There is little doubt that dramatic increases in prescriptions for opioid analgesics during the 21st century have been a major contributor to the current opioid crisis. Although primary care providers are at the front line of pain management and addiction prevention and treatment, recent research indicates that orthopaedic surgeons frequently overprescribe opioids to their patients. To help support safer prescribing, NEJM Group, through an independent educational grant and with support from Boston University School of Medicine, recently launched a NEJM Knowledge+ Pain Management and Opioids module.
The course, which contains more than 60 case-based questions on this timely and important topic, is available free of charge at https://knowledgeplus.nejm.org/pain-opioids. The activity conforms to the FDA’s Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) Education Blueprint for Health Care Providers Involved in the Treatment and Monitoring of Patients with Pain.
Many of the case-based questions in the module are geared toward primary care physicians, but approximately 50% of them deal with managing pain associated with musculoskeletal conditions. Just like JBJS Clinical Classroom, which was developed with the NEJM Knowledge+ adaptive-learning platform, this new pain management and opioid module delivers each case-based question and then uses an algorithm that identifies individual learners’ knowledge gaps, followed by targeted content that addresses those gaps after each question has been answered.
This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Understanding recent gene technology can be very daunting. The CRISPR/Cas9 method for gene editing is a prominent example. CRISPR stands for Clustered Regularly Interspersed Short Palindromic Repeats, and Cas9 is an acronym for the CRISPER-Associated Protein 9. Scientists became aware of CRISPR in E. coli in 1987, but they only recently realized that CRISPR constituted an adaptive immune system for bacteria and archae, which are primitive bacteria-like cells.
When infected by a virus (phage), a bacteria’s Cas genes are activated. Cas gene products cut viral DNA sequence sites called protospacers and then insert those sequences into the bacterial DNA. The host bacterium identifies the viral sequences by a protospacer adjacent motif (PAM), which is rarely seen in the host genome. Hence, replication of this sequence will not adversely affect the host. In the event of a second phage attack, Cas genes are activated and they generate CRISPR RNA (crRNA), which recognizes the phage sequence. crRNA associates with Cas nucleases to cleave both DNA strands of the invader.
There are numerous CRISPR modules. Type II CRISPR is one of an expanding number of naturally existing CRISPR families that has have been used for gene editing in eukaryotes. The type II CRISPR family uses crRNA and an additional tracrRNA to target specific DNA sequences. These have been combined to create a single guide RNA (gRNA) to direct sequence-specific Cas9 double-stranded DNA cleavage. The result is a simple, programmable RNA method that has been used for genome targeting and genome editing in eukaryotes.
The accuracy of this system has been markedly enhanced to avoid unwanted mutations. The system is being fashioned to block existing gene expression, modify gene expression by inserting DNA sequences, and activate expression of single or multiple genes. CRISPR technology enables researchers to develop mouse models of disease much more quickly and less expensively than traditional approaches. Larger animal models of disease can also now be produced.
Successful treatment of mouse models of human diseases with CRISPR suggests that the technology can be applied to directly treat human diseases in the future. Preclinical research is underway using CRISPR-ed stem cells or mouse models to study human diseases such as retinitis pigmentosa, Fanconi anemia, Duchenne muscular dystrophy, sickle-cell anemia, and cystic fibrosis.
Thanks to Dr. Gary Gibson for his help with this tip.
Gibson GJ, Yang M. What rheumatologists need to know about CRISPR/Cas9. Nat Rev Rheumatol. 2017 Apr;13(4):205-216. doi: 10.1038/nrrheum.2017.6. Epub 2017 Feb 9.
OrthoBuzz occasionally receives posts from guest bloggers. In response to a three recent studies, the following commentary comes from Jeffrey B. Stambough, MD.
