Andrew D. Bowser

Image from Armed Forces Institute of Pathology

The AP-1 transcription factor family is of “major importance” in acute myeloid leukemia (AML), according to researchers.

The team said they identified transcription factor networks specific to AML subtypes, which showed that leukemic growth is dependent upon certain transcription factors, and “the global activation of signaling pathways parallels a growth dependence on AP-1 activity in multiple types of AML.”

Constanze Bonifer, PhD, of the University of Birmingham in the U.K., and her colleagues conducted this research and detailed their findings in Nature Genetics.

The researchers noted that previous work revealed the existence of gene regulatory networks in different types of AML classified by gene expression and DNA methylation patterns.

“Our work now defines these networks in detail and shows that leukemic drivers determine the regulatory phenotype by establishing and maintaining specific gene regulatory and signaling networks that are distinct from those in normal cells,” Dr. Bonifer and her colleagues wrote.

The researchers combined data obtained via several analytic techniques to construct transcription factor networks in normal CD34+ cells and cells from AML patients with defined mutations, including RUNX1 mutations, t(8;21) translocations, mutations of both alleles of the CEBPA gene, and FLT3-ITD with or without NPM1 mutation.

The AP-1 family network was of “high regulatory relevance” for all AML subtypes evaluated, the team reported.

Follow-up in vitro and in vivo studies confirmed the importance of AP-1 for different AML subtypes.

In the in vitro study, the researchers transduced AML cells with a doxycycline-inducible version of a dominant-negative (dn) FOS protein.

“AP-1 is a heterodimer formed by members of the FOS, JUN, ATF, CREB, and JDP families of transcription factors,” the researchers wrote. “[T]hus, it is challenging to target by defined RNA interference approaches.”

Results of the in vitro study showed that induction of dnFOS, mediated by doxycycline, inhibited proliferation of t(8;21)+ Kasumi-1 cells and FLT3-ITD-expressing MV4-11 cells.

Induction of dnFOS also inhibited the colony-forming ability of primary CD34+ FLT3-ITD cells but not CD34+ hematopoietic stem and progenitor cells.

To evaluate the relevance of AP-1 for leukemia propagation in vivo, the researchers transplanted either of two cell lines—Kasumi-1 or MV4-11—expressing inducible dnFOS in immunodeficient mice.

With Kasumi-1, granulosarcomas developed in six of seven untreated control mice and two mice treated with doxycycline, neither of which expressed the inducible protein.

With MV4-11, doxycycline inhibited leukemia development, and untreated mice rapidly developed tumors.

The researchers declared no competing interests related to this work, which was funded by Bloodwise, Cancer Research UK, a Kay Kendall Clinical Training Fellowship, and an MRC/Leuka Clinical Training Fellowship.

Image from Armed Forces Institute of Pathology

The AP-1 transcription factor family is of “major importance” in acute myeloid leukemia (AML), according to researchers.

The team said they identified transcription factor networks specific to AML subtypes, which showed that leukemic growth is dependent upon certain transcription factors, and “the global activation of signaling pathways parallels a growth dependence on AP-1 activity in multiple types of AML.”

Constanze Bonifer, PhD, of the University of Birmingham in the U.K., and her colleagues conducted this research and detailed their findings in Nature Genetics.

The researchers noted that previous work revealed the existence of gene regulatory networks in different types of AML classified by gene expression and DNA methylation patterns.

“Our work now defines these networks in detail and shows that leukemic drivers determine the regulatory phenotype by establishing and maintaining specific gene regulatory and signaling networks that are distinct from those in normal cells,” Dr. Bonifer and her colleagues wrote.

The researchers combined data obtained via several analytic techniques to construct transcription factor networks in normal CD34+ cells and cells from AML patients with defined mutations, including RUNX1 mutations, t(8;21) translocations, mutations of both alleles of the CEBPA gene, and FLT3-ITD with or without NPM1 mutation.

The AP-1 family network was of “high regulatory relevance” for all AML subtypes evaluated, the team reported.

Follow-up in vitro and in vivo studies confirmed the importance of AP-1 for different AML subtypes.

In the in vitro study, the researchers transduced AML cells with a doxycycline-inducible version of a dominant-negative (dn) FOS protein.

“AP-1 is a heterodimer formed by members of the FOS, JUN, ATF, CREB, and JDP families of transcription factors,” the researchers wrote. “[T]hus, it is challenging to target by defined RNA interference approaches.”

Results of the in vitro study showed that induction of dnFOS, mediated by doxycycline, inhibited proliferation of t(8;21)+ Kasumi-1 cells and FLT3-ITD-expressing MV4-11 cells.

Induction of dnFOS also inhibited the colony-forming ability of primary CD34+ FLT3-ITD cells but not CD34+ hematopoietic stem and progenitor cells.

To evaluate the relevance of AP-1 for leukemia propagation in vivo, the researchers transplanted either of two cell lines—Kasumi-1 or MV4-11—expressing inducible dnFOS in immunodeficient mice.

With Kasumi-1, granulosarcomas developed in six of seven untreated control mice and two mice treated with doxycycline, neither of which expressed the inducible protein.

With MV4-11, doxycycline inhibited leukemia development, and untreated mice rapidly developed tumors.

The researchers declared no competing interests related to this work, which was funded by Bloodwise, Cancer Research UK, a Kay Kendall Clinical Training Fellowship, and an MRC/Leuka Clinical Training Fellowship.

Image from Armed Forces Institute of Pathology

The AP-1 transcription factor family is of “major importance” in acute myeloid leukemia (AML), according to researchers.

The team said they identified transcription factor networks specific to AML subtypes, which showed that leukemic growth is dependent upon certain transcription factors, and “the global activation of signaling pathways parallels a growth dependence on AP-1 activity in multiple types of AML.”

Constanze Bonifer, PhD, of the University of Birmingham in the U.K., and her colleagues conducted this research and detailed their findings in Nature Genetics.

The researchers noted that previous work revealed the existence of gene regulatory networks in different types of AML classified by gene expression and DNA methylation patterns.

“Our work now defines these networks in detail and shows that leukemic drivers determine the regulatory phenotype by establishing and maintaining specific gene regulatory and signaling networks that are distinct from those in normal cells,” Dr. Bonifer and her colleagues wrote.

The researchers combined data obtained via several analytic techniques to construct transcription factor networks in normal CD34+ cells and cells from AML patients with defined mutations, including RUNX1 mutations, t(8;21) translocations, mutations of both alleles of the CEBPA gene, and FLT3-ITD with or without NPM1 mutation.

The AP-1 family network was of “high regulatory relevance” for all AML subtypes evaluated, the team reported.

Follow-up in vitro and in vivo studies confirmed the importance of AP-1 for different AML subtypes.

In the in vitro study, the researchers transduced AML cells with a doxycycline-inducible version of a dominant-negative (dn) FOS protein.

“AP-1 is a heterodimer formed by members of the FOS, JUN, ATF, CREB, and JDP families of transcription factors,” the researchers wrote. “[T]hus, it is challenging to target by defined RNA interference approaches.”

Results of the in vitro study showed that induction of dnFOS, mediated by doxycycline, inhibited proliferation of t(8;21)+ Kasumi-1 cells and FLT3-ITD-expressing MV4-11 cells.

Induction of dnFOS also inhibited the colony-forming ability of primary CD34+ FLT3-ITD cells but not CD34+ hematopoietic stem and progenitor cells.

To evaluate the relevance of AP-1 for leukemia propagation in vivo, the researchers transplanted either of two cell lines—Kasumi-1 or MV4-11—expressing inducible dnFOS in immunodeficient mice.

With Kasumi-1, granulosarcomas developed in six of seven untreated control mice and two mice treated with doxycycline, neither of which expressed the inducible protein.

With MV4-11, doxycycline inhibited leukemia development, and untreated mice rapidly developed tumors.

The researchers declared no competing interests related to this work, which was funded by Bloodwise, Cancer Research UK, a Kay Kendall Clinical Training Fellowship, and an MRC/Leuka Clinical Training Fellowship.

Bronchoscope reprocessing was ineffective for eliminating all residual biocontamination even when done in accordance with endoscope reprocessing standards, according to results of a prospective, multisite investigation.

CDC/Elizabeth H. White, MS

All clinically used bronchoscopes evaluated in the study had residual contamination after reprocessing, and more than half showed microbial growth, the researchers reported in the journal CHEST.

These findings suggest that systematic changes are needed to improve cleaning and disinfection and to avoid the retention of bioburden, said researcher Cori L. Ofstead, MSPH, and her coinvestigators (Chest 2018 Nov;154[5]:1024-34).

“Evidence-based, bronchoscope-specific reprocessing and maintenance guidelines are needed, along with quality management programs to ensure that these complex processes are carried out effectively,” Ms. Ofstead and her colleagues said in their report.

Institutions also should consider shifting from high-level disinfection (HLD) to sterilization to reduce patient exposure to contaminated bronchoscopes, they added.

The study was conducted in three large, tertiary hospitals that contributed a total of 24 clinically used devices. That total comprised nine therapeutic, nine pediatric, and six endobronchial ultrasound (EBUS) bronchoscopes that were all reprocessed in accordance with each institution’s standard practices.

