COVID-19 Evidence from Dr. Bhandari
We are now experiencing the third human coronavirus epidemic of the 21st century. COVID-19 has rapidly endangered the health and well-being of all people, especially vulnerable populations. The offending pathogen, SARS-CoV-2, is a novel coronavirus hitherto unknown to the medical field.
Some of what is known about the virus and the disease it causes has been compiled into a fast-track JBJS Orthopaedic Forum article by orthopaedic surgeon and researcher Mohit Bhandari, MD, PhD and his colleagues. Whether you are an orthopaedist, health care professional in another specialty, or a patient, you may find the following excerpts from the article useful.
The authors begin with a quote from Microsoft founder and philanthropist Bill Gates, who notes that “we’ve invested a huge amount in nuclear deterrents, but we’ve actually invested very little in a system to stop an epidemic.”
Epidemiology
Evidence suggests that asymptomatic, pre-symptomatic, or mildly symptomatic individuals could be drivers of the community spread of the virus. Early evidence from pre-published studies of 2 cohorts indicate that the virus is spread, on average, 2 to 3 days before symptoms present.
The CDC recently published a report on US patients with COVID-19, using data from February 12, 2020, to March 16, 2020 and found that younger age groups had appreciable risks of both hospitalizations and ICU admissions. This is contrary to data from other countries, where serious cases of COVID-19 occurred predominantly in older people with underlying illnesses.
Infection curves with a steep rise place huge demands on health-care systems and can overwhelm limited health-care resources and force clinicians to make agonizing decisions about which patients receive life-saving treatment and which do not. Hence, all the talk about precautions designed to flatten the curve instead of steepening it.
Vaccine Development
Although there has been impressive and rapid progress toward a vaccine already, a vaccine for widespread use is still likely months or years away, because of the testing, regulatory, and manufacturing hurdles that will need to be cleared.
One possible vaccine-development strategy is a subunit vaccine. Subunit vaccines elicit an immune response against the protein on the surface of a coronavirus to prevent its docking with host receptors. Given the similarities between SARS-CoV (the virus that caused the SARS outbreak in 2002 and 2003) and SARS-CoV-2, focusing on a subunit vaccine may be the most promising short-term approach.
Treatment
No specific treatment is currently recommended for COVID-19. Similar to many other viral illnesses, the current mainstays of treatment include early recognition and isolation, along with symptomatic and oxygen therapy.
A randomized controlled trial of the antiviral lopinavir-ritonavir compared with standard care included 199 adult patients with confirmed COVID-19, pneumonia, and compromised oxygen saturation. There was no significant difference between the 2 groups in terms of time to clinical improvement or mortality, with more adverse events occurring in the intervention group.
Dr. Bhandari and his colleagues also offer 9 pieces of practical guidance for surgeons, one of which echoes the experience of Emory University orthopaedists and the orthopaedic community in Singapore: Create multiple teams of clinicians who are completely isolated from one another.
The authors concede that it is impossible to accurately predict the trajectory of COVID-19. Even with aggressive containment procedures, the outbreak is unlikely to see meaningful resolution for weeks to months. Their final message to the health-care community: Exercise continued vigilance and preparedness for a possible second wave and a high index of suspicion for any new cases of undifferentiated respiratory illness in the weeks to months following a slowdown in new cases.
Platooning Orthopaedic Residents Amid COVID-19
Under the best of circumstances, an orthopaedic residency requires trainees and trainers to balance clinical work, surgical skills, didactics, and academic investigations. The global COVID-19 crisis is certainly not the best of circumstances. A fast-track article just published in JBJS explains how the urban, high-volume orthopaedic department at Emory University School of Medicine in Atlanta created a two-team system that helps residents keep learning, helps maintain a healthy workforce, and addresses the needs of orthopedic patients amid this unprecedented situation.
Emory is now dividing its orthopaedic residents into “active duty” and “working remotely” teams. In observation of the presumed incubation period of COVID-19 symptoms, transitions between active and remote activities occur every two weeks. A similar “platooning” system is in place for both faculty and administrators to safeguard a healthy network of leaders and command-and-control decision makers.
