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Sertraline improves Cryptococcus clearance in HIV meningitis
An open-label pilot study has found adjunct treatment with the SSRI antidepressant sertraline is associated with accelerated clearance of Cryptococcus from the cerebrospinal fluid in HIV-infected individuals with cryptococcal meningitis.
The dose-finding study of 172 HIV-infected Ugandan adults with cryptococcal meningitis showed any dose of sertraline, in combination with standard amphotericin B and high-dose fluconazole therapy, was associated with an average clearance rate of –0.37 log10 colony-forming U/mL CSF per day, compared with –0.30 observed in a previous study in individuals taking standard therapy without sertraline.
According to a paper published online in Lancet Infectious Diseases, the incidence of paradoxical immune reconstitution inflammatory syndrome was 5%, compared with rates of 17%-30% observed in other studies.
The sertraline doses used in the study ranged from 100 mg/day to 400 mg/day but researchers did not observe a significant difference in serious adverse events between the lower and higher doses (Lancet Infect Dis. 2016 Mar 9. doi: 10.1016/S1473-3099[16]00074-8).
Sertraline has previously shown potent fungicidal activity against Cryptococcus in vitro and in mice, suggesting it could be a promising therapeutic option for cryptococcal meningitis, a disease that accounts for 15%-20% of AIDS-related deaths in Africa.
“The current standard therapy for cryptococcal meningitis is based on antifungal regimens that are a half-century old, are associated with a range of toxic effects, and are largely inaccessible in areas of the world where they are needed most,” wrote Dr. Joshua Rhein of the University of Minnesota, Minneapolis, and his coauthors. “For this reason, the discovery of a widely available, nontoxic, and affordable drug effective against Cryptococcus would represent a substantial advance in preventing deaths.”
The study was supported by the National Institutes of Health, Fogarty International Center, Grand Challenges Canada, and the Doris Duke Charitable Foundation. No conflicts of interest were declared.
Cryptococcal meningitis remains a major clinical challenge in Africa. The number of cases of cryptococcal meningitis remains high despite more than a decade of antiretroviral therapy rollout, but the profile of the population developing the disease is changing.
Novel treatments are urgently needed, and Dr. Rhein and his colleagues should be commended for their work to develop practical, affordable, effective new antifungal regimens for HIV-associated cryptococcal meningitis.
Joseph N. Jarvis, Ph.D., is from the Botswana-UPenn Partnership at the University of Pennsylvania, Philadelphia, and Dr. Thomas S. Harrison is from the Institute of Infection and Immunity at St. George’s University of London. These comments are taken from an accompanying editorial (Lancet Infect Dis. 2016 Mar 9. doi: 10.1016/S1473-3099[16]00128-6). Dr. Jarvis declared grants from Gilead Sciences and the National Institutes of Health outside of the submitted work, and Dr. Harrison declared grants from Gilead Sciences and personal fees from Viamet Pharmaceuticals, outside of the submitted work.
Cryptococcal meningitis remains a major clinical challenge in Africa. The number of cases of cryptococcal meningitis remains high despite more than a decade of antiretroviral therapy rollout, but the profile of the population developing the disease is changing.
Novel treatments are urgently needed, and Dr. Rhein and his colleagues should be commended for their work to develop practical, affordable, effective new antifungal regimens for HIV-associated cryptococcal meningitis.
Joseph N. Jarvis, Ph.D., is from the Botswana-UPenn Partnership at the University of Pennsylvania, Philadelphia, and Dr. Thomas S. Harrison is from the Institute of Infection and Immunity at St. George’s University of London. These comments are taken from an accompanying editorial (Lancet Infect Dis. 2016 Mar 9. doi: 10.1016/S1473-3099[16]00128-6). Dr. Jarvis declared grants from Gilead Sciences and the National Institutes of Health outside of the submitted work, and Dr. Harrison declared grants from Gilead Sciences and personal fees from Viamet Pharmaceuticals, outside of the submitted work.
Cryptococcal meningitis remains a major clinical challenge in Africa. The number of cases of cryptococcal meningitis remains high despite more than a decade of antiretroviral therapy rollout, but the profile of the population developing the disease is changing.
Novel treatments are urgently needed, and Dr. Rhein and his colleagues should be commended for their work to develop practical, affordable, effective new antifungal regimens for HIV-associated cryptococcal meningitis.
Joseph N. Jarvis, Ph.D., is from the Botswana-UPenn Partnership at the University of Pennsylvania, Philadelphia, and Dr. Thomas S. Harrison is from the Institute of Infection and Immunity at St. George’s University of London. These comments are taken from an accompanying editorial (Lancet Infect Dis. 2016 Mar 9. doi: 10.1016/S1473-3099[16]00128-6). Dr. Jarvis declared grants from Gilead Sciences and the National Institutes of Health outside of the submitted work, and Dr. Harrison declared grants from Gilead Sciences and personal fees from Viamet Pharmaceuticals, outside of the submitted work.
An open-label pilot study has found adjunct treatment with the SSRI antidepressant sertraline is associated with accelerated clearance of Cryptococcus from the cerebrospinal fluid in HIV-infected individuals with cryptococcal meningitis.
The dose-finding study of 172 HIV-infected Ugandan adults with cryptococcal meningitis showed any dose of sertraline, in combination with standard amphotericin B and high-dose fluconazole therapy, was associated with an average clearance rate of –0.37 log10 colony-forming U/mL CSF per day, compared with –0.30 observed in a previous study in individuals taking standard therapy without sertraline.
According to a paper published online in Lancet Infectious Diseases, the incidence of paradoxical immune reconstitution inflammatory syndrome was 5%, compared with rates of 17%-30% observed in other studies.
The sertraline doses used in the study ranged from 100 mg/day to 400 mg/day but researchers did not observe a significant difference in serious adverse events between the lower and higher doses (Lancet Infect Dis. 2016 Mar 9. doi: 10.1016/S1473-3099[16]00074-8).
Sertraline has previously shown potent fungicidal activity against Cryptococcus in vitro and in mice, suggesting it could be a promising therapeutic option for cryptococcal meningitis, a disease that accounts for 15%-20% of AIDS-related deaths in Africa.
“The current standard therapy for cryptococcal meningitis is based on antifungal regimens that are a half-century old, are associated with a range of toxic effects, and are largely inaccessible in areas of the world where they are needed most,” wrote Dr. Joshua Rhein of the University of Minnesota, Minneapolis, and his coauthors. “For this reason, the discovery of a widely available, nontoxic, and affordable drug effective against Cryptococcus would represent a substantial advance in preventing deaths.”
The study was supported by the National Institutes of Health, Fogarty International Center, Grand Challenges Canada, and the Doris Duke Charitable Foundation. No conflicts of interest were declared.
An open-label pilot study has found adjunct treatment with the SSRI antidepressant sertraline is associated with accelerated clearance of Cryptococcus from the cerebrospinal fluid in HIV-infected individuals with cryptococcal meningitis.
The dose-finding study of 172 HIV-infected Ugandan adults with cryptococcal meningitis showed any dose of sertraline, in combination with standard amphotericin B and high-dose fluconazole therapy, was associated with an average clearance rate of –0.37 log10 colony-forming U/mL CSF per day, compared with –0.30 observed in a previous study in individuals taking standard therapy without sertraline.
According to a paper published online in Lancet Infectious Diseases, the incidence of paradoxical immune reconstitution inflammatory syndrome was 5%, compared with rates of 17%-30% observed in other studies.
The sertraline doses used in the study ranged from 100 mg/day to 400 mg/day but researchers did not observe a significant difference in serious adverse events between the lower and higher doses (Lancet Infect Dis. 2016 Mar 9. doi: 10.1016/S1473-3099[16]00074-8).
Sertraline has previously shown potent fungicidal activity against Cryptococcus in vitro and in mice, suggesting it could be a promising therapeutic option for cryptococcal meningitis, a disease that accounts for 15%-20% of AIDS-related deaths in Africa.
“The current standard therapy for cryptococcal meningitis is based on antifungal regimens that are a half-century old, are associated with a range of toxic effects, and are largely inaccessible in areas of the world where they are needed most,” wrote Dr. Joshua Rhein of the University of Minnesota, Minneapolis, and his coauthors. “For this reason, the discovery of a widely available, nontoxic, and affordable drug effective against Cryptococcus would represent a substantial advance in preventing deaths.”
The study was supported by the National Institutes of Health, Fogarty International Center, Grand Challenges Canada, and the Doris Duke Charitable Foundation. No conflicts of interest were declared.
FROM LANCET INFECTIOUS DISEASES
Key clinical point: Sertraline may improve clearance of Cryptococcus in HIV-infected individuals with cryptococcal meningitis.
Major finding: Adjunct treatment with sertraline was associated with accelerated clearance of Cryptococcus.
Data source: Open-label, randomized, dose-finding pilot study in 172 HIV-infected individuals with cryptococcal meningitis.
Disclosures: The study was supported by the National Institutes of Health, Fogarty International Center, Grand Challenges Canada, and the Doris Duke Charitable Foundation.
