prescribed opioids while being treated for sarcoma continue to use opioids after treatment is completed according to findings published in CANCER, highlighting the need for safe deprescribing.

Individuals with sarcoma, a type of cancer in the bones or soft tissues, often develop damaged and fractured bones and undergo major surgical operations, and physicians may prescribe opioids for pain management. It was not clear whether doing so raises the risk for opioid misuse and overdose in these young patients. 

Melissa Beauchemin, PhD, RN, CPNP-PC, CPON, of Columbia University School of Nursing, and her colleagues sought to determine the rate of new persistent opioid use among adolescents and young adults treated for sarcoma. Persistent opioid use was defined as at least two opioid prescriptions in the 12 months after treatment was completed.  

The team drew from a large insurance claims database to analyse information on patients aged 10–26 years old who had not received prior opioids and who were diagnosed with sarcoma between 2008 and 2016.  

Among the 938 patients in the analysis, 64% received opioid prescriptions during treatment. After completing cancer therapy, 14% of patients overall and 23% of those who used opioids during treatment continued to use opioids and met the criteria for new persistent use. Being covered by Medicaid versus commercial insurance, having bone tumours versus soft tissue tumours, and receiving concurrent lorazepam (often prescribe to treat anxiety and sleeping problems) were associated with persistent opioid use. 

“Adolescents and young adults are a vulnerable population because they have benefitted less than younger and older cancer patients from recent advances. These results highlight the need to monitor young patients with sarcoma for posttreatment opioid use, given the potential negative impacts of long-term opioid use, including misuse and overdose,” said Dr Beauchemin. “Age- and developmentally appropriate strategies to effectively manage pain while minimising opioid exposure are urgently needed.” 

Dr Beauchemin stressed that for young people needing opioids for effective pain management, early and safe discontinuation of opioids should be prioritised. “Further, there is a critical need for clinical practice guidelines to support clinical decision making to safely and effectively manage pain specifically for adolescents and young adults with cancer,” she said. 

Source: Wiley

Categories : Paediatrics Pain ManagementTags :

Fall in Paediatric Post-surgical Opioid Prescriptions

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Children
Photo by Ben Wicks on Unsplash

A large study has shown that opioid prescriptions for children who underwent one of eight common outpatient surgeries declined over a period of five years. These findings, reported in the journal Pediatrics, suggest that clinicians are using more discretion when considering which paediatric patients require an opioid prescription after their procedures.

Opioids are routinely prescribed after a surgery to help paediatric patients manage mild or moderate pain. However, recent studies have suggested that recovery is similar with limited or no opioid use. Additionally, opioids prescribed to children can result in respiratory depression, which causes carbon dioxide to not be expelled from the lungs properly, and the continued use of those opioids, after acute pain has resolved. Despite these findings, no prior studies had looked at recent data on national opioid trends for surgery in children in the context of whether there has been any shift away from prescribing opioids more broadly.

“Children grow throughout their childhood, and because opioids are often prescribed based on weight, we cannot assume that what is appropriate for a 5-year-old could also apply to an adolescent,” said the study’s lead author Tori N. Sutherland, MD, MPH. “In our study, we wanted to be responsible with our data and consider surgical distribution by age group.”

In this study, the researchers used data from a private insurance database to study opioid-naïve patients under the age of 18 who underwent one of eight surgical procedures between 2014 and 2019. The procedures ranged from tonsillectomies to knee surgery. The primary outcome of the study was whether a prescription for opioids was filled within 7 days of surgery, and the secondary outcome was the total amount of opioid dispensed. A total of 124 249 patients were included in the study. Patients were separated by age into adolescents, school-aged children and preschool-aged children.

The researchers found that the percentage of children who had an opioid prescription filled after their surgery fell across all three age categories. For adolescents, prescriptions dropped from 78.2% to 48%; for school-aged children, from 53.9% to 25.5%; and for preschool-aged children, from 30.4% to 11.5%. Additionally, the average morphine milligram equivalent dispensed declined by approximately 50% across all three age groups.

The researchers also found that there was a steeper decline in opioid prescriptions beginning in late 2017, first in the adolescent group and then followed by school- and preschool-aged children. This trend appeared to represent a ‘trickle down’ effect, but more research is needed to explore the difference in trends by age group.

“Our findings demonstrate that pain treatment for children and adolescents undergoing surgery has changed dramatically over the past 5 years,” said Mark Neuman, MD, senior author. “Understanding what these trends mean for patient experiences and health outcomes is a key next step.”

Source: EurekAlert!

Categories : Implants and Prostheses Pain ManagementTags :

Tiny Implantable Electrodes to Treat Drug-resistant Neuropathic Pain

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Woman holding her wrist in pain
Credit: Pixabay CC0

Using a rice-grain sized wireless implant to stimulate peripheral nerves from within blood vessels could potentially treat drug-resistant neuropathic pain, according to a study published in Nature Biomedical Engineering.

After receiving a grant, a team set out to create implantable, wirelessly powered nerve stimulators that can be used in place of opioids for pain management. The 1-millimetre large implants are small enough to be placed on stents and delivered within blood vessels adjacent to specific areas of the central and peripheral nervous system.

Co-principal investigator of the study, Sunil A. Sheth, MD, explained: “We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders—depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection. If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”

Neuropathic pain can be a disabling disorder that accounts for nearly 40% of chronic pain sufferers, often leading to anxiety, depression, and opioid addiction. Previous studies showed that electrical stimulation is an effective treatment for reducing pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. However, existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.

According to the researchers, this new type of technology offers a way to perform minimally invasive bioelectronic therapy that helps with more precise placement of the implant and more predictable outcomes. The team are hoping to move forward with regulatory approval, which Dr Sheth estimates may take a few years.

Source: The University of Texas Health Science Center

Categories : Ageing Pain ManagementTags :

Body Mass Index Impacts Pain in People with Hand Osteoarthritis

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In a study published in Arthritis & Rheumatology, people with hand osteoarthritis, higher body mass index was associated with greater pain severity in the hands, feet, knees, and hips.

Osteoarthritis is one of the most debilitating joint disorders worldwide, affecting up to 10% of men and 13% of women.  Osteoarthritis is characterised by a progressive onset of joint damage, commonly associated with pain. Joints commonly affected include the knee, hip and hand. Various stressors, risk factors and genetics may predispose an individual to developing osteoarthritis in a particular joint.

In a study of 281 patients, researchers noted that observed associations of body mass index with hand pain and total body joint pain seemed to involve certain inflammatory markers (leptin and high-sensitivity C-reactive protein, respectively).  

The researchers suggest that systemic effects of obesity, measured by leptin, could have a larger mediating role for pain in hands than in lower extremities. Low-grade inflammation, measured by hs-CRP, may contribute to generalised pain in overweight or obese individuals.

“Our results highlight the complexity of pain in hand osteoarthritis. Obesity is not only leading to pain through increased loading of joints in the lower extremities, but seems to have systemic effects leading to pain in the hands and overall body,” said lead author Marthe Gløersen, MD, of Diakonhjemmet Hospital, in Norway.

Source: Wiley

Categories : Injury & Trauma Pain ManagementTags :

Chronic Pain in Spinal Cord Injury Increases Mental Health Risk

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Having a spinal cord injury increases risk of developing mental health conditions such as depression and anxiety by nearly 80% compared to those without the traumatic injury, a new study shows. However, chronic pain may have an equally large, negative effect on mental health.

The study, published in Spinal Cord, compared private insurance claims from more than 9000 adults with a traumatic spinal cord injury with those of more than 1 million without. Researchers accounted for a range of psychological conditions, from anxiety and mood disorders to insomnia and dementia.

