In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.

Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.

At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.

In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.

The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.

“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.

The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO₂ concentration, or needed an intravenous infusion of vasopressors.

In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.

Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.

At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.

A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).

In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.

At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.

Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.

“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.

Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).

“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.

Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.

In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.

Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.

At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.

In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.

The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.

“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.

The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO₂ concentration, or needed an intravenous infusion of vasopressors.

In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.

Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.

At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.

A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).

In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.

At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.

Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.

“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.

Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).

“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.

Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.

In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.

Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.

At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.

In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.

The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.

“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.

The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO₂ concentration, or needed an intravenous infusion of vasopressors.

In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.

Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.

At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.

A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).

In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.

At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.

Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.

“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.

Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).

“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.

Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.

It’s bad enough that this month’s historic snowstorm left ordinary Texans scrambling for heat and resorting to melted snow for drinking, washing, and flushing. But what about hospitals, where sanitation is paramount and ample water is a sine qua non?

As pipes burst, pumps froze, and water pressure plummeted, patient care was affected as well as maintenance, food preparation, laundry, and heat. To counter the problems, several Texas hospitals stepped up to the plate with inventive responses.

In Houston, Texas’s largest city and no stranger to natural disasters, such as from Hurricanes Ike and Harvey, water pressure in the municipal supply system dropped after the Feb. 13 storm, creating a series of problems for some of Houston Methodist’s eight-hospital network. “At the worst point, two of our hospitals, Houston Methodist West and Houston Methodist Baytown, had no city water supply, one for over 48 hours and the other for 72 hours,” said Marc L. Boom, MD, MBA, Houston Methodist’s president and CEO.

Although the main hospital had a reserve supply of potable water, a supply of water for laundry, cooking, and cleaning was another matter. “We introduced significant water restrictions and had to have 6,000-gallon tankers bring in extra water,” Dr. Boom said.

One hospital in the network got creative. When it rained the day after the ice storm, the staff rigged up a rain collection system using the huge bins that move linens around the hospital to collect nonpotable water for cleaning and flushing toilets, Dr. Boom said. Another hospital was able to provide showers for staff by bringing in bathroom trailers with self-contained water supplies of the kind used at some sporting events.

And at some facilities, patients were discharged into the lobby as they could not return home with transportation, electricity, and water systems crippled. With widespread challenges continuing, even as temperatures warmed, President Biden signed a major disaster declaration Feb. 20 that will provide emergency assistance to residents and businesses in more than a third of Texas counties, including those surrounding Houston, Dallas, and Austin.

Although conditions forced the rescheduling of some nonemergent surgeries, the water shortage had no impact on COVID-19 care, except for the unavailability of showers in the case of mobile patients. “At the worst, they just had to use bucket flushing for the toilets,” Dr. Boom said.

And in an unexpected win, when a Harris County freezer for COVID-19 vaccine storage failed and threatened to spoil 8,400 precious doses, Dr. Boom’s center was able to take delivery on 1,000 doses and administer them in 3 hours at a hastily set up ad hoc immunization center. 

In all this, the lessons of the pandemic had a positive preparatory role. “2020 taught us to be agile as things change and to align our goals across different medical teams,” said Ben Saldana, MD, medical director of Houston Methodist’s emergency care centers. “And we were prepared for hurricanes, but not for snow.”
 

Increased pressure on emergency departments

As the outages continued and stress levels in the community rose, the network started seeing exacerbations of chronic conditions after the power shut-down incapacitated electrical devices running machines for heart assistance, oxygen delivery, and sleep apnea. “We started seeing food-borne illness and carbon monoxide poisoning, as well as more heart attacks, strokes, and sepsis,” Dr. Saldana said.

One serious strain on the network’s main hospital was the sudden need to accommodate large numbers of patients on dialysis, a procedure that uses a lot of water and is typically performed in small, vulnerable community facilities with limited infrastructure and no generators. “The hospitals are their backup and act as a safety net for them,” Boom said. Some hospital areas generally used for other types of conditions had to be marshaled for renal care.

Emergency rooms became pop-up dialysis centers, Dr. Saldana said. “And if the water pressure dropped, we had to cut dialysis time from the standard 4 hours to 2. That’s like putting a band-aid on patients.”

Fortunately, municipal water pressure in the Houston area has steadily risen and is almost back to normal. And according to Dr. Boom, the brutal storm may yet have a silver lining: a decline in county coronavirus cases as the storm and icy road conditions forced people to stay sequestered at home.

Further north in Austin, a number of hospitals lost municipal water pressure, creating a series of problems. Among them was St. David’s South Austin Medical Center, at which, according to reports in the Austin American-Statesman, staff members were at one point asked to use trash bags to remove waste from toilets, to refrain from showering, and to clean their hands only with sanitizer.

A statement issued by David Huffstutler, CEO of St. David’s HealthCare, acknowledged that the heating system is based on a water-fed boiler. When the building lost heat owing to lack of water, some patients had to be transferred elsewhere or discharged. The hospital distributed jugs and bottles of water for handwashing and drinking, and was working with city officials to obtain portable toilets.

Meanwhile, officials at Austin’s Dell Children’s Medical Center acknowledged in a memo that its toilets no longer had “flushing capabilities.” Other area hospitals in the Ascension Seton network were also suffering from compromised water supplies last week, according to local news reports.

Washroom facilities were affected elsewhere as well. A post on a medical association Facebook page referred to a memo ordering staff to use a single toilet in an outpatient area for bowel movements and warned them to limit their time there. No paper or other products were to be used in other toilets designated for urination.
 

‘The pandemic was the prelude to the ice storm’

Some hospitals fared better. Along the Coastal Bend, Corpus Christi Medical Center managed to maintain its electricity and water supply to ensure continuity of hospital services after the storm, according to a statement.

But back in Houston, Liz Youngblood, MBA, RN, president of Baylor St. Luke’s Medical Center, said a number of hospitals in her network experienced low water pressure after the storm.

“Fortunately, we had water conservation measures and low-water alerts in place for such emergencies,” she said. “And we rely on water tankers to help maintain enough pressure for the basics.”

Some of the challenges posed by the storm are quite similar to what St. Luke’s faced after Hurricane Harvey in 2017. “We had already made plans to address them and so we felt prepared,” Ms. Youngblood said.

And thanks to COVID-19, Texas hospitals have been operating in crisis mode for the past year. “The pandemic was the prelude to the ice storm,” said Gina Blocker, MD, a St. Luke’s ED physician, “so we had measures and teams in place. We did have some reduction in water pressure, though the pressure was still good.”

But the hospital was inundated with patients looking for shelter. “Some were just scared about what might happen to them if their heat didn’t come back on and they wanted to be where they could get care,” Dr. Blocker said. Others came in with expected storm-related injuries such as hypothermia and carbon monoxide poisoning.

According to Ms. Youngblood, little compromise in patient care was necessary except for the cancellation of some operations and vaccinations owing to the treacherous travel conditions. “But one of the biggest remaining issues is that we need plenty of blood, so we’re encouraging people to donate at their local centers.”

A version of this article first appeared on Medscape.com

It’s bad enough that this month’s historic snowstorm left ordinary Texans scrambling for heat and resorting to melted snow for drinking, washing, and flushing. But what about hospitals, where sanitation is paramount and ample water is a sine qua non?

As pipes burst, pumps froze, and water pressure plummeted, patient care was affected as well as maintenance, food preparation, laundry, and heat. To counter the problems, several Texas hospitals stepped up to the plate with inventive responses.

In Houston, Texas’s largest city and no stranger to natural disasters, such as from Hurricanes Ike and Harvey, water pressure in the municipal supply system dropped after the Feb. 13 storm, creating a series of problems for some of Houston Methodist’s eight-hospital network. “At the worst point, two of our hospitals, Houston Methodist West and Houston Methodist Baytown, had no city water supply, one for over 48 hours and the other for 72 hours,” said Marc L. Boom, MD, MBA, Houston Methodist’s president and CEO.

Although the main hospital had a reserve supply of potable water, a supply of water for laundry, cooking, and cleaning was another matter. “We introduced significant water restrictions and had to have 6,000-gallon tankers bring in extra water,” Dr. Boom said.

One hospital in the network got creative. When it rained the day after the ice storm, the staff rigged up a rain collection system using the huge bins that move linens around the hospital to collect nonpotable water for cleaning and flushing toilets, Dr. Boom said. Another hospital was able to provide showers for staff by bringing in bathroom trailers with self-contained water supplies of the kind used at some sporting events.

And at some facilities, patients were discharged into the lobby as they could not return home with transportation, electricity, and water systems crippled. With widespread challenges continuing, even as temperatures warmed, President Biden signed a major disaster declaration Feb. 20 that will provide emergency assistance to residents and businesses in more than a third of Texas counties, including those surrounding Houston, Dallas, and Austin.

Although conditions forced the rescheduling of some nonemergent surgeries, the water shortage had no impact on COVID-19 care, except for the unavailability of showers in the case of mobile patients. “At the worst, they just had to use bucket flushing for the toilets,” Dr. Boom said.

And in an unexpected win, when a Harris County freezer for COVID-19 vaccine storage failed and threatened to spoil 8,400 precious doses, Dr. Boom’s center was able to take delivery on 1,000 doses and administer them in 3 hours at a hastily set up ad hoc immunization center. 

In all this, the lessons of the pandemic had a positive preparatory role. “2020 taught us to be agile as things change and to align our goals across different medical teams,” said Ben Saldana, MD, medical director of Houston Methodist’s emergency care centers. “And we were prepared for hurricanes, but not for snow.”
 

Increased pressure on emergency departments

As the outages continued and stress levels in the community rose, the network started seeing exacerbations of chronic conditions after the power shut-down incapacitated electrical devices running machines for heart assistance, oxygen delivery, and sleep apnea. “We started seeing food-borne illness and carbon monoxide poisoning, as well as more heart attacks, strokes, and sepsis,” Dr. Saldana said.

One serious strain on the network’s main hospital was the sudden need to accommodate large numbers of patients on dialysis, a procedure that uses a lot of water and is typically performed in small, vulnerable community facilities with limited infrastructure and no generators. “The hospitals are their backup and act as a safety net for them,” Boom said. Some hospital areas generally used for other types of conditions had to be marshaled for renal care.