Throughout the last decade, we’ve experienced a boom in anticoagulation options to help prevent venous thromboembolism (VTE) associated with orthopaedic procedures. The use of aggressive anticoagulation, such as warfarin and various heparin formulations, is being questioned, largely due to concerns about bleeding risks and wound complications. Along with the newer direct oral anticoagulants such as rivaroxaban, over-the-counter aspirin (ASA) is gaining prominence as an anticoagulant due to its high efficacy, low cost, convenience for patients, favorable side-effect profile, and cardioprotective attributes. Current guidelines include the use of all these thromboprophylactic agents, but three recent studies lend credence to using aspirin as the primary VTE prophylactic agent when performing total joint arthroplasty (TJA).
In a March 20, 2019 JBJS study analyzing >31,000 TJAs performed at a single institution over 17 years, Rondon et al. found a 3-fold lower 30-day and 2-fold lower 1-year mortality rate in patients receiving ASA (81mg or 325 mg twice daily), compared to those who received non-aspirin thromboprophylaxis (mainly warfarin). No mortality differences were noted between the two ASA dosing regimens. While investigating specific causes of death, the authors discovered that the primary cause of death in the non-ASA cohort was cardiac related at all time points.
A second study, from the April 3, 2019 JBJS, looked into the effects of 3 antithrombotic agents on symptomatic VTE rates and periprosthetic infections in high-risk patients undergoing primary or revision TJA. When compared to the two more potent agents (warfarin and low-molecular-weight heparin), ASA proved more effective at reducing pulmonary embolism (PE) and VTE rates in high-risk patients, and it was also associated with lower rates of periprosthetic joint infection when compared with warfarin. Thus, it seems that even in patients deemed to be higher risk for developing VTE, ASA may be a safe, effective option.
Lastly, Runner et al. gleaned VTE prophylaxis data from >22,000 TJA cases submitted by surgeons sitting for Part 2 of ABOS between 2014 and 2016. The findings, reported in the April 2019 issue of the Journal of Arthroplasty, showed similar trends to those seen in the two previously mentioned studies: Mild (distal or superficial deep vein thrombosis [DVT]), moderate (nonfatal PE, proximal DVT) and severe (fatal PE) VTE events, as well as death, were significantly less frequent in those who received ASA compared to more aggressive agents (heparin or one of its analogs, direct oral agents, or warfarin). Also, patients who received ASA with or without mechanical prophylaxis had significantly lower complication rates (95.5% vs. 93.0%, p<0.001).
One firmly held dogma in medicine is that patients who are at higher risk for VTE should be treated with stronger anticoagulation medications. However, these 3 studies support the idea that less aggressive anticoagulation medication (specifically, low-dose aspirin) may be the more effective and safer option for most patients. In our ongoing quest to improve patient outcomes and mitigate risk around the TJA episode, we should consider using aspirin for thromboprophylaxis unless there is an explicit contraindication in a specific patient.
However, we should also keep in mind that these three studies have the common limitations of all retrospective analyses. Recent randomized trials have shown aspirin to be “noninferior” to other anticoagulants for VTE prevention, and in less than 2 years, we should have even more definitive answers to this question from the randomized, multicenter PEPPER trial, with its estimated 25,000 participants.
Jeffrey B. Stambough, MD is an orthopaedic hip and knee surgeon, an assistant professor of orthopaedic surgery at University of Arkansas for Medical Sciences, and a member of the JBJS Social Media Advisory Board.
OrthoBuzz has previously reported on studies examining the narcotic-prescribing patterns of foot and ankle surgeons. New findings published by Finney et al. in the April 17, 2019 issue of The Journal of Bone & Joint Surgery strongly suggest that the single most powerful and modifiable risk factor for persistent opioid use after bunion surgery was the opioid dose perioperatively prescribed by the surgeon.
The authors analyzed a US private-insurance database to identify >36,500 opioid-naïve patients (mean age, 49 years; 88% female) who underwent one of three surgical bunion treatments. Among those patients, the rate of new persistent opioid use (defined as filling an opioid prescription between 91 and 180 days after the surgery) was 6.2%, or >2,200 individuals. The authors found that patients who underwent a first metatarsal-cuneiform arthrodesis were more likely to have new persistent opioid use, compared with those who received a distal metatarsal osteotomy, which was the most common procedure performed in this cohort. Additional findings included the following:
- Patients who filled an opioid prescription prior to surgery were more likely to continue to use opioids beyond 90 days after surgery.
- Patients who resided in regions outside the Northeastern US demonstrated significantly higher rates of new persistent opioid use.
- The presence of medical comorbidities, preexisting mental health diagnoses, and substance-use disorders were associated with significantly higher new persistent opioid use.
However, physician prescribing patterns had the biggest influence on new persistent opioid use. A total prescribed perioperative opioid dose of >337.5 mg (equivalent to approximately 45 tablets of 5-mg oxycodone) was the major modifiable risk factor for persistent opioid use in this cohort. The authors also pointed out that 45 tablets of 5-mg oxycodone “is a relatively low amount when compared with common orthopaedic prescribing patterns” (see related JBJS study).
As orthopaedic surgeons in all subspecialties rethink their narcotic-analgesic prescribing habits, they should remember that regional anesthesia and non-opiate oral pain-management protocols have had a positive impact on pain management while minimizing narcotic use. The smallest dose of opioids for the shortest period of time seems to be a good rule of thumb.
In the setting of rotator cuff injuries, higher degrees of fatty infiltration into cuff muscles are positively correlated with higher repair failure rates and worse clinical outcomes. MRI continues to be the gold standard imaging modality for evaluating fatty infiltration of the rotator cuff, but ultrasound represents another viable modality for that assessment—at considerably lower cost. Such is the conclusion of Tenbrunsel et al. in a recent issue of JBJS Reviews.
The authors reviewed 32 studies that investigated imaging modalities used to assess fatty infiltration and fatty atrophy. They found that grading fatty infiltration using ultrasound correlated well with grading using MRI. However, the authors identified difficulties distinguishing severe from moderate fatty infiltration on ultrasound, but they added that discerning mild from moderate fatty infiltration is more important clinically. Tenbrunsel et al. also mention sonoelastography, which measures tissue elasticity and can also be used to help determine the severity of fatty atrophy of the rotator cuff.
Overall, the trade-off between MRI and ultrasound comes down to higher precision with the former and lower cost with the latter.
For more information about JBJS Reviews, watch this video featuring JBJS Editor-in-Chief Dr. Marc Swiontkowski.
In 2015, JBJS launched an “article exchange” collaboration with the Journal of Orthopaedic & Sports Physical Therapy (JOSPT) to support multidisciplinary integration, continuity of care, and excellent patient outcomes in orthopaedics and sports medicine.
During the month of April 2019, JBJS and OrthoBuzz readers will have open access to the JOSPT article titled “Repair of the Ulnar Collateral Ligament of the Elbow: Rehabilitation Following Internal Brace Surgery.”
In this Clinical Commentary based on the authors’ experience with >350 cases, Wilk et al. describe the rehabilitation process used for patients following UCL repair with an “internal brace.” This recent surgical advance in managing incomplete UCL tears enhances elbow joint stability while the ligament is healing.
Despite what seems like a new, high-quality study being published on the topic every week or so, orthopaedic surgeons still have an extremely hard time determining whether a prosthetic hip or knee is infected or not. We have an array of available tests and the relatively easy-to-follow criteria for a periprosthetic joint infection (PJI) from the Musculoskeletal Infection Society (MSIS), but a large number of these patients still fall into the gray zone of “possibly infected.” This predicament is especially thorny in patients who received antibiotics just prior to the diagnostic workup, which interferes with the accuracy of many tests for PJI.
