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January 2, 2019

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Stem Cell Transplantation Produces Remarkable Therapeutic Effects on Neuropathic Pain in Animal Models

March 16, 2017, ORLANDO, Fla. – Chronic pain from nerve injury is common and often debilitating. Current treatment options for neuropathic pain include physical, cognitive, behavioral, pharmacological, interventional, and surgical therapies. Unfortunately, none of these therapies is particularly effective, according to Jianguo Cheng, MD PhD, professor of anesthesiology and director of the Cleveland Clinic Multidisciplinary Pain Medicine Fellowship

A recent study presented today by Dr. Cheng and his colleagues in a scientific poster at the 33rd Annual Meeting of the American Academy of Pain Medicine suggests that mesenchymal stem cell transplantation (MSC-TP) may offer an alternate and promising solution to alleviate neuropathic pain based on results achieved in animal models.

The study investigated whether the sources of MSCs and routes of transplantation affect the therapeutic efficacy in rats in order to translate laboratory findings into clinical applications. 
Researchers isolated and characterized bone-marrow-derived MSCs (BM-MSCs) and adiposederived MSCs (AD-MSCs) by flow cytometry and functional differentiation. Rats with chronic constriction injury (CCI) of the sciatic nerve were treated with either intravenous (IV) or intrathecal (IT) transplantation of BM-MSCs or AD-MSCs.
The therapeutic effects were evaluated by paw withdrawal thresholds in response to mechanical and thermal stimuli and immunohistochemistry of the sciatic nerve and dorsal root ganglion (DRG). Both BM-MSCs and AD-MSCs produced powerful analgesic effects. Either IT or IV MSC-TP produced significant long-lasting analgesic effects. MSCs substantially decreased the number of NPY+ fibers (injured fibers) and restored the expression of CGRP in peptidergic C fibers and IB4 in non-peptidergic C fibers in the sciatic nerve and DRG. MSCs decreased inflammatory cell infiltration (monocytes/macrophages) at the sciatic nerve injury site and the DRG. A substantial number of MSCs, labeled with Dil dye, were found at the injury site after either IV or IT MSC-TP.

“This novel therapy may be translated to clinical applications to treat many neuropathic pain conditions that afflict millions of Americans,” says Dr. Cheng. He noted that preclinical and translational studies using human stem cells are needed before clinical trials in humans. 

Poster 239 – Stem Cell Transplantation for Neuropathic Pain in Rats 

Simulation and Immersive Learning Shown to Successfully Teach Safe Opioid Prescribing in a Medical School Setting

 March 16, 2017, ORLANDO, Fla. – Negative consequences from opioid prescribing stem in part from a lack of education and skills training in all levels of medical education. A 2011 study that assessed U.S. and Canadian medical school curricula concluded that pain education for North American medical school students is limited, variable, and often fragmentary, with significant gaps existing between recommended pain curricula and documented educational content (Mezei and Murinson J Pain 2011;12(12):1199-208).

“Pain has historically been understood as a symptom of a disease process, injury or surgery within the context of acute pain,” says Jordan Newmark, MD, associate division chief of education at Stanford University School of Medicine. “More recently, the concept of chronic pain representing a disease itself – associated with changes to the nervous and other body systems – is being appreciated. Given the public health implications of chronic pain and its consequences on our society, medical schools are gradually making the curriculum changes necessary to teach this important knowledge.”

Dr. Newmark recently conducted a study on the effectiveness of using simulation and immersive learning as a teaching modality to augment various pain medicine curricula in order to educate physicians in training on safe opioid prescribing for chronic non-cancer pain. The results were presented today in a scientific poster at the 33rd Annual Meeting of the American Academy of Pain Medicine.

Anesthesiology residents and pain medicine fellows participated in this study by engaging in a simulation experience during which they encountered a standardized patient requesting a refill of oral hydromorphone. The patient in the simulation fit the criteria for a moderate opioid misuse disorder, according to Diagnostic and Statistical Manual of Mental Disorders (DSM–V) criteria.

Study participants were assessed based on their use of management strategies to treat the patient within the simulation. A majority of participants provided a hydromorphone refill with weaning in the patient who fits DSM-V criteria for moderate opioid use disorder. Participants also employed prescription drug monitoring programs and urine drug testing to monitor at-risk patients. The results of this study indicate that simulation and immersive learning techniques are an effective method for teaching and practicing safe opioid prescribing.

