BERLIN – An investigational oral formulation of the glucagonlike peptide–1 receptor agonist (GLP-1 RA) semaglutide reduced glycated hemoglobin (HbA_1c) to a greater extent than did placebo at all doses tested in patients with type 2 diabetes mellitus (T2DM) in the phase 3a PIONEER 1 trial.

The estimated mean change in HbA_1c from baseline to week 26 – the primary endpoint – using an on-treatment analysis was –0.8% with a once-daily dose of 3 mg, –1.3% with a once-daily dose of 7 mg, and –1.5% with a once-daily dose of 14 mg. The corresponding value for placebo was –0.1%, with all comparisons statistically significant (P less than .001).

The on-treatment analysis evaluated treatment effects for all randomized patients (n = 703) and assumed that all subjects remained on-treatment and excluded the effect of any rescue medication. Results for an intention-to-treat (ITT) analysis provided similar results, however, with estimated mean changes in HbA_1c of –0.9%, –1.2%, and –1.4% for the three respective semaglutide doses and –0.3% for placebo.

“There was a very nice dose-dependent decrease in HbA_1c, which was superior to placebo for all doses of semaglutide” said study investigator Martin Haluzík, MD, at the annual meeting of the European Association for the Study of Diabetes.

“I think it’s quite important to stress the magnitude of the decrease of HbA_1c, because with the highest dose it was –1.5% from a baseline of 8%, which I believe is something that hasn’t ever really been seen with any other oral antidiabetic medication,” added Dr. Haluzík, professor of internal medicine at the 1st Faculty of Medicine at Charles University and deputy head of the Institute for Clinical and Experimental Medicine, both in Prague.

Currently, GLP-1 RAs are available only in a subcutaneous formulation, Dr. Haluzík reminded his audience, adding that oral semaglutide was the first GLP-1 RA to be developed in a tablet formulation and was in the late stages of clinical development.

PIONEER 1 is the first of 10 phase 3a trials with oral semaglutide to be reported. “Additional studies, across the full spectrum of diabetes care, in special populations, comparing it with active comparators with varied trial duration, have been completed or will be completed in 2018,” said coinvestigator for the study Vanita Aroda, MD, during a separate presentation at a dedicated symposium on the PIONEER program.

Dr. Aroda, the director of the diabetes research program at Brigham and Women’s Hospital in Boston, observed that oral semaglutide was being evaluated from early care as monotherapy in the PIONEER 1 study. The other trials, such as PIONEER 2, PIONEER 3, PIONEER 4, and PIONEER 7 were looking at oral semaglutide in combination with oral antidiabetic agents versus various active comparators; PIONEER 5 and PIONEER 6 were in special populations; and PIONEER 8 was looking at its use on top of basal insulin. Two further trials are also part of the study program.

“I think this is the first time that we actually have completed data of an entire program, including cardiovascular data, all within the same year,” Dr. Aroda said. “All of the studies are in the process of data analysis or data reporting.”

PIONEER 1 was a multicenter, randomized, double-blind, placebo-controlled trial examining efficacy and safety of semaglutide versus placebo in 703 adults with drug-naive T2DM who were being treated with diet and exercise only.

Three doses of oral semaglutide – 3 mg, 7 mg, and 14 mg – were assessed and compared with placebo. There was a fixed 4-week dose escalation period, with all patients starting treatment with 3 mg of semaglutide and then increasing to 7 mg by week 4 and 14 mg by week 8. This was to try to reduce the risk of gastrointestinal side effects, which are known to occur with GLP-1 RAs.

Secondary outcome measures were change in body weight, fasting plasma glucose, HbA_1c below a target of 7% (53 mmol/mol), which were all measured from baseline to week 26; adverse events, including severe and blood glucose–confirmed symptomatic hypoglycemic episodes, were assessed out to week 31.

The average age of patients in the trial was around 55 years, around half were female, and the starting HbA_1c was approximately 8%.The mean body weight ranged from 86.9 kg to 89 kg in the different treatment groups, with a similar body mass index of about 32 kg/m².

Clinically meaningful weight loss, compared with placebo, was only achieved with the highest dose of oral semaglutide, with a –4.1 kg reduction versus –1.5 kg for placebo from baseline to week 26 (P less than .001, on-treatment analysis). Reductions in body weight for the 3-mg and 7-mg oral semaglutide doses were a respective –1.7 kg and –2.5 kg. ITT results were again similar, with weight losses of –1.5, –2.3, and –3.7 kg for the 3-, 7-, and 14-mg doses of oral semaglutide, respectively, and –1.4 kg for placebo.

More patients treated with oral semaglutide 3, 7, or 14 mg versus placebo achieved an HbA_1c of below 7% (59.1%, 71.9%, and 80.3%, respectively, vs. 33.8%) or a body weight loss of 5% or more (21.3%, 28.7%, and 44.3% vs. 15.7%).

Furthermore, more patients treated with oral semaglutide achieved an HbA_1c of or below 7% without hypoglycemic episodes or body weight gain than did those given placebo. There were also more patients who achieved an HbA_1c reduction of at least 1% and a weight loss of 3% or higher.

“Oral semaglutide demonstrated a safety and tolerability profile consistent with that of [injectable] GLP-1 RAs,” Dr. Haluzík reported. Adverse events were seen in 57.7%, 53.1%, and 56.6%of patients treated with 3, 7, and 14 mg of oral semaglutide and 55.6% of those treated with placebo.

The most common adverse events seen with oral semaglutide affected the gastrointestinal tract, with nausea affecting 8%, 5.1%, and 16% of 3, 7, and 14 mg–treated patients versus 5.6% of placebo-treated patients. Vomiting affected a respective 2.9%, 4.6%, 6.9%, and 2.1%, and diarrhea a respective 8.6%, 5.1%, 5.1%, and 2.2%.

Severe or blood glucose–confirmed, symptomatic hypoglycemia was reported in 2.9%, 1.1%, and 0.6%of those treated with 3, 7, 14 mg of oral semaglutide and 0.6% of placebo-treated patients.

PIONEER 1 represents a “step change in GLP-1 receptor agonist therapy”, said Cliff Bailey, MD, who discussed the trial aa the EASD’s independent commentator during a symposium on the PIONEER program. These data are “leading to a new delivery route for GLP-1 receptor agonists, from injection to oral,” and “this can be done with good metabolic efficacy, with substantial reductions in A_1c and body weight, and with a safety profile that’s comparable to the subcutaneous injection.”

Dr. Bailey, who is professor of clinical science at Aston University in Birmingham, England, noted, however, the oral dosing of semaglutide “requires patient commitment because it needs to be taken before breakfast time, and it may also, to some extent, affect the timing of some of the other medications.”

The study was sponsored by Novo Nordisk. Dr. Haluzík disclosed acting as a consultant to AstraZeneca, Eli Lilly, Johnson & Johnson, Mundipharma, Novatin, Novo Nordisk, and Sanofi Aventis. Dr. Aroda was an investigator in the PIONEER 1 study and disclosed acting as a consultant to Novo Nordisk; she also disclosed relationships with multiple other pharmaceutical companies, including AstraZeneca, BMS, Calbra, Eisai, Elcelyx Therapeutics, Janssen, and Sanofi Aventis. Dr. Bailey acknowledged attending advisory boards, undertaking ad hoc consultancy work, and receiving research and travel support from several pharmaceutical companies that included Novo Nordisk.

SOURCES: Haluzík M et al. EASD 2018, Abstract 38; Aroda V. EASD 2018, Session S18 - PIONEER Trial; Bailey C. EASD 2018, Session S18 - PIONEER Trial.

BERLIN – An investigational oral formulation of the glucagonlike peptide–1 receptor agonist (GLP-1 RA) semaglutide reduced glycated hemoglobin (HbA_1c) to a greater extent than did placebo at all doses tested in patients with type 2 diabetes mellitus (T2DM) in the phase 3a PIONEER 1 trial.

The estimated mean change in HbA_1c from baseline to week 26 – the primary endpoint – using an on-treatment analysis was –0.8% with a once-daily dose of 3 mg, –1.3% with a once-daily dose of 7 mg, and –1.5% with a once-daily dose of 14 mg. The corresponding value for placebo was –0.1%, with all comparisons statistically significant (P less than .001).

The on-treatment analysis evaluated treatment effects for all randomized patients (n = 703) and assumed that all subjects remained on-treatment and excluded the effect of any rescue medication. Results for an intention-to-treat (ITT) analysis provided similar results, however, with estimated mean changes in HbA_1c of –0.9%, –1.2%, and –1.4% for the three respective semaglutide doses and –0.3% for placebo.

“There was a very nice dose-dependent decrease in HbA_1c, which was superior to placebo for all doses of semaglutide” said study investigator Martin Haluzík, MD, at the annual meeting of the European Association for the Study of Diabetes.

“I think it’s quite important to stress the magnitude of the decrease of HbA_1c, because with the highest dose it was –1.5% from a baseline of 8%, which I believe is something that hasn’t ever really been seen with any other oral antidiabetic medication,” added Dr. Haluzík, professor of internal medicine at the 1st Faculty of Medicine at Charles University and deputy head of the Institute for Clinical and Experimental Medicine, both in Prague.

Currently, GLP-1 RAs are available only in a subcutaneous formulation, Dr. Haluzík reminded his audience, adding that oral semaglutide was the first GLP-1 RA to be developed in a tablet formulation and was in the late stages of clinical development.

PIONEER 1 is the first of 10 phase 3a trials with oral semaglutide to be reported. “Additional studies, across the full spectrum of diabetes care, in special populations, comparing it with active comparators with varied trial duration, have been completed or will be completed in 2018,” said coinvestigator for the study Vanita Aroda, MD, during a separate presentation at a dedicated symposium on the PIONEER program.

Dr. Aroda, the director of the diabetes research program at Brigham and Women’s Hospital in Boston, observed that oral semaglutide was being evaluated from early care as monotherapy in the PIONEER 1 study. The other trials, such as PIONEER 2, PIONEER 3, PIONEER 4, and PIONEER 7 were looking at oral semaglutide in combination with oral antidiabetic agents versus various active comparators; PIONEER 5 and PIONEER 6 were in special populations; and PIONEER 8 was looking at its use on top of basal insulin. Two further trials are also part of the study program.

“I think this is the first time that we actually have completed data of an entire program, including cardiovascular data, all within the same year,” Dr. Aroda said. “All of the studies are in the process of data analysis or data reporting.”

PIONEER 1 was a multicenter, randomized, double-blind, placebo-controlled trial examining efficacy and safety of semaglutide versus placebo in 703 adults with drug-naive T2DM who were being treated with diet and exercise only.

Three doses of oral semaglutide – 3 mg, 7 mg, and 14 mg – were assessed and compared with placebo. There was a fixed 4-week dose escalation period, with all patients starting treatment with 3 mg of semaglutide and then increasing to 7 mg by week 4 and 14 mg by week 8. This was to try to reduce the risk of gastrointestinal side effects, which are known to occur with GLP-1 RAs.

Secondary outcome measures were change in body weight, fasting plasma glucose, HbA_1c below a target of 7% (53 mmol/mol), which were all measured from baseline to week 26; adverse events, including severe and blood glucose–confirmed symptomatic hypoglycemic episodes, were assessed out to week 31.

The average age of patients in the trial was around 55 years, around half were female, and the starting HbA_1c was approximately 8%.The mean body weight ranged from 86.9 kg to 89 kg in the different treatment groups, with a similar body mass index of about 32 kg/m².

Clinically meaningful weight loss, compared with placebo, was only achieved with the highest dose of oral semaglutide, with a –4.1 kg reduction versus –1.5 kg for placebo from baseline to week 26 (P less than .001, on-treatment analysis). Reductions in body weight for the 3-mg and 7-mg oral semaglutide doses were a respective –1.7 kg and –2.5 kg. ITT results were again similar, with weight losses of –1.5, –2.3, and –3.7 kg for the 3-, 7-, and 14-mg doses of oral semaglutide, respectively, and –1.4 kg for placebo.