Proteins were detected in 100% of the bronchoscopes after HLD, according to researchers.

Looking at 20 paired postcleaning and post-HLD samples, the researchers found microbial growth in 11 of 20 (55%) manually-cleaned bronchoscopes and 14 of 24 (58%) bronchoscopes after HLD. The post-HLD samples included mold and recognized pathogens such as Escherichia coli, as well as normal flora and environmental bacteria, they said.

All 24 of the bronchoscopes had visible irregularities, including brown, red, or oily residue, retained fluid, debris in channels, scratches, or damage at insertion tubes and distal ends, they added.

Substandard reprocessing practices were found at two of the three participating institutions, according to the investigators. At one site, technicians reused syringes to flush channels with alcohol stored in an uncovered bowl during the day, according to the report, and bronchoscopes at that site were dried with reused towels and stored in a cabinet without active ventilation.

“Nursing staff were observed handling patient-ready bronchoscopes with bare hands,” the investigators reported.

Although clinical outcomes were not measured, the contamination, microbial growth, and defects observed in this study are “worrisome,” according to authors, because of the high infection risk in many patients undergoing bronchoscopy, and because of the infectious outbreaks and patient deaths linked to contaminated bronchoscopes in previous investigations.

Research funding for the study was provided by 3M Company. Study materials were provided by 3M Company and Healthmark Industries. Ms. Ofstead and several coauthors reported employment with Ofstead & Associates, which has received research funding and speaking fees related to infection prevention from 3M Company, Healthmark Industries, Advanced Sterilization Products (Johnson & Johnson), and others.

The senior author of the study was J. Scott Ferguson, MD, of the division of pulmonary and critical care medicine at the University of Wisconsin School of Medicine and Public Health, Madison. Dr. Ferguson provided disclosures related to NewWave Medical, Pharmaceutical Product Development, Oncocyte, Concordia, and PneumRx.

SOURCE: Ofstead C et al. Chest. 2018 Nov;154(5):1024-34.

Bronchoscope reprocessing was ineffective for eliminating all residual biocontamination even when done in accordance with endoscope reprocessing standards, according to results of a prospective, multisite investigation.

CDC/Elizabeth H. White, MS

All clinically used bronchoscopes evaluated in the study had residual contamination after reprocessing, and more than half showed microbial growth, the researchers reported in the journal CHEST.

These findings suggest that systematic changes are needed to improve cleaning and disinfection and to avoid the retention of bioburden, said researcher Cori L. Ofstead, MSPH, and her coinvestigators (Chest 2018 Nov;154[5]:1024-34).

“Evidence-based, bronchoscope-specific reprocessing and maintenance guidelines are needed, along with quality management programs to ensure that these complex processes are carried out effectively,” Ms. Ofstead and her colleagues said in their report.

Institutions also should consider shifting from high-level disinfection (HLD) to sterilization to reduce patient exposure to contaminated bronchoscopes, they added.

The study was conducted in three large, tertiary hospitals that contributed a total of 24 clinically used devices. That total comprised nine therapeutic, nine pediatric, and six endobronchial ultrasound (EBUS) bronchoscopes that were all reprocessed in accordance with each institution’s standard practices.

Proteins were detected in 100% of the bronchoscopes after HLD, according to researchers.

Looking at 20 paired postcleaning and post-HLD samples, the researchers found microbial growth in 11 of 20 (55%) manually-cleaned bronchoscopes and 14 of 24 (58%) bronchoscopes after HLD. The post-HLD samples included mold and recognized pathogens such as Escherichia coli, as well as normal flora and environmental bacteria, they said.

All 24 of the bronchoscopes had visible irregularities, including brown, red, or oily residue, retained fluid, debris in channels, scratches, or damage at insertion tubes and distal ends, they added.

Substandard reprocessing practices were found at two of the three participating institutions, according to the investigators. At one site, technicians reused syringes to flush channels with alcohol stored in an uncovered bowl during the day, according to the report, and bronchoscopes at that site were dried with reused towels and stored in a cabinet without active ventilation.

“Nursing staff were observed handling patient-ready bronchoscopes with bare hands,” the investigators reported.

Although clinical outcomes were not measured, the contamination, microbial growth, and defects observed in this study are “worrisome,” according to authors, because of the high infection risk in many patients undergoing bronchoscopy, and because of the infectious outbreaks and patient deaths linked to contaminated bronchoscopes in previous investigations.

Research funding for the study was provided by 3M Company. Study materials were provided by 3M Company and Healthmark Industries. Ms. Ofstead and several coauthors reported employment with Ofstead & Associates, which has received research funding and speaking fees related to infection prevention from 3M Company, Healthmark Industries, Advanced Sterilization Products (Johnson & Johnson), and others.

The senior author of the study was J. Scott Ferguson, MD, of the division of pulmonary and critical care medicine at the University of Wisconsin School of Medicine and Public Health, Madison. Dr. Ferguson provided disclosures related to NewWave Medical, Pharmaceutical Product Development, Oncocyte, Concordia, and PneumRx.

SOURCE: Ofstead C et al. Chest. 2018 Nov;154(5):1024-34.

Bronchoscope reprocessing was ineffective for eliminating all residual biocontamination even when done in accordance with endoscope reprocessing standards, according to results of a prospective, multisite investigation.

CDC/Elizabeth H. White, MS

All clinically used bronchoscopes evaluated in the study had residual contamination after reprocessing, and more than half showed microbial growth, the researchers reported in the journal CHEST.

These findings suggest that systematic changes are needed to improve cleaning and disinfection and to avoid the retention of bioburden, said researcher Cori L. Ofstead, MSPH, and her coinvestigators (Chest 2018 Nov;154[5]:1024-34).

“Evidence-based, bronchoscope-specific reprocessing and maintenance guidelines are needed, along with quality management programs to ensure that these complex processes are carried out effectively,” Ms. Ofstead and her colleagues said in their report.

Institutions also should consider shifting from high-level disinfection (HLD) to sterilization to reduce patient exposure to contaminated bronchoscopes, they added.

The study was conducted in three large, tertiary hospitals that contributed a total of 24 clinically used devices. That total comprised nine therapeutic, nine pediatric, and six endobronchial ultrasound (EBUS) bronchoscopes that were all reprocessed in accordance with each institution’s standard practices.

Proteins were detected in 100% of the bronchoscopes after HLD, according to researchers.

Looking at 20 paired postcleaning and post-HLD samples, the researchers found microbial growth in 11 of 20 (55%) manually-cleaned bronchoscopes and 14 of 24 (58%) bronchoscopes after HLD. The post-HLD samples included mold and recognized pathogens such as Escherichia coli, as well as normal flora and environmental bacteria, they said.

All 24 of the bronchoscopes had visible irregularities, including brown, red, or oily residue, retained fluid, debris in channels, scratches, or damage at insertion tubes and distal ends, they added.

Substandard reprocessing practices were found at two of the three participating institutions, according to the investigators. At one site, technicians reused syringes to flush channels with alcohol stored in an uncovered bowl during the day, according to the report, and bronchoscopes at that site were dried with reused towels and stored in a cabinet without active ventilation.

“Nursing staff were observed handling patient-ready bronchoscopes with bare hands,” the investigators reported.

Although clinical outcomes were not measured, the contamination, microbial growth, and defects observed in this study are “worrisome,” according to authors, because of the high infection risk in many patients undergoing bronchoscopy, and because of the infectious outbreaks and patient deaths linked to contaminated bronchoscopes in previous investigations.

Research funding for the study was provided by 3M Company. Study materials were provided by 3M Company and Healthmark Industries. Ms. Ofstead and several coauthors reported employment with Ofstead & Associates, which has received research funding and speaking fees related to infection prevention from 3M Company, Healthmark Industries, Advanced Sterilization Products (Johnson & Johnson), and others.

The senior author of the study was J. Scott Ferguson, MD, of the division of pulmonary and critical care medicine at the University of Wisconsin School of Medicine and Public Health, Madison. Dr. Ferguson provided disclosures related to NewWave Medical, Pharmaceutical Product Development, Oncocyte, Concordia, and PneumRx.

SOURCE: Ofstead C et al. Chest. 2018 Nov;154(5):1024-34.

The AP-1 transcription factor family, important in many tumor types, plays a major role in acute myeloid leukemia, according to researchers who conducted a comprehensive global analysis of gene regulatory networks involved in this disease.

©GunarsB/Thinkstock

This observation suggests new opportunities for targeted treatment of AML, according to the researchers, led by Peter N. Cockerill, PhD, and Constanze Bonifer, PhD, with the Institute of Cancer and Genomic Sciences, University of Birmingham, England.

“Induced and aberrantly expressed transcription factors are not bystanders, but are important for network maintenance and leukemic growth,” the investigators wrote in Nature Genetics.

Investigators combined data obtained via several different analytic techniques to construct transcription factor networks in normal CD34+ cells and cells from specific subgroups of subjects with defined mutations, including RUNX1 mutations, t(8;21) translocations, mutations of both alleles of the CEBPA gene, and FLT3-ITD with or without NPM1 mutation.

The AP-1 family network was of “high regulatory relevance” for all AML subtypes evaluated, the investigators reported.

Previous work revealed the existence of gene regulatory networks in different types of AML classified by gene expression and DNA-methylation patterns.

“Our work now defines these networks in detail, and shows that leukemic drivers determine the regulatory phenotype by establishing and maintaining specific gene regulatory and signaling networks that are distinct from those in normal cells,” the authors said in their report.

Follow-up in vitro and in vivo studies confirmed the importance of AP-1 for different AML subtypes.

In the in vitro study, investigators transduced AML cells with a doxycycline-inducible version of a dominant negative FOS protein.

“AP-1 is a heterodimer formed by members of the FOS, JUN, ATF, CREB and JDP families of transcription factors, thus it is challenging to target by defined RNA interference approaches,” the investigators explained.

Results of the in vitro study showed that induction of that protein, mediated by doxycycline, inhibited proliferation and colony-forming ability in AML cell lines.

To evaluate the relevance of AP-1 for leukemia propagation in vivo, they transplanted two different types of cells expressing inducible dominant negative FOS protein in immunodeficient mice.

For the first cell type, granulosarcomas developed in six out of seven mice in a control group, but in only two mice treated with doxycycline, neither of which expressed the inducible protein, suggesting that the transgene was silenced, according to the investigators. For the second cell type, doxycycline inhibited leukemia development, while untreated mice rapidly developed tumors.

“Taken together, these findings demonstrate the importance of AP-1 for several AML subtypes and emphasize the potential of transcriptional network analyses to predict transcription factors crucial for malignant propagation,” the investigators wrote.

They declared no competing interests related to their research, which was funded by Bloodwise, Cancer Research UK, a Kay Kendall Clinical Training Fellowship and a MRC/Leuka Clinical Training Fellowship.

SOURCE: Assi SA et al. Nat Genet. 2018 Nov 12. doi: 10.1038/s41588-018-0270-1.

The AP-1 transcription factor family, important in many tumor types, plays a major role in acute myeloid leukemia, according to researchers who conducted a comprehensive global analysis of gene regulatory networks involved in this disease.

©GunarsB/Thinkstock

This observation suggests new opportunities for targeted treatment of AML, according to the researchers, led by Peter N. Cockerill, PhD, and Constanze Bonifer, PhD, with the Institute of Cancer and Genomic Sciences, University of Birmingham, England.

“Induced and aberrantly expressed transcription factors are not bystanders, but are important for network maintenance and leukemic growth,” the investigators wrote in Nature Genetics.

Investigators combined data obtained via several different analytic techniques to construct transcription factor networks in normal CD34+ cells and cells from specific subgroups of subjects with defined mutations, including RUNX1 mutations, t(8;21) translocations, mutations of both alleles of the CEBPA gene, and FLT3-ITD with or without NPM1 mutation.

The AP-1 family network was of “high regulatory relevance” for all AML subtypes evaluated, the investigators reported.

Previous work revealed the existence of gene regulatory networks in different types of AML classified by gene expression and DNA-methylation patterns.

“Our work now defines these networks in detail, and shows that leukemic drivers determine the regulatory phenotype by establishing and maintaining specific gene regulatory and signaling networks that are distinct from those in normal cells,” the authors said in their report.

Follow-up in vitro and in vivo studies confirmed the importance of AP-1 for different AML subtypes.

In the in vitro study, investigators transduced AML cells with a doxycycline-inducible version of a dominant negative FOS protein.

“AP-1 is a heterodimer formed by members of the FOS, JUN, ATF, CREB and JDP families of transcription factors, thus it is challenging to target by defined RNA interference approaches,” the investigators explained.

Results of the in vitro study showed that induction of that protein, mediated by doxycycline, inhibited proliferation and colony-forming ability in AML cell lines.

To evaluate the relevance of AP-1 for leukemia propagation in vivo, they transplanted two different types of cells expressing inducible dominant negative FOS protein in immunodeficient mice.

For the first cell type, granulosarcomas developed in six out of seven mice in a control group, but in only two mice treated with doxycycline, neither of which expressed the inducible protein, suggesting that the transgene was silenced, according to the investigators. For the second cell type, doxycycline inhibited leukemia development, while untreated mice rapidly developed tumors.

“Taken together, these findings demonstrate the importance of AP-1 for several AML subtypes and emphasize the potential of transcriptional network analyses to predict transcription factors crucial for malignant propagation,” the investigators wrote.

They declared no competing interests related to their research, which was funded by Bloodwise, Cancer Research UK, a Kay Kendall Clinical Training Fellowship and a MRC/Leuka Clinical Training Fellowship.

SOURCE: Assi SA et al. Nat Genet. 2018 Nov 12. doi: 10.1038/s41588-018-0270-1.

The AP-1 transcription factor family, important in many tumor types, plays a major role in acute myeloid leukemia, according to researchers who conducted a comprehensive global analysis of gene regulatory networks involved in this disease.

©GunarsB/Thinkstock

This observation suggests new opportunities for targeted treatment of AML, according to the researchers, led by Peter N. Cockerill, PhD, and Constanze Bonifer, PhD, with the Institute of Cancer and Genomic Sciences, University of Birmingham, England.

“Induced and aberrantly expressed transcription factors are not bystanders, but are important for network maintenance and leukemic growth,” the investigators wrote in Nature Genetics.

Investigators combined data obtained via several different analytic techniques to construct transcription factor networks in normal CD34+ cells and cells from specific subgroups of subjects with defined mutations, including RUNX1 mutations, t(8;21) translocations, mutations of both alleles of the CEBPA gene, and FLT3-ITD with or without NPM1 mutation.

The AP-1 family network was of “high regulatory relevance” for all AML subtypes evaluated, the investigators reported.

Previous work revealed the existence of gene regulatory networks in different types of AML classified by gene expression and DNA-methylation patterns.

“Our work now defines these networks in detail, and shows that leukemic drivers determine the regulatory phenotype by establishing and maintaining specific gene regulatory and signaling networks that are distinct from those in normal cells,” the authors said in their report.

Follow-up in vitro and in vivo studies confirmed the importance of AP-1 for different AML subtypes.

In the in vitro study, investigators transduced AML cells with a doxycycline-inducible version of a dominant negative FOS protein.

“AP-1 is a heterodimer formed by members of the FOS, JUN, ATF, CREB and JDP families of transcription factors, thus it is challenging to target by defined RNA interference approaches,” the investigators explained.

Results of the in vitro study showed that induction of that protein, mediated by doxycycline, inhibited proliferation and colony-forming ability in AML cell lines.

To evaluate the relevance of AP-1 for leukemia propagation in vivo, they transplanted two different types of cells expressing inducible dominant negative FOS protein in immunodeficient mice.

For the first cell type, granulosarcomas developed in six out of seven mice in a control group, but in only two mice treated with doxycycline, neither of which expressed the inducible protein, suggesting that the transgene was silenced, according to the investigators. For the second cell type, doxycycline inhibited leukemia development, while untreated mice rapidly developed tumors.

“Taken together, these findings demonstrate the importance of AP-1 for several AML subtypes and emphasize the potential of transcriptional network analyses to predict transcription factors crucial for malignant propagation,” the investigators wrote.

They declared no competing interests related to their research, which was funded by Bloodwise, Cancer Research UK, a Kay Kendall Clinical Training Fellowship and a MRC/Leuka Clinical Training Fellowship.

SOURCE: Assi SA et al. Nat Genet. 2018 Nov 12. doi: 10.1038/s41588-018-0270-1.

Risk of suicide was doubled in persons who experienced a concussion or mild traumatic brain injury (TBI) earlier in life, according to results of a meta-analysis of 17 studies representing nearly 7 million patients.

However, the absolute risk of suicide remained quite low, according to Michael Fralick, MD, of the University of Toronto, and co-investigators.

“Nearly all patients diagnosed with concussion and/or mild TBI did not die by suicide,” Dr. Fralick and colleagues said in their report on the study, which appears in JAMA Neurology.

Nevertheless, the meta-analysis illustrates evidence for an increased risk of suicide, suicide attempts, and suicidal ideation for persons with a history of these injuries, they said in the report.

The meta-analysis included 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies looking at the risk of suicide, suicide attempts, or suicidal ideation after a concussion or mild TBI. Those studies included a roughly 714,000 individuals with a concussion and/or TBI diagnosis, and 6,236,000 without a diagnosis.

For people diagnosed with at least one concussion and/or mild TBI, the risk of suicide was 2-fold higher (relative risk, 2.03; 95% CI, 1.47-2.80; P less than 0.001), according to the report.

The risk was “slightly stronger,” investigators said, when the analysis was limited to studies adjusting for factors associated with those brain injuries and with suicide (RR, 2.10; 95% CI, 1.40-3.13; P less than 0.01).

Four of the 5 cohort studies reported absolute risk of suicide, according to Dr. Fralick and coauthors. In one study with a median follow-up of 3.6 years, 0.50% of individuals with a concussion and/or TBI subsequently died of suicide, while similarly, 0.59% died in a study with 4.0 years of follow-up, 0.28% in a study with 9.3 years follow-up, and 0.49% in one with a 12.3 year median follow-up.

Most of the studies in the meta-analysis reported an increased risk of suicide attempt after concussion and/or mild TBI, according to Dr. Fralick and his collaborators, while the eight studies looking at suicidal ideation all reported heightened risk after those brain injuries.

The researchers acknowledged some limitations of their analysis. Recall bias could have led to an overestimation of the association between concussion and suicide risk, since suicide attempts may affect reporting of concussion history, they said.

Furthermore, most of the studies were retrospective, and did not include an active comparator group, such as individuals with non-neurologic injuries, they added.

“Until large prospective studies with sufficiently large durations of follow-up are available, we have to rely on the currently available data,” they said in the report.

Dr. Fralick and co-authors reported no conflict of interest disclosures related to the study.

SOURCE: Fralick M, et al. JAMA Neurol. 2018 Nov 12.

Risk of suicide was doubled in persons who experienced a concussion or mild traumatic brain injury (TBI) earlier in life, according to results of a meta-analysis of 17 studies representing nearly 7 million patients.

However, the absolute risk of suicide remained quite low, according to Michael Fralick, MD, of the University of Toronto, and co-investigators.

“Nearly all patients diagnosed with concussion and/or mild TBI did not die by suicide,” Dr. Fralick and colleagues said in their report on the study, which appears in JAMA Neurology.

Nevertheless, the meta-analysis illustrates evidence for an increased risk of suicide, suicide attempts, and suicidal ideation for persons with a history of these injuries, they said in the report.

The meta-analysis included 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies looking at the risk of suicide, suicide attempts, or suicidal ideation after a concussion or mild TBI. Those studies included a roughly 714,000 individuals with a concussion and/or TBI diagnosis, and 6,236,000 without a diagnosis.

For people diagnosed with at least one concussion and/or mild TBI, the risk of suicide was 2-fold higher (relative risk, 2.03; 95% CI, 1.47-2.80; P less than 0.001), according to the report.

The risk was “slightly stronger,” investigators said, when the analysis was limited to studies adjusting for factors associated with those brain injuries and with suicide (RR, 2.10; 95% CI, 1.40-3.13; P less than 0.01).

Four of the 5 cohort studies reported absolute risk of suicide, according to Dr. Fralick and coauthors. In one study with a median follow-up of 3.6 years, 0.50% of individuals with a concussion and/or TBI subsequently died of suicide, while similarly, 0.59% died in a study with 4.0 years of follow-up, 0.28% in a study with 9.3 years follow-up, and 0.49% in one with a 12.3 year median follow-up.

Most of the studies in the meta-analysis reported an increased risk of suicide attempt after concussion and/or mild TBI, according to Dr. Fralick and his collaborators, while the eight studies looking at suicidal ideation all reported heightened risk after those brain injuries.

The researchers acknowledged some limitations of their analysis. Recall bias could have led to an overestimation of the association between concussion and suicide risk, since suicide attempts may affect reporting of concussion history, they said.

Furthermore, most of the studies were retrospective, and did not include an active comparator group, such as individuals with non-neurologic injuries, they added.

“Until large prospective studies with sufficiently large durations of follow-up are available, we have to rely on the currently available data,” they said in the report.

Dr. Fralick and co-authors reported no conflict of interest disclosures related to the study.

SOURCE: Fralick M, et al. JAMA Neurol. 2018 Nov 12.

Risk of suicide was doubled in persons who experienced a concussion or mild traumatic brain injury (TBI) earlier in life, according to results of a meta-analysis of 17 studies representing nearly 7 million patients.

However, the absolute risk of suicide remained quite low, according to Michael Fralick, MD, of the University of Toronto, and co-investigators.

“Nearly all patients diagnosed with concussion and/or mild TBI did not die by suicide,” Dr. Fralick and colleagues said in their report on the study, which appears in JAMA Neurology.

Nevertheless, the meta-analysis illustrates evidence for an increased risk of suicide, suicide attempts, and suicidal ideation for persons with a history of these injuries, they said in the report.

The meta-analysis included 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies looking at the risk of suicide, suicide attempts, or suicidal ideation after a concussion or mild TBI. Those studies included a roughly 714,000 individuals with a concussion and/or TBI diagnosis, and 6,236,000 without a diagnosis.

For people diagnosed with at least one concussion and/or mild TBI, the risk of suicide was 2-fold higher (relative risk, 2.03; 95% CI, 1.47-2.80; P less than 0.001), according to the report.

The risk was “slightly stronger,” investigators said, when the analysis was limited to studies adjusting for factors associated with those brain injuries and with suicide (RR, 2.10; 95% CI, 1.40-3.13; P less than 0.01).

Four of the 5 cohort studies reported absolute risk of suicide, according to Dr. Fralick and coauthors. In one study with a median follow-up of 3.6 years, 0.50% of individuals with a concussion and/or TBI subsequently died of suicide, while similarly, 0.59% died in a study with 4.0 years of follow-up, 0.28% in a study with 9.3 years follow-up, and 0.49% in one with a 12.3 year median follow-up.

Most of the studies in the meta-analysis reported an increased risk of suicide attempt after concussion and/or mild TBI, according to Dr. Fralick and his collaborators, while the eight studies looking at suicidal ideation all reported heightened risk after those brain injuries.

The researchers acknowledged some limitations of their analysis. Recall bias could have led to an overestimation of the association between concussion and suicide risk, since suicide attempts may affect reporting of concussion history, they said.

Furthermore, most of the studies were retrospective, and did not include an active comparator group, such as individuals with non-neurologic injuries, they added.

“Until large prospective studies with sufficiently large durations of follow-up are available, we have to rely on the currently available data,” they said in the report.

Dr. Fralick and co-authors reported no conflict of interest disclosures related to the study.

SOURCE: Fralick M, et al. JAMA Neurol. 2018 Nov 12.

Just over half of infants get 8 hours of uninterrupted sleep at 12 months of age, an analysis of findings from a longitudinal birth cohort study showed.

It also found that whether an infant sleeps through night has no significant associated with any variations in mental or psychomotor development.

However, the rate of breastfeeding was significantly higher among infants who did not sleep through the night, investigators said in their report on the analysis, published in Pediatrics.

Being informed about the normal development of the sleep-wake cycle could be reassuring for parents, according to the authors, who said that new mothers tend to be “greatly surprised” by the sleep disturbance and exhaustion they experience.

“Keeping in mind the wide variability in the age when an infant starts to sleep through the night, expectations for early sleep consolidation could be moderated,” said Marie-Hélène Pennestri, PhD, of the Department of Educational and Counselling Psychology at McGill University, Montreal, and her coauthors.

Dr. Pennestri and colleagues reported on 388 mother-infant dyads in a longitudinal birth cohort study called Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN). Pregnant mothers were recruited from obstetric clinics in Canada. When their infants reached the age of 6 and 12 months, the mothers responded to questionnaires about sleep habits.

At 6 months, 62.4% of infants attained at least 6 hours of uninterrupted sleep, mothers reported, while 43.0% had reached 8 hours, the mothers reported. By 12 months of age, 72.1% of the infants attained 6 hours, and 56.6% attained 8 hours.

There were no associations between sleeping through the night and concurrent mental or psychomotor development, as measured by the Bayley Scales of Infant Development II at both 6 or 12 months of age, with P values greater than 0.05, investigators reported.

A similar lack of association between uninterrupted sleep and development or maternal mood was seen in a follow-up measurement at 36 months of age.

Sleeping through the night was likewise not associated with maternal mood, assessed using a depression scale with items that reflected symptom frequency in the previous week. “This is noteworthy because maternal sleep deprivation is often invoked to support the introduction of early behavioral interventions,” investigators said in a discussion of the results.

By contrast, sleeping through the night was linked to lower rates of breastfeeding as reported by mothers on retrospective questionnaires administered at both 6 and 12 months. At 12 months of age, 22.1% of infants sleeping through the night were breastfed, compared to 47.1% of infants not sleeping through the night (P less than 0.0001), Dr. Pennestri and colleagues reported.

However, that breastfeeding observation needs to be further investigated, according to the authors.

“The results of our study do not allow for the drawing of any causality between not sleeping through the night and breastfeeding,” they wrote.

Dr. Pennestri and coauthors said they had no financial relationships or potential conflicts of interest to disclose relevant to their report. They reported funding from the Ludmer Center for Neuroinformatics and Mental Health, Canadian Institutes of Health Research, and several other research institutions.

SOURCE: Pennestri MH, et al. Pediatrics. 2018;142(6):e20174330.

Just over half of infants get 8 hours of uninterrupted sleep at 12 months of age, an analysis of findings from a longitudinal birth cohort study showed.

It also found that whether an infant sleeps through night has no significant associated with any variations in mental or psychomotor development.

However, the rate of breastfeeding was significantly higher among infants who did not sleep through the night, investigators said in their report on the analysis, published in Pediatrics.

Being informed about the normal development of the sleep-wake cycle could be reassuring for parents, according to the authors, who said that new mothers tend to be “greatly surprised” by the sleep disturbance and exhaustion they experience.

“Keeping in mind the wide variability in the age when an infant starts to sleep through the night, expectations for early sleep consolidation could be moderated,” said Marie-Hélène Pennestri, PhD, of the Department of Educational and Counselling Psychology at McGill University, Montreal, and her coauthors.

Dr. Pennestri and colleagues reported on 388 mother-infant dyads in a longitudinal birth cohort study called Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN). Pregnant mothers were recruited from obstetric clinics in Canada. When their infants reached the age of 6 and 12 months, the mothers responded to questionnaires about sleep habits.

At 6 months, 62.4% of infants attained at least 6 hours of uninterrupted sleep, mothers reported, while 43.0% had reached 8 hours, the mothers reported. By 12 months of age, 72.1% of the infants attained 6 hours, and 56.6% attained 8 hours.

There were no associations between sleeping through the night and concurrent mental or psychomotor development, as measured by the Bayley Scales of Infant Development II at both 6 or 12 months of age, with P values greater than 0.05, investigators reported.

A similar lack of association between uninterrupted sleep and development or maternal mood was seen in a follow-up measurement at 36 months of age.

Sleeping through the night was likewise not associated with maternal mood, assessed using a depression scale with items that reflected symptom frequency in the previous week. “This is noteworthy because maternal sleep deprivation is often invoked to support the introduction of early behavioral interventions,” investigators said in a discussion of the results.

By contrast, sleeping through the night was linked to lower rates of breastfeeding as reported by mothers on retrospective questionnaires administered at both 6 and 12 months. At 12 months of age, 22.1% of infants sleeping through the night were breastfed, compared to 47.1% of infants not sleeping through the night (P less than 0.0001), Dr. Pennestri and colleagues reported.

However, that breastfeeding observation needs to be further investigated, according to the authors.

“The results of our study do not allow for the drawing of any causality between not sleeping through the night and breastfeeding,” they wrote.

Dr. Pennestri and coauthors said they had no financial relationships or potential conflicts of interest to disclose relevant to their report. They reported funding from the Ludmer Center for Neuroinformatics and Mental Health, Canadian Institutes of Health Research, and several other research institutions.

SOURCE: Pennestri MH, et al. Pediatrics. 2018;142(6):e20174330.

Just over half of infants get 8 hours of uninterrupted sleep at 12 months of age, an analysis of findings from a longitudinal birth cohort study showed.

It also found that whether an infant sleeps through night has no significant associated with any variations in mental or psychomotor development.

However, the rate of breastfeeding was significantly higher among infants who did not sleep through the night, investigators said in their report on the analysis, published in Pediatrics.

Being informed about the normal development of the sleep-wake cycle could be reassuring for parents, according to the authors, who said that new mothers tend to be “greatly surprised” by the sleep disturbance and exhaustion they experience.

“Keeping in mind the wide variability in the age when an infant starts to sleep through the night, expectations for early sleep consolidation could be moderated,” said Marie-Hélène Pennestri, PhD, of the Department of Educational and Counselling Psychology at McGill University, Montreal, and her coauthors.

Dr. Pennestri and colleagues reported on 388 mother-infant dyads in a longitudinal birth cohort study called Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN). Pregnant mothers were recruited from obstetric clinics in Canada. When their infants reached the age of 6 and 12 months, the mothers responded to questionnaires about sleep habits.

At 6 months, 62.4% of infants attained at least 6 hours of uninterrupted sleep, mothers reported, while 43.0% had reached 8 hours, the mothers reported. By 12 months of age, 72.1% of the infants attained 6 hours, and 56.6% attained 8 hours.

There were no associations between sleeping through the night and concurrent mental or psychomotor development, as measured by the Bayley Scales of Infant Development II at both 6 or 12 months of age, with P values greater than 0.05, investigators reported.

A similar lack of association between uninterrupted sleep and development or maternal mood was seen in a follow-up measurement at 36 months of age.

Sleeping through the night was likewise not associated with maternal mood, assessed using a depression scale with items that reflected symptom frequency in the previous week. “This is noteworthy because maternal sleep deprivation is often invoked to support the introduction of early behavioral interventions,” investigators said in a discussion of the results.

By contrast, sleeping through the night was linked to lower rates of breastfeeding as reported by mothers on retrospective questionnaires administered at both 6 and 12 months. At 12 months of age, 22.1% of infants sleeping through the night were breastfed, compared to 47.1% of infants not sleeping through the night (P less than 0.0001), Dr. Pennestri and colleagues reported.

However, that breastfeeding observation needs to be further investigated, according to the authors.

“The results of our study do not allow for the drawing of any causality between not sleeping through the night and breastfeeding,” they wrote.

Dr. Pennestri and coauthors said they had no financial relationships or potential conflicts of interest to disclose relevant to their report. They reported funding from the Ludmer Center for Neuroinformatics and Mental Health, Canadian Institutes of Health Research, and several other research institutions.

SOURCE: Pennestri MH, et al. Pediatrics. 2018;142(6):e20174330.

Among direct oral anticoagulants, apixaban (Eliquis) has shown fewer stroke events and bleeding than warfarin in patients with atrial fibrillation, according to results of an updated comparative effectiveness review.

Dabigatran (Pradaxa), by contrast, has shown reductions in stroke events but a similar rate of bleeding events compared to warfarin, according to the report from the Duke Evidence-based Practice Center, Durham, N.C.

Rivaroxaban (Xarelto), meanwhile, is “similar in both benefits and harms with warfarin” in evidence to date, investigators wrote in the report, which was prepared for the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI).

Finally, edoxaban (Savaysa) is “most likely similar” to warfarin with respect to preventing stroke or systemic embolism, with less risk for major bleeding and hemorrhagic stroke, investigators wrote in a summary of their findings on the AHRQ website.

“Effectiveness of these direct oral anticoagulants as compared to one another however is limited by the lack of randomized studies directly comparing their safety and effectiveness,” concluded investigators, led by Gillian D. Sanders, PhD, of Duke University.

The 612-page report details a systematic review based on 320 articles representing 185 unique studies. The review was designed to update a 2013 AHRQ report that evaluated evidence not only for treatment options to prevent stroke in patients with atrial fibrillation, but also for tools used to predict risk of stroke or bleeding.

In the 2013 report, investigators concluded that the newer anticoagulants showed “early promise” in reducing stroke and bleeding events compared with warfarin.

That earlier report said that CHA₂ and CHA₂DS₂-VASc had the best evidence to support prediction of stroke events, while HAS-BLED provided the best discrimination of bleeding risk.

The updated report adds the ABC stroke risk score as a tool that, along with CHADS2 and CHA2DS2-VASc, has the “best evidence” predicting thromboembolic risk, authors said.

Imaging tools, on the other hand, still need more evidence supporting their use to predict thromboembolic risk, Dr. Sanders and colleagues said in their report.

The literature review, which covered the January 2000 through February 2018, turned up 61 studies relevant to predicting thromboembolic risk, 38 on bleeding risk, and 117 on preventing thromboembolic events with anticoagulation therapies, antiplatelet therapies, or procedures.

Direct oral anticoagulants were evaluated in randomized clinical trials that were “often very large, of good quality, and considered definitive in the field,” Dr. Sanders and colleagues wrote in their report.

However, these trials were constrained to comparing direct oral anticoagulants with warfarin or aspirin, and have not involved head-to-head comparison among the newer agents, they added.

“Based on these trials though, clinical leaders and professional societies have determined that these newer agents are better than the prior lone treatment of warfarin in terms of stroke prevention, side effects, and risk of bleeding,” they said in the published report.
 

SOURCE: Sanders GD, et al. 2018 Oct 30. AHRQ Publication No. 18(19)-EHC018-EF.
 

Among direct oral anticoagulants, apixaban (Eliquis) has shown fewer stroke events and bleeding than warfarin in patients with atrial fibrillation, according to results of an updated comparative effectiveness review.

Dabigatran (Pradaxa), by contrast, has shown reductions in stroke events but a similar rate of bleeding events compared to warfarin, according to the report from the Duke Evidence-based Practice Center, Durham, N.C.

Rivaroxaban (Xarelto), meanwhile, is “similar in both benefits and harms with warfarin” in evidence to date, investigators wrote in the report, which was prepared for the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI).

Finally, edoxaban (Savaysa) is “most likely similar” to warfarin with respect to preventing stroke or systemic embolism, with less risk for major bleeding and hemorrhagic stroke, investigators wrote in a summary of their findings on the AHRQ website.

“Effectiveness of these direct oral anticoagulants as compared to one another however is limited by the lack of randomized studies directly comparing their safety and effectiveness,” concluded investigators, led by Gillian D. Sanders, PhD, of Duke University.

The 612-page report details a systematic review based on 320 articles representing 185 unique studies. The review was designed to update a 2013 AHRQ report that evaluated evidence not only for treatment options to prevent stroke in patients with atrial fibrillation, but also for tools used to predict risk of stroke or bleeding.

In the 2013 report, investigators concluded that the newer anticoagulants showed “early promise” in reducing stroke and bleeding events compared with warfarin.

That earlier report said that CHA₂ and CHA₂DS₂-VASc had the best evidence to support prediction of stroke events, while HAS-BLED provided the best discrimination of bleeding risk.

The updated report adds the ABC stroke risk score as a tool that, along with CHADS2 and CHA2DS2-VASc, has the “best evidence” predicting thromboembolic risk, authors said.

Imaging tools, on the other hand, still need more evidence supporting their use to predict thromboembolic risk, Dr. Sanders and colleagues said in their report.

The literature review, which covered the January 2000 through February 2018, turned up 61 studies relevant to predicting thromboembolic risk, 38 on bleeding risk, and 117 on preventing thromboembolic events with anticoagulation therapies, antiplatelet therapies, or procedures.

Direct oral anticoagulants were evaluated in randomized clinical trials that were “often very large, of good quality, and considered definitive in the field,” Dr. Sanders and colleagues wrote in their report.

However, these trials were constrained to comparing direct oral anticoagulants with warfarin or aspirin, and have not involved head-to-head comparison among the newer agents, they added.

“Based on these trials though, clinical leaders and professional societies have determined that these newer agents are better than the prior lone treatment of warfarin in terms of stroke prevention, side effects, and risk of bleeding,” they said in the published report.
 

SOURCE: Sanders GD, et al. 2018 Oct 30. AHRQ Publication No. 18(19)-EHC018-EF.
 

Among direct oral anticoagulants, apixaban (Eliquis) has shown fewer stroke events and bleeding than warfarin in patients with atrial fibrillation, according to results of an updated comparative effectiveness review.

Dabigatran (Pradaxa), by contrast, has shown reductions in stroke events but a similar rate of bleeding events compared to warfarin, according to the report from the Duke Evidence-based Practice Center, Durham, N.C.

Rivaroxaban (Xarelto), meanwhile, is “similar in both benefits and harms with warfarin” in evidence to date, investigators wrote in the report, which was prepared for the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI).

Finally, edoxaban (Savaysa) is “most likely similar” to warfarin with respect to preventing stroke or systemic embolism, with less risk for major bleeding and hemorrhagic stroke, investigators wrote in a summary of their findings on the AHRQ website.

“Effectiveness of these direct oral anticoagulants as compared to one another however is limited by the lack of randomized studies directly comparing their safety and effectiveness,” concluded investigators, led by Gillian D. Sanders, PhD, of Duke University.

The 612-page report details a systematic review based on 320 articles representing 185 unique studies. The review was designed to update a 2013 AHRQ report that evaluated evidence not only for treatment options to prevent stroke in patients with atrial fibrillation, but also for tools used to predict risk of stroke or bleeding.

In the 2013 report, investigators concluded that the newer anticoagulants showed “early promise” in reducing stroke and bleeding events compared with warfarin.

That earlier report said that CHA₂ and CHA₂DS₂-VASc had the best evidence to support prediction of stroke events, while HAS-BLED provided the best discrimination of bleeding risk.

The updated report adds the ABC stroke risk score as a tool that, along with CHADS2 and CHA2DS2-VASc, has the “best evidence” predicting thromboembolic risk, authors said.

Imaging tools, on the other hand, still need more evidence supporting their use to predict thromboembolic risk, Dr. Sanders and colleagues said in their report.

The literature review, which covered the January 2000 through February 2018, turned up 61 studies relevant to predicting thromboembolic risk, 38 on bleeding risk, and 117 on preventing thromboembolic events with anticoagulation therapies, antiplatelet therapies, or procedures.

Direct oral anticoagulants were evaluated in randomized clinical trials that were “often very large, of good quality, and considered definitive in the field,” Dr. Sanders and colleagues wrote in their report.

However, these trials were constrained to comparing direct oral anticoagulants with warfarin or aspirin, and have not involved head-to-head comparison among the newer agents, they added.

“Based on these trials though, clinical leaders and professional societies have determined that these newer agents are better than the prior lone treatment of warfarin in terms of stroke prevention, side effects, and risk of bleeding,” they said in the published report.
 

SOURCE: Sanders GD, et al. 2018 Oct 30. AHRQ Publication No. 18(19)-EHC018-EF.
 

Rates of advanced precancerous neoplasia did not differ between average-risk black and white individuals who underwent screening colonoscopy in a recent meta-analysis, prompting investigators to suggest that the age at which screening starts need not differ based on race.

There was also no difference in advanced neoplasia in the proximal colon between black and white screen-eligible individuals in the most rigorous of the studies included in the meta-analysis, investigators reported.

Those findings support eliminating the age difference at which to begin screening of average-risk individuals, as is currently recommended in some guidelines, said Thomas F. Imperiale, MD, the Lawrence Lumeng Professor of Gastroenterology and Hepatology at Indiana University, Indianapolis, and his coinvestigators.

In areas with no disparities in screening access, average-risk screening could begin at age 50 years, regardless of race, at least based on results of this meta-analysis, Dr. Imperiale and his colleagues said in their report.

“To the extent that advanced adenoma is the precursor lesion for colorectal cancer, tailoring the age at which to begin screening and how to screen based on race is not supported by our findings,” they said in the report, which appears in the journal Gastroenterology.

Dr. Imperiale and his coinvestigators scanned the medical literature and identified nine studies looking at the prevalence of advanced adenomas or advanced precancerous colorectal neoplasms in both black and white individuals of average risk who had undergone screening colonoscopy.

Those nine cross-sectional studies, all published during 2010-2017, represented a total of 302,128 participants. Six studies were of high methodologic quality and had a low risk of bias, while the remaining three failed to adjust for age and sex, authors of the meta-analysis said in their report.

Prevalence of advanced adenomas or advanced precancerous colorectal neoplasms ranged from 2% to 10% for whites and from 5% to 12% for blacks in the nine studies, with only one study, which had no histology results available, showing a higher prevalence in blacks, investigators found.

Taken together, there was no difference between racial groups, with a point prevalence of 6.57% for blacks and 6.20% for whites (odds ratio, 1.03; 95% confidence interval, 0.81-1.30) and an absolute risk difference of zero, according to the statistical analysis.

Of five studies that included data on proximal advanced adenomas or advanced precancerous colorectal neoplasms, two showed a greater prevalence in blacks versus whites, with point prevalences of 3.30% and 2.42%, respectively. However, there was no difference in prevalence for the “best subset” of three studies with a moderate degree of heterogeneity, investigators said.

Given these findings, the higher colorectal cancer incidence and mortality seen in black adults is less likely because of biology, and more likely from differences in symptom recognition, diagnostic evaluation, or acceptance of preventive services, Dr. Imperiale and his coauthors said in a discussion of the results.

Some current guidelines suggest starting colorectal cancer screening at age 40 years for average-risk blacks, which is 5-10 years earlier than for nonblacks, investigators said, though of note, the most recent American Cancer Society recommendations recommend screening starting at age 45 years for all average-risk individuals.

“If this recommendation is followed broadly, it would lessen the clinical and policy implications of our findings,” they wrote. “However, the uptake of this recommendation is yet to be determined, as it differs from those of all other professional organizations.”

The study was supported by Indiana CTSI Collaboration in Translational Research Grants. Dr. Imperiale and hiscoauthors reported no conflicts of interest.
 

SOURCE: Imperiale TF et al. Gastroenterology. 2018 Aug 21. doi: 10.1053/j.gastro.2018.08.020.

Rates of advanced precancerous neoplasia did not differ between average-risk black and white individuals who underwent screening colonoscopy in a recent meta-analysis, prompting investigators to suggest that the age at which screening starts need not differ based on race.

There was also no difference in advanced neoplasia in the proximal colon between black and white screen-eligible individuals in the most rigorous of the studies included in the meta-analysis, investigators reported.

Those findings support eliminating the age difference at which to begin screening of average-risk individuals, as is currently recommended in some guidelines, said Thomas F. Imperiale, MD, the Lawrence Lumeng Professor of Gastroenterology and Hepatology at Indiana University, Indianapolis, and his coinvestigators.

In areas with no disparities in screening access, average-risk screening could begin at age 50 years, regardless of race, at least based on results of this meta-analysis, Dr. Imperiale and his colleagues said in their report.

“To the extent that advanced adenoma is the precursor lesion for colorectal cancer, tailoring the age at which to begin screening and how to screen based on race is not supported by our findings,” they said in the report, which appears in the journal Gastroenterology.

Dr. Imperiale and his coinvestigators scanned the medical literature and identified nine studies looking at the prevalence of advanced adenomas or advanced precancerous colorectal neoplasms in both black and white individuals of average risk who had undergone screening colonoscopy.

Those nine cross-sectional studies, all published during 2010-2017, represented a total of 302,128 participants. Six studies were of high methodologic quality and had a low risk of bias, while the remaining three failed to adjust for age and sex, authors of the meta-analysis said in their report.

Prevalence of advanced adenomas or advanced precancerous colorectal neoplasms ranged from 2% to 10% for whites and from 5% to 12% for blacks in the nine studies, with only one study, which had no histology results available, showing a higher prevalence in blacks, investigators found.

Taken together, there was no difference between racial groups, with a point prevalence of 6.57% for blacks and 6.20% for whites (odds ratio, 1.03; 95% confidence interval, 0.81-1.30) and an absolute risk difference of zero, according to the statistical analysis.

Of five studies that included data on proximal advanced adenomas or advanced precancerous colorectal neoplasms, two showed a greater prevalence in blacks versus whites, with point prevalences of 3.30% and 2.42%, respectively. However, there was no difference in prevalence for the “best subset” of three studies with a moderate degree of heterogeneity, investigators said.

Given these findings, the higher colorectal cancer incidence and mortality seen in black adults is less likely because of biology, and more likely from differences in symptom recognition, diagnostic evaluation, or acceptance of preventive services, Dr. Imperiale and his coauthors said in a discussion of the results.

Some current guidelines suggest starting colorectal cancer screening at age 40 years for average-risk blacks, which is 5-10 years earlier than for nonblacks, investigators said, though of note, the most recent American Cancer Society recommendations recommend screening starting at age 45 years for all average-risk individuals.

“If this recommendation is followed broadly, it would lessen the clinical and policy implications of our findings,” they wrote. “However, the uptake of this recommendation is yet to be determined, as it differs from those of all other professional organizations.”

The study was supported by Indiana CTSI Collaboration in Translational Research Grants. Dr. Imperiale and hiscoauthors reported no conflicts of interest.
 

SOURCE: Imperiale TF et al. Gastroenterology. 2018 Aug 21. doi: 10.1053/j.gastro.2018.08.020.

Rates of advanced precancerous neoplasia did not differ between average-risk black and white individuals who underwent screening colonoscopy in a recent meta-analysis, prompting investigators to suggest that the age at which screening starts need not differ based on race.

There was also no difference in advanced neoplasia in the proximal colon between black and white screen-eligible individuals in the most rigorous of the studies included in the meta-analysis, investigators reported.

Those findings support eliminating the age difference at which to begin screening of average-risk individuals, as is currently recommended in some guidelines, said Thomas F. Imperiale, MD, the Lawrence Lumeng Professor of Gastroenterology and Hepatology at Indiana University, Indianapolis, and his coinvestigators.

In areas with no disparities in screening access, average-risk screening could begin at age 50 years, regardless of race, at least based on results of this meta-analysis, Dr. Imperiale and his colleagues said in their report.

“To the extent that advanced adenoma is the precursor lesion for colorectal cancer, tailoring the age at which to begin screening and how to screen based on race is not supported by our findings,” they said in the report, which appears in the journal Gastroenterology.

Dr. Imperiale and his coinvestigators scanned the medical literature and identified nine studies looking at the prevalence of advanced adenomas or advanced precancerous colorectal neoplasms in both black and white individuals of average risk who had undergone screening colonoscopy.

Those nine cross-sectional studies, all published during 2010-2017, represented a total of 302,128 participants. Six studies were of high methodologic quality and had a low risk of bias, while the remaining three failed to adjust for age and sex, authors of the meta-analysis said in their report.

Prevalence of advanced adenomas or advanced precancerous colorectal neoplasms ranged from 2% to 10% for whites and from 5% to 12% for blacks in the nine studies, with only one study, which had no histology results available, showing a higher prevalence in blacks, investigators found.

Taken together, there was no difference between racial groups, with a point prevalence of 6.57% for blacks and 6.20% for whites (odds ratio, 1.03; 95% confidence interval, 0.81-1.30) and an absolute risk difference of zero, according to the statistical analysis.

Of five studies that included data on proximal advanced adenomas or advanced precancerous colorectal neoplasms, two showed a greater prevalence in blacks versus whites, with point prevalences of 3.30% and 2.42%, respectively. However, there was no difference in prevalence for the “best subset” of three studies with a moderate degree of heterogeneity, investigators said.

Given these findings, the higher colorectal cancer incidence and mortality seen in black adults is less likely because of biology, and more likely from differences in symptom recognition, diagnostic evaluation, or acceptance of preventive services, Dr. Imperiale and his coauthors said in a discussion of the results.

Some current guidelines suggest starting colorectal cancer screening at age 40 years for average-risk blacks, which is 5-10 years earlier than for nonblacks, investigators said, though of note, the most recent American Cancer Society recommendations recommend screening starting at age 45 years for all average-risk individuals.

“If this recommendation is followed broadly, it would lessen the clinical and policy implications of our findings,” they wrote. “However, the uptake of this recommendation is yet to be determined, as it differs from those of all other professional organizations.”

The study was supported by Indiana CTSI Collaboration in Translational Research Grants. Dr. Imperiale and hiscoauthors reported no conflicts of interest.
 

SOURCE: Imperiale TF et al. Gastroenterology. 2018 Aug 21. doi: 10.1053/j.gastro.2018.08.020.

A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.

Centers for Disease Control and Prevention

About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.

The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.

“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.

At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.

Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.

“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.

Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.

A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.

Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.

That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.

“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.

The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.

SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.

A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.

Centers for Disease Control and Prevention

About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.

The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.

“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.

At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.

Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.

“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.

Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.

A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.

Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.

That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.

“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.

The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.

SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.

A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.

Centers for Disease Control and Prevention

About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.

The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.

“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.

At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.

Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.

“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.

Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.

A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.

Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.

That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.

“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.

The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.

SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.

Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.

Lynda Banzi/MDedge News

Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.

By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.

“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.

This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.


Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.

A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.

National Rosacea Society

By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.

Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”

However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.

Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
 

SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.

Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.

Lynda Banzi/MDedge News

Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.

By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.

“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.

This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.


Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.

A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.

National Rosacea Society

By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.

Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”

However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.

Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
 

SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.

Caffeinated coffee intake is linked to a decreased incidence of rosacea, results of a large, observational study suggest.

Lynda Banzi/MDedge News

Increased levels of caffeinated coffee consumption were associated with progressively lower levels of incident rosacea in a study of more than 82,000 participants representing more than 1.1 million person-years of follow-up.

By contrast, caffeine from other foods was not associated with rosacea incidence, reported Wen-Qing Li, PhD, of the department of dermatology at Brown University, Providence, R.I., and his coinvestigators. Those findings may have implications for the “causes and clinical approach” to rosacea.

“Our findings do not support limiting caffeine intake as a preventive strategy for rosacea,” they concluded in the study, published in JAMA Dermatology.

This is not the first study looking for potential links between rosacea and caffeine or coffee intake. However, previous studies didn’t distinguish between caffeinated coffee versus other beverages, and only one previous study made a distinction between the amounts of caffeine and coffee consumed, according to the authors.


Their research was based on data from the Nurses’ Health Study II, a prospective cohort study started in 1989. They looked specifically at 82,737 women who, in 2005, responded to the question about whether they had been diagnosed with rosacea. They identified 4,945 incident rosacea cases over the 1,120,051 person-years of follow-up.

A significant inverse association was found between caffeinated coffee intake and rosacea: Individuals who consumed four or more servings a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001). They also found a dose-dependent effect, with the absolute risk of rosacea decreased by 131 per 100,000 person-years with at least four daily servings of caffeinated coffee, compared with under one serving a month.

National Rosacea Society

By contrast, decaffeinated coffee was not associated with a reduced risk of rosacea, and in further analysis, the investigators found that there was no significant inverse association when they looked just at caffeine intake from sources other than coffee, such as chocolate, tea, and soda.

Caffeine could influence rosacea incidence by one of several mechanisms, including its effect on vascular contractility, the investigators hypothesized. “Increased caffeine intake may decrease vasodilation and consequently lead to diminution of rosacea symptoms.”

However, caffeine also has documented immunosuppressant effects that could possibly decrease rosacea-associated inflammation and has been shown to modulate hormone levels. “Hormonal factors have been implicated in the development of rosacea, and caffeine can modulate hormone levels,” they wrote.

Two study authors reported disclosures related to AbbVie, Amgen, Astellas Pharma, Janssen, Merck, Novartis, and Pfizer, among others. Funding for the study came from several sources, including National Institutes of Health grants for the Nurses’ Health Study II.
 

SOURCE: Li W-Q et al. JAMA Dermatol. 2018 Oct 17. doi: 10.1001/jamadermatol.2018.3301.

A new clinical practice guideline on the management of bradycardia and cardiac conduction system disorders in adults emphasizes the importance of patient-centered care and “shared decision-making” between patient and clinician, particularly with regard to patients who have indications for pacemaker implantation.

Shared decision-making extends to the end-of-life setting where “complex” informed consent and refusal of care decisions need to be patient-specific, and must involve all stakeholders, according to the new 2018 guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS).

“Patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide,” the guidelines read.

The guidelines additionally update the evaluation and treatment of sinus node dysfunction, atrioventricular block, and conduction disorders, based in part on a comprehensive evidence review conducted from January to September 2017. They supersede a 2008 guideline from the three societies on device-based therapy of cardiac rhythm abnormalities, and the focused update to that guideline published in 2012.

These guidelines will be useful not only to arrhythmia specialists, but also to internists and family physicians, cardiologists, surgeons, emergency physicians, and anesthesiologists, according to the guideline writing committee, which included representativens of ACC, AHA, HRS, and several other national organizations. The committee included cardiac electrophysiologists, cardiologists, surgeons, an anesthesiologist, and other clinicians, as well as a patient/lay representative, and was chaired by Fred M. Kusumoto, MD, of Mayo Clinic Florida in Jacksonville.

For sinus node dysfunction, no minimum heart rate or pause duration has been determined for which permanent pacing would be recommended, the guidelines state. To determine whether permanent pacing is necessary in those patients, clinicians should work to establish a temporal correlation bewteen bradycardia and symptoms, according to the guideline authors.

Left bundle branch block, when found on echocardiogram, greatly increases the chances of underlying structural heart disease and of a left ventricular systolic dysfunction diagnosis, according to the guidelines, which state that echocardiography is the most appropriate initial screening test for left ventricular systolic dysfunction and other structural heart disease.

Permanent pacing is recommended for certain types of atrioventricular (AV) block, according to the guidelines, which include high-grade AV block, acquired second-degree Mobitz type II AV block, and third-degree AV block not related to reversible or physiologic causes.

Treatment of sleep apnea can reduce frequency of nocturnal bradycardia and may provide a cardiovascular benefit, the guideline authors state. Patients with nocturnal bradycardias should be screened for sleep apnea, though authors cautioned that these arrhythmias are not, in and of themselves, an indication for permanent pacing.

“Treatment decisions are based not only on the best available evidence, but also on the patient’s goals of care and preferences,” Dr. Kusumoto said in a press release jointly issued by the ACC, AHA, and HRS. Toward that end, patients should receive “trusted material” to help them understand the consequences and risks of any proposed management decision.

Emerging pacing technologies such as His bundle pacing and transcatheter leadless pacing systems need more study to determine which patient populations will benefit most from them, the guidelines state.

“Regardless of technology, for the foreseeable future, pacing therapy requires implantation of a medical device,” Dr. Kusumoto said in the release. “Future studies are warranted to focus on the long-term implications associated with lifelong therapy.”

The 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay is now published in the Journal of the American College of Cardiology, and simultaneously in the journals Circulation and HeartRhythm.

Dr. Kusumoto reported no relationships with industry or other entities. Guideline co-authors provided disclosures related to Boston Scientific, Janssen Pharmaceuticals, Medtronic, Daiichi-Sankyo, Sanofi-Aventis, St. Jude Medical, and Abbott, among others.
 

SOURCE: Kusumoto FM, et al. J Am Coll Cardiol. 2018 Nov 6.

A new clinical practice guideline on the management of bradycardia and cardiac conduction system disorders in adults emphasizes the importance of patient-centered care and “shared decision-making” between patient and clinician, particularly with regard to patients who have indications for pacemaker implantation.

Shared decision-making extends to the end-of-life setting where “complex” informed consent and refusal of care decisions need to be patient-specific, and must involve all stakeholders, according to the new 2018 guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS).

“Patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide,” the guidelines read.

The guidelines additionally update the evaluation and treatment of sinus node dysfunction, atrioventricular block, and conduction disorders, based in part on a comprehensive evidence review conducted from January to September 2017. They supersede a 2008 guideline from the three societies on device-based therapy of cardiac rhythm abnormalities, and the focused update to that guideline published in 2012.

These guidelines will be useful not only to arrhythmia specialists, but also to internists and family physicians, cardiologists, surgeons, emergency physicians, and anesthesiologists, according to the guideline writing committee, which included representativens of ACC, AHA, HRS, and several other national organizations. The committee included cardiac electrophysiologists, cardiologists, surgeons, an anesthesiologist, and other clinicians, as well as a patient/lay representative, and was chaired by Fred M. Kusumoto, MD, of Mayo Clinic Florida in Jacksonville.

For sinus node dysfunction, no minimum heart rate or pause duration has been determined for which permanent pacing would be recommended, the guidelines state. To determine whether permanent pacing is necessary in those patients, clinicians should work to establish a temporal correlation bewteen bradycardia and symptoms, according to the guideline authors.

Left bundle branch block, when found on echocardiogram, greatly increases the chances of underlying structural heart disease and of a left ventricular systolic dysfunction diagnosis, according to the guidelines, which state that echocardiography is the most appropriate initial screening test for left ventricular systolic dysfunction and other structural heart disease.

Permanent pacing is recommended for certain types of atrioventricular (AV) block, according to the guidelines, which include high-grade AV block, acquired second-degree Mobitz type II AV block, and third-degree AV block not related to reversible or physiologic causes.

Treatment of sleep apnea can reduce frequency of nocturnal bradycardia and may provide a cardiovascular benefit, the guideline authors state. Patients with nocturnal bradycardias should be screened for sleep apnea, though authors cautioned that these arrhythmias are not, in and of themselves, an indication for permanent pacing.

“Treatment decisions are based not only on the best available evidence, but also on the patient’s goals of care and preferences,” Dr. Kusumoto said in a press release jointly issued by the ACC, AHA, and HRS. Toward that end, patients should receive “trusted material” to help them understand the consequences and risks of any proposed management decision.

Emerging pacing technologies such as His bundle pacing and transcatheter leadless pacing systems need more study to determine which patient populations will benefit most from them, the guidelines state.

“Regardless of technology, for the foreseeable future, pacing therapy requires implantation of a medical device,” Dr. Kusumoto said in the release. “Future studies are warranted to focus on the long-term implications associated with lifelong therapy.”

The 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay is now published in the Journal of the American College of Cardiology, and simultaneously in the journals Circulation and HeartRhythm.

Dr. Kusumoto reported no relationships with industry or other entities. Guideline co-authors provided disclosures related to Boston Scientific, Janssen Pharmaceuticals, Medtronic, Daiichi-Sankyo, Sanofi-Aventis, St. Jude Medical, and Abbott, among others.
 

SOURCE: Kusumoto FM, et al. J Am Coll Cardiol. 2018 Nov 6.

A new clinical practice guideline on the management of bradycardia and cardiac conduction system disorders in adults emphasizes the importance of patient-centered care and “shared decision-making” between patient and clinician, particularly with regard to patients who have indications for pacemaker implantation.

Shared decision-making extends to the end-of-life setting where “complex” informed consent and refusal of care decisions need to be patient-specific, and must involve all stakeholders, according to the new 2018 guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS).

“Patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide,” the guidelines read.

The guidelines additionally update the evaluation and treatment of sinus node dysfunction, atrioventricular block, and conduction disorders, based in part on a comprehensive evidence review conducted from January to September 2017. They supersede a 2008 guideline from the three societies on device-based therapy of cardiac rhythm abnormalities, and the focused update to that guideline published in 2012.

These guidelines will be useful not only to arrhythmia specialists, but also to internists and family physicians, cardiologists, surgeons, emergency physicians, and anesthesiologists, according to the guideline writing committee, which included representativens of ACC, AHA, HRS, and several other national organizations. The committee included cardiac electrophysiologists, cardiologists, surgeons, an anesthesiologist, and other clinicians, as well as a patient/lay representative, and was chaired by Fred M. Kusumoto, MD, of Mayo Clinic Florida in Jacksonville.

For sinus node dysfunction, no minimum heart rate or pause duration has been determined for which permanent pacing would be recommended, the guidelines state. To determine whether permanent pacing is necessary in those patients, clinicians should work to establish a temporal correlation bewteen bradycardia and symptoms, according to the guideline authors.

Left bundle branch block, when found on echocardiogram, greatly increases the chances of underlying structural heart disease and of a left ventricular systolic dysfunction diagnosis, according to the guidelines, which state that echocardiography is the most appropriate initial screening test for left ventricular systolic dysfunction and other structural heart disease.

Permanent pacing is recommended for certain types of atrioventricular (AV) block, according to the guidelines, which include high-grade AV block, acquired second-degree Mobitz type II AV block, and third-degree AV block not related to reversible or physiologic causes.

Treatment of sleep apnea can reduce frequency of nocturnal bradycardia and may provide a cardiovascular benefit, the guideline authors state. Patients with nocturnal bradycardias should be screened for sleep apnea, though authors cautioned that these arrhythmias are not, in and of themselves, an indication for permanent pacing.

“Treatment decisions are based not only on the best available evidence, but also on the patient’s goals of care and preferences,” Dr. Kusumoto said in a press release jointly issued by the ACC, AHA, and HRS. Toward that end, patients should receive “trusted material” to help them understand the consequences and risks of any proposed management decision.

Emerging pacing technologies such as His bundle pacing and transcatheter leadless pacing systems need more study to determine which patient populations will benefit most from them, the guidelines state.

“Regardless of technology, for the foreseeable future, pacing therapy requires implantation of a medical device,” Dr. Kusumoto said in the release. “Future studies are warranted to focus on the long-term implications associated with lifelong therapy.”

The 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay is now published in the Journal of the American College of Cardiology, and simultaneously in the journals Circulation and HeartRhythm.

Dr. Kusumoto reported no relationships with industry or other entities. Guideline co-authors provided disclosures related to Boston Scientific, Janssen Pharmaceuticals, Medtronic, Daiichi-Sankyo, Sanofi-Aventis, St. Jude Medical, and Abbott, among others.
 

SOURCE: Kusumoto FM, et al. J Am Coll Cardiol. 2018 Nov 6.