Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.

The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).

Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.

The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 10⁷ cells/100 mL per month for four cycles beginning 4 months after HSCT

Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.

The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).

The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.

The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.

The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.

Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.

The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).

Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.

The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 10⁷ cells/100 mL per month for four cycles beginning 4 months after HSCT

Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.

The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).

The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.

The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.

The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.

Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.

The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).

Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.

The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 10⁷ cells/100 mL per month for four cycles beginning 4 months after HSCT

Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.

The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).

The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.

The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.

The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.

Standard oncology measures are acceptable indicators of good-quality end of life care for hematologic malignancies, investigators report.

Six out of eight standard end of life (EOL) care measures were deemed acceptable (defined as greater than 55% agreement) based on 349 returned surveys from hematologic oncologists. Hospice enrollment more than 7 days before death, no chemotherapy less than 14 days before death, and no CPR and intubation within the last 30 days of life were acceptable measures to more than 75% of those surveyed.

No more than one hospitalization within 30 days of death and no more than one emergency room visit within 30 days of death did not meet the threshold for acceptance by the oncologists.

“These data suggest that the absence of hematology-specific measures is unlikely to be a major barrier to quality care and that more resources should be directed toward addressing barriers to compliance with established EOL quality measures than toward creating new ones,” Oreofe O. Odejide, MD, of the Dana-Farber Cancer Institute, Boston, and her associates reported (J Clin Oncol. 2016 July. doi: 10.1200/JCO.2016.67.8177).

The top barriers to end of life care were unrealistic patient expectations (97.3%), clinician concern about diminishing patient and family hope (71.3%), and unrealistic clinician expectations (59.0%), according to investigators.

Surveyed oncologists also reported that increasing access to palliative care services (93.7%), increasing access to inpatient hospice facilities (92.2%), and allowing hospice enrollment with disease-directed treatment (90.1%) would be the most helpful interventions to improve end of life care.

The Lymphoma Research Foundation, the Conquer Cancer Foundation, and investigators’ respective institutions funded this research. Dr. Odejide and four of her associates had no disclosures to report. Two investigators reported serving in advisory roles, holding patents, or having stock or ownership interest in UnitedHealthcare, UpToDate, or Recap Information Systems.

[email protected]

On Twitter @jessnicolecraig

Standard oncology measures are acceptable indicators of good-quality end of life care for hematologic malignancies, investigators report.

Six out of eight standard end of life (EOL) care measures were deemed acceptable (defined as greater than 55% agreement) based on 349 returned surveys from hematologic oncologists. Hospice enrollment more than 7 days before death, no chemotherapy less than 14 days before death, and no CPR and intubation within the last 30 days of life were acceptable measures to more than 75% of those surveyed.

No more than one hospitalization within 30 days of death and no more than one emergency room visit within 30 days of death did not meet the threshold for acceptance by the oncologists.

“These data suggest that the absence of hematology-specific measures is unlikely to be a major barrier to quality care and that more resources should be directed toward addressing barriers to compliance with established EOL quality measures than toward creating new ones,” Oreofe O. Odejide, MD, of the Dana-Farber Cancer Institute, Boston, and her associates reported (J Clin Oncol. 2016 July. doi: 10.1200/JCO.2016.67.8177).

The top barriers to end of life care were unrealistic patient expectations (97.3%), clinician concern about diminishing patient and family hope (71.3%), and unrealistic clinician expectations (59.0%), according to investigators.

Surveyed oncologists also reported that increasing access to palliative care services (93.7%), increasing access to inpatient hospice facilities (92.2%), and allowing hospice enrollment with disease-directed treatment (90.1%) would be the most helpful interventions to improve end of life care.

The Lymphoma Research Foundation, the Conquer Cancer Foundation, and investigators’ respective institutions funded this research. Dr. Odejide and four of her associates had no disclosures to report. Two investigators reported serving in advisory roles, holding patents, or having stock or ownership interest in UnitedHealthcare, UpToDate, or Recap Information Systems.

[email protected]

On Twitter @jessnicolecraig

Standard oncology measures are acceptable indicators of good-quality end of life care for hematologic malignancies, investigators report.

Six out of eight standard end of life (EOL) care measures were deemed acceptable (defined as greater than 55% agreement) based on 349 returned surveys from hematologic oncologists. Hospice enrollment more than 7 days before death, no chemotherapy less than 14 days before death, and no CPR and intubation within the last 30 days of life were acceptable measures to more than 75% of those surveyed.

No more than one hospitalization within 30 days of death and no more than one emergency room visit within 30 days of death did not meet the threshold for acceptance by the oncologists.

“These data suggest that the absence of hematology-specific measures is unlikely to be a major barrier to quality care and that more resources should be directed toward addressing barriers to compliance with established EOL quality measures than toward creating new ones,” Oreofe O. Odejide, MD, of the Dana-Farber Cancer Institute, Boston, and her associates reported (J Clin Oncol. 2016 July. doi: 10.1200/JCO.2016.67.8177).

The top barriers to end of life care were unrealistic patient expectations (97.3%), clinician concern about diminishing patient and family hope (71.3%), and unrealistic clinician expectations (59.0%), according to investigators.

Surveyed oncologists also reported that increasing access to palliative care services (93.7%), increasing access to inpatient hospice facilities (92.2%), and allowing hospice enrollment with disease-directed treatment (90.1%) would be the most helpful interventions to improve end of life care.

The Lymphoma Research Foundation, the Conquer Cancer Foundation, and investigators’ respective institutions funded this research. Dr. Odejide and four of her associates had no disclosures to report. Two investigators reported serving in advisory roles, holding patents, or having stock or ownership interest in UnitedHealthcare, UpToDate, or Recap Information Systems.

[email protected]

On Twitter @jessnicolecraig

Many commonly used prescription drugs, many OTC agents, and also several complimentary or alternative medications, can either trigger heart failure or exacerbate the disease in patients with existing heart failure according to a Scientific Statement written by a committee of the American Heart Association and released on July 11.

This first-ever authoritative U.S. overview of what is known about drugs that can affect heart failure was compiled to address an important practice issue for the large and growing number of U.S. patients with heart failure, estimated to be nearly 6 million Americans, and “provide some guidance to health care providers in how to minimize polypharmacy, improve medication safety, as well as identify the medications that could exacerbate or cause heart failure,” said Robert L. Page II, PharmD, chair of the committee and a professor of clinical pharmacy at the University of Colorado at Denver, Aurora.

Although the comprehensive statement lists 88 distinct prescription drugs or drug classes as agents that pose major or moderate threats for causing or worsening heart failure, “from the American public’s perspective, importance should be placed on educating patients regarding the impact that OTC medications can have on their heart failure,” Dr. Page said in an interview. “For example, nonsteroidal anti-inflammatory drugs like ibuprofen or naproxen can cause sodium and water retention and antagonize the effects of evidence-based heart failure pharmacotherapies. Additionally, OTC medications like pseudoephedrine, which many cough and cold products contain, can increase blood pressure and afterload,” he noted. The risks these drugs pose becomes even greater when they are taken at higher doses.

NSAIDs

The statement cites already existing guidance from the American College of Cardiology and American Heart Association that for patients with existing heart failure, use of NSAIDs should either be avoided or withdrawn when possible. The statement advises educating patients to communicate with their health care provider before taking any OTC medication or complimentary or alternative medication, avoid these agents when their efficacy and safety is uncertain, and evaluate the labels of these products for their sodium content (although the sodium content from inactive ingredients may be difficult to find in labeling).

“Currently, we teach patients to read food labels for sodium content, but we also need to educate patients on how to read OTC medication labels for both ingredients and sodium content. Many OTC antacids may have a large sodium load,” Dr. Page said. The statement includes a list of 14 prescription drugs and also highlights several OTC formulations that have an especially high sodium content.

Metformin

Among the many prescription drugs listed, one notable entry is for the oral hypoglycemic agent metformin that today is among the most widely used drugs for treating type 2 diabetes and is especially relevant for heart failure patients because, as the statement notes, 38% also have diabetes. The statement details the long history of metformin and heart failure, noting that until a decade ago, the drug had a contraindication for patients with heart failure, that metformin’s label still carries a black box warning for cautious use in heart failure patients, and that earlier in 2016, the Food and Drug Administration cautioned that metformin should not be used in patients with an estimated glomerular filtration rate of less than 30 mL/minute per 1.73 m². The statement also endorsed a recommendation from the American Diabetes Association that metformin not be used in patients with unstable heart failure or those hospitalized for heart failure.

Antihypertensives, biologics, and more

Other notable prescription drugs listed as potentially having a major impact on causing or worsening heart failure include the antihypertensive drugs diltiazem, verapamil, and moxonidine, the tumor necrosis factor–inhibitors that are widely used to treat rheumatologic and gastroenterologic diseases, the antipsychotic clozapine, and a long list of anticancer medications, including several anthracyclines and many types of newer biologic agents.

