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Study highlights importance of genotyping in von Willebrand disease
Patients with genetically confirmed von Willebrand disease (VWD) type 2M have a relatively mild clinical phenotype, according to findings from a retrospective cross-sectional study.
In fact, three of 31 patients included in the study had a near normal laboratory phenotype. Additionally, patients with the p.Val1360Ala mutation had significantly higher values of all von Willebrand factor (VWF)-related laboratory parameters, compared with those with the p.Arg1374Cys or p.Phe1293Leu mutation, Dominique Maas reported at the European Association for Haemophilia and Allied Disorders annual meeting.
The findings underscore the importance of genotyping for making a correct diagnosis of VWD type 2M, said Ms. Maas of Radboud University Medical Center, Nijmegen, The Netherlands.
The study subjects, who had a least one VWD type 2M mutation, had a median age of 34 years and a median bleeding score of 6. Most suffered from mucocutaneous bleeding, but with low frequency compared with other VWD subtypes. The incidence of muscle hematomas, postpartum hemorrhage, and postsurgery bleeding were relatively high, however. Age and bleeding score were strongly positively correlated.
Subjects had a median VWF antigen level of 24 IU dL-1, median VWF ristocetin cofactor activity of 6 IU dL-1, and median VSF:RCo/VWF:Ag ratio of 0.29. The VSF collagen binding activity and VWF:Ag ratio was normal, she said.
Genotyping is a powerful diagnostic tool for making an appropriate diagnosis and classification of VWD. The current findings are important because understanding the correlation between genotype and phenotype improves the understanding of VWD pathogenesis and has important implications for treatment, follow-up, and genetic counseling, but has not been throughly investigated in fully genotyped patients with VWD type 2M, she said.
Ms. Maas reported having no disclosures.
Patients with genetically confirmed von Willebrand disease (VWD) type 2M have a relatively mild clinical phenotype, according to findings from a retrospective cross-sectional study.
In fact, three of 31 patients included in the study had a near normal laboratory phenotype. Additionally, patients with the p.Val1360Ala mutation had significantly higher values of all von Willebrand factor (VWF)-related laboratory parameters, compared with those with the p.Arg1374Cys or p.Phe1293Leu mutation, Dominique Maas reported at the European Association for Haemophilia and Allied Disorders annual meeting.
The findings underscore the importance of genotyping for making a correct diagnosis of VWD type 2M, said Ms. Maas of Radboud University Medical Center, Nijmegen, The Netherlands.
The study subjects, who had a least one VWD type 2M mutation, had a median age of 34 years and a median bleeding score of 6. Most suffered from mucocutaneous bleeding, but with low frequency compared with other VWD subtypes. The incidence of muscle hematomas, postpartum hemorrhage, and postsurgery bleeding were relatively high, however. Age and bleeding score were strongly positively correlated.
Subjects had a median VWF antigen level of 24 IU dL-1, median VWF ristocetin cofactor activity of 6 IU dL-1, and median VSF:RCo/VWF:Ag ratio of 0.29. The VSF collagen binding activity and VWF:Ag ratio was normal, she said.
Genotyping is a powerful diagnostic tool for making an appropriate diagnosis and classification of VWD. The current findings are important because understanding the correlation between genotype and phenotype improves the understanding of VWD pathogenesis and has important implications for treatment, follow-up, and genetic counseling, but has not been throughly investigated in fully genotyped patients with VWD type 2M, she said.
Ms. Maas reported having no disclosures.
Patients with genetically confirmed von Willebrand disease (VWD) type 2M have a relatively mild clinical phenotype, according to findings from a retrospective cross-sectional study.
In fact, three of 31 patients included in the study had a near normal laboratory phenotype. Additionally, patients with the p.Val1360Ala mutation had significantly higher values of all von Willebrand factor (VWF)-related laboratory parameters, compared with those with the p.Arg1374Cys or p.Phe1293Leu mutation, Dominique Maas reported at the European Association for Haemophilia and Allied Disorders annual meeting.
The findings underscore the importance of genotyping for making a correct diagnosis of VWD type 2M, said Ms. Maas of Radboud University Medical Center, Nijmegen, The Netherlands.
The study subjects, who had a least one VWD type 2M mutation, had a median age of 34 years and a median bleeding score of 6. Most suffered from mucocutaneous bleeding, but with low frequency compared with other VWD subtypes. The incidence of muscle hematomas, postpartum hemorrhage, and postsurgery bleeding were relatively high, however. Age and bleeding score were strongly positively correlated.
Subjects had a median VWF antigen level of 24 IU dL-1, median VWF ristocetin cofactor activity of 6 IU dL-1, and median VSF:RCo/VWF:Ag ratio of 0.29. The VSF collagen binding activity and VWF:Ag ratio was normal, she said.
Genotyping is a powerful diagnostic tool for making an appropriate diagnosis and classification of VWD. The current findings are important because understanding the correlation between genotype and phenotype improves the understanding of VWD pathogenesis and has important implications for treatment, follow-up, and genetic counseling, but has not been throughly investigated in fully genotyped patients with VWD type 2M, she said.
Ms. Maas reported having no disclosures.
FROM EAHAD 2017
Key clinical point:
Major finding: Three of 31 patients included in the study had a near normal laboratory phenotype.
Data source: A retrospective cross-sectional study of 31 patients.
Disclosures: Ms. Maas reported having no disclosures.
Solulin variants activate TAFI in vitro
A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.
The in vitro production and characterization of these solulin variants – F376A-, M388A-, and F376A/M388A-solulin – showed that while they lost their abilities to activate protein C (an inhibitor of thrombin generation), they were still capable of activating thrombin activatable fibrinolysis inhibitor (TAFI), Yohann Repesse, PhD reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Additionally, the double mutant F376A/M388A-solulin, which was tested ex vivo using blood samples from hemophilic A patients, was found on thromboelastography to increase clot firmness and stability. As opposed to wild type solulin, the effects were maintained even at high concentrations of F376A/M388A-solulin, said Dr. Repesse of the National Institute of Health and Medical Research, Caen, France.
An important aggravating factor when it comes to treating hemophilia involves premature fibrinolysis, which means that antifibrinolytics are of interest, he explained. Thrombomodulin is a key player in the coagulation cascade, because it activates protein C, and also in the fibrinolytic cascade, as it activates TAFI. Solulin, a soluble form of thrombomodulin, has both capabilities.
The findings with respect to the new generation of solulin variants tested in this study open new opportunities for the development of specific medications for hemophilia patients, he concluded.
Dr. Repesse reported having no disclosures.
A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.
The in vitro production and characterization of these solulin variants – F376A-, M388A-, and F376A/M388A-solulin – showed that while they lost their abilities to activate protein C (an inhibitor of thrombin generation), they were still capable of activating thrombin activatable fibrinolysis inhibitor (TAFI), Yohann Repesse, PhD reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Additionally, the double mutant F376A/M388A-solulin, which was tested ex vivo using blood samples from hemophilic A patients, was found on thromboelastography to increase clot firmness and stability. As opposed to wild type solulin, the effects were maintained even at high concentrations of F376A/M388A-solulin, said Dr. Repesse of the National Institute of Health and Medical Research, Caen, France.
An important aggravating factor when it comes to treating hemophilia involves premature fibrinolysis, which means that antifibrinolytics are of interest, he explained. Thrombomodulin is a key player in the coagulation cascade, because it activates protein C, and also in the fibrinolytic cascade, as it activates TAFI. Solulin, a soluble form of thrombomodulin, has both capabilities.
The findings with respect to the new generation of solulin variants tested in this study open new opportunities for the development of specific medications for hemophilia patients, he concluded.
Dr. Repesse reported having no disclosures.
A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.
The in vitro production and characterization of these solulin variants – F376A-, M388A-, and F376A/M388A-solulin – showed that while they lost their abilities to activate protein C (an inhibitor of thrombin generation), they were still capable of activating thrombin activatable fibrinolysis inhibitor (TAFI), Yohann Repesse, PhD reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Additionally, the double mutant F376A/M388A-solulin, which was tested ex vivo using blood samples from hemophilic A patients, was found on thromboelastography to increase clot firmness and stability. As opposed to wild type solulin, the effects were maintained even at high concentrations of F376A/M388A-solulin, said Dr. Repesse of the National Institute of Health and Medical Research, Caen, France.
An important aggravating factor when it comes to treating hemophilia involves premature fibrinolysis, which means that antifibrinolytics are of interest, he explained. Thrombomodulin is a key player in the coagulation cascade, because it activates protein C, and also in the fibrinolytic cascade, as it activates TAFI. Solulin, a soluble form of thrombomodulin, has both capabilities.
The findings with respect to the new generation of solulin variants tested in this study open new opportunities for the development of specific medications for hemophilia patients, he concluded.
Dr. Repesse reported having no disclosures.
FROM EAHAD 2017
Key clinical point:
Major finding: F376A-, M388A-, and F376A/M388A-solulin lost their abilities to activate protein C but were still capable of activating TAFI.
Data source: An in vitro and ex vivo evaluation of solulin variants.
Disclosures: Dr. Repesse reported having no disclosures.
Boys with severe hemophilia have good physical function
Children with severe hemophilia in a U.K. study had generally good self-reported health-related quality of life and physical functioning, but impairment on both measures was greater in those who reported pain.
Of 123 boys with a mean age of 12 years who were included in the multicenter SO-FIT study, 110 had hemophilia A, 25 had a past inhibitor, and 9 had a current inhibitor. Prophylactic treatment was given in 120 of the boys, Kate Khair, PhD of Great Ormond Street Hospital for Children, London, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
In the preceding 6 months, participants experienced a median of 0 joint bleeds (range of 0-8), and a median Hemophilia Joint Health Score (HJHS) of 1 (range, 0-37). Physical function scores were good; the Haemophilia & Exercise Project questionnaire (HEP-Test-Q) mean score was 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21), and the Paediatric Haemophilia Activities List (PedHAL) mean score was 85.13, with the highest impairments seen in the domains of “leisure activities and sports” and “lying/sitting/kneeling/standing” (mean, 82.04 and 82.97, respectively).
Health-related quality of life as assessed by the Haemo-QoL Short Form was also generally good (mean, 23.07), with the highest impairments seen in the domains of “friends” and “family” (mean, 27.08 and 26.59, respectively).
In the 27% of participants with pain, a high correlation was seen between the HEP-Test-Q and Haemo-QoL, and moderate correlation was seen between the PedHAL and Haemo-QoL, which implies that good physical functioning is related to good health-related quality of life, Dr. Khair explained.
In fact, patients who said they often or always had pain reported significantly worse subjective physical functioning in all HEP-Test-Q and PedHAL domains, as well as higher impairments in their HRQoL vs. those who said they sometimes, rarely, or never experienced pain, she said.
Interestingly, data completion by study participants was improved with use of an iPad vs. “paper and pencil” for questionnaire completion, Dr. Khair said in an interview.
“They preferred this method – it was more in keeping with how they communicate and learn at school,” she said, noting that the iPad database was set up to give real time scores, which could then be used to tailor assessments.
This is an approach that could be undertaken at home pre-clinic visits, she said.
“Gaining the views of children and young adults in patient-reported outcomes is complex, but reveals their views of their care and their lives – an area we should address more,” she added.
Dr. Khair received grant or research support from Pfizer ASPIRE.
Children with severe hemophilia in a U.K. study had generally good self-reported health-related quality of life and physical functioning, but impairment on both measures was greater in those who reported pain.
Of 123 boys with a mean age of 12 years who were included in the multicenter SO-FIT study, 110 had hemophilia A, 25 had a past inhibitor, and 9 had a current inhibitor. Prophylactic treatment was given in 120 of the boys, Kate Khair, PhD of Great Ormond Street Hospital for Children, London, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
In the preceding 6 months, participants experienced a median of 0 joint bleeds (range of 0-8), and a median Hemophilia Joint Health Score (HJHS) of 1 (range, 0-37). Physical function scores were good; the Haemophilia & Exercise Project questionnaire (HEP-Test-Q) mean score was 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21), and the Paediatric Haemophilia Activities List (PedHAL) mean score was 85.13, with the highest impairments seen in the domains of “leisure activities and sports” and “lying/sitting/kneeling/standing” (mean, 82.04 and 82.97, respectively).
Health-related quality of life as assessed by the Haemo-QoL Short Form was also generally good (mean, 23.07), with the highest impairments seen in the domains of “friends” and “family” (mean, 27.08 and 26.59, respectively).
In the 27% of participants with pain, a high correlation was seen between the HEP-Test-Q and Haemo-QoL, and moderate correlation was seen between the PedHAL and Haemo-QoL, which implies that good physical functioning is related to good health-related quality of life, Dr. Khair explained.
In fact, patients who said they often or always had pain reported significantly worse subjective physical functioning in all HEP-Test-Q and PedHAL domains, as well as higher impairments in their HRQoL vs. those who said they sometimes, rarely, or never experienced pain, she said.
Interestingly, data completion by study participants was improved with use of an iPad vs. “paper and pencil” for questionnaire completion, Dr. Khair said in an interview.
“They preferred this method – it was more in keeping with how they communicate and learn at school,” she said, noting that the iPad database was set up to give real time scores, which could then be used to tailor assessments.
This is an approach that could be undertaken at home pre-clinic visits, she said.
“Gaining the views of children and young adults in patient-reported outcomes is complex, but reveals their views of their care and their lives – an area we should address more,” she added.
Dr. Khair received grant or research support from Pfizer ASPIRE.
Children with severe hemophilia in a U.K. study had generally good self-reported health-related quality of life and physical functioning, but impairment on both measures was greater in those who reported pain.
Of 123 boys with a mean age of 12 years who were included in the multicenter SO-FIT study, 110 had hemophilia A, 25 had a past inhibitor, and 9 had a current inhibitor. Prophylactic treatment was given in 120 of the boys, Kate Khair, PhD of Great Ormond Street Hospital for Children, London, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
In the preceding 6 months, participants experienced a median of 0 joint bleeds (range of 0-8), and a median Hemophilia Joint Health Score (HJHS) of 1 (range, 0-37). Physical function scores were good; the Haemophilia & Exercise Project questionnaire (HEP-Test-Q) mean score was 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21), and the Paediatric Haemophilia Activities List (PedHAL) mean score was 85.13, with the highest impairments seen in the domains of “leisure activities and sports” and “lying/sitting/kneeling/standing” (mean, 82.04 and 82.97, respectively).
Health-related quality of life as assessed by the Haemo-QoL Short Form was also generally good (mean, 23.07), with the highest impairments seen in the domains of “friends” and “family” (mean, 27.08 and 26.59, respectively).
In the 27% of participants with pain, a high correlation was seen between the HEP-Test-Q and Haemo-QoL, and moderate correlation was seen between the PedHAL and Haemo-QoL, which implies that good physical functioning is related to good health-related quality of life, Dr. Khair explained.
In fact, patients who said they often or always had pain reported significantly worse subjective physical functioning in all HEP-Test-Q and PedHAL domains, as well as higher impairments in their HRQoL vs. those who said they sometimes, rarely, or never experienced pain, she said.
Interestingly, data completion by study participants was improved with use of an iPad vs. “paper and pencil” for questionnaire completion, Dr. Khair said in an interview.
“They preferred this method – it was more in keeping with how they communicate and learn at school,” she said, noting that the iPad database was set up to give real time scores, which could then be used to tailor assessments.
This is an approach that could be undertaken at home pre-clinic visits, she said.
“Gaining the views of children and young adults in patient-reported outcomes is complex, but reveals their views of their care and their lives – an area we should address more,” she added.
Dr. Khair received grant or research support from Pfizer ASPIRE.
FROM EAHAD 2017
Key clinical point:
Major finding: Physical function score (HEP-Test-Q) was a mean of 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21).
Data source: The SO-FIT study of 123 boys with severe hemophilia.
Disclosures: Dr. Khair received grant or research support from Pfizer ASPIRE.
Group identifies ‘essential’ genes in AML
CRISPR-based genetic screens have revealed essential genes—those required for cellular proliferation and survival—in 14 acute myeloid leukemia (AML) cell lines, according to investigators.
By combining this information with the existing genomic information on these cell lines, the investigators believe they have identified vulnerabilities that could potentially be exploited with new therapies.
The group described their research in Cell.
A major aspect of their study focused on the genes and protein pathways connected to the Ras oncogene, which is the most commonly mutated oncogene in human cancers and plays a role in AML.
“For the most part, the mutant Ras protein itself has been considered to be ‘undruggable,’” said study author Tim Wang, a doctoral student at the Massachusetts Institute of Technology in Cambridge.
“An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable. Unfortunately, such ‘Ras-synthetic-lethal’ genes have been difficult to identify.”
Using CRISPR-based screens, the investigators were able to gauge the impact of individually knocking out each of the 18,000 protein-coding genes in the human genome.
“This process rapidly enabled us to identify the short list of genes that were selectively required in only the Ras-mutant cells,” explained study author David Sabatini, MD, PhD, of the Massachusetts Institute of Technology.
He and his colleagues found that the enzymes catalyzing the latter steps of the Ras processing pathway, Rce1 and Icmt, displayed synthetic lethality with oncogenic Ras, which suggests they might be therapeutic targets in AML and other cancers driven by oncogenic Ras.
The investigators also said their findings provide further support for the central role of MAPK signaling in Ras-driven cancers, suggest PREX1 and the Rac pathway are critical regulators of MAPK pathway activation, and indicate that c-Raf could be a therapeutic target in cancers driven by oncogenic Ras.
In addition to defining the Ras-specific gene essentiality network, the investigators said they were able to determine the function of previously unstudied genes.
The team started by focusing on genes that were essential in some of the AML cell lines but dispensable for others. For each of these genes, the investigators sifted through their data to find others that showed a matching pattern of essentiality, with the idea that all of them had similar functions.
Indeed, this analysis revealed gene groups that were already known to act together and uncovered novel associations between genes that were not known to be related or had been previously unstudied.
“What’s particularly exciting about this work is that we have just begun to scratch the surface with our method,” Wang concluded. “By applying it broadly, we could reveal a huge amount of information about the functional organization of human genes and their roles in many diseases.” 
CRISPR-based genetic screens have revealed essential genes—those required for cellular proliferation and survival—in 14 acute myeloid leukemia (AML) cell lines, according to investigators.
By combining this information with the existing genomic information on these cell lines, the investigators believe they have identified vulnerabilities that could potentially be exploited with new therapies.
The group described their research in Cell.
A major aspect of their study focused on the genes and protein pathways connected to the Ras oncogene, which is the most commonly mutated oncogene in human cancers and plays a role in AML.
“For the most part, the mutant Ras protein itself has been considered to be ‘undruggable,’” said study author Tim Wang, a doctoral student at the Massachusetts Institute of Technology in Cambridge.
“An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable. Unfortunately, such ‘Ras-synthetic-lethal’ genes have been difficult to identify.”
Using CRISPR-based screens, the investigators were able to gauge the impact of individually knocking out each of the 18,000 protein-coding genes in the human genome.
“This process rapidly enabled us to identify the short list of genes that were selectively required in only the Ras-mutant cells,” explained study author David Sabatini, MD, PhD, of the Massachusetts Institute of Technology.
He and his colleagues found that the enzymes catalyzing the latter steps of the Ras processing pathway, Rce1 and Icmt, displayed synthetic lethality with oncogenic Ras, which suggests they might be therapeutic targets in AML and other cancers driven by oncogenic Ras.
The investigators also said their findings provide further support for the central role of MAPK signaling in Ras-driven cancers, suggest PREX1 and the Rac pathway are critical regulators of MAPK pathway activation, and indicate that c-Raf could be a therapeutic target in cancers driven by oncogenic Ras.
In addition to defining the Ras-specific gene essentiality network, the investigators said they were able to determine the function of previously unstudied genes.
The team started by focusing on genes that were essential in some of the AML cell lines but dispensable for others. For each of these genes, the investigators sifted through their data to find others that showed a matching pattern of essentiality, with the idea that all of them had similar functions.
Indeed, this analysis revealed gene groups that were already known to act together and uncovered novel associations between genes that were not known to be related or had been previously unstudied.
“What’s particularly exciting about this work is that we have just begun to scratch the surface with our method,” Wang concluded. “By applying it broadly, we could reveal a huge amount of information about the functional organization of human genes and their roles in many diseases.”
CRISPR-based genetic screens have revealed essential genes—those required for cellular proliferation and survival—in 14 acute myeloid leukemia (AML) cell lines, according to investigators.
By combining this information with the existing genomic information on these cell lines, the investigators believe they have identified vulnerabilities that could potentially be exploited with new therapies.
The group described their research in Cell.
A major aspect of their study focused on the genes and protein pathways connected to the Ras oncogene, which is the most commonly mutated oncogene in human cancers and plays a role in AML.
“For the most part, the mutant Ras protein itself has been considered to be ‘undruggable,’” said study author Tim Wang, a doctoral student at the Massachusetts Institute of Technology in Cambridge.
“An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable. Unfortunately, such ‘Ras-synthetic-lethal’ genes have been difficult to identify.”
Using CRISPR-based screens, the investigators were able to gauge the impact of individually knocking out each of the 18,000 protein-coding genes in the human genome.
“This process rapidly enabled us to identify the short list of genes that were selectively required in only the Ras-mutant cells,” explained study author David Sabatini, MD, PhD, of the Massachusetts Institute of Technology.
He and his colleagues found that the enzymes catalyzing the latter steps of the Ras processing pathway, Rce1 and Icmt, displayed synthetic lethality with oncogenic Ras, which suggests they might be therapeutic targets in AML and other cancers driven by oncogenic Ras.
The investigators also said their findings provide further support for the central role of MAPK signaling in Ras-driven cancers, suggest PREX1 and the Rac pathway are critical regulators of MAPK pathway activation, and indicate that c-Raf could be a therapeutic target in cancers driven by oncogenic Ras.
In addition to defining the Ras-specific gene essentiality network, the investigators said they were able to determine the function of previously unstudied genes.
The team started by focusing on genes that were essential in some of the AML cell lines but dispensable for others. For each of these genes, the investigators sifted through their data to find others that showed a matching pattern of essentiality, with the idea that all of them had similar functions.
Indeed, this analysis revealed gene groups that were already known to act together and uncovered novel associations between genes that were not known to be related or had been previously unstudied.
“What’s particularly exciting about this work is that we have just begun to scratch the surface with our method,” Wang concluded. “By applying it broadly, we could reveal a huge amount of information about the functional organization of human genes and their roles in many diseases.”
Worse outcomes with video laryngoscopy in ICU
When used in intensive care units, video laryngoscopy did not improve the chances of successful intubation on the first try, compared with direct laryngoscopy, and was associated with a significantly higher risk of severe life-threatening complications, researchers reported.
In a multicenter, randomized trial of 371 patients, first-pass intubation rates did not differ significantly whether video or direct laryngoscopy was used, at 67.7% and 70.3%, respectively, Jean Baptiste Lascarrou, MD, of District Hospital Centre, La Roche-sur-Yon, France, and his associates wrote. Meanwhile, the combined rate of death, cardiac arrest, severe cardiovascular collapse, and hypoxemia was 9.5% with video laryngoscopy and just 2.8% with direct laryngoscopy, a significant difference (JAMA. 2017 Jan 24;317[5]:483-93).
“Improved glottis visualization with video laryngoscopy did not translate into a higher success rate for first-pass intubation, because tracheal catheterization under indirect vision was more difficult, in keeping with earlier data,” the researchers concluded. “Further studies are needed to assess the comparative effectiveness of these two strategies in different clinical settings and among operators with diverse skill levels.”
Intubation in the ICU carries an inherently high risk because patients are often acutely unstable, and the intubating clinician is usually a nonexpert, the investigators noted. At the same time, the procedure must be done quickly to prevent aspiration because patients usually have not fasted. Care bundles and training on simulators have improved safety, but ICU intubations remain riskier than those done in the operating room.
Observational studies and smaller trials in ICUs seemed to support video laryngoscopy over the Macintosh laryngoscope, but raised questions about intubation time and mortality, the investigators noted. To help resolve these issues, they randomly assigned adults needing orotracheal intubation at seven ICUs in France to either video or direct Macintosh laryngoscopy, and followed them for 28 days. Patients averaged 63 years of age, and 37% were women.
For both arms, residents performed the initial intubation attempt in about 80% of cases, and successful intubation usually took 3 minutes. Video laryngoscopy did not significantly increase the combined risk of esophageal intubation, aspiration, arrhythmia, or dental injury (5.4% versus 7.7% for direct laryngoscopy). But the only death in the study occurred after video laryngoscopy, and there were four cardiac arrests after video laryngoscopy and none after direct laryngoscopy, the researchers said. Furthermore, the rate of severe hypoxemia was nearly six times higher after video laryngoscopy than with direct laryngoscopy, and the rate of hypotension was twice as high.
The researchers did not identify predictors of life-threatening complications with video laryngoscopy, but hypothesized that being able to clearly visualize the glottis might create “a false impression of safety,” especially among nonexperts. “In addition, poorer alignment of the pharyngeal axis, laryngeal axis, and mouth opening despite good glottis visualization by video laryngoscopy can lead to mechanical upper airway obstruction and faster progression to hypoxemia,” they wrote.
Centre Hospitalier Département de la Vendée sponsored the study. Dr. Lascarrou reported having no relevant conflicts of interest. Four coinvestigators disclosed ties to Fisher & Paykel, LFB, Merck Sharp & Dohme, Astellas, Basilea Pharmaceutica. Gilead, Alexion, and Cubist. The remaining coinvestigators had no disclosures.
The results of this trial illustrate the fundamental problem with video laryngoscopy: It generates excellent views of the larynx but may not facilitate tracheal intubation.
The use of video laryngoscopy can lead to the creation of blind spots, both visual and cognitive. Because the lens of the laryngoscope is located at the tip of the device, the pharynx and hypopharynx are not visualized during video laryngoscopy. Manipulating the endotracheal tube into view therefore occurs within this blind spot, and this can be difficult depending on the patient’s pharyngeal anatomy. This phenomenon has been linked to higher rates of pharyngeal soft tissue injury and longer intubation times in patients undergoing video laryngoscopy as compared with direct laryngoscopy.
The view during video laryngoscopy can also create a cognitive blind spot: laryngoscopists may fail to abort a laryngoscopy attempt in a timely manner because they have such a clear view of the larynx.
Brian O’Gara, MD, and Daniel Talmor, MD, of Harvard University, Boston, and Samuel Brown, MD, MS, of the University of Utah School, Murray, Utah, made these comments in an accompanying editorial (JAMA. 2017 Feb 7; doi: 10.1001/jama.2016.21036) . None of the authors had relevant financial disclosures.
The results of this trial illustrate the fundamental problem with video laryngoscopy: It generates excellent views of the larynx but may not facilitate tracheal intubation.
The use of video laryngoscopy can lead to the creation of blind spots, both visual and cognitive. Because the lens of the laryngoscope is located at the tip of the device, the pharynx and hypopharynx are not visualized during video laryngoscopy. Manipulating the endotracheal tube into view therefore occurs within this blind spot, and this can be difficult depending on the patient’s pharyngeal anatomy. This phenomenon has been linked to higher rates of pharyngeal soft tissue injury and longer intubation times in patients undergoing video laryngoscopy as compared with direct laryngoscopy.
The view during video laryngoscopy can also create a cognitive blind spot: laryngoscopists may fail to abort a laryngoscopy attempt in a timely manner because they have such a clear view of the larynx.
Brian O’Gara, MD, and Daniel Talmor, MD, of Harvard University, Boston, and Samuel Brown, MD, MS, of the University of Utah School, Murray, Utah, made these comments in an accompanying editorial (JAMA. 2017 Feb 7; doi: 10.1001/jama.2016.21036) . None of the authors had relevant financial disclosures.
The results of this trial illustrate the fundamental problem with video laryngoscopy: It generates excellent views of the larynx but may not facilitate tracheal intubation.
The use of video laryngoscopy can lead to the creation of blind spots, both visual and cognitive. Because the lens of the laryngoscope is located at the tip of the device, the pharynx and hypopharynx are not visualized during video laryngoscopy. Manipulating the endotracheal tube into view therefore occurs within this blind spot, and this can be difficult depending on the patient’s pharyngeal anatomy. This phenomenon has been linked to higher rates of pharyngeal soft tissue injury and longer intubation times in patients undergoing video laryngoscopy as compared with direct laryngoscopy.
The view during video laryngoscopy can also create a cognitive blind spot: laryngoscopists may fail to abort a laryngoscopy attempt in a timely manner because they have such a clear view of the larynx.
Brian O’Gara, MD, and Daniel Talmor, MD, of Harvard University, Boston, and Samuel Brown, MD, MS, of the University of Utah School, Murray, Utah, made these comments in an accompanying editorial (JAMA. 2017 Feb 7; doi: 10.1001/jama.2016.21036) . None of the authors had relevant financial disclosures.
When used in intensive care units, video laryngoscopy did not improve the chances of successful intubation on the first try, compared with direct laryngoscopy, and was associated with a significantly higher risk of severe life-threatening complications, researchers reported.
In a multicenter, randomized trial of 371 patients, first-pass intubation rates did not differ significantly whether video or direct laryngoscopy was used, at 67.7% and 70.3%, respectively, Jean Baptiste Lascarrou, MD, of District Hospital Centre, La Roche-sur-Yon, France, and his associates wrote. Meanwhile, the combined rate of death, cardiac arrest, severe cardiovascular collapse, and hypoxemia was 9.5% with video laryngoscopy and just 2.8% with direct laryngoscopy, a significant difference (JAMA. 2017 Jan 24;317[5]:483-93).
“Improved glottis visualization with video laryngoscopy did not translate into a higher success rate for first-pass intubation, because tracheal catheterization under indirect vision was more difficult, in keeping with earlier data,” the researchers concluded. “Further studies are needed to assess the comparative effectiveness of these two strategies in different clinical settings and among operators with diverse skill levels.”
Intubation in the ICU carries an inherently high risk because patients are often acutely unstable, and the intubating clinician is usually a nonexpert, the investigators noted. At the same time, the procedure must be done quickly to prevent aspiration because patients usually have not fasted. Care bundles and training on simulators have improved safety, but ICU intubations remain riskier than those done in the operating room.
Observational studies and smaller trials in ICUs seemed to support video laryngoscopy over the Macintosh laryngoscope, but raised questions about intubation time and mortality, the investigators noted. To help resolve these issues, they randomly assigned adults needing orotracheal intubation at seven ICUs in France to either video or direct Macintosh laryngoscopy, and followed them for 28 days. Patients averaged 63 years of age, and 37% were women.
For both arms, residents performed the initial intubation attempt in about 80% of cases, and successful intubation usually took 3 minutes. Video laryngoscopy did not significantly increase the combined risk of esophageal intubation, aspiration, arrhythmia, or dental injury (5.4% versus 7.7% for direct laryngoscopy). But the only death in the study occurred after video laryngoscopy, and there were four cardiac arrests after video laryngoscopy and none after direct laryngoscopy, the researchers said. Furthermore, the rate of severe hypoxemia was nearly six times higher after video laryngoscopy than with direct laryngoscopy, and the rate of hypotension was twice as high.
The researchers did not identify predictors of life-threatening complications with video laryngoscopy, but hypothesized that being able to clearly visualize the glottis might create “a false impression of safety,” especially among nonexperts. “In addition, poorer alignment of the pharyngeal axis, laryngeal axis, and mouth opening despite good glottis visualization by video laryngoscopy can lead to mechanical upper airway obstruction and faster progression to hypoxemia,” they wrote.
Centre Hospitalier Département de la Vendée sponsored the study. Dr. Lascarrou reported having no relevant conflicts of interest. Four coinvestigators disclosed ties to Fisher & Paykel, LFB, Merck Sharp & Dohme, Astellas, Basilea Pharmaceutica. Gilead, Alexion, and Cubist. The remaining coinvestigators had no disclosures.
When used in intensive care units, video laryngoscopy did not improve the chances of successful intubation on the first try, compared with direct laryngoscopy, and was associated with a significantly higher risk of severe life-threatening complications, researchers reported.
In a multicenter, randomized trial of 371 patients, first-pass intubation rates did not differ significantly whether video or direct laryngoscopy was used, at 67.7% and 70.3%, respectively, Jean Baptiste Lascarrou, MD, of District Hospital Centre, La Roche-sur-Yon, France, and his associates wrote. Meanwhile, the combined rate of death, cardiac arrest, severe cardiovascular collapse, and hypoxemia was 9.5% with video laryngoscopy and just 2.8% with direct laryngoscopy, a significant difference (JAMA. 2017 Jan 24;317[5]:483-93).
“Improved glottis visualization with video laryngoscopy did not translate into a higher success rate for first-pass intubation, because tracheal catheterization under indirect vision was more difficult, in keeping with earlier data,” the researchers concluded. “Further studies are needed to assess the comparative effectiveness of these two strategies in different clinical settings and among operators with diverse skill levels.”
Intubation in the ICU carries an inherently high risk because patients are often acutely unstable, and the intubating clinician is usually a nonexpert, the investigators noted. At the same time, the procedure must be done quickly to prevent aspiration because patients usually have not fasted. Care bundles and training on simulators have improved safety, but ICU intubations remain riskier than those done in the operating room.
Observational studies and smaller trials in ICUs seemed to support video laryngoscopy over the Macintosh laryngoscope, but raised questions about intubation time and mortality, the investigators noted. To help resolve these issues, they randomly assigned adults needing orotracheal intubation at seven ICUs in France to either video or direct Macintosh laryngoscopy, and followed them for 28 days. Patients averaged 63 years of age, and 37% were women.
For both arms, residents performed the initial intubation attempt in about 80% of cases, and successful intubation usually took 3 minutes. Video laryngoscopy did not significantly increase the combined risk of esophageal intubation, aspiration, arrhythmia, or dental injury (5.4% versus 7.7% for direct laryngoscopy). But the only death in the study occurred after video laryngoscopy, and there were four cardiac arrests after video laryngoscopy and none after direct laryngoscopy, the researchers said. Furthermore, the rate of severe hypoxemia was nearly six times higher after video laryngoscopy than with direct laryngoscopy, and the rate of hypotension was twice as high.
The researchers did not identify predictors of life-threatening complications with video laryngoscopy, but hypothesized that being able to clearly visualize the glottis might create “a false impression of safety,” especially among nonexperts. “In addition, poorer alignment of the pharyngeal axis, laryngeal axis, and mouth opening despite good glottis visualization by video laryngoscopy can lead to mechanical upper airway obstruction and faster progression to hypoxemia,” they wrote.
Centre Hospitalier Département de la Vendée sponsored the study. Dr. Lascarrou reported having no relevant conflicts of interest. Four coinvestigators disclosed ties to Fisher & Paykel, LFB, Merck Sharp & Dohme, Astellas, Basilea Pharmaceutica. Gilead, Alexion, and Cubist. The remaining coinvestigators had no disclosures.
FROM JAMA
Key clinical point: Among patients in intensive care units, video laryngoscopy did not improve the chances of successful intubation on the first try, when compared with standard Macintosh laryngoscopy, and was associated with a significantly higher risk of severe life-threatening events.
Major finding: Rates of first-pass intubation were 67.7% for video laryngoscopy and 70.3% for direct laryngoscopy (P = .6). The combined rate of death, cardiac arrest, severe cardiovascular collapse, and hypoxemia was 9.5% with video laryngoscopy and 2.8% with direct laryngoscopy (P = .01).
Data source: A multicenter randomized trial of 371 ICU patients.
Disclosures: Centre Hospitalier Département de la Vendée sponsored the study. Dr. Lascarrou reported having no relevant conflicts of interest. Four coinvestigators disclosed ties to Fisher & Paykel, LFB, Merck Sharp & Dohme, Astellas, Basilea Pharmaceutica. Gilead, Alexion, and Cubist. The remaining coinvestigators had no disclosures.
ITI protects against bleeding in hemophilia A with factor VIII inhibitors
Immune tolerance induction, or ITI, in hemophilia A patients with inhibitor development against factor VIII (FVIII) appears to provide some protection against bleeding, as bleeding during ITI in patients from the PedNet registry was dependent on inhibitor titer and ITI regimen, according to Kathelijn Fischer, MD.
Of 218 registry patients who were born during 1990-2009 and who had clinically relevant inhibitors and available data on joint bleeding, 157 had bleeding for at least 3 months. They were followed for a median of 26 months starting at age 16 months, and most had high titer inhibitors (52% had titers of 5-199 BU, and 32% had titers greater than 200 BU).
The bleeding rates in 12 patients without ITI who were on prophylaxis were similar to those in 89 such patients without prophylaxis (0.3 and 0.4 bleeds/month, respectively); no significant difference was seen between the groups based on inhibitor titer, Dr. Fischer of University Medical Center Utrecht, The Netherlands reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Similarly, the bleeding rate during ITI among those on prophylaxis did not differ significantly from the rate in those without prophylaxis (0.4 vs. 0.3/month, respectively), but the rate did increase significantly according to inhibitor titer: The rate increased from 0.05/month in the group with less than 5 BU, to 0.2/month in those with 5-199 BU, and to 0.5/month in the group with greater than 200 BU.
Further, while ITI dose did not affect bleeding, dosing frequency had a strong effect. The median rate with nondaily dosing in 36 patients vs. daily dosing in 63 patients was 0.4/month vs. 0.2/month, respectively, Dr. Fischer said.
She reported having no disclosures.
Immune tolerance induction, or ITI, in hemophilia A patients with inhibitor development against factor VIII (FVIII) appears to provide some protection against bleeding, as bleeding during ITI in patients from the PedNet registry was dependent on inhibitor titer and ITI regimen, according to Kathelijn Fischer, MD.
Of 218 registry patients who were born during 1990-2009 and who had clinically relevant inhibitors and available data on joint bleeding, 157 had bleeding for at least 3 months. They were followed for a median of 26 months starting at age 16 months, and most had high titer inhibitors (52% had titers of 5-199 BU, and 32% had titers greater than 200 BU).
The bleeding rates in 12 patients without ITI who were on prophylaxis were similar to those in 89 such patients without prophylaxis (0.3 and 0.4 bleeds/month, respectively); no significant difference was seen between the groups based on inhibitor titer, Dr. Fischer of University Medical Center Utrecht, The Netherlands reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Similarly, the bleeding rate during ITI among those on prophylaxis did not differ significantly from the rate in those without prophylaxis (0.4 vs. 0.3/month, respectively), but the rate did increase significantly according to inhibitor titer: The rate increased from 0.05/month in the group with less than 5 BU, to 0.2/month in those with 5-199 BU, and to 0.5/month in the group with greater than 200 BU.
Further, while ITI dose did not affect bleeding, dosing frequency had a strong effect. The median rate with nondaily dosing in 36 patients vs. daily dosing in 63 patients was 0.4/month vs. 0.2/month, respectively, Dr. Fischer said.
She reported having no disclosures.
Immune tolerance induction, or ITI, in hemophilia A patients with inhibitor development against factor VIII (FVIII) appears to provide some protection against bleeding, as bleeding during ITI in patients from the PedNet registry was dependent on inhibitor titer and ITI regimen, according to Kathelijn Fischer, MD.
Of 218 registry patients who were born during 1990-2009 and who had clinically relevant inhibitors and available data on joint bleeding, 157 had bleeding for at least 3 months. They were followed for a median of 26 months starting at age 16 months, and most had high titer inhibitors (52% had titers of 5-199 BU, and 32% had titers greater than 200 BU).
The bleeding rates in 12 patients without ITI who were on prophylaxis were similar to those in 89 such patients without prophylaxis (0.3 and 0.4 bleeds/month, respectively); no significant difference was seen between the groups based on inhibitor titer, Dr. Fischer of University Medical Center Utrecht, The Netherlands reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Similarly, the bleeding rate during ITI among those on prophylaxis did not differ significantly from the rate in those without prophylaxis (0.4 vs. 0.3/month, respectively), but the rate did increase significantly according to inhibitor titer: The rate increased from 0.05/month in the group with less than 5 BU, to 0.2/month in those with 5-199 BU, and to 0.5/month in the group with greater than 200 BU.
Further, while ITI dose did not affect bleeding, dosing frequency had a strong effect. The median rate with nondaily dosing in 36 patients vs. daily dosing in 63 patients was 0.4/month vs. 0.2/month, respectively, Dr. Fischer said.
She reported having no disclosures.
FROM EAHAD 2017
Key clinical point:
Major finding: Median bleeding rate with nondaily vs. daily ITI dosing was 0.4/month vs. 0.2/month, respectively.
Data source: An analysis of 218 patients from the PedNet registry.
Disclosures: Dr. Fischer reported having no disclosures.
Study: No link between vaccines, inhibitor development
The administration of pediatric vaccinations in close proximity to factor VIII (FVIII) exposure was not associated with inhibitor development in previously untreated patients with severe hemophilia A in the PedNet Registry.
Similarly, no association was seen between recurrent vaccinations and inhibitor development, Dr. van den Berg reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Inhibitor development in this patient population is a multifactorial event, but these findings show no association between vaccinations administered early in life and increased inhibitor risk, she concluded.
Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
The administration of pediatric vaccinations in close proximity to factor VIII (FVIII) exposure was not associated with inhibitor development in previously untreated patients with severe hemophilia A in the PedNet Registry.
Similarly, no association was seen between recurrent vaccinations and inhibitor development, Dr. van den Berg reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Inhibitor development in this patient population is a multifactorial event, but these findings show no association between vaccinations administered early in life and increased inhibitor risk, she concluded.
Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
The administration of pediatric vaccinations in close proximity to factor VIII (FVIII) exposure was not associated with inhibitor development in previously untreated patients with severe hemophilia A in the PedNet Registry.
Similarly, no association was seen between recurrent vaccinations and inhibitor development, Dr. van den Berg reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Inhibitor development in this patient population is a multifactorial event, but these findings show no association between vaccinations administered early in life and increased inhibitor risk, she concluded.
Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
FROM EAHAD 2017
Key clinical point:
Major finding: The adjusted hazard ratio for any inhibitor development related to vaccinations in close proximity to FVIII was 0.65.
Data source: A review of data from 375 children in the PedNet Registry.
Disclosures: Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
Biannual HCC ultrasound cost-effective, lifesaving in cirrhosis
Twice-yearly ultrasound screening for liver cancer increases survival an average of almost 5 months in cirrhosis patients and costs about $32,415 per life-year gained, according to new economic modeling.
“The overall gain in life expectancy might be considered modest,” but it’s “good by cancer screening standards.” The cost, meanwhile, is within the accepted threshold in the United States of $30,000-50,000 per life-year gained (LYG), said French investigators led by statistician Benjamin Cadier of the French National Institute of Health and Medical Research, Paris (Hepatology. 2017 Feb 8. doi:10.1002/hep.28961).
To estimate probabilities and costs for various scenarios, the team combined data from two large French cohorts – one of viral cirrhosis, another of HCC – with French and U.S. pricing data, among other information. French costs with biannual screening were far less, at $1,754 per LYG, because of a 4-10–fold difference in the price of surveillance and first-line curative treatment. The team estimated that 10-year overall survival was 67% with current monitoring practices, and 76% with biannual ultrasound.
The mean survival increase from 6.8 to 7.2 years was attributed to earlier detection, higher access to curative first-line treatment, and better treatment results. Radiofrequency ablation (RFA), as opposed to liver resection or transplant, provided the best value for the money. “Our results indicate that [guideline-directed] monitoring for patients with cirrhosis is cost-effective,” the team said.
“Later detection not only reduced the likelihood of curative treatment, but also increased the proportion of [liver transplants] among the curative treatments,” they said.
In the modeling, when biannual ultrasound surveillance detected a suspicious nodule, the recall policy included magnetic resonance imaging or computerized tomography, and liver biopsy, if needed, based on recent international guidelines, with subsequent treatment.
There was no outside funding for the work. The lead investigator had no conflicts. Other investigators were consultants for Bayer, General Electric, AbbVie, Janssen, Bristol-Meyer Squibb, Gilead, and other companies.
Twice-yearly ultrasound screening for liver cancer increases survival an average of almost 5 months in cirrhosis patients and costs about $32,415 per life-year gained, according to new economic modeling.
“The overall gain in life expectancy might be considered modest,” but it’s “good by cancer screening standards.” The cost, meanwhile, is within the accepted threshold in the United States of $30,000-50,000 per life-year gained (LYG), said French investigators led by statistician Benjamin Cadier of the French National Institute of Health and Medical Research, Paris (Hepatology. 2017 Feb 8. doi:10.1002/hep.28961).
To estimate probabilities and costs for various scenarios, the team combined data from two large French cohorts – one of viral cirrhosis, another of HCC – with French and U.S. pricing data, among other information. French costs with biannual screening were far less, at $1,754 per LYG, because of a 4-10–fold difference in the price of surveillance and first-line curative treatment. The team estimated that 10-year overall survival was 67% with current monitoring practices, and 76% with biannual ultrasound.
The mean survival increase from 6.8 to 7.2 years was attributed to earlier detection, higher access to curative first-line treatment, and better treatment results. Radiofrequency ablation (RFA), as opposed to liver resection or transplant, provided the best value for the money. “Our results indicate that [guideline-directed] monitoring for patients with cirrhosis is cost-effective,” the team said.
“Later detection not only reduced the likelihood of curative treatment, but also increased the proportion of [liver transplants] among the curative treatments,” they said.
In the modeling, when biannual ultrasound surveillance detected a suspicious nodule, the recall policy included magnetic resonance imaging or computerized tomography, and liver biopsy, if needed, based on recent international guidelines, with subsequent treatment.
There was no outside funding for the work. The lead investigator had no conflicts. Other investigators were consultants for Bayer, General Electric, AbbVie, Janssen, Bristol-Meyer Squibb, Gilead, and other companies.
Twice-yearly ultrasound screening for liver cancer increases survival an average of almost 5 months in cirrhosis patients and costs about $32,415 per life-year gained, according to new economic modeling.
“The overall gain in life expectancy might be considered modest,” but it’s “good by cancer screening standards.” The cost, meanwhile, is within the accepted threshold in the United States of $30,000-50,000 per life-year gained (LYG), said French investigators led by statistician Benjamin Cadier of the French National Institute of Health and Medical Research, Paris (Hepatology. 2017 Feb 8. doi:10.1002/hep.28961).
To estimate probabilities and costs for various scenarios, the team combined data from two large French cohorts – one of viral cirrhosis, another of HCC – with French and U.S. pricing data, among other information. French costs with biannual screening were far less, at $1,754 per LYG, because of a 4-10–fold difference in the price of surveillance and first-line curative treatment. The team estimated that 10-year overall survival was 67% with current monitoring practices, and 76% with biannual ultrasound.
The mean survival increase from 6.8 to 7.2 years was attributed to earlier detection, higher access to curative first-line treatment, and better treatment results. Radiofrequency ablation (RFA), as opposed to liver resection or transplant, provided the best value for the money. “Our results indicate that [guideline-directed] monitoring for patients with cirrhosis is cost-effective,” the team said.
“Later detection not only reduced the likelihood of curative treatment, but also increased the proportion of [liver transplants] among the curative treatments,” they said.
In the modeling, when biannual ultrasound surveillance detected a suspicious nodule, the recall policy included magnetic resonance imaging or computerized tomography, and liver biopsy, if needed, based on recent international guidelines, with subsequent treatment.
There was no outside funding for the work. The lead investigator had no conflicts. Other investigators were consultants for Bayer, General Electric, AbbVie, Janssen, Bristol-Meyer Squibb, Gilead, and other companies.
FROM HEPATOLOGY
Key clinical point:
Major finding: Twice-a-year ultrasound to catch liver cancer early increases survival an average of nearly 5 months in cirrhosis patients, and costs about $32,415 per life-year gained.
Data source: Economic modeling of two French cohorts.
Disclosures: There was no outside funding for the work. The lead investigator had no conflicts. Other investigators were consultants for Bayer, General Electric, AbbVie, Janssen, Bristol-Meyer Squibb, Gilead, and other companies.
Psoriatic arthritis raises diabetes risk
Psoriatic arthritis raises the risk of type 2 diabetes, and the risk correlates with higher disease activity, according to Canadian investigators.
They reviewed 1,065 patients free of diabetes when they entered treatment at the University of Toronto psoriatic arthritis (PsA) clinic during 1978-2014; 73 developed type 2 diabetes.
“This finding highlights the need to screen for DM [diabetes mellitis] in patients with PsA, especially in those with more active joint disease and elevated inflammatory markers. The control of inflammation may reduce the risk of developing DM,” said investigators led by Lihi Eder, MD, a research fellow at the University of Toronto (J Rheumatol. 2017 Feb 1; doi: 10.3899/jrheum.160861).
Psoriasis has been linked to diabetes before; the association with PsA, at least until now, has been less well supported.
Chronic inflammation could be part of the issue; it’s also been linked before to diabetes, independently of insulin resistance and obesity. More severe psoriasis, as indicated by higher Psoriasis Area and Severity Index scores, was associated with diabetes risk in the study, but fell out as an independent predictor after adjustment for obesity and other confounders.
Also, “part of the increased risk of cardiovascular in PsA may be attributed to the higher prevalence of DM, which was found in our study,” the investigators said.
Data about smoking, metabolic syndrome, and C-reactive protein weren’t routinely collected in the earlier years of the cohort, so could not be assessed. “It is possible that some of these variables could have modified the identified link between the extent of inflammation and DM risk,” they said.
Patients were 54 years old on average at baseline, and 56% were men. The mean duration of psoriasis at clinic presentation was 15.4 years, and of psoriatic arthritis 6.5 years. The mean duration of follow-up was 9.1 years.
Dr. Eder was supported by the Krembil Foundation and a Canadian Institutes of Health Research fellowship award.
Psoriatic arthritis raises the risk of type 2 diabetes, and the risk correlates with higher disease activity, according to Canadian investigators.
They reviewed 1,065 patients free of diabetes when they entered treatment at the University of Toronto psoriatic arthritis (PsA) clinic during 1978-2014; 73 developed type 2 diabetes.
“This finding highlights the need to screen for DM [diabetes mellitis] in patients with PsA, especially in those with more active joint disease and elevated inflammatory markers. The control of inflammation may reduce the risk of developing DM,” said investigators led by Lihi Eder, MD, a research fellow at the University of Toronto (J Rheumatol. 2017 Feb 1; doi: 10.3899/jrheum.160861).
Psoriasis has been linked to diabetes before; the association with PsA, at least until now, has been less well supported.
Chronic inflammation could be part of the issue; it’s also been linked before to diabetes, independently of insulin resistance and obesity. More severe psoriasis, as indicated by higher Psoriasis Area and Severity Index scores, was associated with diabetes risk in the study, but fell out as an independent predictor after adjustment for obesity and other confounders.
Also, “part of the increased risk of cardiovascular in PsA may be attributed to the higher prevalence of DM, which was found in our study,” the investigators said.
Data about smoking, metabolic syndrome, and C-reactive protein weren’t routinely collected in the earlier years of the cohort, so could not be assessed. “It is possible that some of these variables could have modified the identified link between the extent of inflammation and DM risk,” they said.
Patients were 54 years old on average at baseline, and 56% were men. The mean duration of psoriasis at clinic presentation was 15.4 years, and of psoriatic arthritis 6.5 years. The mean duration of follow-up was 9.1 years.
Dr. Eder was supported by the Krembil Foundation and a Canadian Institutes of Health Research fellowship award.
Psoriatic arthritis raises the risk of type 2 diabetes, and the risk correlates with higher disease activity, according to Canadian investigators.
They reviewed 1,065 patients free of diabetes when they entered treatment at the University of Toronto psoriatic arthritis (PsA) clinic during 1978-2014; 73 developed type 2 diabetes.
“This finding highlights the need to screen for DM [diabetes mellitis] in patients with PsA, especially in those with more active joint disease and elevated inflammatory markers. The control of inflammation may reduce the risk of developing DM,” said investigators led by Lihi Eder, MD, a research fellow at the University of Toronto (J Rheumatol. 2017 Feb 1; doi: 10.3899/jrheum.160861).
Psoriasis has been linked to diabetes before; the association with PsA, at least until now, has been less well supported.
Chronic inflammation could be part of the issue; it’s also been linked before to diabetes, independently of insulin resistance and obesity. More severe psoriasis, as indicated by higher Psoriasis Area and Severity Index scores, was associated with diabetes risk in the study, but fell out as an independent predictor after adjustment for obesity and other confounders.
Also, “part of the increased risk of cardiovascular in PsA may be attributed to the higher prevalence of DM, which was found in our study,” the investigators said.
Data about smoking, metabolic syndrome, and C-reactive protein weren’t routinely collected in the earlier years of the cohort, so could not be assessed. “It is possible that some of these variables could have modified the identified link between the extent of inflammation and DM risk,” they said.
Patients were 54 years old on average at baseline, and 56% were men. The mean duration of psoriasis at clinic presentation was 15.4 years, and of psoriatic arthritis 6.5 years. The mean duration of follow-up was 9.1 years.
Dr. Eder was supported by the Krembil Foundation and a Canadian Institutes of Health Research fellowship award.
FROM THE JOURNAL OF RHEUMATOLOGY
Key clinical point:
Major finding: Morning tender joint count (HR 1.53), morning erythrocyte sedimentation rate (HR 1.21), and body mass index (HR 1.09) significantly predicted diabetes.
Data source: A review of 1,065 patients free of diabetes when they entered treatment at the University of Toronto psoriatic arthritis (PsA) clinic during 1978-2014.
Disclosures: The lead investigator was supported by the Krembil Foundation and a Canadian Institutes of Health Research fellowship award.
New ACC guidance on periprocedural management of anticoagulation in A-fib falls short
SNOWMASS, COLO. – The 2017 American College of Cardiology Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation is a dense, 28-page document filled with multicolored flow charts and six separate management algorithms. But this complex scheme is no substitute for practical clinical judgment and individualized decision making, N.A. Mark Estes, MD, said at the Annual Cardiovascular Conference at Snowmass.
The decision pathway attempts to guide physicians in making decisions about whether and how to interrupt anticoagulation or bridge with a parenteral agent such as low-molecular-weight heparin, and how to restart oral anticoagulation post-procedure (J Am Coll Cardiol. 2017 Jan 5; doi: 10.1016/j.jacc.2016.11.024).
The document defies concise summary. Dr. Estes chose instead to describe the approach he uses in clinical decision-making regarding anticoagulation in patients with atrial fibrillation undergoing invasive procedures. He relies upon three elements: stroke risk as assessed by CHA2DS2-VASc score; bleeding risk using the HAS-BLED score; and the inherent bleeding risk of the procedure itself.
“An important thing to remember is, any procedure done along the spinal cord or intracranially carries an extremely high risk of bleeding,” the cardiologist noted by way of example.
If a patient with atrial fibrillation has a CHA2DS2-VASc score of 2 or less, he doesn’t offer bridging regardless of the HAS-BLED score. If the stroke risk is high as defined by a CHA2DS2-VASc score of 7 or more, and the patient’s bleeding risk isn’t high, meaning the HAS-BLED score is less than 3, he seriously considers bridging, provided that the patient’s oral anticoagulant is warfarin.
“I don’t think at this point we should be bridging with the DOACs [the direct oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban]. All the available data on bridging with the DOACs indicates that it results in a high risk of bleeding with no reduction in risk of stroke,” Dr. Estes said.
The “vast majority” of patients with atrial fibrillation facing surgery have a CHA2DS2-VASc score of 3-7 and thus fall into a category where individualized consideration of the risks and benefits of bridging rules. The large, randomized, double-blind BRIDGE trial speaks to this population. In this study of atrial fibrillation patients on warfarin prior to their procedure, bridging with low-molecular-weight heparin resulted in an increased risk of major bleeding with no reduction in stroke risk compared with a temporary halt of warfarin with no bridging (N Engl J Med. 2015 Aug 27;373[9]:823-33).
“This is a no-brainer,” Dr. Estes said. “When you bridge, your patients bleed more, and you don’t reduce strokes.”
The real challenge is the type of patient who falls into what he called “the dilemma zone,” with a CHA2DS2-VASc score of 7 or more and a HAS-BLED score of 3 or higher, meaning they are at very high risk for both stroke and bleeding.
“I have a discussion with those patients. I usually do not bridge. I’m biased because of having done a lot more harm than good in bridging,” the cardiologist said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
In reviewing Dr. Estes’ comments on a consensus statement regarding anticoagulation bridging for patients with atrial fibrillation, the most important point is that there are minimal good data to support decision making; therefore, treatments need to be individualized to the patient. He provides a reasonable paradigm for his own decision making in these complex patients. Ultimately, until there is better evidence, the decision on whether to bridge or not to bridge patients’ anticoagulation will continue to be an individual choice based upon bleeding risk with the planned surgical procedure, potential for significant adverse outcomes if bleeding occurs, and the risk of stroke or other embolic phenomenon with cessation of anticoagulation.
Dr. Linda Harris is the division chief, vascular surgery, at the State University of New York at Buffalo and an associate editor of Vascular Specialist.
In reviewing Dr. Estes’ comments on a consensus statement regarding anticoagulation bridging for patients with atrial fibrillation, the most important point is that there are minimal good data to support decision making; therefore, treatments need to be individualized to the patient. He provides a reasonable paradigm for his own decision making in these complex patients. Ultimately, until there is better evidence, the decision on whether to bridge or not to bridge patients’ anticoagulation will continue to be an individual choice based upon bleeding risk with the planned surgical procedure, potential for significant adverse outcomes if bleeding occurs, and the risk of stroke or other embolic phenomenon with cessation of anticoagulation.
Dr. Linda Harris is the division chief, vascular surgery, at the State University of New York at Buffalo and an associate editor of Vascular Specialist.
In reviewing Dr. Estes’ comments on a consensus statement regarding anticoagulation bridging for patients with atrial fibrillation, the most important point is that there are minimal good data to support decision making; therefore, treatments need to be individualized to the patient. He provides a reasonable paradigm for his own decision making in these complex patients. Ultimately, until there is better evidence, the decision on whether to bridge or not to bridge patients’ anticoagulation will continue to be an individual choice based upon bleeding risk with the planned surgical procedure, potential for significant adverse outcomes if bleeding occurs, and the risk of stroke or other embolic phenomenon with cessation of anticoagulation.
Dr. Linda Harris is the division chief, vascular surgery, at the State University of New York at Buffalo and an associate editor of Vascular Specialist.
SNOWMASS, COLO. – The 2017 American College of Cardiology Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation is a dense, 28-page document filled with multicolored flow charts and six separate management algorithms. But this complex scheme is no substitute for practical clinical judgment and individualized decision making, N.A. Mark Estes, MD, said at the Annual Cardiovascular Conference at Snowmass.
The decision pathway attempts to guide physicians in making decisions about whether and how to interrupt anticoagulation or bridge with a parenteral agent such as low-molecular-weight heparin, and how to restart oral anticoagulation post-procedure (J Am Coll Cardiol. 2017 Jan 5; doi: 10.1016/j.jacc.2016.11.024).
The document defies concise summary. Dr. Estes chose instead to describe the approach he uses in clinical decision-making regarding anticoagulation in patients with atrial fibrillation undergoing invasive procedures. He relies upon three elements: stroke risk as assessed by CHA2DS2-VASc score; bleeding risk using the HAS-BLED score; and the inherent bleeding risk of the procedure itself.
“An important thing to remember is, any procedure done along the spinal cord or intracranially carries an extremely high risk of bleeding,” the cardiologist noted by way of example.
If a patient with atrial fibrillation has a CHA2DS2-VASc score of 2 or less, he doesn’t offer bridging regardless of the HAS-BLED score. If the stroke risk is high as defined by a CHA2DS2-VASc score of 7 or more, and the patient’s bleeding risk isn’t high, meaning the HAS-BLED score is less than 3, he seriously considers bridging, provided that the patient’s oral anticoagulant is warfarin.
“I don’t think at this point we should be bridging with the DOACs [the direct oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban]. All the available data on bridging with the DOACs indicates that it results in a high risk of bleeding with no reduction in risk of stroke,” Dr. Estes said.
The “vast majority” of patients with atrial fibrillation facing surgery have a CHA2DS2-VASc score of 3-7 and thus fall into a category where individualized consideration of the risks and benefits of bridging rules. The large, randomized, double-blind BRIDGE trial speaks to this population. In this study of atrial fibrillation patients on warfarin prior to their procedure, bridging with low-molecular-weight heparin resulted in an increased risk of major bleeding with no reduction in stroke risk compared with a temporary halt of warfarin with no bridging (N Engl J Med. 2015 Aug 27;373[9]:823-33).
“This is a no-brainer,” Dr. Estes said. “When you bridge, your patients bleed more, and you don’t reduce strokes.”
The real challenge is the type of patient who falls into what he called “the dilemma zone,” with a CHA2DS2-VASc score of 7 or more and a HAS-BLED score of 3 or higher, meaning they are at very high risk for both stroke and bleeding.
“I have a discussion with those patients. I usually do not bridge. I’m biased because of having done a lot more harm than good in bridging,” the cardiologist said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
SNOWMASS, COLO. – The 2017 American College of Cardiology Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation is a dense, 28-page document filled with multicolored flow charts and six separate management algorithms. But this complex scheme is no substitute for practical clinical judgment and individualized decision making, N.A. Mark Estes, MD, said at the Annual Cardiovascular Conference at Snowmass.
The decision pathway attempts to guide physicians in making decisions about whether and how to interrupt anticoagulation or bridge with a parenteral agent such as low-molecular-weight heparin, and how to restart oral anticoagulation post-procedure (J Am Coll Cardiol. 2017 Jan 5; doi: 10.1016/j.jacc.2016.11.024).
The document defies concise summary. Dr. Estes chose instead to describe the approach he uses in clinical decision-making regarding anticoagulation in patients with atrial fibrillation undergoing invasive procedures. He relies upon three elements: stroke risk as assessed by CHA2DS2-VASc score; bleeding risk using the HAS-BLED score; and the inherent bleeding risk of the procedure itself.
“An important thing to remember is, any procedure done along the spinal cord or intracranially carries an extremely high risk of bleeding,” the cardiologist noted by way of example.
If a patient with atrial fibrillation has a CHA2DS2-VASc score of 2 or less, he doesn’t offer bridging regardless of the HAS-BLED score. If the stroke risk is high as defined by a CHA2DS2-VASc score of 7 or more, and the patient’s bleeding risk isn’t high, meaning the HAS-BLED score is less than 3, he seriously considers bridging, provided that the patient’s oral anticoagulant is warfarin.
“I don’t think at this point we should be bridging with the DOACs [the direct oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban]. All the available data on bridging with the DOACs indicates that it results in a high risk of bleeding with no reduction in risk of stroke,” Dr. Estes said.
The “vast majority” of patients with atrial fibrillation facing surgery have a CHA2DS2-VASc score of 3-7 and thus fall into a category where individualized consideration of the risks and benefits of bridging rules. The large, randomized, double-blind BRIDGE trial speaks to this population. In this study of atrial fibrillation patients on warfarin prior to their procedure, bridging with low-molecular-weight heparin resulted in an increased risk of major bleeding with no reduction in stroke risk compared with a temporary halt of warfarin with no bridging (N Engl J Med. 2015 Aug 27;373[9]:823-33).
“This is a no-brainer,” Dr. Estes said. “When you bridge, your patients bleed more, and you don’t reduce strokes.”
The real challenge is the type of patient who falls into what he called “the dilemma zone,” with a CHA2DS2-VASc score of 7 or more and a HAS-BLED score of 3 or higher, meaning they are at very high risk for both stroke and bleeding.
“I have a discussion with those patients. I usually do not bridge. I’m biased because of having done a lot more harm than good in bridging,” the cardiologist said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS