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The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

The potential harms of excessive Internet use are serious enough for the medical community to debate whether it should be included as a disorder associated with addiction. One question is Where do you draw the line between excessive use—considered nonpathologic behavior—and addiction?

Researchers surveyed 374 university students about social network habits, testing for obsession, lack of personal control, and excessive use. The questionnaire included questions such as “I feel a great need to stay connected to social media” and “I feel anxious when I cannot connect to social media.” The researchers also used a questionnaire about suicidal ideation.

More than half the students reported that WhatsApp is their most important social network, followed by Facebook. The respondents used social media for an average of nearly 7 hours a day. They used social media mainly for contact with friends, entertainment, conversing with a partner, maintaining contact with colleagues for academic matters, and contact with family.

The researchers divided the participants into 3 groups, based on their risk of addiction. The majority were considered “moderate risk.” Approximately 10% were considered “high risk.” The high-risk students spent roughly 11 hours a day on social media compared with the low-risk students who spent about 4 hours. Greater risk also implied more depressive symptoms, more mobile use, and less positive suicidal ideation.

Almost 4 in 10 students had thoughts and wishes about their death at least once in the 2 weeks before the survey. Interestingly, however, the researchers found no relationship between suicidal ideation and addictive behavior. But adding depression did make a difference. Unlike excessive use, addictive behavior was significantly related to depression and suicidal ideation.  

The researchers cite other studies that have found addiction to social networks predicts depression and can worsen symptoms. But they also say their findings confirm other research that suggests social media communication can be protective for people who have suicidal thoughts. What looks like addiction may be “an act of escape” from unpleasant thoughts and feelings. Social media, they say, can be a “refuge.”

The potential harms of excessive Internet use are serious enough for the medical community to debate whether it should be included as a disorder associated with addiction. One question is Where do you draw the line between excessive use—considered nonpathologic behavior—and addiction?

Researchers surveyed 374 university students about social network habits, testing for obsession, lack of personal control, and excessive use. The questionnaire included questions such as “I feel a great need to stay connected to social media” and “I feel anxious when I cannot connect to social media.” The researchers also used a questionnaire about suicidal ideation.

More than half the students reported that WhatsApp is their most important social network, followed by Facebook. The respondents used social media for an average of nearly 7 hours a day. They used social media mainly for contact with friends, entertainment, conversing with a partner, maintaining contact with colleagues for academic matters, and contact with family.

The researchers divided the participants into 3 groups, based on their risk of addiction. The majority were considered “moderate risk.” Approximately 10% were considered “high risk.” The high-risk students spent roughly 11 hours a day on social media compared with the low-risk students who spent about 4 hours. Greater risk also implied more depressive symptoms, more mobile use, and less positive suicidal ideation.

Almost 4 in 10 students had thoughts and wishes about their death at least once in the 2 weeks before the survey. Interestingly, however, the researchers found no relationship between suicidal ideation and addictive behavior. But adding depression did make a difference. Unlike excessive use, addictive behavior was significantly related to depression and suicidal ideation.  

The researchers cite other studies that have found addiction to social networks predicts depression and can worsen symptoms. But they also say their findings confirm other research that suggests social media communication can be protective for people who have suicidal thoughts. What looks like addiction may be “an act of escape” from unpleasant thoughts and feelings. Social media, they say, can be a “refuge.”

The potential harms of excessive Internet use are serious enough for the medical community to debate whether it should be included as a disorder associated with addiction. One question is Where do you draw the line between excessive use—considered nonpathologic behavior—and addiction?

Researchers surveyed 374 university students about social network habits, testing for obsession, lack of personal control, and excessive use. The questionnaire included questions such as “I feel a great need to stay connected to social media” and “I feel anxious when I cannot connect to social media.” The researchers also used a questionnaire about suicidal ideation.

More than half the students reported that WhatsApp is their most important social network, followed by Facebook. The respondents used social media for an average of nearly 7 hours a day. They used social media mainly for contact with friends, entertainment, conversing with a partner, maintaining contact with colleagues for academic matters, and contact with family.