The statement also lists several specific recommendations to health care providers for improving oversight of the drugs taken by patients with heart failure or those at risk for heart failure. These include a comprehensive medication review during each clinical encounter. The statement also suggests a “medication flow sheet” for each patient that contains the basic information regarding the regimen for each medication taken by a patient: the brand and generic name, the purpose of the medication, and its dosage. “These medication flow sheets should be used by patients as a tool to enhance safety and adherence, and they should show their flow sheets at each provider visit,” Dr. Page said.

Managing myriad meds

The statement also calls for stopping medications without a well defined indication for a patient, avoid prescribing new drugs to address side effects of other drugs, and suggests establishing a “captain” among the health care providers seen by each patient who would be particularly responsible for overseeing and keeping track of the medications the patient takes.

“Ideally, this ‘captain’ would be the patient’s primary care provider, who should be in contact with the other specialists that the patient may be seeing. However, this does not always happen,” said Dr. Page. “Therefore, I encourage each patient with heart failure to contact both their primary care provider and their health care provider who is managing their heart failure before taking or stopping any new medication including prescription, OTC, herbal, complimentary or alternative medication or supplement. Health care providers need to encourage patients to be actively engaged in their medication management.”

Dr. Page had no disclosures.

[email protected]

On Twitter @mitchelzoler

Many commonly used prescription drugs, many OTC agents, and also several complimentary or alternative medications, can either trigger heart failure or exacerbate the disease in patients with existing heart failure according to a Scientific Statement written by a committee of the American Heart Association and released on July 11.

This first-ever authoritative U.S. overview of what is known about drugs that can affect heart failure was compiled to address an important practice issue for the large and growing number of U.S. patients with heart failure, estimated to be nearly 6 million Americans, and “provide some guidance to health care providers in how to minimize polypharmacy, improve medication safety, as well as identify the medications that could exacerbate or cause heart failure,” said Robert L. Page II, PharmD, chair of the committee and a professor of clinical pharmacy at the University of Colorado at Denver, Aurora.

Although the comprehensive statement lists 88 distinct prescription drugs or drug classes as agents that pose major or moderate threats for causing or worsening heart failure, “from the American public’s perspective, importance should be placed on educating patients regarding the impact that OTC medications can have on their heart failure,” Dr. Page said in an interview. “For example, nonsteroidal anti-inflammatory drugs like ibuprofen or naproxen can cause sodium and water retention and antagonize the effects of evidence-based heart failure pharmacotherapies. Additionally, OTC medications like pseudoephedrine, which many cough and cold products contain, can increase blood pressure and afterload,” he noted. The risks these drugs pose becomes even greater when they are taken at higher doses.

NSAIDs

The statement cites already existing guidance from the American College of Cardiology and American Heart Association that for patients with existing heart failure, use of NSAIDs should either be avoided or withdrawn when possible. The statement advises educating patients to communicate with their health care provider before taking any OTC medication or complimentary or alternative medication, avoid these agents when their efficacy and safety is uncertain, and evaluate the labels of these products for their sodium content (although the sodium content from inactive ingredients may be difficult to find in labeling).

“Currently, we teach patients to read food labels for sodium content, but we also need to educate patients on how to read OTC medication labels for both ingredients and sodium content. Many OTC antacids may have a large sodium load,” Dr. Page said. The statement includes a list of 14 prescription drugs and also highlights several OTC formulations that have an especially high sodium content.

Metformin

Among the many prescription drugs listed, one notable entry is for the oral hypoglycemic agent metformin that today is among the most widely used drugs for treating type 2 diabetes and is especially relevant for heart failure patients because, as the statement notes, 38% also have diabetes. The statement details the long history of metformin and heart failure, noting that until a decade ago, the drug had a contraindication for patients with heart failure, that metformin’s label still carries a black box warning for cautious use in heart failure patients, and that earlier in 2016, the Food and Drug Administration cautioned that metformin should not be used in patients with an estimated glomerular filtration rate of less than 30 mL/minute per 1.73 m². The statement also endorsed a recommendation from the American Diabetes Association that metformin not be used in patients with unstable heart failure or those hospitalized for heart failure.

Antihypertensives, biologics, and more

Other notable prescription drugs listed as potentially having a major impact on causing or worsening heart failure include the antihypertensive drugs diltiazem, verapamil, and moxonidine, the tumor necrosis factor–inhibitors that are widely used to treat rheumatologic and gastroenterologic diseases, the antipsychotic clozapine, and a long list of anticancer medications, including several anthracyclines and many types of newer biologic agents.

The statement also lists several specific recommendations to health care providers for improving oversight of the drugs taken by patients with heart failure or those at risk for heart failure. These include a comprehensive medication review during each clinical encounter. The statement also suggests a “medication flow sheet” for each patient that contains the basic information regarding the regimen for each medication taken by a patient: the brand and generic name, the purpose of the medication, and its dosage. “These medication flow sheets should be used by patients as a tool to enhance safety and adherence, and they should show their flow sheets at each provider visit,” Dr. Page said.

Managing myriad meds

The statement also calls for stopping medications without a well defined indication for a patient, avoid prescribing new drugs to address side effects of other drugs, and suggests establishing a “captain” among the health care providers seen by each patient who would be particularly responsible for overseeing and keeping track of the medications the patient takes.

“Ideally, this ‘captain’ would be the patient’s primary care provider, who should be in contact with the other specialists that the patient may be seeing. However, this does not always happen,” said Dr. Page. “Therefore, I encourage each patient with heart failure to contact both their primary care provider and their health care provider who is managing their heart failure before taking or stopping any new medication including prescription, OTC, herbal, complimentary or alternative medication or supplement. Health care providers need to encourage patients to be actively engaged in their medication management.”

Dr. Page had no disclosures.

[email protected]

On Twitter @mitchelzoler

Many commonly used prescription drugs, many OTC agents, and also several complimentary or alternative medications, can either trigger heart failure or exacerbate the disease in patients with existing heart failure according to a Scientific Statement written by a committee of the American Heart Association and released on July 11.

This first-ever authoritative U.S. overview of what is known about drugs that can affect heart failure was compiled to address an important practice issue for the large and growing number of U.S. patients with heart failure, estimated to be nearly 6 million Americans, and “provide some guidance to health care providers in how to minimize polypharmacy, improve medication safety, as well as identify the medications that could exacerbate or cause heart failure,” said Robert L. Page II, PharmD, chair of the committee and a professor of clinical pharmacy at the University of Colorado at Denver, Aurora.

Although the comprehensive statement lists 88 distinct prescription drugs or drug classes as agents that pose major or moderate threats for causing or worsening heart failure, “from the American public’s perspective, importance should be placed on educating patients regarding the impact that OTC medications can have on their heart failure,” Dr. Page said in an interview. “For example, nonsteroidal anti-inflammatory drugs like ibuprofen or naproxen can cause sodium and water retention and antagonize the effects of evidence-based heart failure pharmacotherapies. Additionally, OTC medications like pseudoephedrine, which many cough and cold products contain, can increase blood pressure and afterload,” he noted. The risks these drugs pose becomes even greater when they are taken at higher doses.

NSAIDs

The statement cites already existing guidance from the American College of Cardiology and American Heart Association that for patients with existing heart failure, use of NSAIDs should either be avoided or withdrawn when possible. The statement advises educating patients to communicate with their health care provider before taking any OTC medication or complimentary or alternative medication, avoid these agents when their efficacy and safety is uncertain, and evaluate the labels of these products for their sodium content (although the sodium content from inactive ingredients may be difficult to find in labeling).

“Currently, we teach patients to read food labels for sodium content, but we also need to educate patients on how to read OTC medication labels for both ingredients and sodium content. Many OTC antacids may have a large sodium load,” Dr. Page said. The statement includes a list of 14 prescription drugs and also highlights several OTC formulations that have an especially high sodium content.

Metformin

Among the many prescription drugs listed, one notable entry is for the oral hypoglycemic agent metformin that today is among the most widely used drugs for treating type 2 diabetes and is especially relevant for heart failure patients because, as the statement notes, 38% also have diabetes. The statement details the long history of metformin and heart failure, noting that until a decade ago, the drug had a contraindication for patients with heart failure, that metformin’s label still carries a black box warning for cautious use in heart failure patients, and that earlier in 2016, the Food and Drug Administration cautioned that metformin should not be used in patients with an estimated glomerular filtration rate of less than 30 mL/minute per 1.73 m². The statement also endorsed a recommendation from the American Diabetes Association that metformin not be used in patients with unstable heart failure or those hospitalized for heart failure.

Antihypertensives, biologics, and more

Other notable prescription drugs listed as potentially having a major impact on causing or worsening heart failure include the antihypertensive drugs diltiazem, verapamil, and moxonidine, the tumor necrosis factor–inhibitors that are widely used to treat rheumatologic and gastroenterologic diseases, the antipsychotic clozapine, and a long list of anticancer medications, including several anthracyclines and many types of newer biologic agents.

