A few days ago, I had a heartfelt conversation with my good friend Dr Omayra Mansfield. Dr Mansfield has been an Emergency Department Physician for more than 12 years. She is also the wife of another physician and the mother of two young children, the recently appointed Chief Medical Officer at a hospital at AdventHealth, and one of the first graduates of the Physician Leader Development Course I teach.

“During the leadership course, you always provided examples of how physicians are like soldiers,” she began. She reminded me of my words describing how both doctors and soldiers are part of a professional body, how both have a cherished ethos and a set of directing values to guide both their path and their actions as a very special part of our society, and how of all the professions in our society, the military and medicine are the only two that deal in life and death, albeit in very different ways.

She had certainly paid attention in our seminars. Now, as she and her team faced the COVID-19 pandemic, she realized their daily challenges are expanding and they are now going to war. The leadership discussions that had sparked so much debate in our colloquia had now become real.

Dr Mansfield explained that beyond caring for patients, one of her key concerns was the physical and emotional well-­being of the clinical staff at her hospital: the physicians, nurses, technicians, and clinicians under her care. Getting to her point, she asked if I might have any suggestions based on my time and experiences in combat that might be helpful to her as she “cared for her troops” as they faced the battle ahead.

Her request was a good one. Lessons from my military past immediately rushed to my mind. I started scribbling and came up with a Top Ten list of recommendations for anyone going into a tough fight. Here’s what I sent to her:

1. Find a battle-buddy. On the first day of Army basic training, drill sergeants pair new recruits with one another. That’s primarily for accountability purposes throughout the weeks of training—to ensure soldiers hold each other responsible for getting to the right place, at the right time, in the right uniform—but it’s also part of a larger psychological dynamic related to building teams and mutual support within organizations. Your battle-buddy is charged with keeping you out of trouble, having your back, and being there when you need it most. In combat, battle-buddies do all those things and then some; they protect you from harm in so many other ways. Healthcare providers during this crisis will sometimes feel all alone, and they need to rely on someone else to help them when times get really tough. Having a battle-buddy—for those at the healthcare team level, of course, but also among those at the level of clinical director, hospital administrator, CMO, or even CEO—will help get you through the tough times and provide sanity when you need it the most. So my first piece of advice: Find a battle-buddy.
2. Plan and prepare for things you don’t expect will happen. During a preparatory training exercise for our unit’s deployment to Iraq during the surge, when we thought the exercise was about to end, the trainers surprised us with a final crisis we had to solve. According to the scenario, Al Qaida had blown up a major bridge in our area, causing dire logistical problems for the security forces and challenges to the population as they brought their goods to market. I remember my initial reaction: “They don’t have the strength to do that. This’ll never happen,” I said to the Chief of Staff under my breath, as we started developing the required drill to counter the action and please the trainers. I quickly forgot about that lesson, until after we deployed. Two weeks into our 15-month tour in Iraq, the enemy blew the exact bridge that was part of the scenario, causing the exact problems that were predicted. Because we had prepared for the unexpected, we were able to quickly repair the bridge, reestablish the logistics flow, and satisfy the worried population. The lesson: Teams can hope for the best, but it’s always important to prepare for the worst—a lack of equipment, a key member of the team not being available to contribute, an overwhelming surge of patients—and then develop a plan to mitigate it. Take time to reflect, and ask yourself, What is the worst that can happen, what can the “enemy” do to disrupt our lives, and how do we prepare to counter it?
3. Get everyone into the fight. In every organizations, it’s often true that some people take on too much and try and do it all themselves, others do only what they’re told to do, there’s the unique few who want to contribute but don’t know how they can to help, and then there’s some who even attempt to avoid contributing at all. It’s important for leaders to know who on their team fits each of these categories. It’s even more critical for leaders to be able to find ways to relieve the overworked, assign tasks to those who might not know their role, bring those who want to contribute into the fold, and cross-train teams to help relieve those who are exhausted. Leaders must look across their “battlespace” and ensure everyone is contributing. Leaders assign everyone tasks and do their best to level—and lighten—the load of the overworked.
4. “Fatigue makes cowards of us all.” During any type of crisis, the body and mind will rapidly break down from lack of sleep, emotional strain, or overwhelming stress. While a 12-hour shift in a hospital is exceedingly tough even during normal operations, the COVID-19 crisis will demand dramatically more of all the members of any healthcare team. For that reason, leaders must incorporate rest cycles, team rotations, and half-days away from the hospitals even when all hands are on deck, as well as consider reducing shift times, if possible. Many who have experienced the disease in hot spots say this is really tough, but not attempting to plan for this will cause eventual breakdown and dysfunction. Take a break, do all you can to maintain a modicum of balance, and get away for a while.
5. Take time to huddle. Communication and information are always key, but especially critical during any crisis. One technique that has proven valuable, beyond meetings and shift changes, is a preshift and postshift huddle. Different from the formal passing of critical information, the huddle is a brief opportunity for teams to pass informal information, look each other in the eye, and perhaps even pray together. As a two-star general, I did that every morning in combat with my small team of sergeants, captains, and privates before we left the headquarters to visit units, and it gave us all the power of knowing we had shared information, and we had a common operating picture. It gave us strength. During a crisis, all kinds of communication, formal and informal, are key.
6. This ain’t peacetime. In a crisis, the enemy gets a vote. If leaders don’t find ways to counter the enemy’s action (and fast!), they’ll be behind the curve! It’s important to find the techniques and procedures that are bureaucratic (or even dumb) and overturn or eliminate them quickly. Decisions must be made with alacrity and with an understood flow, and people must be assigned responsibilities and held accountable to make things happen. In a crisis, speed in action will almost always trump perfection in understanding. Stay calm but ensure that those who might not understand this come around to the dynamics associated with the threat. A crisis isn’t the time for business as usual.
7. Force adaptation—don’t wait ’til things are over to adjust. In a crisis, faults and disconnects in techniques and procedures often bubble to the surface and cause consternation. Don’t wait for a break in the action to adjust and find new ways to do things because a break in the action will usually never happen. The military has an expression: “Those who adapt the fastest on the battlefield win.” Find ways to look for and then publicize your methods of adaptation to the team, pin the rose on someone to ensure the changes are made, and then have someone make a historical record so other teams might also learn from your scar tissue. Lessons from the fight must be incorporated by the organization, or they’re not “lessons learned.”
8. Talkin’ ain’t fightin’. During a crisis, it’s important to establish techniques of verbal shorthand between the members of a team, and everyone must know their responsibilities and required actions. In the military, this is called a battle drill; in medicine, you know it as a code. In these situations, leaders must find ways to pass information quickly, and the reaction should be immediate response. In a crisis, normal process must take on the dynamics of a “code.” All members of the team must understand that there are just times when things can’t be explained, but it’s also important that leaders know when to use this abbreviated format. Explain when you can, but act when you must.
9. Cherish your teams. Every single team will experience things that human beings aren’t designed or meant to handle—even those in the medical profession, who likely thought they had seen it all. There will be repeated and overwhelming trauma, with the expected emotional reactions. The approach during these situations requires empathy, humility, emotional understanding, and validation. Praise your team at every opportunity, find ways to turn mistakes into learning opportunities, but most importantly be human and find ways to provide memories that your team can cherish and look back upon. Give them memories.
10. Leaders don’t have the right to have a bad day. In 2004, after a 12-month deployment in Iraq, our unit was on our way home. We had been a long time away from our families, and we had experienced some tough fighting. A third of our unit had already returned to their families in Germany when we were told we would be extended because of a changing situation on the ground. A wave of frustration went through our 18,000 soldiers. Our commander then pulled us together, communicated our new mission, and told us he was also disappointed, but it was time we had to show our grit by getting those soldiers who had already returned to Europe back, unpack our equipment, and return to the fight. Then he said something I will always remember: “It’s tough, but understand your soldiers are looking at you to lead in this crisis … and leaders don’t have the right to have a bad day.” He didn’t mean we couldn’t be frustrated, or disappointed, or emotional, or even pissed off. He meant we just couldn’t show it when others were around. That’s one of the toughest things about leading during a crisis: The unimaginable is expected of leaders. And leaders have to be ready to lead.

All this advice may seem like philosophical musings rather than pragmatic thoughts for a crisis, but hopefully this advice will make a difference as healthcare providers tackle the issues ahead. Stay healthy, mitigate risks, but know that the calm provided by leaders will make a difference.

A few days ago, I had a heartfelt conversation with my good friend Dr Omayra Mansfield. Dr Mansfield has been an Emergency Department Physician for more than 12 years. She is also the wife of another physician and the mother of two young children, the recently appointed Chief Medical Officer at a hospital at AdventHealth, and one of the first graduates of the Physician Leader Development Course I teach.

“During the leadership course, you always provided examples of how physicians are like soldiers,” she began. She reminded me of my words describing how both doctors and soldiers are part of a professional body, how both have a cherished ethos and a set of directing values to guide both their path and their actions as a very special part of our society, and how of all the professions in our society, the military and medicine are the only two that deal in life and death, albeit in very different ways.

She had certainly paid attention in our seminars. Now, as she and her team faced the COVID-19 pandemic, she realized their daily challenges are expanding and they are now going to war. The leadership discussions that had sparked so much debate in our colloquia had now become real.

Dr Mansfield explained that beyond caring for patients, one of her key concerns was the physical and emotional well-­being of the clinical staff at her hospital: the physicians, nurses, technicians, and clinicians under her care. Getting to her point, she asked if I might have any suggestions based on my time and experiences in combat that might be helpful to her as she “cared for her troops” as they faced the battle ahead.

Her request was a good one. Lessons from my military past immediately rushed to my mind. I started scribbling and came up with a Top Ten list of recommendations for anyone going into a tough fight. Here’s what I sent to her:

1. Find a battle-buddy. On the first day of Army basic training, drill sergeants pair new recruits with one another. That’s primarily for accountability purposes throughout the weeks of training—to ensure soldiers hold each other responsible for getting to the right place, at the right time, in the right uniform—but it’s also part of a larger psychological dynamic related to building teams and mutual support within organizations. Your battle-buddy is charged with keeping you out of trouble, having your back, and being there when you need it most. In combat, battle-buddies do all those things and then some; they protect you from harm in so many other ways. Healthcare providers during this crisis will sometimes feel all alone, and they need to rely on someone else to help them when times get really tough. Having a battle-buddy—for those at the healthcare team level, of course, but also among those at the level of clinical director, hospital administrator, CMO, or even CEO—will help get you through the tough times and provide sanity when you need it the most. So my first piece of advice: Find a battle-buddy.
2. Plan and prepare for things you don’t expect will happen. During a preparatory training exercise for our unit’s deployment to Iraq during the surge, when we thought the exercise was about to end, the trainers surprised us with a final crisis we had to solve. According to the scenario, Al Qaida had blown up a major bridge in our area, causing dire logistical problems for the security forces and challenges to the population as they brought their goods to market. I remember my initial reaction: “They don’t have the strength to do that. This’ll never happen,” I said to the Chief of Staff under my breath, as we started developing the required drill to counter the action and please the trainers. I quickly forgot about that lesson, until after we deployed. Two weeks into our 15-month tour in Iraq, the enemy blew the exact bridge that was part of the scenario, causing the exact problems that were predicted. Because we had prepared for the unexpected, we were able to quickly repair the bridge, reestablish the logistics flow, and satisfy the worried population. The lesson: Teams can hope for the best, but it’s always important to prepare for the worst—a lack of equipment, a key member of the team not being available to contribute, an overwhelming surge of patients—and then develop a plan to mitigate it. Take time to reflect, and ask yourself, What is the worst that can happen, what can the “enemy” do to disrupt our lives, and how do we prepare to counter it?
3. Get everyone into the fight. In every organizations, it’s often true that some people take on too much and try and do it all themselves, others do only what they’re told to do, there’s the unique few who want to contribute but don’t know how they can to help, and then there’s some who even attempt to avoid contributing at all. It’s important for leaders to know who on their team fits each of these categories. It’s even more critical for leaders to be able to find ways to relieve the overworked, assign tasks to those who might not know their role, bring those who want to contribute into the fold, and cross-train teams to help relieve those who are exhausted. Leaders must look across their “battlespace” and ensure everyone is contributing. Leaders assign everyone tasks and do their best to level—and lighten—the load of the overworked.
4. “Fatigue makes cowards of us all.” During any type of crisis, the body and mind will rapidly break down from lack of sleep, emotional strain, or overwhelming stress. While a 12-hour shift in a hospital is exceedingly tough even during normal operations, the COVID-19 crisis will demand dramatically more of all the members of any healthcare team. For that reason, leaders must incorporate rest cycles, team rotations, and half-days away from the hospitals even when all hands are on deck, as well as consider reducing shift times, if possible. Many who have experienced the disease in hot spots say this is really tough, but not attempting to plan for this will cause eventual breakdown and dysfunction. Take a break, do all you can to maintain a modicum of balance, and get away for a while.
5. Take time to huddle. Communication and information are always key, but especially critical during any crisis. One technique that has proven valuable, beyond meetings and shift changes, is a preshift and postshift huddle. Different from the formal passing of critical information, the huddle is a brief opportunity for teams to pass informal information, look each other in the eye, and perhaps even pray together. As a two-star general, I did that every morning in combat with my small team of sergeants, captains, and privates before we left the headquarters to visit units, and it gave us all the power of knowing we had shared information, and we had a common operating picture. It gave us strength. During a crisis, all kinds of communication, formal and informal, are key.
6. This ain’t peacetime. In a crisis, the enemy gets a vote. If leaders don’t find ways to counter the enemy’s action (and fast!), they’ll be behind the curve! It’s important to find the techniques and procedures that are bureaucratic (or even dumb) and overturn or eliminate them quickly. Decisions must be made with alacrity and with an understood flow, and people must be assigned responsibilities and held accountable to make things happen. In a crisis, speed in action will almost always trump perfection in understanding. Stay calm but ensure that those who might not understand this come around to the dynamics associated with the threat. A crisis isn’t the time for business as usual.
7. Force adaptation—don’t wait ’til things are over to adjust. In a crisis, faults and disconnects in techniques and procedures often bubble to the surface and cause consternation. Don’t wait for a break in the action to adjust and find new ways to do things because a break in the action will usually never happen. The military has an expression: “Those who adapt the fastest on the battlefield win.” Find ways to look for and then publicize your methods of adaptation to the team, pin the rose on someone to ensure the changes are made, and then have someone make a historical record so other teams might also learn from your scar tissue. Lessons from the fight must be incorporated by the organization, or they’re not “lessons learned.”
8. Talkin’ ain’t fightin’. During a crisis, it’s important to establish techniques of verbal shorthand between the members of a team, and everyone must know their responsibilities and required actions. In the military, this is called a battle drill; in medicine, you know it as a code. In these situations, leaders must find ways to pass information quickly, and the reaction should be immediate response. In a crisis, normal process must take on the dynamics of a “code.” All members of the team must understand that there are just times when things can’t be explained, but it’s also important that leaders know when to use this abbreviated format. Explain when you can, but act when you must.
9. Cherish your teams. Every single team will experience things that human beings aren’t designed or meant to handle—even those in the medical profession, who likely thought they had seen it all. There will be repeated and overwhelming trauma, with the expected emotional reactions. The approach during these situations requires empathy, humility, emotional understanding, and validation. Praise your team at every opportunity, find ways to turn mistakes into learning opportunities, but most importantly be human and find ways to provide memories that your team can cherish and look back upon. Give them memories.
10. Leaders don’t have the right to have a bad day. In 2004, after a 12-month deployment in Iraq, our unit was on our way home. We had been a long time away from our families, and we had experienced some tough fighting. A third of our unit had already returned to their families in Germany when we were told we would be extended because of a changing situation on the ground. A wave of frustration went through our 18,000 soldiers. Our commander then pulled us together, communicated our new mission, and told us he was also disappointed, but it was time we had to show our grit by getting those soldiers who had already returned to Europe back, unpack our equipment, and return to the fight. Then he said something I will always remember: “It’s tough, but understand your soldiers are looking at you to lead in this crisis … and leaders don’t have the right to have a bad day.” He didn’t mean we couldn’t be frustrated, or disappointed, or emotional, or even pissed off. He meant we just couldn’t show it when others were around. That’s one of the toughest things about leading during a crisis: The unimaginable is expected of leaders. And leaders have to be ready to lead.

All this advice may seem like philosophical musings rather than pragmatic thoughts for a crisis, but hopefully this advice will make a difference as healthcare providers tackle the issues ahead. Stay healthy, mitigate risks, but know that the calm provided by leaders will make a difference.

A few days ago, I had a heartfelt conversation with my good friend Dr Omayra Mansfield. Dr Mansfield has been an Emergency Department Physician for more than 12 years. She is also the wife of another physician and the mother of two young children, the recently appointed Chief Medical Officer at a hospital at AdventHealth, and one of the first graduates of the Physician Leader Development Course I teach.

“During the leadership course, you always provided examples of how physicians are like soldiers,” she began. She reminded me of my words describing how both doctors and soldiers are part of a professional body, how both have a cherished ethos and a set of directing values to guide both their path and their actions as a very special part of our society, and how of all the professions in our society, the military and medicine are the only two that deal in life and death, albeit in very different ways.

She had certainly paid attention in our seminars. Now, as she and her team faced the COVID-19 pandemic, she realized their daily challenges are expanding and they are now going to war. The leadership discussions that had sparked so much debate in our colloquia had now become real.

Dr Mansfield explained that beyond caring for patients, one of her key concerns was the physical and emotional well-­being of the clinical staff at her hospital: the physicians, nurses, technicians, and clinicians under her care. Getting to her point, she asked if I might have any suggestions based on my time and experiences in combat that might be helpful to her as she “cared for her troops” as they faced the battle ahead.

Her request was a good one. Lessons from my military past immediately rushed to my mind. I started scribbling and came up with a Top Ten list of recommendations for anyone going into a tough fight. Here’s what I sent to her:

1. Find a battle-buddy. On the first day of Army basic training, drill sergeants pair new recruits with one another. That’s primarily for accountability purposes throughout the weeks of training—to ensure soldiers hold each other responsible for getting to the right place, at the right time, in the right uniform—but it’s also part of a larger psychological dynamic related to building teams and mutual support within organizations. Your battle-buddy is charged with keeping you out of trouble, having your back, and being there when you need it most. In combat, battle-buddies do all those things and then some; they protect you from harm in so many other ways. Healthcare providers during this crisis will sometimes feel all alone, and they need to rely on someone else to help them when times get really tough. Having a battle-buddy—for those at the healthcare team level, of course, but also among those at the level of clinical director, hospital administrator, CMO, or even CEO—will help get you through the tough times and provide sanity when you need it the most. So my first piece of advice: Find a battle-buddy.
2. Plan and prepare for things you don’t expect will happen. During a preparatory training exercise for our unit’s deployment to Iraq during the surge, when we thought the exercise was about to end, the trainers surprised us with a final crisis we had to solve. According to the scenario, Al Qaida had blown up a major bridge in our area, causing dire logistical problems for the security forces and challenges to the population as they brought their goods to market. I remember my initial reaction: “They don’t have the strength to do that. This’ll never happen,” I said to the Chief of Staff under my breath, as we started developing the required drill to counter the action and please the trainers. I quickly forgot about that lesson, until after we deployed. Two weeks into our 15-month tour in Iraq, the enemy blew the exact bridge that was part of the scenario, causing the exact problems that were predicted. Because we had prepared for the unexpected, we were able to quickly repair the bridge, reestablish the logistics flow, and satisfy the worried population. The lesson: Teams can hope for the best, but it’s always important to prepare for the worst—a lack of equipment, a key member of the team not being available to contribute, an overwhelming surge of patients—and then develop a plan to mitigate it. Take time to reflect, and ask yourself, What is the worst that can happen, what can the “enemy” do to disrupt our lives, and how do we prepare to counter it?
3. Get everyone into the fight. In every organizations, it’s often true that some people take on too much and try and do it all themselves, others do only what they’re told to do, there’s the unique few who want to contribute but don’t know how they can to help, and then there’s some who even attempt to avoid contributing at all. It’s important for leaders to know who on their team fits each of these categories. It’s even more critical for leaders to be able to find ways to relieve the overworked, assign tasks to those who might not know their role, bring those who want to contribute into the fold, and cross-train teams to help relieve those who are exhausted. Leaders must look across their “battlespace” and ensure everyone is contributing. Leaders assign everyone tasks and do their best to level—and lighten—the load of the overworked.
4. “Fatigue makes cowards of us all.” During any type of crisis, the body and mind will rapidly break down from lack of sleep, emotional strain, or overwhelming stress. While a 12-hour shift in a hospital is exceedingly tough even during normal operations, the COVID-19 crisis will demand dramatically more of all the members of any healthcare team. For that reason, leaders must incorporate rest cycles, team rotations, and half-days away from the hospitals even when all hands are on deck, as well as consider reducing shift times, if possible. Many who have experienced the disease in hot spots say this is really tough, but not attempting to plan for this will cause eventual breakdown and dysfunction. Take a break, do all you can to maintain a modicum of balance, and get away for a while.
5. Take time to huddle. Communication and information are always key, but especially critical during any crisis. One technique that has proven valuable, beyond meetings and shift changes, is a preshift and postshift huddle. Different from the formal passing of critical information, the huddle is a brief opportunity for teams to pass informal information, look each other in the eye, and perhaps even pray together. As a two-star general, I did that every morning in combat with my small team of sergeants, captains, and privates before we left the headquarters to visit units, and it gave us all the power of knowing we had shared information, and we had a common operating picture. It gave us strength. During a crisis, all kinds of communication, formal and informal, are key.
6. This ain’t peacetime. In a crisis, the enemy gets a vote. If leaders don’t find ways to counter the enemy’s action (and fast!), they’ll be behind the curve! It’s important to find the techniques and procedures that are bureaucratic (or even dumb) and overturn or eliminate them quickly. Decisions must be made with alacrity and with an understood flow, and people must be assigned responsibilities and held accountable to make things happen. In a crisis, speed in action will almost always trump perfection in understanding. Stay calm but ensure that those who might not understand this come around to the dynamics associated with the threat. A crisis isn’t the time for business as usual.
7. Force adaptation—don’t wait ’til things are over to adjust. In a crisis, faults and disconnects in techniques and procedures often bubble to the surface and cause consternation. Don’t wait for a break in the action to adjust and find new ways to do things because a break in the action will usually never happen. The military has an expression: “Those who adapt the fastest on the battlefield win.” Find ways to look for and then publicize your methods of adaptation to the team, pin the rose on someone to ensure the changes are made, and then have someone make a historical record so other teams might also learn from your scar tissue. Lessons from the fight must be incorporated by the organization, or they’re not “lessons learned.”
8. Talkin’ ain’t fightin’. During a crisis, it’s important to establish techniques of verbal shorthand between the members of a team, and everyone must know their responsibilities and required actions. In the military, this is called a battle drill; in medicine, you know it as a code. In these situations, leaders must find ways to pass information quickly, and the reaction should be immediate response. In a crisis, normal process must take on the dynamics of a “code.” All members of the team must understand that there are just times when things can’t be explained, but it’s also important that leaders know when to use this abbreviated format. Explain when you can, but act when you must.
9. Cherish your teams. Every single team will experience things that human beings aren’t designed or meant to handle—even those in the medical profession, who likely thought they had seen it all. There will be repeated and overwhelming trauma, with the expected emotional reactions. The approach during these situations requires empathy, humility, emotional understanding, and validation. Praise your team at every opportunity, find ways to turn mistakes into learning opportunities, but most importantly be human and find ways to provide memories that your team can cherish and look back upon. Give them memories.
10. Leaders don’t have the right to have a bad day. In 2004, after a 12-month deployment in Iraq, our unit was on our way home. We had been a long time away from our families, and we had experienced some tough fighting. A third of our unit had already returned to their families in Germany when we were told we would be extended because of a changing situation on the ground. A wave of frustration went through our 18,000 soldiers. Our commander then pulled us together, communicated our new mission, and told us he was also disappointed, but it was time we had to show our grit by getting those soldiers who had already returned to Europe back, unpack our equipment, and return to the fight. Then he said something I will always remember: “It’s tough, but understand your soldiers are looking at you to lead in this crisis … and leaders don’t have the right to have a bad day.” He didn’t mean we couldn’t be frustrated, or disappointed, or emotional, or even pissed off. He meant we just couldn’t show it when others were around. That’s one of the toughest things about leading during a crisis: The unimaginable is expected of leaders. And leaders have to be ready to lead.