The researchers divided the participants into 3 groups, based on their risk of addiction. The majority were considered “moderate risk.” Approximately 10% were considered “high risk.” The high-risk students spent roughly 11 hours a day on social media compared with the low-risk students who spent about 4 hours. Greater risk also implied more depressive symptoms, more mobile use, and less positive suicidal ideation.

Almost 4 in 10 students had thoughts and wishes about their death at least once in the 2 weeks before the survey. Interestingly, however, the researchers found no relationship between suicidal ideation and addictive behavior. But adding depression did make a difference. Unlike excessive use, addictive behavior was significantly related to depression and suicidal ideation.  

The researchers cite other studies that have found addiction to social networks predicts depression and can worsen symptoms. But they also say their findings confirm other research that suggests social media communication can be protective for people who have suicidal thoughts. What looks like addiction may be “an act of escape” from unpleasant thoughts and feelings. Social media, they say, can be a “refuge.”

In 2017, the number of cases of tickborne spotted fever rickettsiosis (SFR) reported to the CDC jumped 46%—from 4,269 in 2016 to a “record” 6,248 cases. The New England, East North Central, and Mid-Atlantic regions in 2017 alone experienced a 215%, 78%, and 65% increase, respectively, although they typically report only a handful of cases each year.

Rocky Mountain spotted fever (RMSF) is the most severe of the SFR. It begins with nonspecific symptoms such as fever and headache, and sometimes rash, but when left untreated, the disease can have serious consequences, including amputation. Roughly 1 in 5 untreated cases is fatal; half of those deaths occur within the first 8 days of illness.

However, RMSF is treatable with doxycycline, which can prevent disability and death if prescribed within the first 5 days of illness, meaning that early recognition and treatment can save lives. Yet cases “often go unrecognized because the signs and symptoms are similar to those of many other diseases,” says CDC Director Robert Redfield, MD. Less than 1% of the reported SFR cases in 2017 had sufficient laboratory evidence to be confirmed. And although the annual incidence of SFR in the US increased from 6.4 to 19.2 cases per million persons between years 2010 and 2017, the proportion of confirmed cases went down.

Citing the need to train health care providers (HCPs) on the best methods to diagnose tickborne diseases, the CDC has created a “first of its kind” clinical education tool that uses scenarios based on real cases to help clinicians recognize and differentiate among the various possibilities. The module is self-directed with knowledge checks, reference materials, and an interactive rash identification tool that allows HCPs to compare the rash seen in RMSF with that of other illnesses.

Continuing education credit is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators. To access the module, go to https://www.cdc.gov/rmsf/resources/module.html

In 2017, the number of cases of tickborne spotted fever rickettsiosis (SFR) reported to the CDC jumped 46%—from 4,269 in 2016 to a “record” 6,248 cases. The New England, East North Central, and Mid-Atlantic regions in 2017 alone experienced a 215%, 78%, and 65% increase, respectively, although they typically report only a handful of cases each year.

Rocky Mountain spotted fever (RMSF) is the most severe of the SFR. It begins with nonspecific symptoms such as fever and headache, and sometimes rash, but when left untreated, the disease can have serious consequences, including amputation. Roughly 1 in 5 untreated cases is fatal; half of those deaths occur within the first 8 days of illness.

However, RMSF is treatable with doxycycline, which can prevent disability and death if prescribed within the first 5 days of illness, meaning that early recognition and treatment can save lives. Yet cases “often go unrecognized because the signs and symptoms are similar to those of many other diseases,” says CDC Director Robert Redfield, MD. Less than 1% of the reported SFR cases in 2017 had sufficient laboratory evidence to be confirmed. And although the annual incidence of SFR in the US increased from 6.4 to 19.2 cases per million persons between years 2010 and 2017, the proportion of confirmed cases went down.