The statement also lists several specific recommendations to health care providers for improving oversight of the drugs taken by patients with heart failure or those at risk for heart failure. These include a comprehensive medication review during each clinical encounter. The statement also suggests a “medication flow sheet” for each patient that contains the basic information regarding the regimen for each medication taken by a patient: the brand and generic name, the purpose of the medication, and its dosage. “These medication flow sheets should be used by patients as a tool to enhance safety and adherence, and they should show their flow sheets at each provider visit,” Dr. Page said.

Managing myriad meds

The statement also calls for stopping medications without a well defined indication for a patient, avoid prescribing new drugs to address side effects of other drugs, and suggests establishing a “captain” among the health care providers seen by each patient who would be particularly responsible for overseeing and keeping track of the medications the patient takes.

“Ideally, this ‘captain’ would be the patient’s primary care provider, who should be in contact with the other specialists that the patient may be seeing. However, this does not always happen,” said Dr. Page. “Therefore, I encourage each patient with heart failure to contact both their primary care provider and their health care provider who is managing their heart failure before taking or stopping any new medication including prescription, OTC, herbal, complimentary or alternative medication or supplement. Health care providers need to encourage patients to be actively engaged in their medication management.”

Dr. Page had no disclosures.

[email protected]

On Twitter @mitchelzoler

The multikinase inhibitor cabozantinib did not significantly improve overall survival, compared with prednisone in men with previously treated metastatic castration-resistant prostate cancer, reported investigators in the phase III COMET-1 trial.

Among 1,028 men with metastatic castration-resistant prostate cancer (mCRPC) median overall survival was 11.0 months for 682 patients randomly assigned to cabozantinib (Cabometyx), compared with 9.8 months for patients assigned to prednisone, a difference that was not statistically significant, reported Matthew Smith, MD, PhD, of Massachusetts General Hospital in Boston, and his colleagues.

©alexdans/Thinkstock

Cabozantinib was, however, associated with significant improvements over prednisone in bone scan response (BSR) at 12 weeks, radiographic progression-free survival (rPFS), and in effects on circulating tumor cells (CTCs), bone biomarkers, and symptomatic skeletal events (SSE), but not prostate-specific antigen (PSA)-related outcomes, the investigators reported (J Clin Oncol. 2016 Jul 11. doi: 10.1200/JCO.2015.65.5597).

“The biologic activities of cabozantinib are diverse, with bone effects, direct effects on cancer cells, and anti-angiogenic effects being demonstrated in preclinical models. It could be argued that the observed changes in BSR, bone biomarkers, and SSEs in our study are consistent with biologic effects in bone and bone metastases, and the improvements in CTCs suggest a direct antitumor effect, although the lack of improvement in PSA outcomes argues against such an effect,” they wrote.

Cabozantinib is an oral inhibitor of tyrosine kinases believed to be important factors in prostate cancer development and progression, including MET and vascular endothelial growth factor (VEGF) receptor 2.

In a phase II­ randomized discontinuation trial in men with mCRPC, cabozantinib was associated with reductions in soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in markers of bone turnover, pain, and use of narcotics.

To see whether the promising clinical activity observed in earlier studies could be sustained, the investigators conducted a phase III study comparing cabozantinib with prednisone in men with mCRPC who had experienced bone metastases and disease progression after therapy with docetaxel and abiraterone acetate and/or enzalutamide.

Patients were randomly assigned on a 2:1 basis to cabozantinib 60 mg once daily or prednisone 5 mg twice daily.

As noted before, there was no difference in overall survival, the primary endpoint, between the treatment groups, but BSR at 12 weeks was superior with cabozantinib, occurring in 42% vs. 3% of patients on prednisone (P less than .001). Radiographic PFS was also better with cabozantinib, at 5.6 vs. 2.8 months (hazard ratio, 0.48; P less than .001).

More patients on cabozantinib experienced grade 3 or greater adverse events (71% vs. 56%) and nearly three times as many patients discontinued the assigned drug because of adverse events (33% vs, 12%, respectively).

The study was supported by Exelixis. Dr. Smith disclosed a consulting/advisory role for Exelixis, and several coauthors reported research funding from the company. Dr. Alumkal and Dr. Beer disclosed research funding and/or consulting with various companies, not including Exelixis.

[email protected]

The multikinase inhibitor cabozantinib did not significantly improve overall survival, compared with prednisone in men with previously treated metastatic castration-resistant prostate cancer, reported investigators in the phase III COMET-1 trial.

Among 1,028 men with metastatic castration-resistant prostate cancer (mCRPC) median overall survival was 11.0 months for 682 patients randomly assigned to cabozantinib (Cabometyx), compared with 9.8 months for patients assigned to prednisone, a difference that was not statistically significant, reported Matthew Smith, MD, PhD, of Massachusetts General Hospital in Boston, and his colleagues.

©alexdans/Thinkstock

Cabozantinib was, however, associated with significant improvements over prednisone in bone scan response (BSR) at 12 weeks, radiographic progression-free survival (rPFS), and in effects on circulating tumor cells (CTCs), bone biomarkers, and symptomatic skeletal events (SSE), but not prostate-specific antigen (PSA)-related outcomes, the investigators reported (J Clin Oncol. 2016 Jul 11. doi: 10.1200/JCO.2015.65.5597).

“The biologic activities of cabozantinib are diverse, with bone effects, direct effects on cancer cells, and anti-angiogenic effects being demonstrated in preclinical models. It could be argued that the observed changes in BSR, bone biomarkers, and SSEs in our study are consistent with biologic effects in bone and bone metastases, and the improvements in CTCs suggest a direct antitumor effect, although the lack of improvement in PSA outcomes argues against such an effect,” they wrote.

Cabozantinib is an oral inhibitor of tyrosine kinases believed to be important factors in prostate cancer development and progression, including MET and vascular endothelial growth factor (VEGF) receptor 2.

In a phase II­ randomized discontinuation trial in men with mCRPC, cabozantinib was associated with reductions in soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in markers of bone turnover, pain, and use of narcotics.

To see whether the promising clinical activity observed in earlier studies could be sustained, the investigators conducted a phase III study comparing cabozantinib with prednisone in men with mCRPC who had experienced bone metastases and disease progression after therapy with docetaxel and abiraterone acetate and/or enzalutamide.

Patients were randomly assigned on a 2:1 basis to cabozantinib 60 mg once daily or prednisone 5 mg twice daily.

As noted before, there was no difference in overall survival, the primary endpoint, between the treatment groups, but BSR at 12 weeks was superior with cabozantinib, occurring in 42% vs. 3% of patients on prednisone (P less than .001). Radiographic PFS was also better with cabozantinib, at 5.6 vs. 2.8 months (hazard ratio, 0.48; P less than .001).

More patients on cabozantinib experienced grade 3 or greater adverse events (71% vs. 56%) and nearly three times as many patients discontinued the assigned drug because of adverse events (33% vs, 12%, respectively).

The study was supported by Exelixis. Dr. Smith disclosed a consulting/advisory role for Exelixis, and several coauthors reported research funding from the company. Dr. Alumkal and Dr. Beer disclosed research funding and/or consulting with various companies, not including Exelixis.

[email protected]

The multikinase inhibitor cabozantinib did not significantly improve overall survival, compared with prednisone in men with previously treated metastatic castration-resistant prostate cancer, reported investigators in the phase III COMET-1 trial.

Among 1,028 men with metastatic castration-resistant prostate cancer (mCRPC) median overall survival was 11.0 months for 682 patients randomly assigned to cabozantinib (Cabometyx), compared with 9.8 months for patients assigned to prednisone, a difference that was not statistically significant, reported Matthew Smith, MD, PhD, of Massachusetts General Hospital in Boston, and his colleagues.

©alexdans/Thinkstock

Cabozantinib was, however, associated with significant improvements over prednisone in bone scan response (BSR) at 12 weeks, radiographic progression-free survival (rPFS), and in effects on circulating tumor cells (CTCs), bone biomarkers, and symptomatic skeletal events (SSE), but not prostate-specific antigen (PSA)-related outcomes, the investigators reported (J Clin Oncol. 2016 Jul 11. doi: 10.1200/JCO.2015.65.5597).

“The biologic activities of cabozantinib are diverse, with bone effects, direct effects on cancer cells, and anti-angiogenic effects being demonstrated in preclinical models. It could be argued that the observed changes in BSR, bone biomarkers, and SSEs in our study are consistent with biologic effects in bone and bone metastases, and the improvements in CTCs suggest a direct antitumor effect, although the lack of improvement in PSA outcomes argues against such an effect,” they wrote.

Cabozantinib is an oral inhibitor of tyrosine kinases believed to be important factors in prostate cancer development and progression, including MET and vascular endothelial growth factor (VEGF) receptor 2.

In a phase II­ randomized discontinuation trial in men with mCRPC, cabozantinib was associated with reductions in soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in markers of bone turnover, pain, and use of narcotics.

