BARCELONA – An investigational drug that targets the hepatitis B virus (HBV) core protein is a “totally new approach” to treating chronic HBV infection according to the results of an early-phase clinical study.

In an ongoing, international, phase I study presented during the late-breaker session at the International Liver Congress, 4 weeks of treatment with NVR 3-778 was well tolerated and did not result in any drug discontinuations in chronically infected patients. There were dose-related reductions in HBV DNA and early reductions in HBeAg were observed.

“NVR 3-778 is a first-in-class HBV core inhibitor,” study investigator Dr. Man-Fung Yuen, Queen Mary Hospital, Hong Kong, said at a press briefing held at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL). “The HBV core protein has many functions and is responsible for the most important pathway of the virus’ replication – nucleocapsid formation,” he explained.

The rationale behind its development is that although there are effective treatments such as nucleoside and nucleotide analogs (NAs) and pegylated interferon (peg-IFN) that can suppress the activity of HBV for many years and thus slow down damage to the liver, it is unusual to clear the virus permanently. Furthermore, as most patients require potentially life-long treatment, issues such as long-term safety, patients’ adherence, resistance, and cost of therapy come into play.

Dr. Yuen observed that achieving durable responses in patients with chronic HBV is likely to require combinations of potential agents, probably with complementary modes of action.

Preclinical data have shown that NVR 3-778 induces the rapid assembly of nonfunctional capsids and that it inhibits viral replication in a humanized mouse hepatocyte cell model. It has also been shown to reduce HBV DNA to a comparable extent as entecavir when used alone in a mouse model, with undetectable levels reached when used in combination with peg-IFN alpha-2a.

Dr. Yuen reported the preliminary results from the second part of the phase I study in 64 adults with chronic HBV, noting that the first part of the study in healthy volunteers had been completed successfully.

The aim was to examine the safety and efficacy of NVR 3-778 alone and in combination with peg-IFN alpha-2a in previously untreated patients aged between 18 and 65 years who were HBsAg- and HbeAg-positive, had HBV DNA of 20,000 or more copies per IU/mL, with no cirrhosis of the liver, as determined by liver biopsy or imaging.

Patients were randomly assigned to six groups, with four groups receiving the investigational therapy alone at four increasing doses (100, 200, 400, once daily and 600 mg twice daily). There was a staged initiation of each escalating dose of NVR 3-778 used in these groups, with the 100 mg initiated first and if, after 2 weeks, there were no interim safety concerns, the next dose groups, 200 mg, then 400 mg, then 600 mg were started. The other two groups of patients received NVR 3-788 (600 mg) with peg-IFN alpha-2a (180 microg/week) or peg-IFN alpha-2a plus placebo. Treatment for all groups was for 28 days with 28 days of follow-up.

The mean age of patients in each group ranged from 32 to 48 years, with the older patients more likely to be treated with peg-IFN alpha-2a alone or with NVR 3-788. Most of the patients studied were Chinese and the mean baseline HBV DNA was 7.5-8.3 log₁₀ IU/mL.

A total of 98 adverse events were seen in 40 of 64 patients treated, although there was not any trend for more effects with the investigational treatment versus placebo as doses escalated. There were 21 adverse events seen in 20 of 46 patients that were possibly or probably related to the study drug, of which most were grade 1 nausea. Grade 2 nausea occurred only once in a patient given the 100-mg dose. There was one serious adverse event, a grade 3 papulovesicular rash on the hands and feet that occurred in a patient in the 100-mg group, but this responded to therapy. This side effect started about 20 days after treatment and resolved over a period of 7 months.

Although generally mild, more adverse effects were seen in the patients treated with a combination of NVR 3-788 and peg-IFN alpha-2a, which Dr. Yuen noted was thought to be more likely a result of the IFN therapy.

There was not much difference in the mean change in HBV DNA from baseline for the 100-400-mg groups, but there was a 1.72-log₁₀ IU/mL decrease achieved with the 600-mg twice-daily dose. The greatest reduction, however, was seen when NVR 3-788 was combined with peg-IFN alpha-2a, with a 1.97-log₁₀ IU/mL change.

“Encouraging early reductions in HBV RNA and quantitative serum HBeAg were observed,” Dr. Yuen said. He noted that the longer-term safety and efficacy of the novel agent in combination with peg-IFN alpha-2a and first-line HBV NAs will now be further assessed in phase II studies.

“At the moment we do not have a cure for hepatitis B, only treatment,” said Dr. Frank Tacke of the University Hospital Aachen (Germany), who chaired the press briefing where Dr. Yuen first aired the findings. NVR 3-788 represents “a totally new approach to this disease that we hope will lead to a cure,” Dr. Tacke said.

In an EASL-issued press release, Dr. Tacke also noted: “The results from this study are certainly interesting and promising for the treatment of patients with hepatitis B. The medical community is always on the lookout for treatments which can cure this condition, as opposed to simply suppressing the replication of the virus. More research is needed to confirm whether NVR 3-778 could really change the treatment paradigm.”

Novira Therapeutics financed the study. Dr. Yuen has been a consultant, speaker, or both for Arrowhead, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Novartis, and Roche. Dr. Tacke did not have any relevant disclosures.

BARCELONA – An investigational drug that targets the hepatitis B virus (HBV) core protein is a “totally new approach” to treating chronic HBV infection according to the results of an early-phase clinical study.

In an ongoing, international, phase I study presented during the late-breaker session at the International Liver Congress, 4 weeks of treatment with NVR 3-778 was well tolerated and did not result in any drug discontinuations in chronically infected patients. There were dose-related reductions in HBV DNA and early reductions in HBeAg were observed.

“NVR 3-778 is a first-in-class HBV core inhibitor,” study investigator Dr. Man-Fung Yuen, Queen Mary Hospital, Hong Kong, said at a press briefing held at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL). “The HBV core protein has many functions and is responsible for the most important pathway of the virus’ replication – nucleocapsid formation,” he explained.

The rationale behind its development is that although there are effective treatments such as nucleoside and nucleotide analogs (NAs) and pegylated interferon (peg-IFN) that can suppress the activity of HBV for many years and thus slow down damage to the liver, it is unusual to clear the virus permanently. Furthermore, as most patients require potentially life-long treatment, issues such as long-term safety, patients’ adherence, resistance, and cost of therapy come into play.

Dr. Yuen observed that achieving durable responses in patients with chronic HBV is likely to require combinations of potential agents, probably with complementary modes of action.

Preclinical data have shown that NVR 3-778 induces the rapid assembly of nonfunctional capsids and that it inhibits viral replication in a humanized mouse hepatocyte cell model. It has also been shown to reduce HBV DNA to a comparable extent as entecavir when used alone in a mouse model, with undetectable levels reached when used in combination with peg-IFN alpha-2a.

Dr. Yuen reported the preliminary results from the second part of the phase I study in 64 adults with chronic HBV, noting that the first part of the study in healthy volunteers had been completed successfully.

The aim was to examine the safety and efficacy of NVR 3-778 alone and in combination with peg-IFN alpha-2a in previously untreated patients aged between 18 and 65 years who were HBsAg- and HbeAg-positive, had HBV DNA of 20,000 or more copies per IU/mL, with no cirrhosis of the liver, as determined by liver biopsy or imaging.

Patients were randomly assigned to six groups, with four groups receiving the investigational therapy alone at four increasing doses (100, 200, 400, once daily and 600 mg twice daily). There was a staged initiation of each escalating dose of NVR 3-778 used in these groups, with the 100 mg initiated first and if, after 2 weeks, there were no interim safety concerns, the next dose groups, 200 mg, then 400 mg, then 600 mg were started. The other two groups of patients received NVR 3-788 (600 mg) with peg-IFN alpha-2a (180 microg/week) or peg-IFN alpha-2a plus placebo. Treatment for all groups was for 28 days with 28 days of follow-up.

The mean age of patients in each group ranged from 32 to 48 years, with the older patients more likely to be treated with peg-IFN alpha-2a alone or with NVR 3-788. Most of the patients studied were Chinese and the mean baseline HBV DNA was 7.5-8.3 log₁₀ IU/mL.

A total of 98 adverse events were seen in 40 of 64 patients treated, although there was not any trend for more effects with the investigational treatment versus placebo as doses escalated. There were 21 adverse events seen in 20 of 46 patients that were possibly or probably related to the study drug, of which most were grade 1 nausea. Grade 2 nausea occurred only once in a patient given the 100-mg dose. There was one serious adverse event, a grade 3 papulovesicular rash on the hands and feet that occurred in a patient in the 100-mg group, but this responded to therapy. This side effect started about 20 days after treatment and resolved over a period of 7 months.

Although generally mild, more adverse effects were seen in the patients treated with a combination of NVR 3-788 and peg-IFN alpha-2a, which Dr. Yuen noted was thought to be more likely a result of the IFN therapy.

There was not much difference in the mean change in HBV DNA from baseline for the 100-400-mg groups, but there was a 1.72-log₁₀ IU/mL decrease achieved with the 600-mg twice-daily dose. The greatest reduction, however, was seen when NVR 3-788 was combined with peg-IFN alpha-2a, with a 1.97-log₁₀ IU/mL change.

“Encouraging early reductions in HBV RNA and quantitative serum HBeAg were observed,” Dr. Yuen said. He noted that the longer-term safety and efficacy of the novel agent in combination with peg-IFN alpha-2a and first-line HBV NAs will now be further assessed in phase II studies.

“At the moment we do not have a cure for hepatitis B, only treatment,” said Dr. Frank Tacke of the University Hospital Aachen (Germany), who chaired the press briefing where Dr. Yuen first aired the findings. NVR 3-788 represents “a totally new approach to this disease that we hope will lead to a cure,” Dr. Tacke said.

In an EASL-issued press release, Dr. Tacke also noted: “The results from this study are certainly interesting and promising for the treatment of patients with hepatitis B. The medical community is always on the lookout for treatments which can cure this condition, as opposed to simply suppressing the replication of the virus. More research is needed to confirm whether NVR 3-778 could really change the treatment paradigm.”

Novira Therapeutics financed the study. Dr. Yuen has been a consultant, speaker, or both for Arrowhead, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Novartis, and Roche. Dr. Tacke did not have any relevant disclosures.

BARCELONA – An investigational drug that targets the hepatitis B virus (HBV) core protein is a “totally new approach” to treating chronic HBV infection according to the results of an early-phase clinical study.

In an ongoing, international, phase I study presented during the late-breaker session at the International Liver Congress, 4 weeks of treatment with NVR 3-778 was well tolerated and did not result in any drug discontinuations in chronically infected patients. There were dose-related reductions in HBV DNA and early reductions in HBeAg were observed.

“NVR 3-778 is a first-in-class HBV core inhibitor,” study investigator Dr. Man-Fung Yuen, Queen Mary Hospital, Hong Kong, said at a press briefing held at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL). “The HBV core protein has many functions and is responsible for the most important pathway of the virus’ replication – nucleocapsid formation,” he explained.

The rationale behind its development is that although there are effective treatments such as nucleoside and nucleotide analogs (NAs) and pegylated interferon (peg-IFN) that can suppress the activity of HBV for many years and thus slow down damage to the liver, it is unusual to clear the virus permanently. Furthermore, as most patients require potentially life-long treatment, issues such as long-term safety, patients’ adherence, resistance, and cost of therapy come into play.

Dr. Yuen observed that achieving durable responses in patients with chronic HBV is likely to require combinations of potential agents, probably with complementary modes of action.

Preclinical data have shown that NVR 3-778 induces the rapid assembly of nonfunctional capsids and that it inhibits viral replication in a humanized mouse hepatocyte cell model. It has also been shown to reduce HBV DNA to a comparable extent as entecavir when used alone in a mouse model, with undetectable levels reached when used in combination with peg-IFN alpha-2a.

Dr. Yuen reported the preliminary results from the second part of the phase I study in 64 adults with chronic HBV, noting that the first part of the study in healthy volunteers had been completed successfully.

The aim was to examine the safety and efficacy of NVR 3-778 alone and in combination with peg-IFN alpha-2a in previously untreated patients aged between 18 and 65 years who were HBsAg- and HbeAg-positive, had HBV DNA of 20,000 or more copies per IU/mL, with no cirrhosis of the liver, as determined by liver biopsy or imaging.

Patients were randomly assigned to six groups, with four groups receiving the investigational therapy alone at four increasing doses (100, 200, 400, once daily and 600 mg twice daily). There was a staged initiation of each escalating dose of NVR 3-778 used in these groups, with the 100 mg initiated first and if, after 2 weeks, there were no interim safety concerns, the next dose groups, 200 mg, then 400 mg, then 600 mg were started. The other two groups of patients received NVR 3-788 (600 mg) with peg-IFN alpha-2a (180 microg/week) or peg-IFN alpha-2a plus placebo. Treatment for all groups was for 28 days with 28 days of follow-up.

The mean age of patients in each group ranged from 32 to 48 years, with the older patients more likely to be treated with peg-IFN alpha-2a alone or with NVR 3-788. Most of the patients studied were Chinese and the mean baseline HBV DNA was 7.5-8.3 log₁₀ IU/mL.

A total of 98 adverse events were seen in 40 of 64 patients treated, although there was not any trend for more effects with the investigational treatment versus placebo as doses escalated. There were 21 adverse events seen in 20 of 46 patients that were possibly or probably related to the study drug, of which most were grade 1 nausea. Grade 2 nausea occurred only once in a patient given the 100-mg dose. There was one serious adverse event, a grade 3 papulovesicular rash on the hands and feet that occurred in a patient in the 100-mg group, but this responded to therapy. This side effect started about 20 days after treatment and resolved over a period of 7 months.

Although generally mild, more adverse effects were seen in the patients treated with a combination of NVR 3-788 and peg-IFN alpha-2a, which Dr. Yuen noted was thought to be more likely a result of the IFN therapy.

There was not much difference in the mean change in HBV DNA from baseline for the 100-400-mg groups, but there was a 1.72-log₁₀ IU/mL decrease achieved with the 600-mg twice-daily dose. The greatest reduction, however, was seen when NVR 3-788 was combined with peg-IFN alpha-2a, with a 1.97-log₁₀ IU/mL change.

“Encouraging early reductions in HBV RNA and quantitative serum HBeAg were observed,” Dr. Yuen said. He noted that the longer-term safety and efficacy of the novel agent in combination with peg-IFN alpha-2a and first-line HBV NAs will now be further assessed in phase II studies.

“At the moment we do not have a cure for hepatitis B, only treatment,” said Dr. Frank Tacke of the University Hospital Aachen (Germany), who chaired the press briefing where Dr. Yuen first aired the findings. NVR 3-788 represents “a totally new approach to this disease that we hope will lead to a cure,” Dr. Tacke said.

In an EASL-issued press release, Dr. Tacke also noted: “The results from this study are certainly interesting and promising for the treatment of patients with hepatitis B. The medical community is always on the lookout for treatments which can cure this condition, as opposed to simply suppressing the replication of the virus. More research is needed to confirm whether NVR 3-778 could really change the treatment paradigm.”

Novira Therapeutics financed the study. Dr. Yuen has been a consultant, speaker, or both for Arrowhead, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Novartis, and Roche. Dr. Tacke did not have any relevant disclosures.

Now that the Food and Drug Administration has approved Inflectra as the first biosimilar version of the anti–tumor necrosis factor-alpha agent Remicade, rheumatologists and patient advocacy groups are taking stock of how it may be used in practice, and what the future holds for biosimilar drugs, with so many questions still unanswered regarding price, substitution, and safety.

Joseph Riccio/Adirondack Health

Inflectra, approved in early April and given the generic name of infliximab-dyyb under the FDA’s nomenclature for biosimilar products, will have the same indications as Remicade. The agency extrapolated the clinical trial data that Inflectra’s South Korea–based manufacturer, Celltrion, submitted for rheumatoid arthritis and ankylosing spondylitis to all other indications for which Remicade is approved.

It’s currently unclear how the FDA will note which clinical data in Inflectra’s labeling come from Inflectra and which from Remicade, and the same concerns lie with future biosimilar approvals if their results are extrapolated to indications not tested to show biosimilarity in clinical trials.

Labeling questions

It’s concerning to rheumatologists and the patients who will be using them that biosimilars such as Inflectra are not subject to the same pivotal trial experience as the reference biologics on which they are based, according to Dr. Jonathan Krant, section chief of rheumatology for Adirondack Health Systems in Saranac Lake, N.Y., and medical director for CreakyJoints, a community of patients with arthritis and caregivers, and its larger parent nonprofit advocacy organization, the Global Healthy Living Foundation (GHLF).

While the unique regulatory requirements in the biosimilar approval pathway reduce development costs and could potentially make Inflectra’s average wholesale price 30% less than Remicade – as was the case when Inflectra was first on the market in Europe – it’s not known how reduced costs may affect the safety of biosimilars.

“It worries all of us that manufacturers may cut corners to manage the cost constraints imposed by managed care,” Dr. Krant said in an interview.

Given that U.S. rheumatologists don’t have experience with biosimilars, Dr. Krant is anticipating some push back. “I think some physicians are going to fight back and won’t want to prescribe them, even if mandated, because of concerns regarding patient safety,” he said.

In a written statement, Dr. Joan Von Feldt, president of the American College of Rheumatology, welcomed the potential benefits on access to care that cost-saving biosimilars may bring to the U.S. health care system, but also said that “the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.”

Inflectra met the FDA’s “very similar” criteria to be approved as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade, the agency said. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

However, it may not hold true that Inflectra will have the same efficacy and safety for all indications that Remicade had due to potential differences in the mechanism of action through which Remicade exerts its effect across indications, which in this case may apply to the indications for Crohn’s disease and ulcerative colitis.

Health Canada chose not to extrapolate the indications for Inflectra (known as Remsima in Canada) to Crohn’s disease and ulcerative colitis because of “observed differences in the level of afucosylation, Fc-gammaRIIIa receptor binding, and some in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays” that could not rule out the possibility that Inflectra and Remicade differ in their ability to induce ADCC. Unlike the other indications for Remicade, Health Canada said “ADCC cannot be ruled out as a mechanism of action in the inflammatory bowel diseases. This position is supported by the observation that certolizumab pegol, another anti-TNF [anti–tumor necrosis factor] that lacks the ability to induce ADCC, displays only marginal efficacy in Crohn’s patients, compared with other anti-TNFs, namely infliximab.”

Other organizations suggest that extrapolation of indications is only appropriate when it is benefiting the patient to the greatest extent possible.

“GHLF is okay with extrapolation of indication unless the mechanism of action for the therapy is either scientifically or therapeutically outdated,” Stephen Marmaras, state and national advocacy manager for the GHLF, said in an interview. “Patients are okay with extrapolating data in order to expedite the approval process as long as you are extrapolating to best in class therapy for a particular indication. What [the GHLF is] saying is we want biosimilars to be an improvement on what we have, not the lowest common denominator. We shouldn’t be extrapolating indications data from products that aren’t considered to be the best product for that indication.”

“If we’re just judging on expediting the approval process for indications that are not considered to be really treated well by this particular drug, you have to always assume that the insurance company is going to go with the lowest common denominator,” he added. “What that could lead to, from a slippery-slope perspective, is the chipping away of the use of cutting-edge therapies.”

Substitution concerns

Inflectra was not approved as interchangeable with Remicade or other infliximab biosimilars. The FDA has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”

A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

One of the biggest concerns that physicians have is that biosimilars will be substituted for the reference products without notification, Dr. Krant said. “State by state we’re looking at potential substitution rules which allow pharmacists to switch out these cheaper molecules for the reference product,” he said, and without timely notification, patients and rheumatologists won’t know whether it was the reference product or a biosimilar that was associated with an adverse event or loss of efficacy.

The ACR and patient advocacy organizations such as the GHLF are against forced switching of patients for nonmedical reasons. Patients’ and rheumatologists’ confidence in biosimilar safety will be key to their uptake and the overall expansion of access to biologics to more patients, Mr. Marmaras said.

Patient costs uncertain

Although rheumatologists hope that with biosimilars’ lower costs, access will expand, there is no guarantee it will do so by saving patients money.

“It’s a common misperception that a 30% decrease in the cost of a several thousand dollar-a-month drug is going to automatically open all the doors to access,” said Dr. Sean Fahey, a rheumatologist in Mooresville, N.C., and chair of the insurance subcommittee of the ACR’s Committee on Rheumatologic Care. “Most of my patients who use biologics do so either through copay cards from the pharmaceutical industry or through Medicare and a secondary [payer] covering their out-of-pocket costs for the infusible biologics. This is clearly saving the system money, which is important no doubt, but unless it’s significantly less expensive, it actually might not change the patient’s out-of pocket [cost] all that much.”

The patient assistance programs from biologics manufacturers that offer copay assistance, access hotlines, and administration benefits could be in jeopardy with the rise of biosimilars. Since the programs are bundled into the average wholesale price of the drug, the savings offered by the reduced wholesale price of biosimilars may squeeze them out, Dr. Krant said.

“There’s going to be a lot of hue and cry from the patients who cannot self-administer or have problems with compliance because of copays in the first place,” he predicted.

Another factor that could affect how much biosimilars such as Inflectra will be used is the amount of rebates or discounts that payers receive directly from the pharmaceutical manufacturers.

“We know for the Medicaid population what the average sales prices are, but for private payers, we don’t know if they’re giving 2%, 5%, 18%; we have no idea what the data are. This could affect how much market share Inflectra gets,” said Dr. Fahey, who is also president of the North Carolina Rheumatology Association.

It may be awhile before Inflectra is available on the U.S. market. In a statement following the approval of Inflectra, Remicade-maker Janssen said the “patents for Remicade remain valid and enforceable until September 2018. A commercial launch of Celltrion’s infliximab-dyyb in advance of this date would be an infringement of our patents, and we intend to defend our intellectual property rights.”

Janssen notes that its patient support program for Remicade “continues to offer a copay card for patients with commercial insurance that reduces the patient out-of-pocket cost to no more than $5 per infusion. Eligible uninsured and underinsured patients may be able to access Remicade through the Johnson & Johnson Patient Assistance Foundation.”

Pfizer, which owns the rights to marketing Inflectra in the United States, did not respond directly to a question about whether it would have a payment assistance program for Inflectra. “While we cannot comment on specific commercialization strategies at this time, we are working to bring these important therapies to market in the U.S. as quickly as possible,” said Rachel Hooper, Director of Public Affairs, West, for Pfizer.

It seems likely that once Inflectra does come to the market, new starts will account for many patients who will use the drug because of the lack of information available about whether there is, or is not, significant risk of immunogenicity with switching or loss of efficacy, Dr. Fahey said. “What is less certain is whether the payers will try to force us to move people from the Remicade brand to the infliximab biosimilar, and what the potential consequences of that is going to be.”

Dr. Krant, Dr. Fahey, and Mr. Marmaras had no relevant disclosures.