More patients treated with oral semaglutide 3, 7, or 14 mg versus placebo achieved an HbA_1c of below 7% (59.1%, 71.9%, and 80.3%, respectively, vs. 33.8%) or a body weight loss of 5% or more (21.3%, 28.7%, and 44.3% vs. 15.7%).

Furthermore, more patients treated with oral semaglutide achieved an HbA_1c of or below 7% without hypoglycemic episodes or body weight gain than did those given placebo. There were also more patients who achieved an HbA_1c reduction of at least 1% and a weight loss of 3% or higher.

“Oral semaglutide demonstrated a safety and tolerability profile consistent with that of [injectable] GLP-1 RAs,” Dr. Haluzík reported. Adverse events were seen in 57.7%, 53.1%, and 56.6%of patients treated with 3, 7, and 14 mg of oral semaglutide and 55.6% of those treated with placebo.

The most common adverse events seen with oral semaglutide affected the gastrointestinal tract, with nausea affecting 8%, 5.1%, and 16% of 3, 7, and 14 mg–treated patients versus 5.6% of placebo-treated patients. Vomiting affected a respective 2.9%, 4.6%, 6.9%, and 2.1%, and diarrhea a respective 8.6%, 5.1%, 5.1%, and 2.2%.

Severe or blood glucose–confirmed, symptomatic hypoglycemia was reported in 2.9%, 1.1%, and 0.6%of those treated with 3, 7, 14 mg of oral semaglutide and 0.6% of placebo-treated patients.

PIONEER 1 represents a “step change in GLP-1 receptor agonist therapy”, said Cliff Bailey, MD, who discussed the trial aa the EASD’s independent commentator during a symposium on the PIONEER program. These data are “leading to a new delivery route for GLP-1 receptor agonists, from injection to oral,” and “this can be done with good metabolic efficacy, with substantial reductions in A_1c and body weight, and with a safety profile that’s comparable to the subcutaneous injection.”

Dr. Bailey, who is professor of clinical science at Aston University in Birmingham, England, noted, however, the oral dosing of semaglutide “requires patient commitment because it needs to be taken before breakfast time, and it may also, to some extent, affect the timing of some of the other medications.”

The study was sponsored by Novo Nordisk. Dr. Haluzík disclosed acting as a consultant to AstraZeneca, Eli Lilly, Johnson & Johnson, Mundipharma, Novatin, Novo Nordisk, and Sanofi Aventis. Dr. Aroda was an investigator in the PIONEER 1 study and disclosed acting as a consultant to Novo Nordisk; she also disclosed relationships with multiple other pharmaceutical companies, including AstraZeneca, BMS, Calbra, Eisai, Elcelyx Therapeutics, Janssen, and Sanofi Aventis. Dr. Bailey acknowledged attending advisory boards, undertaking ad hoc consultancy work, and receiving research and travel support from several pharmaceutical companies that included Novo Nordisk.

SOURCES: Haluzík M et al. EASD 2018, Abstract 38; Aroda V. EASD 2018, Session S18 - PIONEER Trial; Bailey C. EASD 2018, Session S18 - PIONEER Trial.

BERLIN – An investigational oral formulation of the glucagonlike peptide–1 receptor agonist (GLP-1 RA) semaglutide reduced glycated hemoglobin (HbA_1c) to a greater extent than did placebo at all doses tested in patients with type 2 diabetes mellitus (T2DM) in the phase 3a PIONEER 1 trial.

The estimated mean change in HbA_1c from baseline to week 26 – the primary endpoint – using an on-treatment analysis was –0.8% with a once-daily dose of 3 mg, –1.3% with a once-daily dose of 7 mg, and –1.5% with a once-daily dose of 14 mg. The corresponding value for placebo was –0.1%, with all comparisons statistically significant (P less than .001).

The on-treatment analysis evaluated treatment effects for all randomized patients (n = 703) and assumed that all subjects remained on-treatment and excluded the effect of any rescue medication. Results for an intention-to-treat (ITT) analysis provided similar results, however, with estimated mean changes in HbA_1c of –0.9%, –1.2%, and –1.4% for the three respective semaglutide doses and –0.3% for placebo.

“There was a very nice dose-dependent decrease in HbA_1c, which was superior to placebo for all doses of semaglutide” said study investigator Martin Haluzík, MD, at the annual meeting of the European Association for the Study of Diabetes.

“I think it’s quite important to stress the magnitude of the decrease of HbA_1c, because with the highest dose it was –1.5% from a baseline of 8%, which I believe is something that hasn’t ever really been seen with any other oral antidiabetic medication,” added Dr. Haluzík, professor of internal medicine at the 1st Faculty of Medicine at Charles University and deputy head of the Institute for Clinical and Experimental Medicine, both in Prague.

Currently, GLP-1 RAs are available only in a subcutaneous formulation, Dr. Haluzík reminded his audience, adding that oral semaglutide was the first GLP-1 RA to be developed in a tablet formulation and was in the late stages of clinical development.

PIONEER 1 is the first of 10 phase 3a trials with oral semaglutide to be reported. “Additional studies, across the full spectrum of diabetes care, in special populations, comparing it with active comparators with varied trial duration, have been completed or will be completed in 2018,” said coinvestigator for the study Vanita Aroda, MD, during a separate presentation at a dedicated symposium on the PIONEER program.

Dr. Aroda, the director of the diabetes research program at Brigham and Women’s Hospital in Boston, observed that oral semaglutide was being evaluated from early care as monotherapy in the PIONEER 1 study. The other trials, such as PIONEER 2, PIONEER 3, PIONEER 4, and PIONEER 7 were looking at oral semaglutide in combination with oral antidiabetic agents versus various active comparators; PIONEER 5 and PIONEER 6 were in special populations; and PIONEER 8 was looking at its use on top of basal insulin. Two further trials are also part of the study program.

“I think this is the first time that we actually have completed data of an entire program, including cardiovascular data, all within the same year,” Dr. Aroda said. “All of the studies are in the process of data analysis or data reporting.”

PIONEER 1 was a multicenter, randomized, double-blind, placebo-controlled trial examining efficacy and safety of semaglutide versus placebo in 703 adults with drug-naive T2DM who were being treated with diet and exercise only.

Three doses of oral semaglutide – 3 mg, 7 mg, and 14 mg – were assessed and compared with placebo. There was a fixed 4-week dose escalation period, with all patients starting treatment with 3 mg of semaglutide and then increasing to 7 mg by week 4 and 14 mg by week 8. This was to try to reduce the risk of gastrointestinal side effects, which are known to occur with GLP-1 RAs.

Secondary outcome measures were change in body weight, fasting plasma glucose, HbA_1c below a target of 7% (53 mmol/mol), which were all measured from baseline to week 26; adverse events, including severe and blood glucose–confirmed symptomatic hypoglycemic episodes, were assessed out to week 31.

The average age of patients in the trial was around 55 years, around half were female, and the starting HbA_1c was approximately 8%.The mean body weight ranged from 86.9 kg to 89 kg in the different treatment groups, with a similar body mass index of about 32 kg/m².

Clinically meaningful weight loss, compared with placebo, was only achieved with the highest dose of oral semaglutide, with a –4.1 kg reduction versus –1.5 kg for placebo from baseline to week 26 (P less than .001, on-treatment analysis). Reductions in body weight for the 3-mg and 7-mg oral semaglutide doses were a respective –1.7 kg and –2.5 kg. ITT results were again similar, with weight losses of –1.5, –2.3, and –3.7 kg for the 3-, 7-, and 14-mg doses of oral semaglutide, respectively, and –1.4 kg for placebo.

More patients treated with oral semaglutide 3, 7, or 14 mg versus placebo achieved an HbA_1c of below 7% (59.1%, 71.9%, and 80.3%, respectively, vs. 33.8%) or a body weight loss of 5% or more (21.3%, 28.7%, and 44.3% vs. 15.7%).

Furthermore, more patients treated with oral semaglutide achieved an HbA_1c of or below 7% without hypoglycemic episodes or body weight gain than did those given placebo. There were also more patients who achieved an HbA_1c reduction of at least 1% and a weight loss of 3% or higher.

“Oral semaglutide demonstrated a safety and tolerability profile consistent with that of [injectable] GLP-1 RAs,” Dr. Haluzík reported. Adverse events were seen in 57.7%, 53.1%, and 56.6%of patients treated with 3, 7, and 14 mg of oral semaglutide and 55.6% of those treated with placebo.

The most common adverse events seen with oral semaglutide affected the gastrointestinal tract, with nausea affecting 8%, 5.1%, and 16% of 3, 7, and 14 mg–treated patients versus 5.6% of placebo-treated patients. Vomiting affected a respective 2.9%, 4.6%, 6.9%, and 2.1%, and diarrhea a respective 8.6%, 5.1%, 5.1%, and 2.2%.

Severe or blood glucose–confirmed, symptomatic hypoglycemia was reported in 2.9%, 1.1%, and 0.6%of those treated with 3, 7, 14 mg of oral semaglutide and 0.6% of placebo-treated patients.

PIONEER 1 represents a “step change in GLP-1 receptor agonist therapy”, said Cliff Bailey, MD, who discussed the trial aa the EASD’s independent commentator during a symposium on the PIONEER program. These data are “leading to a new delivery route for GLP-1 receptor agonists, from injection to oral,” and “this can be done with good metabolic efficacy, with substantial reductions in A_1c and body weight, and with a safety profile that’s comparable to the subcutaneous injection.”

Dr. Bailey, who is professor of clinical science at Aston University in Birmingham, England, noted, however, the oral dosing of semaglutide “requires patient commitment because it needs to be taken before breakfast time, and it may also, to some extent, affect the timing of some of the other medications.”

The study was sponsored by Novo Nordisk. Dr. Haluzík disclosed acting as a consultant to AstraZeneca, Eli Lilly, Johnson & Johnson, Mundipharma, Novatin, Novo Nordisk, and Sanofi Aventis. Dr. Aroda was an investigator in the PIONEER 1 study and disclosed acting as a consultant to Novo Nordisk; she also disclosed relationships with multiple other pharmaceutical companies, including AstraZeneca, BMS, Calbra, Eisai, Elcelyx Therapeutics, Janssen, and Sanofi Aventis. Dr. Bailey acknowledged attending advisory boards, undertaking ad hoc consultancy work, and receiving research and travel support from several pharmaceutical companies that included Novo Nordisk.

SOURCES: Haluzík M et al. EASD 2018, Abstract 38; Aroda V. EASD 2018, Session S18 - PIONEER Trial; Bailey C. EASD 2018, Session S18 - PIONEER Trial.

SAN FRANCISCO – Patients with hepatocellular carcinoma (HCC) who have a response to first-line kinase inhibitors based on modified RECIST (mRECIST) criteria live almost a year longer than counterparts who have stable or progressive disease, finds a retrospective post hoc analysis of the REFLECT trial.

Susan London/MDedge News

“The inability to accurately evaluate response to targeted or locoregional therapies resulted in the adaptation of RECIST to mRECIST, guidelines specifically designed to evaluate response to treatment in HCC,” noted lead investigator Masatoshi Kudo, MD, PhD, of the department of gastroenterology and hepatology, Kindai University Faculty of Medicine, Osaka, Japan. “Based on recommendations from the EASL [European Association for the Study of the Liver] consensus conference in 2000, mRECIST was developed to assess response based on the reduction of viable tumor burden … rather than overall tumor shrinkage. However, EASL clinical practice guidelines also suggested additional studies are needed to validate this approach.”

The investigators analyzed data from REFLECT, a global phase 3 noninferiority, randomized, controlled trial that showed overall survival with the novel kinase inhibitor lenvatinib (Lenvima) was not inferior to that with the older kinase inhibitor sorafenib (Nexavar) in 954 patients with untreated, unresectable HCC (Lancet. 2018;391:1163-73).