“Safe prescribing of opioids requires a number of skills, including proper utilization of monitoring techniques,” says Dr. Newmark. “Simulation provides several impactful advantages over traditional, didactic-style instruction, as well as over real world clinical experiences, when it teaching comes to safe opioid prescribing. Students learning through simulation experience deliberate practice with timely performance feedback, leading to enhanced opioid-related education, and ultimately improved patient care.”

Poster 159 – Use of Simulation and Immersive Learning to Teach Safe Opioid Prescribing

Novel Naloxone Device Offers Hope to Community Organizations Grappling with Drug Overdose Epidemic

March 16, 2017, ORLANDO, Fla. – Deaths from drug overdose have increased sharply in the past decade, an unfortunate trend that is associated with overdoes of prescription opioid pain relievers more than tripling from 1983 to 2013 (Mack MMWR Suppl. 2013;62(3):161-3). The drug naloxone has been established as a safe and effective medication to treat drug overdose. Naloxone is often administered intranasally, allowing emergency responders to proficiently and quickly administer the drug without needles (Wermeling Drug Deliv Transl Res. 2013 3(1): 63- 74). 

A recent study, led by George Avetian, DO, FCPP, a family physician in Upper Darby, Pa., assessed real-world experiences with intranasal naloxone formulation for opioid overdose reversal by surveying first responders and community-based organizations. The results were presented today in a scientific poster at the 33rd Annual Meeting of the American Academy of Pain Medicine.
To conduct this research, Dr. Avetian’s team contacted 152 U.S. organizations known to have received units of a novel naloxone nasal spray device (4-mg dose/unit). Researchers sought to collect case report data to assess organizations’ experiences using naloxone nasal spray within their communities.
Based on timing and available data, eight law enforcement or community-based organizations participated in this study by providing case report summary data on 261 attempted overdose reversals (time period: 4/5/16 to 8/10/16; age of individuals with overdose: 17-63 years). The presumed substance involved in the overdose was heroin in 95.4% (165/173) and fentanyl in 5.2% (9/173) of cases.
Of the 245 cases with outcomes reported, 242 of 245 were described as successful. Three deaths were reported (naloxone nasal spray administration was reported to have been too late to be effective for 2 cases and details were not provided for the third case). Many reversals (97.6%; 248/254) involved 1 or 2 units of naloxone nasal spray administration, and most cases (73.5%; 125/170) reported a time-to-response of ≤5 minutes after administration. The most commonly reported observed events were “withdrawal” (14.3%; 28/196), “nausea” or “vomiting” (10.2%; 20/196), and “irritability” or “anger” (8.7%; 17/196). 
Researchers concluded through this data analysis that naloxone nasal spray was successful at reversing the effects of opioid overdose in most reported cases. The majority of events observed for the reversal cases were consistent with other naloxone formulations (opioid withdrawal). 
“The most impressive and important aspect of this research are the outcomes observed,” says Dr. Avetian. “The high reversal rate is a welcome surprise given that ‘success’ truly means lives saved. This data shows that intranasal naloxone 4mg works in the community setting, and that it can, will and does play a vital role in impacting the opioid epidemic our communities face.”

Dr. Avetian emphasizes that naloxone programs are most successful in combating drug overdose when they are implemented at the community-level as a collaborative effort by public health stakeholders, including medical professionals, local leadership, law enforcement, and members of the public. “From medical professionals to family members, a comprehensive strategy that educates, informs, provides preventative tools, and supports those in need for rehabilitation and longer-term recovery is key to making an impact on the epidemic.”

Poster LB001 – Use of Naloxone Nasal Spray in the Community Setting: A Survey of Use by Community Organizations Funding: Survey data collection and medical writing/editorial support were provided by Synchrony Medical Communications, LLC, West Chester, PA, and sponsored by Adapt Pharma, Inc., Radnor, PA.

Interdisciplinary Chronic Pain Rehabilitation Program Shown as Successful Method for Treating Older Adults with Chronic Pain

 March 16, 2017, ORLANDO, Fla. – Up to half of older adults (aged 60 years or more) report experiencing chronic pain. A study presented today at the American Academy of Pain Medicine’s 33rd Annual Meeting as a scientific poster abstract considered the utility of interdisciplinary chronic rehabilitation programs in treating this patient population.