[email protected]

Now that the Food and Drug Administration has approved Inflectra as the first biosimilar version of the anti–tumor necrosis factor-alpha agent Remicade, rheumatologists and patient advocacy groups are taking stock of how it may be used in practice, and what the future holds for biosimilar drugs, with so many questions still unanswered regarding price, substitution, and safety.

Joseph Riccio/Adirondack Health

Inflectra, approved in early April and given the generic name of infliximab-dyyb under the FDA’s nomenclature for biosimilar products, will have the same indications as Remicade. The agency extrapolated the clinical trial data that Inflectra’s South Korea–based manufacturer, Celltrion, submitted for rheumatoid arthritis and ankylosing spondylitis to all other indications for which Remicade is approved.

It’s currently unclear how the FDA will note which clinical data in Inflectra’s labeling come from Inflectra and which from Remicade, and the same concerns lie with future biosimilar approvals if their results are extrapolated to indications not tested to show biosimilarity in clinical trials.

Labeling questions

It’s concerning to rheumatologists and the patients who will be using them that biosimilars such as Inflectra are not subject to the same pivotal trial experience as the reference biologics on which they are based, according to Dr. Jonathan Krant, section chief of rheumatology for Adirondack Health Systems in Saranac Lake, N.Y., and medical director for CreakyJoints, a community of patients with arthritis and caregivers, and its larger parent nonprofit advocacy organization, the Global Healthy Living Foundation (GHLF).

While the unique regulatory requirements in the biosimilar approval pathway reduce development costs and could potentially make Inflectra’s average wholesale price 30% less than Remicade – as was the case when Inflectra was first on the market in Europe – it’s not known how reduced costs may affect the safety of biosimilars.

“It worries all of us that manufacturers may cut corners to manage the cost constraints imposed by managed care,” Dr. Krant said in an interview.

Given that U.S. rheumatologists don’t have experience with biosimilars, Dr. Krant is anticipating some push back. “I think some physicians are going to fight back and won’t want to prescribe them, even if mandated, because of concerns regarding patient safety,” he said.

In a written statement, Dr. Joan Von Feldt, president of the American College of Rheumatology, welcomed the potential benefits on access to care that cost-saving biosimilars may bring to the U.S. health care system, but also said that “the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.”

Inflectra met the FDA’s “very similar” criteria to be approved as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade, the agency said. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

However, it may not hold true that Inflectra will have the same efficacy and safety for all indications that Remicade had due to potential differences in the mechanism of action through which Remicade exerts its effect across indications, which in this case may apply to the indications for Crohn’s disease and ulcerative colitis.

Health Canada chose not to extrapolate the indications for Inflectra (known as Remsima in Canada) to Crohn’s disease and ulcerative colitis because of “observed differences in the level of afucosylation, Fc-gammaRIIIa receptor binding, and some in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays” that could not rule out the possibility that Inflectra and Remicade differ in their ability to induce ADCC. Unlike the other indications for Remicade, Health Canada said “ADCC cannot be ruled out as a mechanism of action in the inflammatory bowel diseases. This position is supported by the observation that certolizumab pegol, another anti-TNF [anti–tumor necrosis factor] that lacks the ability to induce ADCC, displays only marginal efficacy in Crohn’s patients, compared with other anti-TNFs, namely infliximab.”

Other organizations suggest that extrapolation of indications is only appropriate when it is benefiting the patient to the greatest extent possible.

“GHLF is okay with extrapolation of indication unless the mechanism of action for the therapy is either scientifically or therapeutically outdated,” Stephen Marmaras, state and national advocacy manager for the GHLF, said in an interview. “Patients are okay with extrapolating data in order to expedite the approval process as long as you are extrapolating to best in class therapy for a particular indication. What [the GHLF is] saying is we want biosimilars to be an improvement on what we have, not the lowest common denominator. We shouldn’t be extrapolating indications data from products that aren’t considered to be the best product for that indication.”

“If we’re just judging on expediting the approval process for indications that are not considered to be really treated well by this particular drug, you have to always assume that the insurance company is going to go with the lowest common denominator,” he added. “What that could lead to, from a slippery-slope perspective, is the chipping away of the use of cutting-edge therapies.”

Substitution concerns

Inflectra was not approved as interchangeable with Remicade or other infliximab biosimilars. The FDA has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”

A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

One of the biggest concerns that physicians have is that biosimilars will be substituted for the reference products without notification, Dr. Krant said. “State by state we’re looking at potential substitution rules which allow pharmacists to switch out these cheaper molecules for the reference product,” he said, and without timely notification, patients and rheumatologists won’t know whether it was the reference product or a biosimilar that was associated with an adverse event or loss of efficacy.

The ACR and patient advocacy organizations such as the GHLF are against forced switching of patients for nonmedical reasons. Patients’ and rheumatologists’ confidence in biosimilar safety will be key to their uptake and the overall expansion of access to biologics to more patients, Mr. Marmaras said.

Patient costs uncertain

Although rheumatologists hope that with biosimilars’ lower costs, access will expand, there is no guarantee it will do so by saving patients money.

“It’s a common misperception that a 30% decrease in the cost of a several thousand dollar-a-month drug is going to automatically open all the doors to access,” said Dr. Sean Fahey, a rheumatologist in Mooresville, N.C., and chair of the insurance subcommittee of the ACR’s Committee on Rheumatologic Care. “Most of my patients who use biologics do so either through copay cards from the pharmaceutical industry or through Medicare and a secondary [payer] covering their out-of-pocket costs for the infusible biologics. This is clearly saving the system money, which is important no doubt, but unless it’s significantly less expensive, it actually might not change the patient’s out-of pocket [cost] all that much.”

The patient assistance programs from biologics manufacturers that offer copay assistance, access hotlines, and administration benefits could be in jeopardy with the rise of biosimilars. Since the programs are bundled into the average wholesale price of the drug, the savings offered by the reduced wholesale price of biosimilars may squeeze them out, Dr. Krant said.

“There’s going to be a lot of hue and cry from the patients who cannot self-administer or have problems with compliance because of copays in the first place,” he predicted.

Another factor that could affect how much biosimilars such as Inflectra will be used is the amount of rebates or discounts that payers receive directly from the pharmaceutical manufacturers.

“We know for the Medicaid population what the average sales prices are, but for private payers, we don’t know if they’re giving 2%, 5%, 18%; we have no idea what the data are. This could affect how much market share Inflectra gets,” said Dr. Fahey, who is also president of the North Carolina Rheumatology Association.

It may be awhile before Inflectra is available on the U.S. market. In a statement following the approval of Inflectra, Remicade-maker Janssen said the “patents for Remicade remain valid and enforceable until September 2018. A commercial launch of Celltrion’s infliximab-dyyb in advance of this date would be an infringement of our patents, and we intend to defend our intellectual property rights.”

Janssen notes that its patient support program for Remicade “continues to offer a copay card for patients with commercial insurance that reduces the patient out-of-pocket cost to no more than $5 per infusion. Eligible uninsured and underinsured patients may be able to access Remicade through the Johnson & Johnson Patient Assistance Foundation.”

Pfizer, which owns the rights to marketing Inflectra in the United States, did not respond directly to a question about whether it would have a payment assistance program for Inflectra. “While we cannot comment on specific commercialization strategies at this time, we are working to bring these important therapies to market in the U.S. as quickly as possible,” said Rachel Hooper, Director of Public Affairs, West, for Pfizer.

It seems likely that once Inflectra does come to the market, new starts will account for many patients who will use the drug because of the lack of information available about whether there is, or is not, significant risk of immunogenicity with switching or loss of efficacy, Dr. Fahey said. “What is less certain is whether the payers will try to force us to move people from the Remicade brand to the infliximab biosimilar, and what the potential consequences of that is going to be.”

Dr. Krant, Dr. Fahey, and Mr. Marmaras had no relevant disclosures.

[email protected]

Now that the Food and Drug Administration has approved Inflectra as the first biosimilar version of the anti–tumor necrosis factor-alpha agent Remicade, rheumatologists and patient advocacy groups are taking stock of how it may be used in practice, and what the future holds for biosimilar drugs, with so many questions still unanswered regarding price, substitution, and safety.

Joseph Riccio/Adirondack Health

Inflectra, approved in early April and given the generic name of infliximab-dyyb under the FDA’s nomenclature for biosimilar products, will have the same indications as Remicade. The agency extrapolated the clinical trial data that Inflectra’s South Korea–based manufacturer, Celltrion, submitted for rheumatoid arthritis and ankylosing spondylitis to all other indications for which Remicade is approved.

It’s currently unclear how the FDA will note which clinical data in Inflectra’s labeling come from Inflectra and which from Remicade, and the same concerns lie with future biosimilar approvals if their results are extrapolated to indications not tested to show biosimilarity in clinical trials.

Labeling questions

It’s concerning to rheumatologists and the patients who will be using them that biosimilars such as Inflectra are not subject to the same pivotal trial experience as the reference biologics on which they are based, according to Dr. Jonathan Krant, section chief of rheumatology for Adirondack Health Systems in Saranac Lake, N.Y., and medical director for CreakyJoints, a community of patients with arthritis and caregivers, and its larger parent nonprofit advocacy organization, the Global Healthy Living Foundation (GHLF).

While the unique regulatory requirements in the biosimilar approval pathway reduce development costs and could potentially make Inflectra’s average wholesale price 30% less than Remicade – as was the case when Inflectra was first on the market in Europe – it’s not known how reduced costs may affect the safety of biosimilars.

“It worries all of us that manufacturers may cut corners to manage the cost constraints imposed by managed care,” Dr. Krant said in an interview.

Given that U.S. rheumatologists don’t have experience with biosimilars, Dr. Krant is anticipating some push back. “I think some physicians are going to fight back and won’t want to prescribe them, even if mandated, because of concerns regarding patient safety,” he said.

In a written statement, Dr. Joan Von Feldt, president of the American College of Rheumatology, welcomed the potential benefits on access to care that cost-saving biosimilars may bring to the U.S. health care system, but also said that “the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.”

Inflectra met the FDA’s “very similar” criteria to be approved as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade, the agency said. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

However, it may not hold true that Inflectra will have the same efficacy and safety for all indications that Remicade had due to potential differences in the mechanism of action through which Remicade exerts its effect across indications, which in this case may apply to the indications for Crohn’s disease and ulcerative colitis.

Health Canada chose not to extrapolate the indications for Inflectra (known as Remsima in Canada) to Crohn’s disease and ulcerative colitis because of “observed differences in the level of afucosylation, Fc-gammaRIIIa receptor binding, and some in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays” that could not rule out the possibility that Inflectra and Remicade differ in their ability to induce ADCC. Unlike the other indications for Remicade, Health Canada said “ADCC cannot be ruled out as a mechanism of action in the inflammatory bowel diseases. This position is supported by the observation that certolizumab pegol, another anti-TNF [anti–tumor necrosis factor] that lacks the ability to induce ADCC, displays only marginal efficacy in Crohn’s patients, compared with other anti-TNFs, namely infliximab.”

Other organizations suggest that extrapolation of indications is only appropriate when it is benefiting the patient to the greatest extent possible.

“GHLF is okay with extrapolation of indication unless the mechanism of action for the therapy is either scientifically or therapeutically outdated,” Stephen Marmaras, state and national advocacy manager for the GHLF, said in an interview. “Patients are okay with extrapolating data in order to expedite the approval process as long as you are extrapolating to best in class therapy for a particular indication. What [the GHLF is] saying is we want biosimilars to be an improvement on what we have, not the lowest common denominator. We shouldn’t be extrapolating indications data from products that aren’t considered to be the best product for that indication.”

“If we’re just judging on expediting the approval process for indications that are not considered to be really treated well by this particular drug, you have to always assume that the insurance company is going to go with the lowest common denominator,” he added. “What that could lead to, from a slippery-slope perspective, is the chipping away of the use of cutting-edge therapies.”

Substitution concerns

Inflectra was not approved as interchangeable with Remicade or other infliximab biosimilars. The FDA has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”

A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

One of the biggest concerns that physicians have is that biosimilars will be substituted for the reference products without notification, Dr. Krant said. “State by state we’re looking at potential substitution rules which allow pharmacists to switch out these cheaper molecules for the reference product,” he said, and without timely notification, patients and rheumatologists won’t know whether it was the reference product or a biosimilar that was associated with an adverse event or loss of efficacy.

The ACR and patient advocacy organizations such as the GHLF are against forced switching of patients for nonmedical reasons. Patients’ and rheumatologists’ confidence in biosimilar safety will be key to their uptake and the overall expansion of access to biologics to more patients, Mr. Marmaras said.

Patient costs uncertain

Although rheumatologists hope that with biosimilars’ lower costs, access will expand, there is no guarantee it will do so by saving patients money.

“It’s a common misperception that a 30% decrease in the cost of a several thousand dollar-a-month drug is going to automatically open all the doors to access,” said Dr. Sean Fahey, a rheumatologist in Mooresville, N.C., and chair of the insurance subcommittee of the ACR’s Committee on Rheumatologic Care. “Most of my patients who use biologics do so either through copay cards from the pharmaceutical industry or through Medicare and a secondary [payer] covering their out-of-pocket costs for the infusible biologics. This is clearly saving the system money, which is important no doubt, but unless it’s significantly less expensive, it actually might not change the patient’s out-of pocket [cost] all that much.”

The patient assistance programs from biologics manufacturers that offer copay assistance, access hotlines, and administration benefits could be in jeopardy with the rise of biosimilars. Since the programs are bundled into the average wholesale price of the drug, the savings offered by the reduced wholesale price of biosimilars may squeeze them out, Dr. Krant said.

“There’s going to be a lot of hue and cry from the patients who cannot self-administer or have problems with compliance because of copays in the first place,” he predicted.

Another factor that could affect how much biosimilars such as Inflectra will be used is the amount of rebates or discounts that payers receive directly from the pharmaceutical manufacturers.

“We know for the Medicaid population what the average sales prices are, but for private payers, we don’t know if they’re giving 2%, 5%, 18%; we have no idea what the data are. This could affect how much market share Inflectra gets,” said Dr. Fahey, who is also president of the North Carolina Rheumatology Association.

It may be awhile before Inflectra is available on the U.S. market. In a statement following the approval of Inflectra, Remicade-maker Janssen said the “patents for Remicade remain valid and enforceable until September 2018. A commercial launch of Celltrion’s infliximab-dyyb in advance of this date would be an infringement of our patents, and we intend to defend our intellectual property rights.”

Janssen notes that its patient support program for Remicade “continues to offer a copay card for patients with commercial insurance that reduces the patient out-of-pocket cost to no more than $5 per infusion. Eligible uninsured and underinsured patients may be able to access Remicade through the Johnson & Johnson Patient Assistance Foundation.”

Pfizer, which owns the rights to marketing Inflectra in the United States, did not respond directly to a question about whether it would have a payment assistance program for Inflectra. “While we cannot comment on specific commercialization strategies at this time, we are working to bring these important therapies to market in the U.S. as quickly as possible,” said Rachel Hooper, Director of Public Affairs, West, for Pfizer.

It seems likely that once Inflectra does come to the market, new starts will account for many patients who will use the drug because of the lack of information available about whether there is, or is not, significant risk of immunogenicity with switching or loss of efficacy, Dr. Fahey said. “What is less certain is whether the payers will try to force us to move people from the Remicade brand to the infliximab biosimilar, and what the potential consequences of that is going to be.”

Dr. Krant, Dr. Fahey, and Mr. Marmaras had no relevant disclosures.

[email protected]

Hospital air is a potential route of transmission of beta-lactam–resistant bacteria (BLRB), which are important causative agents of nosocomial infections, according to research published in the American Journal of Infection Control.

Dr. Mahnaz Nikaeen of the department of environmental health engineering at Isfahan (Iran) University of Medical Sciences, and his coauthors collected and tested 64 air samples from four hospital wards to determine the prevalence of airborne BLRB in different teaching hospitals, to evaluate the frequency of five common beta-lactamase–encoding genes in isolated resistant bacteria, and to identify the most predominant BLRB by 16s rRNA gene sequencing. The sampling locations in each hospital included operating rooms, ICUs, surgery wards, and internal medicine wards.

©Andrei Malov/ThinkStock.com

The investigators detected airborne bacteria by using culture plates with and without beta-lactams.

The prevalence of BLRB in the air samples ranged between 3% and 34%, Dr. Nikaeen said. Oxacillin-resistant bacteria had the highest prevalence, followed by ceftazidime- and cefazolin-resistant bacteria. Acinetobacter spp, Acinetobacter baumannii, and Staphylococcus spp were the most predominant BLRB.

Gene sequencing revealed that the frequency of beta-lactamase–encoding genes in isolated BLRB ranged between 0% and 47%, with the highest and lowest detection for OXA-23, commonly found in Acinetobacter spp, and CTX-m-32, a gene prevalent in extended-spectrum beta-lactamase–producing Enterobacteriaceae, respectively. MecA, a genetic element found in methicillin-resistant Staphylococcus spp, had a relatively high frequency in surgery wards and operating rooms, whereas the frequency of blaTEM, another common extended-spectrum beta-lactamase produced by Enterobacteriaceae, was higher in intensive care units and internal medicine wards. OXA-51, a chromosomally located intrinsic gene in A. baumannii, was detected in four wards.

“Isolation of beta-lactam–resistant Staphylococcus spp and A. baumannii as the most predominant BLRB indicated the potential role of airborne bacteria in dissemination of nosocomial infections,” Dr. Nikaeen and his coauthors said. “The results confirm the necessity for application of effective control measures that significantly decrease the exposure of high-risk patients to potentially airborne nosocomial infections.”

The authors reported having no conflicts.

Read the complete study in the American Journal of Infection Control (doi:10.1016/j.ajic.2016.01.041).

[email protected]

On Twitter @richpizzi

Hospital air is a potential route of transmission of beta-lactam–resistant bacteria (BLRB), which are important causative agents of nosocomial infections, according to research published in the American Journal of Infection Control.

Dr. Mahnaz Nikaeen of the department of environmental health engineering at Isfahan (Iran) University of Medical Sciences, and his coauthors collected and tested 64 air samples from four hospital wards to determine the prevalence of airborne BLRB in different teaching hospitals, to evaluate the frequency of five common beta-lactamase–encoding genes in isolated resistant bacteria, and to identify the most predominant BLRB by 16s rRNA gene sequencing. The sampling locations in each hospital included operating rooms, ICUs, surgery wards, and internal medicine wards.

©Andrei Malov/ThinkStock.com

The investigators detected airborne bacteria by using culture plates with and without beta-lactams.

The prevalence of BLRB in the air samples ranged between 3% and 34%, Dr. Nikaeen said. Oxacillin-resistant bacteria had the highest prevalence, followed by ceftazidime- and cefazolin-resistant bacteria. Acinetobacter spp, Acinetobacter baumannii, and Staphylococcus spp were the most predominant BLRB.

Gene sequencing revealed that the frequency of beta-lactamase–encoding genes in isolated BLRB ranged between 0% and 47%, with the highest and lowest detection for OXA-23, commonly found in Acinetobacter spp, and CTX-m-32, a gene prevalent in extended-spectrum beta-lactamase–producing Enterobacteriaceae, respectively. MecA, a genetic element found in methicillin-resistant Staphylococcus spp, had a relatively high frequency in surgery wards and operating rooms, whereas the frequency of blaTEM, another common extended-spectrum beta-lactamase produced by Enterobacteriaceae, was higher in intensive care units and internal medicine wards. OXA-51, a chromosomally located intrinsic gene in A. baumannii, was detected in four wards.

“Isolation of beta-lactam–resistant Staphylococcus spp and A. baumannii as the most predominant BLRB indicated the potential role of airborne bacteria in dissemination of nosocomial infections,” Dr. Nikaeen and his coauthors said. “The results confirm the necessity for application of effective control measures that significantly decrease the exposure of high-risk patients to potentially airborne nosocomial infections.”

The authors reported having no conflicts.

Read the complete study in the American Journal of Infection Control (doi:10.1016/j.ajic.2016.01.041).

[email protected]

On Twitter @richpizzi

Hospital air is a potential route of transmission of beta-lactam–resistant bacteria (BLRB), which are important causative agents of nosocomial infections, according to research published in the American Journal of Infection Control.

Dr. Mahnaz Nikaeen of the department of environmental health engineering at Isfahan (Iran) University of Medical Sciences, and his coauthors collected and tested 64 air samples from four hospital wards to determine the prevalence of airborne BLRB in different teaching hospitals, to evaluate the frequency of five common beta-lactamase–encoding genes in isolated resistant bacteria, and to identify the most predominant BLRB by 16s rRNA gene sequencing. The sampling locations in each hospital included operating rooms, ICUs, surgery wards, and internal medicine wards.

©Andrei Malov/ThinkStock.com

The investigators detected airborne bacteria by using culture plates with and without beta-lactams.

The prevalence of BLRB in the air samples ranged between 3% and 34%, Dr. Nikaeen said. Oxacillin-resistant bacteria had the highest prevalence, followed by ceftazidime- and cefazolin-resistant bacteria. Acinetobacter spp, Acinetobacter baumannii, and Staphylococcus spp were the most predominant BLRB.

Gene sequencing revealed that the frequency of beta-lactamase–encoding genes in isolated BLRB ranged between 0% and 47%, with the highest and lowest detection for OXA-23, commonly found in Acinetobacter spp, and CTX-m-32, a gene prevalent in extended-spectrum beta-lactamase–producing Enterobacteriaceae, respectively. MecA, a genetic element found in methicillin-resistant Staphylococcus spp, had a relatively high frequency in surgery wards and operating rooms, whereas the frequency of blaTEM, another common extended-spectrum beta-lactamase produced by Enterobacteriaceae, was higher in intensive care units and internal medicine wards. OXA-51, a chromosomally located intrinsic gene in A. baumannii, was detected in four wards.

“Isolation of beta-lactam–resistant Staphylococcus spp and A. baumannii as the most predominant BLRB indicated the potential role of airborne bacteria in dissemination of nosocomial infections,” Dr. Nikaeen and his coauthors said. “The results confirm the necessity for application of effective control measures that significantly decrease the exposure of high-risk patients to potentially airborne nosocomial infections.”

The authors reported having no conflicts.

Read the complete study in the American Journal of Infection Control (doi:10.1016/j.ajic.2016.01.041).

[email protected]

On Twitter @richpizzi

Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.

In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.

CDC/D. Holdeman

The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.

Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.

During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).

“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.

The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.

Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.

In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.

CDC/D. Holdeman

The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.

Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.

During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).

“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.

The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.

Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.

In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.

CDC/D. Holdeman

The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.

Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.

During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).

“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.

The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.

(Reuters Health) - Some cancer patients may turn down care that could ease their pain and improve their quality of life because they think this type of "palliative" treatment amounts

to giving up and simply waiting to die, a small Canadian study suggests.

Even though the World Health Organization recommends early palliative care for patients living with any serious illness, negative attitudes among patients and family caregivers often lead them to reject this option, researchers note in the Canadian Medical Association Journal.