People living with a spinal cord injury had a diagnosis of a mental health condition more often than those without – 59.1% versus 30.9%. While depression and adverse mental health effects are not inevitable consequences of every traumatic spinal injury, previous studies have consistently echoed higher levels of psychological morbidity among this group than the general population without spinal cord injuries.

However, this study found that chronic centralised and neuropathic pain among adults living with a spinal cord injury were robustly associated with post-traumatic stress disorder, substance use disorders and other mental health conditions. In most cases, chronic pain was an even greater influence on these conditions than exposure to living with the injury itself.

The study authors said the findings should prompt physicians to identify mental health conditions when seeing patients with spinal cord injuries and refer them for treatment.

“Improved clinical efforts are needed to facilitate screening of, and early treatment for, both chronic pain and psychological health in this higher-risk population,” said lead author Dr Mark Peterson, associate professor of physical medicine and rehabilitation at Michigan Medicine.

However, researchers note a lack of insurance coverage and limited available services will likely cause the issue to remain largely unaddressed.

“Stakeholders need to work together to lobby for more federal research funding and special policy amendments to ensure adequate and long-term insurance coverage for both physical and mental health to meet the needs of folks living with spinal cord injuries,” Dr Peterson said.

Source: EurekAlert!

Categories : Pain ManagementTags :

Duloxetine Flops for Osteoarthritis Pain Relief

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Photo by Nino Liverani on Unsplash

A new study found that duloxetine, a medication that is prescribed to treat depression and may also reduce chronic pain, did not benefit patients with hip or knee osteoarthritis.

Off-label uses for duloxetine include chemotherapy-induced peripheral neuropathy and stress urinary incontinence. It is in the Serotonin and norepinephrine reuptake inhibitors (SNRIs) class of medications. 

An open label, cluster randomised trial was conducted in patients experiencing chronic osteoarthritis-related pain in the hip or knee that did not go away with paracetamol and NSAIDs. Of 133 patients, 66 were assigned to duloxetine 60mg/day plus usual care and 66 were assigned to only usual care. 

The findings, published in Arthritis & Rheumatology howed that duloxetine did not lessen WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain at 3 months or 12 months. For the subgroup of patients with symptoms of centralised pain no effect of duloxetine was found either.

“There was no clinically relevant effect of duloxetine added to usual care compared to usual care alone for chronic osteoarthritis pain, and it should not be implemented,” the authors concluded.

Source: Wiley

Categories : Pain ManagementTags :

Most Hangover Cures Don’t Work

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A new systematic review has found only very low-quality evidence that substances claiming to treat or prevent alcohol-induced hangover have any effectiveness. In light of this, the researchers called for more rigorous scientific exploration of the effectiveness of these remedies for hangovers to provide practitioners and the public with accurate evidence-based information for decision making.

Numerous remedies claim to be effective against hangover symptoms; however, up-to-date scientific examination of the literature is lacking. To address this gap, a team of researchers from King’s College London and South London and Maudsley NHS Foundation Trust conducted a systematic review to consolidate and assess the current evidence for hangover treatments.

The study, published today by the scientific journal Addiction, assessed 21 placebo-controlled randomised trials of clove extract, red ginseng, Korean pear juice, and other hangover cures. Although some studies showed statistically significant improvements in hangover symptoms, all evidence was of very low quality, usually because of methodological limitations or imprecise measurements. In addition, no two studies reported on the same hangover remedy and no results have been independently replicated.

Of the 21 included studies, eight were conducted exclusively with male participants. The studies were generally limited in their reporting of the nature and timing of alcohol challenge that was used to assess the hangover cures and there were considerable differences in the type of alcohol given and whether it was given alongside food.

Common painkillers such as paracetamol or aspirin have not been evaluated in placebo controlled randomised controlled trials for hangover. Future studies ought to be more rigorous, such as using validated scales to assess hangover symptoms, the researchers advised. More female participants are also needed in hangover research.

