MDedge Rheumatology

Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.

Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.

However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.

“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.

The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.

The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.

Symptoms developed within 11.5 days for 97.5% of patients in the study.

Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.

In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.

“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.

Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.

“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.

Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.

“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
 

SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.

Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.

Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.

However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.

“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.

The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.

The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.

Symptoms developed within 11.5 days for 97.5% of patients in the study.

Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.

In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.

“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.

Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.

“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.

Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.

“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
 

SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.

Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.

Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.

However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.

“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.

The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.

The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.

Symptoms developed within 11.5 days for 97.5% of patients in the study.

Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.

In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.

“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.

Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.

“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.

Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.

“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
 

SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.

Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.

Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.

“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”

The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.

Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.

However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.

That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.

The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.

All PPE samples tested negative, except for the front of one shoe.

“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.

While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).

“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”

Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.

SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.

The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.

Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.

Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.

“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”

The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.

Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.

However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.

That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.

The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.

All PPE samples tested negative, except for the front of one shoe.

“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.

While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).

“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”

Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.

SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.

The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.

Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.

Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.

“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”

The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.

Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.

However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.

That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.

The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.

All PPE samples tested negative, except for the front of one shoe.

“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.

While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).

“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”

Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.

SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.

Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).

Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.

The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”

While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.

The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.

In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.

An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.

In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.

However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.

The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.

The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.

The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.

Are healthcare systems prepared?

Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.

It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.

Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”

Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.

He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”

Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”

Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.

If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”

Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.

Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.

This article first appeared on Medscape.com.

Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.

Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).

Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.

The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”

While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.

The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.

In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.

An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.

In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.

However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.

The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.

The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.

The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.

Are healthcare systems prepared?

Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.

It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.

Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”

Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.

He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”

Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”

Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.

If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”

Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.

Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.

This article first appeared on Medscape.com.

Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.

Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).

Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.

The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”

While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.

The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.

In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.

An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.

In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.

However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.

The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.

The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.

The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.

Are healthcare systems prepared?

Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.

It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.

Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”

Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.

He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”

Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”

Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.

If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”

Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.

Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.

This article first appeared on Medscape.com.

MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.

“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Several audience members were less restrained in their assessments.

“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.

Bruce Jancin/MDedge News

“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.

Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”

That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.

A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
 

In the OA pipeline

“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.

Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.

“I’m not sure this is going anywhere,” Dr. Ruderman commented.

Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.

“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.

This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.

Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)

Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.

“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.

Welcome to the wild, wild West

Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.

“It’s the wild, wild West out there,” the rheumatologist warned.

He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.

As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.

These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.

“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.

The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.

Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.

“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”


 

On a brighter note

Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.

Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.

“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”

As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.

“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.

He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.

Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.

Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.

“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Several audience members were less restrained in their assessments.

“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.

Bruce Jancin/MDedge News

“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.

Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”

That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.

A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
 

In the OA pipeline

“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.

Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.

“I’m not sure this is going anywhere,” Dr. Ruderman commented.

Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.

“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.

This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.

Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)

Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.

“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.

Welcome to the wild, wild West

Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.

“It’s the wild, wild West out there,” the rheumatologist warned.

He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.

As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.

These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.

“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.

The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.

Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.

“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”


 

On a brighter note

Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.

Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.

“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”

As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.

“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.

He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.

Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.

Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.

“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Several audience members were less restrained in their assessments.

“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.

Bruce Jancin/MDedge News

“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.

Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”

That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.

A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
 

In the OA pipeline

“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.

Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.

“I’m not sure this is going anywhere,” Dr. Ruderman commented.

Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.

“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.

This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.

Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)

Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.

“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.

Welcome to the wild, wild West

Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.

“It’s the wild, wild West out there,” the rheumatologist warned.

He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.

As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.

These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.

“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.

The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.

Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.

“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”


 

On a brighter note

Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.

Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.

“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”

As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.

“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.

He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.

Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.

Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.

bjancin@mdedge.com

A team of researchers has discovered important commonalities between SARS-CoV-2 and SARS-CoV infection that could lead to a potential targets for antiviral intervention.