April 2016: Click for Credit
Here are 4 articles in the April issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Later Menopause Lowers Risk for Later Depression
To take the posttest, go to: http://bit.ly/1U7I7f3
Expires January 6, 2017
VITALS
Key clinical point: Later menopause, with its longer estrogen exposure, appears tied to a lower risk of postmenopausal depression.
Major finding: The risk of depression decreased by 2% for each 2 premenopausal years after age 40.
Data source: The meta-analysis comprised 14 studies with more than 67,700 women.
Disclosures: Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.
2. Preschool ASD Prevalence Estimates Lower Than Grade School Estimates
To take the posttest, go to: http://bit.ly/24Mec0X
Expires January 5, 2017
VITALS
Key clinical point: The prevalence of autism spectrum disorders among 4-year-olds is about 30% lower than among 8-year-olds.
Major finding: Prevalence of ASD among 4-year-olds was 13/1,000 children across five U.S. states.
Data source: A comparison of health and medical records for nationally representative cohorts involving 58,467 4-year-olds and 56,727 8-year-olds in five U.S. states in 2010.
Disclosures: The Centers for Disease Control and Prevention funded the research. Dr. Christensen and her associates reported no disclosures.
3. Long-term PPI Use Linked to Increased Risk for Dementia
To take the posttest, go to: http://bit.ly/1nrCdsb
Expires February 24, 2017
VITALS
Key clinical point: Proton pump inhibitors may add to the risk of dementia in older adults.
Major finding: The risk of incident dementia was 44% higher in adults who used PPIs long term, compared with those who did not.
Data source: The prospective cohort study included 73,679 adults aged 75 years and older.
Disclosures: The researchers had no financial conflicts to disclose.
4. Elevated Cardiovascular Risks Linked to Hidradenitis Suppurativa
To take the posttest, go to: http://bit.ly/1nrEFz3
Expires February 17, 2017
VITALS
Key clinical point: Hidradenitis suppurativa is associated with a significantly increased risk of adverse cardiovascular events and all-cause mortality.
Major finding: Individuals with hidradenitis suppurativa had a 57% greater risk of myocardial infarction and 33% greater risk of ischemic stroke, compared with the general population.
Data source: A population-based cohort study in 5,964 patients with hidradenitis suppurativa.
Disclosures: No conflicts of interest were declared.
Here are 4 articles in the April issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Later Menopause Lowers Risk for Later Depression
To take the posttest, go to: http://bit.ly/1U7I7f3
Expires January 6, 2017
VITALS
Key clinical point: Later menopause, with its longer estrogen exposure, appears tied to a lower risk of postmenopausal depression.
Major finding: The risk of depression decreased by 2% for each 2 premenopausal years after age 40.
Data source: The meta-analysis comprised 14 studies with more than 67,700 women.
Disclosures: Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.
2. Preschool ASD Prevalence Estimates Lower Than Grade School Estimates
To take the posttest, go to: http://bit.ly/24Mec0X
Expires January 5, 2017
VITALS
Key clinical point: The prevalence of autism spectrum disorders among 4-year-olds is about 30% lower than among 8-year-olds.
Major finding: Prevalence of ASD among 4-year-olds was 13/1,000 children across five U.S. states.
Data source: A comparison of health and medical records for nationally representative cohorts involving 58,467 4-year-olds and 56,727 8-year-olds in five U.S. states in 2010.
Disclosures: The Centers for Disease Control and Prevention funded the research. Dr. Christensen and her associates reported no disclosures.
3. Long-term PPI Use Linked to Increased Risk for Dementia
To take the posttest, go to: http://bit.ly/1nrCdsb
Expires February 24, 2017
VITALS
Key clinical point: Proton pump inhibitors may add to the risk of dementia in older adults.
Major finding: The risk of incident dementia was 44% higher in adults who used PPIs long term, compared with those who did not.
Data source: The prospective cohort study included 73,679 adults aged 75 years and older.
Disclosures: The researchers had no financial conflicts to disclose.
4. Elevated Cardiovascular Risks Linked to Hidradenitis Suppurativa
To take the posttest, go to: http://bit.ly/1nrEFz3
Expires February 17, 2017
VITALS
Key clinical point: Hidradenitis suppurativa is associated with a significantly increased risk of adverse cardiovascular events and all-cause mortality.
Major finding: Individuals with hidradenitis suppurativa had a 57% greater risk of myocardial infarction and 33% greater risk of ischemic stroke, compared with the general population.
Data source: A population-based cohort study in 5,964 patients with hidradenitis suppurativa.
Disclosures: No conflicts of interest were declared.
Here are 4 articles in the April issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Later Menopause Lowers Risk for Later Depression
To take the posttest, go to: http://bit.ly/1U7I7f3
Expires January 6, 2017
VITALS
Key clinical point: Later menopause, with its longer estrogen exposure, appears tied to a lower risk of postmenopausal depression.
Major finding: The risk of depression decreased by 2% for each 2 premenopausal years after age 40.
Data source: The meta-analysis comprised 14 studies with more than 67,700 women.
Disclosures: Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.
2. Preschool ASD Prevalence Estimates Lower Than Grade School Estimates
To take the posttest, go to: http://bit.ly/24Mec0X
Expires January 5, 2017
VITALS
Key clinical point: The prevalence of autism spectrum disorders among 4-year-olds is about 30% lower than among 8-year-olds.
Major finding: Prevalence of ASD among 4-year-olds was 13/1,000 children across five U.S. states.
Data source: A comparison of health and medical records for nationally representative cohorts involving 58,467 4-year-olds and 56,727 8-year-olds in five U.S. states in 2010.
Disclosures: The Centers for Disease Control and Prevention funded the research. Dr. Christensen and her associates reported no disclosures.
3. Long-term PPI Use Linked to Increased Risk for Dementia
To take the posttest, go to: http://bit.ly/1nrCdsb
Expires February 24, 2017
VITALS
Key clinical point: Proton pump inhibitors may add to the risk of dementia in older adults.
Major finding: The risk of incident dementia was 44% higher in adults who used PPIs long term, compared with those who did not.
Data source: The prospective cohort study included 73,679 adults aged 75 years and older.
Disclosures: The researchers had no financial conflicts to disclose.
4. Elevated Cardiovascular Risks Linked to Hidradenitis Suppurativa
To take the posttest, go to: http://bit.ly/1nrEFz3
Expires February 17, 2017
VITALS
Key clinical point: Hidradenitis suppurativa is associated with a significantly increased risk of adverse cardiovascular events and all-cause mortality.
Major finding: Individuals with hidradenitis suppurativa had a 57% greater risk of myocardial infarction and 33% greater risk of ischemic stroke, compared with the general population.
Data source: A population-based cohort study in 5,964 patients with hidradenitis suppurativa.
Disclosures: No conflicts of interest were declared.
Study links microcephaly to first trimester Zika infection
A new analysis of the Zika virus outbreak in French Polynesia supports the theory that infection during the first trimester of pregnancy poses the greatest risk of the fetus developing microcephaly.
Researchers examined serological and surveillance data from a Zika outbreak in French Polynesia that lasted from October 2013 to April 2014, and searched medical records to identify cases of microcephaly diagnosed between September 2013 and July 2015. Of 8,750 suspected Zika virus infections, 383 (4.4%) were confirmed in the laboratory. There were a total of eight cases of microcephaly among pregnant women with Zika virus during the study period, including three live births, reported Simon Cauchemez, Ph.D., of Institut Pasteur, Paris, and colleagues.
Of those eight cases, all but one occurred during the four-month period from March 1 to July 10, 2014, leading researchers to suspect that the period of risk was during the first trimester of pregnancy.
Using a mathematical and statistical model that used the first trimester as the period of risk during pregnancy, the risk of microcephaly was 95 cases per 10,000 women infected during the first trimester for a risk ratio of 53.4 (95% CI 6.5-1061.2). The baseline prevalence was two cases per 10,000 neonates.
Though the researchers could not rule out an increased risk of microcephaly in other trimesters, the first trimester risk model was the best fit, they reported (The Lancet. 2016 March 15. doi: 10.1016/S0140-6736(16)00651-6).
The researchers estimated that the risk of microcephaly in the first trimester was about 1%, which is low compared to other viral infections associated with birth defects such as cytomegalovirus or congenital rubella syndrome. But the high incidence of Zika virus in the general population – reaching 66% in French Polynesia at the end of the outbreak – is a cause for concern.
“Although infection with Zika virus is associated with a low fetal risk, it is an important public health issue,” the researchers wrote. “No treatment is available for Zika virus and development of a vaccine will take time. Our findings highlight the need to inform pregnant women and women trying to become pregnant to protect themselves from mosquito bites and avoid travel to affected countries as far as possible.”
The study was supported by the French government, the National Institutes of Health, the AXA Research fund, and the European Union. The researchers reported having no financial disclosures.
The finding that the highest risk of microcephaly was associated with infection in the first trimester of pregnancy is biologically plausible, given the timing of brain development and the type and severity of the neurological abnormalities.
The risk estimate in this study is lower than that found in other studies, but are they consistent with a single underlying risk or, alternatively, will risk be dependent on other factors, such as the presence of clinical symptoms or previous dengue infection? Further data will soon be available from Pernambuco, Colombia, Rio de Janeiro, and maybe other sites that will gradually answer these questions.