Lead author Dr Emmert Roberts said: “Hangover symptoms can cause significant distress and affect people’s employment and academic performance. Given the continuing speculation in the media as to which hangover remedies work or not, the question around the effectiveness of substances that claim to treat or prevent a hangover appears to be one with considerable public interest. Our study has found that evidence on these hangover remedies is of very low quality and there is a need to provide more rigorous assessment. For now, the surest way of preventing hangover symptoms is to abstain from alcohol or drink in moderation.”

The hangover cures assessed in this study included Curcumin, Duolac ProAP4 (probiotics), L-cysteine, N-Acetyl-L-Cysteine (NAC), Rapid Recovery (L-cysteine, thiamine, pyridoxine and ascorbic acid), Loxoprofen (loxoprofen sodium), SJP-001 (naproxen and fexofenadine), Phyllpro (Phyllanthus amarus), Clovinol (extract of clove buds), Hovenia dulcis Thunb. fruit extract (HDE), Polysaccharide rich extract of Acanthopanax (PEA), Red Ginseng, Korean Pear Juice, L-ornithine, Prickly Pear, Artichoke extract, ‘Morning-Fit’ (dried yeast, thiamine nitrate, pyridoxine hydrochloride, and riboflavin), Propranolol, Tolfenamic acid, Chlormethiazole, and Pyritinol.

Source: Medical Xpress

Categories : Pain ManagementTags :

Topical Medication Trumps Opioids for Knee Osteoarthritis Pain

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Photo by Matthias Zomer from Pexels

In treating knee osteoarthritis pain, topical medication for pain relief is safer and more effective than opioids, according to a new meta-analysis.

The paper, which appears in BMJ, compared the benefits and harms of different doses of commonly prescribed treatments for hip and knee osteoarthritis, including oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, opioids, and acetaminophen (Tylenol). The meta-analysis looked at 192 large, randomised clinical trials with a total of over 102 000 participants.

Researchers found, regardless of preparation or dose, opioids did not significantly relieve pain for osteoarthritis patients. They also found that topical Diclofenac – known to consumers as Voltaren – is effective in treating knee osteoarthritis.

The topical treatment, which can be purchased over-the-counter, is generally safer than oral NSAIDs and should be considered as first-line pharmacological treatment for knee osteoarthritis, the study authors say. Osteoarthritis affects millions of Canadians.

Study lead author, Dr. Bruno R. da Costa, Acting Director of the Applied Health Research Centre (AHRC) at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, stated that recent clinical practice guidelines recommend the lowest possible dose to minimise the risk of adverse events.

However, he said, “it is currently unclear what the lowest but still effective doses of these drugs are. Osteoarthritis affects more than 4.6 million people in Canada. Our findings allow physicians, patients, or their caregivers to have a better understanding of which of these treatments at their lowest doses would be safest while still being effective.”

“Although there is robust evidence about the harmful effects of opioids, and international concerns around the opioid epidemic, opioids remain among the most prescribed drugs for osteoarthritis pain in Canada, the United States, the United Kingdom and Australia.”

Dr da Costa said that none of the opioid interventions, regardless of dose, seemed to have a clinically relevant effect on pain or physical function. Opioids should therefore only play a secondary role in osteoarthritis treatment, when conventional treatment is exhausted.

What was most surprising was that maximum recommended daily doses of opioids do not have an effect in osteoarthritis pain that patients would consider relevant. They did not see an association between higher opioid doses and greater pain relief.

Lower doses of topical diclofenac (Voltaren) also have a similar beneficial effect to the most effective oral NSAIDs in knee osteoarthritis – an important finding as some patients with gastrointestinal complaints and other comorbidities. Adverse events of topical NSAIDs are minimal. The topical diclofenac trials had only knee osteoarthritis, and in hip osteoarthritis the depth is likely too great for any benefit.

The next step is to better understand the safety of oral NSAIDs in patients with comorbidities, and long-term use on an as-needed-basis with varying versus fixed daily doses. It would also be useful to identify if there are patients who have exhausted treatment options but could benefit from opioids or acetaminophen.

Source: Unity Health