Emergency rooms became pop-up dialysis centers, Dr. Saldana said. “And if the water pressure dropped, we had to cut dialysis time from the standard 4 hours to 2. That’s like putting a band-aid on patients.”

Fortunately, municipal water pressure in the Houston area has steadily risen and is almost back to normal. And according to Dr. Boom, the brutal storm may yet have a silver lining: a decline in county coronavirus cases as the storm and icy road conditions forced people to stay sequestered at home.

Further north in Austin, a number of hospitals lost municipal water pressure, creating a series of problems. Among them was St. David’s South Austin Medical Center, at which, according to reports in the Austin American-Statesman, staff members were at one point asked to use trash bags to remove waste from toilets, to refrain from showering, and to clean their hands only with sanitizer.

A statement issued by David Huffstutler, CEO of St. David’s HealthCare, acknowledged that the heating system is based on a water-fed boiler. When the building lost heat owing to lack of water, some patients had to be transferred elsewhere or discharged. The hospital distributed jugs and bottles of water for handwashing and drinking, and was working with city officials to obtain portable toilets.

Meanwhile, officials at Austin’s Dell Children’s Medical Center acknowledged in a memo that its toilets no longer had “flushing capabilities.” Other area hospitals in the Ascension Seton network were also suffering from compromised water supplies last week, according to local news reports.

Washroom facilities were affected elsewhere as well. A post on a medical association Facebook page referred to a memo ordering staff to use a single toilet in an outpatient area for bowel movements and warned them to limit their time there. No paper or other products were to be used in other toilets designated for urination.
 

‘The pandemic was the prelude to the ice storm’

Some hospitals fared better. Along the Coastal Bend, Corpus Christi Medical Center managed to maintain its electricity and water supply to ensure continuity of hospital services after the storm, according to a statement.

But back in Houston, Liz Youngblood, MBA, RN, president of Baylor St. Luke’s Medical Center, said a number of hospitals in her network experienced low water pressure after the storm.

“Fortunately, we had water conservation measures and low-water alerts in place for such emergencies,” she said. “And we rely on water tankers to help maintain enough pressure for the basics.”

Some of the challenges posed by the storm are quite similar to what St. Luke’s faced after Hurricane Harvey in 2017. “We had already made plans to address them and so we felt prepared,” Ms. Youngblood said.

And thanks to COVID-19, Texas hospitals have been operating in crisis mode for the past year. “The pandemic was the prelude to the ice storm,” said Gina Blocker, MD, a St. Luke’s ED physician, “so we had measures and teams in place. We did have some reduction in water pressure, though the pressure was still good.”

But the hospital was inundated with patients looking for shelter. “Some were just scared about what might happen to them if their heat didn’t come back on and they wanted to be where they could get care,” Dr. Blocker said. Others came in with expected storm-related injuries such as hypothermia and carbon monoxide poisoning.

According to Ms. Youngblood, little compromise in patient care was necessary except for the cancellation of some operations and vaccinations owing to the treacherous travel conditions. “But one of the biggest remaining issues is that we need plenty of blood, so we’re encouraging people to donate at their local centers.”

A version of this article first appeared on Medscape.com

It’s bad enough that this month’s historic snowstorm left ordinary Texans scrambling for heat and resorting to melted snow for drinking, washing, and flushing. But what about hospitals, where sanitation is paramount and ample water is a sine qua non?

As pipes burst, pumps froze, and water pressure plummeted, patient care was affected as well as maintenance, food preparation, laundry, and heat. To counter the problems, several Texas hospitals stepped up to the plate with inventive responses.

In Houston, Texas’s largest city and no stranger to natural disasters, such as from Hurricanes Ike and Harvey, water pressure in the municipal supply system dropped after the Feb. 13 storm, creating a series of problems for some of Houston Methodist’s eight-hospital network. “At the worst point, two of our hospitals, Houston Methodist West and Houston Methodist Baytown, had no city water supply, one for over 48 hours and the other for 72 hours,” said Marc L. Boom, MD, MBA, Houston Methodist’s president and CEO.

Although the main hospital had a reserve supply of potable water, a supply of water for laundry, cooking, and cleaning was another matter. “We introduced significant water restrictions and had to have 6,000-gallon tankers bring in extra water,” Dr. Boom said.

One hospital in the network got creative. When it rained the day after the ice storm, the staff rigged up a rain collection system using the huge bins that move linens around the hospital to collect nonpotable water for cleaning and flushing toilets, Dr. Boom said. Another hospital was able to provide showers for staff by bringing in bathroom trailers with self-contained water supplies of the kind used at some sporting events.

And at some facilities, patients were discharged into the lobby as they could not return home with transportation, electricity, and water systems crippled. With widespread challenges continuing, even as temperatures warmed, President Biden signed a major disaster declaration Feb. 20 that will provide emergency assistance to residents and businesses in more than a third of Texas counties, including those surrounding Houston, Dallas, and Austin.

Although conditions forced the rescheduling of some nonemergent surgeries, the water shortage had no impact on COVID-19 care, except for the unavailability of showers in the case of mobile patients. “At the worst, they just had to use bucket flushing for the toilets,” Dr. Boom said.

And in an unexpected win, when a Harris County freezer for COVID-19 vaccine storage failed and threatened to spoil 8,400 precious doses, Dr. Boom’s center was able to take delivery on 1,000 doses and administer them in 3 hours at a hastily set up ad hoc immunization center. 

In all this, the lessons of the pandemic had a positive preparatory role. “2020 taught us to be agile as things change and to align our goals across different medical teams,” said Ben Saldana, MD, medical director of Houston Methodist’s emergency care centers. “And we were prepared for hurricanes, but not for snow.”
 

Increased pressure on emergency departments

As the outages continued and stress levels in the community rose, the network started seeing exacerbations of chronic conditions after the power shut-down incapacitated electrical devices running machines for heart assistance, oxygen delivery, and sleep apnea. “We started seeing food-borne illness and carbon monoxide poisoning, as well as more heart attacks, strokes, and sepsis,” Dr. Saldana said.

One serious strain on the network’s main hospital was the sudden need to accommodate large numbers of patients on dialysis, a procedure that uses a lot of water and is typically performed in small, vulnerable community facilities with limited infrastructure and no generators. “The hospitals are their backup and act as a safety net for them,” Boom said. Some hospital areas generally used for other types of conditions had to be marshaled for renal care.

Emergency rooms became pop-up dialysis centers, Dr. Saldana said. “And if the water pressure dropped, we had to cut dialysis time from the standard 4 hours to 2. That’s like putting a band-aid on patients.”

Fortunately, municipal water pressure in the Houston area has steadily risen and is almost back to normal. And according to Dr. Boom, the brutal storm may yet have a silver lining: a decline in county coronavirus cases as the storm and icy road conditions forced people to stay sequestered at home.

Further north in Austin, a number of hospitals lost municipal water pressure, creating a series of problems. Among them was St. David’s South Austin Medical Center, at which, according to reports in the Austin American-Statesman, staff members were at one point asked to use trash bags to remove waste from toilets, to refrain from showering, and to clean their hands only with sanitizer.

A statement issued by David Huffstutler, CEO of St. David’s HealthCare, acknowledged that the heating system is based on a water-fed boiler. When the building lost heat owing to lack of water, some patients had to be transferred elsewhere or discharged. The hospital distributed jugs and bottles of water for handwashing and drinking, and was working with city officials to obtain portable toilets.

Meanwhile, officials at Austin’s Dell Children’s Medical Center acknowledged in a memo that its toilets no longer had “flushing capabilities.” Other area hospitals in the Ascension Seton network were also suffering from compromised water supplies last week, according to local news reports.

Washroom facilities were affected elsewhere as well. A post on a medical association Facebook page referred to a memo ordering staff to use a single toilet in an outpatient area for bowel movements and warned them to limit their time there. No paper or other products were to be used in other toilets designated for urination.
 

‘The pandemic was the prelude to the ice storm’

Some hospitals fared better. Along the Coastal Bend, Corpus Christi Medical Center managed to maintain its electricity and water supply to ensure continuity of hospital services after the storm, according to a statement.

But back in Houston, Liz Youngblood, MBA, RN, president of Baylor St. Luke’s Medical Center, said a number of hospitals in her network experienced low water pressure after the storm.

“Fortunately, we had water conservation measures and low-water alerts in place for such emergencies,” she said. “And we rely on water tankers to help maintain enough pressure for the basics.”

Some of the challenges posed by the storm are quite similar to what St. Luke’s faced after Hurricane Harvey in 2017. “We had already made plans to address them and so we felt prepared,” Ms. Youngblood said.

And thanks to COVID-19, Texas hospitals have been operating in crisis mode for the past year. “The pandemic was the prelude to the ice storm,” said Gina Blocker, MD, a St. Luke’s ED physician, “so we had measures and teams in place. We did have some reduction in water pressure, though the pressure was still good.”

But the hospital was inundated with patients looking for shelter. “Some were just scared about what might happen to them if their heat didn’t come back on and they wanted to be where they could get care,” Dr. Blocker said. Others came in with expected storm-related injuries such as hypothermia and carbon monoxide poisoning.

According to Ms. Youngblood, little compromise in patient care was necessary except for the cancellation of some operations and vaccinations owing to the treacherous travel conditions. “But one of the biggest remaining issues is that we need plenty of blood, so we’re encouraging people to donate at their local centers.”

A version of this article first appeared on Medscape.com

Long-term use of continuous positive airway pressure (CPAP) was associated with higher self-reported physical activity levels in adults with co-occurring obstructive sleep apnea (OSA) and cardiovascular disease (CVD), in new research.

“The aim of this study was to determine whether long-term CPAP treatment affects self-reported physical activity among participants with moderate-severe OSA and comorbid CV disease,” wrote David Stevens, PhD, of Flinders University, Adelaide, Australia, and his colleagues. The findings were recently published in the Journal of Clinical Sleep Medicine.

Researchers conducted a secondary analysis of the Sleep apnea cardiovascular endpoints (SAVE) trial that enrolled 2,687 adults aged 45-75 years old with OSA and confirmed CVD. In the study, participants were randomized to receive either CPAP plus usual care or usual care alone.