All this advice may seem like philosophical musings rather than pragmatic thoughts for a crisis, but hopefully this advice will make a difference as healthcare providers tackle the issues ahead. Stay healthy, mitigate risks, but know that the calm provided by leaders will make a difference.

Younger women treated for uterine or ovarian cancer are at increased risk for decreased bone mineral density and osteoporosis, especially in the first year after diagnosis, and they should be screened for bone changes, investigators advise.

This recommendation is based on results from a retrospective study of women, age 65 years and younger, all of whom underwent oophorectomy and most of whom received chemotherapy. Half of the women who had normal bone mineral density (BMD) at baseline were at risk for osteopenia or osteoporosis 5 years after diagnosis.

Rates of patients at risk for osteoporosis roughly doubled each year for the first 3 years of follow-up, reported study author Janelle Sobecki, MD, of the University of Wisconsin–Madison, and colleagues.

Their research is detailed in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

“Clinicians should follow current National Comprehensive Cancer Network guidelines regarding bone mineral density screening in women under 65 years old with cancer who have undergone therapy affecting their ovarian function [ovarian removal and/or antiestrogen therapies],” Dr. Sobecki said in an interview.

“Our findings indicate women with gynecologic cancer undergoing ovarian removal and chemotherapy may warrant sooner bone density evaluation, as early as 1 year following treatment. Bone loss screening in this population is feasible using opportunistic CT imaging,” she added.

Current guidelines recommending routine BMD evaluation every 2 years in women who received treatments impairing ovarian function are based largely on data in breast cancer patients, but there is a paucity of data on women who undergo oophorectomy and cancer therapies, both of which are known risk factors for bone loss, Dr. Sobecki noted.

“Bone loss is an important issue for women’s cancer survivorship, particularly for women who we expect to have long survival,” she said. “Identifying bone loss early is important for long-term bone health and prevention of osteoporosis in cancer survivors.”
 

Patient analysis

To get a better picture of long-term BMD changes and osteoporosis risk in younger patients, Dr. Sobecki and colleagues conducted a retrospective cohort study of women with uterine or ovarian cancers who underwent oophorectomy from 2010 to 2015.

The investigators calculated CT-based L1 trabecular attenuation BMD measurements (Hounsfield units, HU) on CT scans performed at baseline and at 1 year, 3 years, 5 years, and beyond 5 years after cancer diagnosis.

Osteoporosis risk was defined based on HU. Less than 100 HU was deemed “concerning” for osteoporosis, 100-150 HU was suggestive of osteopenia, and more than 150 HU indicated normal BMD.

The investigators reviewed scans for 185 patients with a median age of 55 years and a mean body mass index of 32 kg/m². Each patient had at least a baseline scan and one additional CT scan during follow-up.

The majority of patients (78.1%) had ovarian cancer, 78.1% underwent chemotherapy, and 17.1% were treated with external beam radiation. As of 2019, 118 patients (63.6%) were still alive.
 

Results and next steps

The investigators found that BMD decreased from a mean of 179.4 HU at baseline to 146.5 HU at 1 year, a significant decline (P < .001), and to 123.63 HU beyond 5 years (P < .001). As noted before, half of the patients with normal BMD at baseline were at risk for osteopenia or osteoporosis at 5 years.

The proportion of patients at risk for osteoporosis at baseline was 4.3%, compared with 7.4% at 1 year, 15.7% at 3 years, 18% at 5 years, and 23.3% beyond 5 years. BMD at baseline was a significant predictor for bone loss at all time points. In multivariate analysis, chemotherapy predicted bone loss at 1 year (P = .03), and current smoking predicted BMD decrease at 5 years (^P < .01).

“We plan to further investigate the role of chemotherapy in bone loss in gynecologic cancer patients, including chemotherapy dose-related bone loss,” Dr. Sobecki said. “We also plan to investigate bone loss in older women [over the age of 65] undergoing treatment for gynecologic cancer as they may be at greater risk than their baseline age-related risk.”

This study was internally funded. Dr. Sobecki reported no conflicts of interest.

SOURCE: Sobecki J et al. SGO 2020, Abstract 130.

Younger women treated for uterine or ovarian cancer are at increased risk for decreased bone mineral density and osteoporosis, especially in the first year after diagnosis, and they should be screened for bone changes, investigators advise.

This recommendation is based on results from a retrospective study of women, age 65 years and younger, all of whom underwent oophorectomy and most of whom received chemotherapy. Half of the women who had normal bone mineral density (BMD) at baseline were at risk for osteopenia or osteoporosis 5 years after diagnosis.

Rates of patients at risk for osteoporosis roughly doubled each year for the first 3 years of follow-up, reported study author Janelle Sobecki, MD, of the University of Wisconsin–Madison, and colleagues.