The new analysis, reported at the 2019 GI Cancers Symposium, showed that, among all randomized patients, those having an objective response according to mRECIST criteria were 39% less likely to die after other factors were taken into account. The finding was consistent in a landmark analysis, which addresses the issue of lead-time bias.

“Objective response by mRECIST was an independent predictor of overall survival in patients with HCC regardless of treatment,” Dr. Kudo concluded, adding that the findings are consistent with those of several previous studies. “Thus, patients who achieve an objective response can potentially expect a longer overall survival. However, additional studies are needed to further validate the correlation between objective response and overall survival.”
 

Findings in context

Although the mRECIST criteria overcome some issues with the size-based RECIST criteria in assessing HCC, the former are not without their limitations, noted invited discussant Andrew X. Zhu, MD, PhD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

Susan London/MDedge News

These limitations include, for example, the need for more stringent selection of target lesions and the potential for antiangiogenic agents to cause vasoconstriction, complicating measurement. “There is tremendous intraobserver and interobserver variability, and a tremendous learning curve,” he added, noting that in REFLECT the mRECIST overall response rate assessed by independent reviewers was considerably higher than that assessed by investigators.

To date, three other trials of targeted therapies have similarly found an association between mRECIST response and overall survival. But a fourth did not.

“In the era of immunotherapy being actively applied to HCC, it’s important to recognize that this association actually may be agent dependent,” Dr. Zhu said. “Even though the TKIs with antiangiogenic [activity] have shown an improved overall response [going] from RECIST to mRECIST, this has not been recapitulated, at least based on the current experience that we have, with checkpoint inhibitors.”

The REFLECT investigators’ conclusion “is certainly backed by the large dataset from a positive phase 3 trial. It has very sound statistical methodology, and it may actually provide the initial evidence that this biomarker may serve as a potentially relevant surrogate to predict overall survival,” he said.

At the same time, there is reason to be cautious given the post hoc, retrospective nature of the study; the lack of a comparison with conventional RECIST response; absence of analysis of the potential correlation of stable disease with overall survival; and the lumping together of two agents, among other issues.

“For these reasons, I do think additional studies are warranted for prospective validation of the findings,” Dr. Zhu concluded.

Study details

REFLECT patients had an investigator-assessed mRECIST objective response rate of 16.7% overall (24.1% with lenvatinib and 9.2% with sorafenib) and a median overall survival of 13.0 months (13.6 months with lenvatinib and 12.3 months with sorafenib).

Median overall survival was 22.4 months for mRECIST responders and 11.4 months for nonresponders (P less than .001), Dr. Kudo reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

In a multivariate analysis, this difference translated to a 39% reduction in risk of death for responders (hazard ratio, 0.61; P less than .0001).

Moreover, the survival advantage of response was evident in landmark analyses, whether response was assessed at 2 months (HR, 0.75; P = .033), at 4 months (HR, 0.72; P = .009), or at 6 months (HR, 0.73; P = .010).

Dr. Kudo disclosed that he receives honoraria or has a consulting or advisory role with several pharmaceutical companies. The presentation was sponsored by Eisai and Merck.

SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 186.

SAN FRANCISCO – Patients with hepatocellular carcinoma (HCC) who have a response to first-line kinase inhibitors based on modified RECIST (mRECIST) criteria live almost a year longer than counterparts who have stable or progressive disease, finds a retrospective post hoc analysis of the REFLECT trial.

Susan London/MDedge News

“The inability to accurately evaluate response to targeted or locoregional therapies resulted in the adaptation of RECIST to mRECIST, guidelines specifically designed to evaluate response to treatment in HCC,” noted lead investigator Masatoshi Kudo, MD, PhD, of the department of gastroenterology and hepatology, Kindai University Faculty of Medicine, Osaka, Japan. “Based on recommendations from the EASL [European Association for the Study of the Liver] consensus conference in 2000, mRECIST was developed to assess response based on the reduction of viable tumor burden … rather than overall tumor shrinkage. However, EASL clinical practice guidelines also suggested additional studies are needed to validate this approach.”

The investigators analyzed data from REFLECT, a global phase 3 noninferiority, randomized, controlled trial that showed overall survival with the novel kinase inhibitor lenvatinib (Lenvima) was not inferior to that with the older kinase inhibitor sorafenib (Nexavar) in 954 patients with untreated, unresectable HCC (Lancet. 2018;391:1163-73).

The new analysis, reported at the 2019 GI Cancers Symposium, showed that, among all randomized patients, those having an objective response according to mRECIST criteria were 39% less likely to die after other factors were taken into account. The finding was consistent in a landmark analysis, which addresses the issue of lead-time bias.

“Objective response by mRECIST was an independent predictor of overall survival in patients with HCC regardless of treatment,” Dr. Kudo concluded, adding that the findings are consistent with those of several previous studies. “Thus, patients who achieve an objective response can potentially expect a longer overall survival. However, additional studies are needed to further validate the correlation between objective response and overall survival.”
 

Findings in context

Although the mRECIST criteria overcome some issues with the size-based RECIST criteria in assessing HCC, the former are not without their limitations, noted invited discussant Andrew X. Zhu, MD, PhD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

Susan London/MDedge News

These limitations include, for example, the need for more stringent selection of target lesions and the potential for antiangiogenic agents to cause vasoconstriction, complicating measurement. “There is tremendous intraobserver and interobserver variability, and a tremendous learning curve,” he added, noting that in REFLECT the mRECIST overall response rate assessed by independent reviewers was considerably higher than that assessed by investigators.

To date, three other trials of targeted therapies have similarly found an association between mRECIST response and overall survival. But a fourth did not.

“In the era of immunotherapy being actively applied to HCC, it’s important to recognize that this association actually may be agent dependent,” Dr. Zhu said. “Even though the TKIs with antiangiogenic [activity] have shown an improved overall response [going] from RECIST to mRECIST, this has not been recapitulated, at least based on the current experience that we have, with checkpoint inhibitors.”

The REFLECT investigators’ conclusion “is certainly backed by the large dataset from a positive phase 3 trial. It has very sound statistical methodology, and it may actually provide the initial evidence that this biomarker may serve as a potentially relevant surrogate to predict overall survival,” he said.

At the same time, there is reason to be cautious given the post hoc, retrospective nature of the study; the lack of a comparison with conventional RECIST response; absence of analysis of the potential correlation of stable disease with overall survival; and the lumping together of two agents, among other issues.

“For these reasons, I do think additional studies are warranted for prospective validation of the findings,” Dr. Zhu concluded.

Study details

REFLECT patients had an investigator-assessed mRECIST objective response rate of 16.7% overall (24.1% with lenvatinib and 9.2% with sorafenib) and a median overall survival of 13.0 months (13.6 months with lenvatinib and 12.3 months with sorafenib).

Median overall survival was 22.4 months for mRECIST responders and 11.4 months for nonresponders (P less than .001), Dr. Kudo reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

In a multivariate analysis, this difference translated to a 39% reduction in risk of death for responders (hazard ratio, 0.61; P less than .0001).

Moreover, the survival advantage of response was evident in landmark analyses, whether response was assessed at 2 months (HR, 0.75; P = .033), at 4 months (HR, 0.72; P = .009), or at 6 months (HR, 0.73; P = .010).

Dr. Kudo disclosed that he receives honoraria or has a consulting or advisory role with several pharmaceutical companies. The presentation was sponsored by Eisai and Merck.

SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 186.

SAN FRANCISCO – Patients with hepatocellular carcinoma (HCC) who have a response to first-line kinase inhibitors based on modified RECIST (mRECIST) criteria live almost a year longer than counterparts who have stable or progressive disease, finds a retrospective post hoc analysis of the REFLECT trial.

Susan London/MDedge News

“The inability to accurately evaluate response to targeted or locoregional therapies resulted in the adaptation of RECIST to mRECIST, guidelines specifically designed to evaluate response to treatment in HCC,” noted lead investigator Masatoshi Kudo, MD, PhD, of the department of gastroenterology and hepatology, Kindai University Faculty of Medicine, Osaka, Japan. “Based on recommendations from the EASL [European Association for the Study of the Liver] consensus conference in 2000, mRECIST was developed to assess response based on the reduction of viable tumor burden … rather than overall tumor shrinkage. However, EASL clinical practice guidelines also suggested additional studies are needed to validate this approach.”

The investigators analyzed data from REFLECT, a global phase 3 noninferiority, randomized, controlled trial that showed overall survival with the novel kinase inhibitor lenvatinib (Lenvima) was not inferior to that with the older kinase inhibitor sorafenib (Nexavar) in 954 patients with untreated, unresectable HCC (Lancet. 2018;391:1163-73).

The new analysis, reported at the 2019 GI Cancers Symposium, showed that, among all randomized patients, those having an objective response according to mRECIST criteria were 39% less likely to die after other factors were taken into account. The finding was consistent in a landmark analysis, which addresses the issue of lead-time bias.

“Objective response by mRECIST was an independent predictor of overall survival in patients with HCC regardless of treatment,” Dr. Kudo concluded, adding that the findings are consistent with those of several previous studies. “Thus, patients who achieve an objective response can potentially expect a longer overall survival. However, additional studies are needed to further validate the correlation between objective response and overall survival.”
 

Findings in context

Although the mRECIST criteria overcome some issues with the size-based RECIST criteria in assessing HCC, the former are not without their limitations, noted invited discussant Andrew X. Zhu, MD, PhD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

Susan London/MDedge News

These limitations include, for example, the need for more stringent selection of target lesions and the potential for antiangiogenic agents to cause vasoconstriction, complicating measurement. “There is tremendous intraobserver and interobserver variability, and a tremendous learning curve,” he added, noting that in REFLECT the mRECIST overall response rate assessed by independent reviewers was considerably higher than that assessed by investigators.

To date, three other trials of targeted therapies have similarly found an association between mRECIST response and overall survival. But a fourth did not.

“In the era of immunotherapy being actively applied to HCC, it’s important to recognize that this association actually may be agent dependent,” Dr. Zhu said. “Even though the TKIs with antiangiogenic [activity] have shown an improved overall response [going] from RECIST to mRECIST, this has not been recapitulated, at least based on the current experience that we have, with checkpoint inhibitors.”

The REFLECT investigators’ conclusion “is certainly backed by the large dataset from a positive phase 3 trial. It has very sound statistical methodology, and it may actually provide the initial evidence that this biomarker may serve as a potentially relevant surrogate to predict overall survival,” he said.

At the same time, there is reason to be cautious given the post hoc, retrospective nature of the study; the lack of a comparison with conventional RECIST response; absence of analysis of the potential correlation of stable disease with overall survival; and the lumping together of two agents, among other issues.

“For these reasons, I do think additional studies are warranted for prospective validation of the findings,” Dr. Zhu concluded.

Study details

REFLECT patients had an investigator-assessed mRECIST objective response rate of 16.7% overall (24.1% with lenvatinib and 9.2% with sorafenib) and a median overall survival of 13.0 months (13.6 months with lenvatinib and 12.3 months with sorafenib).

Median overall survival was 22.4 months for mRECIST responders and 11.4 months for nonresponders (P less than .001), Dr. Kudo reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

In a multivariate analysis, this difference translated to a 39% reduction in risk of death for responders (hazard ratio, 0.61; P less than .0001).

Moreover, the survival advantage of response was evident in landmark analyses, whether response was assessed at 2 months (HR, 0.75; P = .033), at 4 months (HR, 0.72; P = .009), or at 6 months (HR, 0.73; P = .010).

Dr. Kudo disclosed that he receives honoraria or has a consulting or advisory role with several pharmaceutical companies. The presentation was sponsored by Eisai and Merck.

SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 186.

A sign on the wall of the Sip of Hope Coffee Bar in the Logan Square area of Chicago reads: “It’s OK not to be OK.” The slogan is more than a way to distinguish the coffee shop from competitors. According to a report published recently in the Chicago Sun-Times, all money spent on beverages and pastries is donated to suicide prevention and mental health programs in the Windy City.