"Patients and caregivers in our study saw palliative care as being equated with death, loss of hope, dependency, and going into places you never get out of again," said lead study author Dr. Camilla Zimmermann, head of the division of palliative care at the University Health Network in Toronto.

"This is in stark contrast with the actual definition of palliative care, which is interdisciplinary care that provides quality of life for patients with any serious illness and their families, and that is provided throughout the course of the illness rather than only at the end of life," Zimmermann added by email.

Zimmermann and colleagues interviewed 48 cancer patients and 23 of their family caregivers in cases when life expectancy was six to 24 months.

The researchers randomly assigned 26 patients to receive palliative care in addition to standard cancer care, while another 22 patients had only standard care.

Twenty-two patients in the palliative care group and 20 in the control group were receiving chemotherapy.

Over four months, patients in the palliative care group had at least monthly palliative care clinic visits, while those in the standard care group didn't receive any formal interventions. Caregivers could attend clinic visits for the palliative care participants, but they weren't required to do so.

Patients were typically in their early to mid 60s. Most were married and had at least some education beyond high school.

Most family caregivers were spouses, but a few were children or other relatives.

Initial perceptions of palliative care were similar in both groups - patients generally thought this was done only for the dying. While patients in both groups thought of palliative care

as providing comfort, they also associated it with giving up on treatment.

Once some patients received palliative care, however, their thinking shifted. Some patients now saw this as a way to live life to the fullest despite the terminal diagnosis, while others

suggested that doctors might have better luck renaming this as something other than "palliative care."

Calling palliative care providers "pain specialists" because they treat discomfort and focus on quality of life would make this sound more appealing and less frightening, some patients

said after getting this type of care.

But in the control group, without any experience with palliative care during the study, patients didn't see the point of renaming it because they thought it would still carry the stigma of giving up and waiting to die.

"Palliative care should not be framed as a last resort option," said Dr. Anthony Caprio, a geriatrician and hospice and palliative medicine physician at Carolinas HealthCare System in

North Carolina.

"These `nothing left to do' conversations often frame palliative care as a way to help people die comfortably, rather than an approach to care that allows them to live with the highest quality of life for as long as possible," said Caprio, who wrote an editorial that was published with the study.

Using different language in discussions with patients can make a big difference, Caprio added.

"I often describe palliative care as an extra layer of support," Caprio said. "Who wouldn't want more support, especially during a difficult illness?"

(Reuters Health) - Some cancer patients may turn down care that could ease their pain and improve their quality of life because they think this type of "palliative" treatment amounts

to giving up and simply waiting to die, a small Canadian study suggests.

Even though the World Health Organization recommends early palliative care for patients living with any serious illness, negative attitudes among patients and family caregivers often lead them to reject this option, researchers note in the Canadian Medical Association Journal.

"Patients and caregivers in our study saw palliative care as being equated with death, loss of hope, dependency, and going into places you never get out of again," said lead study author Dr. Camilla Zimmermann, head of the division of palliative care at the University Health Network in Toronto.

"This is in stark contrast with the actual definition of palliative care, which is interdisciplinary care that provides quality of life for patients with any serious illness and their families, and that is provided throughout the course of the illness rather than only at the end of life," Zimmermann added by email.

Zimmermann and colleagues interviewed 48 cancer patients and 23 of their family caregivers in cases when life expectancy was six to 24 months.

The researchers randomly assigned 26 patients to receive palliative care in addition to standard cancer care, while another 22 patients had only standard care.

Twenty-two patients in the palliative care group and 20 in the control group were receiving chemotherapy.

Over four months, patients in the palliative care group had at least monthly palliative care clinic visits, while those in the standard care group didn't receive any formal interventions. Caregivers could attend clinic visits for the palliative care participants, but they weren't required to do so.

Patients were typically in their early to mid 60s. Most were married and had at least some education beyond high school.

Most family caregivers were spouses, but a few were children or other relatives.

Initial perceptions of palliative care were similar in both groups - patients generally thought this was done only for the dying. While patients in both groups thought of palliative care

as providing comfort, they also associated it with giving up on treatment.

Once some patients received palliative care, however, their thinking shifted. Some patients now saw this as a way to live life to the fullest despite the terminal diagnosis, while others

suggested that doctors might have better luck renaming this as something other than "palliative care."

Calling palliative care providers "pain specialists" because they treat discomfort and focus on quality of life would make this sound more appealing and less frightening, some patients

said after getting this type of care.

But in the control group, without any experience with palliative care during the study, patients didn't see the point of renaming it because they thought it would still carry the stigma of giving up and waiting to die.

"Palliative care should not be framed as a last resort option," said Dr. Anthony Caprio, a geriatrician and hospice and palliative medicine physician at Carolinas HealthCare System in

North Carolina.

"These `nothing left to do' conversations often frame palliative care as a way to help people die comfortably, rather than an approach to care that allows them to live with the highest quality of life for as long as possible," said Caprio, who wrote an editorial that was published with the study.

Using different language in discussions with patients can make a big difference, Caprio added.

"I often describe palliative care as an extra layer of support," Caprio said. "Who wouldn't want more support, especially during a difficult illness?"

(Reuters Health) - Some cancer patients may turn down care that could ease their pain and improve their quality of life because they think this type of "palliative" treatment amounts

to giving up and simply waiting to die, a small Canadian study suggests.

Even though the World Health Organization recommends early palliative care for patients living with any serious illness, negative attitudes among patients and family caregivers often lead them to reject this option, researchers note in the Canadian Medical Association Journal.

"Patients and caregivers in our study saw palliative care as being equated with death, loss of hope, dependency, and going into places you never get out of again," said lead study author Dr. Camilla Zimmermann, head of the division of palliative care at the University Health Network in Toronto.

"This is in stark contrast with the actual definition of palliative care, which is interdisciplinary care that provides quality of life for patients with any serious illness and their families, and that is provided throughout the course of the illness rather than only at the end of life," Zimmermann added by email.

Zimmermann and colleagues interviewed 48 cancer patients and 23 of their family caregivers in cases when life expectancy was six to 24 months.

The researchers randomly assigned 26 patients to receive palliative care in addition to standard cancer care, while another 22 patients had only standard care.

Twenty-two patients in the palliative care group and 20 in the control group were receiving chemotherapy.

Over four months, patients in the palliative care group had at least monthly palliative care clinic visits, while those in the standard care group didn't receive any formal interventions. Caregivers could attend clinic visits for the palliative care participants, but they weren't required to do so.

Patients were typically in their early to mid 60s. Most were married and had at least some education beyond high school.

Most family caregivers were spouses, but a few were children or other relatives.

Initial perceptions of palliative care were similar in both groups - patients generally thought this was done only for the dying. While patients in both groups thought of palliative care

as providing comfort, they also associated it with giving up on treatment.

Once some patients received palliative care, however, their thinking shifted. Some patients now saw this as a way to live life to the fullest despite the terminal diagnosis, while others

suggested that doctors might have better luck renaming this as something other than "palliative care."

Calling palliative care providers "pain specialists" because they treat discomfort and focus on quality of life would make this sound more appealing and less frightening, some patients

said after getting this type of care.

But in the control group, without any experience with palliative care during the study, patients didn't see the point of renaming it because they thought it would still carry the stigma of giving up and waiting to die.

"Palliative care should not be framed as a last resort option," said Dr. Anthony Caprio, a geriatrician and hospice and palliative medicine physician at Carolinas HealthCare System in

North Carolina.

"These `nothing left to do' conversations often frame palliative care as a way to help people die comfortably, rather than an approach to care that allows them to live with the highest quality of life for as long as possible," said Caprio, who wrote an editorial that was published with the study.

Using different language in discussions with patients can make a big difference, Caprio added.

"I often describe palliative care as an extra layer of support," Caprio said. "Who wouldn't want more support, especially during a difficult illness?"

Total knee arthroplasty (TKA) continues to be a widely utilized treatment option for end-stage knee osteoarthritis, and the number of patients undergoing TKA is projected to continually increase over the next decade.¹ Although TKA is highly successful for many patients, studies continue to report that approximately 20% of patients are dissatisfied after undergoing TKA, and nearly 25% of knee revisions are performed for instability or malalignment.^2,3 Technological advances have been developed to help improve clinical outcomes and implant survivorship. Over the past decade, computer navigation and intraoperative guides have been introduced to help control surgical variables and overcome the limitations and inaccuracies of traditional mechanical instrumentation. Currently, there are a variety of technologies available to assist surgeons with component alignment, including extramedullary devices, computer-assisted navigation systems (CAS), and patient-specific instrumentation (PSI) that help achieve desired alignment goals.^4,5

Computer-assisted navigation tools were introduced in an effort to improve implant alignment and clinical outcomes compared to traditional mechanical guides. Some argue that the use of computer-assisted surgery has a steep learning curve and successful use is dependent on the user’s experience; however, studies have suggested computer-assisted surgery may allow less experienced surgeons to reliably achieve anticipated intraoperative alignment goals with a low complication rate.^6,7 Various studies have looked at computer-assisted TKA at short to mid-term follow-up, but few studies have reported long-term outcomes.^6-9 de Steiger and colleagues¹⁰ recently found that computer-assisted TKA reduced the overall revision rate for aseptic loosening following TKA in patients younger than age 65 years, which suggests benefit of CAS for younger patients. Short-term follow-up has also shown the benefit of CAS TKA in patients with severe extra-articular deformity, where traditional instrumentation cannot be utilized.¹¹ Currently, there is no consensus that computer-assisted TKA leads to improved postoperative patient reported outcomes, because many studies are limited by study design or small cohorts; however, current literature does show an improvement in component alignment as compared to mechanical instrumentation.^9,12,13 As future implant and position targets are defined to improve implant survivorship and clinical outcomes in total joint arthroplasty, computer-assisted devices will be useful to help achieve more precise and accurate component positioning.

In addition to CAS devices, some companies have sought to improve TKA surgery by introducing PSI. PSI was introduced to improve component alignment in TKA, with the purported advantages of a shorter surgical time, decrease in the number of instruments needed, and improved clinical outcomes. PSI accuracy remains variable, which may be attributed to the various systems and implant designs in each study.^14-17 In addition, advanced preoperative imaging is necessary, which further adds to the overall cost.¹⁷ While the recent advancement in technology may provide decreased costs at the time of surgery, the increased cost and time incurred by the patient preoperatively has not resulted in significantly better clinical outcomes.^18,19 Additionally, recent work has not shown PSI to have superior accuracy as compared to currently available CAS devices.¹⁴ These findings suggest that the additional cost and time incurred by patients may limit the widespread use of PSI.

Although computer navigation has been shown to be more accurate than conventional instrumentation and PSI, the lack of improvement in long-term clinical outcome data has limited its use. In a meta-analysis, Bauwens and colleagues²⁰ suggested that while navigated TKAs have improved component alignment outcomes as compared to conventional surgery, the clinical benefit remains unclear. Less than 5% of surgeons are currently using navigation systems due to the perceived learning curve, cost, additional surgical time, and imaging required to utilize these systems. Certain navigation systems can be seemingly cumbersome, with large consoles, increased number of instruments required, and optical instruments with line-of-sight issues. Recent technological advances have worked to decrease this challenge by using accelerometer- and gyroscope-based electronic components, which combine the accuracy of computer-assisted technology with the ease of use of mechanical guides.

Accelerometer and gyroscope technology systems, such as the iAssist system, are portable devices that do not require a large computer console or navigation arrays. This technology relies on accelerator-based navigation without additional preoperative imaging. A recent study demonstrated the iAssist had reproducible accuracy in component alignment that could be easily incorporated into the operating room without optical trackers.²¹ The use of portable computer-assisted devices provides a more compact and easily accessible technology that can be used to achieve accurate component alignment without additional large equipment in the operating room.²² These new handheld intraoperative tools have been introduced to place implants according to a preoperative plan in order to minimize failure due to preoperative extra-articular deformity or intraoperative technical miscues.²³ Nam and colleagues²⁴ used an accelerometer-based surgical navigation system to perform tibial resections in cadaveric models, and found that the accelerometer-based guide was accurate for tibial resection in both the coronal and sagittal planes. In a prospective randomized controlled trial evaluating 100 patients undergoing a TKA using either an accelerometer-based guide or conventional alignment methods, the authors showed that the accelerometer-based guide decreased outliers in tibial component alignment compared to conventional guides.²⁵ In the accelerometer-based guide cohort, 95.7% of tibial components were within 2° of perpendicular to the tibial mechanical axis, compared to 68.1% in the conventional group (P < .001). These results suggested that portable accelerometer-based navigation allows surgeons to achieve satisfactory tibial component alignment with a decrease in the number of potential outliers.^24,25 Similarly, Bugbee and colleagues²⁶ found that accelerometer-based handheld navigation was accurate for tibial coronal and sagittal alignment and no additional surgical time was required compared to conventional techniques.

The relationship between knee alignment and clinical outcomes for TKA remains controversial. Regardless of the surgeon’s alignment preference, it is important to reliably and accurately execute the preoperative plan in a reproducible fashion. Advances in technology that assist with intraoperative component alignment can be useful, and may help decrease the incidence of implant malalignment in clinical practice.

Preoperative Planning and Intraoperative Technique

Preoperative planning is carried out in a manner identical to the use of conventional mechanical guides. Long leg films are taken for evaluation of overall limb alignment, and calibrated lateral images are taken for templating implant sizes. Lines are drawn on the images to determine the difference between the mechanical and anatomic axis of the femur, and a line drawn perpendicular to the mechanical axis is placed to show the expected bone cut. In similar fashion a perpendicular line to the tibial mechanical axis is also drawn to show the expected tibial resection. This preoperative plan allows the surgeon to have an additional intraoperative guide to ensure accuracy of the computer-assisted device.

After standard exposure, the distal femoral or proximal tibial cut can be made based on surgeon preference. The system being demonstrated in the accompanying photos is the KneeAlign 2 system (OrthAlign).

Distal Femoral Cut

The KneeAlign 2 femoral cutting guide is attached to the distal femur with a central pin that is placed in the middle of the distal femur measured from medial to lateral, and 1 cm anterior to the intercondylar notch. It is important to note that this spot is often more medial than traditionally used for insertion of an intramedullary rod. This central point sets the distal point of the femoral mechanical axis. The device is then held in place with 2 oblique pins, and is solidly fixed to the bone. Using a rotating motion, the femur is rotated around the hip joint. The accelerometer and gyroscope in the unit are able to determine the center of the hip joint from this motion, creating the proximal point of the mechanical axis of the femur. Once the mechanical axis of the femur is determined, varus/valgus and flexion/extension can be adjusted on the guide. One adjustment screw is available for varus/valgus, and a second is available for flexion/extension. Numbers on the device screen show real-time alignment, and are easily adjusted to set the desired alignment (Figure 1). Once alignment is obtained, a mechanical stylus is used to determine depth of resection, and the distal femoral cutting block is pinned. After pinning the block, the 3 pins in the device are removed, and the device is removed from the bone. This leaves only the distal femoral cutting block in place. In experienced hands, this part of the procedure takes less than 3 minutes.

Proximal Tibial Cut

The KneeAlign 2 proximal tibial guide is similar in appearance to a standard mechanical tibial cutting guide. It is attached to the proximal tibia with a spring around the calf and 2 pins that hold the device aligned with the medial third of the tibial tubercle. A stylus is then centered on the anterior cruciate ligament (ACL) footprint, which sets the proximal mechanical axis point of the tibia (Figure 2). An offset number is read off the stylus on the ACL footprint, and this number is matched on the ankle offset portion of the guide. The device has 2 sensors. One sensor is on the chassis of the device, and the other is on a mobile arm. Movements between the 2 are monitored by the accelerometers, allowing for accurate maintenance of alignment position even with motion in the leg. A point is taken from the lateral malleolus and then a second point is taken from the medial malleolus. These points are used to determine the center of the ankle joint, which sets the distal mechanical axis point. Once mechanical axis of the tibia is determined, the tibial cutting guide is pinned in place, and can be adjusted with real-time guidance of the varus/valgus and posterior slope values seen on the device (Figure 3). Cut depth is once again determined with a mechanical stylus.

Limitations

Although these devices have proven to be very accurate, surgeons must continue to recognize that all tools can have errors. With computerized guides of any sort, these errors are usually user errors that cannot be detected by the device. Surgeons need to be able to recognize this and always double-check bone cuts for accuracy. Templating the bone cuts prior to surgery is an effective double-check. In addition, many handheld accelerometer devices do not currently assist with the rotational alignment of the femoral component. This is still performed using the surgeon’s preferred technique, and is a limitation of these systems.

Discussion

Currently, TKA provides satisfactory 10-year results with modern implant designs and survival rates as high as 90% to 95%.^27,28 Even with good survival rates, a percentage of patients fail within the first 5 years.³ At a single institution, 50% of revision TKAs were related to instability, malalignment, or failure of fixation that occurred less than 2 years after the index procedure.²⁹ In general, TKA with mechanical instrumentation provides satisfactory pain relief and postoperative knee function; however, studies have consistently shown that the use of advanced technology decreases the risk of implant malalignment, which may decrease early implant failure rates as compared to mechanical and some PSI.^13,14,22 While there is a paucity of literature that has shown better clinical outcomes with the use of advanced technology, there are studies supporting the notion that proper limb alignment and component positioning improves implant survivorship.^23,30

CAS may have additional advantages if the surgeon chooses to place the TKA in an alignment other than a neutral mechanical axis. Kinematic alignment for TKA has gained increasing popularity, where the target of a neutral mechanical axis alignment is not always the goal.^31,32 The reported benefit is a more natural ligament tension with the hope of improving patient satisfaction. One concern with this technique is that it is a departure from the long-held teaching that a TKA aligned to a neutral mechanical axis is necessary for long-term implant survivorship.^33,34 In addition, if the goal of surgery is to cut the tibia and femur at a specific varus/valgus cut, standard instrumentation may not allow for this level of accuracy. This in turn increases the risk of having a tibial or femoral cut that is outside the commonly accepted standards of alignment, which may lead to early implant failure. If further research suggests alignment is a variable that differs from patient to patient, the use of precise tools to ensure accuracy of executing the preoperatively templated alignment becomes even more important.

As the number of TKAs continues to rise each year, even a small percentage of malaligned knees that go on to revision surgery will create a large burden on the healthcare system.^1,3 Although the short-term clinical benefits of CAS have not shown substantial differences as compared to conventional TKA, the number of knees aligned outside of a desired neutral mechanical axis alignment has been shown in multiple studies to be decreased with the use of advanced technology.^7,12,34 Although CAS is an additional cost to a primary TKA, if the orthopedic community can decrease the number of TKA revisions due to malalignment from 6.6% to nearly zero, this may decrease the revision burden and overall cost to the healthcare system.^1,3

TKA technology continues to evolve, and we must continue to assess each new advance not only to understand how it works, but also to ensure it addresses a specific clinical problem, and to be aware of the costs associated before incorporating it into routine practice. Some argue that the use of advanced technology requires increased surgical time, which in turn ultimately increases costs; however, one study has documented no increase in surgical time with handheld navigation while maintaining the accuracy of the device.³⁴ In addition, no significant radiographic or clinical differences have been found between handheld navigation and larger console CAS systems, but large console systems have been associated with increased surgical times.²² The use of handheld accelerometer- and gyroscope-based guides has proven to provide reliable coronal and sagittal implant alignment that can easily be incorporated into the operating room. More widespread use of such technology will help decrease alignment outliers for TKA, and future long-term clinical outcome studies will be necessary to assess functional outcomes.

Conclusion

Advanced computer based technology offers an additional tool to the surgeon for reliably improving component positioning during TKA. The use of handheld accelerometer- and gyroscope-based guides increases the accuracy of component placement while decreasing the incidence of outliers compared to standard mechanical guides, without the need for a large computer console. Long-term radiographic and patient-reported outcomes are necessary to further validate these devices.

Total knee arthroplasty (TKA) continues to be a widely utilized treatment option for end-stage knee osteoarthritis, and the number of patients undergoing TKA is projected to continually increase over the next decade.¹ Although TKA is highly successful for many patients, studies continue to report that approximately 20% of patients are dissatisfied after undergoing TKA, and nearly 25% of knee revisions are performed for instability or malalignment.^2,3 Technological advances have been developed to help improve clinical outcomes and implant survivorship. Over the past decade, computer navigation and intraoperative guides have been introduced to help control surgical variables and overcome the limitations and inaccuracies of traditional mechanical instrumentation. Currently, there are a variety of technologies available to assist surgeons with component alignment, including extramedullary devices, computer-assisted navigation systems (CAS), and patient-specific instrumentation (PSI) that help achieve desired alignment goals.^4,5

Computer-assisted navigation tools were introduced in an effort to improve implant alignment and clinical outcomes compared to traditional mechanical guides. Some argue that the use of computer-assisted surgery has a steep learning curve and successful use is dependent on the user’s experience; however, studies have suggested computer-assisted surgery may allow less experienced surgeons to reliably achieve anticipated intraoperative alignment goals with a low complication rate.^6,7 Various studies have looked at computer-assisted TKA at short to mid-term follow-up, but few studies have reported long-term outcomes.^6-9 de Steiger and colleagues¹⁰ recently found that computer-assisted TKA reduced the overall revision rate for aseptic loosening following TKA in patients younger than age 65 years, which suggests benefit of CAS for younger patients. Short-term follow-up has also shown the benefit of CAS TKA in patients with severe extra-articular deformity, where traditional instrumentation cannot be utilized.¹¹ Currently, there is no consensus that computer-assisted TKA leads to improved postoperative patient reported outcomes, because many studies are limited by study design or small cohorts; however, current literature does show an improvement in component alignment as compared to mechanical instrumentation.^9,12,13 As future implant and position targets are defined to improve implant survivorship and clinical outcomes in total joint arthroplasty, computer-assisted devices will be useful to help achieve more precise and accurate component positioning.

In addition to CAS devices, some companies have sought to improve TKA surgery by introducing PSI. PSI was introduced to improve component alignment in TKA, with the purported advantages of a shorter surgical time, decrease in the number of instruments needed, and improved clinical outcomes. PSI accuracy remains variable, which may be attributed to the various systems and implant designs in each study.^14-17 In addition, advanced preoperative imaging is necessary, which further adds to the overall cost.¹⁷ While the recent advancement in technology may provide decreased costs at the time of surgery, the increased cost and time incurred by the patient preoperatively has not resulted in significantly better clinical outcomes.^18,19 Additionally, recent work has not shown PSI to have superior accuracy as compared to currently available CAS devices.¹⁴ These findings suggest that the additional cost and time incurred by patients may limit the widespread use of PSI.