Physical activity levels were self-reported using the Leisure-Time Exercise Questionnaire (LTEQ) at baseline and at 6-, 24-, and 48-month follow-up intervals. The physical functioning subscale of the 36-item short form questionnaire (SF-36) was used to determine if activity levels were consistent with expert recommendations and to evaluate the effects on any self-perceived limitation of physical activity.
 

Moderate physical activity was higher among CPAP users

After a mean follow-up duration of 3.7 years, participants in the CPAP arm had approximately 20% higher levels of moderate physical activity, compared with the control arm (adjusted mean scores]: 8.7 points vs. 7.3 points; 95% confidence interval, 7.5-9.9 vs. 6.1-8.5; P = .003).

However, no significant difference was observed between treatment arms for mild physical activity (adjusted mean scores, 14.4 points vs. 14.2 points; 95% CI, 13.5-15.3 vs. 13.3-15.1; P = 0.599) or vigorous physical activity (adjusted mean scores, 3.4 points vs. 2.9 points; 95% CI 2.6-4.2 vs. 2.1-3.7; P = .125).

In addition, participants in the CPAP group reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score = 1.66; 95% CI, 0.87-2.45; P < .001) and were more likely to report activity levels consistent with guideline recommendations.

“We were pleasantly surprised to find that people assigned to CPAP reported more physical activity than their counterparts who received usual care, despite being given no specific exercise instructions,” Kelly A. Loffler, PhD, a coauthor of the study, said in an interview.

“While I don’t think this will result in any immediate changes to guidelines, it is a helpful reminder to clinicians who are treating such patients, that the symptomatic benefits people experience with CPAP present a window of opportunity to improve health more holistically,” Dr. Loffler explained.

The researchers acknowledged that a key limitation of the study was the use of self-reported outcome measures. In future studies, they recommended that recent technological innovations, such as the availability of activity tracking devices, should be used to measure physical activity.

They also noted that patients with excessive sleepiness and severe hypoxemia were excluded from the SAVE trial; thus, the findings may not be generalizable to all patients.
 

Study reinforces CPAP’s health benefits

Emerson M. Wickwire, PhD, associate professor of psychiatry and medicine at the University of Maryland, Baltimore, explained that CPAP treatment is associated with well-documented health benefits among patients with CVD, as well as enhanced quality of life.

“These results provide further evidence that treating OSA can provide direct and indirect health benefits, suggesting that increased physical activity can be a vital pathway to improved cardiovascular health and enjoyment of life,” Dr. Wickwire, who is also director of the Insomnia Program at the University of Maryland Midtown Medical Center, Baltimore, said in an interview.

Steven M. Scharf, MD, a pulmonologist who is director of the Sleep Disorders Center (Adults) at the University of Maryland, also said the study findings were consistent with previous research involving patients treated for OSA.

“It is no surprise that treatment of OSA improves patient’s daily physical functioning,” explained Dr. Scharf, who is also a clinical professor, in an interview. “These results are expected, but very welcome, and I was glad to see them.”

The study was funded by the National Health and Medical Research Council of Australia, the Respironics Sleep and Respiratory Research Foundation, and Philips Respironics. Some authors reported financial affiliations with medical device and pharmaceutical companies. Dr. Loffler, Dr. Wickwire, and Dr. Scharf reported no conflicts of interest related to this work.

Long-term use of continuous positive airway pressure (CPAP) was associated with higher self-reported physical activity levels in adults with co-occurring obstructive sleep apnea (OSA) and cardiovascular disease (CVD), in new research.

“The aim of this study was to determine whether long-term CPAP treatment affects self-reported physical activity among participants with moderate-severe OSA and comorbid CV disease,” wrote David Stevens, PhD, of Flinders University, Adelaide, Australia, and his colleagues. The findings were recently published in the Journal of Clinical Sleep Medicine.

Researchers conducted a secondary analysis of the Sleep apnea cardiovascular endpoints (SAVE) trial that enrolled 2,687 adults aged 45-75 years old with OSA and confirmed CVD. In the study, participants were randomized to receive either CPAP plus usual care or usual care alone.

Physical activity levels were self-reported using the Leisure-Time Exercise Questionnaire (LTEQ) at baseline and at 6-, 24-, and 48-month follow-up intervals. The physical functioning subscale of the 36-item short form questionnaire (SF-36) was used to determine if activity levels were consistent with expert recommendations and to evaluate the effects on any self-perceived limitation of physical activity.
 

Moderate physical activity was higher among CPAP users

After a mean follow-up duration of 3.7 years, participants in the CPAP arm had approximately 20% higher levels of moderate physical activity, compared with the control arm (adjusted mean scores]: 8.7 points vs. 7.3 points; 95% confidence interval, 7.5-9.9 vs. 6.1-8.5; P = .003).

However, no significant difference was observed between treatment arms for mild physical activity (adjusted mean scores, 14.4 points vs. 14.2 points; 95% CI, 13.5-15.3 vs. 13.3-15.1; P = 0.599) or vigorous physical activity (adjusted mean scores, 3.4 points vs. 2.9 points; 95% CI 2.6-4.2 vs. 2.1-3.7; P = .125).

In addition, participants in the CPAP group reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score = 1.66; 95% CI, 0.87-2.45; P < .001) and were more likely to report activity levels consistent with guideline recommendations.

“We were pleasantly surprised to find that people assigned to CPAP reported more physical activity than their counterparts who received usual care, despite being given no specific exercise instructions,” Kelly A. Loffler, PhD, a coauthor of the study, said in an interview.

“While I don’t think this will result in any immediate changes to guidelines, it is a helpful reminder to clinicians who are treating such patients, that the symptomatic benefits people experience with CPAP present a window of opportunity to improve health more holistically,” Dr. Loffler explained.

The researchers acknowledged that a key limitation of the study was the use of self-reported outcome measures. In future studies, they recommended that recent technological innovations, such as the availability of activity tracking devices, should be used to measure physical activity.

They also noted that patients with excessive sleepiness and severe hypoxemia were excluded from the SAVE trial; thus, the findings may not be generalizable to all patients.
 

Study reinforces CPAP’s health benefits

Emerson M. Wickwire, PhD, associate professor of psychiatry and medicine at the University of Maryland, Baltimore, explained that CPAP treatment is associated with well-documented health benefits among patients with CVD, as well as enhanced quality of life.

“These results provide further evidence that treating OSA can provide direct and indirect health benefits, suggesting that increased physical activity can be a vital pathway to improved cardiovascular health and enjoyment of life,” Dr. Wickwire, who is also director of the Insomnia Program at the University of Maryland Midtown Medical Center, Baltimore, said in an interview.

Steven M. Scharf, MD, a pulmonologist who is director of the Sleep Disorders Center (Adults) at the University of Maryland, also said the study findings were consistent with previous research involving patients treated for OSA.

“It is no surprise that treatment of OSA improves patient’s daily physical functioning,” explained Dr. Scharf, who is also a clinical professor, in an interview. “These results are expected, but very welcome, and I was glad to see them.”

The study was funded by the National Health and Medical Research Council of Australia, the Respironics Sleep and Respiratory Research Foundation, and Philips Respironics. Some authors reported financial affiliations with medical device and pharmaceutical companies. Dr. Loffler, Dr. Wickwire, and Dr. Scharf reported no conflicts of interest related to this work.

Long-term use of continuous positive airway pressure (CPAP) was associated with higher self-reported physical activity levels in adults with co-occurring obstructive sleep apnea (OSA) and cardiovascular disease (CVD), in new research.

“The aim of this study was to determine whether long-term CPAP treatment affects self-reported physical activity among participants with moderate-severe OSA and comorbid CV disease,” wrote David Stevens, PhD, of Flinders University, Adelaide, Australia, and his colleagues. The findings were recently published in the Journal of Clinical Sleep Medicine.

Researchers conducted a secondary analysis of the Sleep apnea cardiovascular endpoints (SAVE) trial that enrolled 2,687 adults aged 45-75 years old with OSA and confirmed CVD. In the study, participants were randomized to receive either CPAP plus usual care or usual care alone.

Physical activity levels were self-reported using the Leisure-Time Exercise Questionnaire (LTEQ) at baseline and at 6-, 24-, and 48-month follow-up intervals. The physical functioning subscale of the 36-item short form questionnaire (SF-36) was used to determine if activity levels were consistent with expert recommendations and to evaluate the effects on any self-perceived limitation of physical activity.
 

Moderate physical activity was higher among CPAP users

After a mean follow-up duration of 3.7 years, participants in the CPAP arm had approximately 20% higher levels of moderate physical activity, compared with the control arm (adjusted mean scores]: 8.7 points vs. 7.3 points; 95% confidence interval, 7.5-9.9 vs. 6.1-8.5; P = .003).

However, no significant difference was observed between treatment arms for mild physical activity (adjusted mean scores, 14.4 points vs. 14.2 points; 95% CI, 13.5-15.3 vs. 13.3-15.1; P = 0.599) or vigorous physical activity (adjusted mean scores, 3.4 points vs. 2.9 points; 95% CI 2.6-4.2 vs. 2.1-3.7; P = .125).

In addition, participants in the CPAP group reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score = 1.66; 95% CI, 0.87-2.45; P < .001) and were more likely to report activity levels consistent with guideline recommendations.

“We were pleasantly surprised to find that people assigned to CPAP reported more physical activity than their counterparts who received usual care, despite being given no specific exercise instructions,” Kelly A. Loffler, PhD, a coauthor of the study, said in an interview.

“While I don’t think this will result in any immediate changes to guidelines, it is a helpful reminder to clinicians who are treating such patients, that the symptomatic benefits people experience with CPAP present a window of opportunity to improve health more holistically,” Dr. Loffler explained.

The researchers acknowledged that a key limitation of the study was the use of self-reported outcome measures. In future studies, they recommended that recent technological innovations, such as the availability of activity tracking devices, should be used to measure physical activity.

They also noted that patients with excessive sleepiness and severe hypoxemia were excluded from the SAVE trial; thus, the findings may not be generalizable to all patients.
 

Study reinforces CPAP’s health benefits

Emerson M. Wickwire, PhD, associate professor of psychiatry and medicine at the University of Maryland, Baltimore, explained that CPAP treatment is associated with well-documented health benefits among patients with CVD, as well as enhanced quality of life.

