The continuing outbreak of Ebola in the Democratic Republic of the Congo (DRC) was the subject of a special United Nations high-level event organized by the World Health Organization (WHO) and the United Nations Office for the Coordination of Humanitarian Affairs (OCHA). It was comoderated by Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization, and Mark Lowcock, the UN Under-Secretary-General for Humanitarian Affairs and Emergency Relief Coordinator.

CDC/Athalia Christie

The DRC Ebola outbreak has drawn continuing concern and was highlighted by an even greater feeling of urgency as a case of Ebola was reported to have spread to Goma, the largest city in the eastern part of the DRC and a major trading port “on the eve of the conference,” according to one speaker.

That same infected individual – a priest arriving by bus to the city from an affected area – died of the disease the day after the conference concluded, according to the DRC authorities.

In his opening remarks, Mr. Lowcock stressed the importance of coordinating international efforts with the on-the-ground responses being carried out under the direction of Oly Ilunga Kalenga, MD, the DRC’s Minister of Public Health, who was also present and spoke at the meeting. Dr. Kalenga resigned his post on July 22, 2019.*

Mr. Lowcock stressed three points in particular that make for unique changes to the current response, compared with the earlier outbreak of 2014-2016.

First, in the previous outbreak in West Africa, “we didn’t have the vaccine and we didn’t have some of the successful treatments” that are currently available. Furthermore, more than 160,000 people have now been vaccinated and “the vaccine has a high degree of effectiveness.” This is an asset compared to the previous situation, he stated.

In his second point, he warned that the outbreak in the DRC “is taking place in an insecure and complex area with multiple armed groups present and large-scale preexisting humanitarian needs. Special interests distort the context. A history of disaffection with national authorities and foreigners generates distrust and makes the response more complicated. And one manifestation of that is attacks against health facilities and health care workers.” He added that “two more of our colleagues, trying to be part of the solution,” were killed in the past few days before the meeting. “Therefore, security for the response is of absolutely paramount importance, and we are trying to strengthen the way the UN family supports the government’s own security.”

The third major difference from the West Africa outbreak, Mr. Lowcock pointed out, was the issue of money. There was more than $2 billion in international support available for that earlier response. However, “what we have available for us in the DRC is just a small fraction of that. Donors released funds early on ... but much more is needed.” He warned that the cost of reaching zero cases must not be underestimated, and that the fourth strategic response plan for this outbreak, currently under development, “will be budgeted at a much higher level than the previous three plans, and that’s because it’s our assessment that we need a bigger, more comprehensive response if we’re to get to zero cases than we’ve had hitherto.”

In fact, he said, “unless there is a big scale up in the response, we’re unlikely to get to zero cases.”

The meeting also featured speakers outlining more local aspects of the response and discussing how international workers were coordinating more and more with local authorities and health practitioners in order to deliver health care on the ground while attempting to avoid the distrust created in the past, while still ensuring security for foreign personnel.

Commenting on the issue of security, Rory Stewart, the United Kingdom’s Secretary of State for International Development, described how a major DRC Ebola treatment center was attacked and burned by military insurgents, but is now rebuilt. He said that, while there have been some improvements and reasons to be hopeful, “this isn’t a moment for complacency; [the situation] is literally on the knife-edge.” He added: “If you go into that treatment center now, you will see that, although there are very good medical procedures, there are really, really worrying security procedures. The entire protection for the medical staff consists of a small square of sandbags about the height of this table [he raised his hand just above the standard conference table he was sitting at], behind which the doctors and nurses are supposed to hide if armed men get into the compound.”

In his presentation, David Gressly, the UN Emergency Ebola Response Coordinator (speaking by video from the DRC), stressed the need to cooperate with local authorities and to build local trust, stating that “the UN is putting together a tight, disciplined, coordinated system for rapid response and operational adjustments so that we can shift from chasing the disease to getting ahead of it. We need to quickly detect cases ... that have moved into areas of risk to stop the transmission early.”

Matshidiso Moeti, MD, WHO Regional Director for Africa, added in her presentation: “We’ve identified nine high-risk countries. Among those, Burundi, South Sudan, and Uganda face the highest risk and require our concerted and continued efforts.” She said that more than 10,000 health care workers in areas of high risk have so far been vaccinated against the disease.

In his concluding statement, Dr. Kalenga described the current state of affairs in his country with a modicum of hope. “A community that has been told it has a case of Ebola is a community that is traumatized by the very announcement of this epidemic. With time, the community has learned to face up to this epidemic differently. In some villages we are given a very different welcome than before. ... The villagers ask: ‘What should we do to make sure the Ebola case is the only one? The first and the last one?’ Throughout this epidemic, we have seen the people become more aware, and a certain acceptance of the very difficult and lethal diagnosis. ... So we have seen that work in the community has been maturing and bearing fruit.”

However, he pointed out, “there is a whole debate around the area of vaccinations, and we do need to close down this debate. At this point in time, we have a vaccine that is highly effective, a vaccine that is accepted by the population, after whole periods of mistrust. So we’ve come to a point in time when the population is accepting a vaccine, a vaccine that works, so we decided to no longer open the debate on vaccines and vaccination. ....We don’t want contradictory messages going out here, we don’t want different schemes going out. ...We have an effective weapon, we have an effective molecule. Let’s focus on that. Let’s all go in the same direction,” he concluded.

On July 11, an announcement by DRC officials stated that Merck’s rVSV-ZEBOV would be the only vaccine that will be used during the current Ebola outbreak in North Kivu and Ituri provinces, and that no other clinical vaccine trials to be allowed in the country so as not to confuse the population.

In that same announcement, the DRC reported that, since the beginning of the epidemic, the cumulative number of Ebola cases was 2,451, of which 2,357 were confirmed and 94 probable. There were 1,647 deaths (1,553 confirmed and 94 probable) and 683 people who survived. An additional 364 suspected cases were under investigation.

*Updated Aug. 1, 2019.

[email protected]

SOURCE: United Nations WHO/OCHA Webcast and Media Stakeout. July 15, 2019.

The continuing outbreak of Ebola in the Democratic Republic of the Congo (DRC) was the subject of a special United Nations high-level event organized by the World Health Organization (WHO) and the United Nations Office for the Coordination of Humanitarian Affairs (OCHA). It was comoderated by Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization, and Mark Lowcock, the UN Under-Secretary-General for Humanitarian Affairs and Emergency Relief Coordinator.

CDC/Athalia Christie

The DRC Ebola outbreak has drawn continuing concern and was highlighted by an even greater feeling of urgency as a case of Ebola was reported to have spread to Goma, the largest city in the eastern part of the DRC and a major trading port “on the eve of the conference,” according to one speaker.

That same infected individual – a priest arriving by bus to the city from an affected area – died of the disease the day after the conference concluded, according to the DRC authorities.

In his opening remarks, Mr. Lowcock stressed the importance of coordinating international efforts with the on-the-ground responses being carried out under the direction of Oly Ilunga Kalenga, MD, the DRC’s Minister of Public Health, who was also present and spoke at the meeting. Dr. Kalenga resigned his post on July 22, 2019.*

Mr. Lowcock stressed three points in particular that make for unique changes to the current response, compared with the earlier outbreak of 2014-2016.

First, in the previous outbreak in West Africa, “we didn’t have the vaccine and we didn’t have some of the successful treatments” that are currently available. Furthermore, more than 160,000 people have now been vaccinated and “the vaccine has a high degree of effectiveness.” This is an asset compared to the previous situation, he stated.

In his second point, he warned that the outbreak in the DRC “is taking place in an insecure and complex area with multiple armed groups present and large-scale preexisting humanitarian needs. Special interests distort the context. A history of disaffection with national authorities and foreigners generates distrust and makes the response more complicated. And one manifestation of that is attacks against health facilities and health care workers.” He added that “two more of our colleagues, trying to be part of the solution,” were killed in the past few days before the meeting. “Therefore, security for the response is of absolutely paramount importance, and we are trying to strengthen the way the UN family supports the government’s own security.”

The third major difference from the West Africa outbreak, Mr. Lowcock pointed out, was the issue of money. There was more than $2 billion in international support available for that earlier response. However, “what we have available for us in the DRC is just a small fraction of that. Donors released funds early on ... but much more is needed.” He warned that the cost of reaching zero cases must not be underestimated, and that the fourth strategic response plan for this outbreak, currently under development, “will be budgeted at a much higher level than the previous three plans, and that’s because it’s our assessment that we need a bigger, more comprehensive response if we’re to get to zero cases than we’ve had hitherto.”

In fact, he said, “unless there is a big scale up in the response, we’re unlikely to get to zero cases.”

The meeting also featured speakers outlining more local aspects of the response and discussing how international workers were coordinating more and more with local authorities and health practitioners in order to deliver health care on the ground while attempting to avoid the distrust created in the past, while still ensuring security for foreign personnel.

Commenting on the issue of security, Rory Stewart, the United Kingdom’s Secretary of State for International Development, described how a major DRC Ebola treatment center was attacked and burned by military insurgents, but is now rebuilt. He said that, while there have been some improvements and reasons to be hopeful, “this isn’t a moment for complacency; [the situation] is literally on the knife-edge.” He added: “If you go into that treatment center now, you will see that, although there are very good medical procedures, there are really, really worrying security procedures. The entire protection for the medical staff consists of a small square of sandbags about the height of this table [he raised his hand just above the standard conference table he was sitting at], behind which the doctors and nurses are supposed to hide if armed men get into the compound.”

In his presentation, David Gressly, the UN Emergency Ebola Response Coordinator (speaking by video from the DRC), stressed the need to cooperate with local authorities and to build local trust, stating that “the UN is putting together a tight, disciplined, coordinated system for rapid response and operational adjustments so that we can shift from chasing the disease to getting ahead of it. We need to quickly detect cases ... that have moved into areas of risk to stop the transmission early.”

Matshidiso Moeti, MD, WHO Regional Director for Africa, added in her presentation: “We’ve identified nine high-risk countries. Among those, Burundi, South Sudan, and Uganda face the highest risk and require our concerted and continued efforts.” She said that more than 10,000 health care workers in areas of high risk have so far been vaccinated against the disease.

In his concluding statement, Dr. Kalenga described the current state of affairs in his country with a modicum of hope. “A community that has been told it has a case of Ebola is a community that is traumatized by the very announcement of this epidemic. With time, the community has learned to face up to this epidemic differently. In some villages we are given a very different welcome than before. ... The villagers ask: ‘What should we do to make sure the Ebola case is the only one? The first and the last one?’ Throughout this epidemic, we have seen the people become more aware, and a certain acceptance of the very difficult and lethal diagnosis. ... So we have seen that work in the community has been maturing and bearing fruit.”

However, he pointed out, “there is a whole debate around the area of vaccinations, and we do need to close down this debate. At this point in time, we have a vaccine that is highly effective, a vaccine that is accepted by the population, after whole periods of mistrust. So we’ve come to a point in time when the population is accepting a vaccine, a vaccine that works, so we decided to no longer open the debate on vaccines and vaccination. ....We don’t want contradictory messages going out here, we don’t want different schemes going out. ...We have an effective weapon, we have an effective molecule. Let’s focus on that. Let’s all go in the same direction,” he concluded.

On July 11, an announcement by DRC officials stated that Merck’s rVSV-ZEBOV would be the only vaccine that will be used during the current Ebola outbreak in North Kivu and Ituri provinces, and that no other clinical vaccine trials to be allowed in the country so as not to confuse the population.

In that same announcement, the DRC reported that, since the beginning of the epidemic, the cumulative number of Ebola cases was 2,451, of which 2,357 were confirmed and 94 probable. There were 1,647 deaths (1,553 confirmed and 94 probable) and 683 people who survived. An additional 364 suspected cases were under investigation.

*Updated Aug. 1, 2019.

[email protected]

SOURCE: United Nations WHO/OCHA Webcast and Media Stakeout. July 15, 2019.

The continuing outbreak of Ebola in the Democratic Republic of the Congo (DRC) was the subject of a special United Nations high-level event organized by the World Health Organization (WHO) and the United Nations Office for the Coordination of Humanitarian Affairs (OCHA). It was comoderated by Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization, and Mark Lowcock, the UN Under-Secretary-General for Humanitarian Affairs and Emergency Relief Coordinator.

CDC/Athalia Christie

The DRC Ebola outbreak has drawn continuing concern and was highlighted by an even greater feeling of urgency as a case of Ebola was reported to have spread to Goma, the largest city in the eastern part of the DRC and a major trading port “on the eve of the conference,” according to one speaker.

That same infected individual – a priest arriving by bus to the city from an affected area – died of the disease the day after the conference concluded, according to the DRC authorities.

