Bianca Nogrady

Stress cardiac magnetic resonance is highly feasible and prognostically useful in obese patients, a population in which stress imaging methods are limited, according to a study of nearly 300 patients reported online in JACC: Cardiovascular Imaging on April 9.

Dr. Ravi V. Shah of Harvard Medical School, Boston, and his colleagues, said stress echocardiography and nuclear perfusion can be challenging in obese patients, and PET has issues around ionizing radiation and cost, but the use of stress cardiac magnetic resonance had also been limited by concerns about claustrophobia and safety monitoring.

In this feasibility study in 285 patients with a mean body mass index of 35.4 kg/m², the primary outcome was a composite of cardiac death or MI (MACE). During a mean follow-up of 2.1 years, 19 patients died, 7 from cardiovascular causes.

The incidence of MACE increased with both inducible ischemia and late gadolinium enhancement (LGE). The patients with no evidence of inducible ischemia, infarction, or LGE had a very low annualized MACE rate of 0.3%, while those who had no inducible ischemia who did have LGE had a rate of 2.4%. The MACE rate jumped significantly, to 6.3%, in patients with inducible ischemia and no LGE, and further yet in patients with evidence of both to 6.7%.

Diabetes, age, prior MI, prior revascularization, and reduced left ventricular ejection fraction were all associated with MACE in the study.

The investigators noted that only 13 (5%) of patients failed to complete the study protocol because of claustrophobia, intolerance to the stress agent, or poor gating, and sedation was required in 19 (7%) of patients.

However diagnostic-quality imaging was achieved in more than 89% of patients (JACC Cardiovasc. Imaging 2014 [dx.doi.org/10.1016/j.jcmg.2013.11.011]).

These results "confirm, in an obese population, that inducible ischemia and LGE by stress perfusion CMR are robust markers of risk even in those patients without a clinical history of prior infarction," the authors concluded.

Researchers declared grants and awards from the American Heart Association, the National Institutes of Health and the Alberta Heritage Foundation for Medical Research, and one author declared research support from Astellas Pharma US.

Stress cardiac magnetic resonance is highly feasible and prognostically useful in obese patients, a population in which stress imaging methods are limited, according to a study of nearly 300 patients reported online in JACC: Cardiovascular Imaging on April 9.

Dr. Ravi V. Shah of Harvard Medical School, Boston, and his colleagues, said stress echocardiography and nuclear perfusion can be challenging in obese patients, and PET has issues around ionizing radiation and cost, but the use of stress cardiac magnetic resonance had also been limited by concerns about claustrophobia and safety monitoring.

In this feasibility study in 285 patients with a mean body mass index of 35.4 kg/m², the primary outcome was a composite of cardiac death or MI (MACE). During a mean follow-up of 2.1 years, 19 patients died, 7 from cardiovascular causes.

The incidence of MACE increased with both inducible ischemia and late gadolinium enhancement (LGE). The patients with no evidence of inducible ischemia, infarction, or LGE had a very low annualized MACE rate of 0.3%, while those who had no inducible ischemia who did have LGE had a rate of 2.4%. The MACE rate jumped significantly, to 6.3%, in patients with inducible ischemia and no LGE, and further yet in patients with evidence of both to 6.7%.

Diabetes, age, prior MI, prior revascularization, and reduced left ventricular ejection fraction were all associated with MACE in the study.

The investigators noted that only 13 (5%) of patients failed to complete the study protocol because of claustrophobia, intolerance to the stress agent, or poor gating, and sedation was required in 19 (7%) of patients.

However diagnostic-quality imaging was achieved in more than 89% of patients (JACC Cardiovasc. Imaging 2014 [dx.doi.org/10.1016/j.jcmg.2013.11.011]).

These results "confirm, in an obese population, that inducible ischemia and LGE by stress perfusion CMR are robust markers of risk even in those patients without a clinical history of prior infarction," the authors concluded.

Researchers declared grants and awards from the American Heart Association, the National Institutes of Health and the Alberta Heritage Foundation for Medical Research, and one author declared research support from Astellas Pharma US.

Stress cardiac magnetic resonance is highly feasible and prognostically useful in obese patients, a population in which stress imaging methods are limited, according to a study of nearly 300 patients reported online in JACC: Cardiovascular Imaging on April 9.

Dr. Ravi V. Shah of Harvard Medical School, Boston, and his colleagues, said stress echocardiography and nuclear perfusion can be challenging in obese patients, and PET has issues around ionizing radiation and cost, but the use of stress cardiac magnetic resonance had also been limited by concerns about claustrophobia and safety monitoring.

In this feasibility study in 285 patients with a mean body mass index of 35.4 kg/m², the primary outcome was a composite of cardiac death or MI (MACE). During a mean follow-up of 2.1 years, 19 patients died, 7 from cardiovascular causes.

The incidence of MACE increased with both inducible ischemia and late gadolinium enhancement (LGE). The patients with no evidence of inducible ischemia, infarction, or LGE had a very low annualized MACE rate of 0.3%, while those who had no inducible ischemia who did have LGE had a rate of 2.4%. The MACE rate jumped significantly, to 6.3%, in patients with inducible ischemia and no LGE, and further yet in patients with evidence of both to 6.7%.

Diabetes, age, prior MI, prior revascularization, and reduced left ventricular ejection fraction were all associated with MACE in the study.

The investigators noted that only 13 (5%) of patients failed to complete the study protocol because of claustrophobia, intolerance to the stress agent, or poor gating, and sedation was required in 19 (7%) of patients.

However diagnostic-quality imaging was achieved in more than 89% of patients (JACC Cardiovasc. Imaging 2014 [dx.doi.org/10.1016/j.jcmg.2013.11.011]).

These results "confirm, in an obese population, that inducible ischemia and LGE by stress perfusion CMR are robust markers of risk even in those patients without a clinical history of prior infarction," the authors concluded.

Researchers declared grants and awards from the American Heart Association, the National Institutes of Health and the Alberta Heritage Foundation for Medical Research, and one author declared research support from Astellas Pharma US.

Experts have signaled a need for the development of validated patient-reported outcomes for inflammatory bowel disease based on Food and Drug Administration guidance, in the face of a move toward the use of patient-reported outcomes and objective measures of disease as the primary endpoint for clinical trials.

Dr. Nicolas Williet, from the Université Henri Poincaré, Vandoeuvre-lès-Nancy, France, and his colleagues wrote that the FDA was moving away from use of the Crohn’s Disease Activity Index in the assessment of inflammatory bowel disease (IBD) outcomes, and would likely soon require patient-reported outcomes as a coprimary endpoint with objective measures such as endoscopic assessment.

Patient-reported outcomes should be obtained by using a validated, self-administered questionnaire with items that are generated solely by patients, the authors wrote online Feb. 19 in Clinical Gastroenterology and Hepatology.

"A PRO [patient-reported outcome] is any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient’ s response by a clinician or anyone else," they wrote. "The items measured by PRO instruments that are used most often in support of labeling claims refer to a patient symptom, sign, or an aspect of functioning directly related to disease status."

However, the authors said that no existing patient-reported outcomes for IBD, such as the Inflammatory Bowel Disease Questionnaire assessing quality of life and the IBD Disability Index, were developed according to the recently developed FDA guidelines. There is a need for international consensus to develop validated patient-reported outcomes using FDA guidance, they asserted.

"During the development of PROs, the disease characteristics of the patients (type of IBD, extent of the disease, the presence or absence of objectively measured inflammation, presence or absence of disease complications such as stricture, fistula, and abscess, and so forth) must be documented carefully to determine the impact of various disease characteristics on the operating characteristics of the PRO."

Particularly in irritable bowel syndrome, there is still debate about how best to measure patient-reported outcomes, the authors said (Clin. Gastroenterol. Hepatol. 2014 Feb. 19 [doi: 10.1016/j.cgh.2014.02.016]).

"Depending on their structure and format, PROs can have different levels of sensitivity to core IBS symptoms and can be influenced by psychological and somatic complaints."

Patient-reported outcomes are already used in other chronic conditions such as rheumatoid arthritis and multiple sclerosis, with studies showing that patient-reported outcomes offer important endpoints for drug approval in these conditions.

"In the near future, PROs may evolve to be used as the primary or major secondary endpoints in clinical trials in patients with IBD, possibly leading to drug approval and labeling, similar to the JAK inhibitor in the treatment of myelofibrosis," the authors reported.

Two of the three authors disclosed consulting and lecture fees, as well as research support, from numerous pharmaceutical companies.

Experts have signaled a need for the development of validated patient-reported outcomes for inflammatory bowel disease based on Food and Drug Administration guidance, in the face of a move toward the use of patient-reported outcomes and objective measures of disease as the primary endpoint for clinical trials.

Dr. Nicolas Williet, from the Université Henri Poincaré, Vandoeuvre-lès-Nancy, France, and his colleagues wrote that the FDA was moving away from use of the Crohn’s Disease Activity Index in the assessment of inflammatory bowel disease (IBD) outcomes, and would likely soon require patient-reported outcomes as a coprimary endpoint with objective measures such as endoscopic assessment.

Patient-reported outcomes should be obtained by using a validated, self-administered questionnaire with items that are generated solely by patients, the authors wrote online Feb. 19 in Clinical Gastroenterology and Hepatology.

"A PRO [patient-reported outcome] is any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient’ s response by a clinician or anyone else," they wrote. "The items measured by PRO instruments that are used most often in support of labeling claims refer to a patient symptom, sign, or an aspect of functioning directly related to disease status."

However, the authors said that no existing patient-reported outcomes for IBD, such as the Inflammatory Bowel Disease Questionnaire assessing quality of life and the IBD Disability Index, were developed according to the recently developed FDA guidelines. There is a need for international consensus to develop validated patient-reported outcomes using FDA guidance, they asserted.

"During the development of PROs, the disease characteristics of the patients (type of IBD, extent of the disease, the presence or absence of objectively measured inflammation, presence or absence of disease complications such as stricture, fistula, and abscess, and so forth) must be documented carefully to determine the impact of various disease characteristics on the operating characteristics of the PRO."

Particularly in irritable bowel syndrome, there is still debate about how best to measure patient-reported outcomes, the authors said (Clin. Gastroenterol. Hepatol. 2014 Feb. 19 [doi: 10.1016/j.cgh.2014.02.016]).

"Depending on their structure and format, PROs can have different levels of sensitivity to core IBS symptoms and can be influenced by psychological and somatic complaints."

Patient-reported outcomes are already used in other chronic conditions such as rheumatoid arthritis and multiple sclerosis, with studies showing that patient-reported outcomes offer important endpoints for drug approval in these conditions.

"In the near future, PROs may evolve to be used as the primary or major secondary endpoints in clinical trials in patients with IBD, possibly leading to drug approval and labeling, similar to the JAK inhibitor in the treatment of myelofibrosis," the authors reported.

Two of the three authors disclosed consulting and lecture fees, as well as research support, from numerous pharmaceutical companies.

Experts have signaled a need for the development of validated patient-reported outcomes for inflammatory bowel disease based on Food and Drug Administration guidance, in the face of a move toward the use of patient-reported outcomes and objective measures of disease as the primary endpoint for clinical trials.

Dr. Nicolas Williet, from the Université Henri Poincaré, Vandoeuvre-lès-Nancy, France, and his colleagues wrote that the FDA was moving away from use of the Crohn’s Disease Activity Index in the assessment of inflammatory bowel disease (IBD) outcomes, and would likely soon require patient-reported outcomes as a coprimary endpoint with objective measures such as endoscopic assessment.

Patient-reported outcomes should be obtained by using a validated, self-administered questionnaire with items that are generated solely by patients, the authors wrote online Feb. 19 in Clinical Gastroenterology and Hepatology.

"A PRO [patient-reported outcome] is any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient’ s response by a clinician or anyone else," they wrote. "The items measured by PRO instruments that are used most often in support of labeling claims refer to a patient symptom, sign, or an aspect of functioning directly related to disease status."

However, the authors said that no existing patient-reported outcomes for IBD, such as the Inflammatory Bowel Disease Questionnaire assessing quality of life and the IBD Disability Index, were developed according to the recently developed FDA guidelines. There is a need for international consensus to develop validated patient-reported outcomes using FDA guidance, they asserted.

"During the development of PROs, the disease characteristics of the patients (type of IBD, extent of the disease, the presence or absence of objectively measured inflammation, presence or absence of disease complications such as stricture, fistula, and abscess, and so forth) must be documented carefully to determine the impact of various disease characteristics on the operating characteristics of the PRO."

Particularly in irritable bowel syndrome, there is still debate about how best to measure patient-reported outcomes, the authors said (Clin. Gastroenterol. Hepatol. 2014 Feb. 19 [doi: 10.1016/j.cgh.2014.02.016]).

"Depending on their structure and format, PROs can have different levels of sensitivity to core IBS symptoms and can be influenced by psychological and somatic complaints."

Patient-reported outcomes are already used in other chronic conditions such as rheumatoid arthritis and multiple sclerosis, with studies showing that patient-reported outcomes offer important endpoints for drug approval in these conditions.

"In the near future, PROs may evolve to be used as the primary or major secondary endpoints in clinical trials in patients with IBD, possibly leading to drug approval and labeling, similar to the JAK inhibitor in the treatment of myelofibrosis," the authors reported.

Two of the three authors disclosed consulting and lecture fees, as well as research support, from numerous pharmaceutical companies.

Data suggesting that circumcision rates in neonates have declined in recent years have prompted a renewed call for universal Medicaid coverage for the procedure and inclusion of circumcision as part of public health policy, according to a report published online in the April 2 issue of Mayo Clinic Proceedings.

A review examining trends in U.S. male circumcision rates and the impact of the 2012 American Academy of Pediatrics policy has found that the overall rate of circumcision in the United States declined from 83% in 1960-1969 to 77% by 2010.

Brian Morris, Ph.D., of the University of Sydney and his colleagues suggested that the decline was partly the result of demographic changes, such as the increase in the proportion of Hispanic people, who are traditionally noncircumcising, but also was likely influenced by the withdrawal of Medicaid coverage for circumcision in 18 states.

The review was prompted by a recent report from the Centers for Disease Control and Prevention, which used data from the National Health and Nutrition Examination Surveys to estimate that total circumcision prevalence had risen from 79% to 81% over the past decade, with increases to 90.8% in non-Hispanic white, 75.7% in non-Hispanic black, and 44.0% in Mexican American males.

"Because these data are for males aged 14 to 59 years – and most circumcisions in the United States take place during the neonatal period – they largely reflect past practice," Dr. Morris and his associates wrote.

Instead, they used hospital discharge data, corrected for so-called unreported circumcisions that take place after neonates are discharged from the hospital, to reveal the six percentage point decline since the 1960s.

The authors also conducted a risk-benefit analysis of circumcision, finding that the benefits – such as a reduced risk of urinary tract infection, human papillomavirus, herpes simplex, and HIV infections – exceeded the risks by at least 100 to 1 (Mayo Clin. Proc. 2014 Apr. 2 [doi:10.1016/j.mayocp.2014.01.001]).

They concluded that, over the course of a lifetime, around one in two uncircumcised men would require treatment for some medical condition associated with retention of the foreskin.

"It would be unethical for medical practitioners not to recommend circumcision for a baby boy," Dr. Morris said in an interview. "That’s what the AAP says, and it recommends that parents be educated about the benefits and also the risks early in the pregnancy so they’ve got plenty of time to make up their minds should they have a baby boy."

The most common risk associated with circumcision was local bruising at the site of the local anesthetic injection, affecting approximately one-quarter of individuals. More serious adverse effects such as infection, bleeding, or loss of the penis were extremely rare.

Commenting on the often-quoted risk of reduced penile sensitivity and enjoyment of sex, Dr. Morris said that the overwhelming majority of studies, including those conducted in adult men undergoing circumcision, showed no difference or even an improvement in sexual pleasure.

The reviewers also argued that circumcision was extremely cost effective, citing one study of infant urinary tract infections and sexually transmitted infections suggesting that, if male circumcision rates declined to those seen in Europe – around 10% – it would result in additional medical costs exceeding $4.4 billion.

"When considered together with ethical and human rights arguments, neonatal circumcision should logically be strongly supported and encouraged as an important evidence-based intervention akin to childhood vaccination," the authors wrote.

No conflicts of interest were disclosed.

Data suggesting that circumcision rates in neonates have declined in recent years have prompted a renewed call for universal Medicaid coverage for the procedure and inclusion of circumcision as part of public health policy, according to a report published online in the April 2 issue of Mayo Clinic Proceedings.