In the April 17, 2019 issue of The Journal, Shahi et al. remind orthopaedic surgeons about a valuable tool that can be used in this scenario. Their retrospective study looked at 121 patients who had undergone revision hip or knee arthroplasty due to an MSIS criteria-confirmed periprosthetic infection. Shahi et al. sought to determine which diagnostic tests were least affected by prior antibiotic administration. The authors found that erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil (PMN) percentage were all significantly lower in the 32% of patients who had received antibiotics within 2 weeks of those tests, compared with the 68% who did not receive antibiotics. The only test that was found not to be significantly affected by the prior admission of antibiotics was the urine-based leukocyte esterase strip test.
Considering the ease and rapidity with which a leukocyte esterase test can be performed and evaluated (at a patient’s bedside, with immediate results), its low cost, and the fact that it is included in the MSIS criteria, these findings are very important and useful. While we would prefer that patients with a possibly infected total hip or knee not receive antibiotics prior to their diagnostic workup, previous antibiotic exposure remains a relatively common scenario. The findings from this study can assist us in those difficult cases, and they add further evidence to support the value and reliability of the easy-to-perform leukocyte esterase test.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, Albert Gee, MD, a co-author of the April 17, 2019 “What’s New in Sports Medicine,” selected the five most clinically compelling findings from among the 30 noteworthy studies summarized in the article.
Anterior Cruciate Ligament (ACL) Reconstruction
–Norwegian researchers randomized 120 patients to undergo either single-bundle or double-bundle ACL reconstruction and followed them for 2 years.1 They found no difference between the 2 techniques in any patient-reported outcome, knee laxity measurements, or activity levels. These results, along with the preponderance of evidence from other comparative trials over the last 5 years, strongly suggest that routine use of 2 bundles to primarily reconstruct a torn ACL adds no clinical benefit over a well-positioned single-bundle reconstruction.
Knee Cartilage Repair
–A randomized study compared long-term patient outcomes after knee cartilage repair using microfracture versus mosaicplasty.2 Included patients had 1 or 2 focal femoral lesions measuring between 2 and 6 cm2. Better outcomes after a minimum of 15 years of follow-up were found in the mosaicplasty group. Although there were only 20 patients in each arm, the Lysholm-score differences between the groups were both clinically important and statistically significant. More patients in the mosaicplasty group than in the microfracture group said they would have the surgery again, knowing their 15-year outcome.
–UK researchers randomized 313 patients with ≥3 months of subacromial pain and an intact rotator cuff who had completed a nonoperative program of physical therapy and injection to 1 of 3 groups: arthroscopic subacromial decompression, diagnostic arthroscopy (“sham” surgery), or no intervention.3 At 6 months and 1 year, all groups demonstrated statistically significant and clinically important improvement, but patient-reported outcome scores were significantly better in both surgical groups compared with the no-treatment group. The data suggest that patients such as these improve over time, regardless of management, but that surgical decompression may offer a slight benefit over nonoperative management because of the placebo effect.
–A randomized controlled trial investigated the effect of a formal preoperative education program (2-minute video plus handout)4 about postoperative narcotic use, side effects, dependence risk, and addiction potential among >130 patients undergoing arthroscopic rotator cuff repair surgery. The education group consumed 33% less narcotic medication at 6 weeks and 42% less at 12 weeks compared with the control group. Among the more than one-quarter of the patients who had used opioids prior to surgery, those randomized to the education group were 6.8 times more likely than controls to discontinue narcotic use during the study period.
–A randomized controlled trial of >300 patients compared hip arthroscopy and “best conservative care” for treating femoroacetabular impingement (FAI).5 Only 8% of patients crossed over from conservative care to the surgical group. The mean adjusted difference in iHOT-33 scores at 1 year was 6.8, in favor of hip arthroscopy. However, adverse events were more frequent in the arthroscopy cohort, and a within-trial economic evaluation suggested that hip arthroscopy was not cost-effective compared with conservative care during the 1-year trial period.
- Aga C, Risberg MA, Fagerland MW, Johansen S, Trøan I, Heir S, Engebretsen L. No difference in the KOOS Quality of Life Subscore between anatomic double-bundle and anatomic single-bundle anterior cruciate ligament reconstruction of the knee: a prospective randomized controlled trial with 2 years’ follow-up. Am J Sports Med.2018 Aug;46(10):2341-54. Epub 2018 Jul 18.
- Solheim E, Hegna J, Strand T, Harlem T, Inderhaug E. Randomized study of long-term (15-17 years) outcome after microfracture versus mosaicplasty in knee articular cartilage defects. Am J Sports Med.2018 Mar;46(4):826-31. Epub 2017 Dec 18.
- Beard DJ, Rees JL, Cook JA, Rombach I, Cooper C, Merritt N, Shirkey BA, Donovan JL, Gwilym S, Savulescu J,Moser J, Gray A, Jepson M, Tracey I, Judge A, Wartolowska K, Carr AJ; CSAW Study Group. Arthroscopic subacromial decompression for subacromial shoulder pain (CSAW): a multicentre, pragmatic, parallel group, placebo-controlled, three-group, randomised surgical trial. Lancet. 2018 Jan 27;391(10118):329-38. Epub 2017 Nov 20.
- Syed UAM, Aleem AW, Wowkanech C, Weekes D, Freedman M, Tjoumakaris F, Abboud JA, Austin LS. Neer Award 2018: the effect of preoperative education on opioid consumption in patients undergoing arthroscopic rotator cuff repair: a prospective, randomized clinical trial. J Shoulder Elbow Surg.2018 Jun;27(6):962-7. Epub 2018 Mar 26.
- Griffin DR, Dickenson EJ, Wall PDH, Achana F, Donovan JL, Griffin J, Hobson R, Hutchinson CE, Jepson M,Parsons NR, Petrou S, Realpe A, Smith J, Foster NE; FASHIoN Study Group. Hip arthroscopy versus best conservative care for the treatment of femoroacetabular impingement syndrome (UK FASHIoN): a multicentre randomised controlled trial. Lancet. 2018 Jun 2;391(10136):2225-35. Epub 2018 Jun 1.
The practice of using a geriatrician- or a hospitalist-based co-management team to care for elderly patients who are admitted to the hospital for treatment of fragility fractures or other orthopaedic procedures is now more than a decade old. These services have grown in popularity because patients are living longer with comorbidities and becoming more complex to manage medically, and because shift-based hospitalist practices have become more common. These coordinated partnerships help the hospitalist- or geriatrician-led medical team optimize the patient’s care medically, while allowing the orthopaedic surgeon to focus on the patient’s musculoskeletal condition. The consensus I have heard is that patients are better off with these co-management systems, but hard evidence has been sparse.
In the April 17, 2019 issue of The Journal, Blood et al. report on the use of the Institute for Healthcare Improvement (IHI) Global Trigger Tool to assess the adverse-event impact of a Geriatric Hip Fracture Program (GHFP). In a bivariate analysis of pre- and post-GHFP data, the authors document a decrease in the rate of adverse events and shorter lengths of stay among elderly hip-fracture patients after GHFP implementation. However, multivariable analysis confirmed only a trend toward decreasing adverse-event rates after the implementation of the program. This study also seems to confirm what many of us already know empirically—that hip-fracture patients with severe medical comorbidities (i.e., a high Charlson Comorbidity Index) are at increased risk of adverse events no matter what system of care they receive.
Still, what most orthopaedic surgeons have felt was a “no-brainer,” coordinated approach to optimizing patient care and decreasing adverse events now has more evidence of effectiveness. Because such programs decrease both adverse events and length of stay among elderly patients hospitalized for a hip fracture, orthopaedic surgeons everywhere should advocate for increased geriatrician training to support this movement. Furthermore, these findings should encourage further research into additional patient-centric medical care strategies that could improve outcomes for these patients.
Marc Swiontkowski, MD