“A hurdle to treating patients with more advanced age is that they will frequently present with complex medical comorbidities,” says Kelly Martincin, PhD, a postdoctoral fellow at Cleveland Clinic, and lead author of the scientific poster abstract. “The power of an interdisciplinary program is in multiple clinicians sitting down together to examine a patient’s unique concerns from a number of different angles, and this is especially important for patients who present with complex comorbidities.”

This study included a retrospective analysis of 225 older adults and 1249 younger adults treated in an interdisciplinary chronic pain rehabilitation program between 2007 and 2012. Analysis showed that, while all patients included in the study showed significant improvement after being discharged from the interdisciplinary chronic rehabilitation program, significant differences were identified based on patient age and improvement achieved for depression, anxiety, and functional impairment, with older adults reporting fewer symptoms than younger adults. The study ultimately found that older adults benefit equally to – if not more than – younger adults in interdisciplinary chronic rehabilitation programs for the treatment of chronic pain.

Dr. Martincin believes that this research will improve treatment options for older adults suffering from chronic pain. “Physicians are always seeking the safest and most effective forms of treatment and prefer options that will not run the risks of impairing cognition, increase fall risks, etcetera. Establishing the value of an interdisciplinary program for the older adult non-cancer chronic pain population specifically provides physicians another tool to offer their patients.”

Poster 230 – Older Adults with Chronic Non-Cancer Pain Benefit from Treatment in an Interdisciplinary Chronic Pain Rehabilitation Program

Intensive Outpatient Pain Management Shown as Cost-Effective Method for Treating High Utilizer Chronic Pain Patients

March 16, 2017, ORLANDO, Fla. – High utilizers of medical services account for disproportionate healthcare costs, with up to 21% of expenditures spent treating the top 1% of patients (Jiang et al, Characteristics of Hospital Stays for Super-Utilizers by Payer, 2012. Agency for Healthcare Research and Quality H-CUP Nov 2014), and chronic pain patients account for a substantial proportion of high utilizers (Harris et al J Emerg Med. 2016;50(4);e203-14).

A recent study at Duke University presented as a scientific poster abstract today at the 33rd Annual Meeting of the American Academy of Pain Medicine assessed how the development of an intensive, individualized pain management program for high utilizers affected an institutions’ financial outcome metrics.

To conduct this study, researchers established a cohort of 31 high utilizer patients with a comorbid diagnosis of chronic pain from April 2014 to July 2015. Patients in the cohort were referred to the Duke Medical Pain Service (MPS), an intensive outpatient pharmacologic management program that employs a physician-led care team specializing in both psychiatry and pain medicine.

After having been in MPS’s care for approximately one year, the cohort’s inpatient and outpatient financial data were analyzed to determine utilization patterns before and after the cohort initiated MPS treatment. Looking at 14 cost centers, the study found that care costs for patients in the cohort (calculated for total and yearly amounts) were reduced by 55% and 45% respectively. The cost per patient was reduced by nearly $9,000 per year.

According to Steven Prakken, MD, lead author of the study and a pain medicine specialist at Duke Health, MPS staff use a functional pharmacology approach to treat patients with an expanded array of medications in order to optimize both pain and its psychiatric comorbidities. “The focus of MPS intervention is not simply reduction of pain. It is optimized patient function across multiple domains, both somatic and psychological,” says Dr. Prakken. “Our method is unique in that a multidisciplinary approach can be encompassed in a single visit with a single practitioner, therefore addressing more adequately the patients’ many needs.”

This study supports the notion that an interdisciplinary treatment modality is especially effective when treating high utilizer patients in order to provide cost-effective, quality care; a finding that is especially important as the financial burden of health care in the U.S. continues to grow and more than 100 million Americans suffer from chronic pain. “This research shows a clear path forward in containing the cost of an ever-expanding population. Reproducing effective treatment modalities such as that of the Medical Pain Service, which dramatically reduces hospital system costs, may well lead the way to successful health care cost containment in the future,” says Dr. Prakken.

Poster 181 – Cost Savings Associated with Intensive Outpatient Pain Management of Duke Health System High Utilizers

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