Courtesy NIAID-RML

Markus Hoffmann, of the Leibniz Institute for Primate Research, Göttingen, Germany, and a team of investigators also found that antibody responses raised against SARS-S during infection or vaccination might offer some level of protection against SARS-CoV-2 infection. Their findings were published in Cell.

In order for coronaviruses to enter a cell, they must first bind their viral spike (S) proteins to cellular receptors and depend on S protein priming by host cell proteases. The study found that the SARS-CoV-2, causal agent for COVID-19, uses the same SARS-CoV receptor, ACE2, for entry and uses the serine protease TMPRSS2 for S protein priming as the original SARS-CoV-1 (SARS). Importantly, the researchers also found that the cellular serine protease TMPRSS2 primes SARS-CoV-2-S for entry and that a serine protease inhibitor blocks SARS-CoV-2 infection of lung cells, providing opportunities for potential therapeutic intervention.

The researchers performed a sequence analysis that showed SARS-CoV-2 clusters with SARS-CoV–related viruses from bats, of which some – but not all – can use ACE2 for host cell entry. Further analysis of the receptor binding motif known to make contact with ACE2 showed that most amino acid residues essential for ACE2 binding by SARS-S were conserved in SARS-2-S but were absent from S proteins of those SARS-related coronaviruses previously found not to use ACE2.

In addition, the researchers found that SARS-CoV-2–infected BHK-21 cells transfected to express ACE2 with high efficiency, but not the parental BHK-21 cells indicating that SARS-CoV-2-S, like the original SARS virus S protein, uses ACE2 for cellular entry.

Using cultured cells, the researchers found that the protease inhibitor, camostat mesylate, inhibited SARS-S and SARS-2-S entry into primary human lung cells, demonstrating that SARS-CoV-2 can use TMPRSS2 for S protein priming and that camostat mesylate can block SARS-CoV-2 infection of lung cells. Camostat mesylate has been used as a therapy for some forms of cancer and other viral infections.

In addition to their research on the protease inhibitor, the researchers also found that sera from convalescent SARS patients cross-neutralized SARS-2-S–driven entry. They found that four sera obtained from three convalescent SARS patients inhibited SARS-S entry into cell lines in a concentration dependent fashion.

“We demonstrate that SARS-CoV-2 uses the SARS55 CoV receptor, ACE2, for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S–driven entry,” the authors concluded.

The study was supported by BMBF (RAPID Consortium) and German Research Foundation (DFG). The authors reported that they had no conflicts.
 

mlesney@mdedge.com

SOURCE: Hoffmann M et al. Cell 2020. doi: 10.1016/j.cell.2020.02.052.

A team of researchers has discovered important commonalities between SARS-CoV-2 and SARS-CoV infection that could lead to a potential targets for antiviral intervention.

Courtesy NIAID-RML

Markus Hoffmann, of the Leibniz Institute for Primate Research, Göttingen, Germany, and a team of investigators also found that antibody responses raised against SARS-S during infection or vaccination might offer some level of protection against SARS-CoV-2 infection. Their findings were published in Cell.

In order for coronaviruses to enter a cell, they must first bind their viral spike (S) proteins to cellular receptors and depend on S protein priming by host cell proteases. The study found that the SARS-CoV-2, causal agent for COVID-19, uses the same SARS-CoV receptor, ACE2, for entry and uses the serine protease TMPRSS2 for S protein priming as the original SARS-CoV-1 (SARS). Importantly, the researchers also found that the cellular serine protease TMPRSS2 primes SARS-CoV-2-S for entry and that a serine protease inhibitor blocks SARS-CoV-2 infection of lung cells, providing opportunities for potential therapeutic intervention.