Lynda Banzi/IMNG Medical Media

“Sip of Hope is the brick-and-mortar version of what we do every day,” Jonny Boucher, who started a nonprofit called Hope for the Day in 2011 in an effort to make mental health issues part of the everyday conversation, said in the article. “I’ve lost 16 people to suicide, and I thought if I can just take this pain and I can do something with it, then I can allow others to do something with their pain.”

Mr. Boucher organizes a monthly get-together at the coffee shop where people can talk about their mental health struggles and find help and friendship.

“If I got paid $10 for every time someone said I saved their life, this organization would be bankrolled for eternity,” said Mr. Boucher. “There is no magic wand with mental health but I try to tell people – we’re all in this together – it’s not about me, it’s about we.”
 

Housing First program launched

A housing program being offered in some parts of Kansas, including Wichita, is making housing available to people with mental illness without the traditional requirements of a nightly curfew or adherence to sobriety.

“What we’re doing with a program like this is essentially leveling the playing field so that people who have for some reason become homeless have the same opportunity to have and keep housing as the rest of us,” Sam J. Tsemberis, PhD, a psychologist who founded Pathways to Housing in New York City and is spearheading the program in Kansas, said in an interview with the Topeka Capital-Journal. “Most people in Kansas don’t have sobriety and treatment requirements in order to stay housed. And if they did, we’d be in a lot more trouble on the homelessness front.”

Dr. Tsemberis said his philosophy about providing housing for people with mental illness stems from his work years ago at Bellevue Hospital in New York. During his commute, Dr. Tsemberis said, he “passed people on the sidewalk he had just treated as patients, still wearing the hospital pajamas they were dispatched in.”

“A community’s social structure is impaired when people can walk by somebody who is homeless on the street,” Dr. Tsemberis, a psychiatry professor at Columbia University in New York, said in the interview. “It’s not just the person who is homeless, who is isolated and disconnected. It’s everybody else who walks past them that also has to cut off a part of their humanity in order to tolerate being able to walk past another human being who is sitting there.”

More than 2,000 homeless people live in Kansas, and Wichita is the hub. So far, more than 320 Kansas residents have entered the Housing First program, and more than 240 have found permanent housing.
 

Some residents shortchanged on services

Policymakers in Chicago are discussing the possibility of reopening some of the city’s mental health clinics.

A city council committee recently unanimously voted to approve a Public Mental Health Clinic Service Expansion Task Force to look into the possibility.

“We are all aware of the anecdotal issues related to the gaps in mental health care that face our wards,” Alderman Sophia King, who sponsored the measure, said in an article published in the Chicago Sun-Times.

According to the article, six of the city’s mental health clinics were shut down in 2012. Mental health clinics said funding for mental health care in the city has continued to decline. A report issued last year by the Collaborative for Community Wellness focusing on mental health services on the city’s southwest side said there were 0.17 licensed mental health clinicians for every 1,000 residents. Meanwhile, on the city’s near north side, also known as the Gold Coast, there were 4.45 clinicians for every 1,000 residents, the report said.
 

Increase in suicides raising concerns

A recent report from the Tennessee Suicide Prevention Network reveals a dark picture. As reported by the Tennessean, the suicide rate continued to climb last year, continuing an increase that began in 2014. The suicide rate of 17.3 of every 100,000 people is markedly higher than the national rate of 14.5, according to an article in the Tennessean.

For children and adolescents aged 10-17 years, the situation is worse. In that cohort, rate of suicide climbed by more than 24% from 2016 to 2017, and a huge 55% between 2015 and 2017. In 2017, 142 people between 10 and 24 years of age ended their own lives. Overall, there were 1,163 suicides in 2017, an average of 3 every day.

Among the states’ demographics, suicide is three times higher among white non-Hispanics. Whites comprise 79% of the population of Tennessee and account for 91% of the suicides.

A national study in 2015 estimated the total national cost of suicides and suicide attempts at $93.5 billion. A single suicide can cost $1,329,553 in medical treatment and the lost productivity.

But those losses cannot be quantified. “For every number and rate that is provided in the 2019 ‘Status of Suicide in Tennessee’ report, a family member, loved one, neighbor, coworker, and friend suffers an unimaginable loss,” said Scott Ridgway, executive director of the Tennessee Suicide Prevention Network.
 

Anticonversion therapy bill introduced

A state senator in Arizona has reintroduced legislation aimed at preventing mental health professionals from practicing conversion therapy on minors.

Under the bill reintroduced by state Sen. Sean Bowie, a Democrat, psychotherapists who engage in practices aimed at changing the sexual orientation of a person under age 18 years would be “subject to disciplinary action.”

“This (practice) is completely discredited and actually hurtful for young people,” said state Sen. Bowie, according to azcentral.com, which is part of the USA Today network. “There’s really no medical proof that it’s helpful or effective at all.”

Late last year, the American Psychiatric Association reiterated its strong opposition to the practice. “Conversion therapy is banned in 14 states as well as the District of Columbia,” the group said. “The APA calls upon other lawmakers to ban the harmful and discriminatory practice.”

A sign on the wall of the Sip of Hope Coffee Bar in the Logan Square area of Chicago reads: “It’s OK not to be OK.” The slogan is more than a way to distinguish the coffee shop from competitors. According to a report published recently in the Chicago Sun-Times, all money spent on beverages and pastries is donated to suicide prevention and mental health programs in the Windy City.

Lynda Banzi/IMNG Medical Media

“Sip of Hope is the brick-and-mortar version of what we do every day,” Jonny Boucher, who started a nonprofit called Hope for the Day in 2011 in an effort to make mental health issues part of the everyday conversation, said in the article. “I’ve lost 16 people to suicide, and I thought if I can just take this pain and I can do something with it, then I can allow others to do something with their pain.”

Mr. Boucher organizes a monthly get-together at the coffee shop where people can talk about their mental health struggles and find help and friendship.

“If I got paid $10 for every time someone said I saved their life, this organization would be bankrolled for eternity,” said Mr. Boucher. “There is no magic wand with mental health but I try to tell people – we’re all in this together – it’s not about me, it’s about we.”
 

Housing First program launched

A housing program being offered in some parts of Kansas, including Wichita, is making housing available to people with mental illness without the traditional requirements of a nightly curfew or adherence to sobriety.

“What we’re doing with a program like this is essentially leveling the playing field so that people who have for some reason become homeless have the same opportunity to have and keep housing as the rest of us,” Sam J. Tsemberis, PhD, a psychologist who founded Pathways to Housing in New York City and is spearheading the program in Kansas, said in an interview with the Topeka Capital-Journal. “Most people in Kansas don’t have sobriety and treatment requirements in order to stay housed. And if they did, we’d be in a lot more trouble on the homelessness front.”

Dr. Tsemberis said his philosophy about providing housing for people with mental illness stems from his work years ago at Bellevue Hospital in New York. During his commute, Dr. Tsemberis said, he “passed people on the sidewalk he had just treated as patients, still wearing the hospital pajamas they were dispatched in.”

“A community’s social structure is impaired when people can walk by somebody who is homeless on the street,” Dr. Tsemberis, a psychiatry professor at Columbia University in New York, said in the interview. “It’s not just the person who is homeless, who is isolated and disconnected. It’s everybody else who walks past them that also has to cut off a part of their humanity in order to tolerate being able to walk past another human being who is sitting there.”

More than 2,000 homeless people live in Kansas, and Wichita is the hub. So far, more than 320 Kansas residents have entered the Housing First program, and more than 240 have found permanent housing.
 

Some residents shortchanged on services

Policymakers in Chicago are discussing the possibility of reopening some of the city’s mental health clinics.

A city council committee recently unanimously voted to approve a Public Mental Health Clinic Service Expansion Task Force to look into the possibility.

“We are all aware of the anecdotal issues related to the gaps in mental health care that face our wards,” Alderman Sophia King, who sponsored the measure, said in an article published in the Chicago Sun-Times.

According to the article, six of the city’s mental health clinics were shut down in 2012. Mental health clinics said funding for mental health care in the city has continued to decline. A report issued last year by the Collaborative for Community Wellness focusing on mental health services on the city’s southwest side said there were 0.17 licensed mental health clinicians for every 1,000 residents. Meanwhile, on the city’s near north side, also known as the Gold Coast, there were 4.45 clinicians for every 1,000 residents, the report said.
 

Increase in suicides raising concerns

A recent report from the Tennessee Suicide Prevention Network reveals a dark picture. As reported by the Tennessean, the suicide rate continued to climb last year, continuing an increase that began in 2014. The suicide rate of 17.3 of every 100,000 people is markedly higher than the national rate of 14.5, according to an article in the Tennessean.

For children and adolescents aged 10-17 years, the situation is worse. In that cohort, rate of suicide climbed by more than 24% from 2016 to 2017, and a huge 55% between 2015 and 2017. In 2017, 142 people between 10 and 24 years of age ended their own lives. Overall, there were 1,163 suicides in 2017, an average of 3 every day.

Among the states’ demographics, suicide is three times higher among white non-Hispanics. Whites comprise 79% of the population of Tennessee and account for 91% of the suicides.

A national study in 2015 estimated the total national cost of suicides and suicide attempts at $93.5 billion. A single suicide can cost $1,329,553 in medical treatment and the lost productivity.

But those losses cannot be quantified. “For every number and rate that is provided in the 2019 ‘Status of Suicide in Tennessee’ report, a family member, loved one, neighbor, coworker, and friend suffers an unimaginable loss,” said Scott Ridgway, executive director of the Tennessee Suicide Prevention Network.
 

Anticonversion therapy bill introduced

A state senator in Arizona has reintroduced legislation aimed at preventing mental health professionals from practicing conversion therapy on minors.

Under the bill reintroduced by state Sen. Sean Bowie, a Democrat, psychotherapists who engage in practices aimed at changing the sexual orientation of a person under age 18 years would be “subject to disciplinary action.”

“This (practice) is completely discredited and actually hurtful for young people,” said state Sen. Bowie, according to azcentral.com, which is part of the USA Today network. “There’s really no medical proof that it’s helpful or effective at all.”

Late last year, the American Psychiatric Association reiterated its strong opposition to the practice. “Conversion therapy is banned in 14 states as well as the District of Columbia,” the group said. “The APA calls upon other lawmakers to ban the harmful and discriminatory practice.”

A sign on the wall of the Sip of Hope Coffee Bar in the Logan Square area of Chicago reads: “It’s OK not to be OK.” The slogan is more than a way to distinguish the coffee shop from competitors. According to a report published recently in the Chicago Sun-Times, all money spent on beverages and pastries is donated to suicide prevention and mental health programs in the Windy City.

Lynda Banzi/IMNG Medical Media

“Sip of Hope is the brick-and-mortar version of what we do every day,” Jonny Boucher, who started a nonprofit called Hope for the Day in 2011 in an effort to make mental health issues part of the everyday conversation, said in the article. “I’ve lost 16 people to suicide, and I thought if I can just take this pain and I can do something with it, then I can allow others to do something with their pain.”

Mr. Boucher organizes a monthly get-together at the coffee shop where people can talk about their mental health struggles and find help and friendship.

“If I got paid $10 for every time someone said I saved their life, this organization would be bankrolled for eternity,” said Mr. Boucher. “There is no magic wand with mental health but I try to tell people – we’re all in this together – it’s not about me, it’s about we.”
 

Housing First program launched

A housing program being offered in some parts of Kansas, including Wichita, is making housing available to people with mental illness without the traditional requirements of a nightly curfew or adherence to sobriety.

“What we’re doing with a program like this is essentially leveling the playing field so that people who have for some reason become homeless have the same opportunity to have and keep housing as the rest of us,” Sam J. Tsemberis, PhD, a psychologist who founded Pathways to Housing in New York City and is spearheading the program in Kansas, said in an interview with the Topeka Capital-Journal. “Most people in Kansas don’t have sobriety and treatment requirements in order to stay housed. And if they did, we’d be in a lot more trouble on the homelessness front.”

Dr. Tsemberis said his philosophy about providing housing for people with mental illness stems from his work years ago at Bellevue Hospital in New York. During his commute, Dr. Tsemberis said, he “passed people on the sidewalk he had just treated as patients, still wearing the hospital pajamas they were dispatched in.”

“A community’s social structure is impaired when people can walk by somebody who is homeless on the street,” Dr. Tsemberis, a psychiatry professor at Columbia University in New York, said in the interview. “It’s not just the person who is homeless, who is isolated and disconnected. It’s everybody else who walks past them that also has to cut off a part of their humanity in order to tolerate being able to walk past another human being who is sitting there.”

More than 2,000 homeless people live in Kansas, and Wichita is the hub. So far, more than 320 Kansas residents have entered the Housing First program, and more than 240 have found permanent housing.
 

Some residents shortchanged on services

Policymakers in Chicago are discussing the possibility of reopening some of the city’s mental health clinics.

A city council committee recently unanimously voted to approve a Public Mental Health Clinic Service Expansion Task Force to look into the possibility.

“We are all aware of the anecdotal issues related to the gaps in mental health care that face our wards,” Alderman Sophia King, who sponsored the measure, said in an article published in the Chicago Sun-Times.

According to the article, six of the city’s mental health clinics were shut down in 2012. Mental health clinics said funding for mental health care in the city has continued to decline. A report issued last year by the Collaborative for Community Wellness focusing on mental health services on the city’s southwest side said there were 0.17 licensed mental health clinicians for every 1,000 residents. Meanwhile, on the city’s near north side, also known as the Gold Coast, there were 4.45 clinicians for every 1,000 residents, the report said.
 

Increase in suicides raising concerns

A recent report from the Tennessee Suicide Prevention Network reveals a dark picture. As reported by the Tennessean, the suicide rate continued to climb last year, continuing an increase that began in 2014. The suicide rate of 17.3 of every 100,000 people is markedly higher than the national rate of 14.5, according to an article in the Tennessean.

For children and adolescents aged 10-17 years, the situation is worse. In that cohort, rate of suicide climbed by more than 24% from 2016 to 2017, and a huge 55% between 2015 and 2017. In 2017, 142 people between 10 and 24 years of age ended their own lives. Overall, there were 1,163 suicides in 2017, an average of 3 every day.

Among the states’ demographics, suicide is three times higher among white non-Hispanics. Whites comprise 79% of the population of Tennessee and account for 91% of the suicides.

A national study in 2015 estimated the total national cost of suicides and suicide attempts at $93.5 billion. A single suicide can cost $1,329,553 in medical treatment and the lost productivity.

But those losses cannot be quantified. “For every number and rate that is provided in the 2019 ‘Status of Suicide in Tennessee’ report, a family member, loved one, neighbor, coworker, and friend suffers an unimaginable loss,” said Scott Ridgway, executive director of the Tennessee Suicide Prevention Network.
 

Anticonversion therapy bill introduced

A state senator in Arizona has reintroduced legislation aimed at preventing mental health professionals from practicing conversion therapy on minors.

Under the bill reintroduced by state Sen. Sean Bowie, a Democrat, psychotherapists who engage in practices aimed at changing the sexual orientation of a person under age 18 years would be “subject to disciplinary action.”

“This (practice) is completely discredited and actually hurtful for young people,” said state Sen. Bowie, according to azcentral.com, which is part of the USA Today network. “There’s really no medical proof that it’s helpful or effective at all.”

Late last year, the American Psychiatric Association reiterated its strong opposition to the practice. “Conversion therapy is banned in 14 states as well as the District of Columbia,” the group said. “The APA calls upon other lawmakers to ban the harmful and discriminatory practice.”

AGA is dedicated to integrity and transparency in the development of clinical guidance.

When preparing guidelines, AGA follows the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process and makes draft guidelines available for public comment. In addition, to keep academic integrity of the AGA guideline, clinical practice update, and clinical pathway process, AGA follows the framework outlined by the Council of Medical Specialty Societies (CMSS) in The Code for Interaction with Companies.

The Code for Interaction with Companies states:

“7.15. Societies will not permit Guideline development panel members or staff to discuss a Guideline’s development with Company employees or representatives, will not accept unpublished data from Companies, and will not permit Companies to review Guidelines in draft form, except if a Society permits public or member comment on draft Guidelines as a part of the Society’s published Guideline development process.”

The Clinical Guidelines Committee and Clinical Practice Updates Committee strive to keep AGA’s clinical practice tools independent of industry influence and remain solely based on scientific evidence. As a result of this effort, AGA’s writing panels and chairs will have no direct communication with industry. Companies will have the opportunity to submit feedback during the public comment period. The panel will review any comments submitted through the online platform along with feedback from the public. The writing panel will take these suggestions into consideration when making revisions following the public comment period.
 

ginews@gastro.org

AGA is dedicated to integrity and transparency in the development of clinical guidance.

When preparing guidelines, AGA follows the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process and makes draft guidelines available for public comment. In addition, to keep academic integrity of the AGA guideline, clinical practice update, and clinical pathway process, AGA follows the framework outlined by the Council of Medical Specialty Societies (CMSS) in The Code for Interaction with Companies.

The Code for Interaction with Companies states:

“7.15. Societies will not permit Guideline development panel members or staff to discuss a Guideline’s development with Company employees or representatives, will not accept unpublished data from Companies, and will not permit Companies to review Guidelines in draft form, except if a Society permits public or member comment on draft Guidelines as a part of the Society’s published Guideline development process.”

The Clinical Guidelines Committee and Clinical Practice Updates Committee strive to keep AGA’s clinical practice tools independent of industry influence and remain solely based on scientific evidence. As a result of this effort, AGA’s writing panels and chairs will have no direct communication with industry. Companies will have the opportunity to submit feedback during the public comment period. The panel will review any comments submitted through the online platform along with feedback from the public. The writing panel will take these suggestions into consideration when making revisions following the public comment period.
 

ginews@gastro.org

AGA is dedicated to integrity and transparency in the development of clinical guidance.

When preparing guidelines, AGA follows the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process and makes draft guidelines available for public comment. In addition, to keep academic integrity of the AGA guideline, clinical practice update, and clinical pathway process, AGA follows the framework outlined by the Council of Medical Specialty Societies (CMSS) in The Code for Interaction with Companies.

The Code for Interaction with Companies states:

“7.15. Societies will not permit Guideline development panel members or staff to discuss a Guideline’s development with Company employees or representatives, will not accept unpublished data from Companies, and will not permit Companies to review Guidelines in draft form, except if a Society permits public or member comment on draft Guidelines as a part of the Society’s published Guideline development process.”

The Clinical Guidelines Committee and Clinical Practice Updates Committee strive to keep AGA’s clinical practice tools independent of industry influence and remain solely based on scientific evidence. As a result of this effort, AGA’s writing panels and chairs will have no direct communication with industry. Companies will have the opportunity to submit feedback during the public comment period. The panel will review any comments submitted through the online platform along with feedback from the public. The writing panel will take these suggestions into consideration when making revisions following the public comment period.
 

ginews@gastro.org

To those who took time to advocate on behalf of your profession and patients, thank you. Because of your efforts, we achieved several key successes that benefit clinicians, researchers and patients.

Together we were able to help advance several AGA policy priorities — administrative burden relief, digestive disease research and funding, and patient access and protection — as well as the science and practice of gastroenterology.

This year, we will be counting on you, our members, to again lead the charge to achieve AGA’s mission — empowering clinicians and researchers to improve digestive health — by calling on legislators and regulators to ensure the voice of gastroenterology continue to be heard.

NIH funding increase

AGA advocated and secured a $2 billion increase in NIH funding for fiscal year (FY) 2019. When added to increases from the two previous fiscal years, NIH’s funding has increased by 30 percent over the past three years, which is the largest increase since the doubling period in the last decade.

IPAB repeal prevents automatic Medicare cuts

Congress repealed the Independent Payment Advisory Board (IPAB) that was created as part of the Affordable Care Act (ACA). AGA and all of organized medicine long opposed IPAB since its sole purpose was to make budgetary cuts to Medicare if it reached a certain threshold of spending.

MIPS changes means more flexibility for physicians

AGA and the physician community were successful in securing flexibility under the new Medicare Quality Payment Program and the Merit-based Incentive Payment System (MIPS) that were created under the Medicare Access and CHIP Reauthorization Act. The changes give CMS more flexibility in implementing the program and will ensure that physicians have an opportunity to be successful in MIPS.

500 AGA members prevent radical changes to outpatient documentation

In response to a CMS proposal to radically change how outpatient evaluation and management (E/M) services are documented, more than 500 AGA members urged CMS not to move forward with its plan. As a result, CMS withdrew or delayed many of the proposed changes to E/M services that negatively impacted reimbursement. CMS did move forward with several changes to E/M documentation in an effort to reduce administrative burden.

AGA members send more than 940 letters to Congress

AGA launched the Congressional Advocates Program to provide an infrastructure and tools for members to effectively advocate on behalf of their profession and patients. AGA members heeded our calls to action and sent more than 940 letters sent to Congress and federal agencies throughout 2018. We thank our advocates whose participation makes a difference.

ginews@gastro.org

To those who took time to advocate on behalf of your profession and patients, thank you. Because of your efforts, we achieved several key successes that benefit clinicians, researchers and patients.

Together we were able to help advance several AGA policy priorities — administrative burden relief, digestive disease research and funding, and patient access and protection — as well as the science and practice of gastroenterology.

This year, we will be counting on you, our members, to again lead the charge to achieve AGA’s mission — empowering clinicians and researchers to improve digestive health — by calling on legislators and regulators to ensure the voice of gastroenterology continue to be heard.

NIH funding increase

AGA advocated and secured a $2 billion increase in NIH funding for fiscal year (FY) 2019. When added to increases from the two previous fiscal years, NIH’s funding has increased by 30 percent over the past three years, which is the largest increase since the doubling period in the last decade.

IPAB repeal prevents automatic Medicare cuts

Congress repealed the Independent Payment Advisory Board (IPAB) that was created as part of the Affordable Care Act (ACA). AGA and all of organized medicine long opposed IPAB since its sole purpose was to make budgetary cuts to Medicare if it reached a certain threshold of spending.

MIPS changes means more flexibility for physicians

AGA and the physician community were successful in securing flexibility under the new Medicare Quality Payment Program and the Merit-based Incentive Payment System (MIPS) that were created under the Medicare Access and CHIP Reauthorization Act. The changes give CMS more flexibility in implementing the program and will ensure that physicians have an opportunity to be successful in MIPS.

500 AGA members prevent radical changes to outpatient documentation

In response to a CMS proposal to radically change how outpatient evaluation and management (E/M) services are documented, more than 500 AGA members urged CMS not to move forward with its plan. As a result, CMS withdrew or delayed many of the proposed changes to E/M services that negatively impacted reimbursement. CMS did move forward with several changes to E/M documentation in an effort to reduce administrative burden.

AGA members send more than 940 letters to Congress

AGA launched the Congressional Advocates Program to provide an infrastructure and tools for members to effectively advocate on behalf of their profession and patients. AGA members heeded our calls to action and sent more than 940 letters sent to Congress and federal agencies throughout 2018. We thank our advocates whose participation makes a difference.

ginews@gastro.org

To those who took time to advocate on behalf of your profession and patients, thank you. Because of your efforts, we achieved several key successes that benefit clinicians, researchers and patients.

Together we were able to help advance several AGA policy priorities — administrative burden relief, digestive disease research and funding, and patient access and protection — as well as the science and practice of gastroenterology.

This year, we will be counting on you, our members, to again lead the charge to achieve AGA’s mission — empowering clinicians and researchers to improve digestive health — by calling on legislators and regulators to ensure the voice of gastroenterology continue to be heard.

NIH funding increase

AGA advocated and secured a $2 billion increase in NIH funding for fiscal year (FY) 2019. When added to increases from the two previous fiscal years, NIH’s funding has increased by 30 percent over the past three years, which is the largest increase since the doubling period in the last decade.