“These results provide further evidence that treating OSA can provide direct and indirect health benefits, suggesting that increased physical activity can be a vital pathway to improved cardiovascular health and enjoyment of life,” Dr. Wickwire, who is also director of the Insomnia Program at the University of Maryland Midtown Medical Center, Baltimore, said in an interview.

Steven M. Scharf, MD, a pulmonologist who is director of the Sleep Disorders Center (Adults) at the University of Maryland, also said the study findings were consistent with previous research involving patients treated for OSA.

“It is no surprise that treatment of OSA improves patient’s daily physical functioning,” explained Dr. Scharf, who is also a clinical professor, in an interview. “These results are expected, but very welcome, and I was glad to see them.”

The study was funded by the National Health and Medical Research Council of Australia, the Respironics Sleep and Respiratory Research Foundation, and Philips Respironics. Some authors reported financial affiliations with medical device and pharmaceutical companies. Dr. Loffler, Dr. Wickwire, and Dr. Scharf reported no conflicts of interest related to this work.

Case

The patient is a 65-year-old female with increasing anxiety and agitation. She completed cycle 2 of chemotherapy for breast cancer several hours ago. Her premedication was Reglan (metoclopramide); her only other medication is tamoxifen. Other than breast cancer, she suffers only from osteoarthritis.

She is found pacing about the ward – almost uncontrollably. She feels she must move, only to have to stop and, shortly afterwards, feels the urge to move again. This has never happened to her before. She must move despite being fatigued. She also complains of an odd overall feeling; something akin to “ant in the pants.” She is nervous and exhausted. What is her diagnosis and what clues to it are in her presentation?
 

Background

The word “akathisia” is derived from the Greek language and means “unable to sit.” It is thought to occur as a consequence of dopaminergic blockade in the midbrain region. The decrease in dopaminergic activity leads to a subsequent decrease in inhibitory motor control which, in turn, manifests as involuntary movements.

In this malady, the patient is seen as perpetually in motion. The patient feels the need to move until they must stop. But once static, they have the urge to move again. They pace, they rock and they ‘fidget’ – they just cannot sit still. This feeling has been likened to having “ants in the pants.” Patients become anxious, agitated, and suffer from insomnia. They cannot rest.

If left unresolved akathisia can torment patients to sheer exhaustion. For some it serves as a harbinger of suicide. This toxicity is more commonly seen in the psychiatric pharmacy with the most common offender being haloperidol. The causative agents of the least notoriety are the non-antipsychotics.
 

Diagnosis and treatment

Akathisia is an extrapyramidal symptom found largely but NOT exclusively with psychiatric medications. There are drugs in the non-psychiatric field that can also cause it, including antiemetics (e.g., metoclopramide), antihypertensives (e.g., diltiazem), and narcotics (e.g., cocaine). Metoclopramide is given under circumstances ranging from diabetic gastroparesis to premedicating chemotherapy. It is a peripheral and centrally acting dopamine antagonist. There are no lab tests or radiographic workups to diagnose akathisia. Its manifestations are erratic and disturbing, and the prognosis is doleful if unresolved.

The primary intervention for the treatment of akathisia is its recognition and the discontinuation of the offending drug. Beyond this, for symptomatic care, there is a compendium of case reports and small studies supporting many drugs, but only a few have received consistent recommendation. Beta-adrenergic antagonists, such as propranolol, are considered the gold standard, the first choice for the treatment of akathisia. Their toxicities include orthostatic hypotension and bradycardia. Additionally, they are contraindicated in the setting of asthma.

Anticholinergics, such as benztropine (cogentin) and trihexylphenidyl (artane) are considered in the literature as 2nd line treatments, behind beta-blockers. However, the data advocating their use is limited. They have multiple side-effects including sedation, memory impairment, visual impairment, and urinary retention. They are also contraindicated in patients with closed-angle glaucoma.

An equivalent alternative to beta-blockers could also be the 5HT2a receptor antagonists such as mirtazapine (remeron) and cyproheptadine (periactin). This class of medications is thought to act by an inhibitory control of dopaminergic neurons. Sedation and weight gain are the primary toxicities, and they are contraindicated in patients who are breastfeeding.

Benzodiazepines, such as clonazepam (klonopin), have shown some efficacy in improving symptoms but the data is very limited. The risk of tolerance and dependence, coupled with the problems of sedation impacting the elderly, prompts their placement in reserve. Vitamin B6 (pyridoxine), when given in a high dose format, causes significant improvement in akathisia. However, it can cause headache and nausea. Chronic administration of high doses has also been found to cause a severe and irreversible sensory neuropathy as well as lead to seizures. Many other agents have been studied, but the data are too small to warrant recommendation.
 

Conclusion

Akathisia remains an extreme reaction to drugs not always in the psychotropic class. The hospitalist will likely deal with the acute onset, a dramatic form, and a potentially poor outcome if untreated. The patient’s only true defense is the physician’s clinical acumen and their ability to recognize it.

Dr. Killeen is a physician in Tampa, Fla. He practices internal medicine, hematology, and oncology, and has worked in hospice and hospital medicine.

Recommended reading

Van Gool AR, Doorduijn JK, Sevnaeve C. Severe akathisia as a side effect of metoclopramide. Pharm World Sci. 2010; 32(6):704-706.

Loonen AJM, Stahl SM. The mechanism of drug-induced akathisia. CNS Spectr. 2010;15(11):491-494.

Forcen FE, Matsoukas K, Alici Y. Antipsychotic-induced akathisia in delirium: A systemic review. Palliat Support Care. 2016;14(1):77-84.

Sethuram K, Gedzior J. Akathisia: Case presentation and review of newer treatment agents. Psychiatric Annals. 2014;44(8):391-396.

Pringsheim T, et al. The assessment and treatment of antipsychotic-induced akathisia. Can J Psychiatry. 2018;63(11): 719-729.

Tachere RO, Mandana M. Beyond anxiety and agitation: A clinical approach to akathisia. Royal Australian Coll Gen Practitioners. 2017;46(5): 296-298.

Key points

• Although associated more with psychiatric medications, akathisia can occur with non-psychotropics as well.
• To recognize the illness, the clinician must notice the repetitive involuntary movements and pacing as well as the “ants in the pants” fidgeting involved.
• Primary treatment consists of medication discontinuation with pharmaceutical intervention as a backup.
• Recognition is the key to successful treatment.

Classic signs of akathisia

• Fidgeting – “ants in the pants”
• Swinging the legs while seated
• Rocking from foot to foot
• Walking while in a static position
• Inability to sit or stand still – pacing
• Onset appears with the initiation or dose adjustment of an offending drug

Quiz

1. Which of the following findings occur in Akathisia?

A. Fidgeting

B. Pacing

C. Swinging the legs while seated

D. All the above

Answer: D

Akathisia is manifest as involuntary hyperactivity of the extremities, particularly the lower extremities. People feel the urge to move, to continue endlessly in motion, stopping only when fatigue sets in. The fidgeting has been described by patients as feeling like “ants in the pants.”
 

2. Which of the following interventions are used to treat akathisia?

A. Drug discontinuation

B. Propranolol

C. Mirtazapine

D. All the above

Answer: D

All the interventions mentioned are used to treat akathisia. The foremost is to stop the offending drug. Failing this, propranolol is the “gold standard” while 5HT2a antagonists, such as mirtazapine, are favored when beta-blockers either fail or are contraindicated.
 

3. The use of pyridoxine (Vitamin B6) in the treatment of akathisia is associated with what toxicities?

A. Headache

B. Nausea

C. Seizures

D. All the above

Answer: D

The use of Vitamin B6 in the treatment of akathisia has several drawbacks. Its administration is associated with headache and nausea, and high dose usage increases the risk of seizure.
 

4. If unresolved, akathisia can lead to which of the following?

A. Insomnia

B. Suicide

C. Physical exhaustion

D. All the above

Answer: D

Akathisia, left unrecognized and untreated, can eventually lead to physical exhaustion, and is compounded by difficulties in trying to rest, hence insomnia. The physical and mental torment of this malady can lead to suicide.

Case

The patient is a 65-year-old female with increasing anxiety and agitation. She completed cycle 2 of chemotherapy for breast cancer several hours ago. Her premedication was Reglan (metoclopramide); her only other medication is tamoxifen. Other than breast cancer, she suffers only from osteoarthritis.

She is found pacing about the ward – almost uncontrollably. She feels she must move, only to have to stop and, shortly afterwards, feels the urge to move again. This has never happened to her before. She must move despite being fatigued. She also complains of an odd overall feeling; something akin to “ant in the pants.” She is nervous and exhausted. What is her diagnosis and what clues to it are in her presentation?
 

Background

The word “akathisia” is derived from the Greek language and means “unable to sit.” It is thought to occur as a consequence of dopaminergic blockade in the midbrain region. The decrease in dopaminergic activity leads to a subsequent decrease in inhibitory motor control which, in turn, manifests as involuntary movements.

In this malady, the patient is seen as perpetually in motion. The patient feels the need to move until they must stop. But once static, they have the urge to move again. They pace, they rock and they ‘fidget’ – they just cannot sit still. This feeling has been likened to having “ants in the pants.” Patients become anxious, agitated, and suffer from insomnia. They cannot rest.

If left unresolved akathisia can torment patients to sheer exhaustion. For some it serves as a harbinger of suicide. This toxicity is more commonly seen in the psychiatric pharmacy with the most common offender being haloperidol. The causative agents of the least notoriety are the non-antipsychotics.
 

Diagnosis and treatment

Akathisia is an extrapyramidal symptom found largely but NOT exclusively with psychiatric medications. There are drugs in the non-psychiatric field that can also cause it, including antiemetics (e.g., metoclopramide), antihypertensives (e.g., diltiazem), and narcotics (e.g., cocaine). Metoclopramide is given under circumstances ranging from diabetic gastroparesis to premedicating chemotherapy. It is a peripheral and centrally acting dopamine antagonist. There are no lab tests or radiographic workups to diagnose akathisia. Its manifestations are erratic and disturbing, and the prognosis is doleful if unresolved.