Their research is detailed in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

“Clinicians should follow current National Comprehensive Cancer Network guidelines regarding bone mineral density screening in women under 65 years old with cancer who have undergone therapy affecting their ovarian function [ovarian removal and/or antiestrogen therapies],” Dr. Sobecki said in an interview.

“Our findings indicate women with gynecologic cancer undergoing ovarian removal and chemotherapy may warrant sooner bone density evaluation, as early as 1 year following treatment. Bone loss screening in this population is feasible using opportunistic CT imaging,” she added.

Current guidelines recommending routine BMD evaluation every 2 years in women who received treatments impairing ovarian function are based largely on data in breast cancer patients, but there is a paucity of data on women who undergo oophorectomy and cancer therapies, both of which are known risk factors for bone loss, Dr. Sobecki noted.

“Bone loss is an important issue for women’s cancer survivorship, particularly for women who we expect to have long survival,” she said. “Identifying bone loss early is important for long-term bone health and prevention of osteoporosis in cancer survivors.”
 

Patient analysis

To get a better picture of long-term BMD changes and osteoporosis risk in younger patients, Dr. Sobecki and colleagues conducted a retrospective cohort study of women with uterine or ovarian cancers who underwent oophorectomy from 2010 to 2015.

The investigators calculated CT-based L1 trabecular attenuation BMD measurements (Hounsfield units, HU) on CT scans performed at baseline and at 1 year, 3 years, 5 years, and beyond 5 years after cancer diagnosis.

Osteoporosis risk was defined based on HU. Less than 100 HU was deemed “concerning” for osteoporosis, 100-150 HU was suggestive of osteopenia, and more than 150 HU indicated normal BMD.

The investigators reviewed scans for 185 patients with a median age of 55 years and a mean body mass index of 32 kg/m². Each patient had at least a baseline scan and one additional CT scan during follow-up.

The majority of patients (78.1%) had ovarian cancer, 78.1% underwent chemotherapy, and 17.1% were treated with external beam radiation. As of 2019, 118 patients (63.6%) were still alive.
 

Results and next steps

The investigators found that BMD decreased from a mean of 179.4 HU at baseline to 146.5 HU at 1 year, a significant decline (P < .001), and to 123.63 HU beyond 5 years (P < .001). As noted before, half of the patients with normal BMD at baseline were at risk for osteopenia or osteoporosis at 5 years.

The proportion of patients at risk for osteoporosis at baseline was 4.3%, compared with 7.4% at 1 year, 15.7% at 3 years, 18% at 5 years, and 23.3% beyond 5 years. BMD at baseline was a significant predictor for bone loss at all time points. In multivariate analysis, chemotherapy predicted bone loss at 1 year (P = .03), and current smoking predicted BMD decrease at 5 years (^P < .01).

“We plan to further investigate the role of chemotherapy in bone loss in gynecologic cancer patients, including chemotherapy dose-related bone loss,” Dr. Sobecki said. “We also plan to investigate bone loss in older women [over the age of 65] undergoing treatment for gynecologic cancer as they may be at greater risk than their baseline age-related risk.”

This study was internally funded. Dr. Sobecki reported no conflicts of interest.

SOURCE: Sobecki J et al. SGO 2020, Abstract 130.

Younger women treated for uterine or ovarian cancer are at increased risk for decreased bone mineral density and osteoporosis, especially in the first year after diagnosis, and they should be screened for bone changes, investigators advise.

This recommendation is based on results from a retrospective study of women, age 65 years and younger, all of whom underwent oophorectomy and most of whom received chemotherapy. Half of the women who had normal bone mineral density (BMD) at baseline were at risk for osteopenia or osteoporosis 5 years after diagnosis.

Rates of patients at risk for osteoporosis roughly doubled each year for the first 3 years of follow-up, reported study author Janelle Sobecki, MD, of the University of Wisconsin–Madison, and colleagues.

Their research is detailed in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

“Clinicians should follow current National Comprehensive Cancer Network guidelines regarding bone mineral density screening in women under 65 years old with cancer who have undergone therapy affecting their ovarian function [ovarian removal and/or antiestrogen therapies],” Dr. Sobecki said in an interview.

“Our findings indicate women with gynecologic cancer undergoing ovarian removal and chemotherapy may warrant sooner bone density evaluation, as early as 1 year following treatment. Bone loss screening in this population is feasible using opportunistic CT imaging,” she added.

Current guidelines recommending routine BMD evaluation every 2 years in women who received treatments impairing ovarian function are based largely on data in breast cancer patients, but there is a paucity of data on women who undergo oophorectomy and cancer therapies, both of which are known risk factors for bone loss, Dr. Sobecki noted.

“Bone loss is an important issue for women’s cancer survivorship, particularly for women who we expect to have long survival,” she said. “Identifying bone loss early is important for long-term bone health and prevention of osteoporosis in cancer survivors.”
 

Patient analysis

To get a better picture of long-term BMD changes and osteoporosis risk in younger patients, Dr. Sobecki and colleagues conducted a retrospective cohort study of women with uterine or ovarian cancers who underwent oophorectomy from 2010 to 2015.

The investigators calculated CT-based L1 trabecular attenuation BMD measurements (Hounsfield units, HU) on CT scans performed at baseline and at 1 year, 3 years, 5 years, and beyond 5 years after cancer diagnosis.

Osteoporosis risk was defined based on HU. Less than 100 HU was deemed “concerning” for osteoporosis, 100-150 HU was suggestive of osteopenia, and more than 150 HU indicated normal BMD.

The investigators reviewed scans for 185 patients with a median age of 55 years and a mean body mass index of 32 kg/m². Each patient had at least a baseline scan and one additional CT scan during follow-up.

The majority of patients (78.1%) had ovarian cancer, 78.1% underwent chemotherapy, and 17.1% were treated with external beam radiation. As of 2019, 118 patients (63.6%) were still alive.
 