Dr. Laura C Rodrigues is from the London School of Hygiene & Tropical Medicine and the Microcephaly Epidemic Research Group in Recife, Brazil. Her comments are adapted from an editorial (The Lancet. 2016 March 15. doi: 10.1016/S0140-6736(16)00742-X). She reported having no financial disclosures.
The finding that the highest risk of microcephaly was associated with infection in the first trimester of pregnancy is biologically plausible, given the timing of brain development and the type and severity of the neurological abnormalities.
The risk estimate in this study is lower than that found in other studies, but are they consistent with a single underlying risk or, alternatively, will risk be dependent on other factors, such as the presence of clinical symptoms or previous dengue infection? Further data will soon be available from Pernambuco, Colombia, Rio de Janeiro, and maybe other sites that will gradually answer these questions.
Dr. Laura C Rodrigues is from the London School of Hygiene & Tropical Medicine and the Microcephaly Epidemic Research Group in Recife, Brazil. Her comments are adapted from an editorial (The Lancet. 2016 March 15. doi: 10.1016/S0140-6736(16)00742-X). She reported having no financial disclosures.
The finding that the highest risk of microcephaly was associated with infection in the first trimester of pregnancy is biologically plausible, given the timing of brain development and the type and severity of the neurological abnormalities.
The risk estimate in this study is lower than that found in other studies, but are they consistent with a single underlying risk or, alternatively, will risk be dependent on other factors, such as the presence of clinical symptoms or previous dengue infection? Further data will soon be available from Pernambuco, Colombia, Rio de Janeiro, and maybe other sites that will gradually answer these questions.
Dr. Laura C Rodrigues is from the London School of Hygiene & Tropical Medicine and the Microcephaly Epidemic Research Group in Recife, Brazil. Her comments are adapted from an editorial (The Lancet. 2016 March 15. doi: 10.1016/S0140-6736(16)00742-X). She reported having no financial disclosures.
A new analysis of the Zika virus outbreak in French Polynesia supports the theory that infection during the first trimester of pregnancy poses the greatest risk of the fetus developing microcephaly.
Researchers examined serological and surveillance data from a Zika outbreak in French Polynesia that lasted from October 2013 to April 2014, and searched medical records to identify cases of microcephaly diagnosed between September 2013 and July 2015. Of 8,750 suspected Zika virus infections, 383 (4.4%) were confirmed in the laboratory. There were a total of eight cases of microcephaly among pregnant women with Zika virus during the study period, including three live births, reported Simon Cauchemez, Ph.D., of Institut Pasteur, Paris, and colleagues.
Of those eight cases, all but one occurred during the four-month period from March 1 to July 10, 2014, leading researchers to suspect that the period of risk was during the first trimester of pregnancy.
Using a mathematical and statistical model that used the first trimester as the period of risk during pregnancy, the risk of microcephaly was 95 cases per 10,000 women infected during the first trimester for a risk ratio of 53.4 (95% CI 6.5-1061.2). The baseline prevalence was two cases per 10,000 neonates.
Though the researchers could not rule out an increased risk of microcephaly in other trimesters, the first trimester risk model was the best fit, they reported (The Lancet. 2016 March 15. doi: 10.1016/S0140-6736(16)00651-6).
The researchers estimated that the risk of microcephaly in the first trimester was about 1%, which is low compared to other viral infections associated with birth defects such as cytomegalovirus or congenital rubella syndrome. But the high incidence of Zika virus in the general population – reaching 66% in French Polynesia at the end of the outbreak – is a cause for concern.
“Although infection with Zika virus is associated with a low fetal risk, it is an important public health issue,” the researchers wrote. “No treatment is available for Zika virus and development of a vaccine will take time. Our findings highlight the need to inform pregnant women and women trying to become pregnant to protect themselves from mosquito bites and avoid travel to affected countries as far as possible.”
The study was supported by the French government, the National Institutes of Health, the AXA Research fund, and the European Union. The researchers reported having no financial disclosures.
A new analysis of the Zika virus outbreak in French Polynesia supports the theory that infection during the first trimester of pregnancy poses the greatest risk of the fetus developing microcephaly.
Researchers examined serological and surveillance data from a Zika outbreak in French Polynesia that lasted from October 2013 to April 2014, and searched medical records to identify cases of microcephaly diagnosed between September 2013 and July 2015. Of 8,750 suspected Zika virus infections, 383 (4.4%) were confirmed in the laboratory. There were a total of eight cases of microcephaly among pregnant women with Zika virus during the study period, including three live births, reported Simon Cauchemez, Ph.D., of Institut Pasteur, Paris, and colleagues.
Of those eight cases, all but one occurred during the four-month period from March 1 to July 10, 2014, leading researchers to suspect that the period of risk was during the first trimester of pregnancy.
Using a mathematical and statistical model that used the first trimester as the period of risk during pregnancy, the risk of microcephaly was 95 cases per 10,000 women infected during the first trimester for a risk ratio of 53.4 (95% CI 6.5-1061.2). The baseline prevalence was two cases per 10,000 neonates.
Though the researchers could not rule out an increased risk of microcephaly in other trimesters, the first trimester risk model was the best fit, they reported (The Lancet. 2016 March 15. doi: 10.1016/S0140-6736(16)00651-6).
The researchers estimated that the risk of microcephaly in the first trimester was about 1%, which is low compared to other viral infections associated with birth defects such as cytomegalovirus or congenital rubella syndrome. But the high incidence of Zika virus in the general population – reaching 66% in French Polynesia at the end of the outbreak – is a cause for concern.
“Although infection with Zika virus is associated with a low fetal risk, it is an important public health issue,” the researchers wrote. “No treatment is available for Zika virus and development of a vaccine will take time. Our findings highlight the need to inform pregnant women and women trying to become pregnant to protect themselves from mosquito bites and avoid travel to affected countries as far as possible.”
The study was supported by the French government, the National Institutes of Health, the AXA Research fund, and the European Union. The researchers reported having no financial disclosures.
FROM THE LANCET
Key clinical point: Infection with Zika virus during the first trimester of pregnancy is associated with a significant increase in the risk of microcephaly in the fetus.
Major finding: The researchers estimated that risk of microcephaly in women infected with Zika virus in the first trimester was 95 cases per 10,000 women infected.
Data source: Retrospective analysis of the 2013-2014 Zika virus outbreak in French Polynesia.
Disclosures: The study was supported by the French government, the National Institutes of Health, the AXA Research fund, and the European Union. The researchers reported having no financial disclosures.
HCV risk sixfold higher with HIV
Individuals with HIV have a sixfold greater likelihood of also being infected with hepatitis C virus, according to a global systematic review and meta-analysis published in Lancet Infectious Diseases.
Researchers analyzed 783 studies of the prevalence of HIV and hepatitis C virus (HCV) infection, providing co-infection estimates for 88 countries, and found the odds of HCV infection among individuals with HIV was 5.8 times higher than in HIV-negative individuals, with an overall co-infection prevalence of 6.2% in HIV-infected individuals.
“People living with HIV without treatment are less likely to spontaneously clear HCV infection, have higher HCV viral loads, and experience more rapid HCV disease progression than those without HIV infection,” wrote Lucy Platt, Ph.D., from the London School of Hygiene & Tropical Medicine, and her coauthors.
The co-infection prevalence was lower in general population samples (2.4%) and pregnant or heterosexually exposed samples (4%), but slightly higher in men who have sex with men (6.4%) and significantly higher among individuals who inject drugs (82.4%).
The highest prevalence of co-infection in general population samples was in North Africa and the Middle East, while the highest prevalence of co-infection among men who have sex with men was found in North America, and the highest prevalence of co-infection among pregnant women was in western and central Africa (Lancet Infect Dis. 2016 Feb 24. doi: 10.1016/S1473-3099(15)00485-5).
The study was funded by the World Health Organization. One author declared funding from the Medical Research Council UK and membership in the STOP-HCV Consortium.
Although these estimates of prevalence are very helpful in drawing attention to geographical areas and risk groups with high prevalence, further data and analysis are now needed to establish the extent of morbidity and mortality that can be attributed to HIV/HCV and how that might differ between populations.
Programs have many other calls on their resources, but it should be their ambition to diagnose and eliminate HCV from their HIV cohorts, and the instruments, with perhaps the exception of appropriate molecular diagnostics, are there to do it if prices for treatment can reach affordable levels.
Dr. Graham S. Cooke is from the Division of Medicine and Dr. Timothy B. Hallett is from the School of Public Health at the Imperial College London. These comments are taken from an accompanying editorial (Lancet Infect Dis. 2016 Feb 24. doi: 10.1016/S1473-3099(15)00535-6). Dr. Hallett declared grants or fees from the World Health Organization, the Bill and Melinda Gates Foundation, Global Fund, Anansi Consulting, Avenir Health, Rush Foundation, WHO, UNAIDS, and the World Bank. Dr. Cooke declared from Gilead, Janssen, and WHO.
Although these estimates of prevalence are very helpful in drawing attention to geographical areas and risk groups with high prevalence, further data and analysis are now needed to establish the extent of morbidity and mortality that can be attributed to HIV/HCV and how that might differ between populations.
Programs have many other calls on their resources, but it should be their ambition to diagnose and eliminate HCV from their HIV cohorts, and the instruments, with perhaps the exception of appropriate molecular diagnostics, are there to do it if prices for treatment can reach affordable levels.
Dr. Graham S. Cooke is from the Division of Medicine and Dr. Timothy B. Hallett is from the School of Public Health at the Imperial College London. These comments are taken from an accompanying editorial (Lancet Infect Dis. 2016 Feb 24. doi: 10.1016/S1473-3099(15)00535-6). Dr. Hallett declared grants or fees from the World Health Organization, the Bill and Melinda Gates Foundation, Global Fund, Anansi Consulting, Avenir Health, Rush Foundation, WHO, UNAIDS, and the World Bank. Dr. Cooke declared from Gilead, Janssen, and WHO.
Although these estimates of prevalence are very helpful in drawing attention to geographical areas and risk groups with high prevalence, further data and analysis are now needed to establish the extent of morbidity and mortality that can be attributed to HIV/HCV and how that might differ between populations.
Programs have many other calls on their resources, but it should be their ambition to diagnose and eliminate HCV from their HIV cohorts, and the instruments, with perhaps the exception of appropriate molecular diagnostics, are there to do it if prices for treatment can reach affordable levels.
Dr. Graham S. Cooke is from the Division of Medicine and Dr. Timothy B. Hallett is from the School of Public Health at the Imperial College London. These comments are taken from an accompanying editorial (Lancet Infect Dis. 2016 Feb 24. doi: 10.1016/S1473-3099(15)00535-6). Dr. Hallett declared grants or fees from the World Health Organization, the Bill and Melinda Gates Foundation, Global Fund, Anansi Consulting, Avenir Health, Rush Foundation, WHO, UNAIDS, and the World Bank. Dr. Cooke declared from Gilead, Janssen, and WHO.
Individuals with HIV have a sixfold greater likelihood of also being infected with hepatitis C virus, according to a global systematic review and meta-analysis published in Lancet Infectious Diseases.
Researchers analyzed 783 studies of the prevalence of HIV and hepatitis C virus (HCV) infection, providing co-infection estimates for 88 countries, and found the odds of HCV infection among individuals with HIV was 5.8 times higher than in HIV-negative individuals, with an overall co-infection prevalence of 6.2% in HIV-infected individuals.
“People living with HIV without treatment are less likely to spontaneously clear HCV infection, have higher HCV viral loads, and experience more rapid HCV disease progression than those without HIV infection,” wrote Lucy Platt, Ph.D., from the London School of Hygiene & Tropical Medicine, and her coauthors.
The co-infection prevalence was lower in general population samples (2.4%) and pregnant or heterosexually exposed samples (4%), but slightly higher in men who have sex with men (6.4%) and significantly higher among individuals who inject drugs (82.4%).
The highest prevalence of co-infection in general population samples was in North Africa and the Middle East, while the highest prevalence of co-infection among men who have sex with men was found in North America, and the highest prevalence of co-infection among pregnant women was in western and central Africa (Lancet Infect Dis. 2016 Feb 24. doi: 10.1016/S1473-3099(15)00485-5).
The study was funded by the World Health Organization. One author declared funding from the Medical Research Council UK and membership in the STOP-HCV Consortium.
Individuals with HIV have a sixfold greater likelihood of also being infected with hepatitis C virus, according to a global systematic review and meta-analysis published in Lancet Infectious Diseases.
Researchers analyzed 783 studies of the prevalence of HIV and hepatitis C virus (HCV) infection, providing co-infection estimates for 88 countries, and found the odds of HCV infection among individuals with HIV was 5.8 times higher than in HIV-negative individuals, with an overall co-infection prevalence of 6.2% in HIV-infected individuals.
“People living with HIV without treatment are less likely to spontaneously clear HCV infection, have higher HCV viral loads, and experience more rapid HCV disease progression than those without HIV infection,” wrote Lucy Platt, Ph.D., from the London School of Hygiene & Tropical Medicine, and her coauthors.
The co-infection prevalence was lower in general population samples (2.4%) and pregnant or heterosexually exposed samples (4%), but slightly higher in men who have sex with men (6.4%) and significantly higher among individuals who inject drugs (82.4%).
The highest prevalence of co-infection in general population samples was in North Africa and the Middle East, while the highest prevalence of co-infection among men who have sex with men was found in North America, and the highest prevalence of co-infection among pregnant women was in western and central Africa (Lancet Infect Dis. 2016 Feb 24. doi: 10.1016/S1473-3099(15)00485-5).
The study was funded by the World Health Organization. One author declared funding from the Medical Research Council UK and membership in the STOP-HCV Consortium.
FROM THE LANCET INFECTIOUS DISEASES
Key clinical point: Individuals with HIV have a sixfold greater likelihood of also being infected with hepatitis C virus.
Major finding: The odds of HCV infection among individuals with HIV are 5.8 times higher than in HIV-negative individuals.
Data source: Systematic review and meta-analysis of 783 studies.
Disclosures: The study was funded by the World Health Organization. One author declared funding from the Medical Research Council UK and membership of the STOP-HCV Consortium.
Birth-cohort HCV Testing Misses One-quarter of Infections
Birth-cohort screening for hepatitis C virus according to U.S. Centers for Disease Control and Prevention guidelines may miss around one-quarter of infections, researchers said.
An 8-week seroprevalence survey in an urban emergency department tested excess blood samples from 4,713 patients for hepatitis C virus, finding an overall prevalence of 13.8%, of which 31.3% was undocumented infection.
According to a paper published in Clinical Infectious Diseases, among the 204 patients with undocumented HCV infection, 48.5% were born between 1945 and 1965 and therefore would have been included in birth-cohort testing, and 26.5% would have been picked up for risk-based testing.
But 25% of the patients found to be infected with HCV in the study would not have been tested based on birth cohort or risk (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw074).
The CDC added the recommendation for one-time testing of individuals born between 1945 and 1965 to its existing advice on risk-based screening in 2012, and this was backed by the U.S. Preventive Services Task Force in 2013.
“Since the CDC’s revised HIV testing recommendations for the health care settings were released, many EDs have had great success in implementing routine HIV testing to the population they serve over the past decade,” wrote Dr. Yu-Hsiang Hsieh of Johns Hopkins University, Baltimore, and coauthors. “This coupled with the availability of effective therapeutics makes EDs a key and strategic component of the national plan to expand HCV testing.”
At the same time, a second study, also in an urban emergency department, tested samples from 924 individuals enrolled in an HIV prevalence survey.
In this study, published in the same issue of Clinical Infectious Diseases, researchers found HCV antibodies in samples from 128 patients (14%); 34% of whom self-reported a history of HCV or hepatitis and 81% of whom were RNA positive.
The researchers noted, however, that, had they only implemented birth-cohort or risk-based screening, they would have missed 28% of individuals with antibodies and 25% of individuals with replicative HCV.
In this study, individuals with HCV infection were more likely to report injection drug use and high-risk sexual behavior, even among individuals reporting neither of these risk factors, but the prevalence of HCV infection was 7% (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw073).
“We also cannot compare our results with the epidemiology of the surrounding population not using the ED, but suggest that as is the case with HIV, EDs are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment,” wrote Dr. Michael S. Lyons and colleagues from the University of Cincinnati.
The authors, however, suggested that their survey may have underestimated the current prevalence of HCV because of an increase in heroin use in the area in more recent years.
Dr. Hsieh and colleagues suggested there was a need to revise the CDC recommendations and expand the age cut-off to all individuals aged 18 years or over.
The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
Birth-cohort screening for hepatitis C virus according to U.S. Centers for Disease Control and Prevention guidelines may miss around one-quarter of infections, researchers said.
An 8-week seroprevalence survey in an urban emergency department tested excess blood samples from 4,713 patients for hepatitis C virus, finding an overall prevalence of 13.8%, of which 31.3% was undocumented infection.
According to a paper published in Clinical Infectious Diseases, among the 204 patients with undocumented HCV infection, 48.5% were born between 1945 and 1965 and therefore would have been included in birth-cohort testing, and 26.5% would have been picked up for risk-based testing.
But 25% of the patients found to be infected with HCV in the study would not have been tested based on birth cohort or risk (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw074).
The CDC added the recommendation for one-time testing of individuals born between 1945 and 1965 to its existing advice on risk-based screening in 2012, and this was backed by the U.S. Preventive Services Task Force in 2013.
“Since the CDC’s revised HIV testing recommendations for the health care settings were released, many EDs have had great success in implementing routine HIV testing to the population they serve over the past decade,” wrote Dr. Yu-Hsiang Hsieh of Johns Hopkins University, Baltimore, and coauthors. “This coupled with the availability of effective therapeutics makes EDs a key and strategic component of the national plan to expand HCV testing.”
At the same time, a second study, also in an urban emergency department, tested samples from 924 individuals enrolled in an HIV prevalence survey.
In this study, published in the same issue of Clinical Infectious Diseases, researchers found HCV antibodies in samples from 128 patients (14%); 34% of whom self-reported a history of HCV or hepatitis and 81% of whom were RNA positive.
The researchers noted, however, that, had they only implemented birth-cohort or risk-based screening, they would have missed 28% of individuals with antibodies and 25% of individuals with replicative HCV.
In this study, individuals with HCV infection were more likely to report injection drug use and high-risk sexual behavior, even among individuals reporting neither of these risk factors, but the prevalence of HCV infection was 7% (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw073).
“We also cannot compare our results with the epidemiology of the surrounding population not using the ED, but suggest that as is the case with HIV, EDs are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment,” wrote Dr. Michael S. Lyons and colleagues from the University of Cincinnati.
The authors, however, suggested that their survey may have underestimated the current prevalence of HCV because of an increase in heroin use in the area in more recent years.
Dr. Hsieh and colleagues suggested there was a need to revise the CDC recommendations and expand the age cut-off to all individuals aged 18 years or over.
The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
Birth-cohort screening for hepatitis C virus according to U.S. Centers for Disease Control and Prevention guidelines may miss around one-quarter of infections, researchers said.
An 8-week seroprevalence survey in an urban emergency department tested excess blood samples from 4,713 patients for hepatitis C virus, finding an overall prevalence of 13.8%, of which 31.3% was undocumented infection.
According to a paper published in Clinical Infectious Diseases, among the 204 patients with undocumented HCV infection, 48.5% were born between 1945 and 1965 and therefore would have been included in birth-cohort testing, and 26.5% would have been picked up for risk-based testing.
But 25% of the patients found to be infected with HCV in the study would not have been tested based on birth cohort or risk (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw074).
The CDC added the recommendation for one-time testing of individuals born between 1945 and 1965 to its existing advice on risk-based screening in 2012, and this was backed by the U.S. Preventive Services Task Force in 2013.
“Since the CDC’s revised HIV testing recommendations for the health care settings were released, many EDs have had great success in implementing routine HIV testing to the population they serve over the past decade,” wrote Dr. Yu-Hsiang Hsieh of Johns Hopkins University, Baltimore, and coauthors. “This coupled with the availability of effective therapeutics makes EDs a key and strategic component of the national plan to expand HCV testing.”
At the same time, a second study, also in an urban emergency department, tested samples from 924 individuals enrolled in an HIV prevalence survey.
In this study, published in the same issue of Clinical Infectious Diseases, researchers found HCV antibodies in samples from 128 patients (14%); 34% of whom self-reported a history of HCV or hepatitis and 81% of whom were RNA positive.
The researchers noted, however, that, had they only implemented birth-cohort or risk-based screening, they would have missed 28% of individuals with antibodies and 25% of individuals with replicative HCV.
In this study, individuals with HCV infection were more likely to report injection drug use and high-risk sexual behavior, even among individuals reporting neither of these risk factors, but the prevalence of HCV infection was 7% (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw073).
“We also cannot compare our results with the epidemiology of the surrounding population not using the ED, but suggest that as is the case with HIV, EDs are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment,” wrote Dr. Michael S. Lyons and colleagues from the University of Cincinnati.
The authors, however, suggested that their survey may have underestimated the current prevalence of HCV because of an increase in heroin use in the area in more recent years.
Dr. Hsieh and colleagues suggested there was a need to revise the CDC recommendations and expand the age cut-off to all individuals aged 18 years or over.
The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
FROM CLINICAL INFECTIOUS DISEASES
Birth-cohort HCV testing misses one-quarter of infections
Birth-cohort screening for hepatitis C virus according to U.S. Centers for Disease Control and Prevention guidelines may miss around one-quarter of infections, researchers said.
An 8-week seroprevalence survey in an urban emergency department tested excess blood samples from 4,713 patients for hepatitis C virus, finding an overall prevalence of 13.8%, of which 31.3% was undocumented infection.
According to a paper published in Clinical Infectious Diseases, among the 204 patients with undocumented HCV infection, 48.5% were born between 1945 and 1965 and therefore would have been included in birth-cohort testing, and 26.5% would have been picked up for risk-based testing.
But 25% of the patients found to be infected with HCV in the study would not have been tested based on birth cohort or risk (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw074).
The CDC added the recommendation for one-time testing of individuals born between 1945 and 1965 to its existing advice on risk-based screening in 2012, and this was backed by the U.S. Preventive Services Task Force in 2013.
“Since the CDC’s revised HIV testing recommendations for the health care settings were released, many EDs have had great success in implementing routine HIV testing to the population they serve over the past decade,” wrote Dr. Yu-Hsiang Hsieh of Johns Hopkins University, Baltimore, and coauthors. “This coupled with the availability of effective therapeutics makes EDs a key and strategic component of the national plan to expand HCV testing.”
At the same time, a second study, also in an urban emergency department, tested samples from 924 individuals enrolled in an HIV prevalence survey.
In this study, published in the same issue of Clinical Infectious Diseases, researchers found HCV antibodies in samples from 128 patients (14%); 34% of whom self-reported a history of HCV or hepatitis and 81% of whom were RNA positive.
The researchers noted, however, that, had they only implemented birth-cohort or risk-based screening, they would have missed 28% of individuals with antibodies and 25% of individuals with replicative HCV.
In this study, individuals with HCV infection were more likely to report injection drug use and high-risk sexual behavior, even among individuals reporting neither of these risk factors, but the prevalence of HCV infection was 7% (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw073).
“We also cannot compare our results with the epidemiology of the surrounding population not using the ED, but suggest that as is the case with HIV, EDs are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment,” wrote Dr. Michael S. Lyons and colleagues from the University of Cincinnati.
The authors, however, suggested that their survey may have underestimated the current prevalence of HCV because of an increase in heroin use in the area in more recent years.
Dr. Hsieh and colleagues suggested there was a need to revise the CDC recommendations and expand the age cut-off to all individuals aged 18 years or over.
The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
Birth-cohort screening for hepatitis C virus according to U.S. Centers for Disease Control and Prevention guidelines may miss around one-quarter of infections, researchers said.
An 8-week seroprevalence survey in an urban emergency department tested excess blood samples from 4,713 patients for hepatitis C virus, finding an overall prevalence of 13.8%, of which 31.3% was undocumented infection.
According to a paper published in Clinical Infectious Diseases, among the 204 patients with undocumented HCV infection, 48.5% were born between 1945 and 1965 and therefore would have been included in birth-cohort testing, and 26.5% would have been picked up for risk-based testing.
But 25% of the patients found to be infected with HCV in the study would not have been tested based on birth cohort or risk (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw074).
The CDC added the recommendation for one-time testing of individuals born between 1945 and 1965 to its existing advice on risk-based screening in 2012, and this was backed by the U.S. Preventive Services Task Force in 2013.
“Since the CDC’s revised HIV testing recommendations for the health care settings were released, many EDs have had great success in implementing routine HIV testing to the population they serve over the past decade,” wrote Dr. Yu-Hsiang Hsieh of Johns Hopkins University, Baltimore, and coauthors. “This coupled with the availability of effective therapeutics makes EDs a key and strategic component of the national plan to expand HCV testing.”
At the same time, a second study, also in an urban emergency department, tested samples from 924 individuals enrolled in an HIV prevalence survey.
In this study, published in the same issue of Clinical Infectious Diseases, researchers found HCV antibodies in samples from 128 patients (14%); 34% of whom self-reported a history of HCV or hepatitis and 81% of whom were RNA positive.
The researchers noted, however, that, had they only implemented birth-cohort or risk-based screening, they would have missed 28% of individuals with antibodies and 25% of individuals with replicative HCV.
In this study, individuals with HCV infection were more likely to report injection drug use and high-risk sexual behavior, even among individuals reporting neither of these risk factors, but the prevalence of HCV infection was 7% (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw073).
“We also cannot compare our results with the epidemiology of the surrounding population not using the ED, but suggest that as is the case with HIV, EDs are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment,” wrote Dr. Michael S. Lyons and colleagues from the University of Cincinnati.
The authors, however, suggested that their survey may have underestimated the current prevalence of HCV because of an increase in heroin use in the area in more recent years.
Dr. Hsieh and colleagues suggested there was a need to revise the CDC recommendations and expand the age cut-off to all individuals aged 18 years or over.
The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
Birth-cohort screening for hepatitis C virus according to U.S. Centers for Disease Control and Prevention guidelines may miss around one-quarter of infections, researchers said.
An 8-week seroprevalence survey in an urban emergency department tested excess blood samples from 4,713 patients for hepatitis C virus, finding an overall prevalence of 13.8%, of which 31.3% was undocumented infection.
According to a paper published in Clinical Infectious Diseases, among the 204 patients with undocumented HCV infection, 48.5% were born between 1945 and 1965 and therefore would have been included in birth-cohort testing, and 26.5% would have been picked up for risk-based testing.
But 25% of the patients found to be infected with HCV in the study would not have been tested based on birth cohort or risk (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw074).
The CDC added the recommendation for one-time testing of individuals born between 1945 and 1965 to its existing advice on risk-based screening in 2012, and this was backed by the U.S. Preventive Services Task Force in 2013.
“Since the CDC’s revised HIV testing recommendations for the health care settings were released, many EDs have had great success in implementing routine HIV testing to the population they serve over the past decade,” wrote Dr. Yu-Hsiang Hsieh of Johns Hopkins University, Baltimore, and coauthors. “This coupled with the availability of effective therapeutics makes EDs a key and strategic component of the national plan to expand HCV testing.”
At the same time, a second study, also in an urban emergency department, tested samples from 924 individuals enrolled in an HIV prevalence survey.
In this study, published in the same issue of Clinical Infectious Diseases, researchers found HCV antibodies in samples from 128 patients (14%); 34% of whom self-reported a history of HCV or hepatitis and 81% of whom were RNA positive.
The researchers noted, however, that, had they only implemented birth-cohort or risk-based screening, they would have missed 28% of individuals with antibodies and 25% of individuals with replicative HCV.
In this study, individuals with HCV infection were more likely to report injection drug use and high-risk sexual behavior, even among individuals reporting neither of these risk factors, but the prevalence of HCV infection was 7% (Clin Infect Dis. 2016 Feb 21. doi: 10.1093/cid/ciw073).
“We also cannot compare our results with the epidemiology of the surrounding population not using the ED, but suggest that as is the case with HIV, EDs are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment,” wrote Dr. Michael S. Lyons and colleagues from the University of Cincinnati.
The authors, however, suggested that their survey may have underestimated the current prevalence of HCV because of an increase in heroin use in the area in more recent years.
Dr. Hsieh and colleagues suggested there was a need to revise the CDC recommendations and expand the age cut-off to all individuals aged 18 years or over.
The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
FROM CLINICAL INFECTIOUS DISEASES
Key clinical point: CDC recommendations for birth-cohort and high-risk screening for hepatitis C infection may miss one-quarter of infections.
Major finding: One in four patients with undocumented HCV infection would not otherwise have been tested based on birth cohort or risk.
Data source: A cross-sectional prevalence study involving 924 individuals and a seroprevalence study of 4,713 individuals.
Disclosures: The first study was supported by the National Institutes of Health and the authors declared no conflicts of interest. The second study was partly supported by Gilead Sciences, the National Institutes of Health, and Bristol-Myers Squibb. Four of the seven authors reported support, research grants, consultancies, or advisory board positions with pharmaceutical companies including Gilead and Bristol-Myers Squibb.
Primary Care Acne Treatment Reduces Dermatology Referrals
If primary care providers initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.
The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.
Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.
If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.
Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).
“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.
In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.
One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
If primary care providers initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.
The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.
Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.
If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.
Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).
“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.
In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.
One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
If primary care providers initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.
The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.
Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.
If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.
Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).
“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.
In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.
One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
FROM JAMA DERMATOLOGY
Primary care acne treatment reduces dermatology referrals
If primary care physicians initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.
The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.
Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.
If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.
Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).
“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.
In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.
One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
If primary care physicians initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.
The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.
Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.
If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.
Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).
“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.
In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.
One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
If primary care physicians initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.
The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.
Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.
If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.
Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).
“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.
In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.
One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
FROM JAMA DERMATOLOGY
Key clinical point: If primary care physicians initiate treatment of mild to moderate acne, they could significantly reduce referrals to dermatologists and patient waiting times for treatment.
Major finding: Primary care treatment can reduce referrals to dermatologists for acne by up to 72%.
Data source: A retrospective study and modeling of 253 referrals.
Disclosures: One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.
ANGPTL4 mutation ties lower triglycerides to lower CAD risk
A genetic link between elevated triglycerides and coronary heart disease has been identified, opening up the possibility of a new treatment target.
Two separate studies have linked mutations in a gene associated with inhibition of the enzyme lipoprotein lipase – which reduces circulating triglycerides – to lower triglyceride levels and a lower risk of coronary artery disease. Both were published online on March 2 in the New England Journal of Medicine.
The first study reported the sequencing of the angiopoietin-like 4 (ANGPTL4) gene, which is responsible for a protein that inhibits the action of lipoprotein lipase.
One known mutation in this gene, the E40K variant, has previously been associated with decreased triglycerides and elevated HDL cholesterol, but its impact on coronary artery disease risk was unclear.
This sequencing, using samples from 42,930 predominantly European individuals, found the 17 (0.04%) participants who were homozygous for E40K had 13% lower triglycerides levels and 7% higher HDL cholesterol, compared with those without the mutation.
E40K mutation carriers also had a 4% lower risk of coronary artery disease per allele, compared with noncarriers, after adjustment for age, sex and ancestry.
In the same study, researchers looked at the effect of a monoclonal antibody against ANGPTL4 in five obese rhesus monkeys with dyslipidemia.
The treatment was associated with a 60% reduction in circulating triglyceride levels from baseline in four of the five monkeys and a 95% reduction in one monkey (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMoa1510926).
“Our data support ANGPTL4 as a therapeutic target for inhibition through an antibody or other mechanism for reducing the risk of cardiovascular disease in humans,” wrote Dr. Frederick E. Dewey of the Regeneron Genetics Center, Tarrytown, N.Y., and coauthors.
Researchers also checked for evidence of the intestinal and mesenteric lymphadenopathy – which had been noted in some preclinical trials of the ANGPTL4 antibody – in individuals with the E40K mutation that inactivates ANGPTL4 – but found no increase in incidence, compared with noncarriers.
The second study reported on the DNA genotyping of 13,715 genes in 72,868 individuals with coronary artery disease and 120,770 controls without heart disease.
This revealed significantly increased risk associated with variants in the LPA and PCSK9 genes, both of which have previously been associated with coronary artery disease, but a significantly decreased risk of coronary artery disease associated with the same E40K variant of ANGPTL4 found in the first study.
When researchers looked at the effect of these variants on risk factors for coronary artery disease, they found the E40K variant was associated with significantly lower triglyceride levels and significantly higher HDL cholesterol levels per copy of the allele (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMoa1507652).
Given the relationship between ANGPTL4, lipoprotein lipase, and heart disease risk, researchers postulated that mutations resulting in decreased function of lipoprotein lipase would increase triglyceride levels and the risk of coronary artery disease.
They identified a loss-of-function mutation in the lipoprotein lipase gene that was associated with an increased risk of coronary artery disease, and a gain-of-function mutation in the same gene that appeared to decrease the risk.
“Our results highlight LPL [lipoprotein lipase] as a significant contributor to the risk of coronary artery disease and support the hypothesis that a gain of LPL function or loss of ANGPTL4 inhibition protects against the disease,” wrote Dr. Nathan O. Stitziel of Washington University, St. Louis, and coauthors.
The first study was supported by Regeneron Pharmaceuticals. Several authors declared employment, stock holdings, institutional funding, and other support from Regeneron. One author declared a patent holding for an ANGPTL4 antibody, and five authors had no conflicts of interest to declare.
The second study’s authors declared a range of supporting grants and awards. Conflicts of interest declared included employment with and funding from pharmaceutical companies but many authors also reported no conflicts of interest.
The key finding in each study was that carriers of the E40K mutation and other rare mutations in ANGPTL4 had a lower risk of coronary artery disease than did noncarriers, a result that is consistent with the lower triglyceride levels and higher HDL cholesterol among mutation carriers.
These two studies that identify ANGPTL4 as a link between triglycerides and coronary heart disease not only improve our understanding of elevated triglycerides in heart disease, but also provide a path to the development of future therapies for dyslipidemia.
Dr. Sander Kersten, Ph.D., of the division of human nutrition at Wageningen University, the Netherlands, made these comments in an accompanying editorial (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMe1601117). Dr. Kersten declared grant support from the Leducq Foundation, the European Foundation for the Study of Diabetes, the Netherlands Heart Foundation, and the Netherlands Organization for Scientific Research.
The key finding in each study was that carriers of the E40K mutation and other rare mutations in ANGPTL4 had a lower risk of coronary artery disease than did noncarriers, a result that is consistent with the lower triglyceride levels and higher HDL cholesterol among mutation carriers.
These two studies that identify ANGPTL4 as a link between triglycerides and coronary heart disease not only improve our understanding of elevated triglycerides in heart disease, but also provide a path to the development of future therapies for dyslipidemia.
Dr. Sander Kersten, Ph.D., of the division of human nutrition at Wageningen University, the Netherlands, made these comments in an accompanying editorial (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMe1601117). Dr. Kersten declared grant support from the Leducq Foundation, the European Foundation for the Study of Diabetes, the Netherlands Heart Foundation, and the Netherlands Organization for Scientific Research.
The key finding in each study was that carriers of the E40K mutation and other rare mutations in ANGPTL4 had a lower risk of coronary artery disease than did noncarriers, a result that is consistent with the lower triglyceride levels and higher HDL cholesterol among mutation carriers.
These two studies that identify ANGPTL4 as a link between triglycerides and coronary heart disease not only improve our understanding of elevated triglycerides in heart disease, but also provide a path to the development of future therapies for dyslipidemia.
Dr. Sander Kersten, Ph.D., of the division of human nutrition at Wageningen University, the Netherlands, made these comments in an accompanying editorial (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMe1601117). Dr. Kersten declared grant support from the Leducq Foundation, the European Foundation for the Study of Diabetes, the Netherlands Heart Foundation, and the Netherlands Organization for Scientific Research.
A genetic link between elevated triglycerides and coronary heart disease has been identified, opening up the possibility of a new treatment target.
Two separate studies have linked mutations in a gene associated with inhibition of the enzyme lipoprotein lipase – which reduces circulating triglycerides – to lower triglyceride levels and a lower risk of coronary artery disease. Both were published online on March 2 in the New England Journal of Medicine.
The first study reported the sequencing of the angiopoietin-like 4 (ANGPTL4) gene, which is responsible for a protein that inhibits the action of lipoprotein lipase.
One known mutation in this gene, the E40K variant, has previously been associated with decreased triglycerides and elevated HDL cholesterol, but its impact on coronary artery disease risk was unclear.
This sequencing, using samples from 42,930 predominantly European individuals, found the 17 (0.04%) participants who were homozygous for E40K had 13% lower triglycerides levels and 7% higher HDL cholesterol, compared with those without the mutation.
E40K mutation carriers also had a 4% lower risk of coronary artery disease per allele, compared with noncarriers, after adjustment for age, sex and ancestry.
In the same study, researchers looked at the effect of a monoclonal antibody against ANGPTL4 in five obese rhesus monkeys with dyslipidemia.
The treatment was associated with a 60% reduction in circulating triglyceride levels from baseline in four of the five monkeys and a 95% reduction in one monkey (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMoa1510926).
“Our data support ANGPTL4 as a therapeutic target for inhibition through an antibody or other mechanism for reducing the risk of cardiovascular disease in humans,” wrote Dr. Frederick E. Dewey of the Regeneron Genetics Center, Tarrytown, N.Y., and coauthors.
Researchers also checked for evidence of the intestinal and mesenteric lymphadenopathy – which had been noted in some preclinical trials of the ANGPTL4 antibody – in individuals with the E40K mutation that inactivates ANGPTL4 – but found no increase in incidence, compared with noncarriers.
The second study reported on the DNA genotyping of 13,715 genes in 72,868 individuals with coronary artery disease and 120,770 controls without heart disease.
This revealed significantly increased risk associated with variants in the LPA and PCSK9 genes, both of which have previously been associated with coronary artery disease, but a significantly decreased risk of coronary artery disease associated with the same E40K variant of ANGPTL4 found in the first study.
When researchers looked at the effect of these variants on risk factors for coronary artery disease, they found the E40K variant was associated with significantly lower triglyceride levels and significantly higher HDL cholesterol levels per copy of the allele (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMoa1507652).
Given the relationship between ANGPTL4, lipoprotein lipase, and heart disease risk, researchers postulated that mutations resulting in decreased function of lipoprotein lipase would increase triglyceride levels and the risk of coronary artery disease.
They identified a loss-of-function mutation in the lipoprotein lipase gene that was associated with an increased risk of coronary artery disease, and a gain-of-function mutation in the same gene that appeared to decrease the risk.
“Our results highlight LPL [lipoprotein lipase] as a significant contributor to the risk of coronary artery disease and support the hypothesis that a gain of LPL function or loss of ANGPTL4 inhibition protects against the disease,” wrote Dr. Nathan O. Stitziel of Washington University, St. Louis, and coauthors.
The first study was supported by Regeneron Pharmaceuticals. Several authors declared employment, stock holdings, institutional funding, and other support from Regeneron. One author declared a patent holding for an ANGPTL4 antibody, and five authors had no conflicts of interest to declare.
The second study’s authors declared a range of supporting grants and awards. Conflicts of interest declared included employment with and funding from pharmaceutical companies but many authors also reported no conflicts of interest.
A genetic link between elevated triglycerides and coronary heart disease has been identified, opening up the possibility of a new treatment target.
Two separate studies have linked mutations in a gene associated with inhibition of the enzyme lipoprotein lipase – which reduces circulating triglycerides – to lower triglyceride levels and a lower risk of coronary artery disease. Both were published online on March 2 in the New England Journal of Medicine.
The first study reported the sequencing of the angiopoietin-like 4 (ANGPTL4) gene, which is responsible for a protein that inhibits the action of lipoprotein lipase.
One known mutation in this gene, the E40K variant, has previously been associated with decreased triglycerides and elevated HDL cholesterol, but its impact on coronary artery disease risk was unclear.
This sequencing, using samples from 42,930 predominantly European individuals, found the 17 (0.04%) participants who were homozygous for E40K had 13% lower triglycerides levels and 7% higher HDL cholesterol, compared with those without the mutation.
E40K mutation carriers also had a 4% lower risk of coronary artery disease per allele, compared with noncarriers, after adjustment for age, sex and ancestry.
In the same study, researchers looked at the effect of a monoclonal antibody against ANGPTL4 in five obese rhesus monkeys with dyslipidemia.
The treatment was associated with a 60% reduction in circulating triglyceride levels from baseline in four of the five monkeys and a 95% reduction in one monkey (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMoa1510926).
“Our data support ANGPTL4 as a therapeutic target for inhibition through an antibody or other mechanism for reducing the risk of cardiovascular disease in humans,” wrote Dr. Frederick E. Dewey of the Regeneron Genetics Center, Tarrytown, N.Y., and coauthors.
Researchers also checked for evidence of the intestinal and mesenteric lymphadenopathy – which had been noted in some preclinical trials of the ANGPTL4 antibody – in individuals with the E40K mutation that inactivates ANGPTL4 – but found no increase in incidence, compared with noncarriers.
The second study reported on the DNA genotyping of 13,715 genes in 72,868 individuals with coronary artery disease and 120,770 controls without heart disease.
This revealed significantly increased risk associated with variants in the LPA and PCSK9 genes, both of which have previously been associated with coronary artery disease, but a significantly decreased risk of coronary artery disease associated with the same E40K variant of ANGPTL4 found in the first study.
When researchers looked at the effect of these variants on risk factors for coronary artery disease, they found the E40K variant was associated with significantly lower triglyceride levels and significantly higher HDL cholesterol levels per copy of the allele (N Engl J Med. 2016 Mar 2. doi: 10.1056/NEJMoa1507652).
Given the relationship between ANGPTL4, lipoprotein lipase, and heart disease risk, researchers postulated that mutations resulting in decreased function of lipoprotein lipase would increase triglyceride levels and the risk of coronary artery disease.
They identified a loss-of-function mutation in the lipoprotein lipase gene that was associated with an increased risk of coronary artery disease, and a gain-of-function mutation in the same gene that appeared to decrease the risk.
“Our results highlight LPL [lipoprotein lipase] as a significant contributor to the risk of coronary artery disease and support the hypothesis that a gain of LPL function or loss of ANGPTL4 inhibition protects against the disease,” wrote Dr. Nathan O. Stitziel of Washington University, St. Louis, and coauthors.
The first study was supported by Regeneron Pharmaceuticals. Several authors declared employment, stock holdings, institutional funding, and other support from Regeneron. One author declared a patent holding for an ANGPTL4 antibody, and five authors had no conflicts of interest to declare.
The second study’s authors declared a range of supporting grants and awards. Conflicts of interest declared included employment with and funding from pharmaceutical companies but many authors also reported no conflicts of interest.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Researchers have identified a genetic link between elevated triglycerides and coronary heart disease.
Major finding: Mutations associated with decreased triglyceride levels and increased HDL cholesterol are also associated with a lower risk of coronary artery disease.
Data source: Two genetic studies, one in 42,930 individuals and the other in 72,868 individuals with coronary artery disease and 120,770 controls without.
Disclosures: The first study was supported by Regeneron Pharmaceuticals. Several authors declared employment, stock holdings, institutional funding, and other support from Regeneron. One author declared a patent holding for an ANGPTL4 antibody, and five authors had no conflicts of interest to declare.
The second study’s authors declared a range of supporting grants and awards. Conflicts of interest declared included employment with and funding from pharmaceutical companies but many authors also reported no conflicts of interest.
Zika more complex public health challenge than Ebola
The vector-borne and often asymptomatic nature of Zika virus infection makes it a more complex public health challenge than Ebola, researchers say.
The Zika virus was first isolated from a macaque in Uganda in 1947, and has historically been restricted to Africa and Asia. However since its introduction to Brazil in 2014 or early 2015, possibly via Polynesia, it has spread rapidly and estimates now point to between 440,000 and 1,300,000 cases of Zika virus infection in Brazil during 2015.
In the past, Zika virus infection in adults has presented with non-life-threatening symptoms including mild fever, maculopapular rash, arthralgia, myalgia, headache, retro-orbital pain and vomiting.
Writing in the March 1 online edition of PLoS Neglected Tropical Diseases, researchers say the viral variant currently associated with the outbreak in Brazil is presenting a new and more challenging public health problem.
“What makes this outbreak a high priority global public health concern is the association with incidence of birth defects involving the central nervous system and the apparent increased incidence of Guillain-Barré syndrome,” wrote Dr. Robert W. Malone, from RW Malone MD, and his coauthors (PLoS Negl Trop Dis. 2016 Mar 1. doi: 10.1371/journal.pntd.0004530).