Active duty residents participate in in-person surgical encounters and virtual ambulatory encounters. Orthopaedic surgical cases deemed essential present an ideal opportunity for active-duty education, the authors observe, and there is also a role for supplementation of surgical education in the form of virtual reality or simulation training. Faculty members cover their in-person clinics without resident assistance when possible, but most musculoskeletal subspecialty visits can be performed with video-enabled telemedicine, and active-duty residents are part of these virtual clinic visits in real time.
Remotely working residents participate by videoconference in daily faculty-led, case-based didactics. The authors recommend virtually conducted one-and-a-half-hour collaborative, interactive learning sessions on predetermined schedules and topics. Each session includes question-based learning, facilitated with the use of an audience-response system. Remotely working residents also study for their boards and work on clinical research projects, grant writing, and quality improvement projects.
Finally, this team system, championed by strong departmental leadership, allows for isolation of any resident who acquires COVID-19, allowing them time to recover, while diminishing the risk of rapid, residency-wide disease transmission.
More Data on Periprosthetic Hip Infections
Among >100,000 total hip arthroplasty (THA) patients ≥55 years of age whose data resides in a Canadian arthroplasty database, the 15-year cumulative incidence of periprosthetic joint infection (PJI) was 1.44%, according to a study by the McMaster Arthroplasty Collaborative in the March 18, 2020 issue of JBJS.
In addition to finding that the overall risk of developing PJI after THA has not changed over the last 15 years in this cohort, the authors found the following factors associated with increased risk of developing a PJI:
- Male sex (absolute increased risk of 0.48% at 10 years)
- Type 2 diabetes (absolute increased risk of 0.64% at 10 years)
- Discharge to a convalescent-care facility (absolute increased risk of 0.46% at 10 years)
The authors view the third bulleted item above as “a surrogate marker of frailty and poorer general health.”
Patient age, surgical approach, surgical setting (academic versus rural), use of cement, and patient income were not associated with an increased risk of PJI. Nearly two-thirds of PJI cases occurred within 2 years after surgery, and 98% occurred within 10 years postoperatively.
The authors conclude that these and other substantiated findings about PJI risk factors “should be reviewed with the patient during preoperative risk counseling.”
COVID-19 Rallies the Orthopaedic Community: Singapore’s Experience
The mind and heart of almost everyone on the planet are now focused to some extent on COVID-19. In the first of what will be a series of fast-tracked JBJS articles about how orthopaedic surgeons are helping mitigate the pandemic, Liang et al. describe orthopaedists’ early experiences in Singapore, where the first case of COVID-19 was confirmed in a tourist from Wuhan, China on January 23, 2020.
Singapore has had a nationwide outbreak-response system (called DORSCON, for Disease Outbreak Response System Condition) since the SARS crisis of 2003 (see Figure). Immediately after the first evidence of community spread of the virus on the island, on February 7, 2020, the Ministry of Health raised the DORSCON status to Orange, which triggered the following outbreak-control measures:
- Ramping up of contact tracing
- Mandatory 14-day quarantining of those in close contact with people who had confirmed infections
- A 2-week mandatory leave of absence for healthcare workers with recent travel histories to China
- Compulsory, twice-daily temperature screenings of all healthcare workers
The COVID-19-driven changes in orthopaedic practice revolved around 2 strategies:
- Clinical Urgency
- Musculoskeletal trauma and tumor patients were operated on as scheduled, but elective surgical cases were postponed to free up beds for confirmed or suspected COVID-19 patients.
- Orthopaedists were encouraged to consider temporary pain-relieving measures (such as corticosteroid injections or nerve-root blocks) for patients with severe pain whose surgeries were postponed.
- Patient and Healthcare-Worker Protection
- Clinicians have been advised to prolong the duration between nonurgent follow-up appointments. All patients attending outpatient clinics are screened for risk factors and have their temperatures checked. Febrile patients are moved to the emergency department for further evaluation.
- Orthopaedic teams wear surgical masks for all patient encounters and practice strict hand-hygiene practices.
- When evaluating orthopaedic patients suspected of or diagnosed with COVID-19, all staff wear full personal protective equipment. Whenever possible, such evaluations take place in pressure-negative isolation units, and these patients are co-managed with infectious-disease colleagues.
- If surgery on a suspected or confirmed COVID-19 patient is needed, it is performed by a dedicated orthopaedic contamination team; these teams are segregated from the rest of the staff to minimize the risk of cross-contamination.
Technology Tools for Training
Telemedicine and telerehabilitation have helped ensure the quality of patient care in Singapore, and technology is also being used to keep orthopaedic training going. Because all interhospital rotations and in-person combined teaching programs have been suspended, residency training programs are relying on videoconferencing platforms for scheduled teaching sessions. For trainees who engage with instructional videos or webinars, faculty members follow up with online discussions.
As residents take shifts in the emergency department to assist with COVID-19 screening, they learn important lessons in management of limited resources and “softer” skills such as empathy and teamwork.
Liang et al. conclude with this admonition to orthopaedic surgeons everywhere: “Stay vigilant even when reviewing low-risk elective patients; be champions of good hygiene practices, and be open-minded in the adoption of novel workplace technologies.”
More Work, Less Pay for Revision TKAs
Time is a valuable commodity for everyone. Most physicians have spent long hours in the clinic or hospital, away from our families, sometimes missing important life events. We accept those aspects of our chosen profession. But everyone, including surgeons, wants to be appropriately reimbursed for their time. It’s logical that more complex surgical cases take more time to perform correctly and safely. But does Medicare (and the private insurers who base their physician payments on Medicare rates) adequately reimburse for that extra time?
The short answer is “no,” at least in terms of revision surgery for infected total knee arthroplasties (TKAs). Samuel et al. tackle that topic in the February 5, 2020 issue of The Journal. The authors reviewed records from the NSQIP database to identify cases of aseptic revision TKA, 1-stage septic revision TKA, and 2-stage septic revision TKA. Using propensity-score matching that controlled for age, sex, race, BMI, and ASA classification, the authors established 4 cohorts that allowed for comparison of the following types of revision TKA:
- 1-stage, 2-component aseptic revisions (n=1,096)
- 1 stage, 2-component septic revisions (n=274)
- First stage of a 2-stage septic revision (n=274)
- Second stage of a 2-stage septic revision (n=274)
The authors then compared the relative value units (RVUs) for each type of revision TKA. (Medicare uses RVU-based algorithms to reimburse physicians for their services.) The authors also identified operative times for the surgery types and made RVU-per-minute and dollars-per-minute calculations.
The mean operative times were statistically different between each cohort (149 minutes for the aseptic group, 160 minutes for the 1-stage septic group, 138 minutes for the first-stage of the 2-stage septic group, and 170 minutes for the second-stage of the 2-stage septic group). The dollar-per-minute calculation in the “easiest case” of aseptic revision was $7.74 per minute, while in the “hardest case” of a 2-stage septic revision, reimbursement was $5.66 per minute for the first stage and $5.19 per minute for the second stage.
The fact that Medicare’s current reimbursement system does not account for the complexity of treating an infected TKA harms not only surgeons. Financially discouraging physicians from taking complex cases could lead to patients having a difficult time finding a doctor to treat their infected knee replacement. This entire predicament warrants further investigation, possible adjustments to the RVU system, and more realistic valuations of time in the OR.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Vancomycin-Soaked ACL Grafts Cut Already-Low Infection Rates
The word “infection” contains 9 letters, but it’s a four-letter word for orthopaedic surgeons. Postoperative infections are complications that we all deal with, but we try hard to avoid them. Infections after elective sports surgeries can have especially devastating long-term consequences. Thankfully, scientific advances such as improved sterile techniques and more powerful prophylactic antibiotics have helped us decrease the rates of perioperative infections. But more can always be done in this arena.
Baron et al. discuss one additional infection-fighting approach in the December 18, 2019 issue of JBJS, where they report on findings from a retrospective cohort study that looked at 90-day infection rates after >1,600 anterior cruciate ligament (ACL) reconstructions. Specifically, they investigated whether the rates of infection differed when the ACL grafts were prepared with or without a vancomycin irrigant. The average patient age was 27 years old, and all the surgeries (84.1% of which were primary reconstructions) were performed by 1 of 6 fellowship-trained surgeons. The graft was soaked in vancomycin solution in 798 cases (48.7%), while the remaining 51.3% did not use vancomycin.
Baron et al. found that 11 of the reconstructions were complicated by infection within 90 days, but only 1 of those 11 infections occurred in the vancomycin group (p=0.032). After controlling for various confounding factors, the authors found that increased body mass index and increased operative time were also significantly associated with postoperative infection, while age, sex, smoking, surgeon, and insurance type were not.
