“Both authoritative and patient-focused, Metabolic Therapies in Orthopedics, 2^nd Edition gives health care practitioner’s a solid hook on which to confidently hang their stethoscope, figuratively speaking. It’s practical, written by clinicians for clinicians. These clinicians “walk the talk,” providing empowerment by teaching effective, safe and valuable practice guidelines. Their work serves the interest of important constituencies of the healthcare system, patients, families, providers, and the community.  It’s a practical tool that allows you to translate its contents into a realistic medical practice.”

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If you would like to purchase this book in advance, please contact Dr. Ingrid Kohlstadt on the Contact page to pre-order your copy from CRC Press.

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This publication is a very well-written explanation of regenerative orthopedics concepts. Below is the link to PubMed’s article:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214280/

The article also includes a list of commonly used abbreviations in the regenerative orthopedics area. If you’d like to read the full publication, click the link below:

http://www.mayoclinicproceedings.org/article/S0025-6196(13)00477-1/pdf

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Posted by: Regenerative Orthopedics.

As doctors consider their role in the nation’s opioid epidemic, much attention has been paid to primary care physicians, who account for fully half of the prescription opioids dispensed.

But orthopedic surgeons — who rank third, behind internists, when it comes to writing opioid prescriptions — have also been attuned to the crisis. A new study of prescribing habits on the athenahealth network found that orthopedic surgeons nationwide have significantly dropped their opioid prescribing over the past three years: a relative decrease of 13.4 percent from early 2014 to early 2017.

It wasn’t a steady decline. Over that three-year period, there were small fluctuations in the length and intensity of prescriptions, with slight increases in the fourth quarters of 2015 and 2016 — often the busiest times of year for orthopedic surgery.

Still, the data suggest that orthopedic surgeons are changing their procedures, and their communication with patients, in response to a national problem.

The analysis looked at about 800 orthopedic surgeons, treating 370,000 patients across the network every quarter between 2014 and 2017. Despite the fluctuations, the average day supply per prescription remained flat, at about 51-55 days. And the share of high-strength prescriptions — of more than 90 morphine milligram equivalents, or MME, per day — was very small, accounting for only 2.3 percent of prescriptions as of the first quarter in 2017.

Primary care providers, by contrast, prescribe an average of four times the share of high-strength prescriptions, and offer day-supply rates that are 1.5 times longer, athenahealth data show.

This could be because primary care physicians receive the majority of marketing from pharmaceutical companies, says David Ring, M.D., a hand surgeon and chair of the committee of patient safety at the American Academy of Orthopaedic Surgeons.

“Some orthopedic surgeons will refuse to give patients more opioids, so then [patients] go to their primary care provider and ask for a prescription,” Ring says. “That’s the doctor they see more often and can be more comfortable with, so it makes sense. And if the primary care doctor isn’t aware of the scope of the situation, you can run into problems.”

A message in the data

Opioid prescribing rates vary across specialties, but athenahealth data show they have been declining across the board: 12.6 percent across all specialty groups since 2014. Among primary care physicians during that time, opioid prescribing rates decreased by 15.7 percent. Among all the specialties, orthopedics had the second-largest relative decrease: 13.4 percent.

For physicians in the field, changing prescribing habits often takes deliberate steps — and a data-driven approach.

Leaders of OSS Health, an orthopedic surgery group that sees 250,000 patients in York County, Pennsylvania, wanted to examine their role in the region’s opioid crisis after a spike in local deaths was attributed to a combination of prescription pills, heroin, and cocaine.

Suzette Song, M.D., an orthopedic surgeon and partner at OSSHealth, said the data they uncovered were shocking. In 2015, OSS Health patients went home with 18,000 prescriptions a year for opioid painkillers, adding up to approximately 800,000 pills.

“We thought we might be better than average because we were conscientious in prescribing, but the numbers were massive,” she says. “We wondered how bad other rates were.”