The primary intervention for the treatment of akathisia is its recognition and the discontinuation of the offending drug. Beyond this, for symptomatic care, there is a compendium of case reports and small studies supporting many drugs, but only a few have received consistent recommendation. Beta-adrenergic antagonists, such as propranolol, are considered the gold standard, the first choice for the treatment of akathisia. Their toxicities include orthostatic hypotension and bradycardia. Additionally, they are contraindicated in the setting of asthma.

Anticholinergics, such as benztropine (cogentin) and trihexylphenidyl (artane) are considered in the literature as 2nd line treatments, behind beta-blockers. However, the data advocating their use is limited. They have multiple side-effects including sedation, memory impairment, visual impairment, and urinary retention. They are also contraindicated in patients with closed-angle glaucoma.

An equivalent alternative to beta-blockers could also be the 5HT2a receptor antagonists such as mirtazapine (remeron) and cyproheptadine (periactin). This class of medications is thought to act by an inhibitory control of dopaminergic neurons. Sedation and weight gain are the primary toxicities, and they are contraindicated in patients who are breastfeeding.

Benzodiazepines, such as clonazepam (klonopin), have shown some efficacy in improving symptoms but the data is very limited. The risk of tolerance and dependence, coupled with the problems of sedation impacting the elderly, prompts their placement in reserve. Vitamin B6 (pyridoxine), when given in a high dose format, causes significant improvement in akathisia. However, it can cause headache and nausea. Chronic administration of high doses has also been found to cause a severe and irreversible sensory neuropathy as well as lead to seizures. Many other agents have been studied, but the data are too small to warrant recommendation.
 

Conclusion

Akathisia remains an extreme reaction to drugs not always in the psychotropic class. The hospitalist will likely deal with the acute onset, a dramatic form, and a potentially poor outcome if untreated. The patient’s only true defense is the physician’s clinical acumen and their ability to recognize it.

Dr. Killeen is a physician in Tampa, Fla. He practices internal medicine, hematology, and oncology, and has worked in hospice and hospital medicine.

Recommended reading

Van Gool AR, Doorduijn JK, Sevnaeve C. Severe akathisia as a side effect of metoclopramide. Pharm World Sci. 2010; 32(6):704-706.

Loonen AJM, Stahl SM. The mechanism of drug-induced akathisia. CNS Spectr. 2010;15(11):491-494.

Forcen FE, Matsoukas K, Alici Y. Antipsychotic-induced akathisia in delirium: A systemic review. Palliat Support Care. 2016;14(1):77-84.

Sethuram K, Gedzior J. Akathisia: Case presentation and review of newer treatment agents. Psychiatric Annals. 2014;44(8):391-396.

Pringsheim T, et al. The assessment and treatment of antipsychotic-induced akathisia. Can J Psychiatry. 2018;63(11): 719-729.

Tachere RO, Mandana M. Beyond anxiety and agitation: A clinical approach to akathisia. Royal Australian Coll Gen Practitioners. 2017;46(5): 296-298.

Key points

• Although associated more with psychiatric medications, akathisia can occur with non-psychotropics as well.
• To recognize the illness, the clinician must notice the repetitive involuntary movements and pacing as well as the “ants in the pants” fidgeting involved.
• Primary treatment consists of medication discontinuation with pharmaceutical intervention as a backup.
• Recognition is the key to successful treatment.

Classic signs of akathisia

• Fidgeting – “ants in the pants”
• Swinging the legs while seated
• Rocking from foot to foot
• Walking while in a static position
• Inability to sit or stand still – pacing
• Onset appears with the initiation or dose adjustment of an offending drug

Quiz

1. Which of the following findings occur in Akathisia?

A. Fidgeting

B. Pacing

C. Swinging the legs while seated

D. All the above

Answer: D

Akathisia is manifest as involuntary hyperactivity of the extremities, particularly the lower extremities. People feel the urge to move, to continue endlessly in motion, stopping only when fatigue sets in. The fidgeting has been described by patients as feeling like “ants in the pants.”
 

2. Which of the following interventions are used to treat akathisia?

A. Drug discontinuation

B. Propranolol

C. Mirtazapine

D. All the above

Answer: D

All the interventions mentioned are used to treat akathisia. The foremost is to stop the offending drug. Failing this, propranolol is the “gold standard” while 5HT2a antagonists, such as mirtazapine, are favored when beta-blockers either fail or are contraindicated.
 

3. The use of pyridoxine (Vitamin B6) in the treatment of akathisia is associated with what toxicities?

A. Headache

B. Nausea

C. Seizures

D. All the above

Answer: D

The use of Vitamin B6 in the treatment of akathisia has several drawbacks. Its administration is associated with headache and nausea, and high dose usage increases the risk of seizure.
 

4. If unresolved, akathisia can lead to which of the following?

A. Insomnia

B. Suicide

C. Physical exhaustion

D. All the above

Answer: D

Akathisia, left unrecognized and untreated, can eventually lead to physical exhaustion, and is compounded by difficulties in trying to rest, hence insomnia. The physical and mental torment of this malady can lead to suicide.

Case

The patient is a 65-year-old female with increasing anxiety and agitation. She completed cycle 2 of chemotherapy for breast cancer several hours ago. Her premedication was Reglan (metoclopramide); her only other medication is tamoxifen. Other than breast cancer, she suffers only from osteoarthritis.

She is found pacing about the ward – almost uncontrollably. She feels she must move, only to have to stop and, shortly afterwards, feels the urge to move again. This has never happened to her before. She must move despite being fatigued. She also complains of an odd overall feeling; something akin to “ant in the pants.” She is nervous and exhausted. What is her diagnosis and what clues to it are in her presentation?
 

Background

The word “akathisia” is derived from the Greek language and means “unable to sit.” It is thought to occur as a consequence of dopaminergic blockade in the midbrain region. The decrease in dopaminergic activity leads to a subsequent decrease in inhibitory motor control which, in turn, manifests as involuntary movements.

In this malady, the patient is seen as perpetually in motion. The patient feels the need to move until they must stop. But once static, they have the urge to move again. They pace, they rock and they ‘fidget’ – they just cannot sit still. This feeling has been likened to having “ants in the pants.” Patients become anxious, agitated, and suffer from insomnia. They cannot rest.

If left unresolved akathisia can torment patients to sheer exhaustion. For some it serves as a harbinger of suicide. This toxicity is more commonly seen in the psychiatric pharmacy with the most common offender being haloperidol. The causative agents of the least notoriety are the non-antipsychotics.
 

Diagnosis and treatment

Akathisia is an extrapyramidal symptom found largely but NOT exclusively with psychiatric medications. There are drugs in the non-psychiatric field that can also cause it, including antiemetics (e.g., metoclopramide), antihypertensives (e.g., diltiazem), and narcotics (e.g., cocaine). Metoclopramide is given under circumstances ranging from diabetic gastroparesis to premedicating chemotherapy. It is a peripheral and centrally acting dopamine antagonist. There are no lab tests or radiographic workups to diagnose akathisia. Its manifestations are erratic and disturbing, and the prognosis is doleful if unresolved.

The primary intervention for the treatment of akathisia is its recognition and the discontinuation of the offending drug. Beyond this, for symptomatic care, there is a compendium of case reports and small studies supporting many drugs, but only a few have received consistent recommendation. Beta-adrenergic antagonists, such as propranolol, are considered the gold standard, the first choice for the treatment of akathisia. Their toxicities include orthostatic hypotension and bradycardia. Additionally, they are contraindicated in the setting of asthma.

Anticholinergics, such as benztropine (cogentin) and trihexylphenidyl (artane) are considered in the literature as 2nd line treatments, behind beta-blockers. However, the data advocating their use is limited. They have multiple side-effects including sedation, memory impairment, visual impairment, and urinary retention. They are also contraindicated in patients with closed-angle glaucoma.

An equivalent alternative to beta-blockers could also be the 5HT2a receptor antagonists such as mirtazapine (remeron) and cyproheptadine (periactin). This class of medications is thought to act by an inhibitory control of dopaminergic neurons. Sedation and weight gain are the primary toxicities, and they are contraindicated in patients who are breastfeeding.

Benzodiazepines, such as clonazepam (klonopin), have shown some efficacy in improving symptoms but the data is very limited. The risk of tolerance and dependence, coupled with the problems of sedation impacting the elderly, prompts their placement in reserve. Vitamin B6 (pyridoxine), when given in a high dose format, causes significant improvement in akathisia. However, it can cause headache and nausea. Chronic administration of high doses has also been found to cause a severe and irreversible sensory neuropathy as well as lead to seizures. Many other agents have been studied, but the data are too small to warrant recommendation.
 

Conclusion

Akathisia remains an extreme reaction to drugs not always in the psychotropic class. The hospitalist will likely deal with the acute onset, a dramatic form, and a potentially poor outcome if untreated. The patient’s only true defense is the physician’s clinical acumen and their ability to recognize it.

Dr. Killeen is a physician in Tampa, Fla. He practices internal medicine, hematology, and oncology, and has worked in hospice and hospital medicine.

Recommended reading

Van Gool AR, Doorduijn JK, Sevnaeve C. Severe akathisia as a side effect of metoclopramide. Pharm World Sci. 2010; 32(6):704-706.

Loonen AJM, Stahl SM. The mechanism of drug-induced akathisia. CNS Spectr. 2010;15(11):491-494.

Forcen FE, Matsoukas K, Alici Y. Antipsychotic-induced akathisia in delirium: A systemic review. Palliat Support Care. 2016;14(1):77-84.

Sethuram K, Gedzior J. Akathisia: Case presentation and review of newer treatment agents. Psychiatric Annals. 2014;44(8):391-396.

Pringsheim T, et al. The assessment and treatment of antipsychotic-induced akathisia. Can J Psychiatry. 2018;63(11): 719-729.

Tachere RO, Mandana M. Beyond anxiety and agitation: A clinical approach to akathisia. Royal Australian Coll Gen Practitioners. 2017;46(5): 296-298.

Key points

• Although associated more with psychiatric medications, akathisia can occur with non-psychotropics as well.
• To recognize the illness, the clinician must notice the repetitive involuntary movements and pacing as well as the “ants in the pants” fidgeting involved.
• Primary treatment consists of medication discontinuation with pharmaceutical intervention as a backup.
• Recognition is the key to successful treatment.

