Mary Ann Moon

Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.

Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.

Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”

All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.

There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” (Br J Dermatol. 2016. doi: 10.1111/bjd.14500).

These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.

“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.

They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.

No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.

Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.

Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.

Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”

All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.

There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” (Br J Dermatol. 2016. doi: 10.1111/bjd.14500).

These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.

“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.

They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.

No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.

Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.

Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.

Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”

All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.

There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” (Br J Dermatol. 2016. doi: 10.1111/bjd.14500).

These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.

“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.

They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.

No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.

In approximately 42% of recent cases of measles in the United States, the patients were intentionally unvaccinated for nonmedical reasons such as religious or philosophical objections to vaccines, according to a report published online March 15 in JAMA.

Vaccine refusal raised the risk of acquiring measles not only among unvaccinated individuals but also among fully vaccinated people living where the outbreaks occurred, said Dr. Varun K. Phadke of the division of infectious diseases, Emory University, Atlanta, and his associates.

To characterize the contribution of vaccine refusal to recent outbreaks of two vaccine-preventable diseases, the investigators reviewed 18 published studies involving 1,416 measles cases and 32 involving 10,609 pertussis cases. They found that 56.8% of the patients who acquired measles and 24%-45% of those who acquired pertussis were unvaccinated or undervaccinated (hadn’t received all the recommended doses of the vaccines).

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

In 970 measles cases for which there were detailed data, 405 patients (42%) were intentionally unvaccinated without any medical indications for avoiding the vaccine; these patients avoided immunization against measles because of personal, philosophical, or religious beliefs or cultural norms. Unvaccinated people were up to 35 times more likely than were vaccinated people to acquire the infection. Nonetheless, a higher frequency of vaccine refusal in the geographic area of an outbreak also correlated with a higher measles incidence among the vaccinated people living there.

In eight of the largest pertussis outbreaks for which there were detailed data, 59%-93% of patients were intentionally unvaccinated for nonmedical reasons. Unvaccinated people were up to 20 times more likely than were vaccinated people to acquire the infection. And among people who hadn’t received all recommended the doses of pertussis vaccine, the risk of the infection was proportional to the number of doses they missed. As with measles, a higher frequency of refusal of the pertussis vaccine in the vicinity of a pertussis outbreak correlated with a higher incidence even among the vaccinated people living there. Waning immunity explained only some, not all, of the increased risk among vaccinated individuals, Dr. Phadke and his associates noted (JAMA 2016 March 15;315[11]:1149-58). These findings “have broad implications” for vaccine practice and policy. For example, to restrict peoples’ individual freedom by mandating vaccination, it must first be demonstrated that exemptions harm others living in the community.

To improve vaccine coverage, communities should strengthen state- or school-level enforcement of existing vaccine mandates, as well as increase the difficulty of obtaining a vaccine exemption. They also should “address the reasons for vaccine hesitancy, which may include parental perceptions regarding the risk and severity of vaccine-preventable diseases, the safety and effectiveness of routine immunizations, and confidence in medical professionals, corporations, and the health care system,” the investigators said.

This study was supported by the National Institute of Allergy and Infectious Diseases’ Emory Vaccinology Training Program. Dr. Phadke reported having no relevant financial disclosures; one of his associates reported ties to Crucell, Pfizer, Merck, and Parents of Kids with Infectious Diseases.

In approximately 42% of recent cases of measles in the United States, the patients were intentionally unvaccinated for nonmedical reasons such as religious or philosophical objections to vaccines, according to a report published online March 15 in JAMA.

Vaccine refusal raised the risk of acquiring measles not only among unvaccinated individuals but also among fully vaccinated people living where the outbreaks occurred, said Dr. Varun K. Phadke of the division of infectious diseases, Emory University, Atlanta, and his associates.

To characterize the contribution of vaccine refusal to recent outbreaks of two vaccine-preventable diseases, the investigators reviewed 18 published studies involving 1,416 measles cases and 32 involving 10,609 pertussis cases. They found that 56.8% of the patients who acquired measles and 24%-45% of those who acquired pertussis were unvaccinated or undervaccinated (hadn’t received all the recommended doses of the vaccines).

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

In 970 measles cases for which there were detailed data, 405 patients (42%) were intentionally unvaccinated without any medical indications for avoiding the vaccine; these patients avoided immunization against measles because of personal, philosophical, or religious beliefs or cultural norms. Unvaccinated people were up to 35 times more likely than were vaccinated people to acquire the infection. Nonetheless, a higher frequency of vaccine refusal in the geographic area of an outbreak also correlated with a higher measles incidence among the vaccinated people living there.

In eight of the largest pertussis outbreaks for which there were detailed data, 59%-93% of patients were intentionally unvaccinated for nonmedical reasons. Unvaccinated people were up to 20 times more likely than were vaccinated people to acquire the infection. And among people who hadn’t received all recommended the doses of pertussis vaccine, the risk of the infection was proportional to the number of doses they missed. As with measles, a higher frequency of refusal of the pertussis vaccine in the vicinity of a pertussis outbreak correlated with a higher incidence even among the vaccinated people living there. Waning immunity explained only some, not all, of the increased risk among vaccinated individuals, Dr. Phadke and his associates noted (JAMA 2016 March 15;315[11]:1149-58). These findings “have broad implications” for vaccine practice and policy. For example, to restrict peoples’ individual freedom by mandating vaccination, it must first be demonstrated that exemptions harm others living in the community.

To improve vaccine coverage, communities should strengthen state- or school-level enforcement of existing vaccine mandates, as well as increase the difficulty of obtaining a vaccine exemption. They also should “address the reasons for vaccine hesitancy, which may include parental perceptions regarding the risk and severity of vaccine-preventable diseases, the safety and effectiveness of routine immunizations, and confidence in medical professionals, corporations, and the health care system,” the investigators said.

This study was supported by the National Institute of Allergy and Infectious Diseases’ Emory Vaccinology Training Program. Dr. Phadke reported having no relevant financial disclosures; one of his associates reported ties to Crucell, Pfizer, Merck, and Parents of Kids with Infectious Diseases.

In approximately 42% of recent cases of measles in the United States, the patients were intentionally unvaccinated for nonmedical reasons such as religious or philosophical objections to vaccines, according to a report published online March 15 in JAMA.

Vaccine refusal raised the risk of acquiring measles not only among unvaccinated individuals but also among fully vaccinated people living where the outbreaks occurred, said Dr. Varun K. Phadke of the division of infectious diseases, Emory University, Atlanta, and his associates.

To characterize the contribution of vaccine refusal to recent outbreaks of two vaccine-preventable diseases, the investigators reviewed 18 published studies involving 1,416 measles cases and 32 involving 10,609 pertussis cases. They found that 56.8% of the patients who acquired measles and 24%-45% of those who acquired pertussis were unvaccinated or undervaccinated (hadn’t received all the recommended doses of the vaccines).

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

In 970 measles cases for which there were detailed data, 405 patients (42%) were intentionally unvaccinated without any medical indications for avoiding the vaccine; these patients avoided immunization against measles because of personal, philosophical, or religious beliefs or cultural norms. Unvaccinated people were up to 35 times more likely than were vaccinated people to acquire the infection. Nonetheless, a higher frequency of vaccine refusal in the geographic area of an outbreak also correlated with a higher measles incidence among the vaccinated people living there.

In eight of the largest pertussis outbreaks for which there were detailed data, 59%-93% of patients were intentionally unvaccinated for nonmedical reasons. Unvaccinated people were up to 20 times more likely than were vaccinated people to acquire the infection. And among people who hadn’t received all recommended the doses of pertussis vaccine, the risk of the infection was proportional to the number of doses they missed. As with measles, a higher frequency of refusal of the pertussis vaccine in the vicinity of a pertussis outbreak correlated with a higher incidence even among the vaccinated people living there. Waning immunity explained only some, not all, of the increased risk among vaccinated individuals, Dr. Phadke and his associates noted (JAMA 2016 March 15;315[11]:1149-58). These findings “have broad implications” for vaccine practice and policy. For example, to restrict peoples’ individual freedom by mandating vaccination, it must first be demonstrated that exemptions harm others living in the community.

To improve vaccine coverage, communities should strengthen state- or school-level enforcement of existing vaccine mandates, as well as increase the difficulty of obtaining a vaccine exemption. They also should “address the reasons for vaccine hesitancy, which may include parental perceptions regarding the risk and severity of vaccine-preventable diseases, the safety and effectiveness of routine immunizations, and confidence in medical professionals, corporations, and the health care system,” the investigators said.

This study was supported by the National Institute of Allergy and Infectious Diseases’ Emory Vaccinology Training Program. Dr. Phadke reported having no relevant financial disclosures; one of his associates reported ties to Crucell, Pfizer, Merck, and Parents of Kids with Infectious Diseases.

In approximately 42% of recent cases of measles in the United States, the patients were intentionally unvaccinated for nonmedical reasons such as religious or philosophical objections to vaccines, according to a report published online March 15 in JAMA.

Vaccine refusal raised the risk of acquiring measles not only among unvaccinated individuals but also among fully vaccinated people living where the outbreaks occurred, said Dr. Varun K. Phadke of the division of infectious diseases, Emory University, Atlanta, and his associates.

To characterize the contribution of vaccine refusal to recent outbreaks of two vaccine-preventable diseases, the investigators reviewed 18 published studies involving 1,416 measles cases and 32 involving 10,609 pertussis cases. They found that 56.8% of the patients who acquired measles and 24%-45% of those who acquired pertussis were unvaccinated or undervaccinated (hadn’t received all the recommended doses of the vaccines).

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

In 970 measles cases for which there were detailed data, 405 patients (42%) were intentionally unvaccinated without any medical indications for avoiding the vaccine; these patients avoided immunization against measles because of personal, philosophical, or religious beliefs or cultural norms. Unvaccinated people were up to 35 times more likely than were vaccinated people to acquire the infection. Nonetheless, a higher frequency of vaccine refusal in the geographic area of an outbreak also correlated with a higher measles incidence among the vaccinated people living there.

In eight of the largest pertussis outbreaks for which there were detailed data, 59%-93% of patients were intentionally unvaccinated for nonmedical reasons. Unvaccinated people were up to 20 times more likely than were vaccinated people to acquire the infection. And among people who hadn’t received all recommended the doses of pertussis vaccine, the risk of the infection was proportional to the number of doses they missed. As with measles, a higher frequency of refusal of the pertussis vaccine in the vicinity of a pertussis outbreak correlated with a higher incidence even among the vaccinated people living there. Waning immunity explained only some, not all, of the increased risk among vaccinated individuals, Dr. Phadke and his associates noted (JAMA 2016 March 15;315[11]:1149-58). These findings “have broad implications” for vaccine practice and policy. For example, to restrict peoples’ individual freedom by mandating vaccination, it must first be demonstrated that exemptions harm others living in the community.

To improve vaccine coverage, communities should strengthen state- or school-level enforcement of existing vaccine mandates, as well as increase the difficulty of obtaining a vaccine exemption. They also should “address the reasons for vaccine hesitancy, which may include parental perceptions regarding the risk and severity of vaccine-preventable diseases, the safety and effectiveness of routine immunizations, and confidence in medical professionals, corporations, and the health care system,” the investigators said.

This study was supported by the National Institute of Allergy and Infectious Diseases’ Emory Vaccinology Training Program. Dr. Phadke reported having no relevant financial disclosures; one of his associates reported ties to Crucell, Pfizer, Merck, and Parents of Kids with Infectious Diseases.

In approximately 42% of recent cases of measles in the United States, the patients were intentionally unvaccinated for nonmedical reasons such as religious or philosophical objections to vaccines, according to a report published online March 15 in JAMA.

Vaccine refusal raised the risk of acquiring measles not only among unvaccinated individuals but also among fully vaccinated people living where the outbreaks occurred, said Dr. Varun K. Phadke of the division of infectious diseases, Emory University, Atlanta, and his associates.

To characterize the contribution of vaccine refusal to recent outbreaks of two vaccine-preventable diseases, the investigators reviewed 18 published studies involving 1,416 measles cases and 32 involving 10,609 pertussis cases. They found that 56.8% of the patients who acquired measles and 24%-45% of those who acquired pertussis were unvaccinated or undervaccinated (hadn’t received all the recommended doses of the vaccines).

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

In 970 measles cases for which there were detailed data, 405 patients (42%) were intentionally unvaccinated without any medical indications for avoiding the vaccine; these patients avoided immunization against measles because of personal, philosophical, or religious beliefs or cultural norms. Unvaccinated people were up to 35 times more likely than were vaccinated people to acquire the infection. Nonetheless, a higher frequency of vaccine refusal in the geographic area of an outbreak also correlated with a higher measles incidence among the vaccinated people living there.

In eight of the largest pertussis outbreaks for which there were detailed data, 59%-93% of patients were intentionally unvaccinated for nonmedical reasons. Unvaccinated people were up to 20 times more likely than were vaccinated people to acquire the infection. And among people who hadn’t received all recommended the doses of pertussis vaccine, the risk of the infection was proportional to the number of doses they missed. As with measles, a higher frequency of refusal of the pertussis vaccine in the vicinity of a pertussis outbreak correlated with a higher incidence even among the vaccinated people living there. Waning immunity explained only some, not all, of the increased risk among vaccinated individuals, Dr. Phadke and his associates noted (JAMA 2016 March 15;315[11]:1149-58). These findings “have broad implications” for vaccine practice and policy. For example, to restrict peoples’ individual freedom by mandating vaccination, it must first be demonstrated that exemptions harm others living in the community.

To improve vaccine coverage, communities should strengthen state- or school-level enforcement of existing vaccine mandates, as well as increase the difficulty of obtaining a vaccine exemption. They also should “address the reasons for vaccine hesitancy, which may include parental perceptions regarding the risk and severity of vaccine-preventable diseases, the safety and effectiveness of routine immunizations, and confidence in medical professionals, corporations, and the health care system,” the investigators said.

This study was supported by the National Institute of Allergy and Infectious Diseases’ Emory Vaccinology Training Program. Dr. Phadke reported having no relevant financial disclosures; one of his associates reported ties to Crucell, Pfizer, Merck, and Parents of Kids with Infectious Diseases.

In approximately 42% of recent cases of measles in the United States, the patients were intentionally unvaccinated for nonmedical reasons such as religious or philosophical objections to vaccines, according to a report published online March 15 in JAMA.

Vaccine refusal raised the risk of acquiring measles not only among unvaccinated individuals but also among fully vaccinated people living where the outbreaks occurred, said Dr. Varun K. Phadke of the division of infectious diseases, Emory University, Atlanta, and his associates.

To characterize the contribution of vaccine refusal to recent outbreaks of two vaccine-preventable diseases, the investigators reviewed 18 published studies involving 1,416 measles cases and 32 involving 10,609 pertussis cases. They found that 56.8% of the patients who acquired measles and 24%-45% of those who acquired pertussis were unvaccinated or undervaccinated (hadn’t received all the recommended doses of the vaccines).

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

In 970 measles cases for which there were detailed data, 405 patients (42%) were intentionally unvaccinated without any medical indications for avoiding the vaccine; these patients avoided immunization against measles because of personal, philosophical, or religious beliefs or cultural norms. Unvaccinated people were up to 35 times more likely than were vaccinated people to acquire the infection. Nonetheless, a higher frequency of vaccine refusal in the geographic area of an outbreak also correlated with a higher measles incidence among the vaccinated people living there.

In eight of the largest pertussis outbreaks for which there were detailed data, 59%-93% of patients were intentionally unvaccinated for nonmedical reasons. Unvaccinated people were up to 20 times more likely than were vaccinated people to acquire the infection. And among people who hadn’t received all recommended the doses of pertussis vaccine, the risk of the infection was proportional to the number of doses they missed. As with measles, a higher frequency of refusal of the pertussis vaccine in the vicinity of a pertussis outbreak correlated with a higher incidence even among the vaccinated people living there. Waning immunity explained only some, not all, of the increased risk among vaccinated individuals, Dr. Phadke and his associates noted (JAMA 2016 March 15;315[11]:1149-58). These findings “have broad implications” for vaccine practice and policy. For example, to restrict peoples’ individual freedom by mandating vaccination, it must first be demonstrated that exemptions harm others living in the community.

To improve vaccine coverage, communities should strengthen state- or school-level enforcement of existing vaccine mandates, as well as increase the difficulty of obtaining a vaccine exemption. They also should “address the reasons for vaccine hesitancy, which may include parental perceptions regarding the risk and severity of vaccine-preventable diseases, the safety and effectiveness of routine immunizations, and confidence in medical professionals, corporations, and the health care system,” the investigators said.

This study was supported by the National Institute of Allergy and Infectious Diseases’ Emory Vaccinology Training Program. Dr. Phadke reported having no relevant financial disclosures; one of his associates reported ties to Crucell, Pfizer, Merck, and Parents of Kids with Infectious Diseases.

An action taken to protect patient privacy – removing claims related to substance abuse from Medicare and Medicaid databases – inadvertently caused an immediate and marked suppression of vital data pertaining to related disorders such as HIV, depression, anxiety, and hepatitis C, according to data published online March 15 in JAMA.

In 2007, the Centers for Medicare & Medicaid Services implemented a federal regulation that prohibits third-party payers from releasing information from federally funded substance abuse treatment programs. To comply, the CMS had to change its longstanding practice of making all claims data available to researchers, instead removing from its database all claims containing a diagnostic or procedure code related to substance abuse, said Kathryn Rough of the division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.

To gauge the effect this had on the information available to researchers, the investigators compared de-identified Medicaid data from before the policy change (2000-2006) against that from afterward (2007-2010). They focused on diagnoses for six disorders that frequently occur in tandem with substance abuse (HIV, tobacco use, depression, anxiety, hepatitis C, and cirrhosis) and four that are unrelated to substance abuse (type 2 diabetes, stroke, hypertension, and kidney disease).

The study period included 63 million inpatient and 13.6 billion outpatient claims. Compared with data available to researchers before the policy change, afterward there was an immediate and substantial reduction. Inpatient diagnosis rates declined 24% for HIV, 51% for tobacco use, 38% for depression, 27% for anxiety, 57% for hepatitis C, and 49% for cirrhosis. Declines in outpatient diagnosis rates were less marked and reached statistical significance only for anxiety, which dropped 6.3%.

In contrast, diagnosis rates for disorders unrelated to substance abuse did not change appreciably after the new policy was implemented, Ms. Rough and her associates said (JAMA. 2016;315:1164-6). “Underestimation of diagnoses has the potential to bias health services research studies and epidemiological analyses” and could lead to “spurious conclusions.” For example, “a hospital that regularly admits substance abusers will [show] artificially low rates of readmission, giving a false appearance of better performance,” they noted.

An action taken to protect patient privacy – removing claims related to substance abuse from Medicare and Medicaid databases – inadvertently caused an immediate and marked suppression of vital data pertaining to related disorders such as HIV, depression, anxiety, and hepatitis C, according to data published online March 15 in JAMA.

In 2007, the Centers for Medicare & Medicaid Services implemented a federal regulation that prohibits third-party payers from releasing information from federally funded substance abuse treatment programs. To comply, the CMS had to change its longstanding practice of making all claims data available to researchers, instead removing from its database all claims containing a diagnostic or procedure code related to substance abuse, said Kathryn Rough of the division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.

To gauge the effect this had on the information available to researchers, the investigators compared de-identified Medicaid data from before the policy change (2000-2006) against that from afterward (2007-2010). They focused on diagnoses for six disorders that frequently occur in tandem with substance abuse (HIV, tobacco use, depression, anxiety, hepatitis C, and cirrhosis) and four that are unrelated to substance abuse (type 2 diabetes, stroke, hypertension, and kidney disease).

The study period included 63 million inpatient and 13.6 billion outpatient claims. Compared with data available to researchers before the policy change, afterward there was an immediate and substantial reduction. Inpatient diagnosis rates declined 24% for HIV, 51% for tobacco use, 38% for depression, 27% for anxiety, 57% for hepatitis C, and 49% for cirrhosis. Declines in outpatient diagnosis rates were less marked and reached statistical significance only for anxiety, which dropped 6.3%.

In contrast, diagnosis rates for disorders unrelated to substance abuse did not change appreciably after the new policy was implemented, Ms. Rough and her associates said (JAMA. 2016;315:1164-6). “Underestimation of diagnoses has the potential to bias health services research studies and epidemiological analyses” and could lead to “spurious conclusions.” For example, “a hospital that regularly admits substance abusers will [show] artificially low rates of readmission, giving a false appearance of better performance,” they noted.

An action taken to protect patient privacy – removing claims related to substance abuse from Medicare and Medicaid databases – inadvertently caused an immediate and marked suppression of vital data pertaining to related disorders such as HIV, depression, anxiety, and hepatitis C, according to data published online March 15 in JAMA.

In 2007, the Centers for Medicare & Medicaid Services implemented a federal regulation that prohibits third-party payers from releasing information from federally funded substance abuse treatment programs. To comply, the CMS had to change its longstanding practice of making all claims data available to researchers, instead removing from its database all claims containing a diagnostic or procedure code related to substance abuse, said Kathryn Rough of the division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.

To gauge the effect this had on the information available to researchers, the investigators compared de-identified Medicaid data from before the policy change (2000-2006) against that from afterward (2007-2010). They focused on diagnoses for six disorders that frequently occur in tandem with substance abuse (HIV, tobacco use, depression, anxiety, hepatitis C, and cirrhosis) and four that are unrelated to substance abuse (type 2 diabetes, stroke, hypertension, and kidney disease).

The study period included 63 million inpatient and 13.6 billion outpatient claims. Compared with data available to researchers before the policy change, afterward there was an immediate and substantial reduction. Inpatient diagnosis rates declined 24% for HIV, 51% for tobacco use, 38% for depression, 27% for anxiety, 57% for hepatitis C, and 49% for cirrhosis. Declines in outpatient diagnosis rates were less marked and reached statistical significance only for anxiety, which dropped 6.3%.

In contrast, diagnosis rates for disorders unrelated to substance abuse did not change appreciably after the new policy was implemented, Ms. Rough and her associates said (JAMA. 2016;315:1164-6). “Underestimation of diagnoses has the potential to bias health services research studies and epidemiological analyses” and could lead to “spurious conclusions.” For example, “a hospital that regularly admits substance abusers will [show] artificially low rates of readmission, giving a false appearance of better performance,” they noted.

Both a low body mass index and a high percentage of body fat are independently associated with an increased risk of all-cause mortality in middle-aged and older adults, according to an observational study reported online in the Annals of Internal Medicine.

The finding that these somewhat contradictory measures are both associated with higher mortality helps account for the so-called obesity paradox – the fact that mortality is lower in overweight, mildly obese, and moderately obese persons than in those who are underweight or of low-normal weight, said Dr. Raj Padwal of the University of Alberta, Edmonton, and his associates.

©wragg/iStockphoto.com

The investigators assessed the relationships among body mass index, body fat, and mortality by analyzing data from a population-based cohort study of 54,420 men and women aged 40 and older. These study participants underwent assessment of body composition as part of a study of bone mineral density, then were followed for a median of 4-7 years. BMI and body fat percentage were categorized into quintiles; men and women were analyzed separately.

Among women (mean age, 63.5 years), 2% were underweight, 38% were of normal weight, 34% were overweight, 17% had class I obesity, and 8% had class II or III obesity. The mean percentage of body fat was 32%. There were 4,965 deaths during follow-up. Among men (mean age, 65.5 years), 1% were underweight, 29% were of normal weight, 45% were overweight, 18% had class I obesity, and 6% had class II or III obesity. The mean percentage of body fat was 30%. There were 984 deaths during follow-up.

Higher BMI correlated with decreased mortality in both sexes. Among women, death rates declined from 18.6/1,000 person-years in the lowest BMI quintile to 13.9/1,000 person-years in the highest BMI quintile. Among men, death rates declined from 51.5/1,000 person-years in the lowest BMI quintile to 32.7/1,000 person-years in the highest BMI quintile.

In contrast, higher body fat percentage correlated with increased mortality. Among women, a high percentage of body fat was associated with significantly higher mortality (hazard ratio, 1.19), as it was among men (HR, 1.59). “Our results suggest that BMI may be an inappropriate surrogate for adiposity, and this limitation may explain the presence of the obesity paradox in many studies,” Dr. Padwal and his associates reported (Ann Intern Med. 2016 March 8. doi: 10.7326/M15-1181).

This study was limited in that the study population was predominantly female and white, and it may have included more “health-seeking” and lower-weight individuals than there are in the general population, the investigators added.

Both a low body mass index and a high percentage of body fat are independently associated with an increased risk of all-cause mortality in middle-aged and older adults, according to an observational study reported online in the Annals of Internal Medicine.

The finding that these somewhat contradictory measures are both associated with higher mortality helps account for the so-called obesity paradox – the fact that mortality is lower in overweight, mildly obese, and moderately obese persons than in those who are underweight or of low-normal weight, said Dr. Raj Padwal of the University of Alberta, Edmonton, and his associates.

©wragg/iStockphoto.com

The investigators assessed the relationships among body mass index, body fat, and mortality by analyzing data from a population-based cohort study of 54,420 men and women aged 40 and older. These study participants underwent assessment of body composition as part of a study of bone mineral density, then were followed for a median of 4-7 years. BMI and body fat percentage were categorized into quintiles; men and women were analyzed separately.

Among women (mean age, 63.5 years), 2% were underweight, 38% were of normal weight, 34% were overweight, 17% had class I obesity, and 8% had class II or III obesity. The mean percentage of body fat was 32%. There were 4,965 deaths during follow-up. Among men (mean age, 65.5 years), 1% were underweight, 29% were of normal weight, 45% were overweight, 18% had class I obesity, and 6% had class II or III obesity. The mean percentage of body fat was 30%. There were 984 deaths during follow-up.

Higher BMI correlated with decreased mortality in both sexes. Among women, death rates declined from 18.6/1,000 person-years in the lowest BMI quintile to 13.9/1,000 person-years in the highest BMI quintile. Among men, death rates declined from 51.5/1,000 person-years in the lowest BMI quintile to 32.7/1,000 person-years in the highest BMI quintile.

In contrast, higher body fat percentage correlated with increased mortality. Among women, a high percentage of body fat was associated with significantly higher mortality (hazard ratio, 1.19), as it was among men (HR, 1.59). “Our results suggest that BMI may be an inappropriate surrogate for adiposity, and this limitation may explain the presence of the obesity paradox in many studies,” Dr. Padwal and his associates reported (Ann Intern Med. 2016 March 8. doi: 10.7326/M15-1181).

This study was limited in that the study population was predominantly female and white, and it may have included more “health-seeking” and lower-weight individuals than there are in the general population, the investigators added.

Both a low body mass index and a high percentage of body fat are independently associated with an increased risk of all-cause mortality in middle-aged and older adults, according to an observational study reported online in the Annals of Internal Medicine.

The finding that these somewhat contradictory measures are both associated with higher mortality helps account for the so-called obesity paradox – the fact that mortality is lower in overweight, mildly obese, and moderately obese persons than in those who are underweight or of low-normal weight, said Dr. Raj Padwal of the University of Alberta, Edmonton, and his associates.

©wragg/iStockphoto.com

The investigators assessed the relationships among body mass index, body fat, and mortality by analyzing data from a population-based cohort study of 54,420 men and women aged 40 and older. These study participants underwent assessment of body composition as part of a study of bone mineral density, then were followed for a median of 4-7 years. BMI and body fat percentage were categorized into quintiles; men and women were analyzed separately.

Among women (mean age, 63.5 years), 2% were underweight, 38% were of normal weight, 34% were overweight, 17% had class I obesity, and 8% had class II or III obesity. The mean percentage of body fat was 32%. There were 4,965 deaths during follow-up. Among men (mean age, 65.5 years), 1% were underweight, 29% were of normal weight, 45% were overweight, 18% had class I obesity, and 6% had class II or III obesity. The mean percentage of body fat was 30%. There were 984 deaths during follow-up.

Higher BMI correlated with decreased mortality in both sexes. Among women, death rates declined from 18.6/1,000 person-years in the lowest BMI quintile to 13.9/1,000 person-years in the highest BMI quintile. Among men, death rates declined from 51.5/1,000 person-years in the lowest BMI quintile to 32.7/1,000 person-years in the highest BMI quintile.

In contrast, higher body fat percentage correlated with increased mortality. Among women, a high percentage of body fat was associated with significantly higher mortality (hazard ratio, 1.19), as it was among men (HR, 1.59). “Our results suggest that BMI may be an inappropriate surrogate for adiposity, and this limitation may explain the presence of the obesity paradox in many studies,” Dr. Padwal and his associates reported (Ann Intern Med. 2016 March 8. doi: 10.7326/M15-1181).

This study was limited in that the study population was predominantly female and white, and it may have included more “health-seeking” and lower-weight individuals than there are in the general population, the investigators added.

Experts in the Society for Thoracic Surgeons and the American College of Cardiology used data from more than 13,000 consecutive transcatheter aortic valve replacement procedures to develop a new tool for predicting the risk of in-hospital mortality in patients undergoing TAVR, according to a report published online March 9 in JAMA Cardiology.

Their risk-prediction model was only “modestly” accurate but performed better than any existing methods for assessing risk in this patient population. It should be considered the first iteration of this tool and will be modified as the procedure itself evolves and as more data concerning TAVR are collected and analyzed. Ongoing analysis “may well define clinical subsets of patients who accrue particular benefit from the procedure or, conversely, reveal subsets not well served by TAVR,” said Dr. Fred H. Edwards and his associates on the steering committee of the STS/ACC Transcatheter Valve Therapy Registry.

They noted that more models soon will be developed to predict 30-day and 1-year mortality after TAVR. Models to predict the risk of neurologic deficit following TAVR are currently being developed, and models for other nonfatal outcomes will be developed soon.

This tool predicting in-hospital mortality is expected to become “a valuable adjunct for patient counseling, performance assessment, local quality improvement, and national monitoring of the appropriateness of patient selection for TAVR,” said Dr. Edwards, who is also in the department of surgery, University of Florida, Jacksonville, and his associates.

They began by analyzing the registry data for virtually every commercial TAVR performed at 265 participating sites in the United States during a 27-month period. In general, patients were selected for TAVR because they were considered unsuitable candidates for surgical aortic valve replacement. The mean patient age was 82.1 years. A total of 730 patients died before leaving the hospital, for an in-hospital mortality of 5.3%.

Working from an initial list of 39 possible patient variables to include in their statistical prediction model, the researchers narrowed it down to the 7 most predictive factors available in the registry data: older age, poorer glomerular filtration rate, the need for hemodialysis, NYHA class IV status, the presence of severe chronic lung disease, a category 2 or 4 critical hemodynamic state (i.e., preprocedural acuity status), and need for a nonfemoral approach during the procedure.

The model was then tested in a separate validation cohort of 6,868 patients (52% men) treated at 314 sites during a 7-month period. It performed better at predicting in-hospital mortality than did either the EuroSCORE (European System for Cardiac Operative Risk Evaluation) or the FRANCE 2 (French Aortic National Corevalve and Edwards 2) models.

This STS/ACC model should assist clinicians in patient selection for TAVR, not by dictating which patients are candidates for TAVR, but by being used as “one element in the selection process, to be considered in concert with history, physical examination, laboratory information, and clinical judgment. The model may also provide useful information for patient counseling,” the investigators said (JAMA Cardiol. 2016 Mar 9. doi: 10.1001/jamacardiol.2015.0326). One factor that is generally recognized as an important risk predictor but isn’t yet incorporated into this tool is a measure of patient frailty. Data on frailty are not yet collected consistently in the STS/ACC registry. As more complete data become available, frailty likely will be included as a predictive factor in this tool.

Another important issue that eventually should be considered alongside survival prediction is the effect TAVR has on quality of life. The STS/ACC registry “is one of the few clinical registries to collect quality-of-life data,” and it could prove to be a critical adjunct to patient selection. A given patient might have a favorable outlook regarding mortality after the procedure, but would still be a poor candidate if he or she wouldn’t derive significant benefit from it, Dr. Edwards and his associates said.

Experts in the Society for Thoracic Surgeons and the American College of Cardiology used data from more than 13,000 consecutive transcatheter aortic valve replacement procedures to develop a new tool for predicting the risk of in-hospital mortality in patients undergoing TAVR, according to a report published online March 9 in JAMA Cardiology.

Their risk-prediction model was only “modestly” accurate but performed better than any existing methods for assessing risk in this patient population. It should be considered the first iteration of this tool and will be modified as the procedure itself evolves and as more data concerning TAVR are collected and analyzed. Ongoing analysis “may well define clinical subsets of patients who accrue particular benefit from the procedure or, conversely, reveal subsets not well served by TAVR,” said Dr. Fred H. Edwards and his associates on the steering committee of the STS/ACC Transcatheter Valve Therapy Registry.

They noted that more models soon will be developed to predict 30-day and 1-year mortality after TAVR. Models to predict the risk of neurologic deficit following TAVR are currently being developed, and models for other nonfatal outcomes will be developed soon.

This tool predicting in-hospital mortality is expected to become “a valuable adjunct for patient counseling, performance assessment, local quality improvement, and national monitoring of the appropriateness of patient selection for TAVR,” said Dr. Edwards, who is also in the department of surgery, University of Florida, Jacksonville, and his associates.

They began by analyzing the registry data for virtually every commercial TAVR performed at 265 participating sites in the United States during a 27-month period. In general, patients were selected for TAVR because they were considered unsuitable candidates for surgical aortic valve replacement. The mean patient age was 82.1 years. A total of 730 patients died before leaving the hospital, for an in-hospital mortality of 5.3%.

Working from an initial list of 39 possible patient variables to include in their statistical prediction model, the researchers narrowed it down to the 7 most predictive factors available in the registry data: older age, poorer glomerular filtration rate, the need for hemodialysis, NYHA class IV status, the presence of severe chronic lung disease, a category 2 or 4 critical hemodynamic state (i.e., preprocedural acuity status), and need for a nonfemoral approach during the procedure.

The model was then tested in a separate validation cohort of 6,868 patients (52% men) treated at 314 sites during a 7-month period. It performed better at predicting in-hospital mortality than did either the EuroSCORE (European System for Cardiac Operative Risk Evaluation) or the FRANCE 2 (French Aortic National Corevalve and Edwards 2) models.

This STS/ACC model should assist clinicians in patient selection for TAVR, not by dictating which patients are candidates for TAVR, but by being used as “one element in the selection process, to be considered in concert with history, physical examination, laboratory information, and clinical judgment. The model may also provide useful information for patient counseling,” the investigators said (JAMA Cardiol. 2016 Mar 9. doi: 10.1001/jamacardiol.2015.0326). One factor that is generally recognized as an important risk predictor but isn’t yet incorporated into this tool is a measure of patient frailty. Data on frailty are not yet collected consistently in the STS/ACC registry. As more complete data become available, frailty likely will be included as a predictive factor in this tool.

Another important issue that eventually should be considered alongside survival prediction is the effect TAVR has on quality of life. The STS/ACC registry “is one of the few clinical registries to collect quality-of-life data,” and it could prove to be a critical adjunct to patient selection. A given patient might have a favorable outlook regarding mortality after the procedure, but would still be a poor candidate if he or she wouldn’t derive significant benefit from it, Dr. Edwards and his associates said.

Experts in the Society for Thoracic Surgeons and the American College of Cardiology used data from more than 13,000 consecutive transcatheter aortic valve replacement procedures to develop a new tool for predicting the risk of in-hospital mortality in patients undergoing TAVR, according to a report published online March 9 in JAMA Cardiology.

Their risk-prediction model was only “modestly” accurate but performed better than any existing methods for assessing risk in this patient population. It should be considered the first iteration of this tool and will be modified as the procedure itself evolves and as more data concerning TAVR are collected and analyzed. Ongoing analysis “may well define clinical subsets of patients who accrue particular benefit from the procedure or, conversely, reveal subsets not well served by TAVR,” said Dr. Fred H. Edwards and his associates on the steering committee of the STS/ACC Transcatheter Valve Therapy Registry.

They noted that more models soon will be developed to predict 30-day and 1-year mortality after TAVR. Models to predict the risk of neurologic deficit following TAVR are currently being developed, and models for other nonfatal outcomes will be developed soon.

This tool predicting in-hospital mortality is expected to become “a valuable adjunct for patient counseling, performance assessment, local quality improvement, and national monitoring of the appropriateness of patient selection for TAVR,” said Dr. Edwards, who is also in the department of surgery, University of Florida, Jacksonville, and his associates.

They began by analyzing the registry data for virtually every commercial TAVR performed at 265 participating sites in the United States during a 27-month period. In general, patients were selected for TAVR because they were considered unsuitable candidates for surgical aortic valve replacement. The mean patient age was 82.1 years. A total of 730 patients died before leaving the hospital, for an in-hospital mortality of 5.3%.

Working from an initial list of 39 possible patient variables to include in their statistical prediction model, the researchers narrowed it down to the 7 most predictive factors available in the registry data: older age, poorer glomerular filtration rate, the need for hemodialysis, NYHA class IV status, the presence of severe chronic lung disease, a category 2 or 4 critical hemodynamic state (i.e., preprocedural acuity status), and need for a nonfemoral approach during the procedure.

The model was then tested in a separate validation cohort of 6,868 patients (52% men) treated at 314 sites during a 7-month period. It performed better at predicting in-hospital mortality than did either the EuroSCORE (European System for Cardiac Operative Risk Evaluation) or the FRANCE 2 (French Aortic National Corevalve and Edwards 2) models.

This STS/ACC model should assist clinicians in patient selection for TAVR, not by dictating which patients are candidates for TAVR, but by being used as “one element in the selection process, to be considered in concert with history, physical examination, laboratory information, and clinical judgment. The model may also provide useful information for patient counseling,” the investigators said (JAMA Cardiol. 2016 Mar 9. doi: 10.1001/jamacardiol.2015.0326). One factor that is generally recognized as an important risk predictor but isn’t yet incorporated into this tool is a measure of patient frailty. Data on frailty are not yet collected consistently in the STS/ACC registry. As more complete data become available, frailty likely will be included as a predictive factor in this tool.

Another important issue that eventually should be considered alongside survival prediction is the effect TAVR has on quality of life. The STS/ACC registry “is one of the few clinical registries to collect quality-of-life data,” and it could prove to be a critical adjunct to patient selection. A given patient might have a favorable outlook regarding mortality after the procedure, but would still be a poor candidate if he or she wouldn’t derive significant benefit from it, Dr. Edwards and his associates said.

A new tool – a clinical risk score – may help identify which children and adolescents who recently sustained a head injury are at risk for persistent postconcussion symptoms, according to a report published online March 7 in JAMA.

Approximately one-third of pediatric patients with concussion will have ongoing somatic, cognitive, psychological, and/or behavioral symptoms at 28 days, and at present, there are no tools to help predict which patients will be affected. The 5P (Preventing Postconcussive Problems in Pediatrics) study was performed to develop and validate a clinical risk score for this purpose, said Dr. Roger Zemek of Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and his associates (JAMA 2016 Mar 8;315[10]:1014-25).

This prospective cohort study involved patients aged 5-17 years (median age, 12 years) who presented to one of nine Canadian pediatric emergency departments within 48 hours of sustaining a concussion.

In the derivation cohort, 510 of 1,701 participants (30%) met the criteria for persistent postconcussion symptoms (PPCS). A total of 47 possible predictive variables were assessed for their usefulness in predicting PPCS in this cohort. They were collected from demographic data, patient history, injury characteristics, physical examination, results on the Acute Concussion Evaluation Inventory and the Postconcussion Symptom Inventory, and patient/parent responses to weekly follow-up surveys during the month following the injury.

The investigators devised a clinical risk score using the nine predictors they found to be most accurate: patient age, patient gender, the presence or absence of prior concussion, migraine history, the presence or absence of current headache, sensitivity to noise, fatigue, slow responses to questions, and an abnormal tandem stance. They then selected three cutoff points to delineate PPCS risk: 0-3 points indicated low risk, 4-8 points indicated intermediate risk, and 9 or more points indicated high risk.

Treating physicians also were asked to predict the likelihood of PPCS.

In the validation cohort, 291 of 883 participants (33%) met the criteria for PPCS.

For low-risk patients, the sensitivity of the clinical risk score was 94%, the specificity was 18%, the negative predictive value was 85%, and the positive predictive value was 36%. For high-risk patients, the sensitivity of the clinical risk score was 20%, the specificity was 94%, the negative predictive value was 70%, and the positive predictive value was 60%.

In both sets of patients, the clinical risk score was significantly better than physician judgment in predicting PPCS. However, in its present form, it is only modestly accurate at distinguishing who will and who will not have the disorder. This tool could be further refined, perhaps by adding information regarding biomarkers, genetic susceptibility, or advanced neuroimaging, Dr. Zemek and his associates wrote.

“Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility,” they concluded.

This work was supported by the Canadian Institutes of Health Research, the Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team, and the Alberta Children’s Hospital Foundation. Dr. Zemek and his associates reported having no relevant financial disclosures.

A new tool – a clinical risk score – may help identify which children and adolescents who recently sustained a head injury are at risk for persistent postconcussion symptoms, according to a report published online March 7 in JAMA.

Approximately one-third of pediatric patients with concussion will have ongoing somatic, cognitive, psychological, and/or behavioral symptoms at 28 days, and at present, there are no tools to help predict which patients will be affected. The 5P (Preventing Postconcussive Problems in Pediatrics) study was performed to develop and validate a clinical risk score for this purpose, said Dr. Roger Zemek of Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and his associates (JAMA 2016 Mar 8;315[10]:1014-25).

This prospective cohort study involved patients aged 5-17 years (median age, 12 years) who presented to one of nine Canadian pediatric emergency departments within 48 hours of sustaining a concussion.

In the derivation cohort, 510 of 1,701 participants (30%) met the criteria for persistent postconcussion symptoms (PPCS). A total of 47 possible predictive variables were assessed for their usefulness in predicting PPCS in this cohort. They were collected from demographic data, patient history, injury characteristics, physical examination, results on the Acute Concussion Evaluation Inventory and the Postconcussion Symptom Inventory, and patient/parent responses to weekly follow-up surveys during the month following the injury.

The investigators devised a clinical risk score using the nine predictors they found to be most accurate: patient age, patient gender, the presence or absence of prior concussion, migraine history, the presence or absence of current headache, sensitivity to noise, fatigue, slow responses to questions, and an abnormal tandem stance. They then selected three cutoff points to delineate PPCS risk: 0-3 points indicated low risk, 4-8 points indicated intermediate risk, and 9 or more points indicated high risk.

Treating physicians also were asked to predict the likelihood of PPCS.

In the validation cohort, 291 of 883 participants (33%) met the criteria for PPCS.

For low-risk patients, the sensitivity of the clinical risk score was 94%, the specificity was 18%, the negative predictive value was 85%, and the positive predictive value was 36%. For high-risk patients, the sensitivity of the clinical risk score was 20%, the specificity was 94%, the negative predictive value was 70%, and the positive predictive value was 60%.

In both sets of patients, the clinical risk score was significantly better than physician judgment in predicting PPCS. However, in its present form, it is only modestly accurate at distinguishing who will and who will not have the disorder. This tool could be further refined, perhaps by adding information regarding biomarkers, genetic susceptibility, or advanced neuroimaging, Dr. Zemek and his associates wrote.

“Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility,” they concluded.

This work was supported by the Canadian Institutes of Health Research, the Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team, and the Alberta Children’s Hospital Foundation. Dr. Zemek and his associates reported having no relevant financial disclosures.

A new tool – a clinical risk score – may help identify which children and adolescents who recently sustained a head injury are at risk for persistent postconcussion symptoms, according to a report published online March 7 in JAMA.

Approximately one-third of pediatric patients with concussion will have ongoing somatic, cognitive, psychological, and/or behavioral symptoms at 28 days, and at present, there are no tools to help predict which patients will be affected. The 5P (Preventing Postconcussive Problems in Pediatrics) study was performed to develop and validate a clinical risk score for this purpose, said Dr. Roger Zemek of Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and his associates (JAMA 2016 Mar 8;315[10]:1014-25).

This prospective cohort study involved patients aged 5-17 years (median age, 12 years) who presented to one of nine Canadian pediatric emergency departments within 48 hours of sustaining a concussion.

In the derivation cohort, 510 of 1,701 participants (30%) met the criteria for persistent postconcussion symptoms (PPCS). A total of 47 possible predictive variables were assessed for their usefulness in predicting PPCS in this cohort. They were collected from demographic data, patient history, injury characteristics, physical examination, results on the Acute Concussion Evaluation Inventory and the Postconcussion Symptom Inventory, and patient/parent responses to weekly follow-up surveys during the month following the injury.

The investigators devised a clinical risk score using the nine predictors they found to be most accurate: patient age, patient gender, the presence or absence of prior concussion, migraine history, the presence or absence of current headache, sensitivity to noise, fatigue, slow responses to questions, and an abnormal tandem stance. They then selected three cutoff points to delineate PPCS risk: 0-3 points indicated low risk, 4-8 points indicated intermediate risk, and 9 or more points indicated high risk.

Treating physicians also were asked to predict the likelihood of PPCS.

In the validation cohort, 291 of 883 participants (33%) met the criteria for PPCS.

For low-risk patients, the sensitivity of the clinical risk score was 94%, the specificity was 18%, the negative predictive value was 85%, and the positive predictive value was 36%. For high-risk patients, the sensitivity of the clinical risk score was 20%, the specificity was 94%, the negative predictive value was 70%, and the positive predictive value was 60%.

In both sets of patients, the clinical risk score was significantly better than physician judgment in predicting PPCS. However, in its present form, it is only modestly accurate at distinguishing who will and who will not have the disorder. This tool could be further refined, perhaps by adding information regarding biomarkers, genetic susceptibility, or advanced neuroimaging, Dr. Zemek and his associates wrote.

“Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility,” they concluded.

This work was supported by the Canadian Institutes of Health Research, the Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team, and the Alberta Children’s Hospital Foundation. Dr. Zemek and his associates reported having no relevant financial disclosures.