The researchers performed a sequence analysis that showed SARS-CoV-2 clusters with SARS-CoV–related viruses from bats, of which some – but not all – can use ACE2 for host cell entry. Further analysis of the receptor binding motif known to make contact with ACE2 showed that most amino acid residues essential for ACE2 binding by SARS-S were conserved in SARS-2-S but were absent from S proteins of those SARS-related coronaviruses previously found not to use ACE2.

In addition, the researchers found that SARS-CoV-2–infected BHK-21 cells transfected to express ACE2 with high efficiency, but not the parental BHK-21 cells indicating that SARS-CoV-2-S, like the original SARS virus S protein, uses ACE2 for cellular entry.

Using cultured cells, the researchers found that the protease inhibitor, camostat mesylate, inhibited SARS-S and SARS-2-S entry into primary human lung cells, demonstrating that SARS-CoV-2 can use TMPRSS2 for S protein priming and that camostat mesylate can block SARS-CoV-2 infection of lung cells. Camostat mesylate has been used as a therapy for some forms of cancer and other viral infections.

In addition to their research on the protease inhibitor, the researchers also found that sera from convalescent SARS patients cross-neutralized SARS-2-S–driven entry. They found that four sera obtained from three convalescent SARS patients inhibited SARS-S entry into cell lines in a concentration dependent fashion.

“We demonstrate that SARS-CoV-2 uses the SARS55 CoV receptor, ACE2, for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S–driven entry,” the authors concluded.

The study was supported by BMBF (RAPID Consortium) and German Research Foundation (DFG). The authors reported that they had no conflicts.
 

mlesney@mdedge.com

SOURCE: Hoffmann M et al. Cell 2020. doi: 10.1016/j.cell.2020.02.052.

A team of researchers has discovered important commonalities between SARS-CoV-2 and SARS-CoV infection that could lead to a potential targets for antiviral intervention.

Courtesy NIAID-RML

Markus Hoffmann, of the Leibniz Institute for Primate Research, Göttingen, Germany, and a team of investigators also found that antibody responses raised against SARS-S during infection or vaccination might offer some level of protection against SARS-CoV-2 infection. Their findings were published in Cell.

In order for coronaviruses to enter a cell, they must first bind their viral spike (S) proteins to cellular receptors and depend on S protein priming by host cell proteases. The study found that the SARS-CoV-2, causal agent for COVID-19, uses the same SARS-CoV receptor, ACE2, for entry and uses the serine protease TMPRSS2 for S protein priming as the original SARS-CoV-1 (SARS). Importantly, the researchers also found that the cellular serine protease TMPRSS2 primes SARS-CoV-2-S for entry and that a serine protease inhibitor blocks SARS-CoV-2 infection of lung cells, providing opportunities for potential therapeutic intervention.

The researchers performed a sequence analysis that showed SARS-CoV-2 clusters with SARS-CoV–related viruses from bats, of which some – but not all – can use ACE2 for host cell entry. Further analysis of the receptor binding motif known to make contact with ACE2 showed that most amino acid residues essential for ACE2 binding by SARS-S were conserved in SARS-2-S but were absent from S proteins of those SARS-related coronaviruses previously found not to use ACE2.

In addition, the researchers found that SARS-CoV-2–infected BHK-21 cells transfected to express ACE2 with high efficiency, but not the parental BHK-21 cells indicating that SARS-CoV-2-S, like the original SARS virus S protein, uses ACE2 for cellular entry.

Using cultured cells, the researchers found that the protease inhibitor, camostat mesylate, inhibited SARS-S and SARS-2-S entry into primary human lung cells, demonstrating that SARS-CoV-2 can use TMPRSS2 for S protein priming and that camostat mesylate can block SARS-CoV-2 infection of lung cells. Camostat mesylate has been used as a therapy for some forms of cancer and other viral infections.

In addition to their research on the protease inhibitor, the researchers also found that sera from convalescent SARS patients cross-neutralized SARS-2-S–driven entry. They found that four sera obtained from three convalescent SARS patients inhibited SARS-S entry into cell lines in a concentration dependent fashion.