To see whether the promising clinical activity observed in earlier studies could be sustained, the investigators conducted a phase III study comparing cabozantinib with prednisone in men with mCRPC who had experienced bone metastases and disease progression after therapy with docetaxel and abiraterone acetate and/or enzalutamide.

Patients were randomly assigned on a 2:1 basis to cabozantinib 60 mg once daily or prednisone 5 mg twice daily.

As noted before, there was no difference in overall survival, the primary endpoint, between the treatment groups, but BSR at 12 weeks was superior with cabozantinib, occurring in 42% vs. 3% of patients on prednisone (P less than .001). Radiographic PFS was also better with cabozantinib, at 5.6 vs. 2.8 months (hazard ratio, 0.48; P less than .001).

More patients on cabozantinib experienced grade 3 or greater adverse events (71% vs. 56%) and nearly three times as many patients discontinued the assigned drug because of adverse events (33% vs, 12%, respectively).

The study was supported by Exelixis. Dr. Smith disclosed a consulting/advisory role for Exelixis, and several coauthors reported research funding from the company. Dr. Alumkal and Dr. Beer disclosed research funding and/or consulting with various companies, not including Exelixis.

[email protected]

SAN DIEGO – Device companies are working hard to bring obesity management to the endoscopy suite.

The field is called endobariatrics, and its goal is to fill the gap between surgery and pharmacotherapy. Drugs and lifestyle counseling don’t work too well, but a lot of people don’t want to go under the knife, so something is needed in the middle. Endobariatrics has the potential to be a boon for both obese patients and gastroenterology practices.

Several new investigational devices and approaches were showcased at the annual Digestive Disease Week; some “are beginning to approach the kind of results we see with surgical techniques,” said Steven Edmundowicz, MD, medical director of the University of Colorado Digestive Health Center, Aurora.

“We are seeing a tremendous amount of development in this space, but it’s early, and we have to be cautious,” he said. There have already been a few disappointments, including the EndoBarrier, a fluoropolymer liner anchored in the duodenal bulb and unfurled down the duodenum to block food absorption. A key U.S. trial was recently halted due to liver abscesses.

Dr. Edmundowicz reviewed the latest developments presented at DDW.

Self-assembling magnets for dual-path enteral anastomoses

The goal of the GI Windows system is to create a partial jejunoileal, side to side bypass without surgery. A 28-mm magnet ring is introduced to the ileum by colonoscopy, and a second ring to the jejunum by endoscopy. The rings snap together and tissue caught between them dies from pressure necrosis, leaving patients with a jejunoileal communication. Once food reaches that point, it either diverts through the anastomosis or continues past it down the digestive track. The magnets pass after the anastomosis forms in a week or so.

In a 6-month feasibility study from the Czech Republic, 10 obese patients lost 28.3% of their excess weight without diet restrictions. Those with diabetes had a mean hemoglobin A_1c drop of 1.8%, and normalization of fasting blood glucose levels. The procedure took just over an hour and a half after the first five cases.

“I am very excited about [this]; I really want to see where the data are going,” Dr. Edmundowicz said.

Duodenal mucosal resurfacing

The idea of the Revita System (Fractyl) is to ablate “diabetic mucosa” in the duodenum so that normal mucosa can replace it. Saline is injected endoscopically under a portion of the duodenal mucosa to lift it off the muscularis; once isolated, the mucosa is destroyed – some in the audience thought “cooked” was a better word – by exposure to a hot water balloon catheter threaded into the lumen.

Thirty-nine overweight or obese type 2 diabetics had a 1.2% improvement at 6 months from a baseline hemoglobin A_1c of 9.6% in a series from Santiago, Chile. Weight loss was modest in the trial; the system is being developed for type 2 diabetics.

There is some histologic support for the notion of a diabetic mucosa with both structural and hormonal aberrations, but it’s unclear if it’s a sign or cause of sickness. Even so, “the mucosa regenerates” and won’t be diabetic “for a while” after the procedure, said investigator Manoel Galvao Neto, MD, of the Gastro Obeso Center, São Paulo.

Gastric balloons

Inflating a balloon in the stomach to make people feel full isn’t new, but the notion of putting the balloon into a capsule that patients can swallow and inflating it through a tether is a more recent notion.

The Obalon (Obalon Therapeutics) is one such device. In an unblinded, sham-controlled trial with 336 obese patients, subjects who got the 250-mL, nitrogen-filled Obalons – most received three – lost about 3% more of their total body weight at 24 weeks than those who did not. Although swallowed, Obalon is removed endoscopically. Meanwhile, 34 obese patients who swallowed the 550-mL, fluid-filled Elipse balloon (Allurion) had a total body weight loss of 9.5% and mean excess weight loss of 37.2% at 4 months, by which time Elipse deflates on its own and passes without endoscopic retrieval.

“This is a very promising approach. I am very excited about digested balloons,” said Dr. Edmundowicz, an investigator in the Obalon study.

Endoscopic sleeve gastroplasty

Endoscopic sleeve gastroplasty duplicates sleeve gastrectomy with stitches placed endoscopically to seal off the greater curvature of the stomach; functionally, patients are left with a narrow sleeve of a stomach. In a multicenter series presented at DDW, 242 patients had a mean total body weight loss of 19.8% at 18 months, with a low incidence of complications. “Weight loss appears to be continuing,” Dr. Edmundowicz said. Investigators used the Apollo OverStitch (Apollo Endosurgery) to place the sutures.

Aspiration therapy

With Food and Drug Administration approval on June 14, AspireAssist (Aspire Bariatrics) is probably the best known of the newer approaches. Patients drain a portion of their meals through an endoscopically placed percutaneous gastrostomy tube a half hour or so after eating. It takes 5-10 minutes. The agency is eager to keep it out of the hands of bulimics.

One-year data were reported at DDW; 111 obese AspireAssist subjects lost a mean of 37.2% of their excess weight versus 13% in 60 patients randomized to lifestyle counseling alone.

“It may not be aesthetically pleasing, but it certainly works. It’s a viable technology,” said Dr. Edmundowicz, who was an investigator.

The studies were funded by companies developing the devices and techniques. Dr. Edmundowicz has stock options, or is a consultant or researcher, Aspire, Obalon, GI Dynamics, Elira, and other firms.

[email protected]

SAN DIEGO – Device companies are working hard to bring obesity management to the endoscopy suite.

The field is called endobariatrics, and its goal is to fill the gap between surgery and pharmacotherapy. Drugs and lifestyle counseling don’t work too well, but a lot of people don’t want to go under the knife, so something is needed in the middle. Endobariatrics has the potential to be a boon for both obese patients and gastroenterology practices.

Several new investigational devices and approaches were showcased at the annual Digestive Disease Week; some “are beginning to approach the kind of results we see with surgical techniques,” said Steven Edmundowicz, MD, medical director of the University of Colorado Digestive Health Center, Aurora.

“We are seeing a tremendous amount of development in this space, but it’s early, and we have to be cautious,” he said. There have already been a few disappointments, including the EndoBarrier, a fluoropolymer liner anchored in the duodenal bulb and unfurled down the duodenum to block food absorption. A key U.S. trial was recently halted due to liver abscesses.

Dr. Edmundowicz reviewed the latest developments presented at DDW.

Self-assembling magnets for dual-path enteral anastomoses

The goal of the GI Windows system is to create a partial jejunoileal, side to side bypass without surgery. A 28-mm magnet ring is introduced to the ileum by colonoscopy, and a second ring to the jejunum by endoscopy. The rings snap together and tissue caught between them dies from pressure necrosis, leaving patients with a jejunoileal communication. Once food reaches that point, it either diverts through the anastomosis or continues past it down the digestive track. The magnets pass after the anastomosis forms in a week or so.

In a 6-month feasibility study from the Czech Republic, 10 obese patients lost 28.3% of their excess weight without diet restrictions. Those with diabetes had a mean hemoglobin A_1c drop of 1.8%, and normalization of fasting blood glucose levels. The procedure took just over an hour and a half after the first five cases.

“I am very excited about [this]; I really want to see where the data are going,” Dr. Edmundowicz said.

Duodenal mucosal resurfacing

The idea of the Revita System (Fractyl) is to ablate “diabetic mucosa” in the duodenum so that normal mucosa can replace it. Saline is injected endoscopically under a portion of the duodenal mucosa to lift it off the muscularis; once isolated, the mucosa is destroyed – some in the audience thought “cooked” was a better word – by exposure to a hot water balloon catheter threaded into the lumen.

Thirty-nine overweight or obese type 2 diabetics had a 1.2% improvement at 6 months from a baseline hemoglobin A_1c of 9.6% in a series from Santiago, Chile. Weight loss was modest in the trial; the system is being developed for type 2 diabetics.

There is some histologic support for the notion of a diabetic mucosa with both structural and hormonal aberrations, but it’s unclear if it’s a sign or cause of sickness. Even so, “the mucosa regenerates” and won’t be diabetic “for a while” after the procedure, said investigator Manoel Galvao Neto, MD, of the Gastro Obeso Center, São Paulo.

Gastric balloons

Inflating a balloon in the stomach to make people feel full isn’t new, but the notion of putting the balloon into a capsule that patients can swallow and inflating it through a tether is a more recent notion.

The Obalon (Obalon Therapeutics) is one such device. In an unblinded, sham-controlled trial with 336 obese patients, subjects who got the 250-mL, nitrogen-filled Obalons – most received three – lost about 3% more of their total body weight at 24 weeks than those who did not. Although swallowed, Obalon is removed endoscopically. Meanwhile, 34 obese patients who swallowed the 550-mL, fluid-filled Elipse balloon (Allurion) had a total body weight loss of 9.5% and mean excess weight loss of 37.2% at 4 months, by which time Elipse deflates on its own and passes without endoscopic retrieval.

“This is a very promising approach. I am very excited about digested balloons,” said Dr. Edmundowicz, an investigator in the Obalon study.

Endoscopic sleeve gastroplasty

Endoscopic sleeve gastroplasty duplicates sleeve gastrectomy with stitches placed endoscopically to seal off the greater curvature of the stomach; functionally, patients are left with a narrow sleeve of a stomach. In a multicenter series presented at DDW, 242 patients had a mean total body weight loss of 19.8% at 18 months, with a low incidence of complications. “Weight loss appears to be continuing,” Dr. Edmundowicz said. Investigators used the Apollo OverStitch (Apollo Endosurgery) to place the sutures.

Aspiration therapy

With Food and Drug Administration approval on June 14, AspireAssist (Aspire Bariatrics) is probably the best known of the newer approaches. Patients drain a portion of their meals through an endoscopically placed percutaneous gastrostomy tube a half hour or so after eating. It takes 5-10 minutes. The agency is eager to keep it out of the hands of bulimics.

One-year data were reported at DDW; 111 obese AspireAssist subjects lost a mean of 37.2% of their excess weight versus 13% in 60 patients randomized to lifestyle counseling alone.

“It may not be aesthetically pleasing, but it certainly works. It’s a viable technology,” said Dr. Edmundowicz, who was an investigator.

The studies were funded by companies developing the devices and techniques. Dr. Edmundowicz has stock options, or is a consultant or researcher, Aspire, Obalon, GI Dynamics, Elira, and other firms.

[email protected]

SAN DIEGO – Device companies are working hard to bring obesity management to the endoscopy suite.

The field is called endobariatrics, and its goal is to fill the gap between surgery and pharmacotherapy. Drugs and lifestyle counseling don’t work too well, but a lot of people don’t want to go under the knife, so something is needed in the middle. Endobariatrics has the potential to be a boon for both obese patients and gastroenterology practices.

Several new investigational devices and approaches were showcased at the annual Digestive Disease Week; some “are beginning to approach the kind of results we see with surgical techniques,” said Steven Edmundowicz, MD, medical director of the University of Colorado Digestive Health Center, Aurora.

“We are seeing a tremendous amount of development in this space, but it’s early, and we have to be cautious,” he said. There have already been a few disappointments, including the EndoBarrier, a fluoropolymer liner anchored in the duodenal bulb and unfurled down the duodenum to block food absorption. A key U.S. trial was recently halted due to liver abscesses.

Dr. Edmundowicz reviewed the latest developments presented at DDW.

Self-assembling magnets for dual-path enteral anastomoses

The goal of the GI Windows system is to create a partial jejunoileal, side to side bypass without surgery. A 28-mm magnet ring is introduced to the ileum by colonoscopy, and a second ring to the jejunum by endoscopy. The rings snap together and tissue caught between them dies from pressure necrosis, leaving patients with a jejunoileal communication. Once food reaches that point, it either diverts through the anastomosis or continues past it down the digestive track. The magnets pass after the anastomosis forms in a week or so.

In a 6-month feasibility study from the Czech Republic, 10 obese patients lost 28.3% of their excess weight without diet restrictions. Those with diabetes had a mean hemoglobin A_1c drop of 1.8%, and normalization of fasting blood glucose levels. The procedure took just over an hour and a half after the first five cases.

“I am very excited about [this]; I really want to see where the data are going,” Dr. Edmundowicz said.

Duodenal mucosal resurfacing

The idea of the Revita System (Fractyl) is to ablate “diabetic mucosa” in the duodenum so that normal mucosa can replace it. Saline is injected endoscopically under a portion of the duodenal mucosa to lift it off the muscularis; once isolated, the mucosa is destroyed – some in the audience thought “cooked” was a better word – by exposure to a hot water balloon catheter threaded into the lumen.

Thirty-nine overweight or obese type 2 diabetics had a 1.2% improvement at 6 months from a baseline hemoglobin A_1c of 9.6% in a series from Santiago, Chile. Weight loss was modest in the trial; the system is being developed for type 2 diabetics.

There is some histologic support for the notion of a diabetic mucosa with both structural and hormonal aberrations, but it’s unclear if it’s a sign or cause of sickness. Even so, “the mucosa regenerates” and won’t be diabetic “for a while” after the procedure, said investigator Manoel Galvao Neto, MD, of the Gastro Obeso Center, São Paulo.

Gastric balloons

Inflating a balloon in the stomach to make people feel full isn’t new, but the notion of putting the balloon into a capsule that patients can swallow and inflating it through a tether is a more recent notion.

The Obalon (Obalon Therapeutics) is one such device. In an unblinded, sham-controlled trial with 336 obese patients, subjects who got the 250-mL, nitrogen-filled Obalons – most received three – lost about 3% more of their total body weight at 24 weeks than those who did not. Although swallowed, Obalon is removed endoscopically. Meanwhile, 34 obese patients who swallowed the 550-mL, fluid-filled Elipse balloon (Allurion) had a total body weight loss of 9.5% and mean excess weight loss of 37.2% at 4 months, by which time Elipse deflates on its own and passes without endoscopic retrieval.

“This is a very promising approach. I am very excited about digested balloons,” said Dr. Edmundowicz, an investigator in the Obalon study.

Endoscopic sleeve gastroplasty

Endoscopic sleeve gastroplasty duplicates sleeve gastrectomy with stitches placed endoscopically to seal off the greater curvature of the stomach; functionally, patients are left with a narrow sleeve of a stomach. In a multicenter series presented at DDW, 242 patients had a mean total body weight loss of 19.8% at 18 months, with a low incidence of complications. “Weight loss appears to be continuing,” Dr. Edmundowicz said. Investigators used the Apollo OverStitch (Apollo Endosurgery) to place the sutures.

Aspiration therapy

With Food and Drug Administration approval on June 14, AspireAssist (Aspire Bariatrics) is probably the best known of the newer approaches. Patients drain a portion of their meals through an endoscopically placed percutaneous gastrostomy tube a half hour or so after eating. It takes 5-10 minutes. The agency is eager to keep it out of the hands of bulimics.

One-year data were reported at DDW; 111 obese AspireAssist subjects lost a mean of 37.2% of their excess weight versus 13% in 60 patients randomized to lifestyle counseling alone.

“It may not be aesthetically pleasing, but it certainly works. It’s a viable technology,” said Dr. Edmundowicz, who was an investigator.

The studies were funded by companies developing the devices and techniques. Dr. Edmundowicz has stock options, or is a consultant or researcher, Aspire, Obalon, GI Dynamics, Elira, and other firms.

[email protected]

New findings suggest childhood trauma and cannabis use disorders have no significant interaction in outcomes for patients with schizophrenia, according to Grégoire Baudin and his associates.

skydie/ThinkStock

The researchers recruited 366 people aged 15-84 years. Two hundred ninety-five of the subjects (80.6%) met the DSM-IV-TR criteria for schizophrenia, and 71 (19.4%) for schizoaffective disorder. They found that 30.49% of the patients reported at least one significant childhood trauma, and 13.77% reported two or more. The proportion of patients reporting childhood traumas were comparable by gender; 33.78% of women and 33% of men reported at least one trauma. The differences between those rates were not statistically significant (P = 0.449), the researchers reported. Among patients with cannabis use disorders, 99 (27.05%) had a lifetime diagnosis of cannabis use disorder. This diagnosis significantly predicted age of onset, age at first hospitalization, and Medication Adherence Rating Scale scores.

Overall, no significant interaction was found between childhood trauma and cannabis use disorders. However, after adjustment for age and gender, a correlation was found (P = 0.004). But “the proportion of patients with a history of trauma among subjects with and without cannabis use disorders did not significantly differ,” the researchers wrote (P = 0.278).

“Our results emphasize the need for clinicians to systematically inquire about the traumatic history of patients with psychotic disorders, and consider trauma-focused therapy” for people with schizophrenia and those at risk, researchers concluded.

Read the full study in Schizophrenia Research (doi: 10.1016/j.schres.2016.04.042).

[email protected]

New findings suggest childhood trauma and cannabis use disorders have no significant interaction in outcomes for patients with schizophrenia, according to Grégoire Baudin and his associates.

skydie/ThinkStock

The researchers recruited 366 people aged 15-84 years. Two hundred ninety-five of the subjects (80.6%) met the DSM-IV-TR criteria for schizophrenia, and 71 (19.4%) for schizoaffective disorder. They found that 30.49% of the patients reported at least one significant childhood trauma, and 13.77% reported two or more. The proportion of patients reporting childhood traumas were comparable by gender; 33.78% of women and 33% of men reported at least one trauma. The differences between those rates were not statistically significant (P = 0.449), the researchers reported. Among patients with cannabis use disorders, 99 (27.05%) had a lifetime diagnosis of cannabis use disorder. This diagnosis significantly predicted age of onset, age at first hospitalization, and Medication Adherence Rating Scale scores.

Overall, no significant interaction was found between childhood trauma and cannabis use disorders. However, after adjustment for age and gender, a correlation was found (P = 0.004). But “the proportion of patients with a history of trauma among subjects with and without cannabis use disorders did not significantly differ,” the researchers wrote (P = 0.278).

“Our results emphasize the need for clinicians to systematically inquire about the traumatic history of patients with psychotic disorders, and consider trauma-focused therapy” for people with schizophrenia and those at risk, researchers concluded.

Read the full study in Schizophrenia Research (doi: 10.1016/j.schres.2016.04.042).

[email protected]

New findings suggest childhood trauma and cannabis use disorders have no significant interaction in outcomes for patients with schizophrenia, according to Grégoire Baudin and his associates.

skydie/ThinkStock

The researchers recruited 366 people aged 15-84 years. Two hundred ninety-five of the subjects (80.6%) met the DSM-IV-TR criteria for schizophrenia, and 71 (19.4%) for schizoaffective disorder. They found that 30.49% of the patients reported at least one significant childhood trauma, and 13.77% reported two or more. The proportion of patients reporting childhood traumas were comparable by gender; 33.78% of women and 33% of men reported at least one trauma. The differences between those rates were not statistically significant (P = 0.449), the researchers reported. Among patients with cannabis use disorders, 99 (27.05%) had a lifetime diagnosis of cannabis use disorder. This diagnosis significantly predicted age of onset, age at first hospitalization, and Medication Adherence Rating Scale scores.

Overall, no significant interaction was found between childhood trauma and cannabis use disorders. However, after adjustment for age and gender, a correlation was found (P = 0.004). But “the proportion of patients with a history of trauma among subjects with and without cannabis use disorders did not significantly differ,” the researchers wrote (P = 0.278).

“Our results emphasize the need for clinicians to systematically inquire about the traumatic history of patients with psychotic disorders, and consider trauma-focused therapy” for people with schizophrenia and those at risk, researchers concluded.

Read the full study in Schizophrenia Research (doi: 10.1016/j.schres.2016.04.042).

[email protected]

NEW ORLEANS – Compared with placebo, canagliflozin improved glycemic control and reduced glycemic variability over 18 weeks in adults with type 1 diabetes that had been inadequately controlled with insulin, according to results from a randomized trial.

“Patients with type 1 diabetes can experience acute and profound glucose fluctuations, which may be related to variability in insulin activity and changes in day-to-day activities,” Maria Alba, MD, said at the annual scientific sessions of the American Diabetes Association. “A major challenge in the treatment of type 1 diabetes is achieving patient-specific glycemic control while avoiding episodes of hyperglycemia and hypoglycemia.”

Canagliflozin is a sodium glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes; it lowers blood glucose through an insulin-dependent mechanism by lowering the renal threshold for glucose and increasing urinary glucose excretion. It is not approved for the treatment of type 1 diabetes. In a phase II study, canagliflozin improved glycemic control and provided reductions in body weight and insulin dose in patients with type 1 diabetes who were on background insulin over 18 weeks (Diabetes Care 2015;39[12]:2258-65).

The purpose of the current study was to assess the effects of canagliflozin on daily mean glucose, glycemic variability, and time spent in glycemic ranges (greater than 70-180 mg/dL) in adults with type 1 diabetes inadequately controlled with insulin therapy, said Dr. Alba of Janssen Research & Development, Raritan, N.J. In all, 351 patients were randomized to placebo or 100 mg or 300 mg of canagliflozin. All had had the disease for at least 1 year, had a baseline hemoglobin A_1c level between 7% and 9%, and had to be on a stable insulin regimen for at least 8 weeks. “On the day before randomization, patients were advised to reduce their basal insulin by 10% or 20%, depending on their baseline A_1c,” she said. “Once randomized, they were instructed to titrate their insulin to reach specific glycemic goals.”

All patients were to record 9-point self-monitoring blood glucose (SMBG) measurements throughout the study. Continuous glucose monitoring (CGM) assessments were performed at selected study centers in a substudy of 89 patients. Efficacy endpoints assessed by 9-point SMBG at week 18 were change from baseline in mean daily glucose and daily glucose standard deviation. Efficacy endpoints in the CGM substudy at week 18 were change from baseline in mean glucose, patterns of glucose variability, and time spent within target glucose (greater than 70-180 mg/dL), above target (greater than 180 mg/dL), or below target (70 mg/dL or less). The mean age of study participants was 43 years, 55% were male, and their mean baseline A_1c was 7.9%.

At 18 weeks, reductions in daily mean glucose were observed in the canagliflozin 100-mg and 300-mg groups, compared with placebo (–22.4 and –19.4 mg/dL, respectively, vs. a rise of 3 mg/dL in the placebo group), as well as reductions in daily glucose standard deviation (–16.4 and –18.1 mg/dL, vs. –1.9 mg/dL), Dr. Alba reported.

The researchers also found that the percentage of time spent within the glycemic target range was greater in the canagliflozin 100- and 300-mg groups, compared with placebo (a change from baseline of 11.6% and 10.1%, respectively, compared with a decrease of 3.5%), while the percentage of time spent above target was lower in both canagliflozin doses, compared with placebo. Canagliflozin was generally well tolerated, with a dose-dependent increase in ketone-related adverse events (5.1% in the 100-mg group and 9.4% in the 300-mg group).

Janssen Research & Development supported the study.

[email protected]

NEW ORLEANS – Compared with placebo, canagliflozin improved glycemic control and reduced glycemic variability over 18 weeks in adults with type 1 diabetes that had been inadequately controlled with insulin, according to results from a randomized trial.

“Patients with type 1 diabetes can experience acute and profound glucose fluctuations, which may be related to variability in insulin activity and changes in day-to-day activities,” Maria Alba, MD, said at the annual scientific sessions of the American Diabetes Association. “A major challenge in the treatment of type 1 diabetes is achieving patient-specific glycemic control while avoiding episodes of hyperglycemia and hypoglycemia.”

Canagliflozin is a sodium glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes; it lowers blood glucose through an insulin-dependent mechanism by lowering the renal threshold for glucose and increasing urinary glucose excretion. It is not approved for the treatment of type 1 diabetes. In a phase II study, canagliflozin improved glycemic control and provided reductions in body weight and insulin dose in patients with type 1 diabetes who were on background insulin over 18 weeks (Diabetes Care 2015;39[12]:2258-65).

The purpose of the current study was to assess the effects of canagliflozin on daily mean glucose, glycemic variability, and time spent in glycemic ranges (greater than 70-180 mg/dL) in adults with type 1 diabetes inadequately controlled with insulin therapy, said Dr. Alba of Janssen Research & Development, Raritan, N.J. In all, 351 patients were randomized to placebo or 100 mg or 300 mg of canagliflozin. All had had the disease for at least 1 year, had a baseline hemoglobin A_1c level between 7% and 9%, and had to be on a stable insulin regimen for at least 8 weeks. “On the day before randomization, patients were advised to reduce their basal insulin by 10% or 20%, depending on their baseline A_1c,” she said. “Once randomized, they were instructed to titrate their insulin to reach specific glycemic goals.”

All patients were to record 9-point self-monitoring blood glucose (SMBG) measurements throughout the study. Continuous glucose monitoring (CGM) assessments were performed at selected study centers in a substudy of 89 patients. Efficacy endpoints assessed by 9-point SMBG at week 18 were change from baseline in mean daily glucose and daily glucose standard deviation. Efficacy endpoints in the CGM substudy at week 18 were change from baseline in mean glucose, patterns of glucose variability, and time spent within target glucose (greater than 70-180 mg/dL), above target (greater than 180 mg/dL), or below target (70 mg/dL or less). The mean age of study participants was 43 years, 55% were male, and their mean baseline A_1c was 7.9%.

At 18 weeks, reductions in daily mean glucose were observed in the canagliflozin 100-mg and 300-mg groups, compared with placebo (–22.4 and –19.4 mg/dL, respectively, vs. a rise of 3 mg/dL in the placebo group), as well as reductions in daily glucose standard deviation (–16.4 and –18.1 mg/dL, vs. –1.9 mg/dL), Dr. Alba reported.

The researchers also found that the percentage of time spent within the glycemic target range was greater in the canagliflozin 100- and 300-mg groups, compared with placebo (a change from baseline of 11.6% and 10.1%, respectively, compared with a decrease of 3.5%), while the percentage of time spent above target was lower in both canagliflozin doses, compared with placebo. Canagliflozin was generally well tolerated, with a dose-dependent increase in ketone-related adverse events (5.1% in the 100-mg group and 9.4% in the 300-mg group).

Janssen Research & Development supported the study.

[email protected]

NEW ORLEANS – Compared with placebo, canagliflozin improved glycemic control and reduced glycemic variability over 18 weeks in adults with type 1 diabetes that had been inadequately controlled with insulin, according to results from a randomized trial.

“Patients with type 1 diabetes can experience acute and profound glucose fluctuations, which may be related to variability in insulin activity and changes in day-to-day activities,” Maria Alba, MD, said at the annual scientific sessions of the American Diabetes Association. “A major challenge in the treatment of type 1 diabetes is achieving patient-specific glycemic control while avoiding episodes of hyperglycemia and hypoglycemia.”

Canagliflozin is a sodium glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes; it lowers blood glucose through an insulin-dependent mechanism by lowering the renal threshold for glucose and increasing urinary glucose excretion. It is not approved for the treatment of type 1 diabetes. In a phase II study, canagliflozin improved glycemic control and provided reductions in body weight and insulin dose in patients with type 1 diabetes who were on background insulin over 18 weeks (Diabetes Care 2015;39[12]:2258-65).

The purpose of the current study was to assess the effects of canagliflozin on daily mean glucose, glycemic variability, and time spent in glycemic ranges (greater than 70-180 mg/dL) in adults with type 1 diabetes inadequately controlled with insulin therapy, said Dr. Alba of Janssen Research & Development, Raritan, N.J. In all, 351 patients were randomized to placebo or 100 mg or 300 mg of canagliflozin. All had had the disease for at least 1 year, had a baseline hemoglobin A_1c level between 7% and 9%, and had to be on a stable insulin regimen for at least 8 weeks. “On the day before randomization, patients were advised to reduce their basal insulin by 10% or 20%, depending on their baseline A_1c,” she said. “Once randomized, they were instructed to titrate their insulin to reach specific glycemic goals.”

All patients were to record 9-point self-monitoring blood glucose (SMBG) measurements throughout the study. Continuous glucose monitoring (CGM) assessments were performed at selected study centers in a substudy of 89 patients. Efficacy endpoints assessed by 9-point SMBG at week 18 were change from baseline in mean daily glucose and daily glucose standard deviation. Efficacy endpoints in the CGM substudy at week 18 were change from baseline in mean glucose, patterns of glucose variability, and time spent within target glucose (greater than 70-180 mg/dL), above target (greater than 180 mg/dL), or below target (70 mg/dL or less). The mean age of study participants was 43 years, 55% were male, and their mean baseline A_1c was 7.9%.

At 18 weeks, reductions in daily mean glucose were observed in the canagliflozin 100-mg and 300-mg groups, compared with placebo (–22.4 and –19.4 mg/dL, respectively, vs. a rise of 3 mg/dL in the placebo group), as well as reductions in daily glucose standard deviation (–16.4 and –18.1 mg/dL, vs. –1.9 mg/dL), Dr. Alba reported.

The researchers also found that the percentage of time spent within the glycemic target range was greater in the canagliflozin 100- and 300-mg groups, compared with placebo (a change from baseline of 11.6% and 10.1%, respectively, compared with a decrease of 3.5%), while the percentage of time spent above target was lower in both canagliflozin doses, compared with placebo. Canagliflozin was generally well tolerated, with a dose-dependent increase in ketone-related adverse events (5.1% in the 100-mg group and 9.4% in the 300-mg group).

Janssen Research & Development supported the study.

[email protected]

NEW YORK - After a decade of follow-up in the Prostate Cancer Research International Active Surveillance (PRIAS) study, researchers have confirmed that active surveillance is a safe treatment option for men with low-risk prostate cancer.

"However," they say, "some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance."

Dr. Leonard P. Bokhorst of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues analyzed data on more than 5,000 men in 18 countries followed in PRIAS, including 622 who were followed more than five years and 107 were followed more than 7.5 years.

The median age at diagnosis was 65.9 years.

Original inclusion criteria included Gleason score 3+3 or lower, stage cT2c or lower, and prostate-specific antigen (PSA) 10 ng/ml or lower. PSA tests were scheduled every three months and digital rectal examinations were scheduled every six months during the first two years of study, then less often later. Criteria to recommend starting active treatment include Gleason score higher than 3+3, more than two positive cores, and stage higher than cT2.

Median PSA for the study population was 5.7 ng/ml. Most men (69%) had one positive biopsy core, with Gleason score of 3+3 (99%) and a clinical stage of T1c (88%).

Almost 3,400 men received at least one repeat biopsy during follow-up and some received up to five biopsies.

Overall, 1,768 men discontinued active surveillance during follow-up, 1,102 due to protocol-based reclassification. Other reasons for discontinuations included anxiety, switch to watchful waiting, death, and loss to follow-up. Two-thirds (67%) of the men were treated with either radical prostatectomy or radiation therapy after discontinuation. Only 3% received hormonal therapy.

Almost half (48%) of the patients were still on active surveillance after five years and 27% were on active surveillance at 10 years, the researchers reported online June 19 in European Urology.

The team had pathology data on 360 men who had radical prostatectomy. Of the men who switched to treatment because of protocol-based reclassification, 82 (30%) had favorable pathological outcomes, 85 (34%) had intermediate outcomes, and 100 (36%) had unfavorable outcomes.

Mortality from prostate cancer was less than 1% during follow-up.

Because of the higher rate of unfavorable treatment outcomes, the researchers recommended a change in the PRIAS protocol.

"Instead of an immediate switch to active treatment if more than two cores are positive, men should receive further investigation to confirm higher risk disease," the researchers write. They recommend examination by magnetic resonance imaging because its negative predictive value for Gleason upgrading is near 100%.

They concluded, "Criteria used to recommend a switch to active treatment do not seem selective enough to avoid unnecessary switches to active treatment."

Dr. Bokhorst did not respond to a request for comment.

The Prostate Cancer Research Foundation, Rotterdam, supports the PRIAS study. The authors made no disclosures.

SOURCE: http://bit.ly/28Q5Cd3

Eur Urol 2016.

NEW YORK - After a decade of follow-up in the Prostate Cancer Research International Active Surveillance (PRIAS) study, researchers have confirmed that active surveillance is a safe treatment option for men with low-risk prostate cancer.

"However," they say, "some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance."

Dr. Leonard P. Bokhorst of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues analyzed data on more than 5,000 men in 18 countries followed in PRIAS, including 622 who were followed more than five years and 107 were followed more than 7.5 years.

The median age at diagnosis was 65.9 years.

Original inclusion criteria included Gleason score 3+3 or lower, stage cT2c or lower, and prostate-specific antigen (PSA) 10 ng/ml or lower. PSA tests were scheduled every three months and digital rectal examinations were scheduled every six months during the first two years of study, then less often later. Criteria to recommend starting active treatment include Gleason score higher than 3+3, more than two positive cores, and stage higher than cT2.

Median PSA for the study population was 5.7 ng/ml. Most men (69%) had one positive biopsy core, with Gleason score of 3+3 (99%) and a clinical stage of T1c (88%).

Almost 3,400 men received at least one repeat biopsy during follow-up and some received up to five biopsies.

Overall, 1,768 men discontinued active surveillance during follow-up, 1,102 due to protocol-based reclassification. Other reasons for discontinuations included anxiety, switch to watchful waiting, death, and loss to follow-up. Two-thirds (67%) of the men were treated with either radical prostatectomy or radiation therapy after discontinuation. Only 3% received hormonal therapy.

Almost half (48%) of the patients were still on active surveillance after five years and 27% were on active surveillance at 10 years, the researchers reported online June 19 in European Urology.

The team had pathology data on 360 men who had radical prostatectomy. Of the men who switched to treatment because of protocol-based reclassification, 82 (30%) had favorable pathological outcomes, 85 (34%) had intermediate outcomes, and 100 (36%) had unfavorable outcomes.

Mortality from prostate cancer was less than 1% during follow-up.

Because of the higher rate of unfavorable treatment outcomes, the researchers recommended a change in the PRIAS protocol.

"Instead of an immediate switch to active treatment if more than two cores are positive, men should receive further investigation to confirm higher risk disease," the researchers write. They recommend examination by magnetic resonance imaging because its negative predictive value for Gleason upgrading is near 100%.

They concluded, "Criteria used to recommend a switch to active treatment do not seem selective enough to avoid unnecessary switches to active treatment."

Dr. Bokhorst did not respond to a request for comment.

The Prostate Cancer Research Foundation, Rotterdam, supports the PRIAS study. The authors made no disclosures.

SOURCE: http://bit.ly/28Q5Cd3

Eur Urol 2016.

NEW YORK - After a decade of follow-up in the Prostate Cancer Research International Active Surveillance (PRIAS) study, researchers have confirmed that active surveillance is a safe treatment option for men with low-risk prostate cancer.

"However," they say, "some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance."

Dr. Leonard P. Bokhorst of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues analyzed data on more than 5,000 men in 18 countries followed in PRIAS, including 622 who were followed more than five years and 107 were followed more than 7.5 years.

The median age at diagnosis was 65.9 years.

Original inclusion criteria included Gleason score 3+3 or lower, stage cT2c or lower, and prostate-specific antigen (PSA) 10 ng/ml or lower. PSA tests were scheduled every three months and digital rectal examinations were scheduled every six months during the first two years of study, then less often later. Criteria to recommend starting active treatment include Gleason score higher than 3+3, more than two positive cores, and stage higher than cT2.

Median PSA for the study population was 5.7 ng/ml. Most men (69%) had one positive biopsy core, with Gleason score of 3+3 (99%) and a clinical stage of T1c (88%).

Almost 3,400 men received at least one repeat biopsy during follow-up and some received up to five biopsies.

Overall, 1,768 men discontinued active surveillance during follow-up, 1,102 due to protocol-based reclassification. Other reasons for discontinuations included anxiety, switch to watchful waiting, death, and loss to follow-up. Two-thirds (67%) of the men were treated with either radical prostatectomy or radiation therapy after discontinuation. Only 3% received hormonal therapy.

Almost half (48%) of the patients were still on active surveillance after five years and 27% were on active surveillance at 10 years, the researchers reported online June 19 in European Urology.

The team had pathology data on 360 men who had radical prostatectomy. Of the men who switched to treatment because of protocol-based reclassification, 82 (30%) had favorable pathological outcomes, 85 (34%) had intermediate outcomes, and 100 (36%) had unfavorable outcomes.

Mortality from prostate cancer was less than 1% during follow-up.

Because of the higher rate of unfavorable treatment outcomes, the researchers recommended a change in the PRIAS protocol.

"Instead of an immediate switch to active treatment if more than two cores are positive, men should receive further investigation to confirm higher risk disease," the researchers write. They recommend examination by magnetic resonance imaging because its negative predictive value for Gleason upgrading is near 100%.

They concluded, "Criteria used to recommend a switch to active treatment do not seem selective enough to avoid unnecessary switches to active treatment."

Dr. Bokhorst did not respond to a request for comment.

The Prostate Cancer Research Foundation, Rotterdam, supports the PRIAS study. The authors made no disclosures.

SOURCE: http://bit.ly/28Q5Cd3

Eur Urol 2016.

HELSINKI, FINLAND – The overall birth rate within 5 years of initiating fertility treatment with homologous gametes was 71% among nearly 20,000 women in a Danish assisted reproductive technology registry.

Conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%, Sara Malchau, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.

©Cathy Yeulet/Thinkstock

The findings allow physicians to give couples a comprehensible, age-stratified, long-term prognosis at the start of treatment, said Dr. Malchau of Copenhagen University Hospital, Hvidovre, Denmark.

To assess long-term outcomes, Dr. Malchau and her colleagues identified all women in the mandatory Danish ART Registry who initiated fertility treatments with homologous gametes in pubic and private clinics in Denmark between 1997 and 2010. The 19,884 subjects’ treatment cycles were cross-linked with the country’s Medical Birth Registry to identify live births after treatment and spontaneous conception. Follow-up was available for up to 2 years for all of the women, up to 3 years for 14,445 women, and up to 5 years for 5,165 women.

The total live birth rates at 2, 3, and 5 years after the first treatment using ART or intrauterine insemination (IUI) were 57%, 65% and 71%, respectively. Dr. Malchau reported.

In women who had ART as the first treatment, the corresponding ART-conception live birth rates were 46.1%, 51.1%, and 52.9%, and the birth rates with spontaneous conception and IUI after 5 years were 11.2% and 0.6%, respectively.

In those with IUI first, 34.2% delivered after IUI conceptions within 2 years, with no significant increase in birth rates after 3 and 5 years. Shifting to ART in these women resulted in birth rates for ART conceptions of 15.1%, 21.1%, and 23.7% after 2, 3, and 5 years, respectively. After 5 years, the birth rate from spontaneous conception in all women starting treatment with IUI was 16.6%, she noted.

Stratification by age showed that the birth rates at 5 years were 80% for women under age 35 years, 60.5% for those aged 35-40 years, and 26.2% for those aged 40 and older.

While the national ART registry in Denmark is compulsory, underreporting can occur. However, it is cycle based, and since most women have repeated treatments, is it unlikely that the number of women with no birth was underestimated in this study, Dr. Malchau noted.

The findings – which reflect the Danish treatment strategy of three to six cycles of IUI followed by ART, explaining why birth rates after IUI did not increase after 2 years – help answer important patient questions, she said.

“Infertility patients have two key questions: What are our chances of having a baby and when will it happen?” said Dr. Malchau. “Overall chances of a live birth are good, but successful treatment takes time. Couples will often need several treatment cycles. And even though the greatest chance of conception is following treatment, there is still a reasonable chance of spontaneous conception.”

Spontaneous conception is most common in women under age 35 starting IUI (18% vs. 8% in those over 35 starting IVF treatment).

The findings are “robust and realistic,” and since those undergoing treatment have no idea how many treatment cycles they will need or have, a “prognosis based on fixed points in time better reflects their prospect of conception and delivery than birth rates after different numbers of attempts,” Dr. Malchau said.

Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.

[email protected]

HELSINKI, FINLAND – The overall birth rate within 5 years of initiating fertility treatment with homologous gametes was 71% among nearly 20,000 women in a Danish assisted reproductive technology registry.

Conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%, Sara Malchau, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.

©Cathy Yeulet/Thinkstock

The findings allow physicians to give couples a comprehensible, age-stratified, long-term prognosis at the start of treatment, said Dr. Malchau of Copenhagen University Hospital, Hvidovre, Denmark.

To assess long-term outcomes, Dr. Malchau and her colleagues identified all women in the mandatory Danish ART Registry who initiated fertility treatments with homologous gametes in pubic and private clinics in Denmark between 1997 and 2010. The 19,884 subjects’ treatment cycles were cross-linked with the country’s Medical Birth Registry to identify live births after treatment and spontaneous conception. Follow-up was available for up to 2 years for all of the women, up to 3 years for 14,445 women, and up to 5 years for 5,165 women.

The total live birth rates at 2, 3, and 5 years after the first treatment using ART or intrauterine insemination (IUI) were 57%, 65% and 71%, respectively. Dr. Malchau reported.

In women who had ART as the first treatment, the corresponding ART-conception live birth rates were 46.1%, 51.1%, and 52.9%, and the birth rates with spontaneous conception and IUI after 5 years were 11.2% and 0.6%, respectively.

In those with IUI first, 34.2% delivered after IUI conceptions within 2 years, with no significant increase in birth rates after 3 and 5 years. Shifting to ART in these women resulted in birth rates for ART conceptions of 15.1%, 21.1%, and 23.7% after 2, 3, and 5 years, respectively. After 5 years, the birth rate from spontaneous conception in all women starting treatment with IUI was 16.6%, she noted.

Stratification by age showed that the birth rates at 5 years were 80% for women under age 35 years, 60.5% for those aged 35-40 years, and 26.2% for those aged 40 and older.

While the national ART registry in Denmark is compulsory, underreporting can occur. However, it is cycle based, and since most women have repeated treatments, is it unlikely that the number of women with no birth was underestimated in this study, Dr. Malchau noted.

The findings – which reflect the Danish treatment strategy of three to six cycles of IUI followed by ART, explaining why birth rates after IUI did not increase after 2 years – help answer important patient questions, she said.

“Infertility patients have two key questions: What are our chances of having a baby and when will it happen?” said Dr. Malchau. “Overall chances of a live birth are good, but successful treatment takes time. Couples will often need several treatment cycles. And even though the greatest chance of conception is following treatment, there is still a reasonable chance of spontaneous conception.”

Spontaneous conception is most common in women under age 35 starting IUI (18% vs. 8% in those over 35 starting IVF treatment).

The findings are “robust and realistic,” and since those undergoing treatment have no idea how many treatment cycles they will need or have, a “prognosis based on fixed points in time better reflects their prospect of conception and delivery than birth rates after different numbers of attempts,” Dr. Malchau said.

Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.

[email protected]

HELSINKI, FINLAND – The overall birth rate within 5 years of initiating fertility treatment with homologous gametes was 71% among nearly 20,000 women in a Danish assisted reproductive technology registry.

Conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%, Sara Malchau, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.

©Cathy Yeulet/Thinkstock

The findings allow physicians to give couples a comprehensible, age-stratified, long-term prognosis at the start of treatment, said Dr. Malchau of Copenhagen University Hