Video

CHICAGO – An integrated analysis of three trials has shown that larotrectinib, an oral selective inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers harboring TRK fusions, netting an impressive 76% overall response rate.

Lead study author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York, discussed highlights of the analysis, larotrectinib’s regulatory status, and implications for TRK fusion testing in clinical care at the annual meeting of the American Society of Clinical Oncology.

Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.

CHICAGO – An integrated analysis of three trials has shown that larotrectinib, an oral selective inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers harboring TRK fusions, netting an impressive 76% overall response rate.

Lead study author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York, discussed highlights of the analysis, larotrectinib’s regulatory status, and implications for TRK fusion testing in clinical care at the annual meeting of the American Society of Clinical Oncology.

Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.

CHICAGO – An integrated analysis of three trials has shown that larotrectinib, an oral selective inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers harboring TRK fusions, netting an impressive 76% overall response rate.

Lead study author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York, discussed highlights of the analysis, larotrectinib’s regulatory status, and implications for TRK fusion testing in clinical care at the annual meeting of the American Society of Clinical Oncology.

Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.

CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?

CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?

CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?

CHICAGO – Oncologists are highly skilled at minimizing side effects associated with toxic but curative therapies, but are less adept at helping patients cope with the distress, anxiety, fear, and other emotions associated with cancer.

Three studies presented at the annual meeting of the American Society of Clinical Oncology detail randomized, controlled trials of psychological interventions aimed at helping patients cope with a new cancer diagnosis, reduce fears of a recurrence, and come to grips with the realities of advanced disease, including fears of death or disability.

Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center, Boston, discusses the social and financial barriers that cancer patients face when they experience distress, and the difficulties that providers face with limited time and financial resources to help patients cope in this video interview.

Dr. Dizon reported having no relevant disclosures.

CHICAGO – Oncologists are highly skilled at minimizing side effects associated with toxic but curative therapies, but are less adept at helping patients cope with the distress, anxiety, fear, and other emotions associated with cancer.

Three studies presented at the annual meeting of the American Society of Clinical Oncology detail randomized, controlled trials of psychological interventions aimed at helping patients cope with a new cancer diagnosis, reduce fears of a recurrence, and come to grips with the realities of advanced disease, including fears of death or disability.

Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center, Boston, discusses the social and financial barriers that cancer patients face when they experience distress, and the difficulties that providers face with limited time and financial resources to help patients cope in this video interview.

Dr. Dizon reported having no relevant disclosures.

CHICAGO – Oncologists are highly skilled at minimizing side effects associated with toxic but curative therapies, but are less adept at helping patients cope with the distress, anxiety, fear, and other emotions associated with cancer.

Three studies presented at the annual meeting of the American Society of Clinical Oncology detail randomized, controlled trials of psychological interventions aimed at helping patients cope with a new cancer diagnosis, reduce fears of a recurrence, and come to grips with the realities of advanced disease, including fears of death or disability.

Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center, Boston, discusses the social and financial barriers that cancer patients face when they experience distress, and the difficulties that providers face with limited time and financial resources to help patients cope in this video interview.

Dr. Dizon reported having no relevant disclosures.

CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have been steadily declining, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health.

Watch our video interview with lead author Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, who reported the data at a press conference at the annual meeting of the American Society of Clinical Oncology.

mdales@frontlinemedcom.com
On Twitter @maryjodales

CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have been steadily declining, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health.

Watch our video interview with lead author Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, who reported the data at a press conference at the annual meeting of the American Society of Clinical Oncology.

mdales@frontlinemedcom.com
On Twitter @maryjodales

CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have been steadily declining, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health.

Watch our video interview with lead author Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, who reported the data at a press conference at the annual meeting of the American Society of Clinical Oncology.

mdales@frontlinemedcom.com
On Twitter @maryjodales

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

Visit the Society of Gynecologic Surgeons online: sgsonline.org

More videos from SGS:

• Approaches to isolating the uterine artery at its origin from the internal iliac artery
• Advanced techniques in cystectomy for mature cystic teratomas
• Novel classification of labial anatomy and evaluation in the treatment of labial agglutination
• Strategies for prophylactic oophoropexy
• Tips and tricks for open laparoscopy
• Complete colpectomy & colpocleisis: Model for simulation
• Natural orifice sacral colpopexy
• Alternative options for visualizing ureteral patency during intraoperative cystoscopy
• Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
• Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
• Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
• Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
• Laparoscopic cystectomy for large, bilateral ovarian dermoids
• Small bowel surgery for the benign gynecologist

Visit the Society of Gynecologic Surgeons online: sgsonline.org

More videos from SGS:

• Approaches to isolating the uterine artery at its origin from the internal iliac artery
• Advanced techniques in cystectomy for mature cystic teratomas
• Novel classification of labial anatomy and evaluation in the treatment of labial agglutination
• Strategies for prophylactic oophoropexy
• Tips and tricks for open laparoscopy
• Complete colpectomy & colpocleisis: Model for simulation
• Natural orifice sacral colpopexy
• Alternative options for visualizing ureteral patency during intraoperative cystoscopy
• Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
• Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
• Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
• Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
• Laparoscopic cystectomy for large, bilateral ovarian dermoids
• Small bowel surgery for the benign gynecologist

Visit the Society of Gynecologic Surgeons online: sgsonline.org

More videos from SGS:

• Approaches to isolating the uterine artery at its origin from the internal iliac artery
• Advanced techniques in cystectomy for mature cystic teratomas
• Novel classification of labial anatomy and evaluation in the treatment of labial agglutination
• Strategies for prophylactic oophoropexy
• Tips and tricks for open laparoscopy
• Complete colpectomy & colpocleisis: Model for simulation
• Natural orifice sacral colpopexy
• Alternative options for visualizing ureteral patency during intraoperative cystoscopy
• Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
• Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
• Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
• Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
• Laparoscopic cystectomy for large, bilateral ovarian dermoids
• Small bowel surgery for the benign gynecologist

Starting probiotics within 2 days of the first antibiotic dose could cut the risk of Clostridium difficile infection among hospitalized adults by more than 50%, according to the results of a systemic review and metaregression analysis.

The protective effect waned when patients delayed starting probiotics, reported Nicole T. Shen, MD, of Cornell University, New York, and her associates. The study appears in Gastroenterology (doi: 10.1053/j.gastro.2017.02.003). “Given the magnitude of benefit and the low cost of probiotics, the decision is likely to be highly cost effective,” they added.

Systematic reviews support the use of probiotics for preventing Clostridium difficile infection (CDI), but guidelines do not reflect these findings. To help guide clinical practice, the reviewers searched MEDLINE, EMBASE, the International Journal of Probiotics and Prebiotics, and the Cochrane Library databases for randomized controlled trials of probiotics and CDI among hospitalized adults taking antibiotics. This search yielded 19 published studies of 6,261 patients. Two reviewers separately extracted data from these studies and examined quality of evidence and risk of bias.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

A total of 54 patients in the probiotic cohort (1.6%) developed CDI, compared with 115 controls (3.9%), a statistically significant difference (P less than .001). In ­regression analysis, the probiotic group was about 58% less likely to develop CDI than controls (hazard ratio, 0.42; 95% confidence interval, 0.30-0.57; P less than .001). Importantly, probiotics were significantly effective against CDI only when started within 2 days of antibiotic initiation (relative risk, 0.32; 95% CI, 0.22-0.48), not when started within 3-7 days (RR, 0.70, 95% CI, 0.40-1.23). The difference between these estimated risk ratios was statistically significant (P = .02).

In 18 of the 19 studies, patients received probiotics within 3 days of starting antibiotics, while patients in the remaining study could start probiotics any time within 7 days of antibiotic initiation. “Not only was [this] study unusual with respect to probiotic timing, it was also much larger than all other studies, and its results were statistically insignificant,” the reviewers wrote. Metaregression analyses of all studies and of all but the outlier study linked delaying probiotics with a decrease in efficacy against CDI, with P values of .04 and .09, respectively. Those findings “suggest that the decrement in efficacy with delay in starting probiotics is not sensitive to inclusion of a single large ‘outlier’ study,” the reviewers emphasized. “In fact, inclusion only dampens the magnitude of the decrement in efficacy, although it is still clinically important and statistically significant.”

The trials included 12 probiotic formulas containing Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus, either alone or in combination. Probiotics were not associated with adverse effects in the trials. Quality of evidence was generally high, but seven trials had missing data on the primary outcome. Furthermore, two studies lacked a placebo group, and lead authors of two studies disclosed ties to the probiotic manufacturers that provided funding.

One reviewer received fellowship support from the Louis and Rachel Rudin Foundation. None had conflicts of interest.

Starting probiotics within 2 days of the first antibiotic dose could cut the risk of Clostridium difficile infection among hospitalized adults by more than 50%, according to the results of a systemic review and metaregression analysis.

The protective effect waned when patients delayed starting probiotics, reported Nicole T. Shen, MD, of Cornell University, New York, and her associates. The study appears in Gastroenterology (doi: 10.1053/j.gastro.2017.02.003). “Given the magnitude of benefit and the low cost of probiotics, the decision is likely to be highly cost effective,” they added.

Systematic reviews support the use of probiotics for preventing Clostridium difficile infection (CDI), but guidelines do not reflect these findings. To help guide clinical practice, the reviewers searched MEDLINE, EMBASE, the International Journal of Probiotics and Prebiotics, and the Cochrane Library databases for randomized controlled trials of probiotics and CDI among hospitalized adults taking antibiotics. This search yielded 19 published studies of 6,261 patients. Two reviewers separately extracted data from these studies and examined quality of evidence and risk of bias.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

A total of 54 patients in the probiotic cohort (1.6%) developed CDI, compared with 115 controls (3.9%), a statistically significant difference (P less than .001). In ­regression analysis, the probiotic group was about 58% less likely to develop CDI than controls (hazard ratio, 0.42; 95% confidence interval, 0.30-0.57; P less than .001). Importantly, probiotics were significantly effective against CDI only when started within 2 days of antibiotic initiation (relative risk, 0.32; 95% CI, 0.22-0.48), not when started within 3-7 days (RR, 0.70, 95% CI, 0.40-1.23). The difference between these estimated risk ratios was statistically significant (P = .02).

In 18 of the 19 studies, patients received probiotics within 3 days of starting antibiotics, while patients in the remaining study could start probiotics any time within 7 days of antibiotic initiation. “Not only was [this] study unusual with respect to probiotic timing, it was also much larger than all other studies, and its results were statistically insignificant,” the reviewers wrote. Metaregression analyses of all studies and of all but the outlier study linked delaying probiotics with a decrease in efficacy against CDI, with P values of .04 and .09, respectively. Those findings “suggest that the decrement in efficacy with delay in starting probiotics is not sensitive to inclusion of a single large ‘outlier’ study,” the reviewers emphasized. “In fact, inclusion only dampens the magnitude of the decrement in efficacy, although it is still clinically important and statistically significant.”

The trials included 12 probiotic formulas containing Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus, either alone or in combination. Probiotics were not associated with adverse effects in the trials. Quality of evidence was generally high, but seven trials had missing data on the primary outcome. Furthermore, two studies lacked a placebo group, and lead authors of two studies disclosed ties to the probiotic manufacturers that provided funding.

One reviewer received fellowship support from the Louis and Rachel Rudin Foundation. None had conflicts of interest.

Starting probiotics within 2 days of the first antibiotic dose could cut the risk of Clostridium difficile infection among hospitalized adults by more than 50%, according to the results of a systemic review and metaregression analysis.

The protective effect waned when patients delayed starting probiotics, reported Nicole T. Shen, MD, of Cornell University, New York, and her associates. The study appears in Gastroenterology (doi: 10.1053/j.gastro.2017.02.003). “Given the magnitude of benefit and the low cost of probiotics, the decision is likely to be highly cost effective,” they added.

Systematic reviews support the use of probiotics for preventing Clostridium difficile infection (CDI), but guidelines do not reflect these findings. To help guide clinical practice, the reviewers searched MEDLINE, EMBASE, the International Journal of Probiotics and Prebiotics, and the Cochrane Library databases for randomized controlled trials of probiotics and CDI among hospitalized adults taking antibiotics. This search yielded 19 published studies of 6,261 patients. Two reviewers separately extracted data from these studies and examined quality of evidence and risk of bias.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

A total of 54 patients in the probiotic cohort (1.6%) developed CDI, compared with 115 controls (3.9%), a statistically significant difference (P less than .001). In ­regression analysis, the probiotic group was about 58% less likely to develop CDI than controls (hazard ratio, 0.42; 95% confidence interval, 0.30-0.57; P less than .001). Importantly, probiotics were significantly effective against CDI only when started within 2 days of antibiotic initiation (relative risk, 0.32; 95% CI, 0.22-0.48), not when started within 3-7 days (RR, 0.70, 95% CI, 0.40-1.23). The difference between these estimated risk ratios was statistically significant (P = .02).

In 18 of the 19 studies, patients received probiotics within 3 days of starting antibiotics, while patients in the remaining study could start probiotics any time within 7 days of antibiotic initiation. “Not only was [this] study unusual with respect to probiotic timing, it was also much larger than all other studies, and its results were statistically insignificant,” the reviewers wrote. Metaregression analyses of all studies and of all but the outlier study linked delaying probiotics with a decrease in efficacy against CDI, with P values of .04 and .09, respectively. Those findings “suggest that the decrement in efficacy with delay in starting probiotics is not sensitive to inclusion of a single large ‘outlier’ study,” the reviewers emphasized. “In fact, inclusion only dampens the magnitude of the decrement in efficacy, although it is still clinically important and statistically significant.”

The trials included 12 probiotic formulas containing Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus, either alone or in combination. Probiotics were not associated with adverse effects in the trials. Quality of evidence was generally high, but seven trials had missing data on the primary outcome. Furthermore, two studies lacked a placebo group, and lead authors of two studies disclosed ties to the probiotic manufacturers that provided funding.

One reviewer received fellowship support from the Louis and Rachel Rudin Foundation. None had conflicts of interest.

WASHINGTON – Researchers have devised a program that can predict severe sepsis or septic shock about 12-30 hours in advance of its onset in hospitalized patients, a feat they hope will allow them to apply early interventions to stave off impending sepsis.

“We’d love to see a change in sepsis mortality. Will earlier recognition and implementation of the sepsis bundle – fluids, antibiotics, etc. – improve outcomes?” wondered Heather M. Giannini, MD, in a video interview at an international conference of the American Thoracic Society.

The computer program works by monitoring all the data that enter a patient’s electronic health record during hospitalization. Researchers developed it and designed it specifically for inpatients who are not in the intensive care unit or emergency department.

Results from initial testing during October-December 2015 in 10,448 patients hospitalized at one of three participating Philadelphia hospitals showed the program predicted subsequent severe sepsis or septic shock with a sensitivity of 26% and a specificity of 98%, reported Dr. Giannini, a researcher in the Center for Evidence-Based Practice at the University of Pennsylvania in Philadelphia. Analysis also showed a positive likelihood ratio of 13 for severe sepsis or septic shock actually occurring following an alert generated by the computer program, a level indicating a “very strong” ability to predict sepsis, she said.

Dr. Giannini and her associates developed the prediction program using a technique called “computational machine learning,” an alternative to standard logistic regression modeling that is better suited to analyzing large data sets and can better integrate outlier data points. They took EHR data for all non-ICU, non-ED inpatients at three Philadelphia hospitals during a 3-year period during 2011-2014 and had the program focus particularly on EHR data gleaned from the nearly 1,000 patients who developed severe sepsis or septic shock during the 12 hours preceding the start of these sepsis events. The analysis identified patients as having developed severe sepsis or shock if they had a blood draw positive for infection at the same time as having a blood lactate level above 2.2 mmol/L or a systolic blood pressure below 90 mm Hg.

To create the algorithm the machine-learning device compared the EHR entries for patients who developed severe sepsis or septic shock with EHR data from patients who did not, a process that involved hundred of thousands of data points, Dr. Giannini said. This identified 587 individual types of relevant EHR data entries and ranked them from most important to least important. Important, novel determinants of impending severe sepsis identified this way included anion gap, blood urea nitrogen, and platelet count. The development process also confirmed an important role for many classic markers of septic shock, such as respiration rate, heart rate, and temperature.

The researchers designed the algorithm to have a moderate level of sensitivity to avoid “alert fatigue” from generating too many alarms for impending severe sepsis. Their goal was for clinicians to receive no more than about 10 alerts per day for each hospital.

“We are satisfied with the sensitivity. We felt it was better to have too few alerts rather than overwhelm clinicians. About 10 alerts a day is reasonable,” Dr. Giannini explained. During initial 2015 testing, the system generated a daily average of 11 alerts.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

WASHINGTON – Researchers have devised a program that can predict severe sepsis or septic shock about 12-30 hours in advance of its onset in hospitalized patients, a feat they hope will allow them to apply early interventions to stave off impending sepsis.

“We’d love to see a change in sepsis mortality. Will earlier recognition and implementation of the sepsis bundle – fluids, antibiotics, etc. – improve outcomes?” wondered Heather M. Giannini, MD, in a video interview at an international conference of the American Thoracic Society.

The computer program works by monitoring all the data that enter a patient’s electronic health record during hospitalization. Researchers developed it and designed it specifically for inpatients who are not in the intensive care unit or emergency department.

Results from initial testing during October-December 2015 in 10,448 patients hospitalized at one of three participating Philadelphia hospitals showed the program predicted subsequent severe sepsis or septic shock with a sensitivity of 26% and a specificity of 98%, reported Dr. Giannini, a researcher in the Center for Evidence-Based Practice at the University of Pennsylvania in Philadelphia. Analysis also showed a positive likelihood ratio of 13 for severe sepsis or septic shock actually occurring following an alert generated by the computer program, a level indicating a “very strong” ability to predict sepsis, she said.

Dr. Giannini and her associates developed the prediction program using a technique called “computational machine learning,” an alternative to standard logistic regression modeling that is better suited to analyzing large data sets and can better integrate outlier data points. They took EHR data for all non-ICU, non-ED inpatients at three Philadelphia hospitals during a 3-year period during 2011-2014 and had the program focus particularly on EHR data gleaned from the nearly 1,000 patients who developed severe sepsis or septic shock during the 12 hours preceding the start of these sepsis events. The analysis identified patients as having developed severe sepsis or shock if they had a blood draw positive for infection at the same time as having a blood lactate level above 2.2 mmol/L or a systolic blood pressure below 90 mm Hg.

To create the algorithm the machine-learning device compared the EHR entries for patients who developed severe sepsis or septic shock with EHR data from patients who did not, a process that involved hundred of thousands of data points, Dr. Giannini said. This identified 587 individual types of relevant EHR data entries and ranked them from most important to least important. Important, novel determinants of impending severe sepsis identified this way included anion gap, blood urea nitrogen, and platelet count. The development process also confirmed an important role for many classic markers of septic shock, such as respiration rate, heart rate, and temperature.

The researchers designed the algorithm to have a moderate level of sensitivity to avoid “alert fatigue” from generating too many alarms for impending severe sepsis. Their goal was for clinicians to receive no more than about 10 alerts per day for each hospital.

“We are satisfied with the sensitivity. We felt it was better to have too few alerts rather than overwhelm clinicians. About 10 alerts a day is reasonable,” Dr. Giannini explained. During initial 2015 testing, the system generated a daily average of 11 alerts.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

WASHINGTON – Researchers have devised a program that can predict severe sepsis or septic shock about 12-30 hours in advance of its onset in hospitalized patients, a feat they hope will allow them to apply early interventions to stave off impending sepsis.

“We’d love to see a change in sepsis mortality. Will earlier recognition and implementation of the sepsis bundle – fluids, antibiotics, etc. – improve outcomes?” wondered Heather M. Giannini, MD, in a video interview at an international conference of the American Thoracic Society.

The computer program works by monitoring all the data that enter a patient’s electronic health record during hospitalization. Researchers developed it and designed it specifically for inpatients who are not in the intensive care unit or emergency department.

Results from initial testing during October-December 2015 in 10,448 patients hospitalized at one of three participating Philadelphia hospitals showed the program predicted subsequent severe sepsis or septic shock with a sensitivity of 26% and a specificity of 98%, reported Dr. Giannini, a researcher in the Center for Evidence-Based Practice at the University of Pennsylvania in Philadelphia. Analysis also showed a positive likelihood ratio of 13 for severe sepsis or septic shock actually occurring following an alert generated by the computer program, a level indicating a “very strong” ability to predict sepsis, she said.