IPAB repeal prevents automatic Medicare cuts

Congress repealed the Independent Payment Advisory Board (IPAB) that was created as part of the Affordable Care Act (ACA). AGA and all of organized medicine long opposed IPAB since its sole purpose was to make budgetary cuts to Medicare if it reached a certain threshold of spending.

MIPS changes means more flexibility for physicians

AGA and the physician community were successful in securing flexibility under the new Medicare Quality Payment Program and the Merit-based Incentive Payment System (MIPS) that were created under the Medicare Access and CHIP Reauthorization Act. The changes give CMS more flexibility in implementing the program and will ensure that physicians have an opportunity to be successful in MIPS.

500 AGA members prevent radical changes to outpatient documentation

In response to a CMS proposal to radically change how outpatient evaluation and management (E/M) services are documented, more than 500 AGA members urged CMS not to move forward with its plan. As a result, CMS withdrew or delayed many of the proposed changes to E/M services that negatively impacted reimbursement. CMS did move forward with several changes to E/M documentation in an effort to reduce administrative burden.

AGA members send more than 940 letters to Congress

AGA launched the Congressional Advocates Program to provide an infrastructure and tools for members to effectively advocate on behalf of their profession and patients. AGA members heeded our calls to action and sent more than 940 letters sent to Congress and federal agencies throughout 2018. We thank our advocates whose participation makes a difference.

ginews@gastro.org

CHICAGO – The short-term risk of developing heart failure in patients with newly identified hypothyroidism, be it overt or subclinical, is double that of euthyroid individuals, Caroline H. Noergaard, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“This is really important clinically. The association with heart failure has previously been shown in both overt and subclinical hyperthyroidism, but it’s actually new knowledge that hypothyroidism is associated with immediate risk of heart failure. And a lot of people have subclinical hypothyroidism,” said Dr. Noergaard, a PhD student in epidemiology at Aalborg (Denmark) University.

Also at the meeting, Jeffrey L. Anderson, MD, reported that free thyroxine levels within the normal reference range were associated in graded fashion with an increased prevalence and incidence of atrial fibrillation in a large Utah study, a finding that provides independent confirmation of an earlier report by investigators from the population-based Rotterdam Study.

“These findings validate those of the Rotterdam Study in a much larger dataset and may have important clinical implications, including a redefinition of the reference range and the target-free T₄ levels for thyroxine replacement therapy,” observed Dr. Anderson, professor of internal medicine at the University of Utah, Salt Lake City, and a research cardiologist at the Intermountain Medical Center Heart Institute.

Hypothyroidism and heart failure

Dr. Noergaard presented a retrospective study of over 1 million Copenhagen-area adults (mean age, 50 years) with no history of heart failure, who had their first thyroid function test. She and her coinvestigators turned to comprehensive Danish national health care registries to determine how many of these individuals were diagnosed with new-onset heart failure within 90 days after their thyroid function test.

Subclinical hypothyroidism was defined by a thyroid-stimulating hormone level greater than 5 mIU/L and a free T₄ of 9-22 pmol/L. Overt hypothyroidism required a TSH greater than 5 mIU/L with a free T₄ less than 9 pmol/L.

Free T₄ predicts atrial fibrillation risk

Dr. Anderson presented a retrospective analysis of 174,914 adult patients in the Intermountain Healthcare EMR database, none of whom were on thyroid replacement at entry. The patients, who were a mean age of 64 years and 65% women, were followed for an average of 6.3 years. Of these, 88.4% had a free T₄ within the normal reference range of 0.75-1.5 ng/dL, 7.4% had a value below the cutoff for normal, and 4.2% had a free T₄ above the reference range.

Upon dividing the patients within the normal range into quartiles based upon their free T₄ level, he and his coinvestigators found that the baseline prevalence of atrial fibrillation was 8.7% in those in quartile 1, 9.3% in quartile 2, 10.5% in quartile 3, and 12.6% in quartile 4. In a multivariate analysis adjusted for potential confounders, the risk of prevalent atrial fibrillation was increased by 11% for patients in quartile 2, compared with those in the first quartile, by 22% in quartile 3, and by 40% in quartile 4.

The incidence of new-onset atrial fibrillation during 3 years of follow-up was 4.1% in patients in normal-range quartile 1, 4.3% in quartile 2, 4.5% in quartile 3, and 5.2% in the top normal-range quartile. The odds of developing atrial fibrillation were increased by 8% and 16% in quartiles 3 and 4, compared with quartile 1.

Serum TSH and free T₃ levels showed no consistent relationship with atrial fibrillation.

The Utah findings confirm in a large U.S. population the earlier report from the Rotterdam Study (J Clin Endocrinol Metab. 2015 Oct;100(10):3718-24).

Dr. Noergaard and Dr. Anderson reported having no financial conflicts regarding their studies, which were carried out free of commercial support.

bjancin@mdedge.com

CHICAGO – The short-term risk of developing heart failure in patients with newly identified hypothyroidism, be it overt or subclinical, is double that of euthyroid individuals, Caroline H. Noergaard, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“This is really important clinically. The association with heart failure has previously been shown in both overt and subclinical hyperthyroidism, but it’s actually new knowledge that hypothyroidism is associated with immediate risk of heart failure. And a lot of people have subclinical hypothyroidism,” said Dr. Noergaard, a PhD student in epidemiology at Aalborg (Denmark) University.

Also at the meeting, Jeffrey L. Anderson, MD, reported that free thyroxine levels within the normal reference range were associated in graded fashion with an increased prevalence and incidence of atrial fibrillation in a large Utah study, a finding that provides independent confirmation of an earlier report by investigators from the population-based Rotterdam Study.

“These findings validate those of the Rotterdam Study in a much larger dataset and may have important clinical implications, including a redefinition of the reference range and the target-free T₄ levels for thyroxine replacement therapy,” observed Dr. Anderson, professor of internal medicine at the University of Utah, Salt Lake City, and a research cardiologist at the Intermountain Medical Center Heart Institute.

Hypothyroidism and heart failure

Dr. Noergaard presented a retrospective study of over 1 million Copenhagen-area adults (mean age, 50 years) with no history of heart failure, who had their first thyroid function test. She and her coinvestigators turned to comprehensive Danish national health care registries to determine how many of these individuals were diagnosed with new-onset heart failure within 90 days after their thyroid function test.

Subclinical hypothyroidism was defined by a thyroid-stimulating hormone level greater than 5 mIU/L and a free T₄ of 9-22 pmol/L. Overt hypothyroidism required a TSH greater than 5 mIU/L with a free T₄ less than 9 pmol/L.

Free T₄ predicts atrial fibrillation risk

Dr. Anderson presented a retrospective analysis of 174,914 adult patients in the Intermountain Healthcare EMR database, none of whom were on thyroid replacement at entry. The patients, who were a mean age of 64 years and 65% women, were followed for an average of 6.3 years. Of these, 88.4% had a free T₄ within the normal reference range of 0.75-1.5 ng/dL, 7.4% had a value below the cutoff for normal, and 4.2% had a free T₄ above the reference range.

Upon dividing the patients within the normal range into quartiles based upon their free T₄ level, he and his coinvestigators found that the baseline prevalence of atrial fibrillation was 8.7% in those in quartile 1, 9.3% in quartile 2, 10.5% in quartile 3, and 12.6% in quartile 4. In a multivariate analysis adjusted for potential confounders, the risk of prevalent atrial fibrillation was increased by 11% for patients in quartile 2, compared with those in the first quartile, by 22% in quartile 3, and by 40% in quartile 4.

The incidence of new-onset atrial fibrillation during 3 years of follow-up was 4.1% in patients in normal-range quartile 1, 4.3% in quartile 2, 4.5% in quartile 3, and 5.2% in the top normal-range quartile. The odds of developing atrial fibrillation were increased by 8% and 16% in quartiles 3 and 4, compared with quartile 1.

Serum TSH and free T₃ levels showed no consistent relationship with atrial fibrillation.

The Utah findings confirm in a large U.S. population the earlier report from the Rotterdam Study (J Clin Endocrinol Metab. 2015 Oct;100(10):3718-24).

Dr. Noergaard and Dr. Anderson reported having no financial conflicts regarding their studies, which were carried out free of commercial support.

bjancin@mdedge.com

CHICAGO – The short-term risk of developing heart failure in patients with newly identified hypothyroidism, be it overt or subclinical, is double that of euthyroid individuals, Caroline H. Noergaard, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“This is really important clinically. The association with heart failure has previously been shown in both overt and subclinical hyperthyroidism, but it’s actually new knowledge that hypothyroidism is associated with immediate risk of heart failure. And a lot of people have subclinical hypothyroidism,” said Dr. Noergaard, a PhD student in epidemiology at Aalborg (Denmark) University.

Also at the meeting, Jeffrey L. Anderson, MD, reported that free thyroxine levels within the normal reference range were associated in graded fashion with an increased prevalence and incidence of atrial fibrillation in a large Utah study, a finding that provides independent confirmation of an earlier report by investigators from the population-based Rotterdam Study.

“These findings validate those of the Rotterdam Study in a much larger dataset and may have important clinical implications, including a redefinition of the reference range and the target-free T₄ levels for thyroxine replacement therapy,” observed Dr. Anderson, professor of internal medicine at the University of Utah, Salt Lake City, and a research cardiologist at the Intermountain Medical Center Heart Institute.

Hypothyroidism and heart failure

Dr. Noergaard presented a retrospective study of over 1 million Copenhagen-area adults (mean age, 50 years) with no history of heart failure, who had their first thyroid function test. She and her coinvestigators turned to comprehensive Danish national health care registries to determine how many of these individuals were diagnosed with new-onset heart failure within 90 days after their thyroid function test.

Subclinical hypothyroidism was defined by a thyroid-stimulating hormone level greater than 5 mIU/L and a free T₄ of 9-22 pmol/L. Overt hypothyroidism required a TSH greater than 5 mIU/L with a free T₄ less than 9 pmol/L.

Free T₄ predicts atrial fibrillation risk

Dr. Anderson presented a retrospective analysis of 174,914 adult patients in the Intermountain Healthcare EMR database, none of whom were on thyroid replacement at entry. The patients, who were a mean age of 64 years and 65% women, were followed for an average of 6.3 years. Of these, 88.4% had a free T₄ within the normal reference range of 0.75-1.5 ng/dL, 7.4% had a value below the cutoff for normal, and 4.2% had a free T₄ above the reference range.

Upon dividing the patients within the normal range into quartiles based upon their free T₄ level, he and his coinvestigators found that the baseline prevalence of atrial fibrillation was 8.7% in those in quartile 1, 9.3% in quartile 2, 10.5% in quartile 3, and 12.6% in quartile 4. In a multivariate analysis adjusted for potential confounders, the risk of prevalent atrial fibrillation was increased by 11% for patients in quartile 2, compared with those in the first quartile, by 22% in quartile 3, and by 40% in quartile 4.

The incidence of new-onset atrial fibrillation during 3 years of follow-up was 4.1% in patients in normal-range quartile 1, 4.3% in quartile 2, 4.5% in quartile 3, and 5.2% in the top normal-range quartile. The odds of developing atrial fibrillation were increased by 8% and 16% in quartiles 3 and 4, compared with quartile 1.

Serum TSH and free T₃ levels showed no consistent relationship with atrial fibrillation.

The Utah findings confirm in a large U.S. population the earlier report from the Rotterdam Study (J Clin Endocrinol Metab. 2015 Oct;100(10):3718-24).

Dr. Noergaard and Dr. Anderson reported having no financial conflicts regarding their studies, which were carried out free of commercial support.

bjancin@mdedge.com

Numerous independent factors – including a history of obstructive/central sleep apnea syndrome (OSAS/CSAS) or myocardial infarction, along with a body mass index greater than 30 g/m² – could be related to ICU admission and subsequent high mortality rates in influenza patients, according to an analysis of patients in the Netherlands who were treated during the influenza epidemic of 2015-2016.

copyright Andrei Malov/Thinkstock

Along with determining these factors, lead author M.C. Beumer, of Radboud University Medical Center, the Netherlands, and his coauthors found that “coinfections with bacterial, fungal, and viral pathogens developed more often in patients who were admitted to the ICU.” The study was published in the Journal of Critical Care.