In his opening remarks, Mr. Lowcock stressed the importance of coordinating international efforts with the on-the-ground responses being carried out under the direction of Oly Ilunga Kalenga, MD, the DRC’s Minister of Public Health, who was also present and spoke at the meeting. Dr. Kalenga resigned his post on July 22, 2019.*

Mr. Lowcock stressed three points in particular that make for unique changes to the current response, compared with the earlier outbreak of 2014-2016.

First, in the previous outbreak in West Africa, “we didn’t have the vaccine and we didn’t have some of the successful treatments” that are currently available. Furthermore, more than 160,000 people have now been vaccinated and “the vaccine has a high degree of effectiveness.” This is an asset compared to the previous situation, he stated.

In his second point, he warned that the outbreak in the DRC “is taking place in an insecure and complex area with multiple armed groups present and large-scale preexisting humanitarian needs. Special interests distort the context. A history of disaffection with national authorities and foreigners generates distrust and makes the response more complicated. And one manifestation of that is attacks against health facilities and health care workers.” He added that “two more of our colleagues, trying to be part of the solution,” were killed in the past few days before the meeting. “Therefore, security for the response is of absolutely paramount importance, and we are trying to strengthen the way the UN family supports the government’s own security.”

The third major difference from the West Africa outbreak, Mr. Lowcock pointed out, was the issue of money. There was more than $2 billion in international support available for that earlier response. However, “what we have available for us in the DRC is just a small fraction of that. Donors released funds early on ... but much more is needed.” He warned that the cost of reaching zero cases must not be underestimated, and that the fourth strategic response plan for this outbreak, currently under development, “will be budgeted at a much higher level than the previous three plans, and that’s because it’s our assessment that we need a bigger, more comprehensive response if we’re to get to zero cases than we’ve had hitherto.”

In fact, he said, “unless there is a big scale up in the response, we’re unlikely to get to zero cases.”

The meeting also featured speakers outlining more local aspects of the response and discussing how international workers were coordinating more and more with local authorities and health practitioners in order to deliver health care on the ground while attempting to avoid the distrust created in the past, while still ensuring security for foreign personnel.

Commenting on the issue of security, Rory Stewart, the United Kingdom’s Secretary of State for International Development, described how a major DRC Ebola treatment center was attacked and burned by military insurgents, but is now rebuilt. He said that, while there have been some improvements and reasons to be hopeful, “this isn’t a moment for complacency; [the situation] is literally on the knife-edge.” He added: “If you go into that treatment center now, you will see that, although there are very good medical procedures, there are really, really worrying security procedures. The entire protection for the medical staff consists of a small square of sandbags about the height of this table [he raised his hand just above the standard conference table he was sitting at], behind which the doctors and nurses are supposed to hide if armed men get into the compound.”

In his presentation, David Gressly, the UN Emergency Ebola Response Coordinator (speaking by video from the DRC), stressed the need to cooperate with local authorities and to build local trust, stating that “the UN is putting together a tight, disciplined, coordinated system for rapid response and operational adjustments so that we can shift from chasing the disease to getting ahead of it. We need to quickly detect cases ... that have moved into areas of risk to stop the transmission early.”

Matshidiso Moeti, MD, WHO Regional Director for Africa, added in her presentation: “We’ve identified nine high-risk countries. Among those, Burundi, South Sudan, and Uganda face the highest risk and require our concerted and continued efforts.” She said that more than 10,000 health care workers in areas of high risk have so far been vaccinated against the disease.

In his concluding statement, Dr. Kalenga described the current state of affairs in his country with a modicum of hope. “A community that has been told it has a case of Ebola is a community that is traumatized by the very announcement of this epidemic. With time, the community has learned to face up to this epidemic differently. In some villages we are given a very different welcome than before. ... The villagers ask: ‘What should we do to make sure the Ebola case is the only one? The first and the last one?’ Throughout this epidemic, we have seen the people become more aware, and a certain acceptance of the very difficult and lethal diagnosis. ... So we have seen that work in the community has been maturing and bearing fruit.”

However, he pointed out, “there is a whole debate around the area of vaccinations, and we do need to close down this debate. At this point in time, we have a vaccine that is highly effective, a vaccine that is accepted by the population, after whole periods of mistrust. So we’ve come to a point in time when the population is accepting a vaccine, a vaccine that works, so we decided to no longer open the debate on vaccines and vaccination. ....We don’t want contradictory messages going out here, we don’t want different schemes going out. ...We have an effective weapon, we have an effective molecule. Let’s focus on that. Let’s all go in the same direction,” he concluded.

On July 11, an announcement by DRC officials stated that Merck’s rVSV-ZEBOV would be the only vaccine that will be used during the current Ebola outbreak in North Kivu and Ituri provinces, and that no other clinical vaccine trials to be allowed in the country so as not to confuse the population.

In that same announcement, the DRC reported that, since the beginning of the epidemic, the cumulative number of Ebola cases was 2,451, of which 2,357 were confirmed and 94 probable. There were 1,647 deaths (1,553 confirmed and 94 probable) and 683 people who survived. An additional 364 suspected cases were under investigation.

*Updated Aug. 1, 2019.

[email protected]

SOURCE: United Nations WHO/OCHA Webcast and Media Stakeout. July 15, 2019.

MELBOURNE – A majority of minor surgeries can be performed in hemophilia A patients receiving emicizumab therapy without requiring prophylactic treatment with coagulation factors, according to data presented at the International Society on Thrombosis and Haemostasis congress.

Bianca Nogrady/MDedge News

Elena Santagostino, MD, PhD, from the Hemophilia and Thrombosis Center at Ospedale Maggiore Policlinico in Milan presented data from 399 patients involved in the four HAVEN trials of the humanized bispecific monoclonal antibody emicizumab (Hemlibra), which is Food and Drug Administration–approved for the prevention of bleeding episodes in individuals with hemophilia A, with or without inhibitors.

The analysis focused on the 126 patients (31.6%) who underwent at least one surgical procedure during the studies. Of the 233 surgeries, there were 215 minor procedures performed in 115 patients, and 18 major surgeries in 18 patients. All patients were receiving ongoing treatment with emicizumab, and there was no change to that treatment regimen during surgery.

“It is clear that surgery is a challenge for hemophilia,” Dr. Santagostino said. “It is a challenge for bleeding, it is a challenge for thrombosis, it is a challenge for any new drug, and this is why there is a lot of interest around this topic.”

Overall, 65.6% of minor surgeries were performed without any prophylactic coagulation factor treatment, and 90.8% of minor surgeries were conducted without postoperative bleeds requiring treatment. There were no cases of thrombosis reported.

The surgeries that did not require prophylactic coagulation factor included 42 dental procedures, 25 central venous access devices, 17 endoscopic procedures, and 12 joint procedures.

While the HAVEN studies did not allow for elective major surgery, there were still 18 unplanned major surgical situations that arose during the course of the studies. These included three hip, one knee, and one ankle arthroplasties; three synovectomies; and some dental, central venous line, and endoscopic biopsy procedures.

Of these, 15 involved prophylactic coagulant factor administration, but three procedures – including one synovectomy – were performed without prophylaxis and none resulted in a bleed.

There was one complicated bleed that occurred in a patient undergoing multiple procedures including a synovectomy, joint debridement and chondroplasty, who received prolonged treatment with recombinant Factor VIIa.

Dr. Santagostino said the findings showed surgery could be safely performed in patients who were being treated with emicizumab, both with and without inhibitors.

“A large number of minor procedures can be done without adding coagulation factors,” she said in an interview. “This is true for less invasive surgeries, such as catheter-related central venous line procedures. Even several endoscopic procedures, like a single biopsy, can be done reasonably safely.”

However she said there was still a lack of experience in dealing with hemophilia A patients who were undergoing cancer surgery, or who had significant comorbidities that might put them at higher risk of thrombosis.

“These are special patients populations that are still not investigated in the trial setting,” she said.

Commenting on the data, session cochair Liane Khoo, MD, from the Haemophilia Treatment Centre at Royal Prince Alfred Hospital in Sydney, said the results showed surgery could be performed in hemophilia A patients with and without inhibitors.

“The more we have the medication and the more experience we have, then we become more confident in using it,” she said.

The study was funded by F. Hoffman-La Roche and Chugai Pharmaceutical. Dr. Santagostino reported consultancies and speakers bureau engagements with the pharmaceutical sector.

SOURCE: Santagostino E et al. 2019 ISTH Congress, Abstract OC 60.1.

MELBOURNE – A majority of minor surgeries can be performed in hemophilia A patients receiving emicizumab therapy without requiring prophylactic treatment with coagulation factors, according to data presented at the International Society on Thrombosis and Haemostasis congress.

Bianca Nogrady/MDedge News

Elena Santagostino, MD, PhD, from the Hemophilia and Thrombosis Center at Ospedale Maggiore Policlinico in Milan presented data from 399 patients involved in the four HAVEN trials of the humanized bispecific monoclonal antibody emicizumab (Hemlibra), which is Food and Drug Administration–approved for the prevention of bleeding episodes in individuals with hemophilia A, with or without inhibitors.

The analysis focused on the 126 patients (31.6%) who underwent at least one surgical procedure during the studies. Of the 233 surgeries, there were 215 minor procedures performed in 115 patients, and 18 major surgeries in 18 patients. All patients were receiving ongoing treatment with emicizumab, and there was no change to that treatment regimen during surgery.

“It is clear that surgery is a challenge for hemophilia,” Dr. Santagostino said. “It is a challenge for bleeding, it is a challenge for thrombosis, it is a challenge for any new drug, and this is why there is a lot of interest around this topic.”

Overall, 65.6% of minor surgeries were performed without any prophylactic coagulation factor treatment, and 90.8% of minor surgeries were conducted without postoperative bleeds requiring treatment. There were no cases of thrombosis reported.

The surgeries that did not require prophylactic coagulation factor included 42 dental procedures, 25 central venous access devices, 17 endoscopic procedures, and 12 joint procedures.

While the HAVEN studies did not allow for elective major surgery, there were still 18 unplanned major surgical situations that arose during the course of the studies. These included three hip, one knee, and one ankle arthroplasties; three synovectomies; and some dental, central venous line, and endoscopic biopsy procedures.

Of these, 15 involved prophylactic coagulant factor administration, but three procedures – including one synovectomy – were performed without prophylaxis and none resulted in a bleed.

There was one complicated bleed that occurred in a patient undergoing multiple procedures including a synovectomy, joint debridement and chondroplasty, who received prolonged treatment with recombinant Factor VIIa.

Dr. Santagostino said the findings showed surgery could be safely performed in patients who were being treated with emicizumab, both with and without inhibitors.

“A large number of minor procedures can be done without adding coagulation factors,” she said in an interview. “This is true for less invasive surgeries, such as catheter-related central venous line procedures. Even several endoscopic procedures, like a single biopsy, can be done reasonably safely.”

However she said there was still a lack of experience in dealing with hemophilia A patients who were undergoing cancer surgery, or who had significant comorbidities that might put them at higher risk of thrombosis.

“These are special patients populations that are still not investigated in the trial setting,” she said.

Commenting on the data, session cochair Liane Khoo, MD, from the Haemophilia Treatment Centre at Royal Prince Alfred Hospital in Sydney, said the results showed surgery could be performed in hemophilia A patients with and without inhibitors.

“The more we have the medication and the more experience we have, then we become more confident in using it,” she said.

The study was funded by F. Hoffman-La Roche and Chugai Pharmaceutical. Dr. Santagostino reported consultancies and speakers bureau engagements with the pharmaceutical sector.

SOURCE: Santagostino E et al. 2019 ISTH Congress, Abstract OC 60.1.

MELBOURNE – A majority of minor surgeries can be performed in hemophilia A patients receiving emicizumab therapy without requiring prophylactic treatment with coagulation factors, according to data presented at the International Society on Thrombosis and Haemostasis congress.

Bianca Nogrady/MDedge News

Elena Santagostino, MD, PhD, from the Hemophilia and Thrombosis Center at Ospedale Maggiore Policlinico in Milan presented data from 399 patients involved in the four HAVEN trials of the humanized bispecific monoclonal antibody emicizumab (Hemlibra), which is Food and Drug Administration–approved for the prevention of bleeding episodes in individuals with hemophilia A, with or without inhibitors.

The analysis focused on the 126 patients (31.6%) who underwent at least one surgical procedure during the studies. Of the 233 surgeries, there were 215 minor procedures performed in 115 patients, and 18 major surgeries in 18 patients. All patients were receiving ongoing treatment with emicizumab, and there was no change to that treatment regimen during surgery.

“It is clear that surgery is a challenge for hemophilia,” Dr. Santagostino said. “It is a challenge for bleeding, it is a challenge for thrombosis, it is a challenge for any new drug, and this is why there is a lot of interest around this topic.”

Overall, 65.6% of minor surgeries were performed without any prophylactic coagulation factor treatment, and 90.8% of minor surgeries were conducted without postoperative bleeds requiring treatment. There were no cases of thrombosis reported.

The surgeries that did not require prophylactic coagulation factor included 42 dental procedures, 25 central venous access devices, 17 endoscopic procedures, and 12 joint procedures.

While the HAVEN studies did not allow for elective major surgery, there were still 18 unplanned major surgical situations that arose during the course of the studies. These included three hip, one knee, and one ankle arthroplasties; three synovectomies; and some dental, central venous line, and endoscopic biopsy procedures.

Of these, 15 involved prophylactic coagulant factor administration, but three procedures – including one synovectomy – were performed without prophylaxis and none resulted in a bleed.

There was one complicated bleed that occurred in a patient undergoing multiple procedures including a synovectomy, joint debridement and chondroplasty, who received prolonged treatment with recombinant Factor VIIa.

Dr. Santagostino said the findings showed surgery could be safely performed in patients who were being treated with emicizumab, both with and without inhibitors.

“A large number of minor procedures can be done without adding coagulation factors,” she said in an interview. “This is true for less invasive surgeries, such as catheter-related central venous line procedures. Even several endoscopic procedures, like a single biopsy, can be done reasonably safely.”

However she said there was still a lack of experience in dealing with hemophilia A patients who were undergoing cancer surgery, or who had significant comorbidities that might put them at higher risk of thrombosis.

“These are special patients populations that are still not investigated in the trial setting,” she said.

Commenting on the data, session cochair Liane Khoo, MD, from the Haemophilia Treatment Centre at Royal Prince Alfred Hospital in Sydney, said the results showed surgery could be performed in hemophilia A patients with and without inhibitors.

“The more we have the medication and the more experience we have, then we become more confident in using it,” she said.

The study was funded by F. Hoffman-La Roche and Chugai Pharmaceutical. Dr. Santagostino reported consultancies and speakers bureau engagements with the pharmaceutical sector.

SOURCE: Santagostino E et al. 2019 ISTH Congress, Abstract OC 60.1.

Since birth, this 5-month-old boy has had a facial rash that comes and goes. At times severe, it is the source of much familial disagreement about its cause: Some say the problem is related to food, while others are sure it represents infection.

Several medications, including triple-antibiotic ointment and nystatin cream, have been tried. None have had much effect.

The child is well in all other respects—gaining weight as expected and experiencing normal growth and development. The rash does not appear to bother him as much as it bothers his family to see.

Further questioning reveals a strong family history of seasonal allergies, eczema, and asthma. Notably, all affected individuals have long since outgrown those problems.

EXAMINATION
The child is in no apparent distress but is noted to have nasal congestion, with continual mouth breathing. Overall, his skin is quite dry and fair.

The rash itself is rather florid, affecting the perioral area and spreading onto the cheeks in a symmetrical configuration. The skin in these areas is focally erythematous, though not swollen. It is also quite scaly in places, giving the appearance of, as his parents note, “chapped” skin. Examination of the diaper area reveals a similar look focally.

What’s the diagnosis?

DISCUSSION
This case is typical of those seen multiple times daily in primary care and dermatology offices—hardly surprising, since atopic dermatitis (AD) affects about 20% of all newborns in this and other developed countries. In very young children, AD primarily affects the face and diaper area, as well as the trunk. About 50% of affected patients will have cradle cap—as did this child in his first month of life, we subsequently learned.

The tendency to develop AD is inherited. It is not related to food, although children with AD could develop a food allergy. However, it would more likely manifest with gastrointestinal symptoms. Another myth embedded in Western culture is that AD is caused by exposure to a particular laundry detergent.

Rather, this child and others like him have inherited dry, thin, overreactive skin that is bathed early on with nasal secretions, bacteria, and saliva. Later, their eczema will migrate to areas that stay moist, such as the antecubital and popliteal folds, or to the area around the neck, where the itching can be intense—which of course causes the child to scratch, in turn worsening the problem.

Patient/parent education is the key to dealing with AD and can be bolstered by handouts or direction to reliable websites. Besides objectifying the problem, these resources detail its nature and outline the need for daily bathing with mild cleansers, generous application of heavy moisturizers, careful use of topical corticosteroid creams or ointments (eg, 2.5% hydrocortisone), and avoidance of woolen clothing or bedding.

Another important component of patient/parent education is the reassurance that eczema will not scar the patient. It does occasionally become severe enough to require a short course of oral antibiotics (eg, cephalexin) or even the use of oral prednisolone. Since AD is not a histamine-driven process, antihistamines are ineffective for eczema.

TAKE-HOME LEARNING POINTS

• Atopic dermatitis (AD) is extremely common, affecting 20% of all newborns in developed countries.
• Infantile eczema typically centers on the face, particularly the perioral area.
• Later, it begins to involve the antecubital and popliteal areas, which stay moist a good part of the time.
• Most children outgrow the worst of the problem—and go on to have children who develop it.

Since birth, this 5-month-old boy has had a facial rash that comes and goes. At times severe, it is the source of much familial disagreement about its cause: Some say the problem is related to food, while others are sure it represents infection.

Several medications, including triple-antibiotic ointment and nystatin cream, have been tried. None have had much effect.

The child is well in all other respects—gaining weight as expected and experiencing normal growth and development. The rash does not appear to bother him as much as it bothers his family to see.

Further questioning reveals a strong family history of seasonal allergies, eczema, and asthma. Notably, all affected individuals have long since outgrown those problems.

EXAMINATION
The child is in no apparent distress but is noted to have nasal congestion, with continual mouth breathing. Overall, his skin is quite dry and fair.

The rash itself is rather florid, affecting the perioral area and spreading onto the cheeks in a symmetrical configuration. The skin in these areas is focally erythematous, though not swollen. It is also quite scaly in places, giving the appearance of, as his parents note, “chapped” skin. Examination of the diaper area reveals a similar look focally.

What’s the diagnosis?

DISCUSSION
This case is typical of those seen multiple times daily in primary care and dermatology offices—hardly surprising, since atopic dermatitis (AD) affects about 20% of all newborns in this and other developed countries. In very young children, AD primarily affects the face and diaper area, as well as the trunk. About 50% of affected patients will have cradle cap—as did this child in his first month of life, we subsequently learned.

The tendency to develop AD is inherited. It is not related to food, although children with AD could develop a food allergy. However, it would more likely manifest with gastrointestinal symptoms. Another myth embedded in Western culture is that AD is caused by exposure to a particular laundry detergent.

Rather, this child and others like him have inherited dry, thin, overreactive skin that is bathed early on with nasal secretions, bacteria, and saliva. Later, their eczema will migrate to areas that stay moist, such as the antecubital and popliteal folds, or to the area around the neck, where the itching can be intense—which of course causes the child to scratch, in turn worsening the problem.

Patient/parent education is the key to dealing with AD and can be bolstered by handouts or direction to reliable websites. Besides objectifying the problem, these resources detail its nature and outline the need for daily bathing with mild cleansers, generous application of heavy moisturizers, careful use of topical corticosteroid creams or ointments (eg, 2.5% hydrocortisone), and avoidance of woolen clothing or bedding.

Another important component of patient/parent education is the reassurance that eczema will not scar the patient. It does occasionally become severe enough to require a short course of oral antibiotics (eg, cephalexin) or even the use of oral prednisolone. Since AD is not a histamine-driven process, antihistamines are ineffective for eczema.

TAKE-HOME LEARNING POINTS

• Atopic dermatitis (AD) is extremely common, affecting 20% of all newborns in developed countries.
• Infantile eczema typically centers on the face, particularly the perioral area.
• Later, it begins to involve the antecubital and popliteal areas, which stay moist a good part of the time.
• Most children outgrow the worst of the problem—and go on to have children who develop it.

Since birth, this 5-month-old boy has had a facial rash that comes and goes. At times severe, it is the source of much familial disagreement about its cause: Some say the problem is related to food, while others are sure it represents infection.

Several medications, including triple-antibiotic ointment and nystatin cream, have been tried. None have had much effect.

The child is well in all other respects—gaining weight as expected and experiencing normal growth and development. The rash does not appear to bother him as much as it bothers his family to see.

Further questioning reveals a strong family history of seasonal allergies, eczema, and asthma. Notably, all affected individuals have long since outgrown those problems.

EXAMINATION
The child is in no apparent distress but is noted to have nasal congestion, with continual mouth breathing. Overall, his skin is quite dry and fair.

The rash itself is rather florid, affecting the perioral area and spreading onto the cheeks in a symmetrical configuration. The skin in these areas is focally erythematous, though not swollen. It is also quite scaly in places, giving the appearance of, as his parents note, “chapped” skin. Examination of the diaper area reveals a similar look focally.

What’s the diagnosis?

DISCUSSION
This case is typical of those seen multiple times daily in primary care and dermatology offices—hardly surprising, since atopic dermatitis (AD) affects about 20% of all newborns in this and other developed countries. In very young children, AD primarily affects the face and diaper area, as well as the trunk. About 50% of affected patients will have cradle cap—as did this child in his first month of life, we subsequently learned.

The tendency to develop AD is inherited. It is not related to food, although children with AD could develop a food allergy. However, it would more likely manifest with gastrointestinal symptoms. Another myth embedded in Western culture is that AD is caused by exposure to a particular laundry detergent.

Rather, this child and others like him have inherited dry, thin, overreactive skin that is bathed early on with nasal secretions, bacteria, and saliva. Later, their eczema will migrate to areas that stay moist, such as the antecubital and popliteal folds, or to the area around the neck, where the itching can be intense—which of course causes the child to scratch, in turn worsening the problem.

Patient/parent education is the key to dealing with AD and can be bolstered by handouts or direction to reliable websites. Besides objectifying the problem, these resources detail its nature and outline the need for daily bathing with mild cleansers, generous application of heavy moisturizers, careful use of topical corticosteroid creams or ointments (eg, 2.5% hydrocortisone), and avoidance of woolen clothing or bedding.

Another important component of patient/parent education is the reassurance that eczema will not scar the patient. It does occasionally become severe enough to require a short course of oral antibiotics (eg, cephalexin) or even the use of oral prednisolone. Since AD is not a histamine-driven process, antihistamines are ineffective for eczema.

TAKE-HOME LEARNING POINTS

• Atopic dermatitis (AD) is extremely common, affecting 20% of all newborns in developed countries.
• Infantile eczema typically centers on the face, particularly the perioral area.
• Later, it begins to involve the antecubital and popliteal areas, which stay moist a good part of the time.
• Most children outgrow the worst of the problem—and go on to have children who develop it.

Based on the target lesions with central epithelial disruption, the FP diagnosed erythema multiforme (EM) in this patient. He also diagnosed genital herpes simplex in the crusting stage and suspected that it was the inciting event for the EM.

EM is considered a hypersensitivity reaction that is often secondary to infections or medications. Herpes simplex viruses (HSVI and HSV2) are the most common causative agents and have been implicated in at least 60% of cases.

The patient did not know that she had genital herpes simplex but remembered having sores in the genital area that preceded the similar rash a year earlier. This was a case of recurrent EM responding to recurrent herpes simplex.

The patient suspected that she had genital herpes simplex on and off for the past 10 years but lacked health insurance, so she never visited a doctor for treatment. She recently obtained health insurance and was willing to be tested for other sexually transmitted diseases. She also wanted to have a test done to confirm this was herpes simplex. The FP explained that it was unlikely that an antiviral agent would help the current case of herpes simplex and the associated EM because of the late timing, but antiviral medication could help to prevent further outbreaks and decrease transmission to her husband.

The patient was enthusiastic to start valacyclovir 500 mg/d for prophylaxis. For symptomatic relief, the FP prescribed a 30-g tube of 0.1% triamcinolone appointment and instructed the patient to apply it to the EM twice daily. The patient was sent for blood tests for syphilis and HIV; fortunately, both came back negative. The herpes simplex PCR test was positive for HSV2.

On a 1-week follow-up visit, the skin lesions were resolving, and the patient had no further symptoms. The patient said she understood that she should refrain from sexual intercourse if she developed lesions while on prophylaxis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Milana C, Smith M. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1161-1168.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Based on the target lesions with central epithelial disruption, the FP diagnosed erythema multiforme (EM) in this patient. He also diagnosed genital herpes simplex in the crusting stage and suspected that it was the inciting event for the EM.

EM is considered a hypersensitivity reaction that is often secondary to infections or medications. Herpes simplex viruses (HSVI and HSV2) are the most common causative agents and have been implicated in at least 60% of cases.

The patient did not know that she had genital herpes simplex but remembered having sores in the genital area that preceded the similar rash a year earlier. This was a case of recurrent EM responding to recurrent herpes simplex.

The patient suspected that she had genital herpes simplex on and off for the past 10 years but lacked health insurance, so she never visited a doctor for treatment. She recently obtained health insurance and was willing to be tested for other sexually transmitted diseases. She also wanted to have a test done to confirm this was herpes simplex. The FP explained that it was unlikely that an antiviral agent would help the current case of herpes simplex and the associated EM because of the late timing, but antiviral medication could help to prevent further outbreaks and decrease transmission to her husband.

The patient was enthusiastic to start valacyclovir 500 mg/d for prophylaxis. For symptomatic relief, the FP prescribed a 30-g tube of 0.1% triamcinolone appointment and instructed the patient to apply it to the EM twice daily. The patient was sent for blood tests for syphilis and HIV; fortunately, both came back negative. The herpes simplex PCR test was positive for HSV2.

On a 1-week follow-up visit, the skin lesions were resolving, and the patient had no further symptoms. The patient said she understood that she should refrain from sexual intercourse if she developed lesions while on prophylaxis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Milana C, Smith M. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1161-1168.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Based on the target lesions with central epithelial disruption, the FP diagnosed erythema multiforme (EM) in this patient. He also diagnosed genital herpes simplex in the crusting stage and suspected that it was the inciting event for the EM.

EM is considered a hypersensitivity reaction that is often secondary to infections or medications. Herpes simplex viruses (HSVI and HSV2) are the most common causative agents and have been implicated in at least 60% of cases.

The patient did not know that she had genital herpes simplex but remembered having sores in the genital area that preceded the similar rash a year earlier. This was a case of recurrent EM responding to recurrent herpes simplex.

The patient suspected that she had genital herpes simplex on and off for the past 10 years but lacked health insurance, so she never visited a doctor for treatment. She recently obtained health insurance and was willing to be tested for other sexually transmitted diseases. She also wanted to have a test done to confirm this was herpes simplex. The FP explained that it was unlikely that an antiviral agent would help the current case of herpes simplex and the associated EM because of the late timing, but antiviral medication could help to prevent further outbreaks and decrease transmission to her husband.

The patient was enthusiastic to start valacyclovir 500 mg/d for prophylaxis. For symptomatic relief, the FP prescribed a 30-g tube of 0.1% triamcinolone appointment and instructed the patient to apply it to the EM twice daily. The patient was sent for blood tests for syphilis and HIV; fortunately, both came back negative. The herpes simplex PCR test was positive for HSV2.

On a 1-week follow-up visit, the skin lesions were resolving, and the patient had no further symptoms. The patient said she understood that she should refrain from sexual intercourse if she developed lesions while on prophylaxis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Milana C, Smith M. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1161-1168.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Both systolic and diastolic hypertension independently predict myocardial infarction and strokes, but systolic blood pressure is more strongly linked to adverse outcomes.

That’s according to a study of more than 1 million patients and 36 million outpatient blood pressure measurements published in the New England Journal of Medicine.

Systolic and diastolic hypertension predicted adverse outcomes at cutpoints of 140/90 and 130/80 mm Hg in the large retrospective cohort study, supporting the recent guideline changes that made blood pressure targets more stringent for higher-risk patients, said lead investigator Alexander C. Flint, MD, of Kaiser Permanente Northern California (KPNC) in Oakland.

“While systolic does count for more, in the fact that it is a stronger driver of the risk of heart attack and stroke, diastolic absolutely does as well, and it does so independently. So we ignore our diastolic hypertension at our own peril,” Dr. Flint said in an interview.

Systolic hypertension began to overshadow diastolic after the Framingham Heart Study and others that suggested it is a more important predictor of adverse cardiovascular outcomes, Dr. Flint and coauthors said in a report on their study.

Those findings caused some to say diastole should be abandoned, and led to a “near-exclusive focus” on systolic hypertension in a 2000 advisory statement from the National High Blood Pressure Education Program, they say in their report.

While current guidelines emphasize the importance of both systolic and diastolic targets, many clinicians today often assign little importance to diastolic blood pressure values, the report adds.

“The pendulum needs to swing back, right down in the middle,” Dr. Flint said in the interview.

The study by Dr. Flint and colleagues comprised a cohort of approximately 1.3 million outpatients from KPNC who had at least one baseline blood pressure reading in during 2007-2008, and two or more follow-up measurements between 2009 and 2016, for a total of about 36.8 million data points.

Systolic hypertension burden was linked to the composite of MI or stroke, with a hazard ratio of 1.18 (95% confidence interval, 1.17-1.18; P less than .001) per unit increase in z score, according to results of a multivariable regression analysis. Likewise, diastolic hypertension burden was linked to those adverse outcomes, with a hazard ratio of 1.06 (95% CI, 1.06-1.07; P less than .001).

Put in terms of estimated risk of MI or stroke, patients with a systolic blood pressure around 160 mm Hg – 3 standard deviations from the mean – was 4.8%, compared to a predicted risk of just 1.9% for a systolic blood pressure near 136 mm Hg, the investigators said in their report.

Similarly, predicted risk was 3.6% for a diastolic pressure of about 96 mm Hg, also 3 standard deviations from the mean, and 1.9% for a diastolic BP near 81 mm Hg.

“The two are not that separate,” Dr. Flint said of the risks associated with systolic and diastolic hypertension at that 3-standard-deviation point. Beyond that, increased systolic blood pressure is associated with more risk relative to increased diastolic blood pressure, the logistic regression modeling shows.

Taken together, findings from this large cohort study emphasize the importance of making lifestyle modifications and adjusting medication to ensure that both systolic and diastolic targets are met, according to Dr. Flint.

“Rises in systolic blood pressure count for more in influencing the risk of heart attack and stroke,” he said, “but diastolic independently counts for quite a lot. It’s a close second.”

Dr. Flint reported no disclosures. Senior author Deepak L. Bhatt, MD, MPH, reported disclosures with Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, Takeda, The Medicines Company, and others. The remaining authors had no disclosures.

SOURCE: Flint AC et al. N Engl J Med. 2019 Jul 18. doi: 10.1056/NEJMoa1803180.

Both systolic and diastolic hypertension independently predict myocardial infarction and strokes, but systolic blood pressure is more strongly linked to adverse outcomes.

That’s according to a study of more than 1 million patients and 36 million outpatient blood pressure measurements published in the New England Journal of Medicine.

Systolic and diastolic hypertension predicted adverse outcomes at cutpoints of 140/90 and 130/80 mm Hg in the large retrospective cohort study, supporting the recent guideline changes that made blood pressure targets more stringent for higher-risk patients, said lead investigator Alexander C. Flint, MD, of Kaiser Permanente Northern California (KPNC) in Oakland.

“While systolic does count for more, in the fact that it is a stronger driver of the risk of heart attack and stroke, diastolic absolutely does as well, and it does so independently. So we ignore our diastolic hypertension at our own peril,” Dr. Flint said in an interview.

Systolic hypertension began to overshadow diastolic after the Framingham Heart Study and others that suggested it is a more important predictor of adverse cardiovascular outcomes, Dr. Flint and coauthors said in a report on their study.

Those findings caused some to say diastole should be abandoned, and led to a “near-exclusive focus” on systolic hypertension in a 2000 advisory statement from the National High Blood Pressure Education Program, they say in their report.

While current guidelines emphasize the importance of both systolic and diastolic targets, many clinicians today often assign little importance to diastolic blood pressure values, the report adds.

“The pendulum needs to swing back, right down in the middle,” Dr. Flint said in the interview.

The study by Dr. Flint and colleagues comprised a cohort of approximately 1.3 million outpatients from KPNC who had at least one baseline blood pressure reading in during 2007-2008, and two or more follow-up measurements between 2009 and 2016, for a total of about 36.8 million data points.

Systolic hypertension burden was linked to the composite of MI or stroke, with a hazard ratio of 1.18 (95% confidence interval, 1.17-1.18; P less than .001) per unit increase in z score, according to results of a multivariable regression analysis. Likewise, diastolic hypertension burden was linked to those adverse outcomes, with a hazard ratio of 1.06 (95% CI, 1.06-1.07; P less than .001).

Put in terms of estimated risk of MI or stroke, patients with a systolic blood pressure around 160 mm Hg – 3 standard deviations from the mean – was 4.8%, compared to a predicted risk of just 1.9% for a systolic blood pressure near 136 mm Hg, the investigators said in their report.

Similarly, predicted risk was 3.6% for a diastolic pressure of about 96 mm Hg, also 3 standard deviations from the mean, and 1.9% for a diastolic BP near 81 mm Hg.

“The two are not that separate,” Dr. Flint said of the risks associated with systolic and diastolic hypertension at that 3-standard-deviation point. Beyond that, increased systolic blood pressure is associated with more risk relative to increased diastolic blood pressure, the logistic regression modeling shows.

Taken together, findings from this large cohort study emphasize the importance of making lifestyle modifications and adjusting medication to ensure that both systolic and diastolic targets are met, according to Dr. Flint.

“Rises in systolic blood pressure count for more in influencing the risk of heart attack and stroke,” he said, “but diastolic independently counts for quite a lot. It’s a close second.”

Dr. Flint reported no disclosures. Senior author Deepak L. Bhatt, MD, MPH, reported disclosures with Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, Takeda, The Medicines Company, and others. The remaining authors had no disclosures.

SOURCE: Flint AC et al. N Engl J Med. 2019 Jul 18. doi: 10.1056/NEJMoa1803180.

Both systolic and diastolic hypertension independently predict myocardial infarction and strokes, but systolic blood pressure is more strongly linked to adverse outcomes.

That’s according to a study of more than 1 million patients and 36 million outpatient blood pressure measurements published in the New England Journal of Medicine.

Systolic and diastolic hypertension predicted adverse outcomes at cutpoints of 140/90 and 130/80 mm Hg in the large retrospective cohort study, supporting the recent guideline changes that made blood pressure targets more stringent for higher-risk patients, said lead investigator Alexander C. Flint, MD, of Kaiser Permanente Northern California (KPNC) in Oakland.

“While systolic does count for more, in the fact that it is a stronger driver of the risk of heart attack and stroke, diastolic absolutely does as well, and it does so independently. So we ignore our diastolic hypertension at our own peril,” Dr. Flint said in an interview.

Systolic hypertension began to overshadow diastolic after the Framingham Heart Study and others that suggested it is a more important predictor of adverse cardiovascular outcomes, Dr. Flint and coauthors said in a report on their study.

Those findings caused some to say diastole should be abandoned, and led to a “near-exclusive focus” on systolic hypertension in a 2000 advisory statement from the National High Blood Pressure Education Program, they say in their report.

While current guidelines emphasize the importance of both systolic and diastolic targets, many clinicians today often assign little importance to diastolic blood pressure values, the report adds.

“The pendulum needs to swing back, right down in the middle,” Dr. Flint said in the interview.

The study by Dr. Flint and colleagues comprised a cohort of approximately 1.3 million outpatients from KPNC who had at least one baseline blood pressure reading in during 2007-2008, and two or more follow-up measurements between 2009 and 2016, for a total of about 36.8 million data points.

Systolic hypertension burden was linked to the composite of MI or stroke, with a hazard ratio of 1.18 (95% confidence interval, 1.17-1.18; P less than .001) per unit increase in z score, according to results of a multivariable regression analysis. Likewise, diastolic hypertension burden was linked to those adverse outcomes, with a hazard ratio of 1.06 (95% CI, 1.06-1.07; P less than .001).

Put in terms of estimated risk of MI or stroke, patients with a systolic blood pressure around 160 mm Hg – 3 standard deviations from the mean – was 4.8%, compared to a predicted risk of just 1.9% for a systolic blood pressure near 136 mm Hg, the investigators said in their report.

Similarly, predicted risk was 3.6% for a diastolic pressure of about 96 mm Hg, also 3 standard deviations from the mean, and 1.9% for a diastolic BP near 81 mm Hg.

“The two are not that separate,” Dr. Flint said of the risks associated with systolic and diastolic hypertension at that 3-standard-deviation point. Beyond that, increased systolic blood pressure is associated with more risk relative to increased diastolic blood pressure, the logistic regression modeling shows.

Taken together, findings from this large cohort study emphasize the importance of making lifestyle modifications and adjusting medication to ensure that both systolic and diastolic targets are met, according to Dr. Flint.

“Rises in systolic blood pressure count for more in influencing the risk of heart attack and stroke,” he said, “but diastolic independently counts for quite a lot. It’s a close second.”

Dr. Flint reported no disclosures. Senior author Deepak L. Bhatt, MD, MPH, reported disclosures with Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, Takeda, The Medicines Company, and others. The remaining authors had no disclosures.

SOURCE: Flint AC et al. N Engl J Med. 2019 Jul 18. doi: 10.1056/NEJMoa1803180.

Reported drug overdose deaths in the United States declined by 4.2% from December 2017 to December 2018, the Centers for Disease Control and Prevention reported on July 17.

“The latest provisional data on overdose deaths show that America’s united efforts to curb opioid use disorder and addiction are working. Lives are being saved, and we’re beginning to win the fight against this crisis,” Health & Human Services Secretary Alex Azar said in a written statement. “Under President Trump’s leadership, and thanks to efforts on the ground by communities across America, the number of patients receiving medication-assisted treatment has risen, distribution of overdose-reversing drugs is up, and nationwide opioid prescriptions are down.”

The new data show that total drug overdose deaths were down from 70,699 in 2017 to 67,744 in 2018, a drop of 4.2%, the CDC said.

States, of course, fell on both sides of that national figure. Alaska had the largest 1-year drop, –25.5%, followed by South Dakota, Ohio, Iowa, and Pennsylvania. Delaware and Missouri wound up on the other end of the scale with increases of 17.0% from 2017 to 2018. Deaths in Vermont, Arizona, and South Carolina also rose by double digits, data from the National Vital Statistics System show.

“While the declining trend of overdose deaths is an encouraging sign, by no means have we declared victory against the epidemic or addiction in general,” Secretary Azar said. “This crisis developed over 2 decades and it will not be solved overnight. We also face other emerging threats, like concerning trends in cocaine and methamphetamine overdoses.”

[email protected]

Reported drug overdose deaths in the United States declined by 4.2% from December 2017 to December 2018, the Centers for Disease Control and Prevention reported on July 17.

“The latest provisional data on overdose deaths show that America’s united efforts to curb opioid use disorder and addiction are working. Lives are being saved, and we’re beginning to win the fight against this crisis,” Health & Human Services Secretary Alex Azar said in a written statement. “Under President Trump’s leadership, and thanks to efforts on the ground by communities across America, the number of patients receiving medication-assisted treatment has risen, distribution of overdose-reversing drugs is up, and nationwide opioid prescriptions are down.”

The new data show that total drug overdose deaths were down from 70,699 in 2017 to 67,744 in 2018, a drop of 4.2%, the CDC said.

States, of course, fell on both sides of that national figure. Alaska had the largest 1-year drop, –25.5%, followed by South Dakota, Ohio, Iowa, and Pennsylvania. Delaware and Missouri wound up on the other end of the scale with increases of 17.0% from 2017 to 2018. Deaths in Vermont, Arizona, and South Carolina also rose by double digits, data from the National Vital Statistics System show.

“While the declining trend of overdose deaths is an encouraging sign, by no means have we declared victory against the epidemic or addiction in general,” Secretary Azar said. “This crisis developed over 2 decades and it will not be solved overnight. We also face other emerging threats, like concerning trends in cocaine and methamphetamine overdoses.”

[email protected]

Reported drug overdose deaths in the United States declined by 4.2% from December 2017 to December 2018, the Centers for Disease Control and Prevention reported on July 17.

“The latest provisional data on overdose deaths show that America’s united efforts to curb opioid use disorder and addiction are working. Lives are being saved, and we’re beginning to win the fight against this crisis,” Health & Human Services Secretary Alex Azar said in a written statement. “Under President Trump’s leadership, and thanks to efforts on the ground by communities across America, the number of patients receiving medication-assisted treatment has risen, distribution of overdose-reversing drugs is up, and nationwide opioid prescriptions are down.”

The new data show that total drug overdose deaths were down from 70,699 in 2017 to 67,744 in 2018, a drop of 4.2%, the CDC said.

States, of course, fell on both sides of that national figure. Alaska had the largest 1-year drop, –25.5%, followed by South Dakota, Ohio, Iowa, and Pennsylvania. Delaware and Missouri wound up on the other end of the scale with increases of 17.0% from 2017 to 2018. Deaths in Vermont, Arizona, and South Carolina also rose by double digits, data from the National Vital Statistics System show.

“While the declining trend of overdose deaths is an encouraging sign, by no means have we declared victory against the epidemic or addiction in general,” Secretary Azar said. “This crisis developed over 2 decades and it will not be solved overnight. We also face other emerging threats, like concerning trends in cocaine and methamphetamine overdoses.”

[email protected]

Spider smoothie, anyone?

Eating spiders, grasshoppers, and cicadas – does that idea BUG you? Plenty of people around the world chomp down on insects as part of a balanced diet. But here in the United States, there’s definitely still an “ick” factor – as in, “ick, that thing has far too many legs to put in my mouth.”

jacoblund/Getty Images

These creepy crawlers, however, could be the key to a healthier lifestyle. Scientists have been recently looking at insects as a source of protein and antioxidants, among other health buzzwords.

Researchers from the University of Teremo in Italy took a look at commercially available insects (ever heard that phrase before?) and found that certain bugs, such as crickets, silkworms, caterpillars, and cicadas, displayed two or three times as much antioxidant activity as orange juice and olive oil. Perhaps you’d like a nice glass of cicada juice to go with your morning cereal?

Barclays also recently predicted that the insect protein market could be worth as much as $8 billion in the next decade, because of several factors. The earth’s population is rising, and people need new sources of food. We know bugs are plentiful – just go outside in the summer and stand with your mouth open, and you’ve got a three-course meal in 5 minutes.

We can also thank the teens: Barclays stated that Gen Z is the “most health-aware and environmentally conscious” generation yet, and therefore are all aboard the bug-eating train.

So, are you ready to start making eggs with a side of fried crickets? Perhaps a nice plant-based burger topped with cicada crumbles? Just make sure to stay away from the zombie ones.
 

Mom, put the joint down!

Way to harsh my mellow. You might think that smoking a little Mary Jane would chill parents out a bit. Turns out, that’s not the case.

manonallard/Getty Images

A study from Ohio State University examined California parents, their substance use, and their disciplinarian styles. This is one of the first studies to look at how substance use relates to parenting, and the news is not good for the kids.

If you’re thinking about getting your parents into pot, think again. Parents who used marijuana in the past year tended to discipline their children more than parents who hadn’t used. Researchers also found similar trends with parents who used alcohol in the past.

Kids, if you’ve got a no-smoking, no-drinking square of a parent, be happy. It might save you a few groundings.
 

The true power of the dark side

When people go the grocery store, the produce department is – for many people – a big waste of space. It’s something to be skipped over. Who wants to buy fruits or vegetables anyway? Sure, they’re healthy, but they’re totally gross.

CostinT/iStock/Getty Images Plus

Turns out, there may be a way to get even your stubborn Uncle Joe, who probably thinks the food pyramid is a communist plot, to buy veggies. The key is a little black dress.

Okay, we’re not literally talking about sticking pineapples or broccoli in actual black dresses. But according to a study published in Food Quality and Preference, placing various types of produce against a black background made them more attractive to consumers over white or shades of gray. Even the lowly carrot, rated least attractive by the study participants when placed in front of every other color, got a big boost when placed on a black background. Something about black just brought out its natural shine.

So, next time you go through the produce department and it looks like it’s been designed by a teenager going through a particularly rough Goth phase, now you’ll know why.
 

The Lyme disease truth is out there

The setting is Rocky Mountain Laboratories in Hamilton, Mont. A man and a woman, both wearing dark suits, are standing in a large, poorly lit room full of file cabinets. Each is holding a flashlight.

Sculder: Explain to me again, Mully, why we couldn’t just ask to see these files?

National Institute of Allergy and Infectious Diseases

Mully: C’mon, Sculder. My very secret and very reliable source said that Dr. Willy Burgdorfer, the scientist who discovered Lyme disease and worked in this lab, was actually a bioweapons specialist. My source said that Burgdorfer and “other bioweapons specialists stuffed ticks with pathogens to cause severe disability, disease – even death – to potential enemies.” If we had asked to see the records, they would have been destroyed by operatives of the shadow government.

Sculder: Where did you find this secret and reliable source, Mully?

Mully: I read his press release.

Sculder: Did the press release say anything about releases of diseased ticks, either accidental or by design?

Mully: Not until I ran it past a Navajo code talker.

Sculder stares at him blankly for several seconds.

Mully: Okay, okay. There’s this congressman, Rep. Chris Smith from New Jersey. The House of Representatives just approved his amendment to the 2020 National Defense Authorization Act. The amendment “directs the Inspector General of the Department of Defense to investigate the possible involvement of DOD biowarfare labs in the weaponization of Lyme disease in ticks and other insects from 1950 to 1975.” Honestly, it does.

Sculder turns around and quickly walks away. Mully follows her.

Mully: It could’ve happened! What if it’s another in the long line of government conspiracies that were too crazy to be true? Like Roswell. Or birtherism. Or New Coke. I suppose you’re going to tell me that Elvis and J. Edgar Hoover didn’t help NASA fake the moon landings?

Spider smoothie, anyone?

Eating spiders, grasshoppers, and cicadas – does that idea BUG you? Plenty of people around the world chomp down on insects as part of a balanced diet. But here in the United States, there’s definitely still an “ick” factor – as in, “ick, that thing has far too many legs to put in my mouth.”

jacoblund/Getty Images

These creepy crawlers, however, could be the key to a healthier lifestyle. Scientists have been recently looking at insects as a source of protein and antioxidants, among other health buzzwords.

Researchers from the University of Teremo in Italy took a look at commercially available insects (ever heard that phrase before?) and found that certain bugs, such as crickets, silkworms, caterpillars, and cicadas, displayed two or three times as much antioxidant activity as orange juice and olive oil. Perhaps you’d like a nice glass of cicada juice to go with your morning cereal?

Barclays also recently predicted that the insect protein market could be worth as much as $8 billion in the next decade, because of several factors. The earth’s population is rising, and people need new sources of food. We know bugs are plentiful – just go outside in the summer and stand with your mouth open, and you’ve got a three-course meal in 5 minutes.

We can also thank the teens: Barclays stated that Gen Z is the “most health-aware and environmentally conscious” generation yet, and therefore are all aboard the bug-eating train.

So, are you ready to start making eggs with a side of fried crickets? Perhaps a nice plant-based burger topped with cicada crumbles? Just make sure to stay away from the zombie ones.
 

Mom, put the joint down!

Way to harsh my mellow. You might think that smoking a little Mary Jane would chill parents out a bit. Turns out, that’s not the case.

manonallard/Getty Images

A study from Ohio State University examined California parents, their substance use, and their disciplinarian styles. This is one of the first studies to look at how substance use relates to parenting, and the news is not good for the kids.

If you’re thinking about getting your parents into pot, think again. Parents who used marijuana in the past year tended to discipline their children more than parents who hadn’t used. Researchers also found similar trends with parents who used alcohol in the past.

Kids, if you’ve got a no-smoking, no-drinking square of a parent, be happy. It might save you a few groundings.
 

The true power of the dark side

When people go the grocery store, the produce department is – for many people – a big waste of space. It’s something to be skipped over. Who wants to buy fruits or vegetables anyway? Sure, they’re healthy, but they’re totally gross.

CostinT/iStock/Getty Images Plus

Turns out, there may be a way to get even your stubborn Uncle Joe, who probably thinks the food pyramid is a communist plot, to buy veggies. The key is a little black dress.

Okay, we’re not literally talking about sticking pineapples or broccoli in actual black dresses. But according to a study published in Food Quality and Preference, placing various types of produce against a black background made them more attractive to consumers over white or shades of gray. Even the lowly carrot, rated least attractive by the study participants when placed in front of every other color, got a big boost when placed on a black background. Something about black just brought out its natural shine.

So, next time you go through the produce department and it looks like it’s been designed by a teenager going through a particularly rough Goth phase, now you’ll know why.
 

The Lyme disease truth is out there

The setting is Rocky Mountain Laboratories in Hamilton, Mont. A man and a woman, both wearing dark suits, are standing in a large, poorly lit room full of file cabinets. Each is holding a flashlight.

Sculder: Explain to me again, Mully, why we couldn’t just ask to see these files?

National Institute of Allergy and Infectious Diseases

Mully: C’mon, Sculder. My very secret and very reliable source said that Dr. Willy Burgdorfer, the scientist who discovered Lyme disease and worked in this lab, was actually a bioweapons specialist. My source said that Burgdorfer and “other bioweapons specialists stuffed ticks with pathogens to cause severe disability, disease – even death – to potential enemies.” If we had asked to see the records, they would have been destroyed by operatives of the shadow government.

Sculder: Where did you find this secret and reliable source, Mully?

Mully: I read his press release.

Sculder: Did the press release say anything about releases of diseased ticks, either accidental or by design?

Mully: Not until I ran it past a Navajo code talker.

Sculder stares at him blankly for several seconds.

Mully: Okay, okay. There’s this congressman, Rep. Chris Smith from New Jersey. The House of Representatives just approved his amendment to the 2020 National Defense Authorization Act. The amendment “directs the Inspector General of the Department of Defense to investigate the possible involvement of DOD biowarfare labs in the weaponization of Lyme disease in ticks and other insects from 1950 to 1975.” Honestly, it does.

Sculder turns around and quickly walks away. Mully follows her.

Mully: It could’ve happened! What if it’s another in the long line of government conspiracies that were too crazy to be true? Like Roswell. Or birtherism. Or New Coke. I suppose you’re going to tell me that Elvis and J. Edgar Hoover didn’t help NASA fake the moon landings?

Spider smoothie, anyone?

Eating spiders, grasshoppers, and cicadas – does that idea BUG you? Plenty of people around the world chomp down on insects as part of a balanced diet. But here in the United States, there’s definitely still an “ick” factor – as in, “ick, that thing has far too many legs to put in my mouth.”

jacoblund/Getty Images

These creepy crawlers, however, could be the key to a healthier lifestyle. Scientists have been recently looking at insects as a source of protein and antioxidants, among other health buzzwords.

Researchers from the University of Teremo in Italy took a look at commercially available insects (ever heard that phrase before?) and found that certain bugs, such as crickets, silkworms, caterpillars, and cicadas, displayed two or three times as much antioxidant activity as orange juice and olive oil. Perhaps you’d like a nice glass of cicada juice to go with your morning cereal?

Barclays also recently predicted that the insect protein market could be worth as much as $8 billion in the next decade, because of several factors. The earth’s population is rising, and people need new sources of food. We know bugs are plentiful – just go outside in the summer and stand with your mouth open, and you’ve got a three-course meal in 5 minutes.

We can also thank the teens: Barclays stated that Gen Z is the “most health-aware and environmentally conscious” generation yet, and therefore are all aboard the bug-eating train.

So, are you ready to start making eggs with a side of fried crickets? Perhaps a nice plant-based burger topped with cicada crumbles? Just make sure to stay away from the zombie ones.
 

Mom, put the joint down!

Way to harsh my mellow. You might think that smoking a little Mary Jane would chill parents out a bit. Turns out, that’s not the case.

manonallard/Getty Images

A study from Ohio State University examined California parents, their substance use, and their disciplinarian styles. This is one of the first studies to look at how substance use relates to parenting, and the news is not good for the kids.

If you’re thinking about getting your parents into pot, think again. Parents who used marijuana in the past year tended to discipline their children more than parents who hadn’t used. Researchers also found similar trends with parents who used alcohol in the past.

Kids, if you’ve got a no-smoking, no-drinking square of a parent, be happy. It might save you a few groundings.
 

The true power of the dark side

When people go the grocery store, the produce department is – for many people – a big waste of space. It’s something to be skipped over. Who wants to buy fruits or vegetables anyway? Sure, they’re healthy, but they’re totally gross.

CostinT/iStock/Getty Images Plus

Turns out, there may be a way to get even your stubborn Uncle Joe, who probably thinks the food pyramid is a communist plot, to buy veggies. The key is a little black dress.

Okay, we’re not literally talking about sticking pineapples or broccoli in actual black dresses. But according to a study published in Food Quality and Preference, placing various types of produce against a black background made them more attractive to consumers over white or shades of gray. Even the lowly carrot, rated least attractive by the study participants when placed in front of every other color, got a big boost when placed on a black background. Something about black just brought out its natural shine.

So, next time you go through the produce department and it looks like it’s been designed by a teenager going through a particularly rough Goth phase, now you’ll know why.
 

The Lyme disease truth is out there

The setting is Rocky Mountain Laboratories in Hamilton, Mont. A man and a woman, both wearing dark suits, are standing in a large, poorly lit room full of file cabinets. Each is holding a flashlight.

Sculder: Explain to me again, Mully, why we couldn’t just ask to see these files?

National Institute of Allergy and Infectious Diseases

Mully: C’mon, Sculder. My very secret and very reliable source said that Dr. Willy Burgdorfer, the scientist who discovered Lyme disease and worked in this lab, was actually a bioweapons specialist. My source said that Burgdorfer and “other bioweapons specialists stuffed ticks with pathogens to cause severe disability, disease – even death – to potential enemies.” If we had asked to see the records, they would have been destroyed by operatives of the shadow government.

Sculder: Where did you find this secret and reliable source, Mully?

Mully: I read his press release.

Sculder: Did the press release say anything about releases of diseased ticks, either accidental or by design?

Mully: Not until I ran it past a Navajo code talker.

Sculder stares at him blankly for several seconds.

Mully: Okay, okay. There’s this congressman, Rep. Chris Smith from New Jersey. The House of Representatives just approved his amendment to the 2020 National Defense Authorization Act. The amendment “directs the Inspector General of the Department of Defense to investigate the possible involvement of DOD biowarfare labs in the weaponization of Lyme disease in ticks and other insects from 1950 to 1975.” Honestly, it does.

Sculder turns around and quickly walks away. Mully follows her.

Mully: It could’ve happened! What if it’s another in the long line of government conspiracies that were too crazy to be true? Like Roswell. Or birtherism. Or New Coke. I suppose you’re going to tell me that Elvis and J. Edgar Hoover didn’t help NASA fake the moon landings?

By measuring parents’ attitudes regarding disease salience and community benefit, high scores on a four-item scale was associated with fivefold greater likelihood of not fully vaccinating their children, according to a study published in the Pediatric Infectious Disease Journal.

Steve Mann/Thinkstock

Mohammad Tahir Yousafzai, MPH, of Aga Khan University, Karachi, Pakistan, and colleagues developed a larger 14-item scale to measure parental attitudes and surveyed 901 households in the Sindh province of Pakistan during 2014. Part of this scale was a short 4-item subscale focusing on disease salience and community benefit, whereas the remaining 10 items form another subscale that measures parents’ perceptions and concerns regarding vaccines directly. The items are presented as 1-5 Likert scales, and scoring higher represents holding more negative attitudes regarding vaccines.

Of the 901 households surveyed, 25% of children were fully vaccinated, which meant children received all primary vaccines up to 14 weeks of age, and 54% were partially vaccinated, which meant at least one of those primary vaccines had been missed. The remaining 21% were unvaccinated.

High scores on the full 14-item scale showed some correlation with no vaccination versus partial or full vaccination (odds ratio, 3.05; 95% confidence interval, 1.75-5.31); the association disappeared after adjustment for children’s age and gender. The subscales performed better after adjustment: The adjusted ORs were 1.52 (95% CI, 1.05-2.21) for the longer subscale and 5.21 (95% CI, 3.60-7.55) for the shorter subscale. The data also showed high association between high scores on the shorter subscale and the likelihood of no or only partial vaccination (aOR, 9.65; 95% CI, 4.81-19.37).

The researchers noted that most similar scales used in developed countries are longer (10 or more items) and have lower internal consistency. This four-item scale, on the other hand, may be especially useful among lower-income populations and those in developing areas that have lower literacy rates.

One of the limitations of the study was that it was conducted only in Pakistan and not multiple developing countries; the researchers acknowledged this could limit generalizability. Another limitation is that the study size was too small for subdomain analysis; the researchers wrote that, although a lack of such analysis is unfortunate, it shouldn’t hamper the shorter subscale’s usability. A further limitation is that there was little variability across Likert scores – mostly answers at the extreme ends rather than a mix. This suggests that interviewees may not have understood how Likert scales work and therefore may not have answered accurately, noted the researchers, who employed a visual chart, trained interviewers, and field monitoring to mitigate this possibility.

“Measurement of the parental attitudes toward childhood vaccination is very important for the appropriate planning of strategies for increasing vaccine coverage and for monitoring,” they wrote.

The study was sponsored by Gavi, The Vaccine Alliance. The authors had no funding or conflicts of interest to disclose.

[email protected]

SOURCE: Yousafzai MT et al. Pediatr Infect Dis J. 2019 Jul;38(7):e143-8.

By measuring parents’ attitudes regarding disease salience and community benefit, high scores on a four-item scale was associated with fivefold greater likelihood of not fully vaccinating their children, according to a study published in the Pediatric Infectious Disease Journal.

Steve Mann/Thinkstock

Mohammad Tahir Yousafzai, MPH, of Aga Khan University, Karachi, Pakistan, and colleagues developed a larger 14-item scale to measure parental attitudes and surveyed 901 households in the Sindh province of Pakistan during 2014. Part of this scale was a short 4-item subscale focusing on disease salience and community benefit, whereas the remaining 10 items form another subscale that measures parents’ perceptions and concerns regarding vaccines directly. The items are presented as 1-5 Likert scales, and scoring higher represents holding more negative attitudes regarding vaccines.

Of the 901 households surveyed, 25% of children were fully vaccinated, which meant children received all primary vaccines up to 14 weeks of age, and 54% were partially vaccinated, which meant at least one of those primary vaccines had been missed. The remaining 21% were unvaccinated.

High scores on the full 14-item scale showed some correlation with no vaccination versus partial or full vaccination (odds ratio, 3.05; 95% confidence interval, 1.75-5.31); the association disappeared after adjustment for children’s age and gender. The subscales performed better after adjustment: The adjusted ORs were 1.52 (95% CI, 1.05-2.21) for the longer subscale and 5.21 (95% CI, 3.60-7.55) for the shorter subscale. The data also showed high association between high scores on the shorter subscale and the likelihood of no or only partial vaccination (aOR, 9.65; 95% CI, 4.81-19.37).

The researchers noted that most similar scales used in developed countries are longer (10 or more items) and have lower internal consistency. This four-item scale, on the other hand, may be especially useful among lower-income populations and those in developing areas that have lower literacy rates.

One of the limitations of the study was that it was conducted only in Pakistan and not multiple developing countries; the researchers acknowledged this could limit generalizability. Another limitation is that the study size was too small for subdomain analysis; the researchers wrote that, although a lack of such analysis is unfortunate, it shouldn’t hamper the shorter subscale’s usability. A further limitation is that there was little variability across Likert scores – mostly answers at the extreme ends rather than a mix. This suggests that interviewees may not have understood how Likert scales work and therefore may not have answered accurately, noted the researchers, who employed a visual chart, trained interviewers, and field monitoring to mitigate this possibility.

“Measurement of the parental attitudes toward childhood vaccination is very important for the appropriate planning of strategies for increasing vaccine coverage and for monitoring,” they wrote.

The study was sponsored by Gavi, The Vaccine Alliance. The authors had no funding or conflicts of interest to disclose.

[email protected]

SOURCE: Yousafzai MT et al. Pediatr Infect Dis J. 2019 Jul;38(7):e143-8.

By measuring parents’ attitudes regarding disease salience and community benefit, high scores on a four-item scale was associated with fivefold greater likelihood of not fully vaccinating their children, according to a study published in the Pediatric Infectious Disease Journal.

Steve Mann/Thinkstock

Mohammad Tahir Yousafzai, MPH, of Aga Khan University, Karachi, Pakistan, and colleagues developed a larger 14-item scale to measure parental attitudes and surveyed 901 households in the Sindh province of Pakistan during 2014. Part of this scale was a short 4-item subscale focusing on disease salience and community benefit, whereas the remaining 10 items form another subscale that measures parents’ perceptions and concerns regarding vaccines directly. The items are presented as 1-5 Likert scales, and scoring higher represents holding more negative attitudes regarding vaccines.

Of the 901 households surveyed, 25% of children were fully vaccinated, which meant children received all primary vaccines up to 14 weeks of age, and 54% were partially vaccinated, which meant at least one of those primary vaccines had been missed. The remaining 21% were unvaccinated.

High scores on the full 14-item scale showed some correlation with no vaccination versus partial or full vaccination (odds ratio, 3.05; 95% confidence interval, 1.75-5.31); the association disappeared after adjustment for children’s age and gender. The subscales performed better after adjustment: The adjusted ORs were 1.52 (95% CI, 1.05-2.21) for the longer subscale and 5.21 (95% CI, 3.60-7.55) for the shorter subscale. The data also showed high association between high scores on the shorter subscale and the likelihood of no or only partial vaccination (aOR, 9.65; 95% CI, 4.81-19.37).

The researchers noted that most similar scales used in developed countries are longer (10 or more items) and have lower internal consistency. This four-item scale, on the other hand, may be especially useful among lower-income populations and those in developing areas that have lower literacy rates.

One of the limitations of the study was that it was conducted only in Pakistan and not multiple developing countries; the researchers acknowledged this could limit generalizability. Another limitation is that the study size was too small for subdomain analysis; the researchers wrote that, although a lack of such analysis is unfortunate, it shouldn’t hamper the shorter subscale’s usability. A further limitation is that there was little variability across Likert scores – mostly answers at the extreme ends rather than a mix. This suggests that interviewees may not have understood how Likert scales work and therefore may not have answered accurately, noted the researchers, who employed a visual chart, trained interviewers, and field monitoring to mitigate this possibility.

“Measurement of the parental attitudes toward childhood vaccination is very important for the appropriate planning of strategies for increasing vaccine coverage and for monitoring,” they wrote.

The study was sponsored by Gavi, The Vaccine Alliance. The authors had no funding or conflicts of interest to disclose.

[email protected]

SOURCE: Yousafzai MT et al. Pediatr Infect Dis J. 2019 Jul;38(7):e143-8.

Although guideline recommended, treating children in shock with a bolus of saline or albumin fluid imposes counterproductive effects on respiratory and neurologic function, ultimately increasing risk of death, according to a detailed analysis of available data, including a randomized trial.

Several sets of guidelines for resuscitation of patients in shock have advocated volume expansion with bolus intravenous fluid, but that recommendation was based on expected physiologic benefits not a randomized trial. The only randomized trial associated this approach showed increased mortality, and a new analysis of these and other data appears to explain why.

According to the findings of a study lead by Michael Levin, MD, of the department of medicine at Imperial College London and colleagues, “volume resuscitation is associated with deterioration of respiratory function and neurological function in some patients.” Their study was published in Lancet Respiratory Medicine. The authors stated that saline-induced hyperchloremic acidosis appears to have been “a major contributor” to the observed increase in adverse outcomes.

The key take home message is that “normal saline and other unbuffered crystalloid solutions should be avoided in resuscitating seriously ill patients,” according to the authors, who believe the findings might be relevant to adults as well as children.

The controversy about the role of volume expansion for management of shock was ignited by a 2011 trial called FEAST (N Engl J Med. 2011;364:2483-95). That trial, which randomized African children with severe febrile illness to a bolus of 20-40 mg of 5% albumin solution, a bolus of 0.9% saline solution, or no bolus, was halted early when 48-hour mortality data showed a lower death rate in the no bolus group (7.3%) than either the albumin (10.6%) or saline (10.5%) bolus groups.

The FEAST result was unexpected and so contrary to accepted thinking that it prompted widespread debate, including whether findings in the resource-poor area of the world where the FEAST trial was conducted could be extrapolated to centers elsewhere in the world. Arguing for benefit, fluid resuscitation is known to increase pulse pressure and urinary output. Arguing against benefit, pulmonary edema is a known complication of bolus fluid replacement.

In an attempt to address and potentially resolve this controversy, data collected in the FEAST trial along with four other sets of data involving volume expansion in critically ill children were evaluated with a focus on changes in cardiovascular, neurological, and respiratory function. Analysis of blood biochemistry and blood oxygen transport were also conducted.

The cardiovascular, respiratory, and neurologic functions were scored on the basis of objective measurements, such as heart rate, respiratory rate, and blood pressure. These measures were evaluated prior to fluid administration and at 1 hour, 4 hours, 8 hours, 24 hours, and 48 hours after fluid administration. Odds ratio (OR) of an adverse outcome were evaluated in the context of each 10-unit change in these scores.

Relative to baseline, there was worsening respiratory and neurological function after fluid administration. Although cardiovascular function improved, hemoglobin concentrations were lower in those who received fluid than in those who did not. Fluid resuscitation was also associated with lower bicarbonate and increased base deficit and chloride at 24 hours.

Regression modeling with physiological variables suggests “that the increased mortality in FEAST can be explained by bolus-induced worsening in respiratory and neurological function, hemodilution, and hyperchloremic acidosis,” according to the authors.

Analyses of the four other sets of data, which included children treated for meningococcal sepsis in the United Kingdom, acutely ill with malaria treated in Malawi, and cohorts of children in South Africa and a London hospital for acute illnesses, provided supportive data.

Although this analysis does not address the value of administering buffered solutions in low volumes, the authors concluded that the data from the FEAST trial are generalizable. They challenge the routine use of bolus infusions of saline or albumin in the initial management of shock, which has been guideline recommended. The risks of fluid resuscitation might be particularly high among children who already have compromised respiratory or neurologic function.

SOURCE: Levin M et al. Lancet Respir Med. 2019;7:581-93.

Although guideline recommended, treating children in shock with a bolus of saline or albumin fluid imposes counterproductive effects on respiratory and neurologic function, ultimately increasing risk of death, according to a detailed analysis of available data, including a randomized trial.

Several sets of guidelines for resuscitation of patients in shock have advocated volume expansion with bolus intravenous fluid, but that recommendation was based on expected physiologic benefits not a randomized trial. The only randomized trial associated this approach showed increased mortality, and a new analysis of these and other data appears to explain why.

According to the findings of a study lead by Michael Levin, MD, of the department of medicine at Imperial College London and colleagues, “volume resuscitation is associated with deterioration of respiratory function and neurological function in some patients.” Their study was published in Lancet Respiratory Medicine. The authors stated that saline-induced hyperchloremic acidosis appears to have been “a major contributor” to the observed increase in adverse outcomes.

The key take home message is that “normal saline and other unbuffered crystalloid solutions should be avoided in resuscitating seriously ill patients,” according to the authors, who believe the findings might be relevant to adults as well as children.

The controversy about the role of volume expansion for management of shock was ignited by a 2011 trial called FEAST (N Engl J Med. 2011;364:2483-95). That trial, which randomized African children with severe febrile illness to a bolus of 20-40 mg of 5% albumin solution, a bolus of 0.9% saline solution, or no bolus, was halted early when 48-hour mortality data showed a lower death rate in the no bolus group (7.3%) than either the albumin (10.6%) or saline (10.5%) bolus groups.

The FEAST result was unexpected and so contrary to accepted thinking that it prompted widespread debate, including whether findings in the resource-poor area of the world where the FEAST trial was conducted could be extrapolated to centers elsewhere in the world. Arguing for benefit, fluid resuscitation is known to increase pulse pressure and urinary output. Arguing against benefit, pulmonary edema is a known complication of bolus fluid replacement.

In an attempt to address and potentially resolve this controversy, data collected in the FEAST trial along with four other sets of data involving volume expansion in critically ill children were evaluated with a focus on changes in cardiovascular, neurological, and respiratory function. Analysis of blood biochemistry and blood oxygen transport were also conducted.

The cardiovascular, respiratory, and neurologic functions were scored on the basis of objective measurements, such as heart rate, respiratory rate, and blood pressure. These measures were evaluated prior to fluid administration and at 1 hour, 4 hours, 8 hours, 24 hours, and 48 hours after fluid administration. Odds ratio (OR) of an adverse outcome were evaluated in the context of each 10-unit change in these scores.

Relative to baseline, there was worsening respiratory and neurological function after fluid administration. Although cardiovascular function improved, hemoglobin concentrations were lower in those who received fluid than in those who did not. Fluid resuscitation was also associated with lower bicarbonate and increased base deficit and chloride at 24 hours.

Regression modeling with physiological variables suggests “that the increased mortality in FEAST can be explained by bolus-induced worsening in respiratory and neurological function, hemodilution, and hyperchloremic acidosis,” according to the authors.

Analyses of the four other sets of data, which included children treated for meningococcal sepsis in the United Kingdom, acutely ill with malaria treated in Malawi, and cohorts of children in South Africa and a London hospital for acute illnesses, provided supportive data.

Although this analysis does not address the value of administering buffered solutions in low volumes, the authors concluded that the data from the FEAST trial are generalizable. They challenge the routine use of bolus infusions of saline or albumin in the initial management of shock, which has been guideline recommended. The risks of fluid resuscitation might be particularly high among children who already have compromised respiratory or neurologic function.

SOURCE: Levin M et al. Lancet Respir Med. 2019;7:581-93.

Although guideline recommended, treating children in shock with a bolus of saline or albumin fluid imposes counterproductive effects on respiratory and neurologic function, ultimately increasing risk of death, according to a detailed analysis of available data, including a randomized trial.

Several sets of guidelines for resuscitation of patients in shock have advocated volume expansion with bolus intravenous fluid, but that recommendation was based on expected physiologic benefits not a randomized trial. The only randomized trial associated this approach showed increased mortality, and a new analysis of these and other data appears to explain why.

According to the findings of a study lead by Michael Levin, MD, of the department of medicine at Imperial College London and colleagues, “volume resuscitation is associated with deterioration of respiratory function and neurological function in some patients.” Their study was published in Lancet Respiratory Medicine. The authors stated that saline-induced hyperchloremic acidosis appears to have been “a major contributor” to the observed increase in adverse outcomes.

The key take home message is that “normal saline and other unbuffered crystalloid solutions should be avoided in resuscitating seriously ill patients,” according to the authors, who believe the findings might be relevant to adults as well as children.

The controversy about the role of volume expansion for management of shock was ignited by a 2011 trial called FEAST (N Engl J Med. 2011;364:2483-95). That trial, which randomized African children with severe febrile illness to a bolus of 20-40 mg of 5% albumin solution, a bolus of 0.9% saline solution, or no bolus, was halted early when 48-hour mortality data showed a lower death rate in the no bolus group (7.3%) than either the albumin (10.6%) or saline (10.5%) bolus groups.

The FEAST result was unexpected and so contrary to accepted thinking that it prompted widespread debate, including whether findings in the resource-poor area of the world where the FEAST trial was conducted could be extrapolated to centers elsewhere in the world. Arguing for benefit, fluid resuscitation is known to increase pulse pressure and urinary output. Arguing against benefit, pulmonary edema is a known complication of bolus fluid replacement.

In an attempt to address and potentially resolve this controversy, data collected in the FEAST trial along with four other sets of data involving volume expansion in critically ill children were evaluated with a focus on changes in cardiovascular, neurological, and respiratory function. Analysis of blood biochemistry and blood oxygen transport were also conducted.

The cardiovascular, respiratory, and neurologic functions were scored on the basis of objective measurements, such as heart rate, respiratory rate, and blood pressure. These measures were evaluated prior to fluid administration and at 1 hour, 4 hours, 8 hours, 24 hours, and 48 hours after fluid administration. Odds ratio (OR) of an adverse outcome were evaluated in the context of each 10-unit change in these scores.

Relative to baseline, there was worsening respiratory and neurological function after fluid administration. Although cardiovascular function improved, hemoglobin concentrations were lower in those who received fluid than in those who did not. Fluid resuscitation was also associated with lower bicarbonate and increased base deficit and chloride at 24 hours.

Regression modeling with physiological variables suggests “that the increased mortality in FEAST can be explained by bolus-induced worsening in respiratory and neurological function, hemodilution, and hyperchloremic acidosis,” according to the authors.

Analyses of the four other sets of data, which included children treated for meningococcal sepsis in the United Kingdom, acutely ill with malaria treated in Malawi, and cohorts of children in South Africa and a London hospital for acute illnesses, provided supportive data.

Although this analysis does not address the value of administering buffered solutions in low volumes, the authors concluded that the data from the FEAST trial are generalizable. They challenge the routine use of bolus infusions of saline or albumin in the initial management of shock, which has been guideline recommended. The risks of fluid resuscitation might be particularly high among children who already have compromised respiratory or neurologic function.

SOURCE: Levin M et al. Lancet Respir Med. 2019;7:581-93.

BANGKOK – Several EEG abnormalities that are readily measured noninvasively using scalp electrodes show considerable promise as epileptogenicity biomarkers of particular interest for speedier diagnosis of West syndrome, Hiroki Nariai, MD, reported at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Among the most promising of these potential EEG biomarkers for development of epilepsy are ictal or interictal high-frequency oscillations (HFOs) at 80 Hz or more, along with cross-frequency coupling of HFOs and delta wave activity, according to Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.

West syndrome, the most common epileptic encephalopathy during the first 2 years of life, has diverse etiologies. For example, in 250 infants with West syndrome enrolled in the United Kingdom National Infantile Spasms Consortium, a cause was identified in 64%. The etiology was genetic in 14% of subjects, a structural-congenital anomaly in 11%, tuberous sclerosis – a genetic-structural abnormality – in 10%, stroke in 22%, a metabolic defect in 5%, and infection in 2% (Epilepsia. 2015 Apr;56[4]:617-25).

West syndrome is rare, with an estimated prevalence of roughly 1 per 6,000 live births, but the associated mortality is high: 31% on average. And West syndrome often brings severe neurodevelopmental morbidity, with normal or near-normal intelligence present in only 25% of survivors.

An intensive search is on for an objective, reliable diagnostic biomarker – be it electroencephalographic, biochemical, or perhaps a neuroimaging finding – because the clinical diagnosis of West syndrome is highly subjective. It relies upon the triad of epileptic spasms, developmental regression or psychomotor delay, and hypsarrhythmia, which is a chaotic, disorganized, patternless form of brain electrical activity. And while that description makes hypsarrhythmia sound as if it should be easily recognizable, in fact that’s often not the case: Interrater reliability was poor in a study of six pediatric EEG experts at four centers who viewed 5-minute-long EEG samples obtained from 22 patients with infantile spasms (Epilepsia. 2015 Jan;56[1]:77-81), Dr. Nariai noted at the congress, sponsored by the International League Against Epilepsy.

“The clinical trial is maybe not so useful,” he observed.

The hunt for a reliable biomarker is further fueled by evidence that early diagnosis and treatment of West syndrome and other etiologies of infantile spasms makes a real difference. Indeed, investigators found in the United Kingdom Infantile Spasms Study that increasing lag time from onset of spasms to initiation of treatment was associated in stepwise fashion with significantly lower IQ at 4 years of age. While infants who started treatment within 7 days of onset of the seizure disorder had a mean IQ of 76.2 at age 4 years, those with an 8- to 14-day lag time between symptom onset and treatment averaged an additional 3.9-point decrement in IQ. A 15- to 30-day delay was associated with a 7.8-point reduction in IQ, compared with the reference group, while the decrease in IQ averaged 11.7 points in infants with a 1- to 2-month lag time and 15.6 points in those with a lag time of more than 2 months (Epilepsia. 2011 Jul;52[7]:1359-64).

At the start of the decade, Dr. Nariai and other investigators demonstrated that pathologic HFOs recorded during invasive EEG monitoring in conjunction with epilepsy surgery served as a reliable biomarker of epilepsy. While this was an important observation, a biomarker obtained through invasive monitoring during brain surgery clearly has very limited clinical applicability. But more recently, Dr. Nariai and his coinvestigators in the Tuberous Sclerosis Complex Autism Center of Excellence Network reported that noninvasive detection of interictal HFO fast ripples in the 250-500 Hz range via scalp EEG showed promise as a biomarker of epilepsy. Sensitivity of this far more practical approach to the detection of fast ripples was excellent, whether analyzed visually or by automatic detector (Clin Neurophysiol. 2018 Jul;129[7]:1458-66).

Moreover, in a recent, not-yet published study that Dr. Nariai and coworkers conducted in 24 infants with active epileptic spasms and 6 controls, noninvasive objective measurement of HFO rate using scalp EEG had an 83% sensitivity and 100% specificity for active epileptic spasms, while the modulation index of HFO and delta coupling in the 3-4 Hz range showed 74% sensitivity and 86% specificity.


If future studies validate the utility of detection of HFOs above a defined threshold or another noninvasively obtained EEG biomarker for diagnosis of epilepsy, the same strategy would presumably also be applicable for monitoring response to antiepileptic therapies, thereby eliminating the traditional trial-and-error approach to treatment. This would be a particularly important application in patients with West syndrome, where it’s believed that the electrical activity itself is contributing to the progressive – and often rapid – loss of cognitive function and behavioral disturbances. Thus, unlike in most other forms of epilepsy, the treatment goal isn’t merely to suppress the seizures, but also to achieve disease modification by eliminating the underlying subclinical EEG abnormalities, he explained.

A reliable biomarker would also be a boon in selecting the best participants for clinical trials of new antiseizure therapies.

Dr. Nariai reported having no financial conflicts regarding his presentation. His work is funded by research foundations and the National Institutes of Health.

[email protected]

BANGKOK – Several EEG abnormalities that are readily measured noninvasively using scalp electrodes show considerable promise as epileptogenicity biomarkers of particular interest for speedier diagnosis of West syndrome, Hiroki Nariai, MD, reported at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Among the most promising of these potential EEG biomarkers for development of epilepsy are ictal or interictal high-frequency oscillations (HFOs) at 80 Hz or more, along with cross-frequency coupling of HFOs and delta wave activity, according to Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.

West syndrome, the most common epileptic encephalopathy during the first 2 years of life, has diverse etiologies. For example, in 250 infants with West syndrome enrolled in the United Kingdom National Infantile Spasms Consortium, a cause was identified in 64%. The etiology was genetic in 14% of subjects, a structural-congenital anomaly in 11%, tuberous sclerosis – a genetic-structural abnormality – in 10%, stroke in 22%, a metabolic defect in 5%, and infection in 2% (Epilepsia. 2015 Apr;56[4]:617-25).

West syndrome is rare, with an estimated prevalence of roughly 1 per 6,000 live births, but the associated mortality is high: 31% on average. And West syndrome often brings severe neurodevelopmental morbidity, with normal or near-normal intelligence present in only 25% of survivors.

An intensive search is on for an objective, reliable diagnostic biomarker – be it electroencephalographic, biochemical, or perhaps a neuroimaging finding – because the clinical diagnosis of West syndrome is highly subjective. It relies upon the triad of epileptic spasms, developmental regression or psychomotor delay, and hypsarrhythmia, which is a chaotic, disorganized, patternless form of brain electrical activity. And while that description makes hypsarrhythmia sound as if it should be easily recognizable, in fact that’s often not the case: Interrater reliability was poor in a study of six pediatric EEG experts at four centers who viewed 5-minute-long EEG samples obtained from 22 patients with infantile spasms (Epilepsia. 2015 Jan;56[1]:77-81), Dr. Nariai noted at the congress, sponsored by the International League Against Epilepsy.

“The clinical trial is maybe not so useful,” he observed.

The hunt for a reliable biomarker is further fueled by evidence that early diagnosis and treatment of West syndrome and other etiologies of infantile spasms makes a real difference. Indeed, investigators found in the United Kingdom Infantile Spasms Study that increasing lag time from onset of spasms to initiation of treatment was associated in stepwise fashion with significantly lower IQ at 4 years of age. While infants who started treatment within 7 days of onset of the seizure disorder had a mean IQ of 76.2 at age 4 years, those with an 8- to 14-day lag time between symptom onset and treatment averaged an additional 3.9-point decrement in IQ. A 15- to 30-day delay was associated with a 7.8-point reduction in IQ, compared with the reference group, while the decrease in IQ averaged 11.7 points in infants with a 1- to 2-month lag time and 15.6 points in those with a lag time of more than 2 months (Epilepsia. 2011 Jul;52[7]:1359-64).

At the start of the decade, Dr. Nariai and other investigators demonstrated that pathologic HFOs recorded during invasive EEG monitoring in conjunction with epilepsy surgery served as a reliable biomarker of epilepsy. While this was an important observation, a biomarker obtained through invasive monitoring during brain surgery clearly has very limited clinical applicability. But more recently, Dr. Nariai and his coinvestigators in the Tuberous Sclerosis Complex Autism Center of Excellence Network reported that noninvasive detection of interictal HFO fast ripples in the 250-500 Hz range via scalp EEG showed promise as a biomarker of epilepsy. Sensitivity of this far more practical approach to the detection of fast ripples was excellent, whether analyzed visually or by automatic detector (Clin Neurophysiol. 2018 Jul;129[7]:1458-66).

Moreover, in a recent, not-yet published study that Dr. Nariai and coworkers conducted in 24 infants with active epileptic spasms and 6 controls, noninvasive objective measurement of HFO rate using scalp EEG had an 83% sensitivity and 100% specificity for active epileptic spasms, while the modulation index of HFO and delta coupling in the 3-4 Hz range showed 74% sensitivity and 86% specificity.


If future studies validate the utility of detection of HFOs above a defined threshold or another noninvasively obtained EEG biomarker for diagnosis of epilepsy, the same strategy would presumably also be applicable for monitoring response to antiepileptic therapies, thereby eliminating the traditional trial-and-error approach to treatment. This would be a particularly important application in patients with West syndrome, where it’s believed that the electrical activity itself is contributing to the progressive – and often rapid – loss of cognitive function and behavioral disturbances. Thus, unlike in most other forms of epilepsy, the treatment goal isn’t merely to suppress the seizures, but also to achieve disease modification by eliminating the underlying subclinical EEG abnormalities, he explained.

A reliable biomarker would also be a boon in selecting the best participants for clinical trials of new antiseizure therapies.

Dr. Nariai reported having no financial conflicts regarding his presentation. His work is funded by research foundations and the National Institutes of Health.

[email protected]

BANGKOK – Several EEG abnormalities that are readily measured noninvasively using scalp electrodes show considerable promise as epileptogenicity biomarkers of particular interest for speedier diagnosis of West syndrome, Hiroki Nariai, MD, reported at the International Epilepsy Congress.

Bruce Jancin/MDedge News

Among the most promising of these potential EEG biomarkers for development of epilepsy are ictal or interictal high-frequency oscillations (HFOs) at 80 Hz or more, along with cross-frequency coupling of HFOs and delta wave activity, according to Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.

West syndrome, the most common epileptic encephalopathy during the first 2 years of life, has diverse etiologies. For example, in 250 infants with West syndrome enrolled in the United Kingdom National Infantile Spasms Consortium, a cause was identified in 64%. The etiology was genetic in 14% of subjects, a structural-congenital anomaly in 11%, tuberous sclerosis – a genetic-structural abnormality – in 10%, stroke in 22%, a metabolic defect in 5%, and infection in 2% (Epilepsia. 2015 Apr;56[4]:617-25).

West syndrome is rare, with an estimated prevalence of roughly 1 per 6,000 live births, but the associated mortality is high: 31% on average. And West syndrome often brings severe neurodevelopmental morbidity, with normal or near-normal intelligence present in only 25% of survivors.

An intensive search is on for an objective, reliable diagnostic biomarker – be it electroencephalographic, biochemical, or perhaps a neuroimaging finding – because the clinical diagnosis of West syndrome is highly subjective. It relies upon the triad of epileptic spasms, developmental regression or psychomotor delay, and hypsarrhythmia, which is a chaotic, disorganized, patternless form of brain electrical activity. And while that description makes hypsarrhythmia sound as if it should be easily recognizable, in fact that’s often not the case: Interrater reliability was poor in a study of six pediatric EEG experts at four centers who viewed 5-minute-long EEG samples obtained from 22 patients with infantile spasms (Epilepsia. 2015 Jan;56[1]:77-81), Dr. Nariai noted at the congress, sponsored by the International League Against Epilepsy.

“The clinical trial is maybe not so useful,” he observed.

The hunt for a reliable biomarker is further fueled by evidence that early diagnosis and treatment of West syndrome and other etiologies of infantile spasms makes a real difference. Indeed, investigators found in the United Kingdom Infantile Spasms Study that increasing lag time from onset of spasms to initiation of treatment was associated in stepwise fashion with significantly lower IQ at 4 years of age. While infants who started treatment within 7 days of onset of the seizure disorder had a mean IQ of 76.2 at age 4 years, those with an 8- to 14-day lag time between symptom onset and treatment averaged an additional 3.9-point decrement in IQ. A 15- to 30-day delay was associated with a 7.8-point reduction in IQ, compared with the reference group, while the decrease in IQ averaged 11.7 points in infants with a 1- to 2-month lag time and 15.6 points in those with a lag time of more than 2 months (Epilepsia. 2011 Jul;52[7]:1359-64).

At the start of the decade, Dr. Nariai and other investigators demonstrated that pathologic HFOs recorded during invasive EEG monitoring in conjunction with epilepsy surgery served as a reliable biomarker of epilepsy. While this was an important observation, a biomarker obtained through invasive monitoring during brain surgery clearly has very limited clinical applicability. But more recently, Dr. Nariai and his coinvestigators in the Tuberous Sclerosis Complex Autism Center of Excellence Network reported that noninvasive detection of interictal HFO fast ripples in the 250-500 Hz range via scalp EEG showed promise as a biomarker of epilepsy. Sensitivity of this far more practical approach to the detection of fast ripples was excellent, whether analyzed visually or by automatic detector (Clin Neurophysiol. 2018 Jul;129[7]:1458-66).

Moreover, in a recent, not-yet published study that Dr. Nariai and coworkers conducted in 24 infants with active epileptic spasms and 6 controls, noninvasive objective measurement of HFO rate using scalp EEG had an 83% sensitivity and 100% specificity for active epileptic spasms, while the modulation index of HFO and delta coupling in the 3-4 Hz range showed 74% sensitivity and 86% specificity.


If future studies validate the utility of detection of HFOs above a defined threshold or another noninvasively obtained EEG biomarker for diagnosis of epilepsy, the same strategy would presumably also be applicable for monitoring response to antiepileptic therapies, thereby eliminating the traditional trial-and-error approach to treatment. This would be a particularly important application in patients with West syndrome, where it’s believed that the electrical activity itself is contributing to the progressive – and often rapid – loss of cognitive function and behavioral disturbances. Thus, unlike in most other forms of epilepsy, the treatment goal isn’t merely to suppress the seizures, but also to achieve disease modification by eliminating the underlying subclinical EEG abnormalities, he explained.

A reliable biomarker would also be a boon in selecting the best participants for clinical trials of new antiseizure therapies.

Dr. Nariai reported having no financial conflicts regarding his presentation. His work is funded by research foundations and the National Institutes of Health.

[email protected]