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Female cancer researchers receive less funding than male counterparts
Female cancer researchers receive significantly less funding than their male counterparts in terms of total investment, number of awards, and mean and median funding, according to an analysis of data on public and philanthropic cancer research funding awarded to U.K. institutions between 2000 and 2013.
In an analysis of 4,186 awards totaling 2.33 billion pounds, 2,890 grants (69%) with a total value of 1.82 billion pounds (78%) were awarded to male primary investigators (PIs), compared with just 1,296 grants (31%) with a total value of 512 million pounds(22%) for female PIs, investigators reported in BMJ Open.
Investigators studied openly accessible information on funding awards from public and philanthropic sources including the Medical Research Council, Department of Health, Biotechnology and Biological Sciences Research Council, Engineering and Physical Science Research Council, Wellcome Trust, European Commission, and nine members of the Association of Medical Research Charities. Awards were excluded if they were not relevant to oncology, led by a non-U.K. institution, and/or not considered a research and development activity, wrote Charlie D. Zhou, MD, of the Royal Free NHS Foundation Trust Department of Nuclear Medicine in London, and coauthors.
Median grant value was greater for men (252,647 pounds; interquartile range, 127,343-553,560 pounds) than for women (198,485 pounds; IQR, 99,317-382,650 pounds) (P less than .001). Mean grant value was also greater for men (630,324 pounds; standard deviation, 1,662,559 pounds) than for women (394,730 pounds; SD, 666,574 pounds), Dr. Zhou and colleagues reported.
Large funding discrepancies were seen for sex-specific cancer research. For instance, males received 13.8, 3.5, and 2.0 times the investment of their female counterparts in total, mean, and median prostate cancer funding, respectively. Likewise, men received 9.9, 6.6, and 2.9 times the funding of women PIs in total, mean, and median funding, respectively, for cervical cancer research. This pattern was true for ovarian cancer and breast cancer research, as well.
Men also received significantly greater median funding at all points of the research and development pipeline. For preclinical, phase 1, 2, or 3 clinical trials; and public health, men received 20%, 90%, and 50% more, respectively (P less than .001); for product development and cross-disciplinary research, the difference was 50% and 20%, respectively (P less than .01).
The results of the analysis demonstrate that “female PIs clearly and consistently receive less funding than their male counterparts,” the authors wrote. Although the study results are descriptive in nature and do not identify the underlying mechanisms for these discrepancies, they “demonstrate substantial gender imbalances in cancer research investment.
“We would strongly urge policy makers, funders and the academic and scientific community to investigate the factors leading to our observed differences and seek to ensure that women are appropriately supported in scientific endeavor,” they concluded.
No disclosures or conflicts of interest were reported.
SOURCE: Zhou CD et al. BMJ Open. 2018 Apr 30. doi: 10.1136/bmjopen-2017-018625.
Female cancer researchers receive significantly less funding than their male counterparts in terms of total investment, number of awards, and mean and median funding, according to an analysis of data on public and philanthropic cancer research funding awarded to U.K. institutions between 2000 and 2013.
In an analysis of 4,186 awards totaling 2.33 billion pounds, 2,890 grants (69%) with a total value of 1.82 billion pounds (78%) were awarded to male primary investigators (PIs), compared with just 1,296 grants (31%) with a total value of 512 million pounds(22%) for female PIs, investigators reported in BMJ Open.
Investigators studied openly accessible information on funding awards from public and philanthropic sources including the Medical Research Council, Department of Health, Biotechnology and Biological Sciences Research Council, Engineering and Physical Science Research Council, Wellcome Trust, European Commission, and nine members of the Association of Medical Research Charities. Awards were excluded if they were not relevant to oncology, led by a non-U.K. institution, and/or not considered a research and development activity, wrote Charlie D. Zhou, MD, of the Royal Free NHS Foundation Trust Department of Nuclear Medicine in London, and coauthors.
Median grant value was greater for men (252,647 pounds; interquartile range, 127,343-553,560 pounds) than for women (198,485 pounds; IQR, 99,317-382,650 pounds) (P less than .001). Mean grant value was also greater for men (630,324 pounds; standard deviation, 1,662,559 pounds) than for women (394,730 pounds; SD, 666,574 pounds), Dr. Zhou and colleagues reported.
Large funding discrepancies were seen for sex-specific cancer research. For instance, males received 13.8, 3.5, and 2.0 times the investment of their female counterparts in total, mean, and median prostate cancer funding, respectively. Likewise, men received 9.9, 6.6, and 2.9 times the funding of women PIs in total, mean, and median funding, respectively, for cervical cancer research. This pattern was true for ovarian cancer and breast cancer research, as well.
Men also received significantly greater median funding at all points of the research and development pipeline. For preclinical, phase 1, 2, or 3 clinical trials; and public health, men received 20%, 90%, and 50% more, respectively (P less than .001); for product development and cross-disciplinary research, the difference was 50% and 20%, respectively (P less than .01).
The results of the analysis demonstrate that “female PIs clearly and consistently receive less funding than their male counterparts,” the authors wrote. Although the study results are descriptive in nature and do not identify the underlying mechanisms for these discrepancies, they “demonstrate substantial gender imbalances in cancer research investment.
“We would strongly urge policy makers, funders and the academic and scientific community to investigate the factors leading to our observed differences and seek to ensure that women are appropriately supported in scientific endeavor,” they concluded.
No disclosures or conflicts of interest were reported.
SOURCE: Zhou CD et al. BMJ Open. 2018 Apr 30. doi: 10.1136/bmjopen-2017-018625.
Female cancer researchers receive significantly less funding than their male counterparts in terms of total investment, number of awards, and mean and median funding, according to an analysis of data on public and philanthropic cancer research funding awarded to U.K. institutions between 2000 and 2013.
In an analysis of 4,186 awards totaling 2.33 billion pounds, 2,890 grants (69%) with a total value of 1.82 billion pounds (78%) were awarded to male primary investigators (PIs), compared with just 1,296 grants (31%) with a total value of 512 million pounds(22%) for female PIs, investigators reported in BMJ Open.
Investigators studied openly accessible information on funding awards from public and philanthropic sources including the Medical Research Council, Department of Health, Biotechnology and Biological Sciences Research Council, Engineering and Physical Science Research Council, Wellcome Trust, European Commission, and nine members of the Association of Medical Research Charities. Awards were excluded if they were not relevant to oncology, led by a non-U.K. institution, and/or not considered a research and development activity, wrote Charlie D. Zhou, MD, of the Royal Free NHS Foundation Trust Department of Nuclear Medicine in London, and coauthors.
Median grant value was greater for men (252,647 pounds; interquartile range, 127,343-553,560 pounds) than for women (198,485 pounds; IQR, 99,317-382,650 pounds) (P less than .001). Mean grant value was also greater for men (630,324 pounds; standard deviation, 1,662,559 pounds) than for women (394,730 pounds; SD, 666,574 pounds), Dr. Zhou and colleagues reported.
Large funding discrepancies were seen for sex-specific cancer research. For instance, males received 13.8, 3.5, and 2.0 times the investment of their female counterparts in total, mean, and median prostate cancer funding, respectively. Likewise, men received 9.9, 6.6, and 2.9 times the funding of women PIs in total, mean, and median funding, respectively, for cervical cancer research. This pattern was true for ovarian cancer and breast cancer research, as well.
Men also received significantly greater median funding at all points of the research and development pipeline. For preclinical, phase 1, 2, or 3 clinical trials; and public health, men received 20%, 90%, and 50% more, respectively (P less than .001); for product development and cross-disciplinary research, the difference was 50% and 20%, respectively (P less than .01).
The results of the analysis demonstrate that “female PIs clearly and consistently receive less funding than their male counterparts,” the authors wrote. Although the study results are descriptive in nature and do not identify the underlying mechanisms for these discrepancies, they “demonstrate substantial gender imbalances in cancer research investment.
“We would strongly urge policy makers, funders and the academic and scientific community to investigate the factors leading to our observed differences and seek to ensure that women are appropriately supported in scientific endeavor,” they concluded.
No disclosures or conflicts of interest were reported.
SOURCE: Zhou CD et al. BMJ Open. 2018 Apr 30. doi: 10.1136/bmjopen-2017-018625.
FROM BMJ OPEN
Key clinical point: Female cancer researchers receive significantly less funding than their male counterparts.
Major finding: Of 4,186 awards, 2,890 grants (69%) were awarded to male primary investigators (PIs), compared with 1,296 grants (31%) for female PIs.
Study details: An analysis of data on public and philanthropic cancer research funding awarded to U.K. institutions between 2000 and 2013.
Disclosures: No disclosures or conflicts of interest were reported.
Source: Zhou CD et al. BMJ Open. 2018 Apr 30. doi: 10.1136/bmjopen-2017-018625.
Oncology postmarketing requirements mostly on schedule
Food and Drug Administration postmarketing requirement (PMR) studies for cancer drugs tend to be completed on schedule, but the drugs can remain on the market even if primary endpoints in those studies are not met, according to a research letter in JAMA Oncology.
“These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators,” wrote Chadi Nabhan, MD, MBA, chief medical officer at Cardinal Health in Dublin, Ohio, and Marjorie Zettler, PhD, MPH, senior scientist at Cardinal Health.
The researchers reviewed the FDA’s Novel Drug Summary and compared the requirements listed there with information in the FDA’s Postmarket Requirements and Commitments database and on the Clinicaltrials.gov website.
The FDA has relied on its accelerated approval program, using surrogate or intermediate endpoints deemed to reasonably predict clinical benefit, in order to balance expeditious approval with patient safety. And it has used postmarketing requirements to try to mitigate the risk of this program.
From January 2011 to December 2016, 49 new drugs were approved in oncology, 23 of which were granted an accelerated approval. Of those 23, 17 had postmarketing requirements to complete, including 34 clinical trials. Of the 34 trials, researchers found, 15 have been completed, 14 are ongoing, 2 have been terminated, and 3 are pending.
Out of the 15 clinical studies that have been completed, 3 failed to meet their primary efficacy end points – for atezolizumab, nivolumab and pembrolizumab. None of the drugs have been pulled from the market, researchers noted.
The two terminated studies, both for idelalisib, were stopped because of safety concerns. One product, ponatinib, was temporarily pulled, and the FDA required further studies, with a risk evaluation and mitigation study. That postmarketing study was eventually resumed and completed.
“Recently, the FDA has been criticized for its oversight of PMR clinical studies. The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late,” the authors wrote. “Our own review of PMR clinical studies for novel oncology drug products granted AA [accelerated approval] within the last 6 years found that no studies were behind their original schedules.”
“However,” they went on to note, “PMR studies identified serious safety concerns in two incidents that resulted in changes to the labeling for both products [idelalisib and ponatinib]. In addition, our analysis identified three instances [20%] where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.”
No disclosures were reported
SOURCE: Nabhan C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0610.
Food and Drug Administration postmarketing requirement (PMR) studies for cancer drugs tend to be completed on schedule, but the drugs can remain on the market even if primary endpoints in those studies are not met, according to a research letter in JAMA Oncology.
“These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators,” wrote Chadi Nabhan, MD, MBA, chief medical officer at Cardinal Health in Dublin, Ohio, and Marjorie Zettler, PhD, MPH, senior scientist at Cardinal Health.
The researchers reviewed the FDA’s Novel Drug Summary and compared the requirements listed there with information in the FDA’s Postmarket Requirements and Commitments database and on the Clinicaltrials.gov website.
The FDA has relied on its accelerated approval program, using surrogate or intermediate endpoints deemed to reasonably predict clinical benefit, in order to balance expeditious approval with patient safety. And it has used postmarketing requirements to try to mitigate the risk of this program.