The coauthors reviewed 199 influenza patients who were admitted to two medical centers in the Netherlands during October 2015–April 2016. Of those patients, 45 (23%) were admitted to the ICU, primarily because of respiratory failure, and their mortality rate was 17/45 (38%) versus an overall mortality rate of 18/199 (9%).

Compared with patients in the normal ward, patients admitted to the ICU more frequently had a history of OSAS/CSAS (11% vs. 3%; P = .03) and MI (20% vs. 6%; P = .007), along with a BMI higher than 30 g/m² (30% vs. 15%; P = .04) and dyspnea as a symptom (77% vs. 48%,; P = .001). In addition, more ICU-admitted patients had influenza A rather than influenza B, compared with those not admitted (87% vs. 66%; P = .009).

Pulmonary coinfections – including bacterial, fungal, and viral pathogens – were also proportionally higher among the 45 ICU patients (56% vs. 20%; P less than .0001). The most common bacterial pathogens were Staphylococcus aureus (11%) and Streptococcus pneumoniae (7%) while Aspergillus fumigatus (18%) and Pneumocystis jirovecii (7%) topped the fungal pathogens.

Mr. Beumer and his colleagues noted potential limitations of their work, including the selection of patients from among the “most severely ill” contributing to an ICU admission rate that surpassed the 5%-10% described elsewhere. They also admitted that their study relied on a “relatively small sample size,” focusing on one seasonal influenza outbreak. However, “despite the limited validity,” they reiterated that “the identified factors may contribute to a complicated disease course and could represent a tool for early recognition of the influenza patients at risk for a complicated disease course.”

The authors reported no conflicts of interest.

SOURCE: Beumer MC et al. J Crit Care. 2019;50:59-65.



.

Numerous independent factors – including a history of obstructive/central sleep apnea syndrome (OSAS/CSAS) or myocardial infarction, along with a body mass index greater than 30 g/m² – could be related to ICU admission and subsequent high mortality rates in influenza patients, according to an analysis of patients in the Netherlands who were treated during the influenza epidemic of 2015-2016.

copyright Andrei Malov/Thinkstock

Along with determining these factors, lead author M.C. Beumer, of Radboud University Medical Center, the Netherlands, and his coauthors found that “coinfections with bacterial, fungal, and viral pathogens developed more often in patients who were admitted to the ICU.” The study was published in the Journal of Critical Care.

The coauthors reviewed 199 influenza patients who were admitted to two medical centers in the Netherlands during October 2015–April 2016. Of those patients, 45 (23%) were admitted to the ICU, primarily because of respiratory failure, and their mortality rate was 17/45 (38%) versus an overall mortality rate of 18/199 (9%).

Compared with patients in the normal ward, patients admitted to the ICU more frequently had a history of OSAS/CSAS (11% vs. 3%; P = .03) and MI (20% vs. 6%; P = .007), along with a BMI higher than 30 g/m² (30% vs. 15%; P = .04) and dyspnea as a symptom (77% vs. 48%,; P = .001). In addition, more ICU-admitted patients had influenza A rather than influenza B, compared with those not admitted (87% vs. 66%; P = .009).

Pulmonary coinfections – including bacterial, fungal, and viral pathogens – were also proportionally higher among the 45 ICU patients (56% vs. 20%; P less than .0001). The most common bacterial pathogens were Staphylococcus aureus (11%) and Streptococcus pneumoniae (7%) while Aspergillus fumigatus (18%) and Pneumocystis jirovecii (7%) topped the fungal pathogens.

Mr. Beumer and his colleagues noted potential limitations of their work, including the selection of patients from among the “most severely ill” contributing to an ICU admission rate that surpassed the 5%-10% described elsewhere. They also admitted that their study relied on a “relatively small sample size,” focusing on one seasonal influenza outbreak. However, “despite the limited validity,” they reiterated that “the identified factors may contribute to a complicated disease course and could represent a tool for early recognition of the influenza patients at risk for a complicated disease course.”

The authors reported no conflicts of interest.

SOURCE: Beumer MC et al. J Crit Care. 2019;50:59-65.



.

Numerous independent factors – including a history of obstructive/central sleep apnea syndrome (OSAS/CSAS) or myocardial infarction, along with a body mass index greater than 30 g/m² – could be related to ICU admission and subsequent high mortality rates in influenza patients, according to an analysis of patients in the Netherlands who were treated during the influenza epidemic of 2015-2016.

copyright Andrei Malov/Thinkstock

Along with determining these factors, lead author M.C. Beumer, of Radboud University Medical Center, the Netherlands, and his coauthors found that “coinfections with bacterial, fungal, and viral pathogens developed more often in patients who were admitted to the ICU.” The study was published in the Journal of Critical Care.

The coauthors reviewed 199 influenza patients who were admitted to two medical centers in the Netherlands during October 2015–April 2016. Of those patients, 45 (23%) were admitted to the ICU, primarily because of respiratory failure, and their mortality rate was 17/45 (38%) versus an overall mortality rate of 18/199 (9%).

Compared with patients in the normal ward, patients admitted to the ICU more frequently had a history of OSAS/CSAS (11% vs. 3%; P = .03) and MI (20% vs. 6%; P = .007), along with a BMI higher than 30 g/m² (30% vs. 15%; P = .04) and dyspnea as a symptom (77% vs. 48%,; P = .001). In addition, more ICU-admitted patients had influenza A rather than influenza B, compared with those not admitted (87% vs. 66%; P = .009).

Pulmonary coinfections – including bacterial, fungal, and viral pathogens – were also proportionally higher among the 45 ICU patients (56% vs. 20%; P less than .0001). The most common bacterial pathogens were Staphylococcus aureus (11%) and Streptococcus pneumoniae (7%) while Aspergillus fumigatus (18%) and Pneumocystis jirovecii (7%) topped the fungal pathogens.

Mr. Beumer and his colleagues noted potential limitations of their work, including the selection of patients from among the “most severely ill” contributing to an ICU admission rate that surpassed the 5%-10% described elsewhere. They also admitted that their study relied on a “relatively small sample size,” focusing on one seasonal influenza outbreak. However, “despite the limited validity,” they reiterated that “the identified factors may contribute to a complicated disease course and could represent a tool for early recognition of the influenza patients at risk for a complicated disease course.”

The authors reported no conflicts of interest.

SOURCE: Beumer MC et al. J Crit Care. 2019;50:59-65.



.

The way we diagnose and treat patients is the result of years of research. But securing the future of the field is no small task. Promising early stage investigators find it increasingly difficult to secure funding, and many leave the field because they are unable to sustain a research career. A donation to the charitable arm of the American Gastroenterological Association (AGA), the AGA Research Foundation, will help fill the funding gap and contribute to this tradition of discovery.

The foundation provides a key source of funding at a critical juncture in a young investigator’s career.

Help spark the scientific breakthroughs of today, so clinicians will have the tools to improve care tomorrow. Your tax-deductible donation will make a critical difference in retaining talented GI scientists, like Won Jae Huh, MD, whose research will impact the future care of patients.

“As a clinical researcher, funding for investigation is critical in scientific breakthroughs to promote more efficient and robust patient care. My project will provide novel insights into the role of distensibility in the treatment of patients with esophageal eosinophilia, potentially resulting in more efficient treatment selection and disease management.”

“This funding mechanism will secure my research time to investigate signaling pathways involved in the pathogenesis of Ménétrier’s disease, and will provide resources and support to launch my research career. The results from my research project will be helpful for treating Ménétrier’s disease patients.”

Help spark the scientific breakthroughs of today, so clinicians will have the tools to improve care tomorrow. Your tax-deductible donation will make a critical difference in retaining talented GI scientists, like Dr. Won Jae Huh, whose research will impact the future care of patients.

Donate on the foundation’s website at www.gastro.org/donateonline or by mail to 4930 Del Ray Avenue, Bethesda, MD 20814.

ginews@gastro.org

The way we diagnose and treat patients is the result of years of research. But securing the future of the field is no small task. Promising early stage investigators find it increasingly difficult to secure funding, and many leave the field because they are unable to sustain a research career. A donation to the charitable arm of the American Gastroenterological Association (AGA), the AGA Research Foundation, will help fill the funding gap and contribute to this tradition of discovery.

The foundation provides a key source of funding at a critical juncture in a young investigator’s career.

Help spark the scientific breakthroughs of today, so clinicians will have the tools to improve care tomorrow. Your tax-deductible donation will make a critical difference in retaining talented GI scientists, like Won Jae Huh, MD, whose research will impact the future care of patients.

“As a clinical researcher, funding for investigation is critical in scientific breakthroughs to promote more efficient and robust patient care. My project will provide novel insights into the role of distensibility in the treatment of patients with esophageal eosinophilia, potentially resulting in more efficient treatment selection and disease management.”

“This funding mechanism will secure my research time to investigate signaling pathways involved in the pathogenesis of Ménétrier’s disease, and will provide resources and support to launch my research career. The results from my research project will be helpful for treating Ménétrier’s disease patients.”

Help spark the scientific breakthroughs of today, so clinicians will have the tools to improve care tomorrow. Your tax-deductible donation will make a critical difference in retaining talented GI scientists, like Dr. Won Jae Huh, whose research will impact the future care of patients.

Donate on the foundation’s website at www.gastro.org/donateonline or by mail to 4930 Del Ray Avenue, Bethesda, MD 20814.

ginews@gastro.org

The way we diagnose and treat patients is the result of years of research. But securing the future of the field is no small task. Promising early stage investigators find it increasingly difficult to secure funding, and many leave the field because they are unable to sustain a research career. A donation to the charitable arm of the American Gastroenterological Association (AGA), the AGA Research Foundation, will help fill the funding gap and contribute to this tradition of discovery.

The foundation provides a key source of funding at a critical juncture in a young investigator’s career.

Help spark the scientific breakthroughs of today, so clinicians will have the tools to improve care tomorrow. Your tax-deductible donation will make a critical difference in retaining talented GI scientists, like Won Jae Huh, MD, whose research will impact the future care of patients.

“As a clinical researcher, funding for investigation is critical in scientific breakthroughs to promote more efficient and robust patient care. My project will provide novel insights into the role of distensibility in the treatment of patients with esophageal eosinophilia, potentially resulting in more efficient treatment selection and disease management.”

“This funding mechanism will secure my research time to investigate signaling pathways involved in the pathogenesis of Ménétrier’s disease, and will provide resources and support to launch my research career. The results from my research project will be helpful for treating Ménétrier’s disease patients.”

Help spark the scientific breakthroughs of today, so clinicians will have the tools to improve care tomorrow. Your tax-deductible donation will make a critical difference in retaining talented GI scientists, like Dr. Won Jae Huh, whose research will impact the future care of patients.

Donate on the foundation’s website at www.gastro.org/donateonline or by mail to 4930 Del Ray Avenue, Bethesda, MD 20814.

ginews@gastro.org

President Trump on Jan. 23 instructed administration officials to investigate how to prevent surprise medical bills, broadening his focus on drug prices to include other issues of price transparency in health care.

DNY59/gettyimages

Flanked by patients and other guests invited to the White House to share their stories of unexpected and outrageous bills, Trump tasked his health secretary, Alex Azar, and labor secretary, Alex Acosta, with working on a solution, several attendees said.

“The pricing is hurting patients, and we’ve stopped a lot of it, but we’re going to stop all of it,” Mr. Trump said during a roundtable discussion when reporters were briefly allowed into the otherwise closed-door meeting.

David Silverstein, the founder of a Colorado-based nonprofit called Broken Healthcare who attended, said Mr. Trump struck an aggressive tone, calling for a solution with “the biggest teeth you can find.”