Classic signs of akathisia

• Fidgeting – “ants in the pants”
• Swinging the legs while seated
• Rocking from foot to foot
• Walking while in a static position
• Inability to sit or stand still – pacing
• Onset appears with the initiation or dose adjustment of an offending drug

Quiz

1. Which of the following findings occur in Akathisia?

A. Fidgeting

B. Pacing

C. Swinging the legs while seated

D. All the above

Answer: D

Akathisia is manifest as involuntary hyperactivity of the extremities, particularly the lower extremities. People feel the urge to move, to continue endlessly in motion, stopping only when fatigue sets in. The fidgeting has been described by patients as feeling like “ants in the pants.”
 

2. Which of the following interventions are used to treat akathisia?

A. Drug discontinuation

B. Propranolol

C. Mirtazapine

D. All the above

Answer: D

All the interventions mentioned are used to treat akathisia. The foremost is to stop the offending drug. Failing this, propranolol is the “gold standard” while 5HT2a antagonists, such as mirtazapine, are favored when beta-blockers either fail or are contraindicated.
 

3. The use of pyridoxine (Vitamin B6) in the treatment of akathisia is associated with what toxicities?

A. Headache

B. Nausea

C. Seizures

D. All the above

Answer: D

The use of Vitamin B6 in the treatment of akathisia has several drawbacks. Its administration is associated with headache and nausea, and high dose usage increases the risk of seizure.
 

4. If unresolved, akathisia can lead to which of the following?

A. Insomnia

B. Suicide

C. Physical exhaustion

D. All the above

Answer: D

Akathisia, left unrecognized and untreated, can eventually lead to physical exhaustion, and is compounded by difficulties in trying to rest, hence insomnia. The physical and mental torment of this malady can lead to suicide.

REFERENCES

1. CDC. COVID-19 vaccination. Accessed February 22, 2021.
2. CDC. COVID data tracker. Accessed February 22, 2021.
3. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2020;69:1922-1924. Accessed February 22, 2021.
4. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2021;69:1653-1656. Accessed February 22, 2021.
5. Gee J, Marquez P, Su J, et al. First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020–January 13, 2021. MMWR Morbid Mortal Wkly Rep. ePub: February 19, 2021. Accessed February 22, 2021.
6. CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:125-129. Accessed February 25, 2021.

REFERENCES

1. CDC. COVID-19 vaccination. Accessed February 22, 2021.
2. CDC. COVID data tracker. Accessed February 22, 2021.
3. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2020;69:1922-1924. Accessed February 22, 2021.
4. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2021;69:1653-1656. Accessed February 22, 2021.
5. Gee J, Marquez P, Su J, et al. First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020–January 13, 2021. MMWR Morbid Mortal Wkly Rep. ePub: February 19, 2021. Accessed February 22, 2021.
6. CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:125-129. Accessed February 25, 2021.

REFERENCES

1. CDC. COVID-19 vaccination. Accessed February 22, 2021.
2. CDC. COVID data tracker. Accessed February 22, 2021.
3. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2020;69:1922-1924. Accessed February 22, 2021.
4. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2021;69:1653-1656. Accessed February 22, 2021.
5. Gee J, Marquez P, Su J, et al. First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020–January 13, 2021. MMWR Morbid Mortal Wkly Rep. ePub: February 19, 2021. Accessed February 22, 2021.
6. CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:125-129. Accessed February 25, 2021.

Doctors say a woman in Michigan contracted COVID-19 and died last fall 2 months after receiving a tainted double-lung transplant from a donor who turned out to harbor the virus that causes the disease – despite showing no signs of illness and initially testing negative.

Officials at the University of Michigan Medical School suggested it may be the first proven case of COVID-19 in the U.S. in which the virus was transmitted via an organ transplant. A surgeon who handled the donor lungs was also infected with the virus and fell ill but later recovered.

The incident appears to be isolated – the only confirmed case among nearly 40,000 transplants in 2020. But it has led to calls for more thorough testing of lung transplant donors, with samples taken from deep within the donor lungs as well as the nose and throat, said Dr. Daniel Kaul, director of Michigan Medicine’s transplant infectious disease service.

“We would absolutely not have used the lungs if we’d had a positive COVID-19 test,” said Dr. Kaul, who coauthored a report about the case in the American Journal of Transplantation.

The virus was transmitted when lungs from a woman from the Upper Midwest, who died after suffering a severe brain injury in a car accident, were transplanted into a woman with chronic obstructive lung disease at University Hospital in Ann Arbor. The nose and throat samples routinely collected from both organ donors and recipients tested negative for SARS-CoV-2, the virus that causes covid.

“All the screening that we normally do and are able to do, we did,” Dr. Kaul said.

Three days after the operation, however, the recipient spiked a fever; her blood pressure fell and her breathing became labored. Imaging showed signs of lung infection.

As her condition worsened, the patient developed septic shock and heart function problems. Doctors decided to test for SARS-CoV-2, Dr. Kaul said. Samples from her new lungs came back positive.

Suspicious about the origin of the infection, doctors returned to samples from the transplant donor. A molecular test of a swab from the donor’s nose and throat, taken 48 hours after her lungs were procured, had been negative for SARS-Cov-2. The donor’s family told doctors she had no history of recent travel or COVID-19 symptoms and no known exposure to anyone with the disease.

But doctors had kept a sample of fluid washed from deep within the donor lungs. When they tested that fluid, it was positive for the virus. Four days after the transplant, the surgeon who handled the donor lungs and performed the surgery tested positive, too. Genetic screening revealed that the transplant recipient and the surgeon had been infected by the donor. Ten other members of the transplant team tested negative for the virus.

The transplant recipient deteriorated rapidly, developing multisystem organ failure. Doctors tried known treatments for COVID-19, including remdesivir, a newly approved drug, and convalescent blood plasma from people previously infected with the disease. Eventually, she was placed on the last-resort option of ECMO, or extracorporeal membrane oxygenation, to no avail. Life support was withdrawn, and she died 61 days after the transplant.

Dr. Kaul called the incident “a tragic case.”

While the Michigan case marks the first confirmed incident in the U.S. of transmission through a transplant, others have been suspected. A recent Centers for Disease Control and Prevention report reviewed eight possible cases of what’s known as donor-derived infection that occurred last spring, but concluded the most likely source of transmission of the COVID-19 virus in those cases was in a community or health care setting.

Before this incident, it was not clear whether the COVID-19 virus could be transmitted through solid organ transplants, though it’s well documented with other respiratory viruses. Donor transmission of H1N1 2009 pandemic influenza has been detected almost exclusively in lung transplant recipients, Dr. Kaul noted.

While it’s not surprising that SARS-CoV-2 can be transmitted through infected lungs, it remains uncertain whether other organs affected by COVID-19 – hearts, livers and kidneys, for instance – can transmit the virus, too.

“It seems for non-lung donors that it may be very difficult to transmit COVID-19, even if the donor has COVID-19,” Dr. Kaul said.

Organ donors have been tested routinely for SARS-CoV-2 during the pandemic, though it’s not required by the Organ Procurement and Transplantation Network, or OPTN, which oversees transplants in the U.S. But the Michigan case underscores the need for more extensive sampling before transplant, especially in areas with high rates of covid transmission, Dr. Kaul said.

When it comes to lungs, that means making sure to test samples from the donor’s lower respiratory tract, as well as from the nose and throat. Obtaining and testing such samples from donors can be difficult to carry out in a timely fashion. There’s also the risk of introducing infection into the donated lungs, Dr. Kaul said.

Because no organs other than lungs were used, the Michigan case doesn’t provide insight into testing protocols for other organs.

Overall, viral transmissions from organ donors to recipients remain rare, occurring in fewer than 1% of transplant recipients, research shows. The medical risks facing ailing patients who reject a donor organ are generally far higher, said Dr. David Klassen, chief medical officer with the United Network for Organ Sharing, the federal contractor that runs the OPTN.

“The risks of turning down transplants are catastrophic,” he said. “I don’t think patients should be afraid of the transplant process.”
 

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Doctors say a woman in Michigan contracted COVID-19 and died last fall 2 months after receiving a tainted double-lung transplant from a donor who turned out to harbor the virus that causes the disease – despite showing no signs of illness and initially testing negative.

Officials at the University of Michigan Medical School suggested it may be the first proven case of COVID-19 in the U.S. in which the virus was transmitted via an organ transplant. A surgeon who handled the donor lungs was also infected with the virus and fell ill but later recovered.

The incident appears to be isolated – the only confirmed case among nearly 40,000 transplants in 2020. But it has led to calls for more thorough testing of lung transplant donors, with samples taken from deep within the donor lungs as well as the nose and throat, said Dr. Daniel Kaul, director of Michigan Medicine’s transplant infectious disease service.

“We would absolutely not have used the lungs if we’d had a positive COVID-19 test,” said Dr. Kaul, who coauthored a report about the case in the American Journal of Transplantation.

The virus was transmitted when lungs from a woman from the Upper Midwest, who died after suffering a severe brain injury in a car accident, were transplanted into a woman with chronic obstructive lung disease at University Hospital in Ann Arbor. The nose and throat samples routinely collected from both organ donors and recipients tested negative for SARS-CoV-2, the virus that causes covid.

“All the screening that we normally do and are able to do, we did,” Dr. Kaul said.

Three days after the operation, however, the recipient spiked a fever; her blood pressure fell and her breathing became labored. Imaging showed signs of lung infection.

As her condition worsened, the patient developed septic shock and heart function problems. Doctors decided to test for SARS-CoV-2, Dr. Kaul said. Samples from her new lungs came back positive.

Suspicious about the origin of the infection, doctors returned to samples from the transplant donor. A molecular test of a swab from the donor’s nose and throat, taken 48 hours after her lungs were procured, had been negative for SARS-Cov-2. The donor’s family told doctors she had no history of recent travel or COVID-19 symptoms and no known exposure to anyone with the disease.

But doctors had kept a sample of fluid washed from deep within the donor lungs. When they tested that fluid, it was positive for the virus. Four days after the transplant, the surgeon who handled the donor lungs and performed the surgery tested positive, too. Genetic screening revealed that the transplant recipient and the surgeon had been infected by the donor. Ten other members of the transplant team tested negative for the virus.

The transplant recipient deteriorated rapidly, developing multisystem organ failure. Doctors tried known treatments for COVID-19, including remdesivir, a newly approved drug, and convalescent blood plasma from people previously infected with the disease. Eventually, she was placed on the last-resort option of ECMO, or extracorporeal membrane oxygenation, to no avail. Life support was withdrawn, and she died 61 days after the transplant.

Dr. Kaul called the incident “a tragic case.”

While the Michigan case marks the first confirmed incident in the U.S. of transmission through a transplant, others have been suspected. A recent Centers for Disease Control and Prevention report reviewed eight possible cases of what’s known as donor-derived infection that occurred last spring, but concluded the most likely source of transmission of the COVID-19 virus in those cases was in a community or health care setting.

Before this incident, it was not clear whether the COVID-19 virus could be transmitted through solid organ transplants, though it’s well documented with other respiratory viruses. Donor transmission of H1N1 2009 pandemic influenza has been detected almost exclusively in lung transplant recipients, Dr. Kaul noted.

While it’s not surprising that SARS-CoV-2 can be transmitted through infected lungs, it remains uncertain whether other organs affected by COVID-19 – hearts, livers and kidneys, for instance – can transmit the virus, too.

“It seems for non-lung donors that it may be very difficult to transmit COVID-19, even if the donor has COVID-19,” Dr. Kaul said.

Organ donors have been tested routinely for SARS-CoV-2 during the pandemic, though it’s not required by the Organ Procurement and Transplantation Network, or OPTN, which oversees transplants in the U.S. But the Michigan case underscores the need for more extensive sampling before transplant, especially in areas with high rates of covid transmission, Dr. Kaul said.

When it comes to lungs, that means making sure to test samples from the donor’s lower respiratory tract, as well as from the nose and throat. Obtaining and testing such samples from donors can be difficult to carry out in a timely fashion. There’s also the risk of introducing infection into the donated lungs, Dr. Kaul said.

Because no organs other than lungs were used, the Michigan case doesn’t provide insight into testing protocols for other organs.

Overall, viral transmissions from organ donors to recipients remain rare, occurring in fewer than 1% of transplant recipients, research shows. The medical risks facing ailing patients who reject a donor organ are generally far higher, said Dr. David Klassen, chief medical officer with the United Network for Organ Sharing, the federal contractor that runs the OPTN.

“The risks of turning down transplants are catastrophic,” he said. “I don’t think patients should be afraid of the transplant process.”
 

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Doctors say a woman in Michigan contracted COVID-19 and died last fall 2 months after receiving a tainted double-lung transplant from a donor who turned out to harbor the virus that causes the disease – despite showing no signs of illness and initially testing negative.

Officials at the University of Michigan Medical School suggested it may be the first proven case of COVID-19 in the U.S. in which the virus was transmitted via an organ transplant. A surgeon who handled the donor lungs was also infected with the virus and fell ill but later recovered.

The incident appears to be isolated – the only confirmed case among nearly 40,000 transplants in 2020. But it has led to calls for more thorough testing of lung transplant donors, with samples taken from deep within the donor lungs as well as the nose and throat, said Dr. Daniel Kaul, director of Michigan Medicine’s transplant infectious disease service.

“We would absolutely not have used the lungs if we’d had a positive COVID-19 test,” said Dr. Kaul, who coauthored a report about the case in the American Journal of Transplantation.

The virus was transmitted when lungs from a woman from the Upper Midwest, who died after suffering a severe brain injury in a car accident, were transplanted into a woman with chronic obstructive lung disease at University Hospital in Ann Arbor. The nose and throat samples routinely collected from both organ donors and recipients tested negative for SARS-CoV-2, the virus that causes covid.

“All the screening that we normally do and are able to do, we did,” Dr. Kaul said.

Three days after the operation, however, the recipient spiked a fever; her blood pressure fell and her breathing became labored. Imaging showed signs of lung infection.

As her condition worsened, the patient developed septic shock and heart function problems. Doctors decided to test for SARS-CoV-2, Dr. Kaul said. Samples from her new lungs came back positive.

Suspicious about the origin of the infection, doctors returned to samples from the transplant donor. A molecular test of a swab from the donor’s nose and throat, taken 48 hours after her lungs were procured, had been negative for SARS-Cov-2. The donor’s family told doctors she had no history of recent travel or COVID-19 symptoms and no known exposure to anyone with the disease.

But doctors had kept a sample of fluid washed from deep within the donor lungs. When they tested that fluid, it was positive for the virus. Four days after the transplant, the surgeon who handled the donor lungs and performed the surgery tested positive, too. Genetic screening revealed that the transplant recipient and the surgeon had been infected by the donor. Ten other members of the transplant team tested negative for the virus.

The transplant recipient deteriorated rapidly, developing multisystem organ failure. Doctors tried known treatments for COVID-19, including remdesivir, a newly approved drug, and convalescent blood plasma from people previously infected with the disease. Eventually, she was placed on the last-resort option of ECMO, or extracorporeal membrane oxygenation, to no avail. Life support was withdrawn, and she died 61 days after the transplant.

Dr. Kaul called the incident “a tragic case.”

While the Michigan case marks the first confirmed incident in the U.S. of transmission through a transplant, others have been suspected. A recent Centers for Disease Control and Prevention report reviewed eight possible cases of what’s known as donor-derived infection that occurred last spring, but concluded the most likely source of transmission of the COVID-19 virus in those cases was in a community or health care setting.

Before this incident, it was not clear whether the COVID-19 virus could be transmitted through solid organ transplants, though it’s well documented with other respiratory viruses. Donor transmission of H1N1 2009 pandemic influenza has been detected almost exclusively in lung transplant recipients, Dr. Kaul noted.

While it’s not surprising that SARS-CoV-2 can be transmitted through infected lungs, it remains uncertain whether other organs affected by COVID-19 – hearts, livers and kidneys, for instance – can transmit the virus, too.

“It seems for non-lung donors that it may be very difficult to transmit COVID-19, even if the donor has COVID-19,” Dr. Kaul said.

Organ donors have been tested routinely for SARS-CoV-2 during the pandemic, though it’s not required by the Organ Procurement and Transplantation Network, or OPTN, which oversees transplants in the U.S. But the Michigan case underscores the need for more extensive sampling before transplant, especially in areas with high rates of covid transmission, Dr. Kaul said.

When it comes to lungs, that means making sure to test samples from the donor’s lower respiratory tract, as well as from the nose and throat. Obtaining and testing such samples from donors can be difficult to carry out in a timely fashion. There’s also the risk of introducing infection into the donated lungs, Dr. Kaul said.

Because no organs other than lungs were used, the Michigan case doesn’t provide insight into testing protocols for other organs.

Overall, viral transmissions from organ donors to recipients remain rare, occurring in fewer than 1% of transplant recipients, research shows. The medical risks facing ailing patients who reject a donor organ are generally far higher, said Dr. David Klassen, chief medical officer with the United Network for Organ Sharing, the federal contractor that runs the OPTN.

“The risks of turning down transplants are catastrophic,” he said. “I don’t think patients should be afraid of the transplant process.”
 

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology
 

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.
 

Future directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Dr. Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Dr. Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Dr. Beg.
 

Ongoing trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Dr. Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Dr. Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Dr. Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Dr. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology
 

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.
 

Future directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Dr. Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Dr. Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Dr. Beg.
 

Ongoing trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Dr. Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Dr. Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Dr. Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Dr. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology
 

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.
 

Future directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Dr. Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Dr. Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Dr. Beg.
 

Ongoing trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Dr. Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Dr. Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Dr. Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Dr. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

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Over 10% of transgender men (females transitioning to male) who take testosterone develop high hematocrit levels that could put them at greater risk for a thrombotic event, and the largest increase in levels occurs in the first year after starting therapy, a new Dutch study indicates.

Erythrocytosis, defined as a hematocrit greater than 0.50 L/L, is a potentially serious side effect of testosterone therapy, say Milou Cecilia Madsen, MD, and colleagues in their article published online Feb. 18, 2021, in the Journal of Clinical Endocrinology & Metabolism.

When hematocrit was measured twice, 11.1% of the cohort of 1073 trans men had levels in excess of 0.50 L/L over a 20-year follow-up.

“Erythrocytosis is common in transgender men treated with testosterone, especially in those who smoke, have [a] high BMI [body mass index], and [who] use testosterone injections,” Dr. Madsen, of the VU University Medical Center Amsterdam, said in a statement from the Endocrine Society.

“A reasonable first step in the care of transgender men with high red blood cells while on testosterone is to advise them to quit smoking, switch injectable testosterone to gel, and, if BMI is high, to lose weight,” she added.
 

First large study of testosterone in trans men with 20-year follow-up

Transgender men often undergo testosterone therapy as part of gender-affirming treatment. 

Secondary erythrocytosis, a condition where the body makes too many red blood cells, is a common side effect of testosterone therapy that can increase the risk of thrombolic events, heart attack, and stroke, Dr. Madsen and colleagues explained.

This is the first study of a large cohort of trans men taking testosterone therapy followed for up to 20 years. Because of the large sample size, statistical analysis with many determinants could be performed. And because of the long follow-up, a clear time relation between initiation of testosterone therapy and hematocrit could be studied, they noted.

Participants were part of the Amsterdam Cohort of Gender Dysphoria study, a large cohort of individuals seen at the Center of Expertise on Gender Dysphoria at Amsterdam University Medical Center between 1972 and 2015.

Laboratory measurements taken between 2004 and 2018 were available for analysis. Trans men visited the center every 3-6 months during their first year of testosterone therapy and were then monitored every year or every other year.

Long-acting undecanoate injection was associated with the highest risk of a hematocrit level greater than 0.50 L/L, and the risk of erythrocytosis in those who took long-acting intramuscular injections was about threefold higher, compared with testosterone gel (adjusted odds ratio, 3.1).

In contrast, short-acting ester injections and oral administration of testosterone had a similar risk for erythrocytosis, as did testosterone gel.

Other determinants of elevated hematocrit included smoking, medical history of a number of comorbid conditions, and older age on initiation of testosterone.

In contrast, “higher testosterone levels per se were not associated with an increased odds of hematocrit greater than 0.50 L/L”, the authors noted.
 

Current advice for trans men based on old guidance for hypogonadism

The authors said that current advice for trans men is based on recommendations for testosterone-treated hypogonadal cis men (those assigned male at birth) from 2008, which advises a hematocrit greater than 0.50 L/L has a moderate to high risk of adverse outcome. For levels greater than 0.54 L/L, cessation of testosterone therapy, a dose reduction, or therapeutic phlebotomy to reduce the risk of adverse events is advised. For levels 0.50-0.54 L/L, no clear advice is given.

But questions remain as to whether these guidelines are applicable to trans men because the duration of testosterone therapy is much longer in trans men and hormone treatment often cannot be discontinued without causing distress.

Meanwhile, hematology guidelines indicate an upper limit for hematocrit for cis females of 0.48 L/L.

“It could be argued that the upper limit for cis females should be applied, as trans men are born with female genetics,” the authors said. “This is a subject for further research.”
 

Duration of testosterone therapy impacts risk of erythrocytosis

In the study, the researchers found that longer duration of testosterone therapy increased the risk of developing hematocrit levels greater than 0.50 L/L. For example, after 1 year, the cumulative incidence of erythrocytosis was 8%; after 10 years, it was 38%; and after 14 years, it was 50%.

Until more specific guidance is developed for trans men, if hematocrit levels rise to 0.50-0.54 L/L, the researchers suggested taking “reasonable” steps to prevent a further increase:

• Consider switching patients who use injectable testosterone to transdermal products.
• Advise patients with a BMI greater than 25 kg/m2 to lose weight to attain a BMI of 18.5-25.
• Advise patients to stop smoking.
• Pursue treatment optimization for chronic lung disease or sleep apnea.

The study had no external funding. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Over 10% of transgender men (females transitioning to male) who take testosterone develop high hematocrit levels that could put them at greater risk for a thrombotic event, and the largest increase in levels occurs in the first year after starting therapy, a new Dutch study indicates.

Erythrocytosis, defined as a hematocrit greater than 0.50 L/L, is a potentially serious side effect of testosterone therapy, say Milou Cecilia Madsen, MD, and colleagues in their article published online Feb. 18, 2021, in the Journal of Clinical Endocrinology & Metabolism.

When hematocrit was measured twice, 11.1% of the cohort of 1073 trans men had levels in excess of 0.50 L/L over a 20-year follow-up.

“Erythrocytosis is common in transgender men treated with testosterone, especially in those who smoke, have [a] high BMI [body mass index], and [who] use testosterone injections,” Dr. Madsen, of the VU University Medical Center Amsterdam, said in a statement from the Endocrine Society.

“A reasonable first step in the care of transgender men with high red blood cells while on testosterone is to advise them to quit smoking, switch injectable testosterone to gel, and, if BMI is high, to lose weight,” she added.
 

First large study of testosterone in trans men with 20-year follow-up

Transgender men often undergo testosterone therapy as part of gender-affirming treatment. 

Secondary erythrocytosis, a condition where the body makes too many red blood cells, is a common side effect of testosterone therapy that can increase the risk of thrombolic events, heart attack, and stroke, Dr. Madsen and colleagues explained.

This is the first study of a large cohort of trans men taking testosterone therapy followed for up to 20 years. Because of the large sample size, statistical analysis with many determinants could be performed. And because of the long follow-up, a clear time relation between initiation of testosterone therapy and hematocrit could be studied, they noted.

Participants were part of the Amsterdam Cohort of Gender Dysphoria study, a large cohort of individuals seen at the Center of Expertise on Gender Dysphoria at Amsterdam University Medical Center between 1972 and 2015.

Laboratory measurements taken between 2004 and 2018 were available for analysis. Trans men visited the center every 3-6 months during their first year of testosterone therapy and were then monitored every year or every other year.

Long-acting undecanoate injection was associated with the highest risk of a hematocrit level greater than 0.50 L/L, and the risk of erythrocytosis in those who took long-acting intramuscular injections was about threefold higher, compared with testosterone gel (adjusted odds ratio, 3.1).

In contrast, short-acting ester injections and oral administration of testosterone had a similar risk for erythrocytosis, as did testosterone gel.

Other determinants of elevated hematocrit included smoking, medical history of a number of comorbid conditions, and older age on initiation of testosterone.

In contrast, “higher testosterone levels per se were not associated with an increased odds of hematocrit greater than 0.50 L/L”, the authors noted.
 

Current advice for trans men based on old guidance for hypogonadism

The authors said that current advice for trans men is based on recommendations for testosterone-treated hypogonadal cis men (those assigned male at birth) from 2008, which advises a hematocrit greater than 0.50 L/L has a moderate to high risk of adverse outcome. For levels greater than 0.54 L/L, cessation of testosterone therapy, a dose reduction, or therapeutic phlebotomy to reduce the risk of adverse events is advised. For levels 0.50-0.54 L/L, no clear advice is given.

But questions remain as to whether these guidelines are applicable to trans men because the duration of testosterone therapy is much longer in trans men and hormone treatment often cannot be discontinued without causing distress.

Meanwhile, hematology guidelines indicate an upper limit for hematocrit for cis females of 0.48 L/L.

“It could be argued that the upper limit for cis females should be applied, as trans men are born with female genetics,” the authors said. “This is a subject for further research.”
 

Duration of testosterone therapy impacts risk of erythrocytosis

In the study, the researchers found that longer duration of testosterone therapy increased the risk of developing hematocrit levels greater than 0.50 L/L. For example, after 1 year, the cumulative incidence of erythrocytosis was 8%; after 10 years, it was 38%; and after 14 years, it was 50%.

Until more specific guidance is developed for trans men, if hematocrit levels rise to 0.50-0.54 L/L, the researchers suggested taking “reasonable” steps to prevent a further increase:

• Consider switching patients who use injectable testosterone to transdermal products.
• Advise patients with a BMI greater than 25 kg/m2 to lose weight to attain a BMI of 18.5-25.
• Advise patients to stop smoking.
• Pursue treatment optimization for chronic lung disease or sleep apnea.

The study had no external funding. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Over 10% of transgender men (females transitioning to male) who take testosterone develop high hematocrit levels that could put them at greater risk for a thrombotic event, and the largest increase in levels occurs in the first year after starting therapy, a new Dutch study indicates.

Erythrocytosis, defined as a hematocrit greater than 0.50 L/L, is a potentially serious side effect of testosterone therapy, say Milou Cecilia Madsen, MD, and colleagues in their article published online Feb. 18, 2021, in the Journal of Clinical Endocrinology & Metabolism.

When hematocrit was measured twice, 11.1% of the cohort of 1073 trans men had levels in excess of 0.50 L/L over a 20-year follow-up.

“Erythrocytosis is common in transgender men treated with testosterone, especially in those who smoke, have [a] high BMI [body mass index], and [who] use testosterone injections,” Dr. Madsen, of the VU University Medical Center Amsterdam, said in a statement from the Endocrine Society.

“A reasonable first step in the care of transgender men with high red blood cells while on testosterone is to advise them to quit smoking, switch injectable testosterone to gel, and, if BMI is high, to lose weight,” she added.
 

First large study of testosterone in trans men with 20-year follow-up

Transgender men often undergo testosterone therapy as part of gender-affirming treatment. 

Secondary erythrocytosis, a condition where the body makes too many red blood cells, is a common side effect of testosterone therapy that can increase the risk of thrombolic events, heart attack, and stroke, Dr. Madsen and colleagues explained.

This is the first study of a large cohort of trans men taking testosterone therapy followed for up to 20 years. Because of the large sample size, statistical analysis with many determinants could be performed. And because of the long follow-up, a clear time relation between initiation of testosterone therapy and hematocrit could be studied, they noted.

Participants were part of the Amsterdam Cohort of Gender Dysphoria study, a large cohort of individuals seen at the Center of Expertise on Gender Dysphoria at Amsterdam University Medical Center between 1972 and 2015.

Laboratory measurements taken between 2004 and 2018 were available for analysis. Trans men visited the center every 3-6 months during their first year of testosterone therapy and were then monitored every year or every other year.

Long-acting undecanoate injection was associated with the highest risk of a hematocrit level greater than 0.50 L/L, and the risk of erythrocytosis in those who took long-acting intramuscular injections was about threefold higher, compared with testosterone gel (adjusted odds ratio, 3.1).

In contrast, short-acting ester injections and oral administration of testosterone had a similar risk for erythrocytosis, as did testosterone gel.

Other determinants of elevated hematocrit included smoking, medical history of a number of comorbid conditions, and older age on initiation of testosterone.

In contrast, “higher testosterone levels per se were not associated with an increased odds of hematocrit greater than 0.50 L/L”, the authors noted.
 

Current advice for trans men based on old guidance for hypogonadism

The authors said that current advice for trans men is based on recommendations for testosterone-treated hypogonadal cis men (those assigned male at birth) from 2008, which advises a hematocrit greater than 0.50 L/L has a moderate to high risk of adverse outcome. For levels greater than 0.54 L/L, cessation of testosterone therapy, a dose reduction, or therapeutic phlebotomy to reduce the risk of adverse events is advised. For levels 0.50-0.54 L/L, no clear advice is given.

But questions remain as to whether these guidelines are applicable to trans men because the duration of testosterone therapy is much longer in trans men and hormone treatment often cannot be discontinued without causing distress.

Meanwhile, hematology guidelines indicate an upper limit for hematocrit for cis females of 0.48 L/L.

“It could be argued that the upper limit for cis females should be applied, as trans men are born with female genetics,” the authors said. “This is a subject for further research.”
 

Duration of testosterone therapy impacts risk of erythrocytosis

In the study, the researchers found that longer duration of testosterone therapy increased the risk of developing hematocrit levels greater than 0.50 L/L. For example, after 1 year, the cumulative incidence of erythrocytosis was 8%; after 10 years, it was 38%; and after 14 years, it was 50%.

Until more specific guidance is developed for trans men, if hematocrit levels rise to 0.50-0.54 L/L, the researchers suggested taking “reasonable” steps to prevent a further increase:

• Consider switching patients who use injectable testosterone to transdermal products.
• Advise patients with a BMI greater than 25 kg/m2 to lose weight to attain a BMI of 18.5-25.
• Advise patients to stop smoking.
• Pursue treatment optimization for chronic lung disease or sleep apnea.

The study had no external funding. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

[email protected]

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

[email protected]

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

[email protected]