Correct answer: C
 

Rationale

This patient has been exposed to HBV in the past and has cleared the virus. The HBVcore total Ab is indicative of prior exposure while the HBV surface Ab is detectable and gives immunity against reinfection under most routine clinical scenarios. Patients who have been exposed to HBV still have HBV ccc DNA within their hepatocytes that is dormant, but under extreme combined B and T cell immunosuppression, the patients are at risk for reverse seroconversion where they can lose HBV surface Ab and manifest HBV surface antigen and present as an acute HBV infection. Prophylaxis is required during therapy and for at least 12-18 months after therapy due to the long-lasting effects of anti-B cell monoclonal antibodies like rituximab. Reactivation of HCV in HCV Ab–positive, RNA-negative patients has not been reported.

Reference

1. Pauly MP, Tucker LY, Szpakowski JL, et al. Incidence of hepatitis B virus reactivation and hepatotoxicity in patients receiving long-term treatment with tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j. cgh.2018.04.033.

ginews@gastro.org

Correct answer: C
 

Rationale

This patient has been exposed to HBV in the past and has cleared the virus. The HBVcore total Ab is indicative of prior exposure while the HBV surface Ab is detectable and gives immunity against reinfection under most routine clinical scenarios. Patients who have been exposed to HBV still have HBV ccc DNA within their hepatocytes that is dormant, but under extreme combined B and T cell immunosuppression, the patients are at risk for reverse seroconversion where they can lose HBV surface Ab and manifest HBV surface antigen and present as an acute HBV infection. Prophylaxis is required during therapy and for at least 12-18 months after therapy due to the long-lasting effects of anti-B cell monoclonal antibodies like rituximab. Reactivation of HCV in HCV Ab–positive, RNA-negative patients has not been reported.

Reference

1. Pauly MP, Tucker LY, Szpakowski JL, et al. Incidence of hepatitis B virus reactivation and hepatotoxicity in patients receiving long-term treatment with tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j. cgh.2018.04.033.

ginews@gastro.org

Correct answer: C
 

Rationale

This patient has been exposed to HBV in the past and has cleared the virus. The HBVcore total Ab is indicative of prior exposure while the HBV surface Ab is detectable and gives immunity against reinfection under most routine clinical scenarios. Patients who have been exposed to HBV still have HBV ccc DNA within their hepatocytes that is dormant, but under extreme combined B and T cell immunosuppression, the patients are at risk for reverse seroconversion where they can lose HBV surface Ab and manifest HBV surface antigen and present as an acute HBV infection. Prophylaxis is required during therapy and for at least 12-18 months after therapy due to the long-lasting effects of anti-B cell monoclonal antibodies like rituximab. Reactivation of HCV in HCV Ab–positive, RNA-negative patients has not been reported.

Reference

1. Pauly MP, Tucker LY, Szpakowski JL, et al. Incidence of hepatitis B virus reactivation and hepatotoxicity in patients receiving long-term treatment with tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j. cgh.2018.04.033.

ginews@gastro.org

Squamous metaplasia

Weight regain can accompany re-emergence of obesity-related comorbidities and, thus, early intervention is important. Although diet, exercise, and behavior modifications are fundamental, they can have limited efficacy. Thus, endoscopic management is important, with specific evaluation for gastrogastric fistulae, pouch dilation, and GJA dilation, all of which can be successfully intervened upon endoscopically. For GJA dilation in particular, APC has been used with promising results.¹

In the normal GI tract, the esophagus is lined with squamous epithelium, and the stomach is lined with columnar epithelium. One of the most well-known and well-documented scenarios in which the typical mucosal lining is replaced by abnormal mucosa is Barrett’s esophagus (BE). BE is defined by the replacement of the normal distal squamous epithelial lining with columnar epithelium with a minimum length of 1 cm (tongues or circumferential) containing specialized intestinal metaplasia on histopathologic examination. It is well-documented that treatment of BE with thermal ablation and acid suppression therapy results in re-epithelialization of the esophagus with neosquamous mucosa.² In contrast with this, in our patients, after we burned the gastric columnar mucosa with APC to treat their dilated GJA, the gastric pouch mucosa has been replaced with squamous epithelium, which we have termed “reverse BE.” To our knowledge, there are no reports of this condition in the literature, nor do we know the precise cause. There is a series of patients without a history of bariatric surgery who developed squamous metaplasia in the proximal gastric cardia.³ The authors hypothesized that this condition may be due to chronic mucosal injury owing to hiatal hernia, reflux, caustic ingestion, chronic gastritis, or pyloric stenosis. We suggest two potential mechanisms for this condition in our patients: 1) extending the ablation to the Z-line on the medial aspect of the pouch may allow for the distal extension of squamous mucosa during the healing process; and 2) acid suppression therapy with proton pump inhibitors after the procedure, in combination with a postoperative decrease in acid production, allows for a shift in the cell proliferation and differentiation in the pouch. Notably, although there are well-defined guidelines for surveillance of BE, owing to the risk of progression to esophageal adenocarcinoma,² it is unclear what clinical significance this reverse BE may have in the future. It is important to continue to monitor these patients and clarify the natural history of this finding.
 

References

1. Brunaldi VO, Jirapinyo P, de Moura DTH et al. Endoscopic treatment of weight regain following Roux-en-Y gastric bypass: a systematic review and meta-analysis. Obes Surg. 2018;28:266-76.

2. Weusten B, Bisschops R, Coron E et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191-8.

3. Fass R, Sampliner RE. Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy. 2000;32:27-32.

Christopher C. Thompson is a consultant for Boston Scientific and Medtronic, a consultant for and has institutional grants from USGI Medical, Olympus, and Apollo Endosurgery.

ginews@gastro.org

Squamous metaplasia

Weight regain can accompany re-emergence of obesity-related comorbidities and, thus, early intervention is important. Although diet, exercise, and behavior modifications are fundamental, they can have limited efficacy. Thus, endoscopic management is important, with specific evaluation for gastrogastric fistulae, pouch dilation, and GJA dilation, all of which can be successfully intervened upon endoscopically. For GJA dilation in particular, APC has been used with promising results.¹

In the normal GI tract, the esophagus is lined with squamous epithelium, and the stomach is lined with columnar epithelium. One of the most well-known and well-documented scenarios in which the typical mucosal lining is replaced by abnormal mucosa is Barrett’s esophagus (BE). BE is defined by the replacement of the normal distal squamous epithelial lining with columnar epithelium with a minimum length of 1 cm (tongues or circumferential) containing specialized intestinal metaplasia on histopathologic examination. It is well-documented that treatment of BE with thermal ablation and acid suppression therapy results in re-epithelialization of the esophagus with neosquamous mucosa.² In contrast with this, in our patients, after we burned the gastric columnar mucosa with APC to treat their dilated GJA, the gastric pouch mucosa has been replaced with squamous epithelium, which we have termed “reverse BE.” To our knowledge, there are no reports of this condition in the literature, nor do we know the precise cause. There is a series of patients without a history of bariatric surgery who developed squamous metaplasia in the proximal gastric cardia.³ The authors hypothesized that this condition may be due to chronic mucosal injury owing to hiatal hernia, reflux, caustic ingestion, chronic gastritis, or pyloric stenosis. We suggest two potential mechanisms for this condition in our patients: 1) extending the ablation to the Z-line on the medial aspect of the pouch may allow for the distal extension of squamous mucosa during the healing process; and 2) acid suppression therapy with proton pump inhibitors after the procedure, in combination with a postoperative decrease in acid production, allows for a shift in the cell proliferation and differentiation in the pouch. Notably, although there are well-defined guidelines for surveillance of BE, owing to the risk of progression to esophageal adenocarcinoma,² it is unclear what clinical significance this reverse BE may have in the future. It is important to continue to monitor these patients and clarify the natural history of this finding.
 