These results reveal an 89.4% relative risk reduction in postoperative infections after ACL reconstructions when grafts are bathed in vancomycin solution, although the absolute rate of infection among non-soaked grafts (1.2%) was still quite low. Time and more rigorous study designs will tell us whether this is a big step forward in the evolution of infection prevention, but these results should at least prompt further investigation.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Vancomycin Powder May Thwart Spinal Fusion
Prompted by relatively high infection rates associated with surgical treatment of pediatric spinal conditions such as scoliosis and spinal-deformity surgery in immunocompromised adults, spine surgeons have led “deep dive” clinical research into the possible benefits of local, intrawound antibiotic therapy. Consequently, the administration of antibiotic powder around the spine’s posterior elements and internal-fixation devices has become fairly widespread. But are there possible downsides to this approach that can impact patient outcomes?
This important question is addressed in the basic-science study by Ishida et al. in the October 2, 2019 issue of The Journal. The authors analyzed the fusion-specific impact of varying concentrations of intrawound vancomycin and tobramycin in a well-characterized rat model of posterolateral fusion performed with syngeneic iliac-crest allograft plus clinical bone-graft substitute. Ishida et al. found that a high dose of vancomycin (71.5 mg/kg, about 5 times higher than spine surgeons typically use) but not tobramycin had detrimental effects on fusion-mass formation in this model, as demonstrated by micro-computed tomography and histological analysis.
We now need further clinical research from the spine community to determine the optimal doses and types of intrawound antibiotics in this setting. Based on the currently available data, power calculations should be performed when designing future trials focused on this question. There seems to be little remaining doubt that locally delivered antibiotics help limit surgical-site and deep infections in spinal surgery. The impact of antibiotics on fusion rates must now be investigated further.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Stop Adding Antibiotics to Irrigation Solutions
The rate of adoption of knowledge gleaned from multiple well-done randomized clinical trials into medical practice is disappointingly slow. This has been well-documented in cardiovascular medicine, and the examples in orthopaedic surgery are embarrassingly similar. A corollary phenomenon exists with the slow rate of transfer of information from basic science studies to orthopaedic clinical practice.
These “disconnects” occur largely because we tend to adopt the practices of our residency faculty, often without any rational inquiry. Having been an oral examiner for the Part II ABOS Oral Boards, I frequently asked, “Why did you decide on that approach to the patient’s problem?” And I often heard in response, “That’s the way it was done in my residency.”
In the September 18, 2019 issue of The Journal, Goswami et al,. report findings from a well-designed in vitro study demonstrating that the common practice of adding the antibiotics polymyxin and bacitracin to irrigation solution to lower the risk of infection is not based on sound evidence. While adding antibiotics might make intuitive sense, according to these authors, it is “a futile exercise.”
After testing 8 different irrigation solutions for efficacy against S. aureus and E. coli and for toxicity to musculoskeletal cells, Goswami et al. concluded that “our results provide further support for the use of dilute povidone-iodine because of its bactericidal properties, relatively limited toxicity,… and modest cost.” They go on to say that their findings bring into question the widespread usage of polymyxin-bacitracin.
Certainly, we need to assemble more evidence from additional research to identify the optimal irrigation solution for orthopaedic surgery, but in the interim, we should probably stop using polymyxin-bacitracin. Doing so would have the added benefits of lowering costs and not exacerbating the serious problem of antimicrobial resistance. There are many areas of clinical practice where we have no evidence either for against a particular approach. But when we do have solid evidence, even if it’s from an in vitro study, we should work together to improve the rates of adoption into clinical practice.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
What’s New in Musculoskeletal Infection 2019
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, Thomas K. Fehring, MD, co-author of the July 17, 2019 “What’s New in Musculoskeletal Infection,” selected the five most clinically compelling findings—all focused on periprosthetic joint infection (PJI)—from among the more than 90 noteworthy studies summarized in the article.
Preventive Irrigation Solutions
–An in vitro study by Campbell et al.1 found that the chlorine-based Dakin solution forms potentially toxic precipitates when mixed with hydrogen peroxide and chlorhexidine. The authors recommend that surgeons not mix irrigation solutions in wounds during surgery.