They cited one retrospective study in French Polynesia that suggested there was a ratio of one case of Zika-associated Guillain-Barré syndrome for every 208 suspected cases of Zika virus infection.
The outbreak has also been linked to an unusually high incidence of the otherwise rare microcephaly, with Brazil recording a 20-fold increase in incidence during 2015. The connection with Zika virus is supported by a case study in which large numbers of viral particles were found in the central nervous system tissue of a microcephalic Zika-infected fetus.
Based on estimates of the overall incidence of Zika virus infection, researchers have calculated that Brazilian mothers infected with the virus are 3,700-11,000 times more likely to deliver infants with primary microcephaly, compared with those who are not infected.
There are still some key uncertainties around the transmission of Zika virus, the authors said.
“The degree to which humans, nonhuman primates, or other animals can amplify and transmit the virus to insect vectors is poorly understood,” they wrote. “The typical range and types of insect vectors observed in the past may not be predictive for the virus now circulating in the Americas [and] infectivity of the circulating strain, viremia levels, duration, and risk of occult persistence are not yet understood.”
The virus is transmitted primarily by mosquito vectors such as Aedes aegypti and Aedes albopictus, with primates – including humans – the best documented animal reservoir.
“Recent reports indicate the potential for both human blood-borne and sexual transmission of Zika virus, including prolonged presence of virus in semen,” the authors wrote.
The virus has also been found in the saliva of infected individuals, and viral sequences have been identified in breast milk.Commenting on possible medical countermeasures to combat the spread and impact of the Zika virus, the paper’s authors noted that due to the absence of an existing vaccine and long potential development times for candidate vaccines, other prophylactics and therapeutics need to be explored.
In particular, they called for development and deployment of Zika diagnostics to regional clinical health laboratories, discussions between obstetricians and patients about the risks to ongoing or planned pregnancies, and resources for neurologists dealing with “unprecedented” Guillain-Barré syndrome outbreaks.
“Perhaps the biggest challenge with Zika will be to recognize it for what it is: a new disease which does not fit the epidemiology or response paradigm of Ebola or dengue and which will demand effort, resources, unparalleled collaboration, and above all, open mindedness in formulating responses.”
Two authors declared employment with and equity holdings in RW Malone MD, and two authors declared employment with – and one of these also declared equity holdings in – Nanotherapeutics.
The vector-borne and often asymptomatic nature of Zika virus infection makes it a more complex public health challenge than Ebola, researchers say.
The Zika virus was first isolated from a macaque in Uganda in 1947, and has historically been restricted to Africa and Asia. However since its introduction to Brazil in 2014 or early 2015, possibly via Polynesia, it has spread rapidly and estimates now point to between 440,000 and 1,300,000 cases of Zika virus infection in Brazil during 2015.
In the past, Zika virus infection in adults has presented with non-life-threatening symptoms including mild fever, maculopapular rash, arthralgia, myalgia, headache, retro-orbital pain and vomiting.
Writing in the March 1 online edition of PLoS Neglected Tropical Diseases, researchers say the viral variant currently associated with the outbreak in Brazil is presenting a new and more challenging public health problem.
“What makes this outbreak a high priority global public health concern is the association with incidence of birth defects involving the central nervous system and the apparent increased incidence of Guillain-Barré syndrome,” wrote Dr. Robert W. Malone, from RW Malone MD, and his coauthors (PLoS Negl Trop Dis. 2016 Mar 1. doi: 10.1371/journal.pntd.0004530).
They cited one retrospective study in French Polynesia that suggested there was a ratio of one case of Zika-associated Guillain-Barré syndrome for every 208 suspected cases of Zika virus infection.
The outbreak has also been linked to an unusually high incidence of the otherwise rare microcephaly, with Brazil recording a 20-fold increase in incidence during 2015. The connection with Zika virus is supported by a case study in which large numbers of viral particles were found in the central nervous system tissue of a microcephalic Zika-infected fetus.
Based on estimates of the overall incidence of Zika virus infection, researchers have calculated that Brazilian mothers infected with the virus are 3,700-11,000 times more likely to deliver infants with primary microcephaly, compared with those who are not infected.
There are still some key uncertainties around the transmission of Zika virus, the authors said.
“The degree to which humans, nonhuman primates, or other animals can amplify and transmit the virus to insect vectors is poorly understood,” they wrote. “The typical range and types of insect vectors observed in the past may not be predictive for the virus now circulating in the Americas [and] infectivity of the circulating strain, viremia levels, duration, and risk of occult persistence are not yet understood.”
The virus is transmitted primarily by mosquito vectors such as Aedes aegypti and Aedes albopictus, with primates – including humans – the best documented animal reservoir.
“Recent reports indicate the potential for both human blood-borne and sexual transmission of Zika virus, including prolonged presence of virus in semen,” the authors wrote.
The virus has also been found in the saliva of infected individuals, and viral sequences have been identified in breast milk.Commenting on possible medical countermeasures to combat the spread and impact of the Zika virus, the paper’s authors noted that due to the absence of an existing vaccine and long potential development times for candidate vaccines, other prophylactics and therapeutics need to be explored.
In particular, they called for development and deployment of Zika diagnostics to regional clinical health laboratories, discussions between obstetricians and patients about the risks to ongoing or planned pregnancies, and resources for neurologists dealing with “unprecedented” Guillain-Barré syndrome outbreaks.
“Perhaps the biggest challenge with Zika will be to recognize it for what it is: a new disease which does not fit the epidemiology or response paradigm of Ebola or dengue and which will demand effort, resources, unparalleled collaboration, and above all, open mindedness in formulating responses.”
Two authors declared employment with and equity holdings in RW Malone MD, and two authors declared employment with – and one of these also declared equity holdings in – Nanotherapeutics.
The vector-borne and often asymptomatic nature of Zika virus infection makes it a more complex public health challenge than Ebola, researchers say.
The Zika virus was first isolated from a macaque in Uganda in 1947, and has historically been restricted to Africa and Asia. However since its introduction to Brazil in 2014 or early 2015, possibly via Polynesia, it has spread rapidly and estimates now point to between 440,000 and 1,300,000 cases of Zika virus infection in Brazil during 2015.
In the past, Zika virus infection in adults has presented with non-life-threatening symptoms including mild fever, maculopapular rash, arthralgia, myalgia, headache, retro-orbital pain and vomiting.
Writing in the March 1 online edition of PLoS Neglected Tropical Diseases, researchers say the viral variant currently associated with the outbreak in Brazil is presenting a new and more challenging public health problem.
“What makes this outbreak a high priority global public health concern is the association with incidence of birth defects involving the central nervous system and the apparent increased incidence of Guillain-Barré syndrome,” wrote Dr. Robert W. Malone, from RW Malone MD, and his coauthors (PLoS Negl Trop Dis. 2016 Mar 1. doi: 10.1371/journal.pntd.0004530).
They cited one retrospective study in French Polynesia that suggested there was a ratio of one case of Zika-associated Guillain-Barré syndrome for every 208 suspected cases of Zika virus infection.
The outbreak has also been linked to an unusually high incidence of the otherwise rare microcephaly, with Brazil recording a 20-fold increase in incidence during 2015. The connection with Zika virus is supported by a case study in which large numbers of viral particles were found in the central nervous system tissue of a microcephalic Zika-infected fetus.
Based on estimates of the overall incidence of Zika virus infection, researchers have calculated that Brazilian mothers infected with the virus are 3,700-11,000 times more likely to deliver infants with primary microcephaly, compared with those who are not infected.
There are still some key uncertainties around the transmission of Zika virus, the authors said.
“The degree to which humans, nonhuman primates, or other animals can amplify and transmit the virus to insect vectors is poorly understood,” they wrote. “The typical range and types of insect vectors observed in the past may not be predictive for the virus now circulating in the Americas [and] infectivity of the circulating strain, viremia levels, duration, and risk of occult persistence are not yet understood.”
The virus is transmitted primarily by mosquito vectors such as Aedes aegypti and Aedes albopictus, with primates – including humans – the best documented animal reservoir.
“Recent reports indicate the potential for both human blood-borne and sexual transmission of Zika virus, including prolonged presence of virus in semen,” the authors wrote.
The virus has also been found in the saliva of infected individuals, and viral sequences have been identified in breast milk.Commenting on possible medical countermeasures to combat the spread and impact of the Zika virus, the paper’s authors noted that due to the absence of an existing vaccine and long potential development times for candidate vaccines, other prophylactics and therapeutics need to be explored.
In particular, they called for development and deployment of Zika diagnostics to regional clinical health laboratories, discussions between obstetricians and patients about the risks to ongoing or planned pregnancies, and resources for neurologists dealing with “unprecedented” Guillain-Barré syndrome outbreaks.
“Perhaps the biggest challenge with Zika will be to recognize it for what it is: a new disease which does not fit the epidemiology or response paradigm of Ebola or dengue and which will demand effort, resources, unparalleled collaboration, and above all, open mindedness in formulating responses.”
Two authors declared employment with and equity holdings in RW Malone MD, and two authors declared employment with – and one of these also declared equity holdings in – Nanotherapeutics.
FROM PLOS NEGLECTED TROPICAL DISEASES