References

1. Brunaldi VO, Jirapinyo P, de Moura DTH et al. Endoscopic treatment of weight regain following Roux-en-Y gastric bypass: a systematic review and meta-analysis. Obes Surg. 2018;28:266-76.

2. Weusten B, Bisschops R, Coron E et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191-8.

3. Fass R, Sampliner RE. Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy. 2000;32:27-32.

Christopher C. Thompson is a consultant for Boston Scientific and Medtronic, a consultant for and has institutional grants from USGI Medical, Olympus, and Apollo Endosurgery.

ginews@gastro.org

Squamous metaplasia

Weight regain can accompany re-emergence of obesity-related comorbidities and, thus, early intervention is important. Although diet, exercise, and behavior modifications are fundamental, they can have limited efficacy. Thus, endoscopic management is important, with specific evaluation for gastrogastric fistulae, pouch dilation, and GJA dilation, all of which can be successfully intervened upon endoscopically. For GJA dilation in particular, APC has been used with promising results.¹

In the normal GI tract, the esophagus is lined with squamous epithelium, and the stomach is lined with columnar epithelium. One of the most well-known and well-documented scenarios in which the typical mucosal lining is replaced by abnormal mucosa is Barrett’s esophagus (BE). BE is defined by the replacement of the normal distal squamous epithelial lining with columnar epithelium with a minimum length of 1 cm (tongues or circumferential) containing specialized intestinal metaplasia on histopathologic examination. It is well-documented that treatment of BE with thermal ablation and acid suppression therapy results in re-epithelialization of the esophagus with neosquamous mucosa.² In contrast with this, in our patients, after we burned the gastric columnar mucosa with APC to treat their dilated GJA, the gastric pouch mucosa has been replaced with squamous epithelium, which we have termed “reverse BE.” To our knowledge, there are no reports of this condition in the literature, nor do we know the precise cause. There is a series of patients without a history of bariatric surgery who developed squamous metaplasia in the proximal gastric cardia.³ The authors hypothesized that this condition may be due to chronic mucosal injury owing to hiatal hernia, reflux, caustic ingestion, chronic gastritis, or pyloric stenosis. We suggest two potential mechanisms for this condition in our patients: 1) extending the ablation to the Z-line on the medial aspect of the pouch may allow for the distal extension of squamous mucosa during the healing process; and 2) acid suppression therapy with proton pump inhibitors after the procedure, in combination with a postoperative decrease in acid production, allows for a shift in the cell proliferation and differentiation in the pouch. Notably, although there are well-defined guidelines for surveillance of BE, owing to the risk of progression to esophageal adenocarcinoma,² it is unclear what clinical significance this reverse BE may have in the future. It is important to continue to monitor these patients and clarify the natural history of this finding.
 

References

1. Brunaldi VO, Jirapinyo P, de Moura DTH et al. Endoscopic treatment of weight regain following Roux-en-Y gastric bypass: a systematic review and meta-analysis. Obes Surg. 2018;28:266-76.

2. Weusten B, Bisschops R, Coron E et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191-8.

3. Fass R, Sampliner RE. Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy. 2000;32:27-32.

Christopher C. Thompson is a consultant for Boston Scientific and Medtronic, a consultant for and has institutional grants from USGI Medical, Olympus, and Apollo Endosurgery.

ginews@gastro.org

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.

A multidisciplinary, patient-centered approach can dramatically reduce inappropriate use of proton pump inhibitors (PPI), based on the success of a quality improvement study conducted at an academic, primary care clinic in New York.

In 1 year, the program reduced inappropriate PPI use from 80% to 30%, reported lead author Naren Nallapeta, MD, an internal medicine resident at the State University of New York at Buffalo, and colleagues.

According to the investigators, inappropriate use of PPIs is a common and growing concern. Recent patent expirations have led to wider availability of generic and over-the-counter options; and the consequences of unnecessary usage can be serious.

“PPI intake has been found to have a significant association with community-acquired pneumonia, Clostridium difficile associated diarrhea, impaired B₁₂ absorption, hypomagnesemia, hip fractures, acute and chronic kidney disease, and spontaneous bacterial peritonitis in patients with cirrhotic ascites,” the investigators wrote in the Journal of Clinical Gastroenterology.

In 2017, the American Gastroenterological Association released guidelines that include indications for PPIs. But these guidelines often go unheeded, the investigators noted. Multiple studies have documented rates of inappropriate PPI use ranging from 54.1% to 82%. Previous studies have yielded mixed results: Simple physician education alone was found insufficient to reduce inappropriate prescriptions in a primary care setting, whereas studies involving pharmacy personnel have had positive results in various treatment centers.

In a survey of their own clinic, the Erie County Medical Center, an internal medicine service located in a tertiary care safety net hospital at the University at Buffalo, the investigators found that 80% of PPI prescriptions were inappropriate. This prompted a goal to reduce inappropriate use to less than 60% within 1 year.

To achieve this goal, the investigators started a quality improvement project based on the Plan-Do-Study-Act Cycle (PDSA) Model of health care improvement. The quality improvement team included internal medicine attending physicians and physician residents, gastroenterologists, patients, nurses, administrative and information technology staff, and a social worker.

After identifying root causes, the team deployed a variety of strategies to cut down on inappropriate PPI use. First, a new prompt in the electronic medical record reminded physicians to discuss PPI use with patients. Physicians were also given additional training concerning appropriate indications for PPIs, as well as a pocket guide and brochures that could be used for patient education. These efforts were supplemented by an enhanced nursing workflow, as well as continuous reinforcement with positive feedback for health care workers involved.

One year later, results exceeded expectations. Based on data from 180 patients, inappropriate use decreased from 80% to 30%, with a mean discontinuation rate of approximately 50%, an average that was maintained for 6 months beyond the end of the study. The annual, direct cost savings of the program totaled $13,992.

When indicated, patients on long-term PPIs were referred to the gastroenterology service for esophagogastroduodenoscopy. About half of the referred patients (49.8%) completed this procedure, which exceeded the baseline completion rate of less than 30%.

SOURCE: Nallapeta N et al. J Clin Gastroenterol. 2020 Feb 14. doi: 10.1097/MCG.0000000000001317.

A multidisciplinary, patient-centered approach can dramatically reduce inappropriate use of proton pump inhibitors (PPI), based on the success of a quality improvement study conducted at an academic, primary care clinic in New York.

In 1 year, the program reduced inappropriate PPI use from 80% to 30%, reported lead author Naren Nallapeta, MD, an internal medicine resident at the State University of New York at Buffalo, and colleagues.

According to the investigators, inappropriate use of PPIs is a common and growing concern. Recent patent expirations have led to wider availability of generic and over-the-counter options; and the consequences of unnecessary usage can be serious.

“PPI intake has been found to have a significant association with community-acquired pneumonia, Clostridium difficile associated diarrhea, impaired B₁₂ absorption, hypomagnesemia, hip fractures, acute and chronic kidney disease, and spontaneous bacterial peritonitis in patients with cirrhotic ascites,” the investigators wrote in the Journal of Clinical Gastroenterology.

In 2017, the American Gastroenterological Association released guidelines that include indications for PPIs. But these guidelines often go unheeded, the investigators noted. Multiple studies have documented rates of inappropriate PPI use ranging from 54.1% to 82%. Previous studies have yielded mixed results: Simple physician education alone was found insufficient to reduce inappropriate prescriptions in a primary care setting, whereas studies involving pharmacy personnel have had positive results in various treatment centers.

In a survey of their own clinic, the Erie County Medical Center, an internal medicine service located in a tertiary care safety net hospital at the University at Buffalo, the investigators found that 80% of PPI prescriptions were inappropriate. This prompted a goal to reduce inappropriate use to less than 60% within 1 year.

To achieve this goal, the investigators started a quality improvement project based on the Plan-Do-Study-Act Cycle (PDSA) Model of health care improvement. The quality improvement team included internal medicine attending physicians and physician residents, gastroenterologists, patients, nurses, administrative and information technology staff, and a social worker.

After identifying root causes, the team deployed a variety of strategies to cut down on inappropriate PPI use. First, a new prompt in the electronic medical record reminded physicians to discuss PPI use with patients. Physicians were also given additional training concerning appropriate indications for PPIs, as well as a pocket guide and brochures that could be used for patient education. These efforts were supplemented by an enhanced nursing workflow, as well as continuous reinforcement with positive feedback for health care workers involved.

One year later, results exceeded expectations. Based on data from 180 patients, inappropriate use decreased from 80% to 30%, with a mean discontinuation rate of approximately 50%, an average that was maintained for 6 months beyond the end of the study. The annual, direct cost savings of the program totaled $13,992.

When indicated, patients on long-term PPIs were referred to the gastroenterology service for esophagogastroduodenoscopy. About half of the referred patients (49.8%) completed this procedure, which exceeded the baseline completion rate of less than 30%.

SOURCE: Nallapeta N et al. J Clin Gastroenterol. 2020 Feb 14. doi: 10.1097/MCG.0000000000001317.

A multidisciplinary, patient-centered approach can dramatically reduce inappropriate use of proton pump inhibitors (PPI), based on the success of a quality improvement study conducted at an academic, primary care clinic in New York.

In 1 year, the program reduced inappropriate PPI use from 80% to 30%, reported lead author Naren Nallapeta, MD, an internal medicine resident at the State University of New York at Buffalo, and colleagues.

According to the investigators, inappropriate use of PPIs is a common and growing concern. Recent patent expirations have led to wider availability of generic and over-the-counter options; and the consequences of unnecessary usage can be serious.

“PPI intake has been found to have a significant association with community-acquired pneumonia, Clostridium difficile associated diarrhea, impaired B₁₂ absorption, hypomagnesemia, hip fractures, acute and chronic kidney disease, and spontaneous bacterial peritonitis in patients with cirrhotic ascites,” the investigators wrote in the Journal of Clinical Gastroenterology.

In 2017, the American Gastroenterological Association released guidelines that include indications for PPIs. But these guidelines often go unheeded, the investigators noted. Multiple studies have documented rates of inappropriate PPI use ranging from 54.1% to 82%. Previous studies have yielded mixed results: Simple physician education alone was found insufficient to reduce inappropriate prescriptions in a primary care setting, whereas studies involving pharmacy personnel have had positive results in various treatment centers.

In a survey of their own clinic, the Erie County Medical Center, an internal medicine service located in a tertiary care safety net hospital at the University at Buffalo, the investigators found that 80% of PPI prescriptions were inappropriate. This prompted a goal to reduce inappropriate use to less than 60% within 1 year.

To achieve this goal, the investigators started a quality improvement project based on the Plan-Do-Study-Act Cycle (PDSA) Model of health care improvement. The quality improvement team included internal medicine attending physicians and physician residents, gastroenterologists, patients, nurses, administrative and information technology staff, and a social worker.

After identifying root causes, the team deployed a variety of strategies to cut down on inappropriate PPI use. First, a new prompt in the electronic medical record reminded physicians to discuss PPI use with patients. Physicians were also given additional training concerning appropriate indications for PPIs, as well as a pocket guide and brochures that could be used for patient education. These efforts were supplemented by an enhanced nursing workflow, as well as continuous reinforcement with positive feedback for health care workers involved.

One year later, results exceeded expectations. Based on data from 180 patients, inappropriate use decreased from 80% to 30%, with a mean discontinuation rate of approximately 50%, an average that was maintained for 6 months beyond the end of the study. The annual, direct cost savings of the program totaled $13,992.

When indicated, patients on long-term PPIs were referred to the gastroenterology service for esophagogastroduodenoscopy. About half of the referred patients (49.8%) completed this procedure, which exceeded the baseline completion rate of less than 30%.

SOURCE: Nallapeta N et al. J Clin Gastroenterol. 2020 Feb 14. doi: 10.1097/MCG.0000000000001317.

National flu activity decreased for the second consecutive week, but pediatric mortality is heading in the opposite direction, according to the Centers for Disease Control and Prevention.

MDedge News

Influenza-like illness (ILI) represented 5.5% of all visits to outpatient health care providers during the week ending Feb. 22, compared with 6.1% the previous week, the CDC’s influenza division reported Feb. 28. The ILI visit rate had reached 6.6% in early February after dropping to 5.0% in mid-January, following a rise to a season-high 7.1% in the last week of December.

Another measure of ILI activity, the percentage of laboratory specimens testing positive, also declined for the second week in a row. The rate was 26.4% for the week ending Feb. 22, which is down from the season high of 30.3% reached 2 weeks before, the influenza division said.

ILI-related deaths among children, however, are not dropping. There were 20 pediatric deaths reported during the week, more than any other single week this season. The total for 2019-2020 is now up to 125, and that “number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

Hospitalization rates, which have been fairly typical in the general population, also are elevated for young adults and school-aged children, the agency said, and “rates among children 0-4 years old are now the highest CDC has on record at this point in the season, surpassing rates reported during the second wave of the 2009 H1N1 pandemic.”

rfranki@mdedge.com

National flu activity decreased for the second consecutive week, but pediatric mortality is heading in the opposite direction, according to the Centers for Disease Control and Prevention.

MDedge News

Influenza-like illness (ILI) represented 5.5% of all visits to outpatient health care providers during the week ending Feb. 22, compared with 6.1% the previous week, the CDC’s influenza division reported Feb. 28. The ILI visit rate had reached 6.6% in early February after dropping to 5.0% in mid-January, following a rise to a season-high 7.1% in the last week of December.

Another measure of ILI activity, the percentage of laboratory specimens testing positive, also declined for the second week in a row. The rate was 26.4% for the week ending Feb. 22, which is down from the season high of 30.3% reached 2 weeks before, the influenza division said.

ILI-related deaths among children, however, are not dropping. There were 20 pediatric deaths reported during the week, more than any other single week this season. The total for 2019-2020 is now up to 125, and that “number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

Hospitalization rates, which have been fairly typical in the general population, also are elevated for young adults and school-aged children, the agency said, and “rates among children 0-4 years old are now the highest CDC has on record at this point in the season, surpassing rates reported during the second wave of the 2009 H1N1 pandemic.”

rfranki@mdedge.com

National flu activity decreased for the second consecutive week, but pediatric mortality is heading in the opposite direction, according to the Centers for Disease Control and Prevention.

MDedge News

Influenza-like illness (ILI) represented 5.5% of all visits to outpatient health care providers during the week ending Feb. 22, compared with 6.1% the previous week, the CDC’s influenza division reported Feb. 28. The ILI visit rate had reached 6.6% in early February after dropping to 5.0% in mid-January, following a rise to a season-high 7.1% in the last week of December.

Another measure of ILI activity, the percentage of laboratory specimens testing positive, also declined for the second week in a row. The rate was 26.4% for the week ending Feb. 22, which is down from the season high of 30.3% reached 2 weeks before, the influenza division said.

ILI-related deaths among children, however, are not dropping. There were 20 pediatric deaths reported during the week, more than any other single week this season. The total for 2019-2020 is now up to 125, and that “number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

Hospitalization rates, which have been fairly typical in the general population, also are elevated for young adults and school-aged children, the agency said, and “rates among children 0-4 years old are now the highest CDC has on record at this point in the season, surpassing rates reported during the second wave of the 2009 H1N1 pandemic.”

rfranki@mdedge.com

Oncology will account for a substantial majority of clinical trials to be launched in 2020, as well as accounting for most of those to be completed this year, according to a new analysis.

“A large number of early stage clinical trials within this field are likely to be due to the demand for novel therapeutic approaches addressing unmet medical need,” commented Mohamed Abukar, pharma analyst at GlobalData.

Most oncology studies planned to start in 2020 are phase 1 and 2, and 61.9% are industry sponsored. Eli Lilly and Novartis have announced the most upcoming studies.

Among the new drugs being evaluated in these clinical trials, four of the top seven drugs in phase 1–3 development are monoclonal antibodies, with the most studies being conducted on the experimental agents ZW25 (Zymeworks) and KSI-301 (Kodiak Sciences), the report notes.

As for clinical trials due for completion this year, many are funded by nonindustry sources, with Memorial Sloan Kettering Cancer Center accounting for the most number of trials.

Top Indications Explored in Clinical Trials

Oncology also accounts for eight of the top ten indications for clinical trials planned to start in 2020, with solid tumors, breast cancer, and non–small cell lung cancer accounting for the second, third, and fourth top spots, respectively, regardless of sponsor type.

However, for industry-sponsored clinical trials, the predominant area is solid tumors for new investigations to start this year, followed by breast cancer, then pain.

“This is attributed to the manner in which the burden of cancer worldwide necessitates industry investment to allow for capitalization on the increasing market size,” Abukar said.

This article first appeared on Medscape.com.

Oncology will account for a substantial majority of clinical trials to be launched in 2020, as well as accounting for most of those to be completed this year, according to a new analysis.

“A large number of early stage clinical trials within this field are likely to be due to the demand for novel therapeutic approaches addressing unmet medical need,” commented Mohamed Abukar, pharma analyst at GlobalData.

Most oncology studies planned to start in 2020 are phase 1 and 2, and 61.9% are industry sponsored. Eli Lilly and Novartis have announced the most upcoming studies.

Among the new drugs being evaluated in these clinical trials, four of the top seven drugs in phase 1–3 development are monoclonal antibodies, with the most studies being conducted on the experimental agents ZW25 (Zymeworks) and KSI-301 (Kodiak Sciences), the report notes.

As for clinical trials due for completion this year, many are funded by nonindustry sources, with Memorial Sloan Kettering Cancer Center accounting for the most number of trials.

Top Indications Explored in Clinical Trials

Oncology also accounts for eight of the top ten indications for clinical trials planned to start in 2020, with solid tumors, breast cancer, and non–small cell lung cancer accounting for the second, third, and fourth top spots, respectively, regardless of sponsor type.

However, for industry-sponsored clinical trials, the predominant area is solid tumors for new investigations to start this year, followed by breast cancer, then pain.

“This is attributed to the manner in which the burden of cancer worldwide necessitates industry investment to allow for capitalization on the increasing market size,” Abukar said.

This article first appeared on Medscape.com.

Oncology will account for a substantial majority of clinical trials to be launched in 2020, as well as accounting for most of those to be completed this year, according to a new analysis.

“A large number of early stage clinical trials within this field are likely to be due to the demand for novel therapeutic approaches addressing unmet medical need,” commented Mohamed Abukar, pharma analyst at GlobalData.

Most oncology studies planned to start in 2020 are phase 1 and 2, and 61.9% are industry sponsored. Eli Lilly and Novartis have announced the most upcoming studies.

Among the new drugs being evaluated in these clinical trials, four of the top seven drugs in phase 1–3 development are monoclonal antibodies, with the most studies being conducted on the experimental agents ZW25 (Zymeworks) and KSI-301 (Kodiak Sciences), the report notes.

As for clinical trials due for completion this year, many are funded by nonindustry sources, with Memorial Sloan Kettering Cancer Center accounting for the most number of trials.

Top Indications Explored in Clinical Trials

Oncology also accounts for eight of the top ten indications for clinical trials planned to start in 2020, with solid tumors, breast cancer, and non–small cell lung cancer accounting for the second, third, and fourth top spots, respectively, regardless of sponsor type.

However, for industry-sponsored clinical trials, the predominant area is solid tumors for new investigations to start this year, followed by breast cancer, then pain.

“This is attributed to the manner in which the burden of cancer worldwide necessitates industry investment to allow for capitalization on the increasing market size,” Abukar said.

This article first appeared on Medscape.com.

LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.

“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.

Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.

A large multicenter, randomized, placebo-controlled, phase 3 clinical trial of topical tapinarof cream for treatment of psoriasis is underway. The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.

“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.

The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).

“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.

A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.

Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.

“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.

Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.

A large multicenter, randomized, placebo-controlled, phase 3 clinical trial of topical tapinarof cream for treatment of psoriasis is underway. The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.

“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.

The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).

“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.

A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.

Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.

“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.

Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.

A large multicenter, randomized, placebo-controlled, phase 3 clinical trial of topical tapinarof cream for treatment of psoriasis is underway. The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.

“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.

The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).

“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.

A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.

Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

This article last updated 4/8/20. (Disclaimer: The information in this article may not be updated regularly. For more COVID-19 coverage, bookmark our COVID-19 updates page. The editors of The Hospitalist encourage clinicians to also review information on the CDC website and on the AHA  website.) 

An infectious disease outbreak that began in December 2019 in Wuhan (Hubei Province), China, was found to be caused by the seventh strain of coronavirus, initially called the novel (new) coronavirus. The virus was later labeled as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 is named COVID-19. Until 2019, only six strains of human coronaviruses had previously been identified.

Courtesy NIAID-RML

As of April 8, 2020, according to the U.S. Centers for Disease Control and Prevention, COVID-19 has been detected in at least 209 countries and has spread to every contintent except Antarctica. More than 1,469,245 people have become infected globally, and at least 86,278 have died. Based on the cases detected and tested in the United States through the U.S. public health surveillance systems, we have had 406,693 confirmed cases and 13,089 deaths.

On March 11, 2020, the World Health Organization formally declared the COVID-19 outbreak to be a pandemic.

As the number of cases increases in the United States, we hope to provide answers about some common questions regarding COVID-19. The information summarized in this article is obtained and modified from the CDC.

What are the clinical features of COVID-19?

Ranges from asymptomatic infection, a mild disease with nonspecific signs and symptoms of acute respiratory illness, to severe pneumonia with respiratory failure and septic shock.

Who is at risk for COVID-19?

Persons who have had prolonged, unprotected close contact with a patient with symptomatic, confirmed COVID-19, and those with recent travel to China, especially Hubei Province.

Who is at risk for severe disease from COVID-19?

Older adults and persons who have underlying chronic medical conditions, such as immunocompromising conditions.

How is COVID-19 spread?

Person-to-person, mainly through respiratory droplets. SARS-CoV-2 has been isolated from upper respiratory tract specimens and bronchoalveolar lavage fluid.

When is someone infectious?

Incubation period may range from 2 to 14 days. Detection of viral RNA does not necessarily mean that infectious virus is present, as it may be detectable in the upper or lower respiratory tract for weeks after illness onset.

Can someone who has been quarantined for COVID-19 spread the illness to others?

For COVID-19, the period of quarantine is 14 days from the last date of exposure, because 14 days is the longest incubation period seen for similar coronaviruses. Someone who has been released from COVID-19 quarantine is not considered a risk for spreading the virus to others because they have not developed illness during the incubation period.

Can a person test negative and later test positive for COVID-19?

Yes. In the early stages of infection, it is possible the virus will not be detected.

Do patients with confirmed or suspected COVID-19 need to be admitted to the hospital?

Not all patients with COVID-19 require hospital admission. Patients whose clinical presentation warrants inpatient clinical management for supportive medical care should be admitted to the hospital under appropriate isolation precautions. The decision to monitor these patients in the inpatient or outpatient setting should be made on a case-by-case basis.

What should you do if you suspect a patient for COVID-19?

Immediately notify both infection control personnel at your health care facility and your local or state health department. State health departments that have identified a person under investigation (PUI) should immediately contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 and complete a COVID-19 PUI case investigation form.

CDC’s EOC will assist local/state health departments to collect, store, and ship specimens appropriately to CDC, including during after-hours or on weekends/holidays.
 

What type of isolation is needed for COVID-19?

Airborne Infection Isolation Room (AIIR) using Standard, Contact, and Airborne Precautions with eye protection.

How should health care personnel protect themselves when evaluating a patient who may have COVID-19?

Standard Precautions, Contact Precautions, Airborne Precautions, and use eye protection (e.g., goggles or a face shield).

What face mask do health care workers wear for respiratory protection?

A fit-tested NIOSH-certified disposable N95 filtering facepiece respirator should be worn before entry into the patient room or care area. Disposable respirators should be removed and discarded after exiting the patient’s room or care area and closing the door. Perform hand hygiene after discarding the respirator.

If reusable respirators (e.g., powered air purifying respirator/PAPR) are used, they must be cleaned and disinfected according to manufacturer’s reprocessing instructions prior to re-use.
 

What should you tell the patient if COVID-19 is suspected or confirmed?

Patients with suspected or confirmed COVID-19 should be asked to wear a surgical mask as soon as they are identified, to prevent spread to others.

Should any diagnostic or therapeutic interventions be withheld because of concerns about the transmission of COVID-19?

No.

How do you test a patient for SARS-CoV-2, the virus that causes COVID-19?

At this time, diagnostic testing for COVID-19 can be conducted only at CDC.

The CDC recommends collecting and testing multiple clinical specimens from different sites, including two specimen types – lower respiratory and upper respiratory (nasopharyngeal and oropharyngeal aspirates or washes, nasopharyngeal and oropharyngeal swabs, bronchioalveolar lavage, tracheal aspirates, sputum, and serum) using a real-time reverse transcription PCR (rRT-PCR) assay for SARS-CoV-2. Specimens should be collected as soon as possible once a PUI is identified regardless of the time of symptom onset. Turnaround time for the PCR assay testing is about 24-48 hours.

Will existing respiratory virus panels detect SARS-CoV-2, the virus that causes COVID-19?

No.

How is COVID-19 treated?

Symptomatic management. Corticosteroids are not routinely recommended for viral pneumonia or acute respiratory distress syndrome and should be avoided unless they are indicated for another reason (e.g., COPD exacerbation, refractory septic shock following Surviving Sepsis Campaign Guidelines). There are currently no antiviral drugs licensed by the U.S. Food and Drug Administration to treat COVID-19.
 

What is considered ‘close contact’ for health care exposures?

Being within approximately 6 feet (2 meters), of a person with COVID-19 for a prolonged period of time (such as caring for or visiting the patient, or sitting within 6 feet of the patient in a health care waiting area or room); or having unprotected direct contact with infectious secretions or excretions of the patient (e.g., being coughed on, touching used tissues with a bare hand). However, until more is known about transmission risks, it would be reasonable to consider anything longer than a brief (e.g., less than 1-2 minutes) exposure as prolonged.

What happens if the health care personnel (HCP) are exposed to confirmed COVID-19 patients? What’s the protocol for HCP exposed to persons under investigation (PUI) if test results are delayed beyond 48-72 hours?

Management is similar in both these scenarios. CDC categorized exposures as high, medium, low, and no identifiable risk. High- and medium-risk exposures are managed similarly with active monitoring for COVID-19 until 14 days after last potential exposure and exclude from work for 14 days after last exposure. Active monitoring means that the state or local public health authority assumes responsibility for establishing regular communication with potentially exposed people to assess for the presence of fever or respiratory symptoms (e.g., cough, shortness of breath, sore throat). For HCP with high- or medium-risk exposures, CDC recommends this communication occurs at least once each day. For full details, please see www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-risk-assesment-hcp.html.

Should postexposure prophylaxis be used for people who may have been exposed to COVID-19?

None available.

COVID-19 test results are negative in a symptomatic patient you suspected of COVID-19? What does it mean?

A negative test result for a sample collected while a person has symptoms likely means that the COVID-19 virus is not causing their current illness.

What if your hospital does not have an Airborne Infection Isolation Room (AIIR) for COVID-19 patients?

Transfer the patient to a facility that has an available AIIR. If a transfer is impractical or not medically appropriate, the patient should be cared for in a single-person room and the door should be kept closed. The room should ideally not have an exhaust that is recirculated within the building without high-efficiency particulate air (HEPA) filtration. Health care personnel should still use gloves, gown, respiratory and eye protection and follow all other recommended infection prevention and control practices when caring for these patients.
 

What if your hospital does not have enough Airborne Infection Isolation Rooms (AIIR) for COVID-19 patients?

Prioritize patients for AIIR who are symptomatic with severe illness (e.g., those requiring ventilator support).

When can patients with confirmed COVID-19 be discharged from the hospital?

Patients can be discharged from the health care facility whenever clinically indicated. Isolation should be maintained at home if the patient returns home before the time period recommended for discontinuation of hospital transmission-based precautions.

Considerations to discontinue transmission-based precautions include all of the following:

• Resolution of fever, without the use of antipyretic medication.
• Improvement in illness signs and symptoms.
• Negative rRT-PCR results from at least two consecutive sets of paired nasopharyngeal and throat swabs specimens collected at least 24 hours apart (total of four negative specimens – two nasopharyngeal and two throat) from a patient with COVID-19 are needed before discontinuing transmission-based precautions.

Should people be concerned about pets or other animals and COVID-19?

To date, CDC has not received any reports of pets or other animals becoming sick with COVID-19.

Should patients avoid contact with pets or other animals if they are sick with COVID-19?

Patients should restrict contact with pets and other animals while they are sick with COVID-19, just like they would around other people.

Does CDC recommend the use of face masks in the community to prevent COVID-19?

CDC does not recommend that people who are well wear a face mask to protect themselves from respiratory illnesses, including COVID-19. A face mask should be used by people who have COVID-19 and are showing symptoms to protect others from the risk of getting infected.

Should medical waste or general waste from health care facilities treating PUIs and patients with confirmed COVID-19 be handled any differently or need any additional disinfection?

No. CDC’s guidance states that management of laundry, food service utensils, and medical waste should be performed in accordance with routine procedures.

Can people who recover from COVID-19 be infected again?

Unknown. The immune response to COVID-19 is not yet understood.

What is the mortality rate of COVID-19, and how does it compare to the mortality rate of influenza (flu)?

The average 10-year mortality rate for flu, using CDC data, is found to be around 0.1%. Even though this percentage appears to be small, influenza is estimated to be responsible for 30,000 to 40,000 deaths annually in the U.S.

According to statistics released by the Chinese Center for Disease Control and Prevention on Feb. 17, the mortality rate of COVID-19 is estimated to be around 2.3%. This calculation was based on cases reported through Feb. 11, and calcuated by dividing the number of coronavirus-related deaths at the time (1,023) by the number of confirmed cases (44,672) of COVID-19 infection. However, this report has its limitations, since Chinese officials have a vague way of defining who has COVID-19 infection.

The World Health Organization (WHO) currently estimates the mortality rate for COVID-19 to be between 2% and 4%.

Dr. Sitammagari is a co-medical director for quality and assistant professor of internal medicine at Atrium Health, Charlotte, N.C. He is also a physician advisor. He currently serves as treasurer for the NC-Triangle Chapter of the Society of Hospital Medicine and as an editorial board member of The Hospitalist.

Dr. Skandhan is a hospitalist and member of the Core Faculty for the Internal Medicine Residency Program at Southeast Health (SEH), Dothan Ala., and an assistant professor at the Alabama College of Osteopathic Medicine. He serves as the medical director/physician liaison for the Clinical Documentation Program at SEH and also as the director for physician integration for Southeast Health Statera Network, an Accountable Care Organization. Dr. Skandhan was a cofounder of the Wiregrass chapter of SHM and currently serves on the Advisory board. He is also a member of the editorial board of The Hospitalist.

Dr. Dahlin is a second-year internal medicine resident at Southeast Health, Dothan, Ala. She serves as her class representative and is the cochair/resident liaison for the research committee at SEH. Dr. Dahlin also serves as a resident liaison for the Wiregrass chapter of SHM.

This article last updated 4/8/20. (Disclaimer: The information in this article may not be updated regularly. For more COVID-19 coverage, bookmark our COVID-19 updates page. The editors of The Hospitalist encourage clinicians to also review information on the CDC website and on the AHA  website.) 

An infectious disease outbreak that began in December 2019 in Wuhan (Hubei Province), China, was found to be caused by the seventh strain of coronavirus, initially called the novel (new) coronavirus. The virus was later labeled as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 is named COVID-19. Until 2019, only six strains of human coronaviruses had previously been identified.

Courtesy NIAID-RML

As of April 8, 2020, according to the U.S. Centers for Disease Control and Prevention, COVID-19 has been detected in at least 209 countries and has spread to every contintent except Antarctica. More than 1,469,245 people have become infected globally, and at least 86,278 have died. Based on the cases detected and tested in the United States through the U.S. public health surveillance systems, we have had 406,693 confirmed cases and 13,089 deaths.

On March 11, 2020, the World Health Organization formally declared the COVID-19 outbreak to be a pandemic.

As the number of cases increases in the United States, we hope to provide answers about some common questions regarding COVID-19. The information summarized in this article is obtained and modified from the CDC.

What are the clinical features of COVID-19?

Ranges from asymptomatic infection, a mild disease with nonspecific signs and symptoms of acute respiratory illness, to severe pneumonia with respiratory failure and septic shock.

Who is at risk for COVID-19?

Persons who have had prolonged, unprotected close contact with a patient with symptomatic, confirmed COVID-19, and those with recent travel to China, especially Hubei Province.

Who is at risk for severe disease from COVID-19?

Older adults and persons who have underlying chronic medical conditions, such as immunocompromising conditions.

How is COVID-19 spread?

Person-to-person, mainly through respiratory droplets. SARS-CoV-2 has been isolated from upper respiratory tract specimens and bronchoalveolar lavage fluid.

When is someone infectious?

Incubation period may range from 2 to 14 days. Detection of viral RNA does not necessarily mean that infectious virus is present, as it may be detectable in the upper or lower respiratory tract for weeks after illness onset.

Can someone who has been quarantined for COVID-19 spread the illness to others?

For COVID-19, the period of quarantine is 14 days from the last date of exposure, because 14 days is the longest incubation period seen for similar coronaviruses. Someone who has been released from COVID-19 quarantine is not considered a risk for spreading the virus to others because they have not developed illness during the incubation period.

Can a person test negative and later test positive for COVID-19?

Yes. In the early stages of infection, it is possible the virus will not be detected.

Do patients with confirmed or suspected COVID-19 need to be admitted to the hospital?

Not all patients with COVID-19 require hospital admission. Patients whose clinical presentation warrants inpatient clinical management for supportive medical care should be admitted to the hospital under appropriate isolation precautions. The decision to monitor these patients in the inpatient or outpatient setting should be made on a case-by-case basis.

What should you do if you suspect a patient for COVID-19?

Immediately notify both infection control personnel at your health care facility and your local or state health department. State health departments that have identified a person under investigation (PUI) should immediately contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 and complete a COVID-19 PUI case investigation form.

CDC’s EOC will assist local/state health departments to collect, store, and ship specimens appropriately to CDC, including during after-hours or on weekends/holidays.
 

What type of isolation is needed for COVID-19?

Airborne Infection Isolation Room (AIIR) using Standard, Contact, and Airborne Precautions with eye protection.

How should health care personnel protect themselves when evaluating a patient who may have COVID-19?

Standard Precautions, Contact Precautions, Airborne Precautions, and use eye protection (e.g., goggles or a face shield).

What face mask do health care workers wear for respiratory protection?

A fit-tested NIOSH-certified disposable N95 filtering facepiece respirator should be worn before entry into the patient room or care area. Disposable respirators should be removed and discarded after exiting the patient’s room or care area and closing the door. Perform hand hygiene after discarding the respirator.

If reusable respirators (e.g., powered air purifying respirator/PAPR) are used, they must be cleaned and disinfected according to manufacturer’s reprocessing instructions prior to re-use.
 

What should you tell the patient if COVID-19 is suspected or confirmed?

Patients with suspected or confirmed COVID-19 should be asked to wear a surgical mask as soon as they are identified, to prevent spread to others.

Should any diagnostic or therapeutic interventions be withheld because of concerns about the transmission of COVID-19?

No.

How do you test a patient for SARS-CoV-2, the virus that causes COVID-19?

At this time, diagnostic testing for COVID-19 can be conducted only at CDC.

The CDC recommends collecting and testing multiple clinical specimens from different sites, including two specimen types – lower respiratory and upper respiratory (nasopharyngeal and oropharyngeal aspirates or washes, nasopharyngeal and oropharyngeal swabs, bronchioalveolar lavage, tracheal aspirates, sputum, and serum) using a real-time reverse transcription PCR (rRT-PCR) assay for SARS-CoV-2. Specimens should be collected as soon as possible once a PUI is identified regardless of the time of symptom onset. Turnaround time for the PCR assay testing is about 24-48 hours.

Will existing respiratory virus panels detect SARS-CoV-2, the virus that causes COVID-19?

No.

How is COVID-19 treated?

Symptomatic management. Corticosteroids are not routinely recommended for viral pneumonia or acute respiratory distress syndrome and should be avoided unless they are indicated for another reason (e.g., COPD exacerbation, refractory septic shock following Surviving Sepsis Campaign Guidelines). There are currently no antiviral drugs licensed by the U.S. Food and Drug Administration to treat COVID-19.
 

What is considered ‘close contact’ for health care exposures?

Being within approximately 6 feet (2 meters), of a person with COVID-19 for a prolonged period of time (such as caring for or visiting the patient, or sitting within 6 feet of the patient in a health care waiting area or room); or having unprotected direct contact with infectious secretions or excretions of the patient (e.g., being coughed on, touching used tissues with a bare hand). However, until more is known about transmission risks, it would be reasonable to consider anything longer than a brief (e.g., less than 1-2 minutes) exposure as prolonged.

What happens if the health care personnel (HCP) are exposed to confirmed COVID-19 patients? What’s the protocol for HCP exposed to persons under investigation (PUI) if test results are delayed beyond 48-72 hours?

Management is similar in both these scenarios. CDC categorized exposures as high, medium, low, and no identifiable risk. High- and medium-risk exposures are managed similarly with active monitoring for COVID-19 until 14 days after last potential exposure and exclude from work for 14 days after last exposure. Active monitoring means that the state or local public health authority assumes responsibility for establishing regular communication with potentially exposed people to assess for the presence of fever or respiratory symptoms (e.g., cough, shortness of breath, sore throat). For HCP with high- or medium-risk exposures, CDC recommends this communication occurs at least once each day. For full details, please see www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-risk-assesment-hcp.html.

Should postexposure prophylaxis be used for people who may have been exposed to COVID-19?

None available.

COVID-19 test results are negative in a symptomatic patient you suspected of COVID-19? What does it mean?

A negative test result for a sample collected while a person has symptoms likely means that the COVID-19 virus is not causing their current illness.

What if your hospital does not have an Airborne Infection Isolation Room (AIIR) for COVID-19 patients?

Transfer the patient to a facility that has an available AIIR. If a transfer is impractical or not medically appropriate, the patient should be cared for in a single-person room and the door should be kept closed. The room should ideally not have an exhaust that is recirculated within the building without high-efficiency particulate air (HEPA) filtration. Health care personnel should still use gloves, gown, respiratory and eye protection and follow all other recommended infection prevention and control practices when caring for these patients.
 

What if your hospital does not have enough Airborne Infection Isolation Rooms (AIIR) for COVID-19 patients?

Prioritize patients for AIIR who are symptomatic with severe illness (e.g., those requiring ventilator support).

When can patients with confirmed COVID-19 be discharged from the hospital?

Patients can be discharged from the health care facility whenever clinically indicated. Isolation should be maintained at home if the patient returns home before the time period recommended for discontinuation of hospital transmission-based precautions.

Considerations to discontinue transmission-based precautions include all of the following:

• Resolution of fever, without the use of antipyretic medication.
• Improvement in illness signs and symptoms.
• Negative rRT-PCR results from at least two consecutive sets of paired nasopharyngeal and throat swabs specimens collected at least 24 hours apart (total of four negative specimens – two nasopharyngeal and two throat) from a patient with COVID-19 are needed before discontinuing transmission-based precautions.

Should people be concerned about pets or other animals and COVID-19?

To date, CDC has not received any reports of pets or other animals becoming sick with COVID-19.

Should patients avoid contact with pets or other animals if they are sick with COVID-19?

Patients should restrict contact with pets and other animals while they are sick with COVID-19, just like they would around other people.

Does CDC recommend the use of face masks in the community to prevent COVID-19?

CDC does not recommend that people who are well wear a face mask to protect themselves from respiratory illnesses, including COVID-19. A face mask should be used by people who have COVID-19 and are showing symptoms to protect others from the risk of getting infected.

Should medical waste or general waste from health care facilities treating PUIs and patients with confirmed COVID-19 be handled any differently or need any additional disinfection?

No. CDC’s guidance states that management of laundry, food service utensils, and medical waste should be performed in accordance with routine procedures.

Can people who recover from COVID-19 be infected again?

Unknown. The immune response to COVID-19 is not yet understood.

What is the mortality rate of COVID-19, and how does it compare to the mortality rate of influenza (flu)?

The average 10-year mortality rate for flu, using CDC data, is found to be around 0.1%. Even though this percentage appears to be small, influenza is estimated to be responsible for 30,000 to 40,000 deaths annually in the U.S.

According to statistics released by the Chinese Center for Disease Control and Prevention on Feb. 17, the mortality rate of COVID-19 is estimated to be around 2.3%. This calculation was based on cases reported through Feb. 11, and calcuated by dividing the number of coronavirus-related deaths at the time (1,023) by the number of confirmed cases (44,672) of COVID-19 infection. However, this report has its limitations, since Chinese officials have a vague way of defining who has COVID-19 infection.

The World Health Organization (WHO) currently estimates the mortality rate for COVID-19 to be between 2% and 4%.

Dr. Sitammagari is a co-medical director for quality and assistant professor of internal medicine at Atrium Health, Charlotte, N.C. He is also a physician advisor. He currently serves as treasurer for the NC-Triangle Chapter of the Society of Hospital Medicine and as an editorial board member of The Hospitalist.

Dr. Skandhan is a hospitalist and member of the Core Faculty for the Internal Medicine Residency Program at Southeast Health (SEH), Dothan Ala., and an assistant professor at the Alabama College of Osteopathic Medicine. He serves as the medical director/physician liaison for the Clinical Documentation Program at SEH and also as the director for physician integration for Southeast Health Statera Network, an Accountable Care Organization. Dr. Skandhan was a cofounder of the Wiregrass chapter of SHM and currently serves on the Advisory board. He is also a member of the editorial board of The Hospitalist.

Dr. Dahlin is a second-year internal medicine resident at Southeast Health, Dothan, Ala. She serves as her class representative and is the cochair/resident liaison for the research committee at SEH. Dr. Dahlin also serves as a resident liaison for the Wiregrass chapter of SHM.

This article last updated 4/8/20. (Disclaimer: The information in this article may not be updated regularly. For more COVID-19 coverage, bookmark our COVID-19 updates page. The editors of The Hospitalist encourage clinicians to also review information on the CDC website and on the AHA  website.) 

An infectious disease outbreak that began in December 2019 in Wuhan (Hubei Province), China, was found to be caused by the seventh strain of coronavirus, initially called the novel (new) coronavirus. The virus was later labeled as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 is named COVID-19. Until 2019, only six strains of human coronaviruses had previously been identified.

Courtesy NIAID-RML

As of April 8, 2020, according to the U.S. Centers for Disease Control and Prevention, COVID-19 has been detected in at least 209 countries and has spread to every contintent except Antarctica. More than 1,469,245 people have become infected globally, and at least 86,278 have died. Based on the cases detected and tested in the United States through the U.S. public health surveillance systems, we have had 406,693 confirmed cases and 13,089 deaths.

On March 11, 2020, the World Health Organization formally declared the COVID-19 outbreak to be a pandemic.

As the number of cases increases in the United States, we hope to provide answers about some common questions regarding COVID-19. The information summarized in this article is obtained and modified from the CDC.

What are the clinical features of COVID-19?

Ranges from asymptomatic infection, a mild disease with nonspecific signs and symptoms of acute respiratory illness, to severe pneumonia with respiratory failure and septic shock.

Who is at risk for COVID-19?

Persons who have had prolonged, unprotected close contact with a patient with symptomatic, confirmed COVID-19, and those with recent travel to China, especially Hubei Province.

Who is at risk for severe disease from COVID-19?

Older adults and persons who have underlying chronic medical conditions, such as immunocompromising conditions.

How is COVID-19 spread?

Person-to-person, mainly through respiratory droplets. SARS-CoV-2 has been isolated from upper respiratory tract specimens and bronchoalveolar lavage fluid.

When is someone infectious?

Incubation period may range from 2 to 14 days. Detection of viral RNA does not necessarily mean that infectious virus is present, as it may be detectable in the upper or lower respiratory tract for weeks after illness onset.

Can someone who has been quarantined for COVID-19 spread the illness to others?

For COVID-19, the period of quarantine is 14 days from the last date of exposure, because 14 days is the longest incubation period seen for similar coronaviruses. Someone who has been released from COVID-19 quarantine is not considered a risk for spreading the virus to others because they have not developed illness during the incubation period.

Can a person test negative and later test positive for COVID-19?

Yes. In the early stages of infection, it is possible the virus will not be detected.

Do patients with confirmed or suspected COVID-19 need to be admitted to the hospital?

Not all patients with COVID-19 require hospital admission. Patients whose clinical presentation warrants inpatient clinical management for supportive medical care should be admitted to the hospital under appropriate isolation precautions. The decision to monitor these patients in the inpatient or outpatient setting should be made on a case-by-case basis.

What should you do if you suspect a patient for COVID-19?

Immediately notify both infection control personnel at your health care facility and your local or state health department. State health departments that have identified a person under investigation (PUI) should immediately contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 and complete a COVID-19 PUI case investigation form.

CDC’s EOC will assist local/state health departments to collect, store, and ship specimens appropriately to CDC, including during after-hours or on weekends/holidays.
 

What type of isolation is needed for COVID-19?

Airborne Infection Isolation Room (AIIR) using Standard, Contact, and Airborne Precautions with eye protection.

How should health care personnel protect themselves when evaluating a patient who may have COVID-19?

Standard Precautions, Contact Precautions, Airborne Precautions, and use eye protection (e.g., goggles or a face shield).

What face mask do health care workers wear for respiratory protection?

A fit-tested NIOSH-certified disposable N95 filtering facepiece respirator should be worn before entry into the patient room or care area. Disposable respirators should be removed and discarded after exiting the patient’s room or care area and closing the door. Perform hand hygiene after discarding the respirator.

If reusable respirators (e.g., powered air purifying respirator/PAPR) are used, they must be cleaned and disinfected according to manufacturer’s reprocessing instructions prior to re-use.
 

What should you tell the patient if COVID-19 is suspected or confirmed?

Patients with suspected or confirmed COVID-19 should be asked to wear a surgical mask as soon as they are identified, to prevent spread to others.

Should any diagnostic or therapeutic interventions be withheld because of concerns about the transmission of COVID-19?

No.

How do you test a patient for SARS-CoV-2, the virus that causes COVID-19?

At this time, diagnostic testing for COVID-19 can be conducted only at CDC.

The CDC recommends collecting and testing multiple clinical specimens from different sites, including two specimen types – lower respiratory and upper respiratory (nasopharyngeal and oropharyngeal aspirates or washes, nasopharyngeal and oropharyngeal swabs, bronchioalveolar lavage, tracheal aspirates, sputum, and serum) using a real-time reverse transcription PCR (rRT-PCR) assay for SARS-CoV-2. Specimens should be collected as soon as possible once a PUI is identified regardless of the time of symptom onset. Turnaround time for the PCR assay testing is about 24-48 hours.

Will existing respiratory virus panels detect SARS-CoV-2, the virus that causes COVID-19?

No.

How is COVID-19 treated?

Symptomatic management. Corticosteroids are not routinely recommended for viral pneumonia or acute respiratory distress syndrome and should be avoided unless they are indicated for another reason (e.g., COPD exacerbation, refractory septic shock following Surviving Sepsis Campaign Guidelines). There are currently no antiviral drugs licensed by the U.S. Food and Drug Administration to treat COVID-19.
 

What is considered ‘close contact’ for health care exposures?

Being within approximately 6 feet (2 meters), of a person with COVID-19 for a prolonged period of time (such as caring for or visiting the patient, or sitting within 6 feet of the patient in a health care waiting area or room); or having unprotected direct contact with infectious secretions or excretions of the patient (e.g., being coughed on, touching used tissues with a bare hand). However, until more is known about transmission risks, it would be reasonable to consider anything longer than a brief (e.g., less than 1-2 minutes) exposure as prolonged.

What happens if the health care personnel (HCP) are exposed to confirmed COVID-19 patients? What’s the protocol for HCP exposed to persons under investigation (PUI) if test results are delayed beyond 48-72 hours?

Management is similar in both these scenarios. CDC categorized exposures as high, medium, low, and no identifiable risk. High- and medium-risk exposures are managed similarly with active monitoring for COVID-19 until 14 days after last potential exposure and exclude from work for 14 days after last exposure. Active monitoring means that the state or local public health authority assumes responsibility for establishing regular communication with potentially exposed people to assess for the presence of fever or respiratory symptoms (e.g., cough, shortness of breath, sore throat). For HCP with high- or medium-risk exposures, CDC recommends this communication occurs at least once each day. For full details, please see www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-risk-assesment-hcp.html.

Should postexposure prophylaxis be used for people who may have been exposed to COVID-19?

None available.

COVID-19 test results are negative in a symptomatic patient you suspected of COVID-19? What does it mean?

A negative test result for a sample collected while a person has symptoms likely means that the COVID-19 virus is not causing their current illness.

What if your hospital does not have an Airborne Infection Isolation Room (AIIR) for COVID-19 patients?

Transfer the patient to a facility that has an available AIIR. If a transfer is impractical or not medically appropriate, the patient should be cared for in a single-person room and the door should be kept closed. The room should ideally not have an exhaust that is recirculated within the building without high-efficiency particulate air (HEPA) filtration. Health care personnel should still use gloves, gown, respiratory and eye protection and follow all other recommended infection prevention and control practices when caring for these patients.
 

What if your hospital does not have enough Airborne Infection Isolation Rooms (AIIR) for COVID-19 patients?

Prioritize patients for AIIR who are symptomatic with severe illness (e.g., those requiring ventilator support).

When can patients with confirmed COVID-19 be discharged from the hospital?

Patients can be discharged from the health care facility whenever clinically indicated. Isolation should be maintained at home if the patient returns home before the time period recommended for discontinuation of hospital transmission-based precautions.

Considerations to discontinue transmission-based precautions include all of the following:

• Resolution of fever, without the use of antipyretic medication.
• Improvement in illness signs and symptoms.
• Negative rRT-PCR results from at least two consecutive sets of paired nasopharyngeal and throat swabs specimens collected at least 24 hours apart (total of four negative specimens – two nasopharyngeal and two throat) from a patient with COVID-19 are needed before discontinuing transmission-based precautions.

Should people be concerned about pets or other animals and COVID-19?

To date, CDC has not received any reports of pets or other animals becoming sick with COVID-19.

Should patients avoid contact with pets or other animals if they are sick with COVID-19?

Patients should restrict contact with pets and other animals while they are sick with COVID-19, just like they would around other people.

Does CDC recommend the use of face masks in the community to prevent COVID-19?

CDC does not recommend that people who are well wear a face mask to protect themselves from respiratory illnesses, including COVID-19. A face mask should be used by people who have COVID-19 and are showing symptoms to protect others from the risk of getting infected.

Should medical waste or general waste from health care facilities treating PUIs and patients with confirmed COVID-19 be handled any differently or need any additional disinfection?

No. CDC’s guidance states that management of laundry, food service utensils, and medical waste should be performed in accordance with routine procedures.

Can people who recover from COVID-19 be infected again?

Unknown. The immune response to COVID-19 is not yet understood.

What is the mortality rate of COVID-19, and how does it compare to the mortality rate of influenza (flu)?

The average 10-year mortality rate for flu, using CDC data, is found to be around 0.1%. Even though this percentage appears to be small, influenza is estimated to be responsible for 30,000 to 40,000 deaths annually in the U.S.

According to statistics released by the Chinese Center for Disease Control and Prevention on Feb. 17, the mortality rate of COVID-19 is estimated to be around 2.3%. This calculation was based on cases reported through Feb. 11, and calcuated by dividing the number of coronavirus-related deaths at the time (1,023) by the number of confirmed cases (44,672) of COVID-19 infection. However, this report has its limitations, since Chinese officials have a vague way of defining who has COVID-19 infection.

The World Health Organization (WHO) currently estimates the mortality rate for COVID-19 to be between 2% and 4%.

Dr. Sitammagari is a co-medical director for quality and assistant professor of internal medicine at Atrium Health, Charlotte, N.C. He is also a physician advisor. He currently serves as treasurer for the NC-Triangle Chapter of the Society of Hospital Medicine and as an editorial board member of The Hospitalist.

Dr. Skandhan is a hospitalist and member of the Core Faculty for the Internal Medicine Residency Program at Southeast Health (SEH), Dothan Ala., and an assistant professor at the Alabama College of Osteopathic Medicine. He serves as the medical director/physician liaison for the Clinical Documentation Program at SEH and also as the director for physician integration for Southeast Health Statera Network, an Accountable Care Organization. Dr. Skandhan was a cofounder of the Wiregrass chapter of SHM and currently serves on the Advisory board. He is also a member of the editorial board of The Hospitalist.

Dr. Dahlin is a second-year internal medicine resident at Southeast Health, Dothan, Ala. She serves as her class representative and is the cochair/resident liaison for the research committee at SEH. Dr. Dahlin also serves as a resident liaison for the Wiregrass chapter of SHM.

WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

Jake Remaly/MDedge News

The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Dr. Glanzman said. Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.

“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.

“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.

Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

jremaly@mdedge.com

SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

Jake Remaly/MDedge News

The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Dr. Glanzman said. Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.

“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.

“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.

Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

jremaly@mdedge.com

SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

Jake Remaly/MDedge News

The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Dr. Glanzman said. Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.

“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.

“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.

Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

jremaly@mdedge.com

SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.