From January 2011 to December 2016, 49 new drugs were approved in oncology, 23 of which were granted an accelerated approval. Of those 23, 17 had postmarketing requirements to complete, including 34 clinical trials. Of the 34 trials, researchers found, 15 have been completed, 14 are ongoing, 2 have been terminated, and 3 are pending.
Out of the 15 clinical studies that have been completed, 3 failed to meet their primary efficacy end points – for atezolizumab, nivolumab and pembrolizumab. None of the drugs have been pulled from the market, researchers noted.
The two terminated studies, both for idelalisib, were stopped because of safety concerns. One product, ponatinib, was temporarily pulled, and the FDA required further studies, with a risk evaluation and mitigation study. That postmarketing study was eventually resumed and completed.
“Recently, the FDA has been criticized for its oversight of PMR clinical studies. The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late,” the authors wrote. “Our own review of PMR clinical studies for novel oncology drug products granted AA [accelerated approval] within the last 6 years found that no studies were behind their original schedules.”
“However,” they went on to note, “PMR studies identified serious safety concerns in two incidents that resulted in changes to the labeling for both products [idelalisib and ponatinib]. In addition, our analysis identified three instances [20%] where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.”
No disclosures were reported
SOURCE: Nabhan C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0610.
Food and Drug Administration postmarketing requirement (PMR) studies for cancer drugs tend to be completed on schedule, but the drugs can remain on the market even if primary endpoints in those studies are not met, according to a research letter in JAMA Oncology.
“These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators,” wrote Chadi Nabhan, MD, MBA, chief medical officer at Cardinal Health in Dublin, Ohio, and Marjorie Zettler, PhD, MPH, senior scientist at Cardinal Health.
The researchers reviewed the FDA’s Novel Drug Summary and compared the requirements listed there with information in the FDA’s Postmarket Requirements and Commitments database and on the Clinicaltrials.gov website.
The FDA has relied on its accelerated approval program, using surrogate or intermediate endpoints deemed to reasonably predict clinical benefit, in order to balance expeditious approval with patient safety. And it has used postmarketing requirements to try to mitigate the risk of this program.
From January 2011 to December 2016, 49 new drugs were approved in oncology, 23 of which were granted an accelerated approval. Of those 23, 17 had postmarketing requirements to complete, including 34 clinical trials. Of the 34 trials, researchers found, 15 have been completed, 14 are ongoing, 2 have been terminated, and 3 are pending.
Out of the 15 clinical studies that have been completed, 3 failed to meet their primary efficacy end points – for atezolizumab, nivolumab and pembrolizumab. None of the drugs have been pulled from the market, researchers noted.
The two terminated studies, both for idelalisib, were stopped because of safety concerns. One product, ponatinib, was temporarily pulled, and the FDA required further studies, with a risk evaluation and mitigation study. That postmarketing study was eventually resumed and completed.
“Recently, the FDA has been criticized for its oversight of PMR clinical studies. The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late,” the authors wrote. “Our own review of PMR clinical studies for novel oncology drug products granted AA [accelerated approval] within the last 6 years found that no studies were behind their original schedules.”
“However,” they went on to note, “PMR studies identified serious safety concerns in two incidents that resulted in changes to the labeling for both products [idelalisib and ponatinib]. In addition, our analysis identified three instances [20%] where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.”
No disclosures were reported
SOURCE: Nabhan C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0610.
FROM JAMA ONCOLOGY
Key clinical point: Of 49 oncology drugs approved by the FDA from January 2011 to December 2016, 23 were given accelerated approval, with 17 needing postmarketing research.
Major finding: None of the pending or ongoing studies are behind their original schedules.
Study details: A review of the FDA’s Novel Drugs Summary, the FDA’s Postmarket Requirements and Commitments database, and Clinicaltrials.gov information.
Disclosures: No disclosures were reported.
Source: Nabhan C et al. JAMA Oncol. 2018 May 10. doi:10.1001/jamaoncol.2018.0610.
What is the microbiology of liver abscess?
Case
A 29-year-old woman with chronic urticaria, previously on omalizumab, presented with 2 weeks of abdominal pain and fever. She had traveled to Nicaragua within the past 10 months. CT showed a 6 x 5 cm liver abscess. Entamoeba histolytica was detected by stool polymerase chain reaction, and E. histolytica antibody was positive. The abscess was drained, and she completed a 10-day course of metronidazole followed by a 7-day course of paromomycin.
Brief overview
Bacterial, parasitic, and fungal organisms can cause liver abscess. Worldwide, bacteria are the most common cause of liver abscess. Infection is usually polymicrobial, though Klebsiella and the Streptococcus milleri group are the most common organisms identified.
Entamoeba histolytica is the most frequent cause of amoebic liver abscess and should be strongly considered in a returning traveler, visitor from another country, or those on monoclonal antibody therapy directed against IgE such as omalizumab. Candida species are the most common fungal etiology; an example being hepatosplenic candidiasis in hematologic malignancies.
Overview of the data
Pyogenic liver abscess. A variety of bacteria have been isolated from pyogenic liver abscesses (PLA) because of differences in mechanism of infection (such as biliary tract interventions, postoperative complications, and hematogenous spread), immunocompromised states, and geographical variation. The literature is not robust for pyogenic liver abscesses, and the microbiology isolated via epidemiologic studies are confounded by the mechanism of infection and thus difficult to generalize.
Initially, the Enterobacteriaceae including Klebsiella pneumoniae and Escherichia coli were the most common cause of PLA in the United States. The emergence of improved culturing techniques, which has improved the yield of facultative anaerobes such as the Streptococcus milleri (also known as Streptococcus anginosus) group, has led to an increased incidence and wider assortment of bacteria, with a more recent study of 38 patients in the Cleveland Clinic system showing that about half of the PLA were polymicrobial with the predominant organism when monomicrobial being of the Strep milleri group in 9/22 patients (Chemaly et al.).
Biliary tract disease, whether from choledocholithiasis, stricture, or malignant obstruction is the most common etiology of PLA. Much of the PLA-focused literature is from Asia, where Klebsiella is more commonly a cause of liver abscess. In a study of 248 Taiwanese patients with PLA, Klebsiella was responsible for 69% of PLA (Yang et al.). In a study of 79 patients hospitalized in New York, Klebsiella was the most common bacteria isolated, although more than half of the patients studied were Asian, and Klebsiella was more common among Asian patients than the other groups studied. An 8-year analysis of patients admitted to a University Hospital in Taiwan with cryptogenic PLA showed that the etiology was Klebsiella in 46/52 patients (Chen et al.). Most patients with Klebsiella liver abscess have documented bacteremia.
The second most common mechanism is bacterial translocation through the portal venous system. E. coli is commonly isolated and is frequently spread from intra-abdominal infections such as appendicitis leading to pylephlebitis. As the diagnosis and management of appendicitis has improved, the incidence of appendicitis causing a PLA has decreased.
PLA should be cultured to guide therapy and catheter drainage may be required. However, common organisms causing liver abscess should also be considered when selecting initial antibiotic therapy as cultures are frequently affected by previous antibiotic exposure or imprecise culturing techniques. Blood cultures should be obtained, and empiric therapy with a beta-lactam/beta-lactamase inhibitor or third-generation cephalosporin plus metronidazole should be started thereafter.
Entamoeba histolytica. E. histolytica, an anaerobic parasite that can lead to amoebic dysentery and liver abscess, affects upwards of 50 million people worldwide, predominantly in India and sub-Saharan Africa. Travel to an endemic area for longer than 1 month carries a high risk of transmission, though cases have been described with less than a week of exposure.
Infection occurs following consumption of affected food or water and can lead to dysentery within 3 weeks. Fever and right upper quadrant pain develop later, anywhere from 3 months to years following initial exposure. To diagnose, both serologic and stool testing for E. histolytica are recommended owing to the high sensitivity and low specificity of the serologic antibody test and the low sensitivity and high specificity of the stool antigen test. Imaging may reveal a single cyst with surrounding edema, which is characteristic.
Effective treatment is a two-step process. Metronidazole targets trophozoites that cause liver abscesses followed by paromomycin or diloxanide furoate to eradicate luminal oocysts and prevent reinfection. Aspiration and catheter drainage is necessary if the microbiology or etiology of the liver abscess remains uncertain, patients are not responding to antibiotics, or there is concern for impending rupture with cyst size greater than 6 cm (Jun et al.).
Hydatid cysts. Serologic testing via enzyme-linked immunoassay and radiographic characteristics are used to diagnose cysts caused by Echinococcus, of which there are many species. Imaging typically shows a well-defined cyst with calcifications and budding daughter cysts. Aspiration of an echinococcal cyst carries a risk of anaphylaxis and spread of infection and should only be undertaken if there is serologic and radiographic uncertainty.
Fungal abscesses. Fungal abscesses are most commonly caused by Candida species. The typical patient presentation includes high fever and elevated alkaline phosphatase, usually during the count recovery phase of patients with hematologic malignancies undergoing chemotherapy.
Fungal abscesses are frequently too small to aspirate. Fortunately, serum and radiographic results, as well as the clinical setting, make diagnosis more straightforward. Serum fungal markers can be checked and empiric treatment with amphotericin B or an echinocandin is recommended, followed by narrowing to oral fluconazole. Treatment should continue until abscesses resolve.
Interestingly, if patients become neutropenic during their antifungal course, the microabscesses may disappear on CT or MRI, only to reappear once neutrophils return. Once patients have a stable neutrophil count and imaging shows no abscesses, antifungal treatment can be discontinued, but must be restarted if patients are to undergo additional chemotherapy with expected neutropenia.
Back to the case
While impossible to state with certainty, infection with E. histolytica while in Nicaragua was thought most likely in this case. This patient was on omalizumab for chronic urticaria immediately prior to acquiring the infection and this anti-IgE monoclonal antibody likely predisposed her to a parasitic infection. Knowing this epidemiology, she may not have required catheter drainage, however, the cyst was causing pain and drainage provided decompression. She was treated with antibiotics followed by paromomycin.
Bottom line
Entamoeba histolytica is the most common cause of liver abscess worldwide, but identifying risk factors and mechanism of infection can lead to the most likely infecting organism.
Dr. Mehra is assistant professor of medicine in the Section of Hospital Medicine at the University of Virginia Medical Center and School of Medicine, Charlottesville. Dr. Parsons is also assistant professor of medicine in the Section of Hospital Medicine at the University of Virginia Medical Center and School of Medicine.
References
Chemaly RF. Microbiology of liver abscesses and the predictive value of abscess gram stain and associated blood cultures. Diagn Microbiol Infect Dis. 2003;46(4):245-8.
Yang CC. Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae. J Microbiol Immunol Infect. 2004;37(3):176.
Chen SC. Comparison of pyogenic liver abscesses of biliary and cryptogenic origin. An eight-year analysis in a University Hospital. Swiss Med Wkly. 2005;135(23-24):344-51.
Yang CC. Pyogenic liver abscess in Taiwan: emphasis on gas-forming liver abscess in diabetics. Am J Gastroenterol. 1993;88:1911-15.
Jun CH. Risk factors and clinical outcomes for spontaneous rupture of pyogenic liver abscess. J Dig Dis. 2015;16(1):31-6.
Smego RA Jr. Treatment options for hepatic cystic echinococcosis. Int J Infect Dis. 2005;9(2):69-76.
Additional reading
Huang CJ et al. Pyogenic hepatic abscess. Changing trends over 42 years. Ann Surg. 1996;223(5):600-7.
Meddings L et al. A population-based study of pyogenic liver abscesses in the United States: incidence, mortality, and temporal trends. Am J Gastroenterol. 2010;105(1):117-24..
Petri WA, Singh U. Diagnosis and management of amoebiasis. Clin Infect Dis. 1999 Nov;29(5):1117-25.