OSS Health launched a comprehensive, multi-step plan to decrease the number of pills its providers prescribed. They began by prescribing fewer pills for the 10 highest volume surgeries, going from 120 pills for a knee replacement to 90, then ultimately down to 60.

Setting expectations for pain

Song said it was important to standardize the approach — and to educate both patients and physicians. Because OSS Health has high patient experience scores, some surgeons expressed concern that patients would get angry if they were prescribed fewer pills.

But everyone, from the nurses on the floor to the surgeons, worked together to warn patients that they would experience discomfort — and to explain that when it was an appropriate time to be weaned off pain management pills, they wouldn’t get a refill.

Surveys have shown that some surgeons prescribe opioids because they are concerned about patient antagonism or dissatisfaction, says Ring of the American Academy of Orthopaedic Surgeons. Instead, he says, physicians need to send the message that pain is a part of life, and start normalizing resiliency.

“Most of the world treats pain without opioids,” he says. “But in America, there seems to be a mindset that says, ‘We’re industrious people. If we do the right thing or pay the right person, we won’t be in pain.'”

Song says that when patients were well-informed, they accepted the new standards.

“We got less people asking for more pills than we feared we would, and we attribute that to setting appropriate expectations, so people felt less anxious about not getting a prescription on their next visit,” Song says. “It helped people get over their fear of change.”

The results have paid off. By the end of 2016, OSS Health had dispensed 220,000 fewer opioid prescriptions than the year before, decreasing its total prescriptions by 15 percent compared to the end of 2015, even though the number of patients increased in that time.

And compared to the year before, the practice saw a 24 percent reduction in hydrocodone prescriptions, and a 45 percent decrease in the number of pills prescribed.

“We wanted a dramatic improvement, not a little improvement,” Song says. “But even if a practice makes one change, whether it’s giving fewer pills for one procedure or managing expectations, the situation can improve. In the end, better is better, in whatever way you can get there.”

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Full Text here: Dehydrated Human Amnion Chorion Membrane dHACM

Regenerative Orthopedics Publication courtesy of open-access article published in Techniques in Orthopaedics: May 19, 2017

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More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunions.

We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatán mini-pigs, a clinically relevant large animal model. A collagen scaffold was implanted in the fracture to facilitate recruitment of endogenous mesenchymal stem/progenitor cells (MSCs) into the fracture site.

Two weeks later, transcutaneous ultrasound-mediated reporter gene delivery successfully transfected 40% of cells at the fracture site, and flow cytometry showed that 80% of the transfected cells expressed MSC markers. Human bone morphogenetic protein-6 (BMP–6) plasmid DNA was delivered using ultrasound in the same animal model, leading to transient expression and secretion of BMP-6 localized to the fracture area. Micro-computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to complete radiographic and functional fracture healing in all animals 6 weeks after treatment, whereas nonunion was evident in control animals.

Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively treat nonhealing bone fractures in large animals, thereby addressing a major orthopedic unmet need and offering new possibilities for clinical translation.

Author info: Bez M^1,2, Sheyn D^2,3, Tawackoli W^2,3,4,5, Avalos P³, Shapiro G¹, Giaconi JC⁶, Da X⁴, David SB^2,3, Gavrity J⁷, Awad HA⁷, Bae HW², Ley EJ², Kremen TJ^2,8, Gazit Z^1,2,3,8, Ferrara KW⁹, Pelled G^1,2,3,4,5, Gazit D^10,2,3,4,5,8.

Regenerative Orthopedic news strives to bring you the latest science updates. If you have regenerative orthopedic news you’d like to post, please contact Dr. Kohlstadt.

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To grow clusters of human stem cells that mimic organs in the lab and might be used someday in tissue implants, Bill Murphy, has, in the past, created tiny scaffolds for the cells made of plastic or rubber.

The task of the three-dimensional scaffolds is to support the cells, feed them, help them organize and allow them to communicate.

One spring day in 2014, Murphy looked out his office window onto the university’s Lakeshore Nature Preserve, and saw structures that do those very things naturally: plants.