A review examining trends in U.S. male circumcision rates and the impact of the 2012 American Academy of Pediatrics policy has found that the overall rate of circumcision in the United States declined from 83% in 1960-1969 to 77% by 2010.

Brian Morris, Ph.D., of the University of Sydney and his colleagues suggested that the decline was partly the result of demographic changes, such as the increase in the proportion of Hispanic people, who are traditionally noncircumcising, but also was likely influenced by the withdrawal of Medicaid coverage for circumcision in 18 states.

The review was prompted by a recent report from the Centers for Disease Control and Prevention, which used data from the National Health and Nutrition Examination Surveys to estimate that total circumcision prevalence had risen from 79% to 81% over the past decade, with increases to 90.8% in non-Hispanic white, 75.7% in non-Hispanic black, and 44.0% in Mexican American males.

"Because these data are for males aged 14 to 59 years – and most circumcisions in the United States take place during the neonatal period – they largely reflect past practice," Dr. Morris and his associates wrote.

Instead, they used hospital discharge data, corrected for so-called unreported circumcisions that take place after neonates are discharged from the hospital, to reveal the six percentage point decline since the 1960s.

The authors also conducted a risk-benefit analysis of circumcision, finding that the benefits – such as a reduced risk of urinary tract infection, human papillomavirus, herpes simplex, and HIV infections – exceeded the risks by at least 100 to 1 (Mayo Clin. Proc. 2014 Apr. 2 [doi:10.1016/j.mayocp.2014.01.001]).

They concluded that, over the course of a lifetime, around one in two uncircumcised men would require treatment for some medical condition associated with retention of the foreskin.

"It would be unethical for medical practitioners not to recommend circumcision for a baby boy," Dr. Morris said in an interview. "That’s what the AAP says, and it recommends that parents be educated about the benefits and also the risks early in the pregnancy so they’ve got plenty of time to make up their minds should they have a baby boy."

The most common risk associated with circumcision was local bruising at the site of the local anesthetic injection, affecting approximately one-quarter of individuals. More serious adverse effects such as infection, bleeding, or loss of the penis were extremely rare.

Commenting on the often-quoted risk of reduced penile sensitivity and enjoyment of sex, Dr. Morris said that the overwhelming majority of studies, including those conducted in adult men undergoing circumcision, showed no difference or even an improvement in sexual pleasure.

The reviewers also argued that circumcision was extremely cost effective, citing one study of infant urinary tract infections and sexually transmitted infections suggesting that, if male circumcision rates declined to those seen in Europe – around 10% – it would result in additional medical costs exceeding $4.4 billion.

"When considered together with ethical and human rights arguments, neonatal circumcision should logically be strongly supported and encouraged as an important evidence-based intervention akin to childhood vaccination," the authors wrote.

No conflicts of interest were disclosed.

Data suggesting that circumcision rates in neonates have declined in recent years have prompted a renewed call for universal Medicaid coverage for the procedure and inclusion of circumcision as part of public health policy, according to a report published online in the April 2 issue of Mayo Clinic Proceedings.

A review examining trends in U.S. male circumcision rates and the impact of the 2012 American Academy of Pediatrics policy has found that the overall rate of circumcision in the United States declined from 83% in 1960-1969 to 77% by 2010.

Brian Morris, Ph.D., of the University of Sydney and his colleagues suggested that the decline was partly the result of demographic changes, such as the increase in the proportion of Hispanic people, who are traditionally noncircumcising, but also was likely influenced by the withdrawal of Medicaid coverage for circumcision in 18 states.

The review was prompted by a recent report from the Centers for Disease Control and Prevention, which used data from the National Health and Nutrition Examination Surveys to estimate that total circumcision prevalence had risen from 79% to 81% over the past decade, with increases to 90.8% in non-Hispanic white, 75.7% in non-Hispanic black, and 44.0% in Mexican American males.

"Because these data are for males aged 14 to 59 years – and most circumcisions in the United States take place during the neonatal period – they largely reflect past practice," Dr. Morris and his associates wrote.

Instead, they used hospital discharge data, corrected for so-called unreported circumcisions that take place after neonates are discharged from the hospital, to reveal the six percentage point decline since the 1960s.

The authors also conducted a risk-benefit analysis of circumcision, finding that the benefits – such as a reduced risk of urinary tract infection, human papillomavirus, herpes simplex, and HIV infections – exceeded the risks by at least 100 to 1 (Mayo Clin. Proc. 2014 Apr. 2 [doi:10.1016/j.mayocp.2014.01.001]).

They concluded that, over the course of a lifetime, around one in two uncircumcised men would require treatment for some medical condition associated with retention of the foreskin.

"It would be unethical for medical practitioners not to recommend circumcision for a baby boy," Dr. Morris said in an interview. "That’s what the AAP says, and it recommends that parents be educated about the benefits and also the risks early in the pregnancy so they’ve got plenty of time to make up their minds should they have a baby boy."

The most common risk associated with circumcision was local bruising at the site of the local anesthetic injection, affecting approximately one-quarter of individuals. More serious adverse effects such as infection, bleeding, or loss of the penis were extremely rare.

Commenting on the often-quoted risk of reduced penile sensitivity and enjoyment of sex, Dr. Morris said that the overwhelming majority of studies, including those conducted in adult men undergoing circumcision, showed no difference or even an improvement in sexual pleasure.

The reviewers also argued that circumcision was extremely cost effective, citing one study of infant urinary tract infections and sexually transmitted infections suggesting that, if male circumcision rates declined to those seen in Europe – around 10% – it would result in additional medical costs exceeding $4.4 billion.

"When considered together with ethical and human rights arguments, neonatal circumcision should logically be strongly supported and encouraged as an important evidence-based intervention akin to childhood vaccination," the authors wrote.

No conflicts of interest were disclosed.

Researchers have identified an optimal pegaspargase dosing regimen for the treatment of adult acute lymphoblastic leukemia using up to six intravenous 2,000 IU/m²-doses given at 4-week intervals and synchronized with other chemotherapy drugs to avoid overlapping toxicities.

Of 51 adults with newly diagnosed acute lymphoblastic leukemia who were treated with some or all of six doses, 49 (96%) achieved remission – most within 4 weeks – and the 7-year disease-free and overall survival were 58% and 51% respectively, according to a study published in the March 20 issue of the Journal of Clinical Oncology (doi:10.1200/JCO.2013.50.2708).

Dr. Dan Douer of Memorial Sloan-Kettering Cancer Center, New York, and his colleagues reported that there were no pegaspargase-related deaths, with the most common grade three or four toxicities being hyperbilirubinemia (31.3%), transaminitis (62.7%), hyperglycemia (33.3%), and hypertriglyceridemia (17.6%), and the most serious being pancreatitis (13.7%) and anaphylaxis (5.9%).

Pegaspargase is standard in the treatment of pediatric acute lymphoblastic leukemia but is used sparingly in adults because of its potential higher toxicity, however in this study, the drug was discontinued in only 20% of patients after serious pegaspargase-related toxicity.

Dr. Douer declared honoraria and research funding from Sigma Tau Pharmaceuticals, which supported the study with a research grant.

[email protected]

Researchers have identified an optimal pegaspargase dosing regimen for the treatment of adult acute lymphoblastic leukemia using up to six intravenous 2,000 IU/m²-doses given at 4-week intervals and synchronized with other chemotherapy drugs to avoid overlapping toxicities.

Of 51 adults with newly diagnosed acute lymphoblastic leukemia who were treated with some or all of six doses, 49 (96%) achieved remission – most within 4 weeks – and the 7-year disease-free and overall survival were 58% and 51% respectively, according to a study published in the March 20 issue of the Journal of Clinical Oncology (doi:10.1200/JCO.2013.50.2708).

Dr. Dan Douer of Memorial Sloan-Kettering Cancer Center, New York, and his colleagues reported that there were no pegaspargase-related deaths, with the most common grade three or four toxicities being hyperbilirubinemia (31.3%), transaminitis (62.7%), hyperglycemia (33.3%), and hypertriglyceridemia (17.6%), and the most serious being pancreatitis (13.7%) and anaphylaxis (5.9%).

Pegaspargase is standard in the treatment of pediatric acute lymphoblastic leukemia but is used sparingly in adults because of its potential higher toxicity, however in this study, the drug was discontinued in only 20% of patients after serious pegaspargase-related toxicity.

Dr. Douer declared honoraria and research funding from Sigma Tau Pharmaceuticals, which supported the study with a research grant.

[email protected]

Researchers have identified an optimal pegaspargase dosing regimen for the treatment of adult acute lymphoblastic leukemia using up to six intravenous 2,000 IU/m²-doses given at 4-week intervals and synchronized with other chemotherapy drugs to avoid overlapping toxicities.

Of 51 adults with newly diagnosed acute lymphoblastic leukemia who were treated with some or all of six doses, 49 (96%) achieved remission – most within 4 weeks – and the 7-year disease-free and overall survival were 58% and 51% respectively, according to a study published in the March 20 issue of the Journal of Clinical Oncology (doi:10.1200/JCO.2013.50.2708).

Dr. Dan Douer of Memorial Sloan-Kettering Cancer Center, New York, and his colleagues reported that there were no pegaspargase-related deaths, with the most common grade three or four toxicities being hyperbilirubinemia (31.3%), transaminitis (62.7%), hyperglycemia (33.3%), and hypertriglyceridemia (17.6%), and the most serious being pancreatitis (13.7%) and anaphylaxis (5.9%).

Pegaspargase is standard in the treatment of pediatric acute lymphoblastic leukemia but is used sparingly in adults because of its potential higher toxicity, however in this study, the drug was discontinued in only 20% of patients after serious pegaspargase-related toxicity.

Dr. Douer declared honoraria and research funding from Sigma Tau Pharmaceuticals, which supported the study with a research grant.

[email protected]

Treatment with metformin failed to show any positive effects on left ventricular function in diabetes-free patients who presented with ST-segment elevation MI, according to the results of a double-blind, placebo-controlled study.

The study in 380 patients undergoing primary percutaneous coronary intervention – 191 of whom were given metformin and 189 of whom were given placebo – found no significant effects of twice-daily metformin (500 mg) on left ventricular ejection fraction (LVEF) after 4 months of treatment, and there was no significant difference in the incidence of major cardiac events between the two groups, Dr. Chris P. H. Lexis said at the annual meeting of the American College of Cardiology.

Specifically, at 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% in the metformin group, compared with 54.8% in the placebo group. NT-proBNP concentration was 167 ng/L in the metformin group and 167 ng/L in the placebo group. Major adverse cardiovascular events were observed in six patients (3.1%) in the metformin group and in two patients (1.1%) in the placebo group. Creatinine concentration (79 micromol/L vs. 79 micromol/L) and glycated hemoglobin (5.9% vs. 5.9%) were not significantly different between both groups. No cases of lactic acidosis were observed, according to the investigators.

Up to half of patients who experience an ST-segment elevation MI (STEMI) develop left ventricular dysfunction, which is the strongest predictor of adverse outcomes, such as heart failure.

Findings from previous animal studies had suggested that metformin may have favorable effects on ventricular function, possibly through enhanced phosphorylation of AMP-activated protein kinase causing changes in intracellular pathways and altering mitochondrial function, in turn resulting in improved systolic and diastolic function.

"Data from experimental studies have suggested that administration of metformin before and during ischemia reperfusion might affect these protective pathways and preserve left ventricular function, independent of glycometabolic state," according to Dr. Lexis of the University of Groningen, the Netherlands, and his associates, in a paper simultaneously published online in JAMA (2014 March 31 [doi:10.1001/jama.2014.3315]).

"Moreover, in observational studies of patients with acute myocardial infarction, concurrent treatment with metformin was associated with lower peak values of CK [creatine kinase], myocardial band of CK, and troponins and with improved survival after STEMI in patients with type 2 diabetes, compared with other antihyperglycemic strategies."

Treatment with metformin failed to show any positive effects on left ventricular function in diabetes-free patients who presented with ST-segment elevation MI, according to the results of a double-blind, placebo-controlled study.

The study in 380 patients undergoing primary percutaneous coronary intervention – 191 of whom were given metformin and 189 of whom were given placebo – found no significant effects of twice-daily metformin (500 mg) on left ventricular ejection fraction (LVEF) after 4 months of treatment, and there was no significant difference in the incidence of major cardiac events between the two groups, Dr. Chris P. H. Lexis said at the annual meeting of the American College of Cardiology.

Specifically, at 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% in the metformin group, compared with 54.8% in the placebo group. NT-proBNP concentration was 167 ng/L in the metformin group and 167 ng/L in the placebo group. Major adverse cardiovascular events were observed in six patients (3.1%) in the metformin group and in two patients (1.1%) in the placebo group. Creatinine concentration (79 micromol/L vs. 79 micromol/L) and glycated hemoglobin (5.9% vs. 5.9%) were not significantly different between both groups. No cases of lactic acidosis were observed, according to the investigators.

Up to half of patients who experience an ST-segment elevation MI (STEMI) develop left ventricular dysfunction, which is the strongest predictor of adverse outcomes, such as heart failure.

Findings from previous animal studies had suggested that metformin may have favorable effects on ventricular function, possibly through enhanced phosphorylation of AMP-activated protein kinase causing changes in intracellular pathways and altering mitochondrial function, in turn resulting in improved systolic and diastolic function.

"Data from experimental studies have suggested that administration of metformin before and during ischemia reperfusion might affect these protective pathways and preserve left ventricular function, independent of glycometabolic state," according to Dr. Lexis of the University of Groningen, the Netherlands, and his associates, in a paper simultaneously published online in JAMA (2014 March 31 [doi:10.1001/jama.2014.3315]).

"Moreover, in observational studies of patients with acute myocardial infarction, concurrent treatment with metformin was associated with lower peak values of CK [creatine kinase], myocardial band of CK, and troponins and with improved survival after STEMI in patients with type 2 diabetes, compared with other antihyperglycemic strategies."

Treatment with metformin failed to show any positive effects on left ventricular function in diabetes-free patients who presented with ST-segment elevation MI, according to the results of a double-blind, placebo-controlled study.

The study in 380 patients undergoing primary percutaneous coronary intervention – 191 of whom were given metformin and 189 of whom were given placebo – found no significant effects of twice-daily metformin (500 mg) on left ventricular ejection fraction (LVEF) after 4 months of treatment, and there was no significant difference in the incidence of major cardiac events between the two groups, Dr. Chris P. H. Lexis said at the annual meeting of the American College of Cardiology.

Specifically, at 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% in the metformin group, compared with 54.8% in the placebo group. NT-proBNP concentration was 167 ng/L in the metformin group and 167 ng/L in the placebo group. Major adverse cardiovascular events were observed in six patients (3.1%) in the metformin group and in two patients (1.1%) in the placebo group. Creatinine concentration (79 micromol/L vs. 79 micromol/L) and glycated hemoglobin (5.9% vs. 5.9%) were not significantly different between both groups. No cases of lactic acidosis were observed, according to the investigators.

Up to half of patients who experience an ST-segment elevation MI (STEMI) develop left ventricular dysfunction, which is the strongest predictor of adverse outcomes, such as heart failure.

Findings from previous animal studies had suggested that metformin may have favorable effects on ventricular function, possibly through enhanced phosphorylation of AMP-activated protein kinase causing changes in intracellular pathways and altering mitochondrial function, in turn resulting in improved systolic and diastolic function.

"Data from experimental studies have suggested that administration of metformin before and during ischemia reperfusion might affect these protective pathways and preserve left ventricular function, independent of glycometabolic state," according to Dr. Lexis of the University of Groningen, the Netherlands, and his associates, in a paper simultaneously published online in JAMA (2014 March 31 [doi:10.1001/jama.2014.3315]).

"Moreover, in observational studies of patients with acute myocardial infarction, concurrent treatment with metformin was associated with lower peak values of CK [creatine kinase], myocardial band of CK, and troponins and with improved survival after STEMI in patients with type 2 diabetes, compared with other antihyperglycemic strategies."

A trial of aleglitazar to improve cardiovascular outcomes in patients with type 2 diabetes who had recent-onset acute coronary syndrome has been terminated early because of a lack of efficacy and an increased risk of adverse events.

The phase III trial found no significant improvements in the primary endpoint of time to cardiovascular death, nonfatal MI, or nonfatal stroke.

Specifically, the primary endpoint occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.83-1.1; P = .57), and a significant increase in gastrointestinal hemorrhages, renal dysfunction, peripheral edema, and hypoglycemia in the aleglitazar arm, Dr. A. Michael Lincoff of the Cleveland Clinic and his colleagues said at the annual meeting of the American College of Cardiology.

"These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk," the authors reported in a study simultaneously published online March 30 in JAMA (2014 [doi:10.1001/jama.2014.3321]).

The double-blind, placebo-controlled trial in 7,226 patients of dual peroxisome proliferator-activated receptor agonist aleglitazar 150 mcg daily followed an earlier phase II trial that showed the drug significantly reduced glycated hemoglobin, triglycerides, and LDL cholesterol, and raised HDL cholesterol.

The trial was sponsored by F. Hoffmann-La Roche, and the authors reported research grants, honoraria and consultancy fees from a range of pharmaceutical companies.

A trial of aleglitazar to improve cardiovascular outcomes in patients with type 2 diabetes who had recent-onset acute coronary syndrome has been terminated early because of a lack of efficacy and an increased risk of adverse events.

The phase III trial found no significant improvements in the primary endpoint of time to cardiovascular death, nonfatal MI, or nonfatal stroke.

Specifically, the primary endpoint occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.83-1.1; P = .57), and a significant increase in gastrointestinal hemorrhages, renal dysfunction, peripheral edema, and hypoglycemia in the aleglitazar arm, Dr. A. Michael Lincoff of the Cleveland Clinic and his colleagues said at the annual meeting of the American College of Cardiology.

"These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk," the authors reported in a study simultaneously published online March 30 in JAMA (2014 [doi:10.1001/jama.2014.3321]).

The double-blind, placebo-controlled trial in 7,226 patients of dual peroxisome proliferator-activated receptor agonist aleglitazar 150 mcg daily followed an earlier phase II trial that showed the drug significantly reduced glycated hemoglobin, triglycerides, and LDL cholesterol, and raised HDL cholesterol.

The trial was sponsored by F. Hoffmann-La Roche, and the authors reported research grants, honoraria and consultancy fees from a range of pharmaceutical companies.

A trial of aleglitazar to improve cardiovascular outcomes in patients with type 2 diabetes who had recent-onset acute coronary syndrome has been terminated early because of a lack of efficacy and an increased risk of adverse events.

The phase III trial found no significant improvements in the primary endpoint of time to cardiovascular death, nonfatal MI, or nonfatal stroke.

Specifically, the primary endpoint occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.83-1.1; P = .57), and a significant increase in gastrointestinal hemorrhages, renal dysfunction, peripheral edema, and hypoglycemia in the aleglitazar arm, Dr. A. Michael Lincoff of the Cleveland Clinic and his colleagues said at the annual meeting of the American College of Cardiology.

"These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk," the authors reported in a study simultaneously published online March 30 in JAMA (2014 [doi:10.1001/jama.2014.3321]).

The double-blind, placebo-controlled trial in 7,226 patients of dual peroxisome proliferator-activated receptor agonist aleglitazar 150 mcg daily followed an earlier phase II trial that showed the drug significantly reduced glycated hemoglobin, triglycerides, and LDL cholesterol, and raised HDL cholesterol.

The trial was sponsored by F. Hoffmann-La Roche, and the authors reported research grants, honoraria and consultancy fees from a range of pharmaceutical companies.

Persistent lymphocytosis lasting more than 12 months in patients with chronic lymphocytic leukemia undergoing treatment with ibrutinib is not associated with a greater likelihood of early relapse.

A prospective observational study in 85 relapsed or refractory patients with chronic lymphocytic leukemia treated with ibrutinib showed lymphocytosis occurred in 77% in patients, persisting at 12 months in 20% of patients.

Dr. Jennifer A. Woyach of Ohio State University, Columbus, and her colleagues found no significant differences in progression-free survival between patients who responded to treatment but showed persistent lymphocytosis, and those with a partial or complete response to treatment without lymphocytosis.

They also found no significant differences in gene expression profiles in persistent lymphocytosis, suggesting that the lymphocytosis most likely represented the movement of quiescent cells (Blood 2014;123:1810-17).

Two authors were unpaid consultants for, three were paid consultants for, and two were employees of Pharmacyclics. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.

Persistent lymphocytosis lasting more than 12 months in patients with chronic lymphocytic leukemia undergoing treatment with ibrutinib is not associated with a greater likelihood of early relapse.

A prospective observational study in 85 relapsed or refractory patients with chronic lymphocytic leukemia treated with ibrutinib showed lymphocytosis occurred in 77% in patients, persisting at 12 months in 20% of patients.

Dr. Jennifer A. Woyach of Ohio State University, Columbus, and her colleagues found no significant differences in progression-free survival between patients who responded to treatment but showed persistent lymphocytosis, and those with a partial or complete response to treatment without lymphocytosis.

They also found no significant differences in gene expression profiles in persistent lymphocytosis, suggesting that the lymphocytosis most likely represented the movement of quiescent cells (Blood 2014;123:1810-17).

Two authors were unpaid consultants for, three were paid consultants for, and two were employees of Pharmacyclics. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.

Persistent lymphocytosis lasting more than 12 months in patients with chronic lymphocytic leukemia undergoing treatment with ibrutinib is not associated with a greater likelihood of early relapse.

A prospective observational study in 85 relapsed or refractory patients with chronic lymphocytic leukemia treated with ibrutinib showed lymphocytosis occurred in 77% in patients, persisting at 12 months in 20% of patients.

Dr. Jennifer A. Woyach of Ohio State University, Columbus, and her colleagues found no significant differences in progression-free survival between patients who responded to treatment but showed persistent lymphocytosis, and those with a partial or complete response to treatment without lymphocytosis.

They also found no significant differences in gene expression profiles in persistent lymphocytosis, suggesting that the lymphocytosis most likely represented the movement of quiescent cells (Blood 2014;123:1810-17).

Two authors were unpaid consultants for, three were paid consultants for, and two were employees of Pharmacyclics. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.

Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.

The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.

Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.

A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.

In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).

"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.

Dr. Batchu and his colleagues reported that they had no conflicts of interest.

Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.

The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.

Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.

A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.

In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).

"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.

Dr. Batchu and his colleagues reported that they had no conflicts of interest.

Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.

The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.

Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.

A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.

In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).

"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.

Dr. Batchu and his colleagues reported that they had no conflicts of interest.

The risk of multidrug-resistant tuberculosis appears similar in children and treatment-naive adults, according to a study published online ahead of World Tuberculosis Day, which is March 24.

This study provides the first global and regional estimates of the incidence of drug-resistant disease in children.

Researchers led by Helen E. Jenkins, Ph.D., of Brigham and Women’s Hospital, Boston, calculated the incidence of tuberculosis in children and conducted a systematic review to estimate the risk of multidrug-resistant disease. They concluded that nearly 1 million children developed tuberculosis in 2010 – a figure substantially higher than the 2011 World Health Organization estimates. Of those, nearly 32,000 had multidrug-resistant disease.

The highest concentrations of pediatric tuberculosis and drug-resistant disease were in Southeast Asia, according to Dr. Jenkins and her associates (Lancet 2014 March 24 [doi: 10.1016/S0140-6736(14)60195-1]).

In an accompanying editorial, Dr. Ben J. Marais of the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Australia, called the study the "most rigorous effort to date to provide contextualized estimates of both tuberculosis and multidrug-resistant tuberculosis incidence in children," and said it was likely to provide a benchmark for future studies in the area.

"Given that treatment outcomes for children with multidrug-resistant tuberculosis are excellent (clinical cure rates in excess of 80%), every effort should be made to reduce the massive case-detection gap and address the vast unmet need for diagnosis and treatment," he said (Lancet 2014 March 24 [doi: 10.1016/S0140-6736(14)60489-X]).

The authors and Dr. Marais declared that they had no competing interests. Funding for the study was provided by awards from the U.S. National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases, as well as various fellowships.

The risk of multidrug-resistant tuberculosis appears similar in children and treatment-naive adults, according to a study published online ahead of World Tuberculosis Day, which is March 24.

This study provides the first global and regional estimates of the incidence of drug-resistant disease in children.

Researchers led by Helen E. Jenkins, Ph.D., of Brigham and Women’s Hospital, Boston, calculated the incidence of tuberculosis in children and conducted a systematic review to estimate the risk of multidrug-resistant disease. They concluded that nearly 1 million children developed tuberculosis in 2010 – a figure substantially higher than the 2011 World Health Organization estimates. Of those, nearly 32,000 had multidrug-resistant disease.

The highest concentrations of pediatric tuberculosis and drug-resistant disease were in Southeast Asia, according to Dr. Jenkins and her associates (Lancet 2014 March 24 [doi: 10.1016/S0140-6736(14)60195-1]).

In an accompanying editorial, Dr. Ben J. Marais of the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Australia, called the study the "most rigorous effort to date to provide contextualized estimates of both tuberculosis and multidrug-resistant tuberculosis incidence in children," and said it was likely to provide a benchmark for future studies in the area.

"Given that treatment outcomes for children with multidrug-resistant tuberculosis are excellent (clinical cure rates in excess of 80%), every effort should be made to reduce the massive case-detection gap and address the vast unmet need for diagnosis and treatment," he said (Lancet 2014 March 24 [doi: 10.1016/S0140-6736(14)60489-X]).

The authors and Dr. Marais declared that they had no competing interests. Funding for the study was provided by awards from the U.S. National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases, as well as various fellowships.

The risk of multidrug-resistant tuberculosis appears similar in children and treatment-naive adults, according to a study published online ahead of World Tuberculosis Day, which is March 24.

This study provides the first global and regional estimates of the incidence of drug-resistant disease in children.

Researchers led by Helen E. Jenkins, Ph.D., of Brigham and Women’s Hospital, Boston, calculated the incidence of tuberculosis in children and conducted a systematic review to estimate the risk of multidrug-resistant disease. They concluded that nearly 1 million children developed tuberculosis in 2010 – a figure substantially higher than the 2011 World Health Organization estimates. Of those, nearly 32,000 had multidrug-resistant disease.

The highest concentrations of pediatric tuberculosis and drug-resistant disease were in Southeast Asia, according to Dr. Jenkins and her associates (Lancet 2014 March 24 [doi: 10.1016/S0140-6736(14)60195-1]).

In an accompanying editorial, Dr. Ben J. Marais of the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Australia, called the study the "most rigorous effort to date to provide contextualized estimates of both tuberculosis and multidrug-resistant tuberculosis incidence in children," and said it was likely to provide a benchmark for future studies in the area.

"Given that treatment outcomes for children with multidrug-resistant tuberculosis are excellent (clinical cure rates in excess of 80%), every effort should be made to reduce the massive case-detection gap and address the vast unmet need for diagnosis and treatment," he said (Lancet 2014 March 24 [doi: 10.1016/S0140-6736(14)60489-X]).

The authors and Dr. Marais declared that they had no competing interests. Funding for the study was provided by awards from the U.S. National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases, as well as various fellowships.