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Vitiligo linked to moles, tanning ability, blistering sunburn
Upper extremity moles were associated with a 37% increase in the likelihood of vitiligo among white women, according to an analysis of the prospective Nurses’ Health Study.
“Women with a higher tanning ability and women who had a history of blistering sunburns in childhood were also found to have a higher risk of developing vitiligo,” Rachel Dunlap, MD, of the department of dermatology, Brown University in Providence, R.I., and her associates wrote in the Journal of Investigative Dermatology.
Vitiligo is the most common cutaneous depigmentation disorder, but associated risk factors are poorly understood, the investigators noted. They examined ties between skin pigmentation, reactions to sun exposure, and new onset vitiligo in the Nurses’ Health Study, a population-based prospective cohort study. Study participants were asked to report the number of moles on their left arms measuring at least 3 mm in diameter, their reactions to sunburn and ability to tan during childhood, and whether they had vitiligo diagnosed by a physician. A total of 51,337 women answered the question about moles, and 68,590 women answered the question about vitiligo, the investigators said (J Invest Dermatol. 2017 Feb 14. doi: 10.1016/j.jid.2017.02.004).
A total of 271 cases of vitiligo developed over 835,594 person-years. Women who reported at least one left arm mole larger than 3 mm were significantly more likely to report incident vitiligo, compared with women without moles (hazard ratio, 1.37; 95% confidence interval, 1.02-1.83), even after controlling for age, hair color, history of exposure to direct sunlight, skin tanning ability, and severity of reaction to sunburn. Developing an “average” tan or a “deep” tan after prolonged sun exposure also were significantly associated with vitiligo with hazard ratios of 2.28 (95% CI, 1.12-4.65) and 2.59 (95% CI, 1.21-5.54), respectively, “when compared to those who had minimal skin reactions or less severe burns when exposed to the sun,” the authors wrote.
A history of at least one blistering sunburn after 2 hours of sun exposure also predicted vitiligo (HR, 2.17; 95% CI, 1.15-4.10), while hair color did not.
“The benefits of good sun protection can be expanded to include potential vitiligo prevention, which may be particularly applicable to adult patients with vitiligo who are concerned about their children developing the condition,” the investigators commented. “Future studies will examine the incidence of other influencing factors, such as melanoma and melanoma associated leukoderma in this population.”
External funding sources included the National Institutes of Health and Dermatology Foundation. The investigators reported having no conflicts of interest.
Upper extremity moles were associated with a 37% increase in the likelihood of vitiligo among white women, according to an analysis of the prospective Nurses’ Health Study.
“Women with a higher tanning ability and women who had a history of blistering sunburns in childhood were also found to have a higher risk of developing vitiligo,” Rachel Dunlap, MD, of the department of dermatology, Brown University in Providence, R.I., and her associates wrote in the Journal of Investigative Dermatology.
Vitiligo is the most common cutaneous depigmentation disorder, but associated risk factors are poorly understood, the investigators noted. They examined ties between skin pigmentation, reactions to sun exposure, and new onset vitiligo in the Nurses’ Health Study, a population-based prospective cohort study. Study participants were asked to report the number of moles on their left arms measuring at least 3 mm in diameter, their reactions to sunburn and ability to tan during childhood, and whether they had vitiligo diagnosed by a physician. A total of 51,337 women answered the question about moles, and 68,590 women answered the question about vitiligo, the investigators said (J Invest Dermatol. 2017 Feb 14. doi: 10.1016/j.jid.2017.02.004).
A total of 271 cases of vitiligo developed over 835,594 person-years. Women who reported at least one left arm mole larger than 3 mm were significantly more likely to report incident vitiligo, compared with women without moles (hazard ratio, 1.37; 95% confidence interval, 1.02-1.83), even after controlling for age, hair color, history of exposure to direct sunlight, skin tanning ability, and severity of reaction to sunburn. Developing an “average” tan or a “deep” tan after prolonged sun exposure also were significantly associated with vitiligo with hazard ratios of 2.28 (95% CI, 1.12-4.65) and 2.59 (95% CI, 1.21-5.54), respectively, “when compared to those who had minimal skin reactions or less severe burns when exposed to the sun,” the authors wrote.
A history of at least one blistering sunburn after 2 hours of sun exposure also predicted vitiligo (HR, 2.17; 95% CI, 1.15-4.10), while hair color did not.
“The benefits of good sun protection can be expanded to include potential vitiligo prevention, which may be particularly applicable to adult patients with vitiligo who are concerned about their children developing the condition,” the investigators commented. “Future studies will examine the incidence of other influencing factors, such as melanoma and melanoma associated leukoderma in this population.”
External funding sources included the National Institutes of Health and Dermatology Foundation. The investigators reported having no conflicts of interest.
Upper extremity moles were associated with a 37% increase in the likelihood of vitiligo among white women, according to an analysis of the prospective Nurses’ Health Study.
“Women with a higher tanning ability and women who had a history of blistering sunburns in childhood were also found to have a higher risk of developing vitiligo,” Rachel Dunlap, MD, of the department of dermatology, Brown University in Providence, R.I., and her associates wrote in the Journal of Investigative Dermatology.
Vitiligo is the most common cutaneous depigmentation disorder, but associated risk factors are poorly understood, the investigators noted. They examined ties between skin pigmentation, reactions to sun exposure, and new onset vitiligo in the Nurses’ Health Study, a population-based prospective cohort study. Study participants were asked to report the number of moles on their left arms measuring at least 3 mm in diameter, their reactions to sunburn and ability to tan during childhood, and whether they had vitiligo diagnosed by a physician. A total of 51,337 women answered the question about moles, and 68,590 women answered the question about vitiligo, the investigators said (J Invest Dermatol. 2017 Feb 14. doi: 10.1016/j.jid.2017.02.004).
A total of 271 cases of vitiligo developed over 835,594 person-years. Women who reported at least one left arm mole larger than 3 mm were significantly more likely to report incident vitiligo, compared with women without moles (hazard ratio, 1.37; 95% confidence interval, 1.02-1.83), even after controlling for age, hair color, history of exposure to direct sunlight, skin tanning ability, and severity of reaction to sunburn. Developing an “average” tan or a “deep” tan after prolonged sun exposure also were significantly associated with vitiligo with hazard ratios of 2.28 (95% CI, 1.12-4.65) and 2.59 (95% CI, 1.21-5.54), respectively, “when compared to those who had minimal skin reactions or less severe burns when exposed to the sun,” the authors wrote.
A history of at least one blistering sunburn after 2 hours of sun exposure also predicted vitiligo (HR, 2.17; 95% CI, 1.15-4.10), while hair color did not.
“The benefits of good sun protection can be expanded to include potential vitiligo prevention, which may be particularly applicable to adult patients with vitiligo who are concerned about their children developing the condition,” the investigators commented. “Future studies will examine the incidence of other influencing factors, such as melanoma and melanoma associated leukoderma in this population.”
External funding sources included the National Institutes of Health and Dermatology Foundation. The investigators reported having no conflicts of interest.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
Key clinical point: Upper extremity moles, tanning ability, and a history of blistering sunburn were significant risk factors for vitiligo among white women.
Major finding: In the multivariate analysis, hazard ratios were 1.37 (95% confidence interval, 1.02-1.83), 2.28 (95% CI, 1.12-4.65), 2.59 (95% CI, 1.21-5.54), and 2.17 (95% CI, 1.15-4.10), respectively.
Data source: An analysis of 51,337 white women from the Nurses’ Health Study.
Disclosures: Funding sources included the National Institutes of Health and Dermatology Foundation. The investigators reported having no conflicts of interest.
Spotlight shifts to active treatment for concussions
The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.
Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.
Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.
“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”
An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).
Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.
The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.
However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.
Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.
Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).
“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.
Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”
At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.
“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”
Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.
Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.
“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.
“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.
Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.
The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”
The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.
The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.
Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.
Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.
“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”
An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).
Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.
The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.
However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.
Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.
Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).
“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.
Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”
At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.
“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”
Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.
Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.
“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.
“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.
Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.
The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”
The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.
The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.
Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.
Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.
“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”
An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).
Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.
The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.
However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.
Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.
Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).
“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.
Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”
At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.
“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”
Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.
Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.
“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.
“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.
Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.
The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”
The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.
Thrombotic microangiopathy may signal IV drug abuse
Extended-release oxymorphone hydrochloride (Opana ER) tablets contain an inert ingredient that can trigger acute microangiopathic hemolytic anemia and thrombocytopenia in those who abuse the drug via intravenous injection, Ryan Hunt, of the Food and Drug Administration, and his colleagues reported.
High-molecular-weight polyethylene oxide appeared to be the cause of acute cases of thrombotic microangiopathy in three patients who were treated in the emergency department of a single hospital in Tennessee. All had chest pain, dyspnea, visual impairment, microangiopathic hemolytic anemia and thrombocytopenia, increased lactate dehydrogenase, and undetectable haptoglobin serum levels. Two patients also had acute renal failure. Plasma exchange therapy was initiated in all three; one required additional hemodialysis.
ADAMTS13 activity was normal in blood samples obtained in two patients before they started plasma exchange. Histologic evidence of thrombotic microangiopathy with endothelial swelling of arterioles and acute tubular injury without deposition of immune complexes was seen in kidney biopsies performed in two patients. In addition, gelatinous material occluded the dialysis catheter and apheresis tubings during the initial plasma exchange sessions, the researchers reported (Blood. 2017;129[7]:896-905).
To test the association of polyethylene oxide with thrombotic microangiopathy, the researchers heated a 40-mg Opana ER tablet cut in several pieces in a spoon with 2 mL water until boiling. They injected guinea pigs with 0.1 or 0.3 mg/kg of the extracted polyethylene oxide, either as a single dose or as five doses given at 1.5-hour intervals. A dose-dependent increase of polyethylene oxide in plasma peaked at 8 hours after the first dose was measured and paralleled with intravascular hemolysis with increased plasma concentration of free hemoglobin, schistocytes in the peripheral blood smear, and thrombocytopenia. Spiking control blood samples in vitro with polyethylene oxide did not result in hemolysis.
“Although injection abuse of prescription opioids is highly concentrated in certain regions of the United States, particularly in rural Appalachia, all physicians should be highly inquisitive of IV drug abuse when presented with cases of [thrombotic microangiopathy],” the researchers concluded.
The researchers had no relevant conflicts of interest. One of the researchers is employed by Quest Diagnostics.
[email protected]
On Twitter @maryjodales
Extended-release oxymorphone hydrochloride (Opana ER) tablets contain an inert ingredient that can trigger acute microangiopathic hemolytic anemia and thrombocytopenia in those who abuse the drug via intravenous injection, Ryan Hunt, of the Food and Drug Administration, and his colleagues reported.
High-molecular-weight polyethylene oxide appeared to be the cause of acute cases of thrombotic microangiopathy in three patients who were treated in the emergency department of a single hospital in Tennessee. All had chest pain, dyspnea, visual impairment, microangiopathic hemolytic anemia and thrombocytopenia, increased lactate dehydrogenase, and undetectable haptoglobin serum levels. Two patients also had acute renal failure. Plasma exchange therapy was initiated in all three; one required additional hemodialysis.
ADAMTS13 activity was normal in blood samples obtained in two patients before they started plasma exchange. Histologic evidence of thrombotic microangiopathy with endothelial swelling of arterioles and acute tubular injury without deposition of immune complexes was seen in kidney biopsies performed in two patients. In addition, gelatinous material occluded the dialysis catheter and apheresis tubings during the initial plasma exchange sessions, the researchers reported (Blood. 2017;129[7]:896-905).
To test the association of polyethylene oxide with thrombotic microangiopathy, the researchers heated a 40-mg Opana ER tablet cut in several pieces in a spoon with 2 mL water until boiling. They injected guinea pigs with 0.1 or 0.3 mg/kg of the extracted polyethylene oxide, either as a single dose or as five doses given at 1.5-hour intervals. A dose-dependent increase of polyethylene oxide in plasma peaked at 8 hours after the first dose was measured and paralleled with intravascular hemolysis with increased plasma concentration of free hemoglobin, schistocytes in the peripheral blood smear, and thrombocytopenia. Spiking control blood samples in vitro with polyethylene oxide did not result in hemolysis.
“Although injection abuse of prescription opioids is highly concentrated in certain regions of the United States, particularly in rural Appalachia, all physicians should be highly inquisitive of IV drug abuse when presented with cases of [thrombotic microangiopathy],” the researchers concluded.
The researchers had no relevant conflicts of interest. One of the researchers is employed by Quest Diagnostics.
[email protected]
On Twitter @maryjodales
Extended-release oxymorphone hydrochloride (Opana ER) tablets contain an inert ingredient that can trigger acute microangiopathic hemolytic anemia and thrombocytopenia in those who abuse the drug via intravenous injection, Ryan Hunt, of the Food and Drug Administration, and his colleagues reported.
High-molecular-weight polyethylene oxide appeared to be the cause of acute cases of thrombotic microangiopathy in three patients who were treated in the emergency department of a single hospital in Tennessee. All had chest pain, dyspnea, visual impairment, microangiopathic hemolytic anemia and thrombocytopenia, increased lactate dehydrogenase, and undetectable haptoglobin serum levels. Two patients also had acute renal failure. Plasma exchange therapy was initiated in all three; one required additional hemodialysis.
ADAMTS13 activity was normal in blood samples obtained in two patients before they started plasma exchange. Histologic evidence of thrombotic microangiopathy with endothelial swelling of arterioles and acute tubular injury without deposition of immune complexes was seen in kidney biopsies performed in two patients. In addition, gelatinous material occluded the dialysis catheter and apheresis tubings during the initial plasma exchange sessions, the researchers reported (Blood. 2017;129[7]:896-905).
To test the association of polyethylene oxide with thrombotic microangiopathy, the researchers heated a 40-mg Opana ER tablet cut in several pieces in a spoon with 2 mL water until boiling. They injected guinea pigs with 0.1 or 0.3 mg/kg of the extracted polyethylene oxide, either as a single dose or as five doses given at 1.5-hour intervals. A dose-dependent increase of polyethylene oxide in plasma peaked at 8 hours after the first dose was measured and paralleled with intravascular hemolysis with increased plasma concentration of free hemoglobin, schistocytes in the peripheral blood smear, and thrombocytopenia. Spiking control blood samples in vitro with polyethylene oxide did not result in hemolysis.
“Although injection abuse of prescription opioids is highly concentrated in certain regions of the United States, particularly in rural Appalachia, all physicians should be highly inquisitive of IV drug abuse when presented with cases of [thrombotic microangiopathy],” the researchers concluded.
The researchers had no relevant conflicts of interest. One of the researchers is employed by Quest Diagnostics.
[email protected]
On Twitter @maryjodales
Key clinical point:
Major finding: Extended-release oxymorphone hydrochloride (Opana ER) tablets contain an inert ingredient that can trigger acute microangiopathic hemolytic anemia and thrombocytopenia in those who abuse the drug via intravenous injection.
Data source: Observational study of three patients and translational research study of inert drug components in guinea pigs.
Disclosures: The researchers had no conflicts of interest. One of the researchers is employed by Quest Diagnostics.
Factors linked to B-NHL in Palestinians, Israelis
New research has revealed factors that may increase the risk of B-cell non-Hodgkin lymphoma (B-NHL) in Israelis and Palestinians.
This large-scale, epidemiological study indicated that each group had its own unique risk factors.
However, in both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a hematopoietic malignancy were all associated with B-NHL.
A team of Palestinian and Israeli researchers reported these findings in PLOS ONE.
The researchers noted that Israelis and Palestinians share the same ecosystem but differ in terms of lifestyle, health behaviors, and medical systems. Yet both populations report high incidences of NHL.
To gain some insight into this phenomenon, the team conducted a study examining risk factors for B-NHL and its subtypes in these two populations.
The researchers looked at medical history, environmental factors, and lifestyle factors in 823 B-NHL patients and 808 healthy controls.
There were 516 Israeli Jews with B-NHL and 307 Palestinian Arabs with B-NHL. The mean age at diagnosis was 60 and 51, respectively.
The proportion of patients with diffuse large B-cell lymphoma was 71% of Palestinian Arabs and 41% of Israeli Jews. The proportion of patients with follicular lymphoma was 14% and 28%, respectively. And the proportion of patients with marginal zone lymphoma was 2% and 14%, respectively.
Using data from questionnaires, pathology review, serology, and genotyping, the researchers uncovered potential risk factors for B-NHL common to both populations and other factors unique to each population.
Results
The data showed that, in both Palestinian Arabs and Israeli Jews, B-NHL was associated with:
- Recreational sun exposure (odds ratio [OR]=1.4)
- Black hair-dye use (OR=1.70)
- A history of hospitalization for infection (OR=1.68)
- Having a first-degree relative with a hematopoietic malignancy (OR=1.69).
Smoking was associated with follicular lymphoma in both populations (OR=1.46). And greater-than-monthly indoor pesticide use was associated with diffuse large B-cell lymphoma in both populations (OR=2.01).
There was an inverse association between alcohol use and B-NHL for both populations (OR=0.46).
Among Palestinian Arabs only, risk factors for B-NHL included gardening (OR=1.93) and a history of herpes (OR=3.73), mononucleosis (OR=6.34), rubella (OR=2.86), and blood transfusion (OR=2.53).
Risk factors that applied to Israeli Jews only included growing fruits and vegetables (OR=1.87) and self-reported autoimmune diseases (OR=1.99).
The researchers said differences in risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by B-NHL subtypes suggest specific causal factors for different types of disease. However, these findings require further investigation to reveal their mechanisms.
“Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions,” said study author Ora Paltiel, of Hadassah-Hebrew University Medical Organization in Jerusalem, Israel.
“The study provided opportunities for training Palestinian and Israeli researchers and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations.” 
New research has revealed factors that may increase the risk of B-cell non-Hodgkin lymphoma (B-NHL) in Israelis and Palestinians.
This large-scale, epidemiological study indicated that each group had its own unique risk factors.
However, in both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a hematopoietic malignancy were all associated with B-NHL.
A team of Palestinian and Israeli researchers reported these findings in PLOS ONE.
The researchers noted that Israelis and Palestinians share the same ecosystem but differ in terms of lifestyle, health behaviors, and medical systems. Yet both populations report high incidences of NHL.
To gain some insight into this phenomenon, the team conducted a study examining risk factors for B-NHL and its subtypes in these two populations.
The researchers looked at medical history, environmental factors, and lifestyle factors in 823 B-NHL patients and 808 healthy controls.
There were 516 Israeli Jews with B-NHL and 307 Palestinian Arabs with B-NHL. The mean age at diagnosis was 60 and 51, respectively.
The proportion of patients with diffuse large B-cell lymphoma was 71% of Palestinian Arabs and 41% of Israeli Jews. The proportion of patients with follicular lymphoma was 14% and 28%, respectively. And the proportion of patients with marginal zone lymphoma was 2% and 14%, respectively.
Using data from questionnaires, pathology review, serology, and genotyping, the researchers uncovered potential risk factors for B-NHL common to both populations and other factors unique to each population.
Results
The data showed that, in both Palestinian Arabs and Israeli Jews, B-NHL was associated with:
- Recreational sun exposure (odds ratio [OR]=1.4)
- Black hair-dye use (OR=1.70)
- A history of hospitalization for infection (OR=1.68)
- Having a first-degree relative with a hematopoietic malignancy (OR=1.69).
Smoking was associated with follicular lymphoma in both populations (OR=1.46). And greater-than-monthly indoor pesticide use was associated with diffuse large B-cell lymphoma in both populations (OR=2.01).
There was an inverse association between alcohol use and B-NHL for both populations (OR=0.46).
Among Palestinian Arabs only, risk factors for B-NHL included gardening (OR=1.93) and a history of herpes (OR=3.73), mononucleosis (OR=6.34), rubella (OR=2.86), and blood transfusion (OR=2.53).
Risk factors that applied to Israeli Jews only included growing fruits and vegetables (OR=1.87) and self-reported autoimmune diseases (OR=1.99).
The researchers said differences in risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by B-NHL subtypes suggest specific causal factors for different types of disease. However, these findings require further investigation to reveal their mechanisms.
“Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions,” said study author Ora Paltiel, of Hadassah-Hebrew University Medical Organization in Jerusalem, Israel.
“The study provided opportunities for training Palestinian and Israeli researchers and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations.”
New research has revealed factors that may increase the risk of B-cell non-Hodgkin lymphoma (B-NHL) in Israelis and Palestinians.
This large-scale, epidemiological study indicated that each group had its own unique risk factors.
However, in both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a hematopoietic malignancy were all associated with B-NHL.
A team of Palestinian and Israeli researchers reported these findings in PLOS ONE.
The researchers noted that Israelis and Palestinians share the same ecosystem but differ in terms of lifestyle, health behaviors, and medical systems. Yet both populations report high incidences of NHL.
To gain some insight into this phenomenon, the team conducted a study examining risk factors for B-NHL and its subtypes in these two populations.
The researchers looked at medical history, environmental factors, and lifestyle factors in 823 B-NHL patients and 808 healthy controls.
There were 516 Israeli Jews with B-NHL and 307 Palestinian Arabs with B-NHL. The mean age at diagnosis was 60 and 51, respectively.
The proportion of patients with diffuse large B-cell lymphoma was 71% of Palestinian Arabs and 41% of Israeli Jews. The proportion of patients with follicular lymphoma was 14% and 28%, respectively. And the proportion of patients with marginal zone lymphoma was 2% and 14%, respectively.
Using data from questionnaires, pathology review, serology, and genotyping, the researchers uncovered potential risk factors for B-NHL common to both populations and other factors unique to each population.
Results
The data showed that, in both Palestinian Arabs and Israeli Jews, B-NHL was associated with:
- Recreational sun exposure (odds ratio [OR]=1.4)
- Black hair-dye use (OR=1.70)
- A history of hospitalization for infection (OR=1.68)
- Having a first-degree relative with a hematopoietic malignancy (OR=1.69).
Smoking was associated with follicular lymphoma in both populations (OR=1.46). And greater-than-monthly indoor pesticide use was associated with diffuse large B-cell lymphoma in both populations (OR=2.01).
There was an inverse association between alcohol use and B-NHL for both populations (OR=0.46).
Among Palestinian Arabs only, risk factors for B-NHL included gardening (OR=1.93) and a history of herpes (OR=3.73), mononucleosis (OR=6.34), rubella (OR=2.86), and blood transfusion (OR=2.53).
Risk factors that applied to Israeli Jews only included growing fruits and vegetables (OR=1.87) and self-reported autoimmune diseases (OR=1.99).
The researchers said differences in risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by B-NHL subtypes suggest specific causal factors for different types of disease. However, these findings require further investigation to reveal their mechanisms.
“Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions,” said study author Ora Paltiel, of Hadassah-Hebrew University Medical Organization in Jerusalem, Israel.
“The study provided opportunities for training Palestinian and Israeli researchers and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations.”
Software predicts HSPC differentiation
Deep learning can be used to determine how murine hematopoietic stem and progenitor cells (HSPCs) will differentiate, according to research published in Nature Methods.
Deep learning algorithms simulate the learning processes in people using artificial neural networks.
Researchers have reported the development of software that uses deep learning to predict which type of cell murine HSPCs will differentiate into, based on microscopy images.
“A hematopoietic stem cell’s decision to become a certain cell type cannot be observed,” said study author Carsten Marr, PhD, of Helmholtz Zentrum München–German Research Center for Environmental Health in Neuherberg, Germany.
“At this time, it is only possible to verify the decision retrospectively with cell surface markers.”
Therefore, Dr Marr and his team set out to develop an algorithm that can predict the decision in advance, and deep learning was key.
“Deep neural networks play a major role in our method,” Dr Marr said. “Our algorithm classifies light microscopic images and videos of individual cells by comparing these data with past experience from the development of such cells. In this way, the algorithm ‘learns’ how certain cells behave.”
Specifically, the researchers examined murine HSPCs filmed under a microscope in the lab. Using information on the cells’ appearance and speed, the software was able to “memorize” the corresponding behavior patterns and then make its prediction.
“Compared to conventional methods, such as fluorescent antibodies against certain surface proteins, we know how the cells will decide 3 cell generations earlier,” said Felix Buggenthin, PhD, of Helmholtz Zentrum München–German Research Center for Environmental Health.
“Since we now know which cells will develop in which way, we can isolate them earlier than before and examine how they differ at a molecular level,” Dr Marr added. “We want to use this information to understand how the choices are made for particular developmental traits.”
Deep learning can be used to determine how murine hematopoietic stem and progenitor cells (HSPCs) will differentiate, according to research published in Nature Methods.
Deep learning algorithms simulate the learning processes in people using artificial neural networks.
Researchers have reported the development of software that uses deep learning to predict which type of cell murine HSPCs will differentiate into, based on microscopy images.
“A hematopoietic stem cell’s decision to become a certain cell type cannot be observed,” said study author Carsten Marr, PhD, of Helmholtz Zentrum München–German Research Center for Environmental Health in Neuherberg, Germany.
“At this time, it is only possible to verify the decision retrospectively with cell surface markers.”
Therefore, Dr Marr and his team set out to develop an algorithm that can predict the decision in advance, and deep learning was key.
“Deep neural networks play a major role in our method,” Dr Marr said. “Our algorithm classifies light microscopic images and videos of individual cells by comparing these data with past experience from the development of such cells. In this way, the algorithm ‘learns’ how certain cells behave.”
Specifically, the researchers examined murine HSPCs filmed under a microscope in the lab. Using information on the cells’ appearance and speed, the software was able to “memorize” the corresponding behavior patterns and then make its prediction.
“Compared to conventional methods, such as fluorescent antibodies against certain surface proteins, we know how the cells will decide 3 cell generations earlier,” said Felix Buggenthin, PhD, of Helmholtz Zentrum München–German Research Center for Environmental Health.
“Since we now know which cells will develop in which way, we can isolate them earlier than before and examine how they differ at a molecular level,” Dr Marr added. “We want to use this information to understand how the choices are made for particular developmental traits.”
Deep learning can be used to determine how murine hematopoietic stem and progenitor cells (HSPCs) will differentiate, according to research published in Nature Methods.
Deep learning algorithms simulate the learning processes in people using artificial neural networks.
Researchers have reported the development of software that uses deep learning to predict which type of cell murine HSPCs will differentiate into, based on microscopy images.
“A hematopoietic stem cell’s decision to become a certain cell type cannot be observed,” said study author Carsten Marr, PhD, of Helmholtz Zentrum München–German Research Center for Environmental Health in Neuherberg, Germany.
“At this time, it is only possible to verify the decision retrospectively with cell surface markers.”
Therefore, Dr Marr and his team set out to develop an algorithm that can predict the decision in advance, and deep learning was key.
“Deep neural networks play a major role in our method,” Dr Marr said. “Our algorithm classifies light microscopic images and videos of individual cells by comparing these data with past experience from the development of such cells. In this way, the algorithm ‘learns’ how certain cells behave.”
Specifically, the researchers examined murine HSPCs filmed under a microscope in the lab. Using information on the cells’ appearance and speed, the software was able to “memorize” the corresponding behavior patterns and then make its prediction.
“Compared to conventional methods, such as fluorescent antibodies against certain surface proteins, we know how the cells will decide 3 cell generations earlier,” said Felix Buggenthin, PhD, of Helmholtz Zentrum München–German Research Center for Environmental Health.
“Since we now know which cells will develop in which way, we can isolate them earlier than before and examine how they differ at a molecular level,” Dr Marr added. “We want to use this information to understand how the choices are made for particular developmental traits.”
European Commission approves rituximab biosimilar
The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.
This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).
Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.
The approval is based on data submitted to the European Medicines Agency.
The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).
Therefore, the European Commission approved Truxima for the following indications.
Non-Hodgkin lymphoma
Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.
Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.
Truxima monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.
Truxima is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.
Chronic lymphocytic leukemia
Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.
The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.
RA, GPA, and MPA
Truxima in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.
Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.
Truxima studies
There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).
Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).
Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635). 
The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.
This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).
Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.
The approval is based on data submitted to the European Medicines Agency.
The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).
Therefore, the European Commission approved Truxima for the following indications.
Non-Hodgkin lymphoma
Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.
Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.
Truxima monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.
Truxima is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.
Chronic lymphocytic leukemia
Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.
The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.
RA, GPA, and MPA
Truxima in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.
Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.
Truxima studies
There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).
Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).
Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).
The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.
This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).
Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.
The approval is based on data submitted to the European Medicines Agency.
The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).
Therefore, the European Commission approved Truxima for the following indications.
Non-Hodgkin lymphoma
Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.
Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.
Truxima monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.
Truxima is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.
Chronic lymphocytic leukemia
Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.
The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.
RA, GPA, and MPA
Truxima in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.
Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.
Truxima studies
There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).
Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).
Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).
Tips for taming atopic dermatitis and managing expectations
MIAMI – Tactics for managing patients with atopic dermatitis can go a long way to educate patients, set realistic expectations, and devise strategies for existing therapies, even as clinicians await some promising agents expected on the market soon.
“The good news is this is the Age of Eczema. In the last couple of years we’ve seen an explosion in the literature,” Adam Friedman, MD, of the department of dermatology, George Washington University, Washington, D.C., said at the Orlando Dermatology Aesthetic and Clinical Conference. Some of this research is spurring new therapeutics. a phosphodiesterase 4 inhibitor.
Crisaborole ointment, 2% (Eucrisa), a phosphodiesterase 4 inhibitor, was approved by the Food and Drug Administration in December 2016 for treating patients aged 2 years and older with mild to moderate AD, for example. It is a novel, nonsteroidal anti-inflammatory and the first prescription agent approved in the United States for atopic dermatitis in more than 10 years.
Dr. Friedman has no personal experience with crisaborole, which just became available. “But the data look encouraging. From what I’ve seen this may be a nonburning alternative to calcineurin inhibitors. It will be interesting to see how this will fit in our practices.”
Systemic management of pruritus
There’s also promise for patients troubled by one of the top manifestations of AD – the itch. “We have new targeted therapies coming down the pike, some hopefully [gaining approval] in the next few months. We have biologics going after the cytokines of itch. It’s a very, very exciting time right now,” Dr. Friedman said.
Current clinical trials are not only focusing on AD but also specifically on pruritus, he added.
In the meantime, itch can be managed with prescription and over-the-counter topical agents, as well as systemic therapies such as gabapentin, some antidepressants, and the antiemetic aprepitant. Aprepitant is a substance P antagonist (through blocking neurokinin 1 receptor) and can be effective for some patients when taken three times a week, but it is not indicated for itch, Dr. Friedman said. Because of its off label indication “it’s a little tricky getting [insurance] coverage.”
Back to basics
“Even with all the excitement, even with the new therapeutics, you have to stick with the basics,” he said. “Put the lotion on, put the cream on. You have to put moisturizer on wet skin and be cautious with soaps.” He added, “don’t be afraid to ask for help. The National Eczema Association has a wonderful website with research, education, tools – you name it.”
Keeping it real
For regional eczemas like hand dermatitis, what are the options? “Tell patients they can glove up, there are various latex alternatives … but it probably won’t fly in the real world,” Dr. Friedman said. Zinc oxide “works like armor, and patients will probably do well,” but the aesthetics are unacceptable for most, he added. “Newer alternatives, such as those with aluminum magnesium hydroxide stearate, have similar protecting power, but are not opaque and rub on easier.”
A goal of topical therapy is to get rid of the inflammation, and steroids have a long history of evidence supporting their use, but “topical steroid phobia in parents” is a problem, he said. To counter the reluctance or refusal to use topical steroids, he suggested exploring reasons for noncompliance, dispelling any myths, and working with parent to make it easier to apply the steroids to their child.
Interestingly, there is some evidence that a simpler regimen may work well for some patients. “We always say ‘apply twice a day.’ Why? Because all the clinical trials had participants apply steroids twice a day. But there is no evidence to show twice a day is better than once a day, and in fact, a meta-analysis suggests once a day works just as well” (Br J Dermatol. 2005 Jan;152[1]:130-41).
Topical calcineurin inhibitors are another option. In general, Dr. Friedman prescribes these agents for delicate areas, for patients with thin skin, or for patients who use a topical steroid “on and on and on and can’t seem to get off it.” Calcineurin inhibitors can also be used on in-between days during steroid maintenance therapy, he added. When prescribing, warn patients about the initial burn (due to substance P release) that commonly occurs so that they have realistic expectations.
Education remains essential
“I encourage you to educate your patients and empathize with them,” he said. “Show them how to apply a moisturizer. Also, use your nurses and assistants to help with education – really empower them to be part of the process.”
“Explain, explain, explain, so they have realistic expectations,” and know that there is no cure, so that when they experience a flare, they understand that “it’s not that the steroid didn’t work – this is a chronic disease,” added Dr. Friedman, who recommends providing patients with handouts that answer many of their questions.
Maximize moisturizing
When it comes to moisturizing, more is usually better. Effective products contain all the key ingredients: emollients to soften the skin, an occlusive to keep the water there, and a humectant to bond the water. “Just one or two is not going to cut it,” he said.
“Something we now know is that starting early is key,” he pointed out, referring to recent studies that have shown that in babies at high risk for AD, starting moisturizers early can decrease their risk for developing AD later (J Allergy Clin Immunol. 2014 Oct; 134[4]: 818-23).
“Another study that received a ton of press was in JAMA Pediatrics recently,” Dr. Friedman said. The study concluded that the use of different moisturizers to prevent AD in high risk babies was likely to be cost-effective (JAMA Pediatr. 2017 Feb 6;171[2]:e163909. doi: 10.1001/jamapediatrics.2016.3909). Although some news reports claimed starting babies with Vaseline as a moisturizer will prevent AD, “that’s actually not what the study showed. All the over-the-counter moisturizers they used worked, but Vaseline was the least expensive,” Dr. Friedman noted
Help patients select the right soap
Educate patients to avoid “true soaps” such as Dial, Ivory, Irish Spring, or Lever 2000. “Soaps can be a real enemy here. You want lower pH types of soaps. Depending on skin type, our skin is somewhere between 5.5 and 6.5 pH,” Dr. Friedman explained. “The paradigm shift for your patients is to hydrate, not to clean. Showers are okay if they’re not blaring hot. Baths are okay ... but you should not be sitting in a sudsy bath.”
Also, instruct patients to avoid irritating fabrics, dryer sheets, or harsh laundry detergents that could exacerbate AD.
‘You’re not alone’
Sometimes it’s helpful to assure patients with AD that they’re not alone, and that many researchers and clinicians are working on effective treatment strategies. “We’re all familiar with atopic dermatitis because there’s so much of it. The numbers are surprisingly high,” Dr. Friedman said. Compared with the estimated 2.2 million Americans with psoriasis, AD eclipses their numbers substantially, affecting about 17 million people.
Dr. Friedman disclosed that he is a speaker for Amgen, Janssen, and Promius; receives research grants from Valeant; and is a consultant and/or advisory board member for Amgen, Aveeno, Biogen, Encore, Exeltis, Ferndale, Galderma, G&W Laboratories, Intraderm, La Roche-Posay, Loreal, Microcures, Nano Bio-Med, Novartis, Oakstone Institute, Occulus, Onset, Pfizer, Promius, Sanova Works, and Valeant. Dr. Friedman is also an editorial advisory board member for Dermatology News.
MIAMI – Tactics for managing patients with atopic dermatitis can go a long way to educate patients, set realistic expectations, and devise strategies for existing therapies, even as clinicians await some promising agents expected on the market soon.
“The good news is this is the Age of Eczema. In the last couple of years we’ve seen an explosion in the literature,” Adam Friedman, MD, of the department of dermatology, George Washington University, Washington, D.C., said at the Orlando Dermatology Aesthetic and Clinical Conference. Some of this research is spurring new therapeutics. a phosphodiesterase 4 inhibitor.
Crisaborole ointment, 2% (Eucrisa), a phosphodiesterase 4 inhibitor, was approved by the Food and Drug Administration in December 2016 for treating patients aged 2 years and older with mild to moderate AD, for example. It is a novel, nonsteroidal anti-inflammatory and the first prescription agent approved in the United States for atopic dermatitis in more than 10 years.
Dr. Friedman has no personal experience with crisaborole, which just became available. “But the data look encouraging. From what I’ve seen this may be a nonburning alternative to calcineurin inhibitors. It will be interesting to see how this will fit in our practices.”
Systemic management of pruritus
There’s also promise for patients troubled by one of the top manifestations of AD – the itch. “We have new targeted therapies coming down the pike, some hopefully [gaining approval] in the next few months. We have biologics going after the cytokines of itch. It’s a very, very exciting time right now,” Dr. Friedman said.
Current clinical trials are not only focusing on AD but also specifically on pruritus, he added.
In the meantime, itch can be managed with prescription and over-the-counter topical agents, as well as systemic therapies such as gabapentin, some antidepressants, and the antiemetic aprepitant. Aprepitant is a substance P antagonist (through blocking neurokinin 1 receptor) and can be effective for some patients when taken three times a week, but it is not indicated for itch, Dr. Friedman said. Because of its off label indication “it’s a little tricky getting [insurance] coverage.”
Back to basics
“Even with all the excitement, even with the new therapeutics, you have to stick with the basics,” he said. “Put the lotion on, put the cream on. You have to put moisturizer on wet skin and be cautious with soaps.” He added, “don’t be afraid to ask for help. The National Eczema Association has a wonderful website with research, education, tools – you name it.”
Keeping it real
For regional eczemas like hand dermatitis, what are the options? “Tell patients they can glove up, there are various latex alternatives … but it probably won’t fly in the real world,” Dr. Friedman said. Zinc oxide “works like armor, and patients will probably do well,” but the aesthetics are unacceptable for most, he added. “Newer alternatives, such as those with aluminum magnesium hydroxide stearate, have similar protecting power, but are not opaque and rub on easier.”
A goal of topical therapy is to get rid of the inflammation, and steroids have a long history of evidence supporting their use, but “topical steroid phobia in parents” is a problem, he said. To counter the reluctance or refusal to use topical steroids, he suggested exploring reasons for noncompliance, dispelling any myths, and working with parent to make it easier to apply the steroids to their child.
Interestingly, there is some evidence that a simpler regimen may work well for some patients. “We always say ‘apply twice a day.’ Why? Because all the clinical trials had participants apply steroids twice a day. But there is no evidence to show twice a day is better than once a day, and in fact, a meta-analysis suggests once a day works just as well” (Br J Dermatol. 2005 Jan;152[1]:130-41).
Topical calcineurin inhibitors are another option. In general, Dr. Friedman prescribes these agents for delicate areas, for patients with thin skin, or for patients who use a topical steroid “on and on and on and can’t seem to get off it.” Calcineurin inhibitors can also be used on in-between days during steroid maintenance therapy, he added. When prescribing, warn patients about the initial burn (due to substance P release) that commonly occurs so that they have realistic expectations.
Education remains essential
“I encourage you to educate your patients and empathize with them,” he said. “Show them how to apply a moisturizer. Also, use your nurses and assistants to help with education – really empower them to be part of the process.”
“Explain, explain, explain, so they have realistic expectations,” and know that there is no cure, so that when they experience a flare, they understand that “it’s not that the steroid didn’t work – this is a chronic disease,” added Dr. Friedman, who recommends providing patients with handouts that answer many of their questions.
Maximize moisturizing
When it comes to moisturizing, more is usually better. Effective products contain all the key ingredients: emollients to soften the skin, an occlusive to keep the water there, and a humectant to bond the water. “Just one or two is not going to cut it,” he said.
“Something we now know is that starting early is key,” he pointed out, referring to recent studies that have shown that in babies at high risk for AD, starting moisturizers early can decrease their risk for developing AD later (J Allergy Clin Immunol. 2014 Oct; 134[4]: 818-23).
“Another study that received a ton of press was in JAMA Pediatrics recently,” Dr. Friedman said. The study concluded that the use of different moisturizers to prevent AD in high risk babies was likely to be cost-effective (JAMA Pediatr. 2017 Feb 6;171[2]:e163909. doi: 10.1001/jamapediatrics.2016.3909). Although some news reports claimed starting babies with Vaseline as a moisturizer will prevent AD, “that’s actually not what the study showed. All the over-the-counter moisturizers they used worked, but Vaseline was the least expensive,” Dr. Friedman noted
Help patients select the right soap
Educate patients to avoid “true soaps” such as Dial, Ivory, Irish Spring, or Lever 2000. “Soaps can be a real enemy here. You want lower pH types of soaps. Depending on skin type, our skin is somewhere between 5.5 and 6.5 pH,” Dr. Friedman explained. “The paradigm shift for your patients is to hydrate, not to clean. Showers are okay if they’re not blaring hot. Baths are okay ... but you should not be sitting in a sudsy bath.”
Also, instruct patients to avoid irritating fabrics, dryer sheets, or harsh laundry detergents that could exacerbate AD.
‘You’re not alone’
Sometimes it’s helpful to assure patients with AD that they’re not alone, and that many researchers and clinicians are working on effective treatment strategies. “We’re all familiar with atopic dermatitis because there’s so much of it. The numbers are surprisingly high,” Dr. Friedman said. Compared with the estimated 2.2 million Americans with psoriasis, AD eclipses their numbers substantially, affecting about 17 million people.
Dr. Friedman disclosed that he is a speaker for Amgen, Janssen, and Promius; receives research grants from Valeant; and is a consultant and/or advisory board member for Amgen, Aveeno, Biogen, Encore, Exeltis, Ferndale, Galderma, G&W Laboratories, Intraderm, La Roche-Posay, Loreal, Microcures, Nano Bio-Med, Novartis, Oakstone Institute, Occulus, Onset, Pfizer, Promius, Sanova Works, and Valeant. Dr. Friedman is also an editorial advisory board member for Dermatology News.
MIAMI – Tactics for managing patients with atopic dermatitis can go a long way to educate patients, set realistic expectations, and devise strategies for existing therapies, even as clinicians await some promising agents expected on the market soon.
“The good news is this is the Age of Eczema. In the last couple of years we’ve seen an explosion in the literature,” Adam Friedman, MD, of the department of dermatology, George Washington University, Washington, D.C., said at the Orlando Dermatology Aesthetic and Clinical Conference. Some of this research is spurring new therapeutics. a phosphodiesterase 4 inhibitor.
Crisaborole ointment, 2% (Eucrisa), a phosphodiesterase 4 inhibitor, was approved by the Food and Drug Administration in December 2016 for treating patients aged 2 years and older with mild to moderate AD, for example. It is a novel, nonsteroidal anti-inflammatory and the first prescription agent approved in the United States for atopic dermatitis in more than 10 years.
Dr. Friedman has no personal experience with crisaborole, which just became available. “But the data look encouraging. From what I’ve seen this may be a nonburning alternative to calcineurin inhibitors. It will be interesting to see how this will fit in our practices.”
Systemic management of pruritus
There’s also promise for patients troubled by one of the top manifestations of AD – the itch. “We have new targeted therapies coming down the pike, some hopefully [gaining approval] in the next few months. We have biologics going after the cytokines of itch. It’s a very, very exciting time right now,” Dr. Friedman said.
Current clinical trials are not only focusing on AD but also specifically on pruritus, he added.
In the meantime, itch can be managed with prescription and over-the-counter topical agents, as well as systemic therapies such as gabapentin, some antidepressants, and the antiemetic aprepitant. Aprepitant is a substance P antagonist (through blocking neurokinin 1 receptor) and can be effective for some patients when taken three times a week, but it is not indicated for itch, Dr. Friedman said. Because of its off label indication “it’s a little tricky getting [insurance] coverage.”
Back to basics
“Even with all the excitement, even with the new therapeutics, you have to stick with the basics,” he said. “Put the lotion on, put the cream on. You have to put moisturizer on wet skin and be cautious with soaps.” He added, “don’t be afraid to ask for help. The National Eczema Association has a wonderful website with research, education, tools – you name it.”
Keeping it real
For regional eczemas like hand dermatitis, what are the options? “Tell patients they can glove up, there are various latex alternatives … but it probably won’t fly in the real world,” Dr. Friedman said. Zinc oxide “works like armor, and patients will probably do well,” but the aesthetics are unacceptable for most, he added. “Newer alternatives, such as those with aluminum magnesium hydroxide stearate, have similar protecting power, but are not opaque and rub on easier.”
A goal of topical therapy is to get rid of the inflammation, and steroids have a long history of evidence supporting their use, but “topical steroid phobia in parents” is a problem, he said. To counter the reluctance or refusal to use topical steroids, he suggested exploring reasons for noncompliance, dispelling any myths, and working with parent to make it easier to apply the steroids to their child.
Interestingly, there is some evidence that a simpler regimen may work well for some patients. “We always say ‘apply twice a day.’ Why? Because all the clinical trials had participants apply steroids twice a day. But there is no evidence to show twice a day is better than once a day, and in fact, a meta-analysis suggests once a day works just as well” (Br J Dermatol. 2005 Jan;152[1]:130-41).
Topical calcineurin inhibitors are another option. In general, Dr. Friedman prescribes these agents for delicate areas, for patients with thin skin, or for patients who use a topical steroid “on and on and on and can’t seem to get off it.” Calcineurin inhibitors can also be used on in-between days during steroid maintenance therapy, he added. When prescribing, warn patients about the initial burn (due to substance P release) that commonly occurs so that they have realistic expectations.
Education remains essential
“I encourage you to educate your patients and empathize with them,” he said. “Show them how to apply a moisturizer. Also, use your nurses and assistants to help with education – really empower them to be part of the process.”
“Explain, explain, explain, so they have realistic expectations,” and know that there is no cure, so that when they experience a flare, they understand that “it’s not that the steroid didn’t work – this is a chronic disease,” added Dr. Friedman, who recommends providing patients with handouts that answer many of their questions.
Maximize moisturizing
When it comes to moisturizing, more is usually better. Effective products contain all the key ingredients: emollients to soften the skin, an occlusive to keep the water there, and a humectant to bond the water. “Just one or two is not going to cut it,” he said.
“Something we now know is that starting early is key,” he pointed out, referring to recent studies that have shown that in babies at high risk for AD, starting moisturizers early can decrease their risk for developing AD later (J Allergy Clin Immunol. 2014 Oct; 134[4]: 818-23).
“Another study that received a ton of press was in JAMA Pediatrics recently,” Dr. Friedman said. The study concluded that the use of different moisturizers to prevent AD in high risk babies was likely to be cost-effective (JAMA Pediatr. 2017 Feb 6;171[2]:e163909. doi: 10.1001/jamapediatrics.2016.3909). Although some news reports claimed starting babies with Vaseline as a moisturizer will prevent AD, “that’s actually not what the study showed. All the over-the-counter moisturizers they used worked, but Vaseline was the least expensive,” Dr. Friedman noted
Help patients select the right soap
Educate patients to avoid “true soaps” such as Dial, Ivory, Irish Spring, or Lever 2000. “Soaps can be a real enemy here. You want lower pH types of soaps. Depending on skin type, our skin is somewhere between 5.5 and 6.5 pH,” Dr. Friedman explained. “The paradigm shift for your patients is to hydrate, not to clean. Showers are okay if they’re not blaring hot. Baths are okay ... but you should not be sitting in a sudsy bath.”
Also, instruct patients to avoid irritating fabrics, dryer sheets, or harsh laundry detergents that could exacerbate AD.
‘You’re not alone’
Sometimes it’s helpful to assure patients with AD that they’re not alone, and that many researchers and clinicians are working on effective treatment strategies. “We’re all familiar with atopic dermatitis because there’s so much of it. The numbers are surprisingly high,” Dr. Friedman said. Compared with the estimated 2.2 million Americans with psoriasis, AD eclipses their numbers substantially, affecting about 17 million people.
Dr. Friedman disclosed that he is a speaker for Amgen, Janssen, and Promius; receives research grants from Valeant; and is a consultant and/or advisory board member for Amgen, Aveeno, Biogen, Encore, Exeltis, Ferndale, Galderma, G&W Laboratories, Intraderm, La Roche-Posay, Loreal, Microcures, Nano Bio-Med, Novartis, Oakstone Institute, Occulus, Onset, Pfizer, Promius, Sanova Works, and Valeant. Dr. Friedman is also an editorial advisory board member for Dermatology News.
AT ODAC 2017
Antibiotic prophylaxis for artificial joints
A 66-year-old woman 3 years status post hip replacement is seen for dental work. The dentist contacts the clinic for an antibiotic prescription. The patient has a penicillin allergy (rash). What do you recommend?
A. Clindamycin one dose before dental work.
B. Amoxicillin one dose before dental work.
C. Amoxicillin one dose before, one dose 4 hours after dental work.
D. Clindamycin one dose before dental work, one dose 4 hours after dental work.
E. No antibiotics.
Many patients with prosthetic joints will request antibiotics to take prior to dental procedures. Sometimes this request comes from the dental office.
When I ask patients why they feel they need antibiotics, they often reply that they were told by their orthopedic surgeons or their dentist that they would need to take antibiotics before dental procedures.
In an era when Clostridium difficile infection is a common and dangerous complication in the elderly, avoidance of unnecessary antibiotics is critical. In the United States, it is estimated that there are 240,000 patients infected with C. difficile annually, with 24,000 deaths at a cost of $6 billion.1
Is there compelling evidence to justify giving antibiotic prophylaxis for dental procedures to patients with prosthetic joints?
This information has called into question the wisdom of giving antibiotic prophylaxis for dental procedures when the same patients have transient bacteremias as a regular part of day-to-day life, and mouth organisms were infrequent causes of prosthetic joint infections.
The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) released an advisory statement 20 years ago on antibiotic prophylaxis for patients with dental replacements, which concluded: “Antibiotic prophylaxis is not indicated for dental patients with pins, plates, and screws, nor is it routinely indicated for most dental patients with total joint replacements.”4
In 2003, the AAOS and the ADA released updated guidelines that stated: “Presently, no scientific evidence supports the position that antibiotic prophylaxis to prevent hematogenous infections is required prior to dental treatment in patients with total joint prostheses. The risk/benefit and cost/effectiveness ratios fail to justify the administration of routine antibiotics.”5
Great confusion arose in 2009 when the AAOS published a position paper on its website that reversed this position.6 Interestingly, the statement was done by the AAOS alone, and not done in conjunction with the ADA.
In this position paper, the AAOS recommended that health care providers consider antibiotic prophylaxis prior to invasive procedures on all patients who had prosthetic joints, regardless of how long those joints have been in place. This major change in recommendations was not based on any new evidence that had been reviewed since the 2003 guidelines.
There are two studies that address outcome of patients with prosthetic joints who have and have not received prophylactic antibiotics.
Elie Berbari, MD, and colleagues reported on the results of a prospective case-control study comparing patients with prosthetic joints hospitalized with hip or knee infections with patients who had prosthetic joints hospitalized at the same time who did not have hip or knee infections.7
There was no increased risk of prosthetic hip or knee infection for patients undergoing a dental procedure who were not receiving antibiotic prophylaxis (odds ratio, 0.8; 95% confidence interval, 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Antibiotic prophylaxis in patients undergoing high and low risk dental procedures did not decrease the risk of prosthetic joint infections.
In 2012, the AAOS and the ADA published updated guidelines with the following summary recommendation: “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”8 They referenced the Berbari study as the best available evidence.
Feng-Chen Kao, MD, and colleagues published a study this year with a design very similar to the Berbari study, with similar results.9 All Taiwanese residents who had received hip or knee replacements over a 12-year period were screened. Those who had received dental procedures were matched with individuals who had not had dental procedures. The dental procedure group was subdivided into a group that received antibiotics and one that didn’t.
There was no difference in infection rates between the group that had received dental procedures and the group that did not, and no difference in infection rates between those who received prophylactic antibiotics and those who didn’t.
I think this myth can be put to rest. There is no evidence to give patients with joint prostheses prophylactic antibiotics before dental procedures.
References
1. Steckelberg J.M., Osmon D.R. Prosthetic joint infections. In: Bisno A.L., Waldvogel F.A., eds. Infections associated with indwelling medical devices. Third ed., Washington, D.C.: American Society of Microbiology Press, 2000:173-209.
2. J Dent Res. 2004 Feb;83(2):170-4.
3. J Clin Periodontol. 2006 Feb;33(6):401-7.
4. J Am Dent Assoc. 1997 Jul;128(7):1004-8.
5. J Am Dent Assoc. 2003 Jul;134(7):895-9.
6. Spec Care Dentist. 2009 Nov-Dec;29(6):229-31.
7. Clin Infect Dis. 2010 Jan 1;50(1):8-16.
8. J Dent (Shiraz). 2013 Mar;14(1):49-52.
9. Infect Control Hosp Epidemiol. 2017 Feb;38(2):154-61.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
A 66-year-old woman 3 years status post hip replacement is seen for dental work. The dentist contacts the clinic for an antibiotic prescription. The patient has a penicillin allergy (rash). What do you recommend?
A. Clindamycin one dose before dental work.
B. Amoxicillin one dose before dental work.
C. Amoxicillin one dose before, one dose 4 hours after dental work.
D. Clindamycin one dose before dental work, one dose 4 hours after dental work.
E. No antibiotics.
Many patients with prosthetic joints will request antibiotics to take prior to dental procedures. Sometimes this request comes from the dental office.
When I ask patients why they feel they need antibiotics, they often reply that they were told by their orthopedic surgeons or their dentist that they would need to take antibiotics before dental procedures.
In an era when Clostridium difficile infection is a common and dangerous complication in the elderly, avoidance of unnecessary antibiotics is critical. In the United States, it is estimated that there are 240,000 patients infected with C. difficile annually, with 24,000 deaths at a cost of $6 billion.1
Is there compelling evidence to justify giving antibiotic prophylaxis for dental procedures to patients with prosthetic joints?
This information has called into question the wisdom of giving antibiotic prophylaxis for dental procedures when the same patients have transient bacteremias as a regular part of day-to-day life, and mouth organisms were infrequent causes of prosthetic joint infections.
The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) released an advisory statement 20 years ago on antibiotic prophylaxis for patients with dental replacements, which concluded: “Antibiotic prophylaxis is not indicated for dental patients with pins, plates, and screws, nor is it routinely indicated for most dental patients with total joint replacements.”4
In 2003, the AAOS and the ADA released updated guidelines that stated: “Presently, no scientific evidence supports the position that antibiotic prophylaxis to prevent hematogenous infections is required prior to dental treatment in patients with total joint prostheses. The risk/benefit and cost/effectiveness ratios fail to justify the administration of routine antibiotics.”5
Great confusion arose in 2009 when the AAOS published a position paper on its website that reversed this position.6 Interestingly, the statement was done by the AAOS alone, and not done in conjunction with the ADA.
In this position paper, the AAOS recommended that health care providers consider antibiotic prophylaxis prior to invasive procedures on all patients who had prosthetic joints, regardless of how long those joints have been in place. This major change in recommendations was not based on any new evidence that had been reviewed since the 2003 guidelines.
There are two studies that address outcome of patients with prosthetic joints who have and have not received prophylactic antibiotics.
Elie Berbari, MD, and colleagues reported on the results of a prospective case-control study comparing patients with prosthetic joints hospitalized with hip or knee infections with patients who had prosthetic joints hospitalized at the same time who did not have hip or knee infections.7
There was no increased risk of prosthetic hip or knee infection for patients undergoing a dental procedure who were not receiving antibiotic prophylaxis (odds ratio, 0.8; 95% confidence interval, 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Antibiotic prophylaxis in patients undergoing high and low risk dental procedures did not decrease the risk of prosthetic joint infections.
In 2012, the AAOS and the ADA published updated guidelines with the following summary recommendation: “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”8 They referenced the Berbari study as the best available evidence.
Feng-Chen Kao, MD, and colleagues published a study this year with a design very similar to the Berbari study, with similar results.9 All Taiwanese residents who had received hip or knee replacements over a 12-year period were screened. Those who had received dental procedures were matched with individuals who had not had dental procedures. The dental procedure group was subdivided into a group that received antibiotics and one that didn’t.
There was no difference in infection rates between the group that had received dental procedures and the group that did not, and no difference in infection rates between those who received prophylactic antibiotics and those who didn’t.
I think this myth can be put to rest. There is no evidence to give patients with joint prostheses prophylactic antibiotics before dental procedures.
References
1. Steckelberg J.M., Osmon D.R. Prosthetic joint infections. In: Bisno A.L., Waldvogel F.A., eds. Infections associated with indwelling medical devices. Third ed., Washington, D.C.: American Society of Microbiology Press, 2000:173-209.
2. J Dent Res. 2004 Feb;83(2):170-4.
3. J Clin Periodontol. 2006 Feb;33(6):401-7.
4. J Am Dent Assoc. 1997 Jul;128(7):1004-8.
5. J Am Dent Assoc. 2003 Jul;134(7):895-9.
6. Spec Care Dentist. 2009 Nov-Dec;29(6):229-31.
7. Clin Infect Dis. 2010 Jan 1;50(1):8-16.
8. J Dent (Shiraz). 2013 Mar;14(1):49-52.
9. Infect Control Hosp Epidemiol. 2017 Feb;38(2):154-61.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
A 66-year-old woman 3 years status post hip replacement is seen for dental work. The dentist contacts the clinic for an antibiotic prescription. The patient has a penicillin allergy (rash). What do you recommend?
A. Clindamycin one dose before dental work.
B. Amoxicillin one dose before dental work.
C. Amoxicillin one dose before, one dose 4 hours after dental work.
D. Clindamycin one dose before dental work, one dose 4 hours after dental work.
E. No antibiotics.
Many patients with prosthetic joints will request antibiotics to take prior to dental procedures. Sometimes this request comes from the dental office.
When I ask patients why they feel they need antibiotics, they often reply that they were told by their orthopedic surgeons or their dentist that they would need to take antibiotics before dental procedures.
In an era when Clostridium difficile infection is a common and dangerous complication in the elderly, avoidance of unnecessary antibiotics is critical. In the United States, it is estimated that there are 240,000 patients infected with C. difficile annually, with 24,000 deaths at a cost of $6 billion.1
Is there compelling evidence to justify giving antibiotic prophylaxis for dental procedures to patients with prosthetic joints?
This information has called into question the wisdom of giving antibiotic prophylaxis for dental procedures when the same patients have transient bacteremias as a regular part of day-to-day life, and mouth organisms were infrequent causes of prosthetic joint infections.
The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) released an advisory statement 20 years ago on antibiotic prophylaxis for patients with dental replacements, which concluded: “Antibiotic prophylaxis is not indicated for dental patients with pins, plates, and screws, nor is it routinely indicated for most dental patients with total joint replacements.”4
In 2003, the AAOS and the ADA released updated guidelines that stated: “Presently, no scientific evidence supports the position that antibiotic prophylaxis to prevent hematogenous infections is required prior to dental treatment in patients with total joint prostheses. The risk/benefit and cost/effectiveness ratios fail to justify the administration of routine antibiotics.”5
Great confusion arose in 2009 when the AAOS published a position paper on its website that reversed this position.6 Interestingly, the statement was done by the AAOS alone, and not done in conjunction with the ADA.
In this position paper, the AAOS recommended that health care providers consider antibiotic prophylaxis prior to invasive procedures on all patients who had prosthetic joints, regardless of how long those joints have been in place. This major change in recommendations was not based on any new evidence that had been reviewed since the 2003 guidelines.
There are two studies that address outcome of patients with prosthetic joints who have and have not received prophylactic antibiotics.
Elie Berbari, MD, and colleagues reported on the results of a prospective case-control study comparing patients with prosthetic joints hospitalized with hip or knee infections with patients who had prosthetic joints hospitalized at the same time who did not have hip or knee infections.7
There was no increased risk of prosthetic hip or knee infection for patients undergoing a dental procedure who were not receiving antibiotic prophylaxis (odds ratio, 0.8; 95% confidence interval, 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Antibiotic prophylaxis in patients undergoing high and low risk dental procedures did not decrease the risk of prosthetic joint infections.
In 2012, the AAOS and the ADA published updated guidelines with the following summary recommendation: “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”8 They referenced the Berbari study as the best available evidence.
Feng-Chen Kao, MD, and colleagues published a study this year with a design very similar to the Berbari study, with similar results.9 All Taiwanese residents who had received hip or knee replacements over a 12-year period were screened. Those who had received dental procedures were matched with individuals who had not had dental procedures. The dental procedure group was subdivided into a group that received antibiotics and one that didn’t.
There was no difference in infection rates between the group that had received dental procedures and the group that did not, and no difference in infection rates between those who received prophylactic antibiotics and those who didn’t.
I think this myth can be put to rest. There is no evidence to give patients with joint prostheses prophylactic antibiotics before dental procedures.
References
1. Steckelberg J.M., Osmon D.R. Prosthetic joint infections. In: Bisno A.L., Waldvogel F.A., eds. Infections associated with indwelling medical devices. Third ed., Washington, D.C.: American Society of Microbiology Press, 2000:173-209.
2. J Dent Res. 2004 Feb;83(2):170-4.
3. J Clin Periodontol. 2006 Feb;33(6):401-7.
4. J Am Dent Assoc. 1997 Jul;128(7):1004-8.
5. J Am Dent Assoc. 2003 Jul;134(7):895-9.
6. Spec Care Dentist. 2009 Nov-Dec;29(6):229-31.
7. Clin Infect Dis. 2010 Jan 1;50(1):8-16.
8. J Dent (Shiraz). 2013 Mar;14(1):49-52.
9. Infect Control Hosp Epidemiol. 2017 Feb;38(2):154-61.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
STEMI team repurposed for rapid treatment of pulmonary emboli
WASHINGTON – The in-hospital team responsible for rapid management of ST-elevation myocardial infarction (STEMI) may also be the right team to manage pulmonary embolism (PE), according to a pilot study associating this approach with rapid treatment times and low overall mortality rates.
The data from the pilot study suggest that arming the STEMI team with a protocol for managing PE “is an effective means to care for patients with massive and submassive pulmonary embolism,” said Michael R. Kendall, MD, of the University of Southern California, Los Angeles. He presented the findings at the 2017 Cardiovascular Research Technologies meeting.
There are obvious parallels between STEMI and PE. Like STEMI, PE requires rapid diagnosis, triage, and when appropriate, an endovascular procedure. This led the USC investigators to consider a formal pilot study to test the premise that the STEMI team is in a position to deliver urgent care and good outcomes to PE patients.
The objective of the pilot study was “to evaluate treatment times and clinical outcome for patients with massive and submassive PE using a dedicated PE protocol,” Dr. Kendall explained. Massive PE was defined as hemodynamic instability with systolic blood pressure below 90 mm Hg or requiring inotropic support. Submassive PE was defined as systolic BP greater than 90 mm Hg with right heart dysfunction, such as a dilated right ventricle and elevated troponin levels.
Over an 18-month period beginning in June 2014, 40 PE patients were treated. The average age was 55 years, 50% were obese, 32% had renal insufficiency, 30% had recent surgery or had recently been immobilized, 30% had a history of deep venous thrombosis, and 28% had an active malignancy. At 43%, the largest single source of cases was the emergency department (ED), while 38% were transferred in from other centers, and 19% were already hospitalized at the time of the PE.
All patients underwent computed tomographic pulmonary angiography (CTPA) as part of the diagnostic procedure prior to an invasive angiogram. Patients received one or more different treatments upon confirmation of the PE, including catheter-directed thrombolytics, rheolytic thrombectomy, mechanical fragmentation, mechanical aspiration, and surgical pulmonary embolectomy. Inferior vena cava filters were used as appropriate.
At presentation, 10% were in cardiac arrest, 22% required intubation, and 12% required extracorporeal membrane oxygenation. On the basis of the diagnostic studies, 57% had a massive PE, and the remainder had submassive disease.
The average time from door to CTPA among those presenting to the ED was roughly 5 hours. It took, on average, an additional 2 hours from CTPA to an invasive angiogram, and another 3 hours to treatment, producing a total average door to treatment time of 10 hours.
Most patients received rheolytic thrombectomy, often with another form of treatment, such as catheter-directed thrombolytics, but 15% were treated with anticoagulation alone. Although a few patients improved sufficiently to obviate the need for an invasive procedure, the remainder of the patients received anticoagulation alone because of contraindications for invasive strategies or treatment refusal.
The average length of a hospital stay was 15 days. Bleeding events occurred in 10% of patients and 18% required a blood transfusion. Survival to hospital discharge was 82%. Although there was no control group, this rate of survival was considered favorable in the context of the severity of the PE.
Overall, delivery of urgent care for PE by a STEMI team was found feasible. Even though treatment approaches were not standardized, the protocol for diagnosing and managing PE on an urgent basis produced encouraging times for delivery of care and outcomes, according to the data presented by Dr. Kendall. Because of the differences in the composition and function of the STEMI team, Dr. Kendall indicated that it is difficult to predict similar success at other centers, but the findings overall were considered positive.
The senior author of the study, David M. Shavelle, MD, also at USC, suggested that the program there might be a template. He believes that the STEMI team has the skills to deliver prompt PE care, and he believes that this approach would be appropriate at other centers. He also suggested that such formal programs may be useful in establishing better treatment protocols.
“For PE, there are no clear guidelines for treatment time intervals, such as time from door to endovascular treatment,” Dr. Shavelle observed. He said that the wide variation of devices currently being used for treatment complicates efforts to develop clear clinical protocols and measure outcomes and “would like to see more standardization of treatment and registries to address these areas.”
Dr. Kendall reported no financial relationships.
WASHINGTON – The in-hospital team responsible for rapid management of ST-elevation myocardial infarction (STEMI) may also be the right team to manage pulmonary embolism (PE), according to a pilot study associating this approach with rapid treatment times and low overall mortality rates.
The data from the pilot study suggest that arming the STEMI team with a protocol for managing PE “is an effective means to care for patients with massive and submassive pulmonary embolism,” said Michael R. Kendall, MD, of the University of Southern California, Los Angeles. He presented the findings at the 2017 Cardiovascular Research Technologies meeting.
There are obvious parallels between STEMI and PE. Like STEMI, PE requires rapid diagnosis, triage, and when appropriate, an endovascular procedure. This led the USC investigators to consider a formal pilot study to test the premise that the STEMI team is in a position to deliver urgent care and good outcomes to PE patients.
The objective of the pilot study was “to evaluate treatment times and clinical outcome for patients with massive and submassive PE using a dedicated PE protocol,” Dr. Kendall explained. Massive PE was defined as hemodynamic instability with systolic blood pressure below 90 mm Hg or requiring inotropic support. Submassive PE was defined as systolic BP greater than 90 mm Hg with right heart dysfunction, such as a dilated right ventricle and elevated troponin levels.
Over an 18-month period beginning in June 2014, 40 PE patients were treated. The average age was 55 years, 50% were obese, 32% had renal insufficiency, 30% had recent surgery or had recently been immobilized, 30% had a history of deep venous thrombosis, and 28% had an active malignancy. At 43%, the largest single source of cases was the emergency department (ED), while 38% were transferred in from other centers, and 19% were already hospitalized at the time of the PE.
All patients underwent computed tomographic pulmonary angiography (CTPA) as part of the diagnostic procedure prior to an invasive angiogram. Patients received one or more different treatments upon confirmation of the PE, including catheter-directed thrombolytics, rheolytic thrombectomy, mechanical fragmentation, mechanical aspiration, and surgical pulmonary embolectomy. Inferior vena cava filters were used as appropriate.
At presentation, 10% were in cardiac arrest, 22% required intubation, and 12% required extracorporeal membrane oxygenation. On the basis of the diagnostic studies, 57% had a massive PE, and the remainder had submassive disease.
The average time from door to CTPA among those presenting to the ED was roughly 5 hours. It took, on average, an additional 2 hours from CTPA to an invasive angiogram, and another 3 hours to treatment, producing a total average door to treatment time of 10 hours.
Most patients received rheolytic thrombectomy, often with another form of treatment, such as catheter-directed thrombolytics, but 15% were treated with anticoagulation alone. Although a few patients improved sufficiently to obviate the need for an invasive procedure, the remainder of the patients received anticoagulation alone because of contraindications for invasive strategies or treatment refusal.
The average length of a hospital stay was 15 days. Bleeding events occurred in 10% of patients and 18% required a blood transfusion. Survival to hospital discharge was 82%. Although there was no control group, this rate of survival was considered favorable in the context of the severity of the PE.
Overall, delivery of urgent care for PE by a STEMI team was found feasible. Even though treatment approaches were not standardized, the protocol for diagnosing and managing PE on an urgent basis produced encouraging times for delivery of care and outcomes, according to the data presented by Dr. Kendall. Because of the differences in the composition and function of the STEMI team, Dr. Kendall indicated that it is difficult to predict similar success at other centers, but the findings overall were considered positive.
The senior author of the study, David M. Shavelle, MD, also at USC, suggested that the program there might be a template. He believes that the STEMI team has the skills to deliver prompt PE care, and he believes that this approach would be appropriate at other centers. He also suggested that such formal programs may be useful in establishing better treatment protocols.
“For PE, there are no clear guidelines for treatment time intervals, such as time from door to endovascular treatment,” Dr. Shavelle observed. He said that the wide variation of devices currently being used for treatment complicates efforts to develop clear clinical protocols and measure outcomes and “would like to see more standardization of treatment and registries to address these areas.”
Dr. Kendall reported no financial relationships.
WASHINGTON – The in-hospital team responsible for rapid management of ST-elevation myocardial infarction (STEMI) may also be the right team to manage pulmonary embolism (PE), according to a pilot study associating this approach with rapid treatment times and low overall mortality rates.
The data from the pilot study suggest that arming the STEMI team with a protocol for managing PE “is an effective means to care for patients with massive and submassive pulmonary embolism,” said Michael R. Kendall, MD, of the University of Southern California, Los Angeles. He presented the findings at the 2017 Cardiovascular Research Technologies meeting.
There are obvious parallels between STEMI and PE. Like STEMI, PE requires rapid diagnosis, triage, and when appropriate, an endovascular procedure. This led the USC investigators to consider a formal pilot study to test the premise that the STEMI team is in a position to deliver urgent care and good outcomes to PE patients.
The objective of the pilot study was “to evaluate treatment times and clinical outcome for patients with massive and submassive PE using a dedicated PE protocol,” Dr. Kendall explained. Massive PE was defined as hemodynamic instability with systolic blood pressure below 90 mm Hg or requiring inotropic support. Submassive PE was defined as systolic BP greater than 90 mm Hg with right heart dysfunction, such as a dilated right ventricle and elevated troponin levels.
Over an 18-month period beginning in June 2014, 40 PE patients were treated. The average age was 55 years, 50% were obese, 32% had renal insufficiency, 30% had recent surgery or had recently been immobilized, 30% had a history of deep venous thrombosis, and 28% had an active malignancy. At 43%, the largest single source of cases was the emergency department (ED), while 38% were transferred in from other centers, and 19% were already hospitalized at the time of the PE.
All patients underwent computed tomographic pulmonary angiography (CTPA) as part of the diagnostic procedure prior to an invasive angiogram. Patients received one or more different treatments upon confirmation of the PE, including catheter-directed thrombolytics, rheolytic thrombectomy, mechanical fragmentation, mechanical aspiration, and surgical pulmonary embolectomy. Inferior vena cava filters were used as appropriate.
At presentation, 10% were in cardiac arrest, 22% required intubation, and 12% required extracorporeal membrane oxygenation. On the basis of the diagnostic studies, 57% had a massive PE, and the remainder had submassive disease.
The average time from door to CTPA among those presenting to the ED was roughly 5 hours. It took, on average, an additional 2 hours from CTPA to an invasive angiogram, and another 3 hours to treatment, producing a total average door to treatment time of 10 hours.
Most patients received rheolytic thrombectomy, often with another form of treatment, such as catheter-directed thrombolytics, but 15% were treated with anticoagulation alone. Although a few patients improved sufficiently to obviate the need for an invasive procedure, the remainder of the patients received anticoagulation alone because of contraindications for invasive strategies or treatment refusal.
The average length of a hospital stay was 15 days. Bleeding events occurred in 10% of patients and 18% required a blood transfusion. Survival to hospital discharge was 82%. Although there was no control group, this rate of survival was considered favorable in the context of the severity of the PE.
Overall, delivery of urgent care for PE by a STEMI team was found feasible. Even though treatment approaches were not standardized, the protocol for diagnosing and managing PE on an urgent basis produced encouraging times for delivery of care and outcomes, according to the data presented by Dr. Kendall. Because of the differences in the composition and function of the STEMI team, Dr. Kendall indicated that it is difficult to predict similar success at other centers, but the findings overall were considered positive.
The senior author of the study, David M. Shavelle, MD, also at USC, suggested that the program there might be a template. He believes that the STEMI team has the skills to deliver prompt PE care, and he believes that this approach would be appropriate at other centers. He also suggested that such formal programs may be useful in establishing better treatment protocols.
“For PE, there are no clear guidelines for treatment time intervals, such as time from door to endovascular treatment,” Dr. Shavelle observed. He said that the wide variation of devices currently being used for treatment complicates efforts to develop clear clinical protocols and measure outcomes and “would like to see more standardization of treatment and registries to address these areas.”
Dr. Kendall reported no financial relationships.
AT THE 2017 CRT MEETING
Key clinical point: The same team assembled for rapid response to STEMI can also treat PE, according to a pilot study.
Major finding: In the initial series of patients, of whom 57% had massive PE, in-hospital mortality was 11%.
Data source: A nonrandomized prospective analysis.
Disclosures: Dr. Kendall reported no financial relationships.
Increased schizophrenia, affective disorder risks associated with infections
Increased risks of schizophrenia and affective disorders were found to be associated with infections treated with anti-infective agents and with infections requiring hospitalization, a large-scale study shows.
Researchers examined health records of all 1,015,447 individuals born in Denmark from 1985 to 2002, their history of treatment of infection, and the risk of schizophrenia and affective disorders.
Infections previously have been shown to be associated with increased risks of mental disorders. The goal of the current study was to investigate whether the use of anti-infective agents in primary care settings had a similar association.
And the researchers did find such an association: an increased risk of schizophrenia (hazard ratio, 1.37; 95% confidence interval, 1.2-1.57) and an increased risk of affective disorders (HR, 1.64; 95% CI, 1.48-1.82) associated with the use of anti-infective agents.
“The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment,” wrote Ole Köhler, MD, of Aarhus University Hospital, Risskov, Denmark, and his associates (Acta Psychiatr Scand. 2017 Feb;135[2]:97-105).
An even higher risk of schizophrenia and affective disorders was found to be associated with individuals with infections requiring hospitalization (HR, 2.05; 95% CI, 1.77-2.38; and HR, 2.59; 95% CI, 2.31-2.89; respectively). Find more details about the study here.
Increased risks of schizophrenia and affective disorders were found to be associated with infections treated with anti-infective agents and with infections requiring hospitalization, a large-scale study shows.
Researchers examined health records of all 1,015,447 individuals born in Denmark from 1985 to 2002, their history of treatment of infection, and the risk of schizophrenia and affective disorders.
Infections previously have been shown to be associated with increased risks of mental disorders. The goal of the current study was to investigate whether the use of anti-infective agents in primary care settings had a similar association.
And the researchers did find such an association: an increased risk of schizophrenia (hazard ratio, 1.37; 95% confidence interval, 1.2-1.57) and an increased risk of affective disorders (HR, 1.64; 95% CI, 1.48-1.82) associated with the use of anti-infective agents.
“The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment,” wrote Ole Köhler, MD, of Aarhus University Hospital, Risskov, Denmark, and his associates (Acta Psychiatr Scand. 2017 Feb;135[2]:97-105).
An even higher risk of schizophrenia and affective disorders was found to be associated with individuals with infections requiring hospitalization (HR, 2.05; 95% CI, 1.77-2.38; and HR, 2.59; 95% CI, 2.31-2.89; respectively). Find more details about the study here.
Increased risks of schizophrenia and affective disorders were found to be associated with infections treated with anti-infective agents and with infections requiring hospitalization, a large-scale study shows.
Researchers examined health records of all 1,015,447 individuals born in Denmark from 1985 to 2002, their history of treatment of infection, and the risk of schizophrenia and affective disorders.
Infections previously have been shown to be associated with increased risks of mental disorders. The goal of the current study was to investigate whether the use of anti-infective agents in primary care settings had a similar association.
And the researchers did find such an association: an increased risk of schizophrenia (hazard ratio, 1.37; 95% confidence interval, 1.2-1.57) and an increased risk of affective disorders (HR, 1.64; 95% CI, 1.48-1.82) associated with the use of anti-infective agents.
“The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment,” wrote Ole Köhler, MD, of Aarhus University Hospital, Risskov, Denmark, and his associates (Acta Psychiatr Scand. 2017 Feb;135[2]:97-105).
An even higher risk of schizophrenia and affective disorders was found to be associated with individuals with infections requiring hospitalization (HR, 2.05; 95% CI, 1.77-2.38; and HR, 2.59; 95% CI, 2.31-2.89; respectively). Find more details about the study here.