PJI Diagnosis
–A clinical evaluation by Stone et al. showed that alpha-defensin levels in combination with synovial C-reactive protein had high sensitivity for PJI diagnosis, but the alpha-defensin biomarker can lead to false-positive results in the presence of metallosis and false-negative results in the presence of low-virulence organisms.
–In an investigation of next-generation molecular sequencing for diagnosis of PJI in synovial fluid and tissue, Tarabichi et al. found that in 28 revision cases considered to be infected, cultures were positive in only 61%, while next-generation sequencing was positive in 89%. However, next-generation sequencing also identified microbes in 25% of aseptic revisions that had negative cultures and in 35% of primary total joint arthroplasties. Identification of pathogens in cases considered to be aseptic is concerning and requires further research.
Treating PJI
–A multicenter study found that irrigation and debridement with component retention to treat PJI after total knee arthroplasty had a failure rate of 57% at 4 years.2
–Findings from an 80-patient study by Ford et al.3 challenge the assumption that 2-stage exchanges are highly successful. Fourteen (17.5%) of the patients in the study never underwent reimplantation, 30% had a serious complication, and of the 66 patients with a successful reimplantation, only 73% remained infection-free. Additionally 11% of the patients required a spacer exchange for persistent infection.
References
- Campbell ST, Goodnough LH, Bennett CG, Giori NJ. Antiseptics commonly used in total joint arthroplasty interact and may form toxic products. J Arthroplasty.2018 Mar;33(3):844-6. Epub 2017 Nov 11.
- Urish KL, Bullock AG, Kreger AM, Shah NB, Jeong K, Rothenberger SD; Infected Implant Consortium. A multicenter study of irrigation and debridement in total knee arthroplasty periprosthetic joint infection: treatment failure is high. J Arthroplasty.2018 Apr;33(4):1154-9. Epub 2017 Nov 21.
- Ford AN, Holzmeister AM, Rees HW, Belich PD. Characterization of outcomes of 2-stage exchange arthroplasty in the treatment of prosthetic joint infections. J Arthroplasty.2018 Jul;33(7S):S224-7. Epub 2018 Feb 17.
Failure Factors after 1-Stage Exchange TKA
Prior to performing a primary total joint arthroplasty, patient optimization is both possible and recommended. However, when a patient with a periprosthetic joint infection (PJI) comes in to your office, opportunities for patient optimization are limited. At that point, the patient’s BMI, kidney/liver values, and HgbA1c/fructosamine levels are not going to be dramatically improved prior to any procedure to eradicate the infection and/or salvage the implant. Still, for the purposes of care optimization and prognostic guidance, it is important to identify specific patient or wound characteristics that may help us flag patients who are at increased risk for failure after treatment of a PJI.
That was the goal of the case-control study by Citak et al. in the June 19, 2019 edition of The Journal. The authors compared 91 patients who experienced a failed 1-stage revision total knee arthroplasty that was performed to treat a PJI to a matched cohort who had a successful 1-stage revision to treat a PJI. (The authors defined “failure” as any subsequent surgical procedure regardless of reason.)
A bivariate logistic analysis revealed that patients who had a history of a previous 1-stage (OR 29.3; p< 0.001) or 2-stage (OR 5.8; p <0.001) exchange due to PJI, or who had Streptococcus (OR 6.0; p = 0.013) or Enterococcus (OR 17.3; p = 0.023) isolated from their wound were at increased risk of reinfection compared to the control group. Just as important, the authors found that patient body weight of 100 kg or above and history of deep vein thrombosis (DVT) were the only patient comorbidities related to an increased risk of a failed revision.
While these findings may not be surprising in light of previous data on this topic, they are important in aggregate. Patients whose wounds contain isolated enterococci or streptococci may not be ideal candidates for 1-stage PJI revision surgery. Additionally, the authors highlight that patients who have failed two or more attempts at a 1-stage revision should be considered for a 2-stage protocol.
While many of the patients in this study who failed the 1-stage revision may have also failed a 2-stage revision, ongoing research comparing the two protocols should help further clarify whether certain infections are more amenable to successful treatment with one protocol or the other. In the meantime, studies such as this add valuable data that surgeons can use to guide patient care and provide meaningful patient education for shared decision-making about how to treat these difficult infections.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
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