Accompanying Photo caption: CT scan showing E. histolytica liver abscess. RELATED PHOTO IS PHOTOMICROGRAPH, NOT CT SCAN. G
Quiz
Microbiology of liver abscesses
Bacterial, parasitic, and fungal organisms can all cause liver abscesses. History, including travel history, is very important in deciphering which organisms are present.
Question 1: What is the most common cause of an amoebic liver abscess worldwide?
A. Echinococcus
B. Klebsiella pneumoniae
C. Entamoeba histolytica
D. Escherichia coli
The best answer is choice C. E. histolytica causes amoebic dysentery and liver abscess. This anaerobic parasite affects 50 million people worldwide, with the highest prevalence in India, sub-Saharan Africa, Mexico, and parts of Central and South America. Travelers spending a month or more in endemic areas are at highest risk, but cases have been reported with less than one week of exposure.
Question 2: Which type of parasitic cyst should not be aspirated?
A. Echinococcus
B. Entamoeba histolytica
C. Schistosomiasis
D. Paramoeba
The best answer is choice A. Aspiration of an echinococcal cyst carries a risk of anaphylaxis and spread of infection and should only be done if there is serologic and radiographic uncertainty. Imaging typically shows a well-defined cyst with calcifications and budding daughter cysts.
Key Points
- Risk factors and mechanism of action will suggest the most likely organisms and guide antibiotic choice.
- Entamoeba histolytica is the most common cause of liver abscess worldwide.
- Stool PCR and antibody testing for E. histolytica should both be ordered in the work-up of a liver abscess.
- Calcifications and daughter cysts budding off the main cyst can distinguish echinococcal cyst from E. histolytica abscess radiographically.
Case
A 29-year-old woman with chronic urticaria, previously on omalizumab, presented with 2 weeks of abdominal pain and fever. She had traveled to Nicaragua within the past 10 months. CT showed a 6 x 5 cm liver abscess. Entamoeba histolytica was detected by stool polymerase chain reaction, and E. histolytica antibody was positive. The abscess was drained, and she completed a 10-day course of metronidazole followed by a 7-day course of paromomycin.
Brief overview
Bacterial, parasitic, and fungal organisms can cause liver abscess. Worldwide, bacteria are the most common cause of liver abscess. Infection is usually polymicrobial, though Klebsiella and the Streptococcus milleri group are the most common organisms identified.
Entamoeba histolytica is the most frequent cause of amoebic liver abscess and should be strongly considered in a returning traveler, visitor from another country, or those on monoclonal antibody therapy directed against IgE such as omalizumab. Candida species are the most common fungal etiology; an example being hepatosplenic candidiasis in hematologic malignancies.
Overview of the data
Pyogenic liver abscess. A variety of bacteria have been isolated from pyogenic liver abscesses (PLA) because of differences in mechanism of infection (such as biliary tract interventions, postoperative complications, and hematogenous spread), immunocompromised states, and geographical variation. The literature is not robust for pyogenic liver abscesses, and the microbiology isolated via epidemiologic studies are confounded by the mechanism of infection and thus difficult to generalize.
Initially, the Enterobacteriaceae including Klebsiella pneumoniae and Escherichia coli were the most common cause of PLA in the United States. The emergence of improved culturing techniques, which has improved the yield of facultative anaerobes such as the Streptococcus milleri (also known as Streptococcus anginosus) group, has led to an increased incidence and wider assortment of bacteria, with a more recent study of 38 patients in the Cleveland Clinic system showing that about half of the PLA were polymicrobial with the predominant organism when monomicrobial being of the Strep milleri group in 9/22 patients (Chemaly et al.).
Biliary tract disease, whether from choledocholithiasis, stricture, or malignant obstruction is the most common etiology of PLA. Much of the PLA-focused literature is from Asia, where Klebsiella is more commonly a cause of liver abscess. In a study of 248 Taiwanese patients with PLA, Klebsiella was responsible for 69% of PLA (Yang et al.). In a study of 79 patients hospitalized in New York, Klebsiella was the most common bacteria isolated, although more than half of the patients studied were Asian, and Klebsiella was more common among Asian patients than the other groups studied. An 8-year analysis of patients admitted to a University Hospital in Taiwan with cryptogenic PLA showed that the etiology was Klebsiella in 46/52 patients (Chen et al.). Most patients with Klebsiella liver abscess have documented bacteremia.
The second most common mechanism is bacterial translocation through the portal venous system. E. coli is commonly isolated and is frequently spread from intra-abdominal infections such as appendicitis leading to pylephlebitis. As the diagnosis and management of appendicitis has improved, the incidence of appendicitis causing a PLA has decreased.
PLA should be cultured to guide therapy and catheter drainage may be required. However, common organisms causing liver abscess should also be considered when selecting initial antibiotic therapy as cultures are frequently affected by previous antibiotic exposure or imprecise culturing techniques. Blood cultures should be obtained, and empiric therapy with a beta-lactam/beta-lactamase inhibitor or third-generation cephalosporin plus metronidazole should be started thereafter.
Entamoeba histolytica. E. histolytica, an anaerobic parasite that can lead to amoebic dysentery and liver abscess, affects upwards of 50 million people worldwide, predominantly in India and sub-Saharan Africa. Travel to an endemic area for longer than 1 month carries a high risk of transmission, though cases have been described with less than a week of exposure.
Infection occurs following consumption of affected food or water and can lead to dysentery within 3 weeks. Fever and right upper quadrant pain develop later, anywhere from 3 months to years following initial exposure. To diagnose, both serologic and stool testing for E. histolytica are recommended owing to the high sensitivity and low specificity of the serologic antibody test and the low sensitivity and high specificity of the stool antigen test. Imaging may reveal a single cyst with surrounding edema, which is characteristic.
Effective treatment is a two-step process. Metronidazole targets trophozoites that cause liver abscesses followed by paromomycin or diloxanide furoate to eradicate luminal oocysts and prevent reinfection. Aspiration and catheter drainage is necessary if the microbiology or etiology of the liver abscess remains uncertain, patients are not responding to antibiotics, or there is concern for impending rupture with cyst size greater than 6 cm (Jun et al.).
Hydatid cysts. Serologic testing via enzyme-linked immunoassay and radiographic characteristics are used to diagnose cysts caused by Echinococcus, of which there are many species. Imaging typically shows a well-defined cyst with calcifications and budding daughter cysts. Aspiration of an echinococcal cyst carries a risk of anaphylaxis and spread of infection and should only be undertaken if there is serologic and radiographic uncertainty.
Fungal abscesses. Fungal abscesses are most commonly caused by Candida species. The typical patient presentation includes high fever and elevated alkaline phosphatase, usually during the count recovery phase of patients with hematologic malignancies undergoing chemotherapy.
Fungal abscesses are frequently too small to aspirate. Fortunately, serum and radiographic results, as well as the clinical setting, make diagnosis more straightforward. Serum fungal markers can be checked and empiric treatment with amphotericin B or an echinocandin is recommended, followed by narrowing to oral fluconazole. Treatment should continue until abscesses resolve.
Interestingly, if patients become neutropenic during their antifungal course, the microabscesses may disappear on CT or MRI, only to reappear once neutrophils return. Once patients have a stable neutrophil count and imaging shows no abscesses, antifungal treatment can be discontinued, but must be restarted if patients are to undergo additional chemotherapy with expected neutropenia.
Back to the case
While impossible to state with certainty, infection with E. histolytica while in Nicaragua was thought most likely in this case. This patient was on omalizumab for chronic urticaria immediately prior to acquiring the infection and this anti-IgE monoclonal antibody likely predisposed her to a parasitic infection. Knowing this epidemiology, she may not have required catheter drainage, however, the cyst was causing pain and drainage provided decompression. She was treated with antibiotics followed by paromomycin.
Bottom line
Entamoeba histolytica is the most common cause of liver abscess worldwide, but identifying risk factors and mechanism of infection can lead to the most likely infecting organism.
Dr. Mehra is assistant professor of medicine in the Section of Hospital Medicine at the University of Virginia Medical Center and School of Medicine, Charlottesville. Dr. Parsons is also assistant professor of medicine in the Section of Hospital Medicine at the University of Virginia Medical Center and School of Medicine.
References
Chemaly RF. Microbiology of liver abscesses and the predictive value of abscess gram stain and associated blood cultures. Diagn Microbiol Infect Dis. 2003;46(4):245-8.
Yang CC. Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae. J Microbiol Immunol Infect. 2004;37(3):176.
Chen SC. Comparison of pyogenic liver abscesses of biliary and cryptogenic origin. An eight-year analysis in a University Hospital. Swiss Med Wkly. 2005;135(23-24):344-51.
Yang CC. Pyogenic liver abscess in Taiwan: emphasis on gas-forming liver abscess in diabetics. Am J Gastroenterol. 1993;88:1911-15.
Jun CH. Risk factors and clinical outcomes for spontaneous rupture of pyogenic liver abscess. J Dig Dis. 2015;16(1):31-6.
Smego RA Jr. Treatment options for hepatic cystic echinococcosis. Int J Infect Dis. 2005;9(2):69-76.
Additional reading
Huang CJ et al. Pyogenic hepatic abscess. Changing trends over 42 years. Ann Surg. 1996;223(5):600-7.
Meddings L et al. A population-based study of pyogenic liver abscesses in the United States: incidence, mortality, and temporal trends. Am J Gastroenterol. 2010;105(1):117-24..
Petri WA, Singh U. Diagnosis and management of amoebiasis. Clin Infect Dis. 1999 Nov;29(5):1117-25.
Accompanying Photo caption: CT scan showing E. histolytica liver abscess. RELATED PHOTO IS PHOTOMICROGRAPH, NOT CT SCAN. G
Quiz
Microbiology of liver abscesses
Bacterial, parasitic, and fungal organisms can all cause liver abscesses. History, including travel history, is very important in deciphering which organisms are present.
Question 1: What is the most common cause of an amoebic liver abscess worldwide?
A. Echinococcus
B. Klebsiella pneumoniae
C. Entamoeba histolytica
D. Escherichia coli
The best answer is choice C. E. histolytica causes amoebic dysentery and liver abscess. This anaerobic parasite affects 50 million people worldwide, with the highest prevalence in India, sub-Saharan Africa, Mexico, and parts of Central and South America. Travelers spending a month or more in endemic areas are at highest risk, but cases have been reported with less than one week of exposure.
Question 2: Which type of parasitic cyst should not be aspirated?
A. Echinococcus
B. Entamoeba histolytica
C. Schistosomiasis
D. Paramoeba
The best answer is choice A. Aspiration of an echinococcal cyst carries a risk of anaphylaxis and spread of infection and should only be done if there is serologic and radiographic uncertainty. Imaging typically shows a well-defined cyst with calcifications and budding daughter cysts.
Key Points
- Risk factors and mechanism of action will suggest the most likely organisms and guide antibiotic choice.
- Entamoeba histolytica is the most common cause of liver abscess worldwide.
- Stool PCR and antibody testing for E. histolytica should both be ordered in the work-up of a liver abscess.
- Calcifications and daughter cysts budding off the main cyst can distinguish echinococcal cyst from E. histolytica abscess radiographically.
Case
A 29-year-old woman with chronic urticaria, previously on omalizumab, presented with 2 weeks of abdominal pain and fever. She had traveled to Nicaragua within the past 10 months. CT showed a 6 x 5 cm liver abscess. Entamoeba histolytica was detected by stool polymerase chain reaction, and E. histolytica antibody was positive. The abscess was drained, and she completed a 10-day course of metronidazole followed by a 7-day course of paromomycin.
Brief overview
Bacterial, parasitic, and fungal organisms can cause liver abscess. Worldwide, bacteria are the most common cause of liver abscess. Infection is usually polymicrobial, though Klebsiella and the Streptococcus milleri group are the most common organisms identified.
Entamoeba histolytica is the most frequent cause of amoebic liver abscess and should be strongly considered in a returning traveler, visitor from another country, or those on monoclonal antibody therapy directed against IgE such as omalizumab. Candida species are the most common fungal etiology; an example being hepatosplenic candidiasis in hematologic malignancies.
Overview of the data
Pyogenic liver abscess. A variety of bacteria have been isolated from pyogenic liver abscesses (PLA) because of differences in mechanism of infection (such as biliary tract interventions, postoperative complications, and hematogenous spread), immunocompromised states, and geographical variation. The literature is not robust for pyogenic liver abscesses, and the microbiology isolated via epidemiologic studies are confounded by the mechanism of infection and thus difficult to generalize.
Initially, the Enterobacteriaceae including Klebsiella pneumoniae and Escherichia coli were the most common cause of PLA in the United States. The emergence of improved culturing techniques, which has improved the yield of facultative anaerobes such as the Streptococcus milleri (also known as Streptococcus anginosus) group, has led to an increased incidence and wider assortment of bacteria, with a more recent study of 38 patients in the Cleveland Clinic system showing that about half of the PLA were polymicrobial with the predominant organism when monomicrobial being of the Strep milleri group in 9/22 patients (Chemaly et al.).
Biliary tract disease, whether from choledocholithiasis, stricture, or malignant obstruction is the most common etiology of PLA. Much of the PLA-focused literature is from Asia, where Klebsiella is more commonly a cause of liver abscess. In a study of 248 Taiwanese patients with PLA, Klebsiella was responsible for 69% of PLA (Yang et al.). In a study of 79 patients hospitalized in New York, Klebsiella was the most common bacteria isolated, although more than half of the patients studied were Asian, and Klebsiella was more common among Asian patients than the other groups studied. An 8-year analysis of patients admitted to a University Hospital in Taiwan with cryptogenic PLA showed that the etiology was Klebsiella in 46/52 patients (Chen et al.). Most patients with Klebsiella liver abscess have documented bacteremia.
The second most common mechanism is bacterial translocation through the portal venous system. E. coli is commonly isolated and is frequently spread from intra-abdominal infections such as appendicitis leading to pylephlebitis. As the diagnosis and management of appendicitis has improved, the incidence of appendicitis causing a PLA has decreased.
PLA should be cultured to guide therapy and catheter drainage may be required. However, common organisms causing liver abscess should also be considered when selecting initial antibiotic therapy as cultures are frequently affected by previous antibiotic exposure or imprecise culturing techniques. Blood cultures should be obtained, and empiric therapy with a beta-lactam/beta-lactamase inhibitor or third-generation cephalosporin plus metronidazole should be started thereafter.
Entamoeba histolytica. E. histolytica, an anaerobic parasite that can lead to amoebic dysentery and liver abscess, affects upwards of 50 million people worldwide, predominantly in India and sub-Saharan Africa. Travel to an endemic area for longer than 1 month carries a high risk of transmission, though cases have been described with less than a week of exposure.
Infection occurs following consumption of affected food or water and can lead to dysentery within 3 weeks. Fever and right upper quadrant pain develop later, anywhere from 3 months to years following initial exposure. To diagnose, both serologic and stool testing for E. histolytica are recommended owing to the high sensitivity and low specificity of the serologic antibody test and the low sensitivity and high specificity of the stool antigen test. Imaging may reveal a single cyst with surrounding edema, which is characteristic.
Effective treatment is a two-step process. Metronidazole targets trophozoites that cause liver abscesses followed by paromomycin or diloxanide furoate to eradicate luminal oocysts and prevent reinfection. Aspiration and catheter drainage is necessary if the microbiology or etiology of the liver abscess remains uncertain, patients are not responding to antibiotics, or there is concern for impending rupture with cyst size greater than 6 cm (Jun et al.).
Hydatid cysts. Serologic testing via enzyme-linked immunoassay and radiographic characteristics are used to diagnose cysts caused by Echinococcus, of which there are many species. Imaging typically shows a well-defined cyst with calcifications and budding daughter cysts. Aspiration of an echinococcal cyst carries a risk of anaphylaxis and spread of infection and should only be undertaken if there is serologic and radiographic uncertainty.
Fungal abscesses. Fungal abscesses are most commonly caused by Candida species. The typical patient presentation includes high fever and elevated alkaline phosphatase, usually during the count recovery phase of patients with hematologic malignancies undergoing chemotherapy.
Fungal abscesses are frequently too small to aspirate. Fortunately, serum and radiographic results, as well as the clinical setting, make diagnosis more straightforward. Serum fungal markers can be checked and empiric treatment with amphotericin B or an echinocandin is recommended, followed by narrowing to oral fluconazole. Treatment should continue until abscesses resolve.
Interestingly, if patients become neutropenic during their antifungal course, the microabscesses may disappear on CT or MRI, only to reappear once neutrophils return. Once patients have a stable neutrophil count and imaging shows no abscesses, antifungal treatment can be discontinued, but must be restarted if patients are to undergo additional chemotherapy with expected neutropenia.
Back to the case
While impossible to state with certainty, infection with E. histolytica while in Nicaragua was thought most likely in this case. This patient was on omalizumab for chronic urticaria immediately prior to acquiring the infection and this anti-IgE monoclonal antibody likely predisposed her to a parasitic infection. Knowing this epidemiology, she may not have required catheter drainage, however, the cyst was causing pain and drainage provided decompression. She was treated with antibiotics followed by paromomycin.
Bottom line
Entamoeba histolytica is the most common cause of liver abscess worldwide, but identifying risk factors and mechanism of infection can lead to the most likely infecting organism.
Dr. Mehra is assistant professor of medicine in the Section of Hospital Medicine at the University of Virginia Medical Center and School of Medicine, Charlottesville. Dr. Parsons is also assistant professor of medicine in the Section of Hospital Medicine at the University of Virginia Medical Center and School of Medicine.
References
Chemaly RF. Microbiology of liver abscesses and the predictive value of abscess gram stain and associated blood cultures. Diagn Microbiol Infect Dis. 2003;46(4):245-8.
Yang CC. Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae. J Microbiol Immunol Infect. 2004;37(3):176.
Chen SC. Comparison of pyogenic liver abscesses of biliary and cryptogenic origin. An eight-year analysis in a University Hospital. Swiss Med Wkly. 2005;135(23-24):344-51.
Yang CC. Pyogenic liver abscess in Taiwan: emphasis on gas-forming liver abscess in diabetics. Am J Gastroenterol. 1993;88:1911-15.
Jun CH. Risk factors and clinical outcomes for spontaneous rupture of pyogenic liver abscess. J Dig Dis. 2015;16(1):31-6.
Smego RA Jr. Treatment options for hepatic cystic echinococcosis. Int J Infect Dis. 2005;9(2):69-76.
Additional reading
Huang CJ et al. Pyogenic hepatic abscess. Changing trends over 42 years. Ann Surg. 1996;223(5):600-7.
Meddings L et al. A population-based study of pyogenic liver abscesses in the United States: incidence, mortality, and temporal trends. Am J Gastroenterol. 2010;105(1):117-24..
Petri WA, Singh U. Diagnosis and management of amoebiasis. Clin Infect Dis. 1999 Nov;29(5):1117-25.
Accompanying Photo caption: CT scan showing E. histolytica liver abscess. RELATED PHOTO IS PHOTOMICROGRAPH, NOT CT SCAN. G
Quiz
Microbiology of liver abscesses
Bacterial, parasitic, and fungal organisms can all cause liver abscesses. History, including travel history, is very important in deciphering which organisms are present.
Question 1: What is the most common cause of an amoebic liver abscess worldwide?
A. Echinococcus
B. Klebsiella pneumoniae
C. Entamoeba histolytica
D. Escherichia coli
The best answer is choice C. E. histolytica causes amoebic dysentery and liver abscess. This anaerobic parasite affects 50 million people worldwide, with the highest prevalence in India, sub-Saharan Africa, Mexico, and parts of Central and South America. Travelers spending a month or more in endemic areas are at highest risk, but cases have been reported with less than one week of exposure.
Question 2: Which type of parasitic cyst should not be aspirated?
A. Echinococcus
B. Entamoeba histolytica
C. Schistosomiasis
D. Paramoeba
The best answer is choice A. Aspiration of an echinococcal cyst carries a risk of anaphylaxis and spread of infection and should only be done if there is serologic and radiographic uncertainty. Imaging typically shows a well-defined cyst with calcifications and budding daughter cysts.
Key Points
- Risk factors and mechanism of action will suggest the most likely organisms and guide antibiotic choice.
- Entamoeba histolytica is the most common cause of liver abscess worldwide.
- Stool PCR and antibody testing for E. histolytica should both be ordered in the work-up of a liver abscess.
- Calcifications and daughter cysts budding off the main cyst can distinguish echinococcal cyst from E. histolytica abscess radiographically.
Patients who record office visits
Question: During an office visit, the patient used a smartphone to record his conversation with the doctor. Which of the following statements is best?
A. This is an intrusion into a private and confidential physician-patient encounter and violates laws against eavesdropping and wiretapping.
B. Recordings are rarely made in the doctor’s office.
C. Both parties must consent before the patient or doctor can legally make such a recording.
D. Surreptitious recording by one party is always illegal.
E. All are incorrect.
Answer: E.
Scholars from Dartmouth recently published their viewpoint on this topic in the Aug. 7, 2017, issue of JAMA.1 Many individuals believe that taping or recording a private conversation is per se illegal.
This is a misconception. Although it is a serious felony to violate wiretapping laws, in fact every jurisdiction permits the taping or recording of doctor-patient conversations where there is all-party consent. A majority of states actually allow the recording even if one party has not given his/her consent. This one-party consent rule is the law in 39 states, including Hawaii and New York. On the other hand, 11 states, such as California, Florida, Massachusetts, and Washington, deem such recordings illegal. A listing of the law in the various states can be found in the JAMA article, in which the authors call for “clear policies that facilitate the positive use of digital recordings.”
In a 2011 case against the Cleveland Clinic, a patient died of a cardiac arrest from hyperkalemia 3 days after elective knee surgery.2 The patient’s children had made a covert recording of a meeting with the chief medical officer when discussing the incident. The hospital attempted to bar the use of the recording, claiming that the information was nondiscoverable under the “peer review” privilege.
Both the trial court and the court of appeals disagreed, being unconvinced that such discussions fell within peer review protection. That the recording was made surreptitiously was not raised as an issue, as Ohio is a one-party consent state, i.e., the law permits a patient to legally tape his/her conversations without obtaining prior approval from the doctor.3
There are clear advantages to having a permanent record of a doctor’s professional opinion. The patient can review the information after the visit for a better understanding or for recall purposes, even sharing the information with family members, caregivers, or others, especially where there is a lack of clarity on instructions.4 In the area of informed consent, this is particularly useful for a reminder of medication side effects and potential complications of proposed surgery.
However, many doctors believe that recordings may be disruptive or prove inhibitory to free and open discussions, and they are concerned about their potential use should litigation arises.
Risk managers and malpractice carriers are divided in their views. For example, it has been stated that, “at the Barrow Neurological Institute, in Phoenix, Arizona, where patients are routinely offered video recordings of their visits, clinicians who participate in these recordings receive a 10% reduction in the cost of their medical defense and $1 million extra liability coverage” (P.J. Barr, unpublished data, 2017, as cited in reference 1). Other carriers are not as supportive, discouraging their insureds from allowing recordings to be made.
In the majority of jurisdictions, recordings are legal if consented to by one of the parties. This means that recordings by the patient with/without consent from or with/without knowledge of the doctor are fully legitimate. It also means that the recordings will be admissible into evidence in a courtroom, unless the information is privileged (protected from discovery) or is otherwise irrelevant or unreliable.
On the other hand, in states requiring all-party consent, such recordings are illegal absent across-the-board consent, and they will be inadmissible into evidence. This cardinal difference in state law raises vital implications for both plaintiff and defendant in litigation, because the recordings may contain incriminating or exculpatory information.
Recordings of conversations in the doctor’s office are by no means rare. A survey in the United Kingdom revealed that 15% of the public had secretly recorded a clinic visit, and 11% were aware of someone else doing the same.5 The concerned physician could proactively prohibit all office recordings by posting a “no recording” sign in the waiting room in the name of confidentiality and privacy. And should a physician discover that a patient is covertly recording, risk managers have suggested terminating the visit with a warning that a repeat attempt will result in discharge.
Like it or not, recordings are here to stay, and the omnipresence of modern communications devices such as smartphones, tablets, etc., is likely to increase the prevalence of recordings. A practical approach for practicing physicians is to familiarize themselves with the law in the individual state in which they practice and to improve their communication skills irrespective of whether or not there is a recording.
They may wish to consider the view attributed to Richard Boothman, JD, chief risk officer at the University of Michigan Health System: “Recording should cause any caregiver to mind their professionalism and be disciplined in their remarks to their patients. … I believe it can be a very powerful tool to cement the patient/physician relationship and the patient’s understanding of the clinical messages and information. Physicians are significantly benefited by an informed patient.”6
References
1. JAMA. 2017 Aug 8;318(6):513-4.
2. Smith v. Cleveland Clinic, 197 Ohio App.3d 524, 2011.
3. Ohio Revised Code 2933.52.
4. JAMA. 2015 Apr 28;313(16):1615-6.
5. BMJ Open. 2015 Aug 11;5(8):e008566.
6. “Your office is being recorded.” Medscape, April 3, 2018.
Dr. Tan is emeritus professor of medicine and a former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].
Question: During an office visit, the patient used a smartphone to record his conversation with the doctor. Which of the following statements is best?
A. This is an intrusion into a private and confidential physician-patient encounter and violates laws against eavesdropping and wiretapping.
B. Recordings are rarely made in the doctor’s office.
C. Both parties must consent before the patient or doctor can legally make such a recording.
D. Surreptitious recording by one party is always illegal.
E. All are incorrect.
Answer: E.
Scholars from Dartmouth recently published their viewpoint on this topic in the Aug. 7, 2017, issue of JAMA.1 Many individuals believe that taping or recording a private conversation is per se illegal.
This is a misconception. Although it is a serious felony to violate wiretapping laws, in fact every jurisdiction permits the taping or recording of doctor-patient conversations where there is all-party consent. A majority of states actually allow the recording even if one party has not given his/her consent. This one-party consent rule is the law in 39 states, including Hawaii and New York. On the other hand, 11 states, such as California, Florida, Massachusetts, and Washington, deem such recordings illegal. A listing of the law in the various states can be found in the JAMA article, in which the authors call for “clear policies that facilitate the positive use of digital recordings.”
In a 2011 case against the Cleveland Clinic, a patient died of a cardiac arrest from hyperkalemia 3 days after elective knee surgery.2 The patient’s children had made a covert recording of a meeting with the chief medical officer when discussing the incident. The hospital attempted to bar the use of the recording, claiming that the information was nondiscoverable under the “peer review” privilege.
Both the trial court and the court of appeals disagreed, being unconvinced that such discussions fell within peer review protection. That the recording was made surreptitiously was not raised as an issue, as Ohio is a one-party consent state, i.e., the law permits a patient to legally tape his/her conversations without obtaining prior approval from the doctor.3
There are clear advantages to having a permanent record of a doctor’s professional opinion. The patient can review the information after the visit for a better understanding or for recall purposes, even sharing the information with family members, caregivers, or others, especially where there is a lack of clarity on instructions.4 In the area of informed consent, this is particularly useful for a reminder of medication side effects and potential complications of proposed surgery.
However, many doctors believe that recordings may be disruptive or prove inhibitory to free and open discussions, and they are concerned about their potential use should litigation arises.
Risk managers and malpractice carriers are divided in their views. For example, it has been stated that, “at the Barrow Neurological Institute, in Phoenix, Arizona, where patients are routinely offered video recordings of their visits, clinicians who participate in these recordings receive a 10% reduction in the cost of their medical defense and $1 million extra liability coverage” (P.J. Barr, unpublished data, 2017, as cited in reference 1). Other carriers are not as supportive, discouraging their insureds from allowing recordings to be made.
In the majority of jurisdictions, recordings are legal if consented to by one of the parties. This means that recordings by the patient with/without consent from or with/without knowledge of the doctor are fully legitimate. It also means that the recordings will be admissible into evidence in a courtroom, unless the information is privileged (protected from discovery) or is otherwise irrelevant or unreliable.
On the other hand, in states requiring all-party consent, such recordings are illegal absent across-the-board consent, and they will be inadmissible into evidence. This cardinal difference in state law raises vital implications for both plaintiff and defendant in litigation, because the recordings may contain incriminating or exculpatory information.
Recordings of conversations in the doctor’s office are by no means rare. A survey in the United Kingdom revealed that 15% of the public had secretly recorded a clinic visit, and 11% were aware of someone else doing the same.5 The concerned physician could proactively prohibit all office recordings by posting a “no recording” sign in the waiting room in the name of confidentiality and privacy. And should a physician discover that a patient is covertly recording, risk managers have suggested terminating the visit with a warning that a repeat attempt will result in discharge.
Like it or not, recordings are here to stay, and the omnipresence of modern communications devices such as smartphones, tablets, etc., is likely to increase the prevalence of recordings. A practical approach for practicing physicians is to familiarize themselves with the law in the individual state in which they practice and to improve their communication skills irrespective of whether or not there is a recording.
They may wish to consider the view attributed to Richard Boothman, JD, chief risk officer at the University of Michigan Health System: “Recording should cause any caregiver to mind their professionalism and be disciplined in their remarks to their patients. … I believe it can be a very powerful tool to cement the patient/physician relationship and the patient’s understanding of the clinical messages and information. Physicians are significantly benefited by an informed patient.”6
References
1. JAMA. 2017 Aug 8;318(6):513-4.
2. Smith v. Cleveland Clinic, 197 Ohio App.3d 524, 2011.
3. Ohio Revised Code 2933.52.
4. JAMA. 2015 Apr 28;313(16):1615-6.
5. BMJ Open. 2015 Aug 11;5(8):e008566.
6. “Your office is being recorded.” Medscape, April 3, 2018.
Dr. Tan is emeritus professor of medicine and a former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].
Question: During an office visit, the patient used a smartphone to record his conversation with the doctor. Which of the following statements is best?
A. This is an intrusion into a private and confidential physician-patient encounter and violates laws against eavesdropping and wiretapping.
B. Recordings are rarely made in the doctor’s office.
C. Both parties must consent before the patient or doctor can legally make such a recording.
D. Surreptitious recording by one party is always illegal.
E. All are incorrect.
Answer: E.
Scholars from Dartmouth recently published their viewpoint on this topic in the Aug. 7, 2017, issue of JAMA.1 Many individuals believe that taping or recording a private conversation is per se illegal.
This is a misconception. Although it is a serious felony to violate wiretapping laws, in fact every jurisdiction permits the taping or recording of doctor-patient conversations where there is all-party consent. A majority of states actually allow the recording even if one party has not given his/her consent. This one-party consent rule is the law in 39 states, including Hawaii and New York. On the other hand, 11 states, such as California, Florida, Massachusetts, and Washington, deem such recordings illegal. A listing of the law in the various states can be found in the JAMA article, in which the authors call for “clear policies that facilitate the positive use of digital recordings.”
In a 2011 case against the Cleveland Clinic, a patient died of a cardiac arrest from hyperkalemia 3 days after elective knee surgery.2 The patient’s children had made a covert recording of a meeting with the chief medical officer when discussing the incident. The hospital attempted to bar the use of the recording, claiming that the information was nondiscoverable under the “peer review” privilege.
Both the trial court and the court of appeals disagreed, being unconvinced that such discussions fell within peer review protection. That the recording was made surreptitiously was not raised as an issue, as Ohio is a one-party consent state, i.e., the law permits a patient to legally tape his/her conversations without obtaining prior approval from the doctor.3
There are clear advantages to having a permanent record of a doctor’s professional opinion. The patient can review the information after the visit for a better understanding or for recall purposes, even sharing the information with family members, caregivers, or others, especially where there is a lack of clarity on instructions.4 In the area of informed consent, this is particularly useful for a reminder of medication side effects and potential complications of proposed surgery.
However, many doctors believe that recordings may be disruptive or prove inhibitory to free and open discussions, and they are concerned about their potential use should litigation arises.
Risk managers and malpractice carriers are divided in their views. For example, it has been stated that, “at the Barrow Neurological Institute, in Phoenix, Arizona, where patients are routinely offered video recordings of their visits, clinicians who participate in these recordings receive a 10% reduction in the cost of their medical defense and $1 million extra liability coverage” (P.J. Barr, unpublished data, 2017, as cited in reference 1). Other carriers are not as supportive, discouraging their insureds from allowing recordings to be made.
In the majority of jurisdictions, recordings are legal if consented to by one of the parties. This means that recordings by the patient with/without consent from or with/without knowledge of the doctor are fully legitimate. It also means that the recordings will be admissible into evidence in a courtroom, unless the information is privileged (protected from discovery) or is otherwise irrelevant or unreliable.
On the other hand, in states requiring all-party consent, such recordings are illegal absent across-the-board consent, and they will be inadmissible into evidence. This cardinal difference in state law raises vital implications for both plaintiff and defendant in litigation, because the recordings may contain incriminating or exculpatory information.
Recordings of conversations in the doctor’s office are by no means rare. A survey in the United Kingdom revealed that 15% of the public had secretly recorded a clinic visit, and 11% were aware of someone else doing the same.5 The concerned physician could proactively prohibit all office recordings by posting a “no recording” sign in the waiting room in the name of confidentiality and privacy. And should a physician discover that a patient is covertly recording, risk managers have suggested terminating the visit with a warning that a repeat attempt will result in discharge.
Like it or not, recordings are here to stay, and the omnipresence of modern communications devices such as smartphones, tablets, etc., is likely to increase the prevalence of recordings. A practical approach for practicing physicians is to familiarize themselves with the law in the individual state in which they practice and to improve their communication skills irrespective of whether or not there is a recording.
They may wish to consider the view attributed to Richard Boothman, JD, chief risk officer at the University of Michigan Health System: “Recording should cause any caregiver to mind their professionalism and be disciplined in their remarks to their patients. … I believe it can be a very powerful tool to cement the patient/physician relationship and the patient’s understanding of the clinical messages and information. Physicians are significantly benefited by an informed patient.”6
References
1. JAMA. 2017 Aug 8;318(6):513-4.
2. Smith v. Cleveland Clinic, 197 Ohio App.3d 524, 2011.
3. Ohio Revised Code 2933.52.
4. JAMA. 2015 Apr 28;313(16):1615-6.
5. BMJ Open. 2015 Aug 11;5(8):e008566.
6. “Your office is being recorded.” Medscape, April 3, 2018.
Dr. Tan is emeritus professor of medicine and a former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].
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ID Practitioner gives you daily updates on twitter on developments in infectious diseases from the United States to the rest of the world. Get the latest news from clinical meetings, FDA, CDC, and the World Health Organization on HIV, HCV, and other current and emerging diseases. See reports on the basic science and the practice of treatment, identification, and control.
ID Practitioner gives you daily updates on twitter on developments in infectious diseases from the United States to the rest of the world. Get the latest news from clinical meetings, FDA, CDC, and the World Health Organization on HIV, HCV, and other current and emerging diseases. See reports on the basic science and the practice of treatment, identification, and control.
ID Practitioner gives you daily updates on twitter on developments in infectious diseases from the United States to the rest of the world. Get the latest news from clinical meetings, FDA, CDC, and the World Health Organization on HIV, HCV, and other current and emerging diseases. See reports on the basic science and the practice of treatment, identification, and control.
ADHD, asthma Rxs up
Use of prescription medication overall decreased in children and adolescents over the past 15 years, but certain medication classes saw increases over that time period, according to a comprehensive analysis of cross-sectional, nationally representative survey data.
Reported use of any prescription medication in the past 30 days decreased from 25% during 1999-2002 to 22% during 2011-2014 (P = .04), according to the analysis based on data from 38,277 children and adolescents aged 0-19 years in the National Health and Nutrition Examination Survey (NHANES).
However, the study showed increases over time in prescribing of medications for asthma, ADHD, and contraception, according to Craig M. Hales, MD, of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and his coinvestigators.
“Monitoring trends in use of prescription medications among children and adolescents provides insights on several important public health concerns, such as shifting disease burden, changes in access to health care and medicines, increases in the adoption of appropriate therapies, and decreases in use of inappropriate or ineffective treatments,” Dr. Hales and his coauthors said.
They found significant linear trends in 14 therapeutic classes or subclasses, including six decreases and eight increases, when looking at combined survey data for reported use of any prescription medication and reported use of two or more prescription medications in the prior 30 days.
Of note, antibiotic usage decreased significantly from 8% during 1999-2002 to 5% during 2011-2014, including decreases in amoxicillin, amoxicillin/clavulanate, and cephalosporins. Likewise, antihistamine use was down over time, from 4% to 2%, as was use of upper respiratory combination medications, which decreased from 2% to 0.5%.
Conversely, they found prevalence of ADHD medication usage increased significantly from 3% during 1999-2002 to 4% during 2011-2014, including significant increases for both amphetamines and centrally acting adrenergic agents.
Asthma medication also increased, from 4% to 6%, including significant increases in inhaled corticosteroids and montelukast. Likewise, a significant increase in proton pump inhibitors was reported from 0.2% to 0.7%, while contraceptive use in girls increased significantly in prevalence, from 1% to 2%.
Taken together, these findings suggest an overall decrease in medication prescribing among children and adolescents, despite significantly increased prevalence of prescribing for certain drug classes, the investigators said.
They noted that the study had limitations. For example, NHANES does not include data on most over-the-counter medications, and for the drugs it does include, there are no data on dosages, frequency of use, or specific formulations, they said.
Dr. Hales and his coauthors had no conflicts of interest.
SOURCE: Hales CM et al. JAMA. 2018;319(19):2009-20.
These thorough analyses of medication prescribing for children and adolescents are much needed, but are “frustrating” because definitive conclusions cannot be drawn because of inherent limitations of the serial, cross-sectional study design, Gary L. Freed, MD, MPH, said in an editorial.
The study by Hales et al. shows an overall decrease in prescription medication use in children and adolescents based on data from the 1999-2014 National Health and Examination Survey (NHANES). The study shows increased use of medications for asthma, ADHD, and contraception, and decreased use of antibiotics, antihistamines, and upper respiratory combination medications.
“Some of these trends likely signal potential improvements in the care of children, others may suggest little progress has been made, and yet others are difficult to interpret with certainty,” Dr. Freed wrote.
One finding that seems clear in the data, according to Dr. Freed, is a decrease in antibiotic use among children and adolescents, from 8% to 5% from the 1999-2002 to 2011-2014 time period. That likely reflects the success of efforts to decrease overuse of these agents in community settings.
On the other hand, the decreased use of antihistamines documented in this study may reflect the success of efforts to reduce overuse, or the fact that several prescription medications became approved for OTC use over the course of the study. NHANES does not include OTC drug data in its survey.
“It is unclear whether there was simply a substitution effect and the actual overall rate of utilization of these medications was unchanged,” Dr. Freed wrote.
Increased amphetamine use for the treatment of children aged 6-11 years with ADHD is “vexing” to see, but again, caution must be exercised in interpreting the results, he said, because they do not clearly demonstrate whether these agents are being overused or underused.
“The findings reported by Hales et al. will require additional studies, using different data sources, to provide clarity in the clinical and policy implications of recent trends in medication use among children,” Dr. Freed wrote.
Dr. Freed is a pediatrician with the Child Health Evaluation and Research Center, University of Michigan, Ann Arbor. These comments are derived from his editorial accompanying the study by Hales et al. (JAMA. 2018;319[19]:1988-9). Dr. Freed had no conflicts of interest.
These thorough analyses of medication prescribing for children and adolescents are much needed, but are “frustrating” because definitive conclusions cannot be drawn because of inherent limitations of the serial, cross-sectional study design, Gary L. Freed, MD, MPH, said in an editorial.
The study by Hales et al. shows an overall decrease in prescription medication use in children and adolescents based on data from the 1999-2014 National Health and Examination Survey (NHANES). The study shows increased use of medications for asthma, ADHD, and contraception, and decreased use of antibiotics, antihistamines, and upper respiratory combination medications.
“Some of these trends likely signal potential improvements in the care of children, others may suggest little progress has been made, and yet others are difficult to interpret with certainty,” Dr. Freed wrote.
One finding that seems clear in the data, according to Dr. Freed, is a decrease in antibiotic use among children and adolescents, from 8% to 5% from the 1999-2002 to 2011-2014 time period. That likely reflects the success of efforts to decrease overuse of these agents in community settings.
On the other hand, the decreased use of antihistamines documented in this study may reflect the success of efforts to reduce overuse, or the fact that several prescription medications became approved for OTC use over the course of the study. NHANES does not include OTC drug data in its survey.
“It is unclear whether there was simply a substitution effect and the actual overall rate of utilization of these medications was unchanged,” Dr. Freed wrote.
Increased amphetamine use for the treatment of children aged 6-11 years with ADHD is “vexing” to see, but again, caution must be exercised in interpreting the results, he said, because they do not clearly demonstrate whether these agents are being overused or underused.
“The findings reported by Hales et al. will require additional studies, using different data sources, to provide clarity in the clinical and policy implications of recent trends in medication use among children,” Dr. Freed wrote.
Dr. Freed is a pediatrician with the Child Health Evaluation and Research Center, University of Michigan, Ann Arbor. These comments are derived from his editorial accompanying the study by Hales et al. (JAMA. 2018;319[19]:1988-9). Dr. Freed had no conflicts of interest.
These thorough analyses of medication prescribing for children and adolescents are much needed, but are “frustrating” because definitive conclusions cannot be drawn because of inherent limitations of the serial, cross-sectional study design, Gary L. Freed, MD, MPH, said in an editorial.
The study by Hales et al. shows an overall decrease in prescription medication use in children and adolescents based on data from the 1999-2014 National Health and Examination Survey (NHANES). The study shows increased use of medications for asthma, ADHD, and contraception, and decreased use of antibiotics, antihistamines, and upper respiratory combination medications.
“Some of these trends likely signal potential improvements in the care of children, others may suggest little progress has been made, and yet others are difficult to interpret with certainty,” Dr. Freed wrote.
One finding that seems clear in the data, according to Dr. Freed, is a decrease in antibiotic use among children and adolescents, from 8% to 5% from the 1999-2002 to 2011-2014 time period. That likely reflects the success of efforts to decrease overuse of these agents in community settings.
On the other hand, the decreased use of antihistamines documented in this study may reflect the success of efforts to reduce overuse, or the fact that several prescription medications became approved for OTC use over the course of the study. NHANES does not include OTC drug data in its survey.
“It is unclear whether there was simply a substitution effect and the actual overall rate of utilization of these medications was unchanged,” Dr. Freed wrote.
Increased amphetamine use for the treatment of children aged 6-11 years with ADHD is “vexing” to see, but again, caution must be exercised in interpreting the results, he said, because they do not clearly demonstrate whether these agents are being overused or underused.
“The findings reported by Hales et al. will require additional studies, using different data sources, to provide clarity in the clinical and policy implications of recent trends in medication use among children,” Dr. Freed wrote.
Dr. Freed is a pediatrician with the Child Health Evaluation and Research Center, University of Michigan, Ann Arbor. These comments are derived from his editorial accompanying the study by Hales et al. (JAMA. 2018;319[19]:1988-9). Dr. Freed had no conflicts of interest.
Use of prescription medication overall decreased in children and adolescents over the past 15 years, but certain medication classes saw increases over that time period, according to a comprehensive analysis of cross-sectional, nationally representative survey data.
Reported use of any prescription medication in the past 30 days decreased from 25% during 1999-2002 to 22% during 2011-2014 (P = .04), according to the analysis based on data from 38,277 children and adolescents aged 0-19 years in the National Health and Nutrition Examination Survey (NHANES).
However, the study showed increases over time in prescribing of medications for asthma, ADHD, and contraception, according to Craig M. Hales, MD, of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and his coinvestigators.
“Monitoring trends in use of prescription medications among children and adolescents provides insights on several important public health concerns, such as shifting disease burden, changes in access to health care and medicines, increases in the adoption of appropriate therapies, and decreases in use of inappropriate or ineffective treatments,” Dr. Hales and his coauthors said.
They found significant linear trends in 14 therapeutic classes or subclasses, including six decreases and eight increases, when looking at combined survey data for reported use of any prescription medication and reported use of two or more prescription medications in the prior 30 days.
Of note, antibiotic usage decreased significantly from 8% during 1999-2002 to 5% during 2011-2014, including decreases in amoxicillin, amoxicillin/clavulanate, and cephalosporins. Likewise, antihistamine use was down over time, from 4% to 2%, as was use of upper respiratory combination medications, which decreased from 2% to 0.5%.
Conversely, they found prevalence of ADHD medication usage increased significantly from 3% during 1999-2002 to 4% during 2011-2014, including significant increases for both amphetamines and centrally acting adrenergic agents.
Asthma medication also increased, from 4% to 6%, including significant increases in inhaled corticosteroids and montelukast. Likewise, a significant increase in proton pump inhibitors was reported from 0.2% to 0.7%, while contraceptive use in girls increased significantly in prevalence, from 1% to 2%.
Taken together, these findings suggest an overall decrease in medication prescribing among children and adolescents, despite significantly increased prevalence of prescribing for certain drug classes, the investigators said.
They noted that the study had limitations. For example, NHANES does not include data on most over-the-counter medications, and for the drugs it does include, there are no data on dosages, frequency of use, or specific formulations, they said.
Dr. Hales and his coauthors had no conflicts of interest.
SOURCE: Hales CM et al. JAMA. 2018;319(19):2009-20.
Use of prescription medication overall decreased in children and adolescents over the past 15 years, but certain medication classes saw increases over that time period, according to a comprehensive analysis of cross-sectional, nationally representative survey data.
Reported use of any prescription medication in the past 30 days decreased from 25% during 1999-2002 to 22% during 2011-2014 (P = .04), according to the analysis based on data from 38,277 children and adolescents aged 0-19 years in the National Health and Nutrition Examination Survey (NHANES).
However, the study showed increases over time in prescribing of medications for asthma, ADHD, and contraception, according to Craig M. Hales, MD, of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and his coinvestigators.
“Monitoring trends in use of prescription medications among children and adolescents provides insights on several important public health concerns, such as shifting disease burden, changes in access to health care and medicines, increases in the adoption of appropriate therapies, and decreases in use of inappropriate or ineffective treatments,” Dr. Hales and his coauthors said.
They found significant linear trends in 14 therapeutic classes or subclasses, including six decreases and eight increases, when looking at combined survey data for reported use of any prescription medication and reported use of two or more prescription medications in the prior 30 days.
Of note, antibiotic usage decreased significantly from 8% during 1999-2002 to 5% during 2011-2014, including decreases in amoxicillin, amoxicillin/clavulanate, and cephalosporins. Likewise, antihistamine use was down over time, from 4% to 2%, as was use of upper respiratory combination medications, which decreased from 2% to 0.5%.
Conversely, they found prevalence of ADHD medication usage increased significantly from 3% during 1999-2002 to 4% during 2011-2014, including significant increases for both amphetamines and centrally acting adrenergic agents.
Asthma medication also increased, from 4% to 6%, including significant increases in inhaled corticosteroids and montelukast. Likewise, a significant increase in proton pump inhibitors was reported from 0.2% to 0.7%, while contraceptive use in girls increased significantly in prevalence, from 1% to 2%.
Taken together, these findings suggest an overall decrease in medication prescribing among children and adolescents, despite significantly increased prevalence of prescribing for certain drug classes, the investigators said.
They noted that the study had limitations. For example, NHANES does not include data on most over-the-counter medications, and for the drugs it does include, there are no data on dosages, frequency of use, or specific formulations, they said.
Dr. Hales and his coauthors had no conflicts of interest.
SOURCE: Hales CM et al. JAMA. 2018;319(19):2009-20.
FROM JAMA
Key clinical point: Nationally representative survey data demonstrate an overall decrease in use of any medication among children and adolescents, although use of certain medications increased.
Major finding: (P = 0.04).
Study details: Analysis of survey data for U.S. children and adolescents aged 0-19 years in the 1999-2014 NHANES.
Disclosures: Dr. Hales and his coauthors had no conflicts of interest.
Source: Hales CM et al. JAMA. 2018;319(19):2009-20.
Exploring Outcomes of Pediatric Status Epilepticus
More attention needs to be paid to evaluating quality of life and cognitive/behavioral outcomes in children with status epilepticus, according to a review of the relevant medical literature.
- An analysis of MEDLINE derived studies looked at the short-term and long-term outcomes in pediatric patients with status epilepticus.
- The review found that mortality in this patient population was relatively low.
- Health-related quality of life, neuroimaging, the use of continuous infusions, and cognitive/behavioral outcomes were not adequately addressed in the studies that were evaluated.
- The researchers point out, however, that the full effects of status epilepticus on the outcomes being evaluated were difficult to accurately establish because there were so many differences in the way the studies were conducted.
Jafarpour S, Stredny CM, Piantino J, Chapman KE. Baseline and outcome assessment in pediatric status epilepticus. [Published online ahead of print April 26, 2018]. Seizure. DOI: https://doi.org/10.1016/j.seizure.2018.04.019
More attention needs to be paid to evaluating quality of life and cognitive/behavioral outcomes in children with status epilepticus, according to a review of the relevant medical literature.
- An analysis of MEDLINE derived studies looked at the short-term and long-term outcomes in pediatric patients with status epilepticus.
- The review found that mortality in this patient population was relatively low.
- Health-related quality of life, neuroimaging, the use of continuous infusions, and cognitive/behavioral outcomes were not adequately addressed in the studies that were evaluated.
- The researchers point out, however, that the full effects of status epilepticus on the outcomes being evaluated were difficult to accurately establish because there were so many differences in the way the studies were conducted.
Jafarpour S, Stredny CM, Piantino J, Chapman KE. Baseline and outcome assessment in pediatric status epilepticus. [Published online ahead of print April 26, 2018]. Seizure. DOI: https://doi.org/10.1016/j.seizure.2018.04.019
More attention needs to be paid to evaluating quality of life and cognitive/behavioral outcomes in children with status epilepticus, according to a review of the relevant medical literature.
- An analysis of MEDLINE derived studies looked at the short-term and long-term outcomes in pediatric patients with status epilepticus.
- The review found that mortality in this patient population was relatively low.
- Health-related quality of life, neuroimaging, the use of continuous infusions, and cognitive/behavioral outcomes were not adequately addressed in the studies that were evaluated.
- The researchers point out, however, that the full effects of status epilepticus on the outcomes being evaluated were difficult to accurately establish because there were so many differences in the way the studies were conducted.
Jafarpour S, Stredny CM, Piantino J, Chapman KE. Baseline and outcome assessment in pediatric status epilepticus. [Published online ahead of print April 26, 2018]. Seizure. DOI: https://doi.org/10.1016/j.seizure.2018.04.019
Epilepsy Research Reporting May Be Biased
A cross-sectional analysis of epilepsy intervention trials suggests there may be bias in the reporting of these investigations according to a recent review of the research.
- Investigators analyzed 126 epilepsy intervention trials, comparing two reporting periods: 2008 to 2011 and 2012 to 2015.
- Twenty five percent of the trials were not reported (31/126).
- 72 of the 126 trials were conducted in at least one US center.
- 56 of 72 trials (78%) met the US Food and Drug Administration’s Amendments Act requirements.
- Researchers found that the time it took to report trial results had become shorter over time, when comparing 2008-2011 to 2012-2015.
- However, only a third of the trials (19/56) reported their results within the FDA’s mandated one-year time frame.
Rayi A, Thompson S, Gloss D, Malhotra K. Reporting bias in completed epilepsy intervention trials: a cross-sectional analysis. Epilepsy Res. 2018;143:1-6
A cross-sectional analysis of epilepsy intervention trials suggests there may be bias in the reporting of these investigations according to a recent review of the research.
- Investigators analyzed 126 epilepsy intervention trials, comparing two reporting periods: 2008 to 2011 and 2012 to 2015.
- Twenty five percent of the trials were not reported (31/126).
- 72 of the 126 trials were conducted in at least one US center.
- 56 of 72 trials (78%) met the US Food and Drug Administration’s Amendments Act requirements.
- Researchers found that the time it took to report trial results had become shorter over time, when comparing 2008-2011 to 2012-2015.
- However, only a third of the trials (19/56) reported their results within the FDA’s mandated one-year time frame.
Rayi A, Thompson S, Gloss D, Malhotra K. Reporting bias in completed epilepsy intervention trials: a cross-sectional analysis. Epilepsy Res. 2018;143:1-6
A cross-sectional analysis of epilepsy intervention trials suggests there may be bias in the reporting of these investigations according to a recent review of the research.
- Investigators analyzed 126 epilepsy intervention trials, comparing two reporting periods: 2008 to 2011 and 2012 to 2015.
- Twenty five percent of the trials were not reported (31/126).
- 72 of the 126 trials were conducted in at least one US center.
- 56 of 72 trials (78%) met the US Food and Drug Administration’s Amendments Act requirements.
- Researchers found that the time it took to report trial results had become shorter over time, when comparing 2008-2011 to 2012-2015.
- However, only a third of the trials (19/56) reported their results within the FDA’s mandated one-year time frame.
Rayi A, Thompson S, Gloss D, Malhotra K. Reporting bias in completed epilepsy intervention trials: a cross-sectional analysis. Epilepsy Res. 2018;143:1-6
E-cigarette usage has changed
, according to a study published online on May 15 by JAMA.
The prevalence of ever use of e-cigarettes among adults aged 18 years and older rose significantly from 12.6% in 2014 to 15.3% in 2016, while the prevalence of current use (defined as use every day or some days) decreased significantly from 3.7% to 3.2% over that same period, suggesting “that some individuals are trying but not continuing use of e-cigarettes,” Wei Bao, MD, PhD, and his associates said in a research letter.
None of the investigators reported any conflicts of interest.
SOURCE: Bao W et al. JAMA. 2018 May 15;319(19):2039-41.
, according to a study published online on May 15 by JAMA.
The prevalence of ever use of e-cigarettes among adults aged 18 years and older rose significantly from 12.6% in 2014 to 15.3% in 2016, while the prevalence of current use (defined as use every day or some days) decreased significantly from 3.7% to 3.2% over that same period, suggesting “that some individuals are trying but not continuing use of e-cigarettes,” Wei Bao, MD, PhD, and his associates said in a research letter.
None of the investigators reported any conflicts of interest.
SOURCE: Bao W et al. JAMA. 2018 May 15;319(19):2039-41.
, according to a study published online on May 15 by JAMA.
The prevalence of ever use of e-cigarettes among adults aged 18 years and older rose significantly from 12.6% in 2014 to 15.3% in 2016, while the prevalence of current use (defined as use every day or some days) decreased significantly from 3.7% to 3.2% over that same period, suggesting “that some individuals are trying but not continuing use of e-cigarettes,” Wei Bao, MD, PhD, and his associates said in a research letter.
None of the investigators reported any conflicts of interest.
SOURCE: Bao W et al. JAMA. 2018 May 15;319(19):2039-41.
FROM JAMA
Fremanezumab may be an effective episodic migraine treatment
Patients with episodic migraines had significantly fewer headache days when treated with a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), results of a recent randomized clinical trial show.
The treatment was generally well tolerated, and also improved secondary efficacy outcomes; however, the investigators qualified the results, noting that the trial included patients who had failed two or fewer previous classes of migraine preventive medication.
“Further research is needed to assess effectiveness against other preventive medications, and in patients in whom multiple preventive drug classes have failed,” wrote David W. Dodick, MD, of Mayo Clinic, Phoenix, Ariz., and his coauthors. Long-term safety and efficacy also are needed, they added. Their report was published in JAMA.
Fremanezumab is a subcutaneously administered, fully humanized monoclonal antibody that binds to the CGRP ligand. A previous randomized phase 2b study showed that the treatment was effective in preventing migraine, with no serious treatment-related adverse events.
The current 12-week phase 3 trial (clinicaltrials.gov Identifier: NCT02629861) was designed to evaluate the efficacy and safety of fremanezumab in two different dosing regimens. A total of 875 patients (742 women; 85%) with episodic migraine were randomly assigned to fremanezumab monthly dosing (225 mg at baseline, 4 weeks, and 8 weeks), a single higher dose of fremanezumab (675 mg at baseline) intended to support a quarterly dosing regimen, or placebo.
Both dosing approaches significantly reduced the mean number of migraine days per month vs. placebo, Dr. Dodick and his coinvestigators reported.
In the monthly dosing group, the mean number of migraine days per month decreased from 8.9 to 4.9, and compared with placebo (with a decrease from 9.1 to 6.5 days), the mean number of migraine days at 12 weeks was 1.5 days lower (P less than .001). Similarly, the mean number of migraine days decreased from 9.2 to 5.3 days in the single higher dose group, with a difference of 1.3 days vs. placebo (P less than .001).
Significantly more patients receiving fremanezumab had a 50% or greater reduction in mean number of migraine days per month, suggesting a clinical response to the CGRP monoclonal antibody, the investigators said.
The most common adverse events leading to discontinuation included erythema at the injection site in three patients, along with induration, diarrhea, anxiety, and depression occurring in two patients each, according to the report. There was one death in the study due to suicide 109 days after the patient received a single higher dose of the study drug. However, the investigators determined that the death was unrelated to treatment.
One limitation of the study, investigators said, is that it excluded patients with treatment refractory migraine who had failed at least two previous preventive drug classes, and those who had continuous headache.
“Further studies are needed to define the full spectrum of efficacy and tolerability of fremanezumab, including in patients who are treatment refractory and who have a range of coexistent diseases,” they wrote.
Teva Pharmaceuticals supported the study. Dr. Dodick and his coauthors reported disclosures related to Teva, Amgen, Novartis, Pfizer, and Merck, among other entities.
SOURCE: Dodick DW et al. JAMA. 2018.319[19]:1999-2008.
While this report on fremanezumab by Dr. Dodick and colleagues adds important evidence on the efficacy and safety of CGRP monoclonal antibodies, authors of a related editorial said several questions remain regarding this particular clinical trial and the drug class in general.
Of note, the study of fremanezumab excluded patients who failed two or more previous classes of medications. “This means the results of this trial may not necessarily apply to patients with severe, treatment-resistant migraine, who are the patients most likely to be prescribed and have access to these treatments in clinical practice,” Elizabeth W. Loder, MD, MPH, and Matthew S. Robbins, MD, wrote in their editorial (JAMA 2018 319[19]:1985-7).
Patients who received monthly fremanezumab had fewer migraine days per month versus placebo, as did patients who received a single higher dose of the medication. However, in both instances, the differences were smaller than the 1.6-day difference that was specified in the sample size calculation, added Dr. Loder and Dr. Robbins.
Though long-term safety data are needed, fremanezumab seemed generally well tolerated over 12 weeks in this study. “An important apparent benefit of fremanezumab and the other 3 CGRP monoclonal antibodies in development is their low burden of common nuisance adverse events,” they wrote.
However, it is “sobering to consider” the three deaths documented in clinical trials of CGRP monoclonal antibodies, they said. That total includes one patient in this study who committed suicide 109 days after receiving a 675-mg dose of fremanezumab.
The death may not have been related to treatment, the editorial authors said, noting that depression and other affective disorders are often comorbid with migraine.
“The [Food and Drug Administration] undoubtedly will scrutinize the deaths and adverse events reported in the trials of fremanezumab and other CGRP monoclonal antibodies,” they wrote. “If the result is restrictive labeling, it could greatly limit the patient population for these drugs, which are in any case likely to prove costly and challenging for patients to access.”
Dr. Loder is in the division of headache, department of neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Robbins is with Montefiore Headache Center, Albert Einstein College of Medicine, New York. These comments are derived from their editorial in JAMA. Dr Loder reported receiving grants and other funds from companies developing CGRP antibodies. Dr. Robbins reported that he is principal investigator for a clinical trial sponsored by eNeura.
While this report on fremanezumab by Dr. Dodick and colleagues adds important evidence on the efficacy and safety of CGRP monoclonal antibodies, authors of a related editorial said several questions remain regarding this particular clinical trial and the drug class in general.
Of note, the study of fremanezumab excluded patients who failed two or more previous classes of medications. “This means the results of this trial may not necessarily apply to patients with severe, treatment-resistant migraine, who are the patients most likely to be prescribed and have access to these treatments in clinical practice,” Elizabeth W. Loder, MD, MPH, and Matthew S. Robbins, MD, wrote in their editorial (JAMA 2018 319[19]:1985-7).
Patients who received monthly fremanezumab had fewer migraine days per month versus placebo, as did patients who received a single higher dose of the medication. However, in both instances, the differences were smaller than the 1.6-day difference that was specified in the sample size calculation, added Dr. Loder and Dr. Robbins.
Though long-term safety data are needed, fremanezumab seemed generally well tolerated over 12 weeks in this study. “An important apparent benefit of fremanezumab and the other 3 CGRP monoclonal antibodies in development is their low burden of common nuisance adverse events,” they wrote.
However, it is “sobering to consider” the three deaths documented in clinical trials of CGRP monoclonal antibodies, they said. That total includes one patient in this study who committed suicide 109 days after receiving a 675-mg dose of fremanezumab.
The death may not have been related to treatment, the editorial authors said, noting that depression and other affective disorders are often comorbid with migraine.
“The [Food and Drug Administration] undoubtedly will scrutinize the deaths and adverse events reported in the trials of fremanezumab and other CGRP monoclonal antibodies,” they wrote. “If the result is restrictive labeling, it could greatly limit the patient population for these drugs, which are in any case likely to prove costly and challenging for patients to access.”
Dr. Loder is in the division of headache, department of neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Robbins is with Montefiore Headache Center, Albert Einstein College of Medicine, New York. These comments are derived from their editorial in JAMA. Dr Loder reported receiving grants and other funds from companies developing CGRP antibodies. Dr. Robbins reported that he is principal investigator for a clinical trial sponsored by eNeura.
While this report on fremanezumab by Dr. Dodick and colleagues adds important evidence on the efficacy and safety of CGRP monoclonal antibodies, authors of a related editorial said several questions remain regarding this particular clinical trial and the drug class in general.
Of note, the study of fremanezumab excluded patients who failed two or more previous classes of medications. “This means the results of this trial may not necessarily apply to patients with severe, treatment-resistant migraine, who are the patients most likely to be prescribed and have access to these treatments in clinical practice,” Elizabeth W. Loder, MD, MPH, and Matthew S. Robbins, MD, wrote in their editorial (JAMA 2018 319[19]:1985-7).
Patients who received monthly fremanezumab had fewer migraine days per month versus placebo, as did patients who received a single higher dose of the medication. However, in both instances, the differences were smaller than the 1.6-day difference that was specified in the sample size calculation, added Dr. Loder and Dr. Robbins.
Though long-term safety data are needed, fremanezumab seemed generally well tolerated over 12 weeks in this study. “An important apparent benefit of fremanezumab and the other 3 CGRP monoclonal antibodies in development is their low burden of common nuisance adverse events,” they wrote.
However, it is “sobering to consider” the three deaths documented in clinical trials of CGRP monoclonal antibodies, they said. That total includes one patient in this study who committed suicide 109 days after receiving a 675-mg dose of fremanezumab.
The death may not have been related to treatment, the editorial authors said, noting that depression and other affective disorders are often comorbid with migraine.
“The [Food and Drug Administration] undoubtedly will scrutinize the deaths and adverse events reported in the trials of fremanezumab and other CGRP monoclonal antibodies,” they wrote. “If the result is restrictive labeling, it could greatly limit the patient population for these drugs, which are in any case likely to prove costly and challenging for patients to access.”
Dr. Loder is in the division of headache, department of neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Robbins is with Montefiore Headache Center, Albert Einstein College of Medicine, New York. These comments are derived from their editorial in JAMA. Dr Loder reported receiving grants and other funds from companies developing CGRP antibodies. Dr. Robbins reported that he is principal investigator for a clinical trial sponsored by eNeura.
Patients with episodic migraines had significantly fewer headache days when treated with a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), results of a recent randomized clinical trial show.
The treatment was generally well tolerated, and also improved secondary efficacy outcomes; however, the investigators qualified the results, noting that the trial included patients who had failed two or fewer previous classes of migraine preventive medication.
“Further research is needed to assess effectiveness against other preventive medications, and in patients in whom multiple preventive drug classes have failed,” wrote David W. Dodick, MD, of Mayo Clinic, Phoenix, Ariz., and his coauthors. Long-term safety and efficacy also are needed, they added. Their report was published in JAMA.
Fremanezumab is a subcutaneously administered, fully humanized monoclonal antibody that binds to the CGRP ligand. A previous randomized phase 2b study showed that the treatment was effective in preventing migraine, with no serious treatment-related adverse events.
The current 12-week phase 3 trial (clinicaltrials.gov Identifier: NCT02629861) was designed to evaluate the efficacy and safety of fremanezumab in two different dosing regimens. A total of 875 patients (742 women; 85%) with episodic migraine were randomly assigned to fremanezumab monthly dosing (225 mg at baseline, 4 weeks, and 8 weeks), a single higher dose of fremanezumab (675 mg at baseline) intended to support a quarterly dosing regimen, or placebo.
Both dosing approaches significantly reduced the mean number of migraine days per month vs. placebo, Dr. Dodick and his coinvestigators reported.
In the monthly dosing group, the mean number of migraine days per month decreased from 8.9 to 4.9, and compared with placebo (with a decrease from 9.1 to 6.5 days), the mean number of migraine days at 12 weeks was 1.5 days lower (P less than .001). Similarly, the mean number of migraine days decreased from 9.2 to 5.3 days in the single higher dose group, with a difference of 1.3 days vs. placebo (P less than .001).
Significantly more patients receiving fremanezumab had a 50% or greater reduction in mean number of migraine days per month, suggesting a clinical response to the CGRP monoclonal antibody, the investigators said.
The most common adverse events leading to discontinuation included erythema at the injection site in three patients, along with induration, diarrhea, anxiety, and depression occurring in two patients each, according to the report. There was one death in the study due to suicide 109 days after the patient received a single higher dose of the study drug. However, the investigators determined that the death was unrelated to treatment.
One limitation of the study, investigators said, is that it excluded patients with treatment refractory migraine who had failed at least two previous preventive drug classes, and those who had continuous headache.
“Further studies are needed to define the full spectrum of efficacy and tolerability of fremanezumab, including in patients who are treatment refractory and who have a range of coexistent diseases,” they wrote.
Teva Pharmaceuticals supported the study. Dr. Dodick and his coauthors reported disclosures related to Teva, Amgen, Novartis, Pfizer, and Merck, among other entities.
SOURCE: Dodick DW et al. JAMA. 2018.319[19]:1999-2008.
Patients with episodic migraines had significantly fewer headache days when treated with a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), results of a recent randomized clinical trial show.
The treatment was generally well tolerated, and also improved secondary efficacy outcomes; however, the investigators qualified the results, noting that the trial included patients who had failed two or fewer previous classes of migraine preventive medication.
“Further research is needed to assess effectiveness against other preventive medications, and in patients in whom multiple preventive drug classes have failed,” wrote David W. Dodick, MD, of Mayo Clinic, Phoenix, Ariz., and his coauthors. Long-term safety and efficacy also are needed, they added. Their report was published in JAMA.
Fremanezumab is a subcutaneously administered, fully humanized monoclonal antibody that binds to the CGRP ligand. A previous randomized phase 2b study showed that the treatment was effective in preventing migraine, with no serious treatment-related adverse events.
The current 12-week phase 3 trial (clinicaltrials.gov Identifier: NCT02629861) was designed to evaluate the efficacy and safety of fremanezumab in two different dosing regimens. A total of 875 patients (742 women; 85%) with episodic migraine were randomly assigned to fremanezumab monthly dosing (225 mg at baseline, 4 weeks, and 8 weeks), a single higher dose of fremanezumab (675 mg at baseline) intended to support a quarterly dosing regimen, or placebo.
Both dosing approaches significantly reduced the mean number of migraine days per month vs. placebo, Dr. Dodick and his coinvestigators reported.
In the monthly dosing group, the mean number of migraine days per month decreased from 8.9 to 4.9, and compared with placebo (with a decrease from 9.1 to 6.5 days), the mean number of migraine days at 12 weeks was 1.5 days lower (P less than .001). Similarly, the mean number of migraine days decreased from 9.2 to 5.3 days in the single higher dose group, with a difference of 1.3 days vs. placebo (P less than .001).
Significantly more patients receiving fremanezumab had a 50% or greater reduction in mean number of migraine days per month, suggesting a clinical response to the CGRP monoclonal antibody, the investigators said.
The most common adverse events leading to discontinuation included erythema at the injection site in three patients, along with induration, diarrhea, anxiety, and depression occurring in two patients each, according to the report. There was one death in the study due to suicide 109 days after the patient received a single higher dose of the study drug. However, the investigators determined that the death was unrelated to treatment.
One limitation of the study, investigators said, is that it excluded patients with treatment refractory migraine who had failed at least two previous preventive drug classes, and those who had continuous headache.
“Further studies are needed to define the full spectrum of efficacy and tolerability of fremanezumab, including in patients who are treatment refractory and who have a range of coexistent diseases,” they wrote.
Teva Pharmaceuticals supported the study. Dr. Dodick and his coauthors reported disclosures related to Teva, Amgen, Novartis, Pfizer, and Merck, among other entities.
SOURCE: Dodick DW et al. JAMA. 2018.319[19]:1999-2008.
FROM JAMA
Key clinical point: The CGRP monoclonal antibody fremanezumab significantly reduced the mean number of migraine days in patients with episodic migraine who had not previously failed multiple medication classes.
Major finding: The mean number of migraine days at 12 weeks was 1.5 days lower with monthly dosing and 1.3 days lower with a single higher dose.
Study details: A randomized clinical trial of 875 patients with episodic migraine who received fremanezumab monthly dosing, a single higher dose of fremanezumab, or placebo.
Disclosures: Teva Pharmaceuticals supported the study. The study authors reported disclosures related to Teva, Amgen, Novartis, Pfizer, and Merck, among other entities.
Source: Dodick DW et al. JAMA. 2018. 319(19):1999-2008.