Dr. Giannini and her associates developed the prediction program using a technique called “computational machine learning,” an alternative to standard logistic regression modeling that is better suited to analyzing large data sets and can better integrate outlier data points. They took EHR data for all non-ICU, non-ED inpatients at three Philadelphia hospitals during a 3-year period during 2011-2014 and had the program focus particularly on EHR data gleaned from the nearly 1,000 patients who developed severe sepsis or septic shock during the 12 hours preceding the start of these sepsis events. The analysis identified patients as having developed severe sepsis or shock if they had a blood draw positive for infection at the same time as having a blood lactate level above 2.2 mmol/L or a systolic blood pressure below 90 mm Hg.

To create the algorithm the machine-learning device compared the EHR entries for patients who developed severe sepsis or septic shock with EHR data from patients who did not, a process that involved hundred of thousands of data points, Dr. Giannini said. This identified 587 individual types of relevant EHR data entries and ranked them from most important to least important. Important, novel determinants of impending severe sepsis identified this way included anion gap, blood urea nitrogen, and platelet count. The development process also confirmed an important role for many classic markers of septic shock, such as respiration rate, heart rate, and temperature.

The researchers designed the algorithm to have a moderate level of sensitivity to avoid “alert fatigue” from generating too many alarms for impending severe sepsis. Their goal was for clinicians to receive no more than about 10 alerts per day for each hospital.

“We are satisfied with the sensitivity. We felt it was better to have too few alerts rather than overwhelm clinicians. About 10 alerts a day is reasonable,” Dr. Giannini explained. During initial 2015 testing, the system generated a daily average of 11 alerts.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VANCOUVER – Although symptoms can start young in endometriosis – sometimes in adolescence – women often suffer for years from bowel problems, pain, dyspareunia, and other complications before the condition is recognized and addressed.

Endometriosis can be “a monster of a disease,” especially if it’s not recognized early, said Deborah Bush, cofounder and CEO of the patient advocacy group Endometriosis New Zealand.

To help, she and her colleagues started an education program in New Zealand to teach secondary school students how to recognize – and seek help – when menstrual symptoms fall outside the norm.

In an interview at the World Congress on Endometriosis, Ms. Bush explained the importance of such efforts, and the impact they’ve had in New Zealand over the past 20 years (Aust N Z J Obstet Gynaecol. 2017 Mar 28. doi: 10.1111/ajo.12614).

She also gave an example from her own endometriosis consulting practice of what it took to turn around a patient who had been suffering with the disease for 15 years. Treatment had to move far beyond pelvic lesions.

aotto@frontlinemedcom.com

VANCOUVER – Although symptoms can start young in endometriosis – sometimes in adolescence – women often suffer for years from bowel problems, pain, dyspareunia, and other complications before the condition is recognized and addressed.

Endometriosis can be “a monster of a disease,” especially if it’s not recognized early, said Deborah Bush, cofounder and CEO of the patient advocacy group Endometriosis New Zealand.

To help, she and her colleagues started an education program in New Zealand to teach secondary school students how to recognize – and seek help – when menstrual symptoms fall outside the norm.

In an interview at the World Congress on Endometriosis, Ms. Bush explained the importance of such efforts, and the impact they’ve had in New Zealand over the past 20 years (Aust N Z J Obstet Gynaecol. 2017 Mar 28. doi: 10.1111/ajo.12614).

She also gave an example from her own endometriosis consulting practice of what it took to turn around a patient who had been suffering with the disease for 15 years. Treatment had to move far beyond pelvic lesions.

aotto@frontlinemedcom.com

VANCOUVER – Although symptoms can start young in endometriosis – sometimes in adolescence – women often suffer for years from bowel problems, pain, dyspareunia, and other complications before the condition is recognized and addressed.

Endometriosis can be “a monster of a disease,” especially if it’s not recognized early, said Deborah Bush, cofounder and CEO of the patient advocacy group Endometriosis New Zealand.

To help, she and her colleagues started an education program in New Zealand to teach secondary school students how to recognize – and seek help – when menstrual symptoms fall outside the norm.

In an interview at the World Congress on Endometriosis, Ms. Bush explained the importance of such efforts, and the impact they’ve had in New Zealand over the past 20 years (Aust N Z J Obstet Gynaecol. 2017 Mar 28. doi: 10.1111/ajo.12614).

She also gave an example from her own endometriosis consulting practice of what it took to turn around a patient who had been suffering with the disease for 15 years. Treatment had to move far beyond pelvic lesions.

aotto@frontlinemedcom.com

VANCOUVER – To define the top 10 research priorities in endometriosis, researchers at the University of Edinburgh, Scotland, and their colleagues did something unusual in the world of medical science. They asked the women who have the disease.

More than 70% of the 1,225 people initially surveyed to define what most needs to be figured out in endometriosis were patients, and most of the rest were clinicians who take care of them. Patients were involved throughout an exhaustive process that whittled down nearly 5,000 initial suggestions to a list of 10 priorities.

The first priority is to determine if endometriosis can be cured, and the second task is to find its cause (Lancet. 2017 May 18. doi: 10.1016/S0140-6736(17)31344-2).

Women who have endometriosis said they want a noninvasive diagnostic test. They also want help managing the emotional and physical impacts of living with the disease, not simply treatments that focus on lesions, according to Andrew Horne, MBChB, PhD, a professor of gynecology and reproductive sciences at the University of Edinburgh, who led the efforts.

In an interview at the World Congress on Endometriosis, Dr. Horne explained why it’s critical to define the top research priorities and what doing so could mean for patients and doctors. He also explained the importance of a recent insight into the pathogenesis of endometriosis: It behaves like cancer.

aotto@frontlinemedcom.com

VANCOUVER – To define the top 10 research priorities in endometriosis, researchers at the University of Edinburgh, Scotland, and their colleagues did something unusual in the world of medical science. They asked the women who have the disease.

More than 70% of the 1,225 people initially surveyed to define what most needs to be figured out in endometriosis were patients, and most of the rest were clinicians who take care of them. Patients were involved throughout an exhaustive process that whittled down nearly 5,000 initial suggestions to a list of 10 priorities.

The first priority is to determine if endometriosis can be cured, and the second task is to find its cause (Lancet. 2017 May 18. doi: 10.1016/S0140-6736(17)31344-2).

Women who have endometriosis said they want a noninvasive diagnostic test. They also want help managing the emotional and physical impacts of living with the disease, not simply treatments that focus on lesions, according to Andrew Horne, MBChB, PhD, a professor of gynecology and reproductive sciences at the University of Edinburgh, who led the efforts.

In an interview at the World Congress on Endometriosis, Dr. Horne explained why it’s critical to define the top research priorities and what doing so could mean for patients and doctors. He also explained the importance of a recent insight into the pathogenesis of endometriosis: It behaves like cancer.

aotto@frontlinemedcom.com

VANCOUVER – To define the top 10 research priorities in endometriosis, researchers at the University of Edinburgh, Scotland, and their colleagues did something unusual in the world of medical science. They asked the women who have the disease.

More than 70% of the 1,225 people initially surveyed to define what most needs to be figured out in endometriosis were patients, and most of the rest were clinicians who take care of them. Patients were involved throughout an exhaustive process that whittled down nearly 5,000 initial suggestions to a list of 10 priorities.

The first priority is to determine if endometriosis can be cured, and the second task is to find its cause (Lancet. 2017 May 18. doi: 10.1016/S0140-6736(17)31344-2).

Women who have endometriosis said they want a noninvasive diagnostic test. They also want help managing the emotional and physical impacts of living with the disease, not simply treatments that focus on lesions, according to Andrew Horne, MBChB, PhD, a professor of gynecology and reproductive sciences at the University of Edinburgh, who led the efforts.

In an interview at the World Congress on Endometriosis, Dr. Horne explained why it’s critical to define the top research priorities and what doing so could mean for patients and doctors. He also explained the importance of a recent insight into the pathogenesis of endometriosis: It behaves like cancer.

aotto@frontlinemedcom.com