Now, three years later, Murphy and Gianluca Fontana, a UW-Madison post-doctoral fellow, have grown skin, brain, bone marrow and blood vessel cells on cellulose from plants such as parsley, spinach, vanilla and bamboo.

Plants could be an alternative to artificial scaffolds for growing stem cells, the researchers reported in their article on their work in the journal Advanced Healthcare Materials.

“Rather than having to manufacture these devices using high-tech approaches, we could literally pick them off of a tree,” said Murphy, co-director of the UW-Madison Stem Cell and Regenerative Medicine Center. He said that the strength, porosity and large surface area of plants could prove superior to making scaffolds than are the current methods, using 3-D printing and injection molding.

“Plants have a huge capacity to grow cell populations,” Murphy said. “They can deliver fluids very efficiently to their leaves…. At the microscale, they’re very well organized.”

There are many species of plants to choose from. After Murphy’s inspirational gaze out the window, he and Fontana tested plants as scaffolds for stem cells using varieties they could easily obtain: parsley, spinach, jewelweed, water horsetail, summer lilac and softstem bulrush.

Then Fontana asked John Wirth, Olbrich Biotanical Gardens’ conservatory curator, about other species that might work. Wirth invited Fontana to walk through the tropical greenhouse and take samples back to his lab.

“I had never had a request like this before; it made me look at plant material in a different way,” Wirth said. “I think it’s a fantastic way of using these pieces of living tissue, to grow human tissue.” Olbrich plants that proved useful include vanilla, bamboo, wasabi, elephant ear, zebra plant and various orchids.

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Total knee replacement provides minimal quality-of-life benefit for patients with less severe disability at baseline, according to new research. Thus, the treatment, as currently practiced in the United States, is not cost-effective.

“Improvements in quality of life with total knee replacement were on average smaller than previously shown,” Bart Ferket, MD, from the Icahan School of Medicine at Mount Sinai, New York City, and colleagues write. “Given its limited effectiveness in individuals with less severely affected physical function, performance of total knee replacement in these patients seems to be economically unjustifiable.”

“If the procedure were restricted to patients with more severe functional status, however, its effectiveness would rise, with practice becoming economically more attractive.”

The study, which was published online March 28 in the BMJ, analyzed data from the Osteoarthritis Initiative (OAI) database, a multicenter cohort of 4498 individuals from the general US population with or at risk for osteoarthritis of the knee. “Study participants were aged 45-79 [years] at enrolment and were tracked with repeated follow-up evaluations for nine years,” study authors state. The authors also validated their findings on a separate cohort of 2907 participants with osteoarthritis of the knee involved in the Multicenter Osteoarthritis Study (MOST). Follow-up of the MOST cohort was 2 years.

Dr Ferket and colleagues modeled the effect knee replacement had on quality of life, using the Short Form (SF)-12 physical component summary (PCS) score, the SF-12 mental component summary score, the SF-6D utility index, the Western Ontario and McMaster Universities arthritis index, and the quality-of-life subscale on the knee injury and osteoarthritis outcome score. They also assessed the effect surgery had on pain medication use out to 96 months.

Perhaps not surprisingly, those with osteoarthritis of the knee at baseline in the OAI cohort had more severely affected function, as reflected with worse SF-12 PCS, SF-6D, and osteoarthritis-specific quality-of-life scores than those at high risk for osteoarthritis of the knee (P < .001). Among this particular cohort, investigators documented 382 knee replacements, most of which were done before the last assessment at 96 months. In the MOST cohort, investigators identified 135 total knee replacements before the last visit at 30 months.

After adjusting for confounding variables both at baseline and across time, investigators documented an absolute improvement of 1.70 points on the SF-12 PCS among participants who had undergone knee surgery compared with those who had not undergone surgery. Changes on the SF-12 mental component summary score as well as the SF-6D utility index were both minor, at −0.22 and 0.008 points, respectively, they add.

Osteoarthritis-specific measures of quality of life indicated that knee replacement surgery improved the Western Ontario and McMaster Universities arthritis index score by 10.69 points, whereas the knee injury and osteoarthritis outcome quality-of-life score improved by 9.16 points.

“These improvements became larger with decreasing functional status at baseline,” the researchers note. For example, one calculation suggested that “total knee replacement would become more effective if it was restricted to patients with SF-12 PCS scores <50.”

Quality-Adjusted Life-Years

Researchers also estimated differences in lifetime costs and quality-adjusted life-years (QALYs) according to the patient’s baseline symptom level. “For the base case analysis, we modeled 10 scenarios, ranging from current practice with rates as observed in the OAI, to lower rates of practice in which the procedure was performed only in individuals with lower SF-12 PCS levels (from <55-<20), to a scenario without total knee replacement,” Dr Ferket and colleagues explain. They also factored in different cost-effectiveness thresholds from $50,000, $100,000, and $200,000 for each QALY for decision-making.

The only scenario in which the incremental cost effectiveness ratio for knee replacement surgery fell below $100,000/QALY was for individuals with a SF-12 PCS score of less than 20, indicating significant baseline disability. At a cost-effectiveness threshold of $200,000 per QALY, the economically most attractive strategy would be to restrict knee replacement surgery to patients with a baseline SF-12 PCS score of under 35, whereas expanding to include those with a score less than 40 would make the procedure borderline cost-effective.

In contrast, extending knee replacement surgery to patients with a baseline SF-12 PCS of 40 and under would be financially viable if hospital costs dropped below $14,000 per hospital admission. As researchers point out, findings were validated in the MOST cohort as well. “Considerable cost savings could be made by limiting eligibility [of surgery] to patients with more symptomatic knee osteoarthritis,” the authors conclude.

Patient Satisfaction

Asked by Medscape Medical News to comment on the study, Daniel Riddle, PT, PhD, from the Department of Orthopaedic Surgery and Rheumatology, Virginia Commonwealth University, Richmond, felt the main limitation to this kind of cost-effectiveness study is that it does not account for patient satisfaction.

“What the OAI does not do is provide information about whether these patients were satisfied with how they were doing after surgery,” Dr Riddle said. “Because it could be that people who had minimal improvement on the SF-12 PCS were still satisfied even though they started out in a place where their symptoms were not as severe as those who had more substantial improvement following surgery.”

Moreover, 20 years ago, knee replacement surgery was intended to help only those patients who had end-stage osteoarthritis and very poor function. “Over the last 20 years, we’ve seen not only improvements in the surgery itself, but the implants surgeons use and also the recovery process, so it’s a different procedure than it was 20 years ago,” Dr Riddle suggested.

Again, it may well be that patients who have less severe pain or less severe functional loss still gain substantially from the surgery, even though it’s not the same order of magnitude as those who are more severely affected.

“Let’s face it, people who are on the very severe end of the spectrum of pain and functional loss have a lot more gain to make, but we already knew that,” Dr Riddle said. “What this study does show us is that the cost associated with these small changes is very high and whether we can afford such minimal benefits for such a great cost is a question that the greater society has to try and answer.”

The cost of performing total knee replacement now exceeds 10 billion a year in the US.

The authors and Dr Riddle have disclosed no relevant financial relationships.

BMJ. Published online March 28, 2017. Full text

For more information on Metabolic Therapies in Orthopedics, click here.

Medscape Medical News © 2017

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Confocal image shows migration of chondrogenic progenitor cells into the cartilage injury site in response to the stromal cell-derived factor 1(SDF1) contained in the hydrogel. Image courtesy of Yin Yu.

Knee injuries are the bane of athletes everywhere, from professionals and college stars to weekend warriors. Current surgical options for repairing damaged cartilage caused by knee injuries are costly, can have complications, and often are not very effective in the long run. Even after surgery, cartilage degeneration can progress leading to painful arthritis.

But a University of Iowa orthopedics research team is working on a solution with hopes it will result in a minimally invasive, practical, and inexpensive approach for repairing cartilage and preventing osteoarthritis.

“We are creating an injectable, bioactive hydrogel that can repair cartilage damage, regenerate stronger cartilage, and hopefully delay or eliminate the development of osteoarthritis, and eliminate the need for total knee replacement,” says Yin Yu, a graduate student in the lab of James Martin, UI assistant professor of orthopedics and rehabilitation. Yu is first author of the study, which is featured on the cover of the May 1 issue of the journal Arthritis and Rheumatology.

Martin’s team had previously identified precursor cells within normal cartilage that can mature into new cartilage tissue. This was a surprising discovery because of the long-held assumption that cartilage is one of the few tissues in the body that cannot repair itself.

When a placebo hydrogel is used to fill the cartilage injury site, very few cells (green dots) migrated into the site over 12 days. In contrast, a significant number of cells migrate from the peripheral area to the center of the defect when the injury site is filled with the SDF1-containing hydrogel.

The team also identified molecular signaling factors that attract these precursor cells, known as chondrogenic progenitor cells (CPC), out of the surrounding healthy tissue into the damaged area and cause them to develop into new, normal cartilage. One of the signals, called stromal derived factor 1 (SDF1), acts like a homing beacon for the precursor cells.

In an experimental model of cartilage injury, Yu loaded the custom-made hydrogel with SDF1 and injected it into holes punched into the model cartilage. The precursor cells migrated toward the SDF1 signal and filled in the injury site. Subsequent application of a growth factor caused the cells to mature into normal cartilage that repaired the injury.

“This process gives us a great result,” Yu says. “The new cartilage integrates seamlessly with the undamaged tissue. It has normal concentrations of proteoglycans, good structural properties, and looks like normal cartilage.”

The new tissue is not as mechanically strong as normal cartilage, but Yu and Martin think that mechanical loading — the type of stress that is exerted during physical therapy and exercise — might improve the mechanical properties.

“There’s really no cure for osteoarthritis except for total joint replacement, which is not particularly suitable for younger patients because the artificial joints wear out and need to be replaced multiple times,” says Martin. “Our approach aims to leverage the body’s own capacity for repair, and what we’ve shown is that cartilage does have regenerative potential—you just have to manipulate it just right.”

To translate this approach into a therapy that can be used in people, the team now needs to include the growth factor in the gel in such a way that there is a stepwise release of the attractant SDF1 followed by the growth factor. Martin and Yu have teamed up with UI pharmacy professor Aliasger Salem, to engineer that property into the gel.

The team will tap Salem’s expertise on microfabrication techniques for creating novel drug and gene delivery devices, to test two technologies — nano-size plasmids carrying genetic instructions for the growth factor or microspheres loaded with the substance — to incorporate the growth factor into gel.

The long-term goal of commercializing the gel as a human therapy has guided the researchers’ thinking from the start of the project, influencing the choices of materials and technologies, and prompting Yu’s participation in UI Venture School where he and several colleagues, including undergraduate student Jaison Marks, developed a business plan for the product.

“We are very aware of the need to do translational research and we are always looking for the best way to develop a treatment that will be usable in humans,” Martin says.

“When we are ready to commercialize this product, we already know all the components are FDA approved for human use,” Yu adds. “That will accelerate this process.”

Yu and Martin plan to start animal trials within a year and, if the results are good, they hope to be ready to start human trials in about five years.

The UI research team also included Marc Brouillette, Dong Rim Seol, Hongjun Zheng, and Joseph Buckwalter. The study was supported in part by grants from the U.S. Department of Defense, and the American Arthritis Society.

Regenerative Orthopedics News article courtesy of Iowa Now, University of Iowa, by Jennifer Brown on  2015.04.30  with full text is available here: https://now.uiowa.edu/2015/04/ui-team-developing-bioactive-gel-treat-knee-injuries.

To learn more about Metabolic Therapies in Orthopedics 2nd Edition, edited by Ingrid Kohlstadt MD, MPH and Kenneth Cintron MD, click here.

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