“We demonstrate that SARS-CoV-2 uses the SARS55 CoV receptor, ACE2, for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S–driven entry,” the authors concluded.

The study was supported by BMBF (RAPID Consortium) and German Research Foundation (DFG). The authors reported that they had no conflicts.
 

mlesney@mdedge.com

SOURCE: Hoffmann M et al. Cell 2020. doi: 10.1016/j.cell.2020.02.052.

Hospital-related infections have been widely reported during the ongoing coronavirus outbreak, with healthcare professionals bearing a disproportionate risk. However, a proactive response in Hong Kong’s public hospital system appears to have bucked this trend and successfully protected both patients and staff from SARS-CoV-2, according to a study published online today in Infection Control & Hospital Epidemiology.

During the first 42 days of the outbreak, the 43 hospitals in the network tested 1275 suspected cases and treated 42 patients with confirmed COVID-19, the disease caused by SARS-CoV-2 infection. Yet, there were no nosocomial infections or infections among healthcare personnel, report Vincent C.C. Cheng, MD, FRCPath, the hospital’s infection control officer, and colleagues.

Cheng and colleagues note that 11 out of 413 healthcare workers who treat patients with confirmed infections had unprotected exposure and were in quarantine for 14 days, but none became ill.

In comparison, they note, the 2003 SARS outbreak saw almost 60% of nosocomial cases occurring in healthcare workers.

Proactive bundle

The Hong Kong success story may be due to a stepped-up proactive bundle of measures that included enhanced laboratory surveillance, early airborne infection isolation, and rapid-turnaround molecular diagnostics. Other strategies included staff forums and one-on-one discussions about infection control, employee training in protective equipment use, hand-hygiene compliance enforcement, and contact tracing for workers with unprotected exposure.

In addition, surgical masks were provided for all healthcare workers, patients, and visitors to clinical areas, a practice previously associated with reduced in-hospital transmission during influenza outbreaks, the authors note.

Hospitals also mandated use of personal protective equipment (PPE) for aerosol-generating procedures (AGPs), such as endotracheal intubation, open suctioning, and high-flow oxygen use, as AGPs had been linked to nosocomial transmission to healthcare workers during the 2003 SARS outbreak.

The infection control measures, which were part of a preparedness plan developed after the SARS outbreak, were initiated on December 31, when the first reports of a cluster of infections came from Wuhan, China.

As the outbreak evolved, the Hong Kong hospitals quickly widened the epidemiologic criteria for screening, from initially including only those who had been to a wet market in Wuhan within 14 days of symptom onset, to eventually including anyone who had been to Hubei province, been in a medical facility in mainland China, or in contact with a known case.  

All suspected cases were sent to an airborne-infection isolation room (AIIR) or a ward with at least a meter of space between patients.

“Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2,” the authors write. “Vigilance in hand hygiene practice, wearing of surgical mask in the hospital, and appropriate use of PPE in patient care, especially [when] performing AGPs, are the key infection control measures to prevent nosocomial transmission of SARS-CoV-2 even before the availability of effective antiviral agents and vaccine.”

Asked for his perspective on the report, Aaron E. Glatt, MD, chairman of the department of medicine and chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York, said that apart from the widespread issuing of surgical masks to workers, patients, and visitors, the measures taken in Hong Kong are not different from standard infection-control practices in American hospitals. Glatt, who is also a hospital epidemiologist, said it was unclear how much impact the masks would have.

“Although the infection control was impressive, I don’t see any evidence of a difference in care,” he told Medscape Medical News.

Could zero infection transmission be achieved in the more far-flung and variable settings of hospitals across the United States? “The ability to get zero transmission is only possible if people adhere to the strictest infection-control guidelines,” Glatt said. “That is clearly the goal, and it will take time to see if our existing strict guidelines are sufficient to maintain zero or close to zero contamination and transmission rates in our hospitals.”

Rather than looking to change US practices, he stressed adherence to widely established tenets of care. “It’s critically important to keep paying close attention to the basics, to the simple blocking and tackling, and to identify which patients are at risk, and therefore, when workers need protective equipment,” he said.

“Follow the recommended standards,” continued Glatt, who is also a spokesperson for the Infectious Diseases Society of America and did not participate in this study.

In a finding from an ancillary pilot experiment, the Hong Kong researchers found exhaled air from a patient with a moderate coronavirus load showed no evidence of the virus, whether the patient was breathing normally or heavily, speaking, or coughing. And spot tests around the room detected the virus in just one location.

“We may not be able to make a definite conclusion based on the analysis of a single patient,” the authors write. “However, it may help to reassure our staff that the exhaled air may be rapidly diluted inside the AIIR with 12 air changes per hour, or probably the SARS-CoV-2 may not be predominantly transmitted by [the] airborne route.”

However, a recent Singapore study showed widespread environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding, underlining the need for strict adherence to environmental and hand hygiene. Post-cleaning samples tested negative, suggesting that standard decontamination practices are effective. 

This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health, Hong Kong Special Administrative Region; and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education of China. The authors and Glatt have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Hospital-related infections have been widely reported during the ongoing coronavirus outbreak, with healthcare professionals bearing a disproportionate risk. However, a proactive response in Hong Kong’s public hospital system appears to have bucked this trend and successfully protected both patients and staff from SARS-CoV-2, according to a study published online today in Infection Control & Hospital Epidemiology.

During the first 42 days of the outbreak, the 43 hospitals in the network tested 1275 suspected cases and treated 42 patients with confirmed COVID-19, the disease caused by SARS-CoV-2 infection. Yet, there were no nosocomial infections or infections among healthcare personnel, report Vincent C.C. Cheng, MD, FRCPath, the hospital’s infection control officer, and colleagues.

Cheng and colleagues note that 11 out of 413 healthcare workers who treat patients with confirmed infections had unprotected exposure and were in quarantine for 14 days, but none became ill.

In comparison, they note, the 2003 SARS outbreak saw almost 60% of nosocomial cases occurring in healthcare workers.

Proactive bundle

The Hong Kong success story may be due to a stepped-up proactive bundle of measures that included enhanced laboratory surveillance, early airborne infection isolation, and rapid-turnaround molecular diagnostics. Other strategies included staff forums and one-on-one discussions about infection control, employee training in protective equipment use, hand-hygiene compliance enforcement, and contact tracing for workers with unprotected exposure.

In addition, surgical masks were provided for all healthcare workers, patients, and visitors to clinical areas, a practice previously associated with reduced in-hospital transmission during influenza outbreaks, the authors note.

Hospitals also mandated use of personal protective equipment (PPE) for aerosol-generating procedures (AGPs), such as endotracheal intubation, open suctioning, and high-flow oxygen use, as AGPs had been linked to nosocomial transmission to healthcare workers during the 2003 SARS outbreak.

The infection control measures, which were part of a preparedness plan developed after the SARS outbreak, were initiated on December 31, when the first reports of a cluster of infections came from Wuhan, China.

As the outbreak evolved, the Hong Kong hospitals quickly widened the epidemiologic criteria for screening, from initially including only those who had been to a wet market in Wuhan within 14 days of symptom onset, to eventually including anyone who had been to Hubei province, been in a medical facility in mainland China, or in contact with a known case.  

All suspected cases were sent to an airborne-infection isolation room (AIIR) or a ward with at least a meter of space between patients.

“Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2,” the authors write. “Vigilance in hand hygiene practice, wearing of surgical mask in the hospital, and appropriate use of PPE in patient care, especially [when] performing AGPs, are the key infection control measures to prevent nosocomial transmission of SARS-CoV-2 even before the availability of effective antiviral agents and vaccine.”

Asked for his perspective on the report, Aaron E. Glatt, MD, chairman of the department of medicine and chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York, said that apart from the widespread issuing of surgical masks to workers, patients, and visitors, the measures taken in Hong Kong are not different from standard infection-control practices in American hospitals. Glatt, who is also a hospital epidemiologist, said it was unclear how much impact the masks would have.

“Although the infection control was impressive, I don’t see any evidence of a difference in care,” he told Medscape Medical News.

Could zero infection transmission be achieved in the more far-flung and variable settings of hospitals across the United States? “The ability to get zero transmission is only possible if people adhere to the strictest infection-control guidelines,” Glatt said. “That is clearly the goal, and it will take time to see if our existing strict guidelines are sufficient to maintain zero or close to zero contamination and transmission rates in our hospitals.”

Rather than looking to change US practices, he stressed adherence to widely established tenets of care. “It’s critically important to keep paying close attention to the basics, to the simple blocking and tackling, and to identify which patients are at risk, and therefore, when workers need protective equipment,” he said.

“Follow the recommended standards,” continued Glatt, who is also a spokesperson for the Infectious Diseases Society of America and did not participate in this study.

In a finding from an ancillary pilot experiment, the Hong Kong researchers found exhaled air from a patient with a moderate coronavirus load showed no evidence of the virus, whether the patient was breathing normally or heavily, speaking, or coughing. And spot tests around the room detected the virus in just one location.

“We may not be able to make a definite conclusion based on the analysis of a single patient,” the authors write. “However, it may help to reassure our staff that the exhaled air may be rapidly diluted inside the AIIR with 12 air changes per hour, or probably the SARS-CoV-2 may not be predominantly transmitted by [the] airborne route.”

However, a recent Singapore study showed widespread environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding, underlining the need for strict adherence to environmental and hand hygiene. Post-cleaning samples tested negative, suggesting that standard decontamination practices are effective. 

This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health, Hong Kong Special Administrative Region; and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education of China. The authors and Glatt have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Hospital-related infections have been widely reported during the ongoing coronavirus outbreak, with healthcare professionals bearing a disproportionate risk. However, a proactive response in Hong Kong’s public hospital system appears to have bucked this trend and successfully protected both patients and staff from SARS-CoV-2, according to a study published online today in Infection Control & Hospital Epidemiology.

During the first 42 days of the outbreak, the 43 hospitals in the network tested 1275 suspected cases and treated 42 patients with confirmed COVID-19, the disease caused by SARS-CoV-2 infection. Yet, there were no nosocomial infections or infections among healthcare personnel, report Vincent C.C. Cheng, MD, FRCPath, the hospital’s infection control officer, and colleagues.

Cheng and colleagues note that 11 out of 413 healthcare workers who treat patients with confirmed infections had unprotected exposure and were in quarantine for 14 days, but none became ill.

In comparison, they note, the 2003 SARS outbreak saw almost 60% of nosocomial cases occurring in healthcare workers.

Proactive bundle

The Hong Kong success story may be due to a stepped-up proactive bundle of measures that included enhanced laboratory surveillance, early airborne infection isolation, and rapid-turnaround molecular diagnostics. Other strategies included staff forums and one-on-one discussions about infection control, employee training in protective equipment use, hand-hygiene compliance enforcement, and contact tracing for workers with unprotected exposure.

In addition, surgical masks were provided for all healthcare workers, patients, and visitors to clinical areas, a practice previously associated with reduced in-hospital transmission during influenza outbreaks, the authors note.

Hospitals also mandated use of personal protective equipment (PPE) for aerosol-generating procedures (AGPs), such as endotracheal intubation, open suctioning, and high-flow oxygen use, as AGPs had been linked to nosocomial transmission to healthcare workers during the 2003 SARS outbreak.

The infection control measures, which were part of a preparedness plan developed after the SARS outbreak, were initiated on December 31, when the first reports of a cluster of infections came from Wuhan, China.

As the outbreak evolved, the Hong Kong hospitals quickly widened the epidemiologic criteria for screening, from initially including only those who had been to a wet market in Wuhan within 14 days of symptom onset, to eventually including anyone who had been to Hubei province, been in a medical facility in mainland China, or in contact with a known case.  

All suspected cases were sent to an airborne-infection isolation room (AIIR) or a ward with at least a meter of space between patients.

“Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2,” the authors write. “Vigilance in hand hygiene practice, wearing of surgical mask in the hospital, and appropriate use of PPE in patient care, especially [when] performing AGPs, are the key infection control measures to prevent nosocomial transmission of SARS-CoV-2 even before the availability of effective antiviral agents and vaccine.”

Asked for his perspective on the report, Aaron E. Glatt, MD, chairman of the department of medicine and chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York, said that apart from the widespread issuing of surgical masks to workers, patients, and visitors, the measures taken in Hong Kong are not different from standard infection-control practices in American hospitals. Glatt, who is also a hospital epidemiologist, said it was unclear how much impact the masks would have.

“Although the infection control was impressive, I don’t see any evidence of a difference in care,” he told Medscape Medical News.

Could zero infection transmission be achieved in the more far-flung and variable settings of hospitals across the United States? “The ability to get zero transmission is only possible if people adhere to the strictest infection-control guidelines,” Glatt said. “That is clearly the goal, and it will take time to see if our existing strict guidelines are sufficient to maintain zero or close to zero contamination and transmission rates in our hospitals.”

Rather than looking to change US practices, he stressed adherence to widely established tenets of care. “It’s critically important to keep paying close attention to the basics, to the simple blocking and tackling, and to identify which patients are at risk, and therefore, when workers need protective equipment,” he said.

“Follow the recommended standards,” continued Glatt, who is also a spokesperson for the Infectious Diseases Society of America and did not participate in this study.

In a finding from an ancillary pilot experiment, the Hong Kong researchers found exhaled air from a patient with a moderate coronavirus load showed no evidence of the virus, whether the patient was breathing normally or heavily, speaking, or coughing. And spot tests around the room detected the virus in just one location.

“We may not be able to make a definite conclusion based on the analysis of a single patient,” the authors write. “However, it may help to reassure our staff that the exhaled air may be rapidly diluted inside the AIIR with 12 air changes per hour, or probably the SARS-CoV-2 may not be predominantly transmitted by [the] airborne route.”

However, a recent Singapore study showed widespread environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding, underlining the need for strict adherence to environmental and hand hygiene. Post-cleaning samples tested negative, suggesting that standard decontamination practices are effective. 

This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health, Hong Kong Special Administrative Region; and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education of China. The authors and Glatt have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The Centers for Medicare & Medicaid Services issued two guidance documents related to helping contain the spread of the coronavirus, primarily aimed at ensuring that health care providers are implementing proper infection control procedures.

The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.

“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”

The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.

The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.

Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”

The CMS also announced that it is suspending all nonemergency survey activity.

“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”

In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”

gtwachtman@mdedge.com

The Centers for Medicare & Medicaid Services issued two guidance documents related to helping contain the spread of the coronavirus, primarily aimed at ensuring that health care providers are implementing proper infection control procedures.

The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.

“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”

The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.

The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.

Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”

The CMS also announced that it is suspending all nonemergency survey activity.

“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”

In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”

gtwachtman@mdedge.com

The Centers for Medicare & Medicaid Services issued two guidance documents related to helping contain the spread of the coronavirus, primarily aimed at ensuring that health care providers are implementing proper infection control procedures.

The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.

“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”

The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.

The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.

Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”

The CMS also announced that it is suspending all nonemergency survey activity.

“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”

In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”

gtwachtman@mdedge.com

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

aotto@mdedge.com

SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

aotto@mdedge.com

SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

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SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.