Results and next steps

The investigators found that BMD decreased from a mean of 179.4 HU at baseline to 146.5 HU at 1 year, a significant decline (P < .001), and to 123.63 HU beyond 5 years (P < .001). As noted before, half of the patients with normal BMD at baseline were at risk for osteopenia or osteoporosis at 5 years.

The proportion of patients at risk for osteoporosis at baseline was 4.3%, compared with 7.4% at 1 year, 15.7% at 3 years, 18% at 5 years, and 23.3% beyond 5 years. BMD at baseline was a significant predictor for bone loss at all time points. In multivariate analysis, chemotherapy predicted bone loss at 1 year (P = .03), and current smoking predicted BMD decrease at 5 years (^P < .01).

“We plan to further investigate the role of chemotherapy in bone loss in gynecologic cancer patients, including chemotherapy dose-related bone loss,” Dr. Sobecki said. “We also plan to investigate bone loss in older women [over the age of 65] undergoing treatment for gynecologic cancer as they may be at greater risk than their baseline age-related risk.”

This study was internally funded. Dr. Sobecki reported no conflicts of interest.

SOURCE: Sobecki J et al. SGO 2020, Abstract 130.

The Food and Drug Administration has approved a new rabbit-derived recombinant analog of human coagulation factor VII (Sevenfact) for the treatment of hemophilia A or B, according to a release from the agency.

The treatment’s approval is for use in patients aged 12 years and older who’ve developed inhibitors (neutralizing antibodies). This factor VII (FVII) analog bypasses the FVIII and FIX reactions, which are no longer effective pathways for treatment in these patients because of the inhibitors they’ve developed.

According to the release, “the active ingredient of Sevenfact is a recombinant analog of human FVII, which is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits’ milk. During purification and processing of the milk, FVII is converted into activated FVII.” The FDA’s Center for Veterinary Medicine has, after “comprehensive analysis of the scientific evidence,” determined that the process is safe for both the rabbits and handlers and that it is an effective means of producing the coagulation factor.

The approval is based on a clinical study that evaluated 27 patients with hemophilia A or B and included treatment for 465 mild to moderate events and 3 severe ones. The low (75 mcg/kg) or high (225 mcg/kg) dose was able to successfully treat 86% of the mild to moderate episodes, and all three of the severe ones were successfully treated with the high dose.

The most common side effects were headache, dizziness, infusion-site discomfort, infusion-related reaction, infusion-site hematoma, and fever. This product is contraindicated in patients with known allergies or hypersensitivities to rabbits or rabbit proteins. There is potential for increased risk of serious arterial or venous thrombotic events among patients with other risk factors for blood clots. More safety information can be found in the prescribing information, and more information about the approval can be found in the full release.

[email protected]

The Food and Drug Administration has approved a new rabbit-derived recombinant analog of human coagulation factor VII (Sevenfact) for the treatment of hemophilia A or B, according to a release from the agency.

The treatment’s approval is for use in patients aged 12 years and older who’ve developed inhibitors (neutralizing antibodies). This factor VII (FVII) analog bypasses the FVIII and FIX reactions, which are no longer effective pathways for treatment in these patients because of the inhibitors they’ve developed.

According to the release, “the active ingredient of Sevenfact is a recombinant analog of human FVII, which is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits’ milk. During purification and processing of the milk, FVII is converted into activated FVII.” The FDA’s Center for Veterinary Medicine has, after “comprehensive analysis of the scientific evidence,” determined that the process is safe for both the rabbits and handlers and that it is an effective means of producing the coagulation factor.

The approval is based on a clinical study that evaluated 27 patients with hemophilia A or B and included treatment for 465 mild to moderate events and 3 severe ones. The low (75 mcg/kg) or high (225 mcg/kg) dose was able to successfully treat 86% of the mild to moderate episodes, and all three of the severe ones were successfully treated with the high dose.

The most common side effects were headache, dizziness, infusion-site discomfort, infusion-related reaction, infusion-site hematoma, and fever. This product is contraindicated in patients with known allergies or hypersensitivities to rabbits or rabbit proteins. There is potential for increased risk of serious arterial or venous thrombotic events among patients with other risk factors for blood clots. More safety information can be found in the prescribing information, and more information about the approval can be found in the full release.

[email protected]

The Food and Drug Administration has approved a new rabbit-derived recombinant analog of human coagulation factor VII (Sevenfact) for the treatment of hemophilia A or B, according to a release from the agency.

The treatment’s approval is for use in patients aged 12 years and older who’ve developed inhibitors (neutralizing antibodies). This factor VII (FVII) analog bypasses the FVIII and FIX reactions, which are no longer effective pathways for treatment in these patients because of the inhibitors they’ve developed.

According to the release, “the active ingredient of Sevenfact is a recombinant analog of human FVII, which is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits’ milk. During purification and processing of the milk, FVII is converted into activated FVII.” The FDA’s Center for Veterinary Medicine has, after “comprehensive analysis of the scientific evidence,” determined that the process is safe for both the rabbits and handlers and that it is an effective means of producing the coagulation factor.

The approval is based on a clinical study that evaluated 27 patients with hemophilia A or B and included treatment for 465 mild to moderate events and 3 severe ones. The low (75 mcg/kg) or high (225 mcg/kg) dose was able to successfully treat 86% of the mild to moderate episodes, and all three of the severe ones were successfully treated with the high dose.

The most common side effects were headache, dizziness, infusion-site discomfort, infusion-related reaction, infusion-site hematoma, and fever. This product is contraindicated in patients with known allergies or hypersensitivities to rabbits or rabbit proteins. There is potential for increased risk of serious arterial or venous thrombotic events among patients with other risk factors for blood clots. More safety information can be found in the prescribing information, and more information about the approval can be found in the full release.

[email protected]

A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

[email protected]

This article was updated 4/7/20.

A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

[email protected]

This article was updated 4/7/20.

A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

[email protected]

This article was updated 4/7/20.

Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.

Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m²) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.

In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.

After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.

At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A_1c, the authors noted.

However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.

Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”

In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.

“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”

The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.

No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.

About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”

None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.

Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”

Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.

The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.

Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.

Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m²) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.

In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.

After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.

At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A_1c, the authors noted.

However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.

Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”

In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.

“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”

The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.

No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.

About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”

None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.

Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”

Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.

The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.

Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.

Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m²) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.

In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.

After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.

At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A_1c, the authors noted.

However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.

Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”

In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.

“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”

The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.

No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.

About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”

None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.

Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”

Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.

The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.

Screening for depression in patients with atopic dermatitis is a vital task that’s woefully neglected – and dermatologists aren’t doing any better a job of it than primary care physicians, Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.

Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.

“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.

For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.

“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.

“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”

If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”


 

Depression and anxiety in AD: How common?

In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.

The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).

“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.

In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).

In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.

HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).

An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.

“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.

[email protected]

Screening for depression in patients with atopic dermatitis is a vital task that’s woefully neglected – and dermatologists aren’t doing any better a job of it than primary care physicians, Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.

Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.

“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.

For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.

“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.

“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”

If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”


 

Depression and anxiety in AD: How common?

In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.

The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).

“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.

In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).

In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.

HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).

An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.

“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.

[email protected]

Screening for depression in patients with atopic dermatitis is a vital task that’s woefully neglected – and dermatologists aren’t doing any better a job of it than primary care physicians, Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.

Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.

“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.

For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.

“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.

“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”

If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”


 

Depression and anxiety in AD: How common?

In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.

The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).

“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.

In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).

In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.

HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).

An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.

“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.

[email protected]

A punch biopsy to rule out other causes of the patient’s signs and symptoms confirmed tattoo granulomas with sarcoidal nodules.

Tattoo granulomas can occur years after the initial placement of the tattoo. They appear, as in this case, as a thickening of the tattooed skin due to a hypersensitivity reaction to the foreign body. It has been more commonly reported in yellow and red inks but also has been reported in black ink. Sarcoidosis has been diagnosed based on occurrence in tattoos, but in this case, the patient’s calcium level was normal, chest X-ray showed no signs of adenopathy, and she had no symptoms of sarcoidosis such as fevers, chills, night sweats, or fatigue. Thus, no further work-up for systemic sarcoidosis was performed.

During the patient’s biopsy visit, she was started on oral montelukast 10 mg/d for a possible allergic reaction to the tattoo ink. By the time pathology results returned 1 week later, her itching and puffiness had resolved. Montelukast is a leukotriene antagonist that is approved by the US Food and Drug Administration (FDA) for use in asthma and allergic rhinitis; it is also used off label for chronic urticaria.

Usual therapies for tattoo granulomas include intralesional steroid injections or laser therapy to destroy the pigment. This patient had a large number of tattoos that would have required extensive laser therapy destruction of the pigment or numerous intralesional injections. Since she was no longer symptomatic, she elected to continue on the montelukast. She was cautioned about the possible development of suicidal ideation on this medication and was instructed to seek care if any such thoughts occurred.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A punch biopsy to rule out other causes of the patient’s signs and symptoms confirmed tattoo granulomas with sarcoidal nodules.

Tattoo granulomas can occur years after the initial placement of the tattoo. They appear, as in this case, as a thickening of the tattooed skin due to a hypersensitivity reaction to the foreign body. It has been more commonly reported in yellow and red inks but also has been reported in black ink. Sarcoidosis has been diagnosed based on occurrence in tattoos, but in this case, the patient’s calcium level was normal, chest X-ray showed no signs of adenopathy, and she had no symptoms of sarcoidosis such as fevers, chills, night sweats, or fatigue. Thus, no further work-up for systemic sarcoidosis was performed.

During the patient’s biopsy visit, she was started on oral montelukast 10 mg/d for a possible allergic reaction to the tattoo ink. By the time pathology results returned 1 week later, her itching and puffiness had resolved. Montelukast is a leukotriene antagonist that is approved by the US Food and Drug Administration (FDA) for use in asthma and allergic rhinitis; it is also used off label for chronic urticaria.

Usual therapies for tattoo granulomas include intralesional steroid injections or laser therapy to destroy the pigment. This patient had a large number of tattoos that would have required extensive laser therapy destruction of the pigment or numerous intralesional injections. Since she was no longer symptomatic, she elected to continue on the montelukast. She was cautioned about the possible development of suicidal ideation on this medication and was instructed to seek care if any such thoughts occurred.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A punch biopsy to rule out other causes of the patient’s signs and symptoms confirmed tattoo granulomas with sarcoidal nodules.

Tattoo granulomas can occur years after the initial placement of the tattoo. They appear, as in this case, as a thickening of the tattooed skin due to a hypersensitivity reaction to the foreign body. It has been more commonly reported in yellow and red inks but also has been reported in black ink. Sarcoidosis has been diagnosed based on occurrence in tattoos, but in this case, the patient’s calcium level was normal, chest X-ray showed no signs of adenopathy, and she had no symptoms of sarcoidosis such as fevers, chills, night sweats, or fatigue. Thus, no further work-up for systemic sarcoidosis was performed.

During the patient’s biopsy visit, she was started on oral montelukast 10 mg/d for a possible allergic reaction to the tattoo ink. By the time pathology results returned 1 week later, her itching and puffiness had resolved. Montelukast is a leukotriene antagonist that is approved by the US Food and Drug Administration (FDA) for use in asthma and allergic rhinitis; it is also used off label for chronic urticaria.

Usual therapies for tattoo granulomas include intralesional steroid injections or laser therapy to destroy the pigment. This patient had a large number of tattoos that would have required extensive laser therapy destruction of the pigment or numerous intralesional injections. Since she was no longer symptomatic, she elected to continue on the montelukast. She was cautioned about the possible development of suicidal ideation on this medication and was instructed to seek care if any such thoughts occurred.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

[email protected]

This article was updated 4/7/20.

A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

[email protected]

This article was updated 4/7/20.

A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

[email protected]

This article was updated 4/7/20.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.