“Reading the tea leaves, I think there’s big change coming,” Mr. Silverstein said.

Surprise billing, or the practice of charging patients for care that is more expensive than anticipated or not covered by their insurance, has received a flood of attention in the past year, particularly as Kaiser Health News and other news organizations have undertaken investigations into patients’ most outrageous medical bills.

Attendees said each of 10 invited guests – among them patients as well as doctors with their own stories of unexpected bills – was given an opportunity to talk, though Mr. Trump did not stay to hear all of their stories during the roughly hour-long gathering.

The group included Paul Davis, a retired doctor from Findlay, Ohio, whose family’s experience with a $17,850 bill for a simple urine test was detailed in a KHN-NPR “Bill of the Month” feature last year.

KHN correspondents Shefali Luthra and Jay Hancock contributed to this report. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

President Trump on Jan. 23 instructed administration officials to investigate how to prevent surprise medical bills, broadening his focus on drug prices to include other issues of price transparency in health care.

DNY59/gettyimages

Flanked by patients and other guests invited to the White House to share their stories of unexpected and outrageous bills, Trump tasked his health secretary, Alex Azar, and labor secretary, Alex Acosta, with working on a solution, several attendees said.

“The pricing is hurting patients, and we’ve stopped a lot of it, but we’re going to stop all of it,” Mr. Trump said during a roundtable discussion when reporters were briefly allowed into the otherwise closed-door meeting.

David Silverstein, the founder of a Colorado-based nonprofit called Broken Healthcare who attended, said Mr. Trump struck an aggressive tone, calling for a solution with “the biggest teeth you can find.”

“Reading the tea leaves, I think there’s big change coming,” Mr. Silverstein said.

Surprise billing, or the practice of charging patients for care that is more expensive than anticipated or not covered by their insurance, has received a flood of attention in the past year, particularly as Kaiser Health News and other news organizations have undertaken investigations into patients’ most outrageous medical bills.

Attendees said each of 10 invited guests – among them patients as well as doctors with their own stories of unexpected bills – was given an opportunity to talk, though Mr. Trump did not stay to hear all of their stories during the roughly hour-long gathering.

The group included Paul Davis, a retired doctor from Findlay, Ohio, whose family’s experience with a $17,850 bill for a simple urine test was detailed in a KHN-NPR “Bill of the Month” feature last year.

KHN correspondents Shefali Luthra and Jay Hancock contributed to this report. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

President Trump on Jan. 23 instructed administration officials to investigate how to prevent surprise medical bills, broadening his focus on drug prices to include other issues of price transparency in health care.

DNY59/gettyimages

Flanked by patients and other guests invited to the White House to share their stories of unexpected and outrageous bills, Trump tasked his health secretary, Alex Azar, and labor secretary, Alex Acosta, with working on a solution, several attendees said.

“The pricing is hurting patients, and we’ve stopped a lot of it, but we’re going to stop all of it,” Mr. Trump said during a roundtable discussion when reporters were briefly allowed into the otherwise closed-door meeting.

David Silverstein, the founder of a Colorado-based nonprofit called Broken Healthcare who attended, said Mr. Trump struck an aggressive tone, calling for a solution with “the biggest teeth you can find.”

“Reading the tea leaves, I think there’s big change coming,” Mr. Silverstein said.

Surprise billing, or the practice of charging patients for care that is more expensive than anticipated or not covered by their insurance, has received a flood of attention in the past year, particularly as Kaiser Health News and other news organizations have undertaken investigations into patients’ most outrageous medical bills.

Attendees said each of 10 invited guests – among them patients as well as doctors with their own stories of unexpected bills – was given an opportunity to talk, though Mr. Trump did not stay to hear all of their stories during the roughly hour-long gathering.

The group included Paul Davis, a retired doctor from Findlay, Ohio, whose family’s experience with a $17,850 bill for a simple urine test was detailed in a KHN-NPR “Bill of the Month” feature last year.

KHN correspondents Shefali Luthra and Jay Hancock contributed to this report. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Most parents are unaware their teenager has been having suicidal thoughts or thinking about death, according to a study published in Pediatrics.

asiseeit/E+/Getty Images

Jason D. Jones, PhD, from the Children’s Hospital of Philadelphia, and his coauthors wrote that more than two-thirds of adolescents who experience suicidal thoughts do not get medical help, and this may be because their parents – the gatekeepers for mental health services – are unaware of what their teen is going through.

In this study, researchers recruited 5,137 adolescents aged 11-17 years and either a parent or step-parent, and interviewed both about the adolescent’s lifetime suicidal thoughts.

While 413 (8%) of the adolescents surveyed said they had had thoughts about killing themselves, 50% of those adolescents’ parents said their teen hadn’t experienced suicidal thoughts. Similarly, 786 (15%) of adolescents surveyed said they had had thoughts about death and dying, but three-quarters of their parents were unaware.

A significant number of parents – 8% – said their teenager had had suicidal thoughts, but in 48% of these cases, the teenager said they had not thought about killing themselves.

Researchers saw more agreement between parents and adolescents when the adolescents were older: The parents were less likely to be unaware that their older teen had had suicidal thoughts, and older adolescents were less likely to deny it.

“This indicates that younger adolescents may be more likely to go unnoticed and not receive services either because their parents are unaware of their suicidal thoughts or because they deny suicidal thoughts that their parents think they are having,” Dr. Jones and his associates wrote. They also suggested younger adolescents may have “interpretive difficulties” around questions of suicidal ideation.

“These age findings are particularly noteworthy in light of recent evidence that deaths by suicide have increased among younger adolescents,” they noted.

There also was an interaction between age and gender. For girls, parents were less likely to be aware of suicidal thoughts in their younger daughters but more likely to be aware of them in their older daughters. However the opposite was true for boys: Parental unawareness increased slightly in older boys.

Parents of Hispanic or Latino ethnicity were less likely to be aware that their offspring had had thoughts about death and dying.

Generally fathers were less likely than mothers to be aware of suicidal thoughts in their adolescents.

However, if adolescents had previously received psychiatric treatment, or there was a family history of suicide, parents were more likely to be aware of suicidal thoughts, and adolescents who had a history of psychiatric hospitalization were less likely to deny suicidal thoughts, the researchers reported.

The study was supported by grants from the National Institutes of Health, the Dowshen Program for Neuroscience, and the Lifespan Brain Institute of the Children’s Hospital of Philadelphia and University of Pennsylvania. The study was funded by NIH. One author declared a board position and stock options in Taliaz Health unrelated to the study subject; the other authors said they had no relevant financial disclosures.

SOURCE: Jones JD et al. Pediatrics. 2019 Jan 14. doi: 10.1542/peds.2018-1771.
 

Most parents are unaware their teenager has been having suicidal thoughts or thinking about death, according to a study published in Pediatrics.

asiseeit/E+/Getty Images

Jason D. Jones, PhD, from the Children’s Hospital of Philadelphia, and his coauthors wrote that more than two-thirds of adolescents who experience suicidal thoughts do not get medical help, and this may be because their parents – the gatekeepers for mental health services – are unaware of what their teen is going through.

In this study, researchers recruited 5,137 adolescents aged 11-17 years and either a parent or step-parent, and interviewed both about the adolescent’s lifetime suicidal thoughts.

While 413 (8%) of the adolescents surveyed said they had had thoughts about killing themselves, 50% of those adolescents’ parents said their teen hadn’t experienced suicidal thoughts. Similarly, 786 (15%) of adolescents surveyed said they had had thoughts about death and dying, but three-quarters of their parents were unaware.

A significant number of parents – 8% – said their teenager had had suicidal thoughts, but in 48% of these cases, the teenager said they had not thought about killing themselves.

Researchers saw more agreement between parents and adolescents when the adolescents were older: The parents were less likely to be unaware that their older teen had had suicidal thoughts, and older adolescents were less likely to deny it.

“This indicates that younger adolescents may be more likely to go unnoticed and not receive services either because their parents are unaware of their suicidal thoughts or because they deny suicidal thoughts that their parents think they are having,” Dr. Jones and his associates wrote. They also suggested younger adolescents may have “interpretive difficulties” around questions of suicidal ideation.

“These age findings are particularly noteworthy in light of recent evidence that deaths by suicide have increased among younger adolescents,” they noted.

There also was an interaction between age and gender. For girls, parents were less likely to be aware of suicidal thoughts in their younger daughters but more likely to be aware of them in their older daughters. However the opposite was true for boys: Parental unawareness increased slightly in older boys.

Parents of Hispanic or Latino ethnicity were less likely to be aware that their offspring had had thoughts about death and dying.

Generally fathers were less likely than mothers to be aware of suicidal thoughts in their adolescents.

However, if adolescents had previously received psychiatric treatment, or there was a family history of suicide, parents were more likely to be aware of suicidal thoughts, and adolescents who had a history of psychiatric hospitalization were less likely to deny suicidal thoughts, the researchers reported.

The study was supported by grants from the National Institutes of Health, the Dowshen Program for Neuroscience, and the Lifespan Brain Institute of the Children’s Hospital of Philadelphia and University of Pennsylvania. The study was funded by NIH. One author declared a board position and stock options in Taliaz Health unrelated to the study subject; the other authors said they had no relevant financial disclosures.

SOURCE: Jones JD et al. Pediatrics. 2019 Jan 14. doi: 10.1542/peds.2018-1771.
 

Most parents are unaware their teenager has been having suicidal thoughts or thinking about death, according to a study published in Pediatrics.

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Jason D. Jones, PhD, from the Children’s Hospital of Philadelphia, and his coauthors wrote that more than two-thirds of adolescents who experience suicidal thoughts do not get medical help, and this may be because their parents – the gatekeepers for mental health services – are unaware of what their teen is going through.

In this study, researchers recruited 5,137 adolescents aged 11-17 years and either a parent or step-parent, and interviewed both about the adolescent’s lifetime suicidal thoughts.

While 413 (8%) of the adolescents surveyed said they had had thoughts about killing themselves, 50% of those adolescents’ parents said their teen hadn’t experienced suicidal thoughts. Similarly, 786 (15%) of adolescents surveyed said they had had thoughts about death and dying, but three-quarters of their parents were unaware.

A significant number of parents – 8% – said their teenager had had suicidal thoughts, but in 48% of these cases, the teenager said they had not thought about killing themselves.

Researchers saw more agreement between parents and adolescents when the adolescents were older: The parents were less likely to be unaware that their older teen had had suicidal thoughts, and older adolescents were less likely to deny it.

“This indicates that younger adolescents may be more likely to go unnoticed and not receive services either because their parents are unaware of their suicidal thoughts or because they deny suicidal thoughts that their parents think they are having,” Dr. Jones and his associates wrote. They also suggested younger adolescents may have “interpretive difficulties” around questions of suicidal ideation.

“These age findings are particularly noteworthy in light of recent evidence that deaths by suicide have increased among younger adolescents,” they noted.

There also was an interaction between age and gender. For girls, parents were less likely to be aware of suicidal thoughts in their younger daughters but more likely to be aware of them in their older daughters. However the opposite was true for boys: Parental unawareness increased slightly in older boys.

Parents of Hispanic or Latino ethnicity were less likely to be aware that their offspring had had thoughts about death and dying.

Generally fathers were less likely than mothers to be aware of suicidal thoughts in their adolescents.

However, if adolescents had previously received psychiatric treatment, or there was a family history of suicide, parents were more likely to be aware of suicidal thoughts, and adolescents who had a history of psychiatric hospitalization were less likely to deny suicidal thoughts, the researchers reported.

The study was supported by grants from the National Institutes of Health, the Dowshen Program for Neuroscience, and the Lifespan Brain Institute of the Children’s Hospital of Philadelphia and University of Pennsylvania. The study was funded by NIH. One author declared a board position and stock options in Taliaz Health unrelated to the study subject; the other authors said they had no relevant financial disclosures.

SOURCE: Jones JD et al. Pediatrics. 2019 Jan 14. doi: 10.1542/peds.2018-1771.