Citing the need to train health care providers (HCPs) on the best methods to diagnose tickborne diseases, the CDC has created a “first of its kind” clinical education tool that uses scenarios based on real cases to help clinicians recognize and differentiate among the various possibilities. The module is self-directed with knowledge checks, reference materials, and an interactive rash identification tool that allows HCPs to compare the rash seen in RMSF with that of other illnesses.

Continuing education credit is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators. To access the module, go to https://www.cdc.gov/rmsf/resources/module.html

In 2017, the number of cases of tickborne spotted fever rickettsiosis (SFR) reported to the CDC jumped 46%—from 4,269 in 2016 to a “record” 6,248 cases. The New England, East North Central, and Mid-Atlantic regions in 2017 alone experienced a 215%, 78%, and 65% increase, respectively, although they typically report only a handful of cases each year.

Rocky Mountain spotted fever (RMSF) is the most severe of the SFR. It begins with nonspecific symptoms such as fever and headache, and sometimes rash, but when left untreated, the disease can have serious consequences, including amputation. Roughly 1 in 5 untreated cases is fatal; half of those deaths occur within the first 8 days of illness.

However, RMSF is treatable with doxycycline, which can prevent disability and death if prescribed within the first 5 days of illness, meaning that early recognition and treatment can save lives. Yet cases “often go unrecognized because the signs and symptoms are similar to those of many other diseases,” says CDC Director Robert Redfield, MD. Less than 1% of the reported SFR cases in 2017 had sufficient laboratory evidence to be confirmed. And although the annual incidence of SFR in the US increased from 6.4 to 19.2 cases per million persons between years 2010 and 2017, the proportion of confirmed cases went down.

Citing the need to train health care providers (HCPs) on the best methods to diagnose tickborne diseases, the CDC has created a “first of its kind” clinical education tool that uses scenarios based on real cases to help clinicians recognize and differentiate among the various possibilities. The module is self-directed with knowledge checks, reference materials, and an interactive rash identification tool that allows HCPs to compare the rash seen in RMSF with that of other illnesses.

Continuing education credit is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators. To access the module, go to https://www.cdc.gov/rmsf/resources/module.html

Methamphetamine (MA) abuse has been linked to psychological problems, such as depression, anxiety, and psychosis. It also has been linked to problems in everyday functioning (eg, impulsivity), and neurocognitive deficits in attention, memory, learning, executive function, and fine motor speed. But researchers from Capital Medical University in Beijing and Fujian Medical University in Fuzhou, both in China, say current understanding is limited about the impact of MA abuse in spatial processing, which affects, among other things, alertness.

The researchers conducted a study with 40 MA abusers and 40 nonusers. Participants performed 3 tasks randomly. During the Simple Reaction Task, they pressed a mouse key as quickly and accurately as possible, discriminating between hand and foot pictures. The Spatial Orientation Task asked them to gauge the direction of fingers or toes shown in pictures. The Mental Rotation Task randomly showed hands and feet in 2 different views (dorsum, palm/plantar) and oriented in 1 of 6 clockwise angles. It also assessed 2 different mental rotation strategies: object based and egocentric based, or the ability to judge which side a body part belongs to in the picture and in the participant’s own body. In this test, the researchers say, the transformation of visuospatial mental image is crucial to action, navigation, and reasoning.

The researchers found no significant difference in either accuracy or reaction time between the 2 groups in the first task. In the second, MA users performed less well on reaction time but not accuracy. The results of that task suggested that MA abuse may induce a deficit in spatial orientation ability, mainly on horizontal surface.

On the third task, however, MA abusers performed worse and committed more errors than did the nonusers. They had worse results at every orientation angle and took longer to judge the orientation of leftward but not rightward foot pictures. Such phenomena likely relate to MA damage to cortical gray and white matter, the researchers say. They note that MA users also have shown less activation in the right hemisphere when performing a facial-affect matching task. MA abuse may mainly target the right hemisphere, the researchers add, but the findings may support other research that has found poor decision-making performance in MA abusers that is related to inadequate activation of many brain areas.

The study confirmed “considerably poor visuospatial ability” in MA users. The Mental Rotation Task findings also showed MA abuse of longer duration had more negative effect on spatial process speed. Because both cognitive speed and accuracy were affected on the Mental Rotation Task, but only cognitive speed on Spatial Orientation, MA abuse may affect visuospatial ability more seriously than spatial orientation ability, the researchers say.

Methamphetamine (MA) abuse has been linked to psychological problems, such as depression, anxiety, and psychosis. It also has been linked to problems in everyday functioning (eg, impulsivity), and neurocognitive deficits in attention, memory, learning, executive function, and fine motor speed. But researchers from Capital Medical University in Beijing and Fujian Medical University in Fuzhou, both in China, say current understanding is limited about the impact of MA abuse in spatial processing, which affects, among other things, alertness.

The researchers conducted a study with 40 MA abusers and 40 nonusers. Participants performed 3 tasks randomly. During the Simple Reaction Task, they pressed a mouse key as quickly and accurately as possible, discriminating between hand and foot pictures. The Spatial Orientation Task asked them to gauge the direction of fingers or toes shown in pictures. The Mental Rotation Task randomly showed hands and feet in 2 different views (dorsum, palm/plantar) and oriented in 1 of 6 clockwise angles. It also assessed 2 different mental rotation strategies: object based and egocentric based, or the ability to judge which side a body part belongs to in the picture and in the participant’s own body. In this test, the researchers say, the transformation of visuospatial mental image is crucial to action, navigation, and reasoning.

The researchers found no significant difference in either accuracy or reaction time between the 2 groups in the first task. In the second, MA users performed less well on reaction time but not accuracy. The results of that task suggested that MA abuse may induce a deficit in spatial orientation ability, mainly on horizontal surface.

On the third task, however, MA abusers performed worse and committed more errors than did the nonusers. They had worse results at every orientation angle and took longer to judge the orientation of leftward but not rightward foot pictures. Such phenomena likely relate to MA damage to cortical gray and white matter, the researchers say. They note that MA users also have shown less activation in the right hemisphere when performing a facial-affect matching task. MA abuse may mainly target the right hemisphere, the researchers add, but the findings may support other research that has found poor decision-making performance in MA abusers that is related to inadequate activation of many brain areas.

The study confirmed “considerably poor visuospatial ability” in MA users. The Mental Rotation Task findings also showed MA abuse of longer duration had more negative effect on spatial process speed. Because both cognitive speed and accuracy were affected on the Mental Rotation Task, but only cognitive speed on Spatial Orientation, MA abuse may affect visuospatial ability more seriously than spatial orientation ability, the researchers say.

Methamphetamine (MA) abuse has been linked to psychological problems, such as depression, anxiety, and psychosis. It also has been linked to problems in everyday functioning (eg, impulsivity), and neurocognitive deficits in attention, memory, learning, executive function, and fine motor speed. But researchers from Capital Medical University in Beijing and Fujian Medical University in Fuzhou, both in China, say current understanding is limited about the impact of MA abuse in spatial processing, which affects, among other things, alertness.

The researchers conducted a study with 40 MA abusers and 40 nonusers. Participants performed 3 tasks randomly. During the Simple Reaction Task, they pressed a mouse key as quickly and accurately as possible, discriminating between hand and foot pictures. The Spatial Orientation Task asked them to gauge the direction of fingers or toes shown in pictures. The Mental Rotation Task randomly showed hands and feet in 2 different views (dorsum, palm/plantar) and oriented in 1 of 6 clockwise angles. It also assessed 2 different mental rotation strategies: object based and egocentric based, or the ability to judge which side a body part belongs to in the picture and in the participant’s own body. In this test, the researchers say, the transformation of visuospatial mental image is crucial to action, navigation, and reasoning.