Although computer navigation has been shown to be more accurate than conventional instrumentation and PSI, the lack of improvement in long-term clinical outcome data has limited its use. In a meta-analysis, Bauwens and colleagues²⁰ suggested that while navigated TKAs have improved component alignment outcomes as compared to conventional surgery, the clinical benefit remains unclear. Less than 5% of surgeons are currently using navigation systems due to the perceived learning curve, cost, additional surgical time, and imaging required to utilize these systems. Certain navigation systems can be seemingly cumbersome, with large consoles, increased number of instruments required, and optical instruments with line-of-sight issues. Recent technological advances have worked to decrease this challenge by using accelerometer- and gyroscope-based electronic components, which combine the accuracy of computer-assisted technology with the ease of use of mechanical guides.

Accelerometer and gyroscope technology systems, such as the iAssist system, are portable devices that do not require a large computer console or navigation arrays. This technology relies on accelerator-based navigation without additional preoperative imaging. A recent study demonstrated the iAssist had reproducible accuracy in component alignment that could be easily incorporated into the operating room without optical trackers.²¹ The use of portable computer-assisted devices provides a more compact and easily accessible technology that can be used to achieve accurate component alignment without additional large equipment in the operating room.²² These new handheld intraoperative tools have been introduced to place implants according to a preoperative plan in order to minimize failure due to preoperative extra-articular deformity or intraoperative technical miscues.²³ Nam and colleagues²⁴ used an accelerometer-based surgical navigation system to perform tibial resections in cadaveric models, and found that the accelerometer-based guide was accurate for tibial resection in both the coronal and sagittal planes. In a prospective randomized controlled trial evaluating 100 patients undergoing a TKA using either an accelerometer-based guide or conventional alignment methods, the authors showed that the accelerometer-based guide decreased outliers in tibial component alignment compared to conventional guides.²⁵ In the accelerometer-based guide cohort, 95.7% of tibial components were within 2° of perpendicular to the tibial mechanical axis, compared to 68.1% in the conventional group (P < .001). These results suggested that portable accelerometer-based navigation allows surgeons to achieve satisfactory tibial component alignment with a decrease in the number of potential outliers.^24,25 Similarly, Bugbee and colleagues²⁶ found that accelerometer-based handheld navigation was accurate for tibial coronal and sagittal alignment and no additional surgical time was required compared to conventional techniques.

The relationship between knee alignment and clinical outcomes for TKA remains controversial. Regardless of the surgeon’s alignment preference, it is important to reliably and accurately execute the preoperative plan in a reproducible fashion. Advances in technology that assist with intraoperative component alignment can be useful, and may help decrease the incidence of implant malalignment in clinical practice.

Preoperative Planning and Intraoperative Technique

Preoperative planning is carried out in a manner identical to the use of conventional mechanical guides. Long leg films are taken for evaluation of overall limb alignment, and calibrated lateral images are taken for templating implant sizes. Lines are drawn on the images to determine the difference between the mechanical and anatomic axis of the femur, and a line drawn perpendicular to the mechanical axis is placed to show the expected bone cut. In similar fashion a perpendicular line to the tibial mechanical axis is also drawn to show the expected tibial resection. This preoperative plan allows the surgeon to have an additional intraoperative guide to ensure accuracy of the computer-assisted device.

After standard exposure, the distal femoral or proximal tibial cut can be made based on surgeon preference. The system being demonstrated in the accompanying photos is the KneeAlign 2 system (OrthAlign).

Distal Femoral Cut

The KneeAlign 2 femoral cutting guide is attached to the distal femur with a central pin that is placed in the middle of the distal femur measured from medial to lateral, and 1 cm anterior to the intercondylar notch. It is important to note that this spot is often more medial than traditionally used for insertion of an intramedullary rod. This central point sets the distal point of the femoral mechanical axis. The device is then held in place with 2 oblique pins, and is solidly fixed to the bone. Using a rotating motion, the femur is rotated around the hip joint. The accelerometer and gyroscope in the unit are able to determine the center of the hip joint from this motion, creating the proximal point of the mechanical axis of the femur. Once the mechanical axis of the femur is determined, varus/valgus and flexion/extension can be adjusted on the guide. One adjustment screw is available for varus/valgus, and a second is available for flexion/extension. Numbers on the device screen show real-time alignment, and are easily adjusted to set the desired alignment (Figure 1). Once alignment is obtained, a mechanical stylus is used to determine depth of resection, and the distal femoral cutting block is pinned. After pinning the block, the 3 pins in the device are removed, and the device is removed from the bone. This leaves only the distal femoral cutting block in place. In experienced hands, this part of the procedure takes less than 3 minutes.

Proximal Tibial Cut

The KneeAlign 2 proximal tibial guide is similar in appearance to a standard mechanical tibial cutting guide. It is attached to the proximal tibia with a spring around the calf and 2 pins that hold the device aligned with the medial third of the tibial tubercle. A stylus is then centered on the anterior cruciate ligament (ACL) footprint, which sets the proximal mechanical axis point of the tibia (Figure 2). An offset number is read off the stylus on the ACL footprint, and this number is matched on the ankle offset portion of the guide. The device has 2 sensors. One sensor is on the chassis of the device, and the other is on a mobile arm. Movements between the 2 are monitored by the accelerometers, allowing for accurate maintenance of alignment position even with motion in the leg. A point is taken from the lateral malleolus and then a second point is taken from the medial malleolus. These points are used to determine the center of the ankle joint, which sets the distal mechanical axis point. Once mechanical axis of the tibia is determined, the tibial cutting guide is pinned in place, and can be adjusted with real-time guidance of the varus/valgus and posterior slope values seen on the device (Figure 3). Cut depth is once again determined with a mechanical stylus.

Limitations

Although these devices have proven to be very accurate, surgeons must continue to recognize that all tools can have errors. With computerized guides of any sort, these errors are usually user errors that cannot be detected by the device. Surgeons need to be able to recognize this and always double-check bone cuts for accuracy. Templating the bone cuts prior to surgery is an effective double-check. In addition, many handheld accelerometer devices do not currently assist with the rotational alignment of the femoral component. This is still performed using the surgeon’s preferred technique, and is a limitation of these systems.

Discussion

Currently, TKA provides satisfactory 10-year results with modern implant designs and survival rates as high as 90% to 95%.^27,28 Even with good survival rates, a percentage of patients fail within the first 5 years.³ At a single institution, 50% of revision TKAs were related to instability, malalignment, or failure of fixation that occurred less than 2 years after the index procedure.²⁹ In general, TKA with mechanical instrumentation provides satisfactory pain relief and postoperative knee function; however, studies have consistently shown that the use of advanced technology decreases the risk of implant malalignment, which may decrease early implant failure rates as compared to mechanical and some PSI.^13,14,22 While there is a paucity of literature that has shown better clinical outcomes with the use of advanced technology, there are studies supporting the notion that proper limb alignment and component positioning improves implant survivorship.^23,30

CAS may have additional advantages if the surgeon chooses to place the TKA in an alignment other than a neutral mechanical axis. Kinematic alignment for TKA has gained increasing popularity, where the target of a neutral mechanical axis alignment is not always the goal.^31,32 The reported benefit is a more natural ligament tension with the hope of improving patient satisfaction. One concern with this technique is that it is a departure from the long-held teaching that a TKA aligned to a neutral mechanical axis is necessary for long-term implant survivorship.^33,34 In addition, if the goal of surgery is to cut the tibia and femur at a specific varus/valgus cut, standard instrumentation may not allow for this level of accuracy. This in turn increases the risk of having a tibial or femoral cut that is outside the commonly accepted standards of alignment, which may lead to early implant failure. If further research suggests alignment is a variable that differs from patient to patient, the use of precise tools to ensure accuracy of executing the preoperatively templated alignment becomes even more important.

As the number of TKAs continues to rise each year, even a small percentage of malaligned knees that go on to revision surgery will create a large burden on the healthcare system.^1,3 Although the short-term clinical benefits of CAS have not shown substantial differences as compared to conventional TKA, the number of knees aligned outside of a desired neutral mechanical axis alignment has been shown in multiple studies to be decreased with the use of advanced technology.^7,12,34 Although CAS is an additional cost to a primary TKA, if the orthopedic community can decrease the number of TKA revisions due to malalignment from 6.6% to nearly zero, this may decrease the revision burden and overall cost to the healthcare system.^1,3

TKA technology continues to evolve, and we must continue to assess each new advance not only to understand how it works, but also to ensure it addresses a specific clinical problem, and to be aware of the costs associated before incorporating it into routine practice. Some argue that the use of advanced technology requires increased surgical time, which in turn ultimately increases costs; however, one study has documented no increase in surgical time with handheld navigation while maintaining the accuracy of the device.³⁴ In addition, no significant radiographic or clinical differences have been found between handheld navigation and larger console CAS systems, but large console systems have been associated with increased surgical times.²² The use of handheld accelerometer- and gyroscope-based guides has proven to provide reliable coronal and sagittal implant alignment that can easily be incorporated into the operating room. More widespread use of such technology will help decrease alignment outliers for TKA, and future long-term clinical outcome studies will be necessary to assess functional outcomes.

Conclusion

Advanced computer based technology offers an additional tool to the surgeon for reliably improving component positioning during TKA. The use of handheld accelerometer- and gyroscope-based guides increases the accuracy of component placement while decreasing the incidence of outliers compared to standard mechanical guides, without the need for a large computer console. Long-term radiographic and patient-reported outcomes are necessary to further validate these devices.

Total knee arthroplasty (TKA) continues to be a widely utilized treatment option for end-stage knee osteoarthritis, and the number of patients undergoing TKA is projected to continually increase over the next decade.¹ Although TKA is highly successful for many patients, studies continue to report that approximately 20% of patients are dissatisfied after undergoing TKA, and nearly 25% of knee revisions are performed for instability or malalignment.^2,3 Technological advances have been developed to help improve clinical outcomes and implant survivorship. Over the past decade, computer navigation and intraoperative guides have been introduced to help control surgical variables and overcome the limitations and inaccuracies of traditional mechanical instrumentation. Currently, there are a variety of technologies available to assist surgeons with component alignment, including extramedullary devices, computer-assisted navigation systems (CAS), and patient-specific instrumentation (PSI) that help achieve desired alignment goals.^4,5

Computer-assisted navigation tools were introduced in an effort to improve implant alignment and clinical outcomes compared to traditional mechanical guides. Some argue that the use of computer-assisted surgery has a steep learning curve and successful use is dependent on the user’s experience; however, studies have suggested computer-assisted surgery may allow less experienced surgeons to reliably achieve anticipated intraoperative alignment goals with a low complication rate.^6,7 Various studies have looked at computer-assisted TKA at short to mid-term follow-up, but few studies have reported long-term outcomes.^6-9 de Steiger and colleagues¹⁰ recently found that computer-assisted TKA reduced the overall revision rate for aseptic loosening following TKA in patients younger than age 65 years, which suggests benefit of CAS for younger patients. Short-term follow-up has also shown the benefit of CAS TKA in patients with severe extra-articular deformity, where traditional instrumentation cannot be utilized.¹¹ Currently, there is no consensus that computer-assisted TKA leads to improved postoperative patient reported outcomes, because many studies are limited by study design or small cohorts; however, current literature does show an improvement in component alignment as compared to mechanical instrumentation.^9,12,13 As future implant and position targets are defined to improve implant survivorship and clinical outcomes in total joint arthroplasty, computer-assisted devices will be useful to help achieve more precise and accurate component positioning.

In addition to CAS devices, some companies have sought to improve TKA surgery by introducing PSI. PSI was introduced to improve component alignment in TKA, with the purported advantages of a shorter surgical time, decrease in the number of instruments needed, and improved clinical outcomes. PSI accuracy remains variable, which may be attributed to the various systems and implant designs in each study.^14-17 In addition, advanced preoperative imaging is necessary, which further adds to the overall cost.¹⁷ While the recent advancement in technology may provide decreased costs at the time of surgery, the increased cost and time incurred by the patient preoperatively has not resulted in significantly better clinical outcomes.^18,19 Additionally, recent work has not shown PSI to have superior accuracy as compared to currently available CAS devices.¹⁴ These findings suggest that the additional cost and time incurred by patients may limit the widespread use of PSI.

Although computer navigation has been shown to be more accurate than conventional instrumentation and PSI, the lack of improvement in long-term clinical outcome data has limited its use. In a meta-analysis, Bauwens and colleagues²⁰ suggested that while navigated TKAs have improved component alignment outcomes as compared to conventional surgery, the clinical benefit remains unclear. Less than 5% of surgeons are currently using navigation systems due to the perceived learning curve, cost, additional surgical time, and imaging required to utilize these systems. Certain navigation systems can be seemingly cumbersome, with large consoles, increased number of instruments required, and optical instruments with line-of-sight issues. Recent technological advances have worked to decrease this challenge by using accelerometer- and gyroscope-based electronic components, which combine the accuracy of computer-assisted technology with the ease of use of mechanical guides.

Accelerometer and gyroscope technology systems, such as the iAssist system, are portable devices that do not require a large computer console or navigation arrays. This technology relies on accelerator-based navigation without additional preoperative imaging. A recent study demonstrated the iAssist had reproducible accuracy in component alignment that could be easily incorporated into the operating room without optical trackers.²¹ The use of portable computer-assisted devices provides a more compact and easily accessible technology that can be used to achieve accurate component alignment without additional large equipment in the operating room.²² These new handheld intraoperative tools have been introduced to place implants according to a preoperative plan in order to minimize failure due to preoperative extra-articular deformity or intraoperative technical miscues.²³ Nam and colleagues²⁴ used an accelerometer-based surgical navigation system to perform tibial resections in cadaveric models, and found that the accelerometer-based guide was accurate for tibial resection in both the coronal and sagittal planes. In a prospective randomized controlled trial evaluating 100 patients undergoing a TKA using either an accelerometer-based guide or conventional alignment methods, the authors showed that the accelerometer-based guide decreased outliers in tibial component alignment compared to conventional guides.²⁵ In the accelerometer-based guide cohort, 95.7% of tibial components were within 2° of perpendicular to the tibial mechanical axis, compared to 68.1% in the conventional group (P < .001). These results suggested that portable accelerometer-based navigation allows surgeons to achieve satisfactory tibial component alignment with a decrease in the number of potential outliers.^24,25 Similarly, Bugbee and colleagues²⁶ found that accelerometer-based handheld navigation was accurate for tibial coronal and sagittal alignment and no additional surgical time was required compared to conventional techniques.

The relationship between knee alignment and clinical outcomes for TKA remains controversial. Regardless of the surgeon’s alignment preference, it is important to reliably and accurately execute the preoperative plan in a reproducible fashion. Advances in technology that assist with intraoperative component alignment can be useful, and may help decrease the incidence of implant malalignment in clinical practice.

Preoperative Planning and Intraoperative Technique

Preoperative planning is carried out in a manner identical to the use of conventional mechanical guides. Long leg films are taken for evaluation of overall limb alignment, and calibrated lateral images are taken for templating implant sizes. Lines are drawn on the images to determine the difference between the mechanical and anatomic axis of the femur, and a line drawn perpendicular to the mechanical axis is placed to show the expected bone cut. In similar fashion a perpendicular line to the tibial mechanical axis is also drawn to show the expected tibial resection. This preoperative plan allows the surgeon to have an additional intraoperative guide to ensure accuracy of the computer-assisted device.

After standard exposure, the distal femoral or proximal tibial cut can be made based on surgeon preference. The system being demonstrated in the accompanying photos is the KneeAlign 2 system (OrthAlign).

Distal Femoral Cut

The KneeAlign 2 femoral cutting guide is attached to the distal femur with a central pin that is placed in the middle of the distal femur measured from medial to lateral, and 1 cm anterior to the intercondylar notch. It is important to note that this spot is often more medial than traditionally used for insertion of an intramedullary rod. This central point sets the distal point of the femoral mechanical axis. The device is then held in place with 2 oblique pins, and is solidly fixed to the bone. Using a rotating motion, the femur is rotated around the hip joint. The accelerometer and gyroscope in the unit are able to determine the center of the hip joint from this motion, creating the proximal point of the mechanical axis of the femur. Once the mechanical axis of the femur is determined, varus/valgus and flexion/extension can be adjusted on the guide. One adjustment screw is available for varus/valgus, and a second is available for flexion/extension. Numbers on the device screen show real-time alignment, and are easily adjusted to set the desired alignment (Figure 1). Once alignment is obtained, a mechanical stylus is used to determine depth of resection, and the distal femoral cutting block is pinned. After pinning the block, the 3 pins in the device are removed, and the device is removed from the bone. This leaves only the distal femoral cutting block in place. In experienced hands, this part of the procedure takes less than 3 minutes.

Proximal Tibial Cut

The KneeAlign 2 proximal tibial guide is similar in appearance to a standard mechanical tibial cutting guide. It is attached to the proximal tibia with a spring around the calf and 2 pins that hold the device aligned with the medial third of the tibial tubercle. A stylus is then centered on the anterior cruciate ligament (ACL) footprint, which sets the proximal mechanical axis point of the tibia (Figure 2). An offset number is read off the stylus on the ACL footprint, and this number is matched on the ankle offset portion of the guide. The device has 2 sensors. One sensor is on the chassis of the device, and the other is on a mobile arm. Movements between the 2 are monitored by the accelerometers, allowing for accurate maintenance of alignment position even with motion in the leg. A point is taken from the lateral malleolus and then a second point is taken from the medial malleolus. These points are used to determine the center of the ankle joint, which sets the distal mechanical axis point. Once mechanical axis of the tibia is determined, the tibial cutting guide is pinned in place, and can be adjusted with real-time guidance of the varus/valgus and posterior slope values seen on the device (Figure 3). Cut depth is once again determined with a mechanical stylus.

Limitations

Although these devices have proven to be very accurate, surgeons must continue to recognize that all tools can have errors. With computerized guides of any sort, these errors are usually user errors that cannot be detected by the device. Surgeons need to be able to recognize this and always double-check bone cuts for accuracy. Templating the bone cuts prior to surgery is an effective double-check. In addition, many handheld accelerometer devices do not currently assist with the rotational alignment of the femoral component. This is still performed using the surgeon’s preferred technique, and is a limitation of these systems.

Discussion

Currently, TKA provides satisfactory 10-year results with modern implant designs and survival rates as high as 90% to 95%.^27,28 Even with good survival rates, a percentage of patients fail within the first 5 years.³ At a single institution, 50% of revision TKAs were related to instability, malalignment, or failure of fixation that occurred less than 2 years after the index procedure.²⁹ In general, TKA with mechanical instrumentation provides satisfactory pain relief and postoperative knee function; however, studies have consistently shown that the use of advanced technology decreases the risk of implant malalignment, which may decrease early implant failure rates as compared to mechanical and some PSI.^13,14,22 While there is a paucity of literature that has shown better clinical outcomes with the use of advanced technology, there are studies supporting the notion that proper limb alignment and component positioning improves implant survivorship.^23,30

CAS may have additional advantages if the surgeon chooses to place the TKA in an alignment other than a neutral mechanical axis. Kinematic alignment for TKA has gained increasing popularity, where the target of a neutral mechanical axis alignment is not always the goal.^31,32 The reported benefit is a more natural ligament tension with the hope of improving patient satisfaction. One concern with this technique is that it is a departure from the long-held teaching that a TKA aligned to a neutral mechanical axis is necessary for long-term implant survivorship.^33,34 In addition, if the goal of surgery is to cut the tibia and femur at a specific varus/valgus cut, standard instrumentation may not allow for this level of accuracy. This in turn increases the risk of having a tibial or femoral cut that is outside the commonly accepted standards of alignment, which may lead to early implant failure. If further research suggests alignment is a variable that differs from patient to patient, the use of precise tools to ensure accuracy of executing the preoperatively templated alignment becomes even more important.

As the number of TKAs continues to rise each year, even a small percentage of malaligned knees that go on to revision surgery will create a large burden on the healthcare system.^1,3 Although the short-term clinical benefits of CAS have not shown substantial differences as compared to conventional TKA, the number of knees aligned outside of a desired neutral mechanical axis alignment has been shown in multiple studies to be decreased with the use of advanced technology.^7,12,34 Although CAS is an additional cost to a primary TKA, if the orthopedic community can decrease the number of TKA revisions due to malalignment from 6.6% to nearly zero, this may decrease the revision burden and overall cost to the healthcare system.^1,3

TKA technology continues to evolve, and we must continue to assess each new advance not only to understand how it works, but also to ensure it addresses a specific clinical problem, and to be aware of the costs associated before incorporating it into routine practice. Some argue that the use of advanced technology requires increased surgical time, which in turn ultimately increases costs; however, one study has documented no increase in surgical time with handheld navigation while maintaining the accuracy of the device.³⁴ In addition, no significant radiographic or clinical differences have been found between handheld navigation and larger console CAS systems, but large console systems have been associated with increased surgical times.²² The use of handheld accelerometer- and gyroscope-based guides has proven to provide reliable coronal and sagittal implant alignment that can easily be incorporated into the operating room. More widespread use of such technology will help decrease alignment outliers for TKA, and future long-term clinical outcome studies will be necessary to assess functional outcomes.

Conclusion

Advanced computer based technology offers an additional tool to the surgeon for reliably improving component positioning during TKA. The use of handheld accelerometer- and gyroscope-based guides increases the accuracy of component placement while decreasing the incidence of outliers compared to standard mechanical guides, without the need for a large computer console. Long-term radiographic and patient-reported outcomes are necessary to further validate these devices.

A mentor told me during my pediatrics residency that going to school is “the main job of a teenager.” This is because at school, teenagers will be spending the majority of their time and energy learning and growing to become a thriving adult. However, the school environment matters. We are familiar with how excellent teachers, the availability of tutoring, and an administration dedicated to academic achievement play a big role. We also should be aware that if teenagers feel unsafe going to school – especially if they are victims of bullying – they are unable to take advantage of these resources.

Bullying is a repetitive, unwanted, and aggressive behavior among children and adolescents that involves a real or perceived power imbalance.¹ Despite the increasing visibility of lesbian, gay, bisexual, and transgender (LGBT) individuals, bullying remains a serious problem for this population. Although between one in four and one in three of all youth experience bullying,² according to the Youth Risk Behavior Survey, LGBT students are two to four times as likely to be threatened or injured with a weapon on school property, two to three times as likely not to go to school because they feel unsafe, and about two times as likely to be bullied at school, compared with their heterosexual peers.³ Alarmingly, more than half of transgender students experience bullying and harassment at school.⁴

A key component of bullying is the power imbalance. Bullying perpetrators feel that they have more power physically (e.g., in size) or socially (e.g., in social status).⁵ LGBT youth are often the victims of bullying because of the societal stigma against same-sex attraction or gender nonconformity. As a result, they tend to have a lower social status, putting them at risk for bullying. Remember, however, that this power imbalance is perceived. Even straight teenagers can be victims of antigay and antitrans bullying because they don’t conform to gender norms (e.g., a straight boy interested in theater instead of sports).⁶ Therefore, any teenager can be a victim of antigay and antitrans bullying.