The researchers found no significant difference in either accuracy or reaction time between the 2 groups in the first task. In the second, MA users performed less well on reaction time but not accuracy. The results of that task suggested that MA abuse may induce a deficit in spatial orientation ability, mainly on horizontal surface.

On the third task, however, MA abusers performed worse and committed more errors than did the nonusers. They had worse results at every orientation angle and took longer to judge the orientation of leftward but not rightward foot pictures. Such phenomena likely relate to MA damage to cortical gray and white matter, the researchers say. They note that MA users also have shown less activation in the right hemisphere when performing a facial-affect matching task. MA abuse may mainly target the right hemisphere, the researchers add, but the findings may support other research that has found poor decision-making performance in MA abusers that is related to inadequate activation of many brain areas.

The study confirmed “considerably poor visuospatial ability” in MA users. The Mental Rotation Task findings also showed MA abuse of longer duration had more negative effect on spatial process speed. Because both cognitive speed and accuracy were affected on the Mental Rotation Task, but only cognitive speed on Spatial Orientation, MA abuse may affect visuospatial ability more seriously than spatial orientation ability, the researchers say.

According to the CDC, the number of reported tickborne diseases more than doubled between 2004-2016 and accounted for > 60% of all reported mosquito-borne, tickborne, and fleaborne disease cases. Which is why it is important to keep an eye out for anyone who has a history of being in a tick-promoting environment. Clinicians from Lehigh Valley Health Network Pocono and Geisinger Commonwealth School of Medicine, both in East Stroudsburg, Pennsylvania, report on a patient whose diagnosis turned on that fact.

The patient, a 71-year-old man, had fever, weakness, headaches, near syncope, and nausea for 4 days. He also had not been eating well.

A complete blood count showed pancytopenia with an excess of band cells, an indicator of inflammation and infection. The patient’s aspartate transaminase levels were elevated. The diagnostic dilemma centered on these findings: Serology tests for HIV 1 and 2 were positive, and a peripheral blood smear showed 0.5% parasitemia consistent with Babesia microti. Both babesiosis and HIV were among the possible diagnoses. Two important factors the clinicians had to consider: The patient had recently been bitten by ticks and was homosexual.

The clinicians note that a variety of infections can lead to false-positive HIV serology, such as malaria, Mycobacterium tuberculosis or Rickettsia species, influenza and hepatitis B vaccinations. Moreover, the Ixodes tick, the same vector that transmits Borrelia burgdorferi, which causes Lyme disease, also transmits B microti. Conversely, HIV infection can exacerbate Lyme disease or babesiosis.

The tests showing B microti were the clincher for the clinicians, who started treatment with fluids, atovaquone, and azithromycin. The patient recovered completely. Repeat HIV serology was negative.

The authors of the report note that babesiosis can be a life-threatening infection in patients with reduced immunity. It is possible that, like malaria and HIV serologies, Babesia and HIV serologies cross-react, the clinicians say. Thus, it is important to screen for both in both infections.

This is the first case, to the clinician’s knowledge, of HIV associated with active babesiosis

According to the CDC, the number of reported tickborne diseases more than doubled between 2004-2016 and accounted for > 60% of all reported mosquito-borne, tickborne, and fleaborne disease cases. Which is why it is important to keep an eye out for anyone who has a history of being in a tick-promoting environment. Clinicians from Lehigh Valley Health Network Pocono and Geisinger Commonwealth School of Medicine, both in East Stroudsburg, Pennsylvania, report on a patient whose diagnosis turned on that fact.

The patient, a 71-year-old man, had fever, weakness, headaches, near syncope, and nausea for 4 days. He also had not been eating well.

A complete blood count showed pancytopenia with an excess of band cells, an indicator of inflammation and infection. The patient’s aspartate transaminase levels were elevated. The diagnostic dilemma centered on these findings: Serology tests for HIV 1 and 2 were positive, and a peripheral blood smear showed 0.5% parasitemia consistent with Babesia microti. Both babesiosis and HIV were among the possible diagnoses. Two important factors the clinicians had to consider: The patient had recently been bitten by ticks and was homosexual.

The clinicians note that a variety of infections can lead to false-positive HIV serology, such as malaria, Mycobacterium tuberculosis or Rickettsia species, influenza and hepatitis B vaccinations. Moreover, the Ixodes tick, the same vector that transmits Borrelia burgdorferi, which causes Lyme disease, also transmits B microti. Conversely, HIV infection can exacerbate Lyme disease or babesiosis.

The tests showing B microti were the clincher for the clinicians, who started treatment with fluids, atovaquone, and azithromycin. The patient recovered completely. Repeat HIV serology was negative.

The authors of the report note that babesiosis can be a life-threatening infection in patients with reduced immunity. It is possible that, like malaria and HIV serologies, Babesia and HIV serologies cross-react, the clinicians say. Thus, it is important to screen for both in both infections.

This is the first case, to the clinician’s knowledge, of HIV associated with active babesiosis

According to the CDC, the number of reported tickborne diseases more than doubled between 2004-2016 and accounted for > 60% of all reported mosquito-borne, tickborne, and fleaborne disease cases. Which is why it is important to keep an eye out for anyone who has a history of being in a tick-promoting environment. Clinicians from Lehigh Valley Health Network Pocono and Geisinger Commonwealth School of Medicine, both in East Stroudsburg, Pennsylvania, report on a patient whose diagnosis turned on that fact.

The patient, a 71-year-old man, had fever, weakness, headaches, near syncope, and nausea for 4 days. He also had not been eating well.

A complete blood count showed pancytopenia with an excess of band cells, an indicator of inflammation and infection. The patient’s aspartate transaminase levels were elevated. The diagnostic dilemma centered on these findings: Serology tests for HIV 1 and 2 were positive, and a peripheral blood smear showed 0.5% parasitemia consistent with Babesia microti. Both babesiosis and HIV were among the possible diagnoses. Two important factors the clinicians had to consider: The patient had recently been bitten by ticks and was homosexual.

The clinicians note that a variety of infections can lead to false-positive HIV serology, such as malaria, Mycobacterium tuberculosis or Rickettsia species, influenza and hepatitis B vaccinations. Moreover, the Ixodes tick, the same vector that transmits Borrelia burgdorferi, which causes Lyme disease, also transmits B microti. Conversely, HIV infection can exacerbate Lyme disease or babesiosis.

The tests showing B microti were the clincher for the clinicians, who started treatment with fluids, atovaquone, and azithromycin. The patient recovered completely. Repeat HIV serology was negative.

The authors of the report note that babesiosis can be a life-threatening infection in patients with reduced immunity. It is possible that, like malaria and HIV serologies, Babesia and HIV serologies cross-react, the clinicians say. Thus, it is important to screen for both in both infections.

This is the first case, to the clinician’s knowledge, of HIV associated with active babesiosis

DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.

Michele G. Sullivan/MDedge News

Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.

But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.

“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”

Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.

“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.

By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.

RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.

reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.

Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”

The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.

The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.

A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.

RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.

There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.

Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.

Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.

“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.

The trial was sponsored by resTORbio.

msullivan@mdedge.com

SOURCE: Mannick J et al. ATS 2019, Abstract A2623.

CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.

DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.

Michele G. Sullivan/MDedge News

Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.

But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.

“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”

Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.

“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.

By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.

RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.

reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.

Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”

The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.

The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.

A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.

RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.

There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.

Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.

Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.

“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.

The trial was sponsored by resTORbio.

msullivan@mdedge.com

SOURCE: Mannick J et al. ATS 2019, Abstract A2623.

CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.

DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.

Michele G. Sullivan/MDedge News

Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.

But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.

“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”

Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.

“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.

By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.

RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.

reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.

Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”

The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.

The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.

A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.

RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.

There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.

Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.

Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.

“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.

The trial was sponsored by resTORbio.

msullivan@mdedge.com

SOURCE: Mannick J et al. ATS 2019, Abstract A2623.

CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.

The AVAHO Program Planning Committee is pleased to announce the call for abstracts for our meeting in Minneapolis, Minnesota, September 20-22, 2019. Abstracts should be submitted online here: https://www.avaho.org/call-for-abstracts.

Abstracts should not exceed 350 words, excluding title and titles should not exceed 300 characters. Illustrations, tables or bullet points are not permitted.

The following categories of abstracts are suitable for submission:

• Research (eg, clinical trials, laboratory studies, translational studies, descriptive studies, qualitative studies)
• Evidence-Based Projects
• Quality Improvement Projects and initiatives
• Clinical Practice (eg, best clinical practice exemplar, case study, disease management, palliative care (non-research), survivorship (nonresearch), symptom management (non-research)
• Program Initiatives (eg, workforce, infrastructure, workflow)
• Projects in Progress

The first author is considered the primary author, is responsible for the content and integrity of the project, and will serve as the contact person by the AVAHO administrator and Planning Committee.  Authors may submit more than one abstract; however, they may be first author on only one abstract.  At least one author must be a member of AVAHO. One author must present the abstract at the meeting. Accepted abstracts will be published in a special edition of Federal Practitioner.

​

The electronic poster session was viewed very favorably by attendees last year and will be used again this year. This requires more logistic hurdles and thus, the June 1 submission deadline is firm. 

Each poster will be assigned to one of two time slots for presentation.  One author must be present to give a brief presentation of the poster. Authors are encouraged to record their poster presentation to provide attendees another option for viewing your poster.  This recording does NOT replace the obligation to be present IN PERSON during the assigned poster session.  Details regarding this recording will be forthcoming.  

All abstracts must be submitted by June 1, 2019. This is a firm deadline. No extensions.

The AVAHO Program Planning Committee is pleased to announce the call for abstracts for our meeting in Minneapolis, Minnesota, September 20-22, 2019. Abstracts should be submitted online here: https://www.avaho.org/call-for-abstracts.

Abstracts should not exceed 350 words, excluding title and titles should not exceed 300 characters. Illustrations, tables or bullet points are not permitted.

The following categories of abstracts are suitable for submission:

• Research (eg, clinical trials, laboratory studies, translational studies, descriptive studies, qualitative studies)
• Evidence-Based Projects
• Quality Improvement Projects and initiatives
• Clinical Practice (eg, best clinical practice exemplar, case study, disease management, palliative care (non-research), survivorship (nonresearch), symptom management (non-research)
• Program Initiatives (eg, workforce, infrastructure, workflow)
• Projects in Progress

The first author is considered the primary author, is responsible for the content and integrity of the project, and will serve as the contact person by the AVAHO administrator and Planning Committee.  Authors may submit more than one abstract; however, they may be first author on only one abstract.  At least one author must be a member of AVAHO. One author must present the abstract at the meeting. Accepted abstracts will be published in a special edition of Federal Practitioner.

​

The electronic poster session was viewed very favorably by attendees last year and will be used again this year. This requires more logistic hurdles and thus, the June 1 submission deadline is firm. 

Each poster will be assigned to one of two time slots for presentation.  One author must be present to give a brief presentation of the poster. Authors are encouraged to record their poster presentation to provide attendees another option for viewing your poster.  This recording does NOT replace the obligation to be present IN PERSON during the assigned poster session.  Details regarding this recording will be forthcoming.  

All abstracts must be submitted by June 1, 2019. This is a firm deadline. No extensions.

The AVAHO Program Planning Committee is pleased to announce the call for abstracts for our meeting in Minneapolis, Minnesota, September 20-22, 2019. Abstracts should be submitted online here: https://www.avaho.org/call-for-abstracts.

Abstracts should not exceed 350 words, excluding title and titles should not exceed 300 characters. Illustrations, tables or bullet points are not permitted.

The following categories of abstracts are suitable for submission:

• Research (eg, clinical trials, laboratory studies, translational studies, descriptive studies, qualitative studies)
• Evidence-Based Projects
• Quality Improvement Projects and initiatives
• Clinical Practice (eg, best clinical practice exemplar, case study, disease management, palliative care (non-research), survivorship (nonresearch), symptom management (non-research)
• Program Initiatives (eg, workforce, infrastructure, workflow)
• Projects in Progress

The first author is considered the primary author, is responsible for the content and integrity of the project, and will serve as the contact person by the AVAHO administrator and Planning Committee.  Authors may submit more than one abstract; however, they may be first author on only one abstract.  At least one author must be a member of AVAHO. One author must present the abstract at the meeting. Accepted abstracts will be published in a special edition of Federal Practitioner.

​

The electronic poster session was viewed very favorably by attendees last year and will be used again this year. This requires more logistic hurdles and thus, the June 1 submission deadline is firm. 

Each poster will be assigned to one of two time slots for presentation.  One author must be present to give a brief presentation of the poster. Authors are encouraged to record their poster presentation to provide attendees another option for viewing your poster.  This recording does NOT replace the obligation to be present IN PERSON during the assigned poster session.  Details regarding this recording will be forthcoming.  

All abstracts must be submitted by June 1, 2019. This is a firm deadline. No extensions.

DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.

Michele G. Sullivan/MDedge News

In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.

“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”

The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.

Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.

Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.

The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.

Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.

Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).

The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.

Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.

More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).

Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).

The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.

msullivan@mdedge.com

SOURCE: Distler O et al. ATS 2019, Abstract A7360.

DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.

Michele G. Sullivan/MDedge News

In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.

“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”

The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.

Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.

Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.

The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.

Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.

Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).

The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.

Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.

More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).

Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).

The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.

msullivan@mdedge.com

SOURCE: Distler O et al. ATS 2019, Abstract A7360.

DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.

Michele G. Sullivan/MDedge News

In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.

“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”

The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.

Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.

Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.

The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.

Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.

Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).

The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.

Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.

More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).

Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).

The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.

msullivan@mdedge.com

SOURCE: Distler O et al. ATS 2019, Abstract A7360.

The U.S. measles count for 2019 had its smallest weekly increase in over 2 months last week as the total for the year hit 880 cases, according to the Centers for Disease Control and Prevention.

The U.S. measles count for 2019 had its smallest weekly increase in over 2 months last week as the total for the year hit 880 cases, according to the Centers for Disease Control and Prevention.

The U.S. measles count for 2019 had its smallest weekly increase in over 2 months last week as the total for the year hit 880 cases, according to the Centers for Disease Control and Prevention.

Liver transplantation (LT) is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital in South Korea. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at 1 year. Readmission rates more than tripled, from 16% at 30 days to 49% at 1 year.

Contrary to other research, living donor liver transplantation was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And although LT using the left liver lobe and pre-existing hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the identified risk factors were unexpected, the researchers say. One was donor age of < 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS)  > 2 weeks also was a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of < 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, the researchers found specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function test  (32% of readmissions) and fever (17% of readmissions and 39% of repeated readmissions). The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.

Liver transplantation (LT) is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital in South Korea. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at 1 year. Readmission rates more than tripled, from 16% at 30 days to 49% at 1 year.

Contrary to other research, living donor liver transplantation was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And although LT using the left liver lobe and pre-existing hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the identified risk factors were unexpected, the researchers say. One was donor age of < 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS)  > 2 weeks also was a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of < 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, the researchers found specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function test  (32% of readmissions) and fever (17% of readmissions and 39% of repeated readmissions). The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.

Liver transplantation (LT) is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital in South Korea. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at 1 year. Readmission rates more than tripled, from 16% at 30 days to 49% at 1 year.

Contrary to other research, living donor liver transplantation was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And although LT using the left liver lobe and pre-existing hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the identified risk factors were unexpected, the researchers say. One was donor age of < 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS)  > 2 weeks also was a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of < 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, the researchers found specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function test  (32% of readmissions) and fever (17% of readmissions and 39% of repeated readmissions). The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.