Although many believe that experiencing bullying is a “rite of passage,” a look at the research on bullying contradicts this. Youth who experience bullying have higher rates of depression, loneliness, and, most worrisome of all, suicide.^7,8 One study showed that LGBT youth who experience bullying are almost six times as likely to consider suicide.⁹ Such sobering statistics prove that bullying is harmful. Furthermore, the effects of bullying can last into adulthood. One study showed that LGBT youth who experienced bullying during high school are more likely to have depressive symptoms and to be dissatisfied with life as a young adult.¹⁰ If rites of passage are designed to make a teenager into a well-adjusted young adult, then bullying does a poor job.

Although antigay bullying and harassment occur outside the clinic, providers can encounter both the perpetrator and the victim as patients and not realize it. Providers who have patients at risk for bullying – such as LGBT or gender-nonconforming youth – should routinely ask them about bullying through such questions as:

• “How many good friends do you have in school?”

• “Do you ever feel afraid to go to school? Why?”

• “Do other kids ever bully you at school, in your neighborhood, or online? Who bullies you?

• When and where does it happen? What do they say or do?”¹¹

Asking these questions is especially important if you or your patient’s caregivers notice school phobia, attention problems, or psychosomatic complaints.11 Once you identify a victim, refer the patient to a mental health provider to develop skills to cope with the stress of bullying. Such skills include how to make friends. Emphasize that it is not the victim’s fault that they are experiencing bullying. Avoid telling victims to fight back or “suck it up.” In addition, work with parents and school authorities to intervene on behalf of the child to stop the bullying behavior.

Lisa Quarfoth/Thinkstock

At the same time, it is especially important to identify perpetrators. Perpetrators tend to have conduct problems, increased depressive symptoms, and poor school adjustment.¹² They may have been bullied themselves. Also refer perpetrators to a mental health provider and other resources to address these problems.

However, with your limited time to screen for bullying or to create an individualized plan to protect bullying victims, approaches to reducing bullying and their adverse effects require a community effort. Use your expertise and access to the latest scientific research to advocate and help create policies schools can use to address antigay bullying. Clark and Tilly recommend a three-tier approach in addressing antigay bullying. In the first tier, schools should create a safe and affirmative environment for all students. An example of such an approach is to have a speaker – such as a physician from the community – talking to students about bullying and encouraging bystanders to speak up (i.e., be an ally) for bullying victims. Although some schools may be hesitant to implement a schoolwide intervention, they may implement a second-tier approach, such as classroom curricula on how to be an ally or incentive programs for helping vulnerable students (e.g., tutoring). Finally, the third tier requires intensive individualized interventions for bullying victims. Schools should have a step-by-step plan involving school authorities that students and their parents can use if students are experiencing bullying.¹³ Implementation of this plan requires timely follow-up from school officials to ensure cessation of the bullying behavior.10

Another way you can advocate for your LGBT patients is to be knowledgeable about the laws surrounding bullying. Bullying laws vary according to state. This is especially true if such laws specifically prohibit bullying based on sexual orientation or gender identity. This is known as “enumeration.” Enumerated laws grant school authorities the power to prevent and to correct any bullying based on sexual orientation and gender identity. Currently, 18 states and the District of Columbia have enumerated antibullying laws.¹⁴ If you live in a state that does not have an enumerated antibullying law, you can contact your state government officials to urge them to pass such a law.

Bullying has a powerful impact on the health and well-being of LGBT youth. Screen for bullying in your LGBT patients and work with schools and parents to protect them from such behaviors. Most importantly, advocate for creating a safe school environment for LGBT youth so that they can focus on their main job of learning and becoming a thriving adult.

Resources

• The website www.stopbullying.gov is a comprehensive resource for bullying and how to address it.

• Society of Adolescent Health & Medicine (SAHM) position statement on bullying (J Adolesc Health. 2005 Jan;36[1]:88-91).

• American Academy of Pediatrics (AAP) position statement on bullying (Pediatrics. 2009 July. doi: 10.1542/peds.2009-0943).

• Gay, Lesbian & Straight Education Network (GLSEN) information on enumerated antibullying laws by state (www.glsen.org/article/state-maps).

References

1. Bullying definition at www.stopbullying.gov.

2. Student Reports of Bullying and Cyber-Bullying: Results From the 2011 School Crime Supplement to the National Crime Victimization Survey.

3. J Adolesc Health. 2014 Sep;55(3):432-8.

4. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. Washington: National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011.

5. Can Fam Physician. 2009 Apr;55(4):356-60.

6. J Adolesc Health. 2016 Feb;58(2):S1-S2.

7. Pediatrics. 2003;111(6 Pt 1):1312-7.

8. Journal of Educational Psychology. 2000 Jun;92(2):349-59.

9. Prev Sci. 2015 Apr;16(3):451-62.

10. Dev Psychol. 2010 Nov;46(6):1580-9.

11. Roles for pediatricians in bullying prevention and intervention (www.stopbullying.gov/resources-files/roles-for-pediatricians-tipsheet.pdf).

12. J Adolesc Health. 2005 Jan;36(1):88-91.

13. Clark JP, Tilly, WD. The evolution of response to intervention. In: Clark JP, Alvarez, Michelle, ed. Response to intervention: A guide for school social worker. (New York: Oxford University Press; 2010:3-18).

14. Enumerated antibullying laws by state(www.glsen.org/article/state-maps).

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh.

A mentor told me during my pediatrics residency that going to school is “the main job of a teenager.” This is because at school, teenagers will be spending the majority of their time and energy learning and growing to become a thriving adult. However, the school environment matters. We are familiar with how excellent teachers, the availability of tutoring, and an administration dedicated to academic achievement play a big role. We also should be aware that if teenagers feel unsafe going to school – especially if they are victims of bullying – they are unable to take advantage of these resources.

Bullying is a repetitive, unwanted, and aggressive behavior among children and adolescents that involves a real or perceived power imbalance.¹ Despite the increasing visibility of lesbian, gay, bisexual, and transgender (LGBT) individuals, bullying remains a serious problem for this population. Although between one in four and one in three of all youth experience bullying,² according to the Youth Risk Behavior Survey, LGBT students are two to four times as likely to be threatened or injured with a weapon on school property, two to three times as likely not to go to school because they feel unsafe, and about two times as likely to be bullied at school, compared with their heterosexual peers.³ Alarmingly, more than half of transgender students experience bullying and harassment at school.⁴

A key component of bullying is the power imbalance. Bullying perpetrators feel that they have more power physically (e.g., in size) or socially (e.g., in social status).⁵ LGBT youth are often the victims of bullying because of the societal stigma against same-sex attraction or gender nonconformity. As a result, they tend to have a lower social status, putting them at risk for bullying. Remember, however, that this power imbalance is perceived. Even straight teenagers can be victims of antigay and antitrans bullying because they don’t conform to gender norms (e.g., a straight boy interested in theater instead of sports).⁶ Therefore, any teenager can be a victim of antigay and antitrans bullying.

Although many believe that experiencing bullying is a “rite of passage,” a look at the research on bullying contradicts this. Youth who experience bullying have higher rates of depression, loneliness, and, most worrisome of all, suicide.^7,8 One study showed that LGBT youth who experience bullying are almost six times as likely to consider suicide.⁹ Such sobering statistics prove that bullying is harmful. Furthermore, the effects of bullying can last into adulthood. One study showed that LGBT youth who experienced bullying during high school are more likely to have depressive symptoms and to be dissatisfied with life as a young adult.¹⁰ If rites of passage are designed to make a teenager into a well-adjusted young adult, then bullying does a poor job.

Although antigay bullying and harassment occur outside the clinic, providers can encounter both the perpetrator and the victim as patients and not realize it. Providers who have patients at risk for bullying – such as LGBT or gender-nonconforming youth – should routinely ask them about bullying through such questions as:

• “How many good friends do you have in school?”

• “Do you ever feel afraid to go to school? Why?”

• “Do other kids ever bully you at school, in your neighborhood, or online? Who bullies you?

• When and where does it happen? What do they say or do?”¹¹

Asking these questions is especially important if you or your patient’s caregivers notice school phobia, attention problems, or psychosomatic complaints.11 Once you identify a victim, refer the patient to a mental health provider to develop skills to cope with the stress of bullying. Such skills include how to make friends. Emphasize that it is not the victim’s fault that they are experiencing bullying. Avoid telling victims to fight back or “suck it up.” In addition, work with parents and school authorities to intervene on behalf of the child to stop the bullying behavior.

Lisa Quarfoth/Thinkstock

At the same time, it is especially important to identify perpetrators. Perpetrators tend to have conduct problems, increased depressive symptoms, and poor school adjustment.¹² They may have been bullied themselves. Also refer perpetrators to a mental health provider and other resources to address these problems.

However, with your limited time to screen for bullying or to create an individualized plan to protect bullying victims, approaches to reducing bullying and their adverse effects require a community effort. Use your expertise and access to the latest scientific research to advocate and help create policies schools can use to address antigay bullying. Clark and Tilly recommend a three-tier approach in addressing antigay bullying. In the first tier, schools should create a safe and affirmative environment for all students. An example of such an approach is to have a speaker – such as a physician from the community – talking to students about bullying and encouraging bystanders to speak up (i.e., be an ally) for bullying victims. Although some schools may be hesitant to implement a schoolwide intervention, they may implement a second-tier approach, such as classroom curricula on how to be an ally or incentive programs for helping vulnerable students (e.g., tutoring). Finally, the third tier requires intensive individualized interventions for bullying victims. Schools should have a step-by-step plan involving school authorities that students and their parents can use if students are experiencing bullying.¹³ Implementation of this plan requires timely follow-up from school officials to ensure cessation of the bullying behavior.10

Another way you can advocate for your LGBT patients is to be knowledgeable about the laws surrounding bullying. Bullying laws vary according to state. This is especially true if such laws specifically prohibit bullying based on sexual orientation or gender identity. This is known as “enumeration.” Enumerated laws grant school authorities the power to prevent and to correct any bullying based on sexual orientation and gender identity. Currently, 18 states and the District of Columbia have enumerated antibullying laws.¹⁴ If you live in a state that does not have an enumerated antibullying law, you can contact your state government officials to urge them to pass such a law.

Bullying has a powerful impact on the health and well-being of LGBT youth. Screen for bullying in your LGBT patients and work with schools and parents to protect them from such behaviors. Most importantly, advocate for creating a safe school environment for LGBT youth so that they can focus on their main job of learning and becoming a thriving adult.

Resources

• The website www.stopbullying.gov is a comprehensive resource for bullying and how to address it.

• Society of Adolescent Health & Medicine (SAHM) position statement on bullying (J Adolesc Health. 2005 Jan;36[1]:88-91).

• American Academy of Pediatrics (AAP) position statement on bullying (Pediatrics. 2009 July. doi: 10.1542/peds.2009-0943).

• Gay, Lesbian & Straight Education Network (GLSEN) information on enumerated antibullying laws by state (www.glsen.org/article/state-maps).

References

1. Bullying definition at www.stopbullying.gov.

2. Student Reports of Bullying and Cyber-Bullying: Results From the 2011 School Crime Supplement to the National Crime Victimization Survey.

3. J Adolesc Health. 2014 Sep;55(3):432-8.

4. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. Washington: National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011.

5. Can Fam Physician. 2009 Apr;55(4):356-60.

6. J Adolesc Health. 2016 Feb;58(2):S1-S2.

7. Pediatrics. 2003;111(6 Pt 1):1312-7.

8. Journal of Educational Psychology. 2000 Jun;92(2):349-59.

9. Prev Sci. 2015 Apr;16(3):451-62.

10. Dev Psychol. 2010 Nov;46(6):1580-9.

11. Roles for pediatricians in bullying prevention and intervention (www.stopbullying.gov/resources-files/roles-for-pediatricians-tipsheet.pdf).

12. J Adolesc Health. 2005 Jan;36(1):88-91.

13. Clark JP, Tilly, WD. The evolution of response to intervention. In: Clark JP, Alvarez, Michelle, ed. Response to intervention: A guide for school social worker. (New York: Oxford University Press; 2010:3-18).

14. Enumerated antibullying laws by state(www.glsen.org/article/state-maps).

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh.

A mentor told me during my pediatrics residency that going to school is “the main job of a teenager.” This is because at school, teenagers will be spending the majority of their time and energy learning and growing to become a thriving adult. However, the school environment matters. We are familiar with how excellent teachers, the availability of tutoring, and an administration dedicated to academic achievement play a big role. We also should be aware that if teenagers feel unsafe going to school – especially if they are victims of bullying – they are unable to take advantage of these resources.

Bullying is a repetitive, unwanted, and aggressive behavior among children and adolescents that involves a real or perceived power imbalance.¹ Despite the increasing visibility of lesbian, gay, bisexual, and transgender (LGBT) individuals, bullying remains a serious problem for this population. Although between one in four and one in three of all youth experience bullying,² according to the Youth Risk Behavior Survey, LGBT students are two to four times as likely to be threatened or injured with a weapon on school property, two to three times as likely not to go to school because they feel unsafe, and about two times as likely to be bullied at school, compared with their heterosexual peers.³ Alarmingly, more than half of transgender students experience bullying and harassment at school.⁴

A key component of bullying is the power imbalance. Bullying perpetrators feel that they have more power physically (e.g., in size) or socially (e.g., in social status).⁵ LGBT youth are often the victims of bullying because of the societal stigma against same-sex attraction or gender nonconformity. As a result, they tend to have a lower social status, putting them at risk for bullying. Remember, however, that this power imbalance is perceived. Even straight teenagers can be victims of antigay and antitrans bullying because they don’t conform to gender norms (e.g., a straight boy interested in theater instead of sports).⁶ Therefore, any teenager can be a victim of antigay and antitrans bullying.

Although many believe that experiencing bullying is a “rite of passage,” a look at the research on bullying contradicts this. Youth who experience bullying have higher rates of depression, loneliness, and, most worrisome of all, suicide.^7,8 One study showed that LGBT youth who experience bullying are almost six times as likely to consider suicide.⁹ Such sobering statistics prove that bullying is harmful. Furthermore, the effects of bullying can last into adulthood. One study showed that LGBT youth who experienced bullying during high school are more likely to have depressive symptoms and to be dissatisfied with life as a young adult.¹⁰ If rites of passage are designed to make a teenager into a well-adjusted young adult, then bullying does a poor job.

Although antigay bullying and harassment occur outside the clinic, providers can encounter both the perpetrator and the victim as patients and not realize it. Providers who have patients at risk for bullying – such as LGBT or gender-nonconforming youth – should routinely ask them about bullying through such questions as:

• “How many good friends do you have in school?”

• “Do you ever feel afraid to go to school? Why?”

• “Do other kids ever bully you at school, in your neighborhood, or online? Who bullies you?

• When and where does it happen? What do they say or do?”¹¹

Asking these questions is especially important if you or your patient’s caregivers notice school phobia, attention problems, or psychosomatic complaints.11 Once you identify a victim, refer the patient to a mental health provider to develop skills to cope with the stress of bullying. Such skills include how to make friends. Emphasize that it is not the victim’s fault that they are experiencing bullying. Avoid telling victims to fight back or “suck it up.” In addition, work with parents and school authorities to intervene on behalf of the child to stop the bullying behavior.

Lisa Quarfoth/Thinkstock

At the same time, it is especially important to identify perpetrators. Perpetrators tend to have conduct problems, increased depressive symptoms, and poor school adjustment.¹² They may have been bullied themselves. Also refer perpetrators to a mental health provider and other resources to address these problems.

However, with your limited time to screen for bullying or to create an individualized plan to protect bullying victims, approaches to reducing bullying and their adverse effects require a community effort. Use your expertise and access to the latest scientific research to advocate and help create policies schools can use to address antigay bullying. Clark and Tilly recommend a three-tier approach in addressing antigay bullying. In the first tier, schools should create a safe and affirmative environment for all students. An example of such an approach is to have a speaker – such as a physician from the community – talking to students about bullying and encouraging bystanders to speak up (i.e., be an ally) for bullying victims. Although some schools may be hesitant to implement a schoolwide intervention, they may implement a second-tier approach, such as classroom curricula on how to be an ally or incentive programs for helping vulnerable students (e.g., tutoring). Finally, the third tier requires intensive individualized interventions for bullying victims. Schools should have a step-by-step plan involving school authorities that students and their parents can use if students are experiencing bullying.¹³ Implementation of this plan requires timely follow-up from school officials to ensure cessation of the bullying behavior.10

Another way you can advocate for your LGBT patients is to be knowledgeable about the laws surrounding bullying. Bullying laws vary according to state. This is especially true if such laws specifically prohibit bullying based on sexual orientation or gender identity. This is known as “enumeration.” Enumerated laws grant school authorities the power to prevent and to correct any bullying based on sexual orientation and gender identity. Currently, 18 states and the District of Columbia have enumerated antibullying laws.¹⁴ If you live in a state that does not have an enumerated antibullying law, you can contact your state government officials to urge them to pass such a law.

Bullying has a powerful impact on the health and well-being of LGBT youth. Screen for bullying in your LGBT patients and work with schools and parents to protect them from such behaviors. Most importantly, advocate for creating a safe school environment for LGBT youth so that they can focus on their main job of learning and becoming a thriving adult.

Resources

• The website www.stopbullying.gov is a comprehensive resource for bullying and how to address it.

• Society of Adolescent Health & Medicine (SAHM) position statement on bullying (J Adolesc Health. 2005 Jan;36[1]:88-91).

• American Academy of Pediatrics (AAP) position statement on bullying (Pediatrics. 2009 July. doi: 10.1542/peds.2009-0943).

• Gay, Lesbian & Straight Education Network (GLSEN) information on enumerated antibullying laws by state (www.glsen.org/article/state-maps).

References

1. Bullying definition at www.stopbullying.gov.

2. Student Reports of Bullying and Cyber-Bullying: Results From the 2011 School Crime Supplement to the National Crime Victimization Survey.

3. J Adolesc Health. 2014 Sep;55(3):432-8.

4. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. Washington: National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011.

5. Can Fam Physician. 2009 Apr;55(4):356-60.

6. J Adolesc Health. 2016 Feb;58(2):S1-S2.

7. Pediatrics. 2003;111(6 Pt 1):1312-7.

8. Journal of Educational Psychology. 2000 Jun;92(2):349-59.

9. Prev Sci. 2015 Apr;16(3):451-62.

10. Dev Psychol. 2010 Nov;46(6):1580-9.

11. Roles for pediatricians in bullying prevention and intervention (www.stopbullying.gov/resources-files/roles-for-pediatricians-tipsheet.pdf).

12. J Adolesc Health. 2005 Jan;36(1):88-91.

13. Clark JP, Tilly, WD. The evolution of response to intervention. In: Clark JP, Alvarez, Michelle, ed. Response to intervention: A guide for school social worker. (New York: Oxford University Press; 2010:3-18).

14. Enumerated antibullying laws by state(www.glsen.org/article/state-maps).

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh.

A transition is underway at AJO. As we discuss the future of the “new journal,” I often think about the future of orthopedics. I’ve decided my vision of the future is centered on 3 components. First, there will be a change in our training paradigm from an apprenticeship model to standardized training, where core competencies must be demonstrated for certification. Second, robots and computers will improve our diagnostic accuracy and will allow us to perform surgery with improved component positioning, while biologics and genetic analysis will accelerate nature’s ability to heal, and perhaps regenerate, injured tissue. Finally, computerized algorithms and technologically improved surgical outcomes will allow us to deliver high-quality healthcare at a lower cost, producing the value our current health systems are striving for, and leveling the playing field between high-volume centers and rural institutions forced to offer complete service lines.

In this issue, we examine robotic-assisted arthroplasty and its role in modern healthcare. I think the best argument for robots in the operating room might come from the airline industry. I’m sitting on a plane as I write this, without once thinking about how much experience my pilot has in the cockpit. I know our pilot has demonstrated the core competencies required to safely operate the plane, trained on emergency simulations, and logged the necessary hours before being handed the controls. I also know that the instrumentation is so good that the plane can essentially fly itself, making pilot skill and experience less relevant. In short, technology has, in all but rare circumstances, made our pilots virtually interchangeable.

Unfortunately, none of the above is true in orthopedics. Our residents are not required to demonstrate their skills before any licensing authority, simulator training is not available in all programs, and we’ve limited resident work hours. Yet it’s that same interchangeability that most healthcare models assume. No one argues that high-volume centers have better results when it comes to arthroplasty, but only a small percentage of total joints are currently performed at these centers. Surgeon training remains a virtual apprenticeship, lacking standardization, and resulting in a wide variation in skill and experience. Surgical residencies are not awarded based on dexterity, and work hour restrictions, Relative Value Unit-based academic contracts, patient expectations, and staffing pressures can lead to reduced hands-on experience for trainees. The results: an entire generation of surgeons with decreased repetitions in the operating room when compared to their predecessors.

That’s why I believe we are on the cusp of a transition in the operating room, and that computer-assisted surgery is here to stay. While studies exist showing robots have tighter control over virtually every identifiable metric, little data currently exists supporting enhanced long-term outcomes. But as long as component malposition remains a leading cause of early failure, there will be a place for technologies that enhance accuracy of component placement. At odds with the drive for increased technology is the necessity of cost containment, leading us to question the value of robotic-assisted surgery, and whether the improved metrics are clinically important and the additional potential complications are worth the risk.

In the articles in this issue, we will take a critical look at the benefits and drawbacks of robotic surgery. As you read, think about the future of orthopedics and how you will implement new technology into your practice. A transition is coming, and I invite each of you to consider leading it.

A transition is underway at AJO. As we discuss the future of the “new journal,” I often think about the future of orthopedics. I’ve decided my vision of the future is centered on 3 components. First, there will be a change in our training paradigm from an apprenticeship model to standardized training, where core competencies must be demonstrated for certification. Second, robots and computers will improve our diagnostic accuracy and will allow us to perform surgery with improved component positioning, while biologics and genetic analysis will accelerate nature’s ability to heal, and perhaps regenerate, injured tissue. Finally, computerized algorithms and technologically improved surgical outcomes will allow us to deliver high-quality healthcare at a lower cost, producing the value our current health systems are striving for, and leveling the playing field between high-volume centers and rural institutions forced to offer complete service lines.

In this issue, we examine robotic-assisted arthroplasty and its role in modern healthcare. I think the best argument for robots in the operating room might come from the airline industry. I’m sitting on a plane as I write this, without once thinking about how much experience my pilot has in the cockpit. I know our pilot has demonstrated the core competencies required to safely operate the plane, trained on emergency simulations, and logged the necessary hours before being handed the controls. I also know that the instrumentation is so good that the plane can essentially fly itself, making pilot skill and experience less relevant. In short, technology has, in all but rare circumstances, made our pilots virtually interchangeable.

Unfortunately, none of the above is true in orthopedics. Our residents are not required to demonstrate their skills before any licensing authority, simulator training is not available in all programs, and we’ve limited resident work hours. Yet it’s that same interchangeability that most healthcare models assume. No one argues that high-volume centers have better results when it comes to arthroplasty, but only a small percentage of total joints are currently performed at these centers. Surgeon training remains a virtual apprenticeship, lacking standardization, and resulting in a wide variation in skill and experience. Surgical residencies are not awarded based on dexterity, and work hour restrictions, Relative Value Unit-based academic contracts, patient expectations, and staffing pressures can lead to reduced hands-on experience for trainees. The results: an entire generation of surgeons with decreased repetitions in the operating room when compared to their predecessors.

That’s why I believe we are on the cusp of a transition in the operating room, and that computer-assisted surgery is here to stay. While studies exist showing robots have tighter control over virtually every identifiable metric, little data currently exists supporting enhanced long-term outcomes. But as long as component malposition remains a leading cause of early failure, there will be a place for technologies that enhance accuracy of component placement. At odds with the drive for increased technology is the necessity of cost containment, leading us to question the value of robotic-assisted surgery, and whether the improved metrics are clinically important and the additional potential complications are worth the risk.

In the articles in this issue, we will take a critical look at the benefits and drawbacks of robotic surgery. As you read, think about the future of orthopedics and how you will implement new technology into your practice. A transition is coming, and I invite each of you to consider leading it.

A transition is underway at AJO. As we discuss the future of the “new journal,” I often think about the future of orthopedics. I’ve decided my vision of the future is centered on 3 components. First, there will be a change in our training paradigm from an apprenticeship model to standardized training, where core competencies must be demonstrated for certification. Second, robots and computers will improve our diagnostic accuracy and will allow us to perform surgery with improved component positioning, while biologics and genetic analysis will accelerate nature’s ability to heal, and perhaps regenerate, injured tissue. Finally, computerized algorithms and technologically improved surgical outcomes will allow us to deliver high-quality healthcare at a lower cost, producing the value our current health systems are striving for, and leveling the playing field between high-volume centers and rural institutions forced to offer complete service lines.

In this issue, we examine robotic-assisted arthroplasty and its role in modern healthcare. I think the best argument for robots in the operating room might come from the airline industry. I’m sitting on a plane as I write this, without once thinking about how much experience my pilot has in the cockpit. I know our pilot has demonstrated the core competencies required to safely operate the plane, trained on emergency simulations, and logged the necessary hours before being handed the controls. I also know that the instrumentation is so good that the plane can essentially fly itself, making pilot skill and experience less relevant. In short, technology has, in all but rare circumstances, made our pilots virtually interchangeable.

Unfortunately, none of the above is true in orthopedics. Our residents are not required to demonstrate their skills before any licensing authority, simulator training is not available in all programs, and we’ve limited resident work hours. Yet it’s that same interchangeability that most healthcare models assume. No one argues that high-volume centers have better results when it comes to arthroplasty, but only a small percentage of total joints are currently performed at these centers. Surgeon training remains a virtual apprenticeship, lacking standardization, and resulting in a wide variation in skill and experience. Surgical residencies are not awarded based on dexterity, and work hour restrictions, Relative Value Unit-based academic contracts, patient expectations, and staffing pressures can lead to reduced hands-on experience for trainees. The results: an entire generation of surgeons with decreased repetitions in the operating room when compared to their predecessors.

That’s why I believe we are on the cusp of a transition in the operating room, and that computer-assisted surgery is here to stay. While studies exist showing robots have tighter control over virtually every identifiable metric, little data currently exists supporting enhanced long-term outcomes. But as long as component malposition remains a leading cause of early failure, there will be a place for technologies that enhance accuracy of component placement. At odds with the drive for increased technology is the necessity of cost containment, leading us to question the value of robotic-assisted surgery, and whether the improved metrics are clinically important and the additional potential complications are worth the risk.

In the articles in this issue, we will take a critical look at the benefits and drawbacks of robotic surgery. As you read, think about the future of orthopedics and how you will implement new technology into your practice. A transition is coming, and I invite each of you to consider leading it.

Unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are 2 reliable treatment options for patients with primary osteoarthritis. Recently published systematic reviews of cohort studies have shown that 10-year survivorship of medial and lateral UKA is 92% and 91%, respectively,¹ while 10-year survivorship of TKA in cohort studies is 95%.² National and annual registries show a similar trend, although the reported survivorship is lower.^1,3-7

In order to improve these survivorship rates, the surgical variables that can intraoperatively be controlled by the orthopedic surgeon have been evaluated. These variables include lower leg alignment, soft tissue balance, joint line maintenance, and alignment, size, and fixation of the tibial and femoral component. Several studies have shown that tight control of lower leg alignment,^8-14 balancing of the soft tissues,^15-19 joint line maintenance,^20-23 component alignment,^24-28 component size,^29-34 and component fixation^35-40 can improve the outcomes of UKA and TKA. As a result, over the past 2 decades, several computer-assisted surgery systems have been developed with the goal of more accurate and reliable control of these factors, and thus improved outcomes of knee arthroplasty.

These systems differ with regard to the number and type of variables they control. Computer navigation systems aim to control one or more of these surgical variables, and several meta-analyses have shown that these systems, when compared to conventional surgery, improve mechanical axis accuracy, decrease the risk for mechanical axis outliers, and improve component positioning in TKA^41-49 and UKA surgery.^50,51 Interestingly, however, meta-analyses have failed to show the expected superiority in clinical outcomes following computer navigation compared to conventional knee arthroplasty.^48,52-55 Furthermore, authors have shown that, despite the fact that computer-navigated surgery increases the accuracy of mechanical alignment and surgical cutting, there is still room for improvement.⁵⁶ As a consequence, robotic-assisted systems have been developed.

Similar to computer navigation, these robotic-assisted systems aim to control the surgical variables; in addition, they aim to improve the surgical precision of the procedure. Interestingly, 2 recent studies have shown that robotic-assisted systems are superior to computer navigation systems with regard to less cutting time and less resection deviations in coronal and sagittal plane in a cadaveric study,⁵⁷ and shorter total surgery time, more accurate mechanical axis, and shorter hospital stay in a clinical study.⁵⁸ Although these results are promising, the exact role of robotic surgery in knee arthroplasty remains unclear. In this review, we aim to report the current state of robotic-assisted knee arthroplasty by discussing (1) the different robotic-assisted knee arthroplasty systems that are available for UKA and TKA surgery, (2) studies that assessed the role of robotic-assisted knee arthroplasty in controlling the aforementioned surgical variables, (3) cadaveric and clinical comparative studies that compared how accurate robotic-assisted and conventional knee surgery control these surgical variables, and (4) studies that assessed the cost-effectiveness of robotic-assisted knee arthroplasty surgery.

Robotic-Assisted Knee Arthroplasty Systems

Several systems have been developed over the years for knee arthroplasty, and these are usually defined as active, semi-active, or passive.⁵⁹ Active systems are capable of performing tasks or processes autonomously under the watchful eye of the surgeon, while passive systems do not perform actions independently but provide the surgeon with information. In semi-active systems, the surgical action is physically constrained in order to follow a predefined strategy.

In the United States, 3 robotic systems are FDA-approved for knee arthroplasty. The Stryker/Mako haptic guided robot (Mako Surgical Corp.) was introduced in 2005 and has been used for over 50,000 UKA procedures (Figure 1). There are nearly 300 robotic systems used nationally, as it has 20% of the market share for UKA in the United States. The Mako system is a semi-active tactile robotic system that requires preoperative imaging, after which a preoperative planning is performed. Intraoperatively, the robotic arm is under direct surgeon control and gives real-time tactile feedback during the procedure (Figure 2).

Furthermore, the surgeon can intraoperatively virtually adjust component positioning and alignment and move the knee through the range of motion, after which the system can provide information on alignment, component position, and balance of the soft tissue (eg, if the knee is overtight or lax through the flexion-arch).⁶⁰ This system has a burr that resects the bone and when the surgeon directs the burr outside the preplanned area, the burr stops and prevents unnecessary and unwanted resections (Figure 3).

The Navio Precision Free-Hand Sculptor (PFS) system (Blue Belt Technologies) has been used for 1500 UKA procedures, with 50 robots in use in the United States (Figure 4). This system is an image-free semi-active robotic system and has the same characteristics as the aforementioned Mako system.⁶¹ Finally, the OmniBotic robotic system (Omnilife Science) has been released for TKA and has been used for over 7300 procedures (Figure 5). This system has an automated cutting-guide technique in which the surgeon designs a virtual plan on the computer system. After this, the cutting-guides are placed by the robotic system at the planned location for all 5 femoral cuts (ie, distal, anterior chamfer, anterior, posterior chamfer, and posterior) and the surgeon then makes the final cuts.^57,62

Three robotic systems for knee arthroplasty surgery have been used in Europe. The Caspar system (URS Ortho) is an active robotic system in which a computed tomography (CT) scan is performed preoperatively, after which a virtual implantation is performed on the screen. The surgeon can then obtain information on lower leg alignment, gap balancing, and component positioning, and after an operative plan is made, the surgical resections are performed by the robot. Reflective markers are attached to the leg and all robotic movements are monitored using an infrared camera system. Any undesired motion will be detected by this camera system and will stop all movements.⁶³ A second and more frequently reported system in the literature is the active Robodoc surgical system (Curexo Technology Corporation). This system is designed for TKA and total hip arthroplasty (THA) surgery. Although initial studies reported a high incidence of system-related complications in THA,⁶⁴ the use of this system for TKA has frequently been reported in the literature.^56,63,65-69 A third robotic system that has been used in Europe is the Acrobot surgical system (Acrobot Company Ltd), which is an image-based semi-active robotic system⁷⁰ used for both UKA and TKA surgery.^70,71

Accuracy of Controlling Surgical Variables in Robotic-Assisted Knee Arthroplasty

Several studies have assessed the accuracy of robotic-assisted surgery in UKA surgery with regard to control of the aforementioned surgical variables. Pearle and colleagues⁷² assessed the mechanical axis accuracy of the Mako system in 10 patients undergoing medial UKA robotic-assisted surgery. They reported that the intraoperative registration lasted 7.5 minutes and the duration of time needed for robotic-assisted burring was 34.8 minutes. They compared the actual postoperative alignment at 6 weeks follow-up with the planned lower leg alignment and found that all measurements were within 1.6° of the planned lower leg alignment. Dunbar and colleagues⁷³ assessed the accuracy of component positioning of the Mako system in 20 patients undergoing medial UKA surgery by comparing preoperative and postoperative 3-dimensional CT scans. They found that the femoral component was within 0.8 mm and 0.9° in all directions and that the tibial component was within 0.9 mm and 1.7° in all directions. They concluded that the accuracy of component positioning with the Mako system was excellent. Finally, Plate and colleagues¹⁷ assessed the accuracy of soft tissue balancing in the Mako system in 52 patients undergoing medial UKA surgery. They compared the balance plan with the soft tissue balance after implantation and the Mako system quantified soft tissue balance as the amount of mm of the knee being tight or loose at 0°, 30°, 60°, 90°, and 110° of flexion. They found that at all flexion angles the ligament balancing was accurate up to 0.53 mm of the original plan. Furthermore, they noted that in 83% of cases the accuracy was within 1 mm at all flexion angles.

For the Navio system, Smith and colleagues⁷⁴ assessed the accuracy of component positioning using 20 synthetic femurs and tibia. They reported a maximum rotational error of 3.2°, an angular error of 1.46° in all orientations, and a maximum translational error of 1.18 mm for both the tibial and femoral implants. Lonner and colleagues⁷⁵ assessed the accuracy of component positioning in 25 cadaveric specimens. They found similar results as were found in the study of Smith and colleagues⁷⁴ and concluded that these results were similar to other semi-active robotic systems designed for UKA.

For TKA surgery, Ponder and colleagues⁷⁶ assessed the accuracy of the OmniBotic system and found that the average error in the anterior-posterior dimension between the targeted and measured cuts was -0.14 mm, and that the standard deviation in guide positioning for the distal, anterior chamfer, and posterior chamfer resections was 0.03° and 0.17 mm. Koenig and colleagues⁶² assessed the accuracy of the OmniBotic system in the first 100 cases and found that 98% of the cases were within 3° of the neutral mechanical axis. Furthermore, they found a learning curve with regard to tourniquet time between the first and second 10 patients in which they performed robotic-assisted TKA surgery. Siebert and colleagues⁶³ assessed the accuracy of mechanical alignment in the Caspar system in 70 patients treated with the robotic system. They found that the difference between preoperatively planned and postoperatively achieved mechanical alignment was 0.8°. Similarly, Bellemans and colleagues⁷⁷ assessed mechanical alignment and the positioning and rotation of the tibial and femoral components in a clinical study of 25 cases using the Caspar system. They noted that none of the patients had mechanical alignment, tibial or femoral component positioning, or rotation beyond 1° of the neutral axis. Liow and colleagues⁵⁶ assessed the accuracy of mechanical axis alignment and component sizing accuracy using the Robodoc system in 25 patients. They reported that the mean postoperative alignment was 0.4° valgus and that all cases were within 3° of the neutral mechanical axis. Furthermore, they reported a mean surgical time of 96 minutes and reported that preoperative planning yielded femoral and tibial component size accuracy of 100%.

These studies have shown that robotic systems for UKA and TKA are accurate in the surgical variables they aim to control. These studies validated tight control of mechanical axis alignment, decrease for outliers, and component positioning and rotation, and also found that the balancing of soft tissues was improved using robotic-assisted surgery.

Robotic-Assisted vs Conventional Knee Arthroplasty

Despite the fact that these systems are accurate in the variables they aim to control, these systems have to be compared to the gold standard of conventional knee arthroplasty. For UKA, Cobb and colleagues⁷⁰ performed a randomized clinical trial for patients treated undergoing UKA with robotic-assistance of the Acrobot systems compared to conventional UKA and assessed differences in mechanical accuracy. A total of 27 patients were randomly assigned to one of both treatments. They found that in the group of robotic-assisted surgery, 100% of the patients had a mechanical axis within 2° of neutral, while this was only 40% in the conventional UKA groups (difference P < .001). They also assessed the increase in functional outcomes and noted a trend towards improvement in performance with increasing accuracy at 6 weeks and 3 months postoperatively. Lonner and colleagues⁷⁸ also compared the tibial component positioning between robotic-assisted UKA surgery using the Mako system and conventional UKA surgery. The authors found that the variance in tibial slope, in coronal plane of the tibial component, and varus/valgus alignment were all larger with conventional UKA when compared to robotic-assisted UKA. Citak and colleagues⁷⁹ compared the accuracy of tibial and femoral implant positioning between robotic-assisted surgery using the Mako system and conventional UKA in a cadaveric study. They reported that the root mean square (RMS) error of femoral component was 1.9 mm and 3.7° in robotic-assisted surgery and 5.4 mm and 10.2° for conventional UKA, while the RMS error for tibial component were 1.4 mm and 5.0° for robotic-assisted surgery and 5.7 mm and 19.2° for conventional UKA surgery. MacCallum and colleagues⁸⁰ compared the tibial base plate position in a prospective clinical study of 177 patients treated with conventional UKA and 87 patients treated with robotic-assisted surgery using the Mako system. They found that surgery with robotic-assistance was more precise in the coronal and sagittal plane and was more accurate in coronal alignment when compared to conventional UKA. Finally, the first results of robotic-assisted UKA surgery have been presented. Coon and colleagues⁸¹ reported the preliminary results of a multicenter study of 854 patients and found a survivorship of 98.9% and satisfaction rate of 92% at minimum 2-year follow-up. Comparing these results to other large conventional UKA cohorts^82,83 suggests that robotic-assisted surgery may improve survivorship at short-term follow-up. However, comparative studies and studies with longer follow-up are necessary to assess the additional value of robotic-assisted UKA surgery. Due to the relatively new concept of robotic-assisted surgery, these studies have not been performed or published yet.

For TKA, several studies also have compared how these robotic-systems control the surgical variables compared to conventional TKA surgery. Siebert and colleagues⁶³ assessed mechanical axis accuracy and mechanical outliers following robotic-assisted TKA surgery using the Caspar system and conventional TKA surgery. They reported the difference between preoperative planned and postoperative achieved alignment was 0.8° for robotic-assisted surgery and 2.6° for conventional TKA surgery. Furthermore, they showed that 1 patient in the robotic-assisted group (1.4%) and 18 patients in the conventional TKA group (35%) had mechanical alignment greater than 3° from the neutral mechanical axis. Liow and colleagues⁵⁶ found similar differences in their prospective randomized study in which they reported that 0% outliers greater than 3° from the neutral mechanical axis were found in the robotic-assisted group while 19.4% of the patients in the conventional TKA group had mechanical axis outliers. They also assessed the joint-line outliers in both procedures and found that 3.2% had joint-line outliers greater than 5 mm in the robotic-assisted group compared to 20.6% in the conventional TKA group. Kim and colleagues⁶⁵ assessed implant accuracy in robotic-assisted surgery using the ROBODOC system and in conventional surgery and reported higher implant accuracy and fewer outliers using robotic-assisted surgery. Moon and colleagues⁶⁶ compared robotic-assisted TKA surgery using the Robodoc system with conventional TKA surgery in 10 cadavers. They found that robotic-assisted surgery had excellent precision in all planes and had better accuracy in femoral rotation alignment compared to conventional TKA surgery. Park and Lee⁶⁷ compared Robodoc robotic-assisted TKA surgery with conventional TKA surgery in a randomized clinical trial of 72 patients. They found that robotic-assisted surgery had definitive advantages in preoperative planning, accuracy of the procedure, and postoperative follow-up regarding femoral and tibial component flexion angles. Finally, Song and colleagues^68,69 performed 2 randomized clinical trials in which they compared mechanical axis alignment, component positioning, soft tissue balancing, and patient preference between conventional TKA surgery and robotic-assisted surgery using the Robodoc system. In the first study,⁶⁸ they simultaneously performed robotic-assisted surgery in one leg and conventional TKA surgery in the other leg. They found that robotic-assisted surgery resulted in less outlier in mechanical axis and component positioning. Furthermore, they found at latest follow-up of 2 years that 12 patients preferred the leg treated with robotic-assisted surgery while 6 preferred the conventional leg. Despite this finding, no significant differences in functional outcome scores were detected between both treatment options. Furthermore, they found that flexion-extension balance was achieved in 92% of patients treated with robotic-assisted TKA surgery and in 77% of patients treated with conventional TKA surgery. In the other study,⁶⁹ the authors found that more patients treated with robotic-assisted surgery had <2 mm flexion-extension gap and more satisfactory posterior cruciate ligament tension when compared to conventional surgery.

These studies have shown that robotic-assisted surgery is accurate in controlling surgical variables, such as mechanical lower leg alignment, maintaining joint-line, implant positioning, and soft tissue balancing. Furthermore, these studies have shown that controlling these variables is better than the current gold standard of manual knee arthroplasty. Until now, not many studies have assessed survivorship of robotic-assisted surgery. Furthermore, no studies have, to our knowledge, compared survivorship of robotic-assisted with conventional knee replacement surgery. Finally, studies comparing functional outcomes following robotic-assisted surgery and conventional knee arthroplasty surgery are frequently underpowered due to their small sample sizes.^68,70 Since many studies have shown that the surgical variables are more tightly controlled using robotic-assisted surgery when compared to conventional surgery, large comparative studies are necessary to assess the role of robotic-assisted surgery in functional outcomes and survivorship of UKA and TKA.

Cost-Effectiveness of Robotic-Assisted Surgery

High initial capital costs of robotic-assisted surgery is one of the factors that constitute a barrier to the widespread implementation of this technique. Multiple authors have suggested that improved implant survivorship afforded by robotic-assisted surgery may justify the expenditure from both societal and provider perspective.^84-86 Two studies have performed a cost-effectiveness analysis for UKA surgery. Swank and colleagues⁸⁴ reviewed the hospital expenditures and profits associated with robot-assisted knee arthroplasty, citing upfront costs of approximately $800,000. The authors estimated a mean per-case contribution profit of $5790 for robotic-assisted UKA, assuming an inpatient-to-outpatient ratio of 1 to 3. Based on this data, Swank and colleagues84 proposed that the capital costs of robotic-assisted UKA may be recovered in as little as 2 years when in the first 3 consecutive years 50, 70, and 90 cases were performed using robotic-assisted UKA. Moschetti and colleagues⁸⁵ recently published the first formal cost-effectiveness analysis of robotic-assisted compared to manual UKA. The authors used an annual revision risk of 0.55% for the first 2 years following robot-assisted UKA, based on the aforementioned presented data by Coon and colleagues.⁸¹ They based their data on the Mako system and assumed an initial capital expenditure of $934,728 with annual servicing costs of 10% (discounted annually) for 4 years thereafter, resulting in a total cost of the robotic system of $1.362 million. These costs were divided by the number of patients estimated to undergo robotic-assisted UKA per year, which was varied to estimate the effect of case volume on cost-effectiveness. The authors reported that robotic-assisted UKA was associated with higher lifetime costs and net utilities compared to manual UKA, at an incremental cost-effectiveness ratio of $47,180 per quality-adjusted life year (QALY) in a high-volume center. This falls well within the societal willingness-to-pay threshold of $100,000/QALY. Sensitivity analysis showed that robotic-assisted UKA is cost-effective under the following conditions: (1) centers performing at least 94 cases annually, (2) in patients younger than age 67 years, and (3) 2-year revision rate does not exceed 1.2%. While the results of this initial analysis are promising, follow-up cost-effectiveness analysis studies will be required as long-term survivorship data become available.

Conclusion

Tighter control of intraoperative surgical variables, such as lower leg alignment, soft tissue balance, joint-line maintenance, and component alignment and positioning, have been associated with improved survivorship and functional outcomes. Upon reviewing the available literature on robotic-assisted surgery, it becomes clear that this technique can improve the accuracy of these surgical variables and is superior to conventional manual UKA and TKA. Although larger and comparative survivorship studies are necessary to compare robotic-assisted knee arthroplasty to conventional techniques, the early results and cost-effectiveness analysis seem promising.

Unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are 2 reliable treatment options for patients with primary osteoarthritis. Recently published systematic reviews of cohort studies have shown that 10-year survivorship of medial and lateral UKA is 92% and 91%, respectively,¹ while 10-year survivorship of TKA in cohort studies is 95%.² National and annual registries show a similar trend, although the reported survivorship is lower.^1,3-7

In order to improve these survivorship rates, the surgical variables that can intraoperatively be controlled by the orthopedic surgeon have been evaluated. These variables include lower leg alignment, soft tissue balance, joint line maintenance, and alignment, size, and fixation of the tibial and femoral component. Several studies have shown that tight control of lower leg alignment,^8-14 balancing of the soft tissues,^15-19 joint line maintenance,^20-23 component alignment,^24-28 component size,^29-34 and component fixation^35-40 can improve the outcomes of UKA and TKA. As a result, over the past 2 decades, several computer-assisted surgery systems have been developed with the goal of more accurate and reliable control of these factors, and thus improved outcomes of knee arthroplasty.

These systems differ with regard to the number and type of variables they control. Computer navigation systems aim to control one or more of these surgical variables, and several meta-analyses have shown that these systems, when compared to conventional surgery, improve mechanical axis accuracy, decrease the risk for mechanical axis outliers, and improve component positioning in TKA^41-49 and UKA surgery.^50,51 Interestingly, however, meta-analyses have failed to show the expected superiority in clinical outcomes following computer navigation compared to conventional knee arthroplasty.^48,52-55 Furthermore, authors have shown that, despite the fact that computer-navigated surgery increases the accuracy of mechanical alignment and surgical cutting, there is still room for improvement.⁵⁶ As a consequence, robotic-assisted systems have been developed.

Similar to computer navigation, these robotic-assisted systems aim to control the surgical variables; in addition, they aim to improve the surgical precision of the procedure. Interestingly, 2 recent studies have shown that robotic-assisted systems are superior to computer navigation systems with regard to less cutting time and less resection deviations in coronal and sagittal plane in a cadaveric study,⁵⁷ and shorter total surgery time, more accurate mechanical axis, and shorter hospital stay in a clinical study.⁵⁸ Although these results are promising, the exact role of robotic surgery in knee arthroplasty remains unclear. In this review, we aim to report the current state of robotic-assisted knee arthroplasty by discussing (1) the different robotic-assisted knee arthroplasty systems that are available for UKA and TKA surgery, (2) studies that assessed the role of robotic-assisted knee arthroplasty in controlling the aforementioned surgical variables, (3) cadaveric and clinical comparative studies that compared how accurate robotic-assisted and conventional knee surgery control these surgical variables, and (4) studies that assessed the cost-effectiveness of robotic-assisted knee arthroplasty surgery.

Robotic-Assisted Knee Arthroplasty Systems

Several systems have been developed over the years for knee arthroplasty, and these are usually defined as active, semi-active, or passive.⁵⁹ Active systems are capable of performing tasks or processes autonomously under the watchful eye of the surgeon, while passive systems do not perform actions independently but provide the surgeon with information. In semi-active systems, the surgical action is physically constrained in order to follow a predefined strategy.

In the United States, 3 robotic systems are FDA-approved for knee arthroplasty. The Stryker/Mako haptic guided robot (Mako Surgical Corp.) was introduced in 2005 and has been used for over 50,000 UKA procedures (Figure 1). There are nearly 300 robotic systems used nationally, as it has 20% of the market share for UKA in the United States. The Mako system is a semi-active tactile robotic system that requires preoperative imaging, after which a preoperative planning is performed. Intraoperatively, the robotic arm is under direct surgeon control and gives real-time tactile feedback during the procedure (Figure 2).

Furthermore, the surgeon can intraoperatively virtually adjust component positioning and alignment and move the knee through the range of motion, after which the system can provide information on alignment, component position, and balance of the soft tissue (eg, if the knee is overtight or lax through the flexion-arch).⁶⁰ This system has a burr that resects the bone and when the surgeon directs the burr outside the preplanned area, the burr stops and prevents unnecessary and unwanted resections (Figure 3).

The Navio Precision Free-Hand Sculptor (PFS) system (Blue Belt Technologies) has been used for 1500 UKA procedures, with 50 robots in use in the United States (Figure 4). This system is an image-free semi-active robotic system and has the same characteristics as the aforementioned Mako system.⁶¹ Finally, the OmniBotic robotic system (Omnilife Science) has been released for TKA and has been used for over 7300 procedures (Figure 5). This system has an automated cutting-guide technique in which the surgeon designs a virtual plan on the computer system. After this, the cutting-guides are placed by the robotic system at the planned location for all 5 femoral cuts (ie, distal, anterior chamfer, anterior, posterior chamfer, and posterior) and the surgeon then makes the final cuts.^57,62

Three robotic systems for knee arthroplasty surgery have been used in Europe. The Caspar system (URS Ortho) is an active robotic system in which a computed tomography (CT) scan is performed preoperatively, after which a virtual implantation is performed on the screen. The surgeon can then obtain information on lower leg alignment, gap balancing, and component positioning, and after an operative plan is made, the surgical resections are performed by the robot. Reflective markers are attached to the leg and all robotic movements are monitored using an infrared camera system. Any undesired motion will be detected by this camera system and will stop all movements.⁶³ A second and more frequently reported system in the literature is the active Robodoc surgical system (Curexo Technology Corporation). This system is designed for TKA and total hip arthroplasty (THA) surgery. Although initial studies reported a high incidence of system-related complications in THA,⁶⁴ the use of this system for TKA has frequently been reported in the literature.^56,63,65-69 A third robotic system that has been used in Europe is the Acrobot surgical system (Acrobot Company Ltd), which is an image-based semi-active robotic system⁷⁰ used for both UKA and TKA surgery.^70,71

Accuracy of Controlling Surgical Variables in Robotic-Assisted Knee Arthroplasty

Several studies have assessed the accuracy of robotic-assisted surgery in UKA surgery with regard to control of the aforementioned surgical variables. Pearle and colleagues⁷² assessed the mechanical axis accuracy of the Mako system in 10 patients undergoing medial UKA robotic-assisted surgery. They reported that the intraoperative registration lasted 7.5 minutes and the duration of time needed for robotic-assisted burring was 34.8 minutes. They compared the actual postoperative alignment at 6 weeks follow-up with the planned lower leg alignment and found that all measurements were within 1.6° of the planned lower leg alignment. Dunbar and colleagues⁷³ assessed the accuracy of component positioning of the Mako system in 20 patients undergoing medial UKA surgery by comparing preoperative and postoperative 3-dimensional CT scans. They found that the femoral component was within 0.8 mm and 0.9° in all directions and that the tibial component was within 0.9 mm and 1.7° in all directions. They concluded that the accuracy of component positioning with the Mako system was excellent. Finally, Plate and colleagues¹⁷ assessed the accuracy of soft tissue balancing in the Mako system in 52 patients undergoing medial UKA surgery. They compared the balance plan with the soft tissue balance after implantation and the Mako system quantified soft tissue balance as the amount of mm of the knee being tight or loose at 0°, 30°, 60°, 90°, and 110° of flexion. They found that at all flexion angles the ligament balancing was accurate up to 0.53 mm of the original plan. Furthermore, they noted that in 83% of cases the accuracy was within 1 mm at all flexion angles.

For the Navio system, Smith and colleagues⁷⁴ assessed the accuracy of component positioning using 20 synthetic femurs and tibia. They reported a maximum rotational error of 3.2°, an angular error of 1.46° in all orientations, and a maximum translational error of 1.18 mm for both the tibial and femoral implants. Lonner and colleagues⁷⁵ assessed the accuracy of component positioning in 25 cadaveric specimens. They found similar results as were found in the study of Smith and colleagues⁷⁴ and concluded that these results were similar to other semi-active robotic systems designed for UKA.

For TKA surgery, Ponder and colleagues⁷⁶ assessed the accuracy of the OmniBotic system and found that the average error in the anterior-posterior dimension between the targeted and measured cuts was -0.14 mm, and that the standard deviation in guide positioning for the distal, anterior chamfer, and posterior chamfer resections was 0.03° and 0.17 mm. Koenig and colleagues⁶² assessed the accuracy of the OmniBotic system in the first 100 cases and found that 98% of the cases were within 3° of the neutral mechanical axis. Furthermore, they found a learning curve with regard to tourniquet time between the first and second 10 patients in which they performed robotic-assisted TKA surgery. Siebert and colleagues⁶³ assessed the accuracy of mechanical alignment in the Caspar system in 70 patients treated with the robotic system. They found that the difference between preoperatively planned and postoperatively achieved mechanical alignment was 0.8°. Similarly, Bellemans and colleagues⁷⁷ assessed mechanical alignment and the positioning and rotation of the tibial and femoral components in a clinical study of 25 cases using the Caspar system. They noted that none of the patients had mechanical alignment, tibial or femoral component positioning, or rotation beyond 1° of the neutral axis. Liow and colleagues⁵⁶ assessed the accuracy of mechanical axis alignment and component sizing accuracy using the Robodoc system in 25 patients. They reported that the mean postoperative alignment was 0.4° valgus and that all cases were within 3° of the neutral mechanical axis. Furthermore, they reported a mean surgical time of 96 minutes and reported that preoperative planning yielded femoral and tibial component size accuracy of 100%.

These studies have shown that robotic systems for UKA and TKA are accurate in the surgical variables they aim to control. These studies validated tight control of mechanical axis alignment, decrease for outliers, and component positioning and rotation, and also found that the balancing of soft tissues was improved using robotic-assisted surgery.

Robotic-Assisted vs Conventional Knee Arthroplasty

Despite the fact that these systems are accurate in the variables they aim to control, these systems have to be compared to the gold standard of conventional knee arthroplasty. For UKA, Cobb and colleagues⁷⁰ performed a randomized clinical trial for patients treated undergoing UKA with robotic-assistance of the Acrobot systems compared to conventional UKA and assessed differences in mechanical accuracy. A total of 27 patients were randomly assigned to one of both treatments. They found that in the group of robotic-assisted surgery, 100% of the patients had a mechanical axis within 2° of neutral, while this was only 40% in the conventional UKA groups (difference P < .001). They also assessed the increase in functional outcomes and noted a trend towards improvement in performance with increasing accuracy at 6 weeks and 3 months postoperatively. Lonner and colleagues⁷⁸ also compared the tibial component positioning between robotic-assisted UKA surgery using the Mako system and conventional UKA surgery. The authors found that the variance in tibial slope, in coronal plane of the tibial component, and varus/valgus alignment were all larger with conventional UKA when compared to robotic-assisted UKA. Citak and colleagues⁷⁹ compared the accuracy of tibial and femoral implant positioning between robotic-assisted surgery using the Mako system and conventional UKA in a cadaveric study. They reported that the root mean square (RMS) error of femoral component was 1.9 mm and 3.7° in robotic-assisted surgery and 5.4 mm and 10.2° for conventional UKA, while the RMS error for tibial component were 1.4 mm and 5.0° for robotic-assisted surgery and 5.7 mm and 19.2° for conventional UKA surgery. MacCallum and colleagues⁸⁰ compared the tibial base plate position in a prospective clinical study of 177 patients treated with conventional UKA and 87 patients treated with robotic-assisted surgery using the Mako system. They found that surgery with robotic-assistance was more precise in the coronal and sagittal plane and was more accurate in coronal alignment when compared to conventional UKA. Finally, the first results of robotic-assisted UKA surgery have been presented. Coon and colleagues⁸¹ reported the preliminary results of a multicenter study of 854 patients and found a survivorship of 98.9% and satisfaction rate of 92% at minimum 2-year follow-up. Comparing these results to other large conventional UKA cohorts^82,83 suggests that robotic-assisted surgery may improve survivorship at short-term follow-up. However, comparative studies and studies with longer follow-up are necessary to assess the additional value of robotic-assisted UKA surgery. Due to the relatively new concept of robotic-assisted surgery, these studies have not been performed or published yet.

For TKA, several studies also have compared how these robotic-systems control the surgical variables compared to conventional TKA surgery. Siebert and colleagues⁶³ assessed mechanical axis accuracy and mechanical outliers following robotic-assisted TKA surgery using the Caspar system and conventional TKA surgery. They reported the difference between preoperative planned and postoperative achieved alignment was 0.8° for robotic-assisted surgery and 2.6° for conventional TKA surgery. Furthermore, they showed that 1 patient in the robotic-assisted group (1.4%) and 18 patients in the conventional TKA group (35%) had mechanical alignment greater than 3° from the neutral mechanical axis. Liow and colleagues⁵⁶ found similar differences in their prospective randomized study in which they reported that 0% outliers greater than 3° from the neutral mechanical axis were found in the robotic-assisted group while 19.4% of the patients in the conventional TKA group had mechanical axis outliers. They also assessed the joint-line outliers in both procedures and found that 3.2% had joint-line outliers greater than 5 mm in the robotic-assisted group compared to 20.6% in the conventional TKA group. Kim and colleagues⁶⁵ assessed implant accuracy in robotic-assisted surgery using the ROBODOC system and in conventional surgery and reported higher implant accuracy and fewer outliers using robotic-assisted surgery. Moon and colleagues⁶⁶ compared robotic-assisted TKA surgery using the Robodoc system with conventional TKA surgery in 10 cadavers. They found that robotic-assisted surgery had excellent precision in all planes and had better accuracy in femoral rotation alignment compared to conventional TKA surgery. Park and Lee⁶⁷ compared Robodoc robotic-assisted TKA surgery with conventional TKA surgery in a randomized clinical trial of 72 patients. They found that robotic-assisted surgery had definitive advantages in preoperative planning, accuracy of the procedure, and postoperative follow-up regarding femoral and tibial component flexion angles. Finally, Song and colleagues^68,69 performed 2 randomized clinical trials in which they compared mechanical axis alignment, component positioning, soft tissue balancing, and patient preference between conventional TKA surgery and robotic-assisted surgery using the Robodoc system. In the first study,⁶⁸ they simultaneously performed robotic-assisted surgery in one leg and conventional TKA surgery in the other leg. They found that robotic-assisted surgery resulted in less outlier in mechanical axis and component positioning. Furthermore, they found at latest follow-up of 2 years that 12 patients preferred the leg treated with robotic-assisted surgery while 6 preferred the conventional leg. Despite this finding, no significant differences in functional outcome scores were detected between both treatment options. Furthermore, they found that flexion-extension balance was achieved in 92% of patients treated with robotic-assisted TKA surgery and in 77% of patients treated with conventional TKA surgery. In the other study,⁶⁹ the authors found that more patients treated with robotic-assisted surgery had <2 mm flexion-extension gap and more satisfactory posterior cruciate ligament tension when compared to conventional surgery.

These studies have shown that robotic-assisted surgery is accurate in controlling surgical variables, such as mechanical lower leg alignment, maintaining joint-line, implant positioning, and soft tissue balancing. Furthermore, these studies have shown that controlling these variables is better than the current gold standard of manual knee arthroplasty. Until now, not many studies have assessed survivorship of robotic-assisted surgery. Furthermore, no studies have, to our knowledge, compared survivorship of robotic-assisted with conventional knee replacement surgery. Finally, studies comparing functional outcomes following robotic-assisted surgery and conventional knee arthroplasty surgery are frequently underpowered due to their small sample sizes.^68,70 Since many studies have shown that the surgical variables are more tightly controlled using robotic-assisted surgery when compared to conventional surgery, large comparative studies are necessary to assess the role of robotic-assisted surgery in functional outcomes and survivorship of UKA and TKA.

Cost-Effectiveness of Robotic-Assisted Surgery

High initial capital costs of robotic-assisted surgery is one of the factors that constitute a barrier to the widespread implementation of this technique. Multiple authors have suggested that improved implant survivorship afforded by robotic-assisted surgery may justify the expenditure from both societal and provider perspective.^84-86 Two studies have performed a cost-effectiveness analysis for UKA surgery. Swank and colleagues⁸⁴ reviewed the hospital expenditures and profits associated with robot-assisted knee arthroplasty, citing upfront costs of approximately $800,000. The authors estimated a mean per-case contribution profit of $5790 for robotic-assisted UKA, assuming an inpatient-to-outpatient ratio of 1 to 3. Based on this data, Swank and colleagues84 proposed that the capital costs of robotic-assisted UKA may be recovered in as little as 2 years when in the first 3 consecutive years 50, 70, and 90 cases were performed using robotic-assisted UKA. Moschetti and colleagues⁸⁵ recently published the first formal cost-effectiveness analysis of robotic-assisted compared to manual UKA. The authors used an annual revision risk of 0.55% for the first 2 years following robot-assisted UKA, based on the aforementioned presented data by Coon and colleagues.⁸¹ They based their data on the Mako system and assumed an initial capital expenditure of $934,728 with annual servicing costs of 10% (discounted annually) for 4 years thereafter, resulting in a total cost of the robotic system of $1.362 million. These costs were divided by the number of patients estimated to undergo robotic-assisted UKA per year, which was varied to estimate the effect of case volume on cost-effectiveness. The authors reported that robotic-assisted UKA was associated with higher lifetime costs and net utilities compared to manual UKA, at an incremental cost-effectiveness ratio of $47,180 per quality-adjusted life year (QALY) in a high-volume center. This falls well within the societal willingness-to-pay threshold of $100,000/QALY. Sensitivity analysis showed that robotic-assisted UKA is cost-effective under the following conditions: (1) centers performing at least 94 cases annually, (2) in patients younger than age 67 years, and (3) 2-year revision rate does not exceed 1.2%. While the results of this initial analysis are promising, follow-up cost-effectiveness analysis studies will be required as long-term survivorship data become available.

Conclusion

Tighter control of intraoperative surgical variables, such as lower leg alignment, soft tissue balance, joint-line maintenance, and component alignment and positioning, have been associated with improved survivorship and functional outcomes. Upon reviewing the available literature on robotic-assisted surgery, it becomes clear that this technique can improve the accuracy of these surgical variables and is superior to conventional manual UKA and TKA. Although larger and comparative survivorship studies are necessary to compare robotic-assisted knee arthroplasty to conventional techniques, the early results and cost-effectiveness analysis seem promising.

Unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are 2 reliable treatment options for patients with primary osteoarthritis. Recently published systematic reviews of cohort studies have shown that 10-year survivorship of medial and lateral UKA is 92% and 91%, respectively,¹ while 10-year survivorship of TKA in cohort studies is 95%.² National and annual registries show a similar trend, although the reported survivorship is lower.^1,3-7

In order to improve these survivorship rates, the surgical variables that can intraoperatively be controlled by the orthopedic surgeon have been evaluated. These variables include lower leg alignment, soft tissue balance, joint line maintenance, and alignment, size, and fixation of the tibial and femoral component. Several studies have shown that tight control of lower leg alignment,^8-14 balancing of the soft tissues,^15-19 joint line maintenance,^20-23 component alignment,^24-28 component size,^29-34 and component fixation^35-40 can improve the outcomes of UKA and TKA. As a result, over the past 2 decades, several computer-assisted surgery systems have been developed with the goal of more accurate and reliable control of these factors, and thus improved outcomes of knee arthroplasty.

These systems differ with regard to the number and type of variables they control. Computer navigation systems aim to control one or more of these surgical variables, and several meta-analyses have shown that these systems, when compared to conventional surgery, improve mechanical axis accuracy, decrease the risk for mechanical axis outliers, and improve component positioning in TKA^41-49 and UKA surgery.^50,51 Interestingly, however, meta-analyses have failed to show the expected superiority in clinical outcomes following computer navigation compared to conventional knee arthroplasty.^48,52-55 Furthermore, authors have shown that, despite the fact that computer-navigated surgery increases the accuracy of mechanical alignment and surgical cutting, there is still room for improvement.⁵⁶ As a consequence, robotic-assisted systems have been developed.

Similar to computer navigation, these robotic-assisted systems aim to control the surgical variables; in addition, they aim to improve the surgical precision of the procedure. Interestingly, 2 recent studies have shown that robotic-assisted systems are superior to computer navigation systems with regard to less cutting time and less resection deviations in coronal and sagittal plane in a cadaveric study,⁵⁷ and shorter total surgery time, more accurate mechanical axis, and shorter hospital stay in a clinical study.⁵⁸ Although these results are promising, the exact role of robotic surgery in knee arthroplasty remains unclear. In this review, we aim to report the current state of robotic-assisted knee arthroplasty by discussing (1) the different robotic-assisted knee arthroplasty systems that are available for UKA and TKA surgery, (2) studies that assessed the role of robotic-assisted knee arthroplasty in controlling the aforementioned surgical variables, (3) cadaveric and clinical comparative studies that compared how accurate robotic-assisted and conventional knee surgery control these surgical variables, and (4) studies that assessed the cost-effectiveness of robotic-assisted knee arthroplasty surgery.

Robotic-Assisted Knee Arthroplasty Systems

Several systems have been developed over the years for knee arthroplasty, and these are usually defined as active, semi-active, or passive.⁵⁹ Active systems are capable of performing tasks or processes autonomously under the watchful eye of the surgeon, while passive systems do not perform actions independently but provide the surgeon with information. In semi-active systems, the surgical action is physically constrained in order to follow a predefined strategy.

In the United States, 3 robotic systems are FDA-approved for knee arthroplasty. The Stryker/Mako haptic guided robot (Mako Surgical Corp.) was introduced in 2005 and has been used for over 50,000 UKA procedures (Figure 1). There are nearly 300 robotic systems used nationally, as it has 20% of the market share for UKA in the United States. The Mako system is a semi-active tactile robotic system that requires preoperative imaging, after which a preoperative planning is performed. Intraoperatively, the robotic arm is under direct surgeon control and gives real-time tactile feedback during the procedure (Figure 2).

Furthermore, the surgeon can intraoperatively virtually adjust component positioning and alignment and move the knee through the range of motion, after which the system can provide information on alignment, component position, and balance of the soft tissue (eg, if the knee is overtight or lax through the flexion-arch).⁶⁰ This system has a burr that resects the bone and when the surgeon directs the burr outside the preplanned area, the burr stops and prevents unnecessary and unwanted resections (Figure 3).

The Navio Precision Free-Hand Sculptor (PFS) system (Blue Belt Technologies) has been used for 1500 UKA procedures, with 50 robots in use in the United States (Figure 4). This system is an image-free semi-active robotic system and has the same characteristics as the aforementioned Mako system.⁶¹ Finally, the OmniBotic robotic system (Omnilife Science) has been released for TKA and has been used for over 7300 procedures (Figure 5). This system has an automated cutting-guide technique in which the surgeon designs a virtual plan on the computer system. After this, the cutting-guides are placed by the robotic system at the planned location for all 5 femoral cuts (ie, distal, anterior chamfer, anterior, posterior chamfer, and posterior) and the surgeon then makes the final cuts.^57,62

Three robotic systems for knee arthroplasty surgery have been used in Europe. The Caspar system (URS Ortho) is an active robotic system in which a computed tomography (CT) scan is performed preoperatively, after which a virtual implantation is performed on the screen. The surgeon can then obtain information on lower leg alignment, gap balancing, and component positioning, and after an operative plan is made, the surgical resections are performed by the robot. Reflective markers are attached to the leg and all robotic movements are monitored using an infrared camera system. Any undesired motion will be detected by this camera system and will stop all movements.⁶³ A second and more frequently reported system in the literature is the active Robodoc surgical system (Curexo Technology Corporation). This system is designed for TKA and total hip arthroplasty (THA) surgery. Although initial studies reported a high incidence of system-related complications in THA,⁶⁴ the use of this system for TKA has frequently been reported in the literature.^56,63,65-69 A third robotic system that has been used in Europe is the Acrobot surgical system (Acrobot Company Ltd), which is an image-based semi-active robotic system⁷⁰ used for both UKA and TKA surgery.^70,71

Accuracy of Controlling Surgical Variables in Robotic-Assisted Knee Arthroplasty

Several studies have assessed the accuracy of robotic-assisted surgery in UKA surgery with regard to control of the aforementioned surgical variables. Pearle and colleagues⁷² assessed the mechanical axis accuracy of the Mako system in 10 patients undergoing medial UKA robotic-assisted surgery. They reported that the intraoperative registration lasted 7.5 minutes and the duration of time needed for robotic-assisted burring was 34.8 minutes. They compared the actual postoperative alignment at 6 weeks follow-up with the planned lower leg alignment and found that all measurements were within 1.6° of the planned lower leg alignment. Dunbar and colleagues⁷³ assessed the accuracy of component positioning of the Mako system in 20 patients undergoing medial UKA surgery by comparing preoperative and postoperative 3-dimensional CT scans. They found that the femoral component was within 0.8 mm and 0.9° in all directions and that the tibial component was within 0.9 mm and 1.7° in all directions. They concluded that the accuracy of component positioning with the Mako system was excellent. Finally, Plate and colleagues¹⁷ assessed the accuracy of soft tissue balancing in the Mako system in 52 patients undergoing medial UKA surgery. They compared the balance plan with the soft tissue balance after implantation and the Mako system quantified soft tissue balance as the amount of mm of the knee being tight or loose at 0°, 30°, 60°, 90°, and 110° of flexion. They found that at all flexion angles the ligament balancing was accurate up to 0.53 mm of the original plan. Furthermore, they noted that in 83% of cases the accuracy was within 1 mm at all flexion angles.

For the Navio system, Smith and colleagues⁷⁴ assessed the accuracy of component positioning using 20 synthetic femurs and tibia. They reported a maximum rotational error of 3.2°, an angular error of 1.46° in all orientations, and a maximum translational error of 1.18 mm for both the tibial and femoral implants. Lonner and colleagues⁷⁵ assessed the accuracy of component positioning in 25 cadaveric specimens. They found similar results as were found in the study of Smith and colleagues⁷⁴ and concluded that these results were similar to other semi-active robotic systems designed for UKA.

For TKA surgery, Ponder and colleagues⁷⁶ assessed the accuracy of the OmniBotic system and found that the average error in the anterior-posterior dimension between the targeted and measured cuts was -0.14 mm, and that the standard deviation in guide positioning for the distal, anterior chamfer, and posterior chamfer resections was 0.03° and 0.17 mm. Koenig and colleagues⁶² assessed the accuracy of the OmniBotic system in the first 100 cases and found that 98% of the cases were within 3° of the neutral mechanical axis. Furthermore, they found a learning curve with regard to tourniquet time between the first and second 10 patients in which they performed robotic-assisted TKA surgery. Siebert and colleagues⁶³ assessed the accuracy of mechanical alignment in the Caspar system in 70 patients treated with the robotic system. They found that the difference between preoperatively planned and postoperatively achieved mechanical alignment was 0.8°. Similarly, Bellemans and colleagues⁷⁷ assessed mechanical alignment and the positioning and rotation of the tibial and femoral components in a clinical study of 25 cases using the Caspar system. They noted that none of the patients had mechanical alignment, tibial or femoral component positioning, or rotation beyond 1° of the neutral axis. Liow and colleagues⁵⁶ assessed the accuracy of mechanical axis alignment and component sizing accuracy using the Robodoc system in 25 patients. They reported that the mean postoperative alignment was 0.4° valgus and that all cases were within 3° of the neutral mechanical axis. Furthermore, they reported a mean surgical time of 96 minutes and reported that preoperative planning yielded femoral and tibial component size accuracy of 100%.

These studies have shown that robotic systems for UKA and TKA are accurate in the surgical variables they aim to control. These studies validated tight control of mechanical axis alignment, decrease for outliers, and component positioning and rotation, and also found that the balancing of soft tissues was improved using robotic-assisted surgery.

Robotic-Assisted vs Conventional Knee Arthroplasty

Despite the fact that these systems are accurate in the variables they aim to control, these systems have to be compared to the gold standard of conventional knee arthroplasty. For UKA, Cobb and colleagues⁷⁰ performed a randomized clinical trial for patients treated undergoing UKA with robotic-assistance of the Acrobot systems compared to conventional UKA and assessed differences in mechanical accuracy. A total of 27 patients were randomly assigned to one of both treatments. They found that in the group of robotic-assisted surgery, 100% of the patients had a mechanical axis within 2° of neutral, while this was only 40% in the conventional UKA groups (difference P < .001). They also assessed the increase in functional outcomes and noted a trend towards improvement in performance with increasing accuracy at 6 weeks and 3 months postoperatively. Lonner and colleagues⁷⁸ also compared the tibial component positioning between robotic-assisted UKA surgery using the Mako system and conventional UKA surgery. The authors found that the variance in tibial slope, in coronal plane of the tibial component, and varus/valgus alignment were all larger with conventional UKA when compared to robotic-assisted UKA. Citak and colleagues⁷⁹ compared the accuracy of tibial and femoral implant positioning between robotic-assisted surgery using the Mako system and conventional UKA in a cadaveric study. They reported that the root mean square (RMS) error of femoral component was 1.9 mm and 3.7° in robotic-assisted surgery and 5.4 mm and 10.2° for conventional UKA, while the RMS error for tibial component were 1.4 mm and 5.0° for robotic-assisted surgery and 5.7 mm and 19.2° for conventional UKA surgery. MacCallum and colleagues⁸⁰ compared the tibial base plate position in a prospective clinical study of 177 patients treated with conventional UKA and 87 patients treated with robotic-assisted surgery using the Mako system. They found that surgery with robotic-assistance was more precise in the coronal and sagittal plane and was more accurate in coronal alignment when compared to conventional UKA. Finally, the first results of robotic-assisted UKA surgery have been presented. Coon and colleagues⁸¹ reported the preliminary results of a multicenter study of 854 patients and found a survivorship of 98.9% and satisfaction rate of 92% at minimum 2-year follow-up. Comparing these results to other large conventional UKA cohorts^82,83 suggests that robotic-assisted surgery may improve survivorship at short-term follow-up. However, comparative studies and studies with longer follow-up are necessary to assess the additional value of robotic-assisted UKA surgery. Due to the relatively new concept of robotic-assisted surgery, these studies have not been performed or published yet.

For TKA, several studies also have compared how these robotic-systems control the surgical variables compared to conventional TKA surgery. Siebert and colleagues⁶³ assessed mechanical axis accuracy and mechanical outliers following robotic-assisted TKA surgery using the Caspar system and conventional TKA surgery. They reported the difference between preoperative planned and postoperative achieved alignment was 0.8° for robotic-assisted surgery and 2.6° for conventional TKA surgery. Furthermore, they showed that 1 patient in the robotic-assisted group (1.4%) and 18 patients in the conventional TKA group (35%) had mechanical alignment greater than 3° from the neutral mechanical axis. Liow and colleagues⁵⁶ found similar differences in their prospective randomized study in which they reported that 0% outliers greater than 3° from the neutral mechanical axis were found in the robotic-assisted group while 19.4% of the patients in the conventional TKA group had mechanical axis outliers. They also assessed the joint-line outliers in both procedures and found that 3.2% had joint-line outliers greater than 5 mm in the robotic-assisted group compared to 20.6% in the conventional TKA group. Kim and colleagues⁶⁵ assessed implant accuracy in robotic-assisted surgery using the ROBODOC system and in conventional surgery and reported higher implant accuracy and fewer outliers using robotic-assisted surgery. Moon and colleagues⁶⁶ compared robotic-assisted TKA surgery using the Robodoc system with conventional TKA surgery in 10 cadavers. They found that robotic-assisted surgery had excellent precision in all planes and had better accuracy in femoral rotation alignment compared to conventional TKA surgery. Park and Lee⁶⁷ compared Robodoc robotic-assisted TKA surgery with conventional TKA surgery in a randomized clinical trial of 72 patients. They found that robotic-assisted surgery had definitive advantages in preoperative planning, accuracy of the procedure, and postoperative follow-up regarding femoral and tibial component flexion angles. Finally, Song and colleagues^68,69 performed 2 randomized clinical trials in which they compared mechanical axis alignment, component positioning, soft tissue balancing, and patient preference between conventional TKA surgery and robotic-assisted surgery using the Robodoc system. In the first study,⁶⁸ they simultaneously performed robotic-assisted surgery in one leg and conventional TKA surgery in the other leg. They found that robotic-assisted surgery resulted in less outlier in mechanical axis and component positioning. Furthermore, they found at latest follow-up of 2 years that 12 patients preferred the leg treated with robotic-assisted surgery while 6 preferred the conventional leg. Despite this finding, no significant differences in functional outcome scores were detected between both treatment options. Furthermore, they found that flexion-extension balance was achieved in 92% of patients treated with robotic-assisted TKA surgery and in 77% of patients treated with conventional TKA surgery. In the other study,⁶⁹ the authors found that more patients treated with robotic-assisted surgery had <2 mm flexion-extension gap and more satisfactory posterior cruciate ligament tension when compared to conventional surgery.

These studies have shown that robotic-assisted surgery is accurate in controlling surgical variables, such as mechanical lower leg alignment, maintaining joint-line, implant positioning, and soft tissue balancing. Furthermore, these studies have shown that controlling these variables is better than the current gold standard of manual knee arthroplasty. Until now, not many studies have assessed survivorship of robotic-assisted surgery. Furthermore, no studies have, to our knowledge, compared survivorship of robotic-assisted with conventional knee replacement surgery. Finally, studies comparing functional outcomes following robotic-assisted surgery and conventional knee arthroplasty surgery are frequently underpowered due to their small sample sizes.^68,70 Since many studies have shown that the surgical variables are more tightly controlled using robotic-assisted surgery when compared to conventional surgery, large comparative studies are necessary to assess the role of robotic-assisted surgery in functional outcomes and survivorship of UKA and TKA.

Cost-Effectiveness of Robotic-Assisted Surgery

High initial capital costs of robotic-assisted surgery is one of the factors that constitute a barrier to the widespread implementation of this technique. Multiple authors have suggested that improved implant survivorship afforded by robotic-assisted surgery may justify the expenditure from both societal and provider perspective.^84-86 Two studies have performed a cost-effectiveness analysis for UKA surgery. Swank and colleagues⁸⁴ reviewed the hospital expenditures and profits associated with robot-assisted knee arthroplasty, citing upfront costs of approximately $800,000. The authors estimated a mean per-case contribution profit of $5790 for robotic-assisted UKA, assuming an inpatient-to-outpatient ratio of 1 to 3. Based on this data, Swank and colleagues84 proposed that the capital costs of robotic-assisted UKA may be recovered in as little as 2 years when in the first 3 consecutive years 50, 70, and 90 cases were performed using robotic-assisted UKA. Moschetti and colleagues⁸⁵ recently published the first formal cost-effectiveness analysis of robotic-assisted compared to manual UKA. The authors used an annual revision risk of 0.55% for the first 2 years following robot-assisted UKA, based on the aforementioned presented data by Coon and colleagues.⁸¹ They based their data on the Mako system and assumed an initial capital expenditure of $934,728 with annual servicing costs of 10% (discounted annually) for 4 years thereafter, resulting in a total cost of the robotic system of $1.362 million. These costs were divided by the number of patients estimated to undergo robotic-assisted UKA per year, which was varied to estimate the effect of case volume on cost-effectiveness. The authors reported that robotic-assisted UKA was associated with higher lifetime costs and net utilities compared to manual UKA, at an incremental cost-effectiveness ratio of $47,180 per quality-adjusted life year (QALY) in a high-volume center. This falls well within the societal willingness-to-pay threshold of $100,000/QALY. Sensitivity analysis showed that robotic-assisted UKA is cost-effective under the following conditions: (1) centers performing at least 94 cases annually, (2) in patients younger than age 67 years, and (3) 2-year revision rate does not exceed 1.2%. While the results of this initial analysis are promising, follow-up cost-effectiveness analysis studies will be required as long-term survivorship data become available.

Conclusion

Tighter control of intraoperative surgical variables, such as lower leg alignment, soft tissue balance, joint-line maintenance, and component alignment and positioning, have been associated with improved survivorship and functional outcomes. Upon reviewing the available literature on robotic-assisted surgery, it becomes clear that this technique can improve the accuracy of these surgical variables and is superior to conventional manual UKA and TKA. Although larger and comparative survivorship studies are necessary to compare robotic-assisted knee arthroplasty to conventional techniques, the early results and cost-effectiveness analysis seem promising.

INDIAN WELLS, CALIF. – Using chlorhexidine-alcohol preoperative skin antisepsis at the time of abdominal hysterectomy is associated with a lower incidence of surgical site infections (SSIs), compared with using povidone-iodine antiseptic solution, a large retrospective study showed.

“Surgical site infections have been linked to longer hospital stays, higher readmission rates, and overall increased healthcare costs,” Ali Bazzi, the lead study author, said at the annual scientific meeting of the Society of Gynecologic Surgeons. “Preoperative topical skin antiseptics have decreased the rate of SSIs over the years and have led to improved patient outcomes. Current published guidelines for skin preparations, specifically abdominal hysterectomies, do not routinely specify a choice of antiseptic. With greater than 500,000 hysterectomies performed each year in the United States, and about half done via laparotomy, this can have significant clinical implications.”

In an effort to determine whether the choice of preoperative topical antisepsis independently affects SSIs, Mr. Bazzi, a fourth-year medical student at the University of Michigan, Ann Arbor, and his associates in the university’s department of gynecologic oncology evaluated chlorhexidine-gluconate in alcohol versus povidone-iodine in aqueous solution. The second objective focused on determining certain patient factors and operative predictors of SSIs.

The researchers used the Michigan Surgical Quality Collaborative database to perform a retrospective cohort analysis of patients who underwent abdominal hysterectomy from July 2012 to February 2015. The primary outcome was diagnosis of a superficial, deep, or organ space SSI within 30 days of surgery, while the primary predictor was whether the individual cases received either the chlorhexidine-alcohol or the povidone-iodine antiseptic solution.

The researchers excluded cases with missing data, preoperative sepsis or emergent operative cases, and patients on chronic steroids due to immunosuppression, since these cases were associated with a higher than baseline risk of developing SSIs. Other types of skin preparation agents did not meet a large enough sample size and thus were underpowered. These cases were not included in the final analysis. Multivariate logistic regression models estimated the independent effect of skin antiseptic choice on the rate of SSI.

Mr. Bazzi reported results from 5,074 abdominal hysterectomies. Compared with patients in the povidone-iodine group, those in the chlorhexidine-alcohol group had several medical comorbidities, demographic and perioperative factors associated with the development of SSIs, including being more likely to have a BMI of 30 kg/m² or greater; American Society of Anesthesiology Class of 3 or greater; dependent functional status; malignancy as a preoperative indication for surgery; estimated blood loss of greater than 250 cc; and surgery lasting longer than 3 hours.

The overall rate of any SSI was 3.6%. The unadjusted SSI rates based on antiseptic choice were 3.5% in the chlorhexidine-alcohol group and 3.8% in the povidone-iodine group. After using multivariate logistic regression adjusted for population differences, the researchers determined that chlorhexidine-alcohol was associated with a 30% lower odds of developing SSIs, compared with those in the povidone-iodine group (odds ratio, 0.71; 95% confidence interval, 0.51-0.98; P = .037).

Mr. Bazzi, who begins an ob.gyn. residency at St. John Hospital and Medical Center in Detroit in July 2016, acknowledged that other qualitative factors not included in the analysis could affect the incidence of SSIs, such as operative experience, surgical technique, resident exposure, type of ligature used, and excessive use of electrosurgical devices.

He noted that future randomized, controlled trials of skin antiseptic preparations given prior to abdominal hysterectomy would be helpful. For now, “we believe that future guidelines should specify the choice of antisepsis prior to abdominal hysterectomy,” he said at the meeting, which is jointly sponsored by the American College of Surgeons.

Mr. Bazzi reported having no financial disclosures.

[email protected]

INDIAN WELLS, CALIF. – Using chlorhexidine-alcohol preoperative skin antisepsis at the time of abdominal hysterectomy is associated with a lower incidence of surgical site infections (SSIs), compared with using povidone-iodine antiseptic solution, a large retrospective study showed.

“Surgical site infections have been linked to longer hospital stays, higher readmission rates, and overall increased healthcare costs,” Ali Bazzi, the lead study author, said at the annual scientific meeting of the Society of Gynecologic Surgeons. “Preoperative topical skin antiseptics have decreased the rate of SSIs over the years and have led to improved patient outcomes. Current published guidelines for skin preparations, specifically abdominal hysterectomies, do not routinely specify a choice of antiseptic. With greater than 500,000 hysterectomies performed each year in the United States, and about half done via laparotomy, this can have significant clinical implications.”

In an effort to determine whether the choice of preoperative topical antisepsis independently affects SSIs, Mr. Bazzi, a fourth-year medical student at the University of Michigan, Ann Arbor, and his associates in the university’s department of gynecologic oncology evaluated chlorhexidine-gluconate in alcohol versus povidone-iodine in aqueous solution. The second objective focused on determining certain patient factors and operative predictors of SSIs.

The researchers used the Michigan Surgical Quality Collaborative database to perform a retrospective cohort analysis of patients who underwent abdominal hysterectomy from July 2012 to February 2015. The primary outcome was diagnosis of a superficial, deep, or organ space SSI within 30 days of surgery, while the primary predictor was whether the individual cases received either the chlorhexidine-alcohol or the povidone-iodine antiseptic solution.

The researchers excluded cases with missing data, preoperative sepsis or emergent operative cases, and patients on chronic steroids due to immunosuppression, since these cases were associated with a higher than baseline risk of developing SSIs. Other types of skin preparation agents did not meet a large enough sample size and thus were underpowered. These cases were not included in the final analysis. Multivariate logistic regression models estimated the independent effect of skin antiseptic choice on the rate of SSI.

Mr. Bazzi reported results from 5,074 abdominal hysterectomies. Compared with patients in the povidone-iodine group, those in the chlorhexidine-alcohol group had several medical comorbidities, demographic and perioperative factors associated with the development of SSIs, including being more likely to have a BMI of 30 kg/m² or greater; American Society of Anesthesiology Class of 3 or greater; dependent functional status; malignancy as a preoperative indication for surgery; estimated blood loss of greater than 250 cc; and surgery lasting longer than 3 hours.

The overall rate of any SSI was 3.6%. The unadjusted SSI rates based on antiseptic choice were 3.5% in the chlorhexidine-alcohol group and 3.8% in the povidone-iodine group. After using multivariate logistic regression adjusted for population differences, the researchers determined that chlorhexidine-alcohol was associated with a 30% lower odds of developing SSIs, compared with those in the povidone-iodine group (odds ratio, 0.71; 95% confidence interval, 0.51-0.98; P = .037).

Mr. Bazzi, who begins an ob.gyn. residency at St. John Hospital and Medical Center in Detroit in July 2016, acknowledged that other qualitative factors not included in the analysis could affect the incidence of SSIs, such as operative experience, surgical technique, resident exposure, type of ligature used, and excessive use of electrosurgical devices.

He noted that future randomized, controlled trials of skin antiseptic preparations given prior to abdominal hysterectomy would be helpful. For now, “we believe that future guidelines should specify the choice of antisepsis prior to abdominal hysterectomy,” he said at the meeting, which is jointly sponsored by the American College of Surgeons.

Mr. Bazzi reported having no financial disclosures.

[email protected]

INDIAN WELLS, CALIF. – Using chlorhexidine-alcohol preoperative skin antisepsis at the time of abdominal hysterectomy is associated with a lower incidence of surgical site infections (SSIs), compared with using povidone-iodine antiseptic solution, a large retrospective study showed.

“Surgical site infections have been linked to longer hospital stays, higher readmission rates, and overall increased healthcare costs,” Ali Bazzi, the lead study author, said at the annual scientific meeting of the Society of Gynecologic Surgeons. “Preoperative topical skin antiseptics have decreased the rate of SSIs over the years and have led to improved patient outcomes. Current published guidelines for skin preparations, specifically abdominal hysterectomies, do not routinely specify a choice of antiseptic. With greater than 500,000 hysterectomies performed each year in the United States, and about half done via laparotomy, this can have significant clinical implications.”

In an effort to determine whether the choice of preoperative topical antisepsis independently affects SSIs, Mr. Bazzi, a fourth-year medical student at the University of Michigan, Ann Arbor, and his associates in the university’s department of gynecologic oncology evaluated chlorhexidine-gluconate in alcohol versus povidone-iodine in aqueous solution. The second objective focused on determining certain patient factors and operative predictors of SSIs.

The researchers used the Michigan Surgical Quality Collaborative database to perform a retrospective cohort analysis of patients who underwent abdominal hysterectomy from July 2012 to February 2015. The primary outcome was diagnosis of a superficial, deep, or organ space SSI within 30 days of surgery, while the primary predictor was whether the individual cases received either the chlorhexidine-alcohol or the povidone-iodine antiseptic solution.

The researchers excluded cases with missing data, preoperative sepsis or emergent operative cases, and patients on chronic steroids due to immunosuppression, since these cases were associated with a higher than baseline risk of developing SSIs. Other types of skin preparation agents did not meet a large enough sample size and thus were underpowered. These cases were not included in the final analysis. Multivariate logistic regression models estimated the independent effect of skin antiseptic choice on the rate of SSI.

Mr. Bazzi reported results from 5,074 abdominal hysterectomies. Compared with patients in the povidone-iodine group, those in the chlorhexidine-alcohol group had several medical comorbidities, demographic and perioperative factors associated with the development of SSIs, including being more likely to have a BMI of 30 kg/m² or greater; American Society of Anesthesiology Class of 3 or greater; dependent functional status; malignancy as a preoperative indication for surgery; estimated blood loss of greater than 250 cc; and surgery lasting longer than 3 hours.

The overall rate of any SSI was 3.6%. The unadjusted SSI rates based on antiseptic choice were 3.5% in the chlorhexidine-alcohol group and 3.8% in the povidone-iodine group. After using multivariate logistic regression adjusted for population differences, the researchers determined that chlorhexidine-alcohol was associated with a 30% lower odds of developing SSIs, compared with those in the povidone-iodine group (odds ratio, 0.71; 95% confidence interval, 0.51-0.98; P = .037).

Mr. Bazzi, who begins an ob.gyn. residency at St. John Hospital and Medical Center in Detroit in July 2016, acknowledged that other qualitative factors not included in the analysis could affect the incidence of SSIs, such as operative experience, surgical technique, resident exposure, type of ligature used, and excessive use of electrosurgical devices.

He noted that future randomized, controlled trials of skin antiseptic preparations given prior to abdominal hysterectomy would be helpful. For now, “we believe that future guidelines should specify the choice of antisepsis prior to abdominal hysterectomy,” he said at the meeting, which is jointly sponsored by the American College of Surgeons.

Mr. Bazzi reported having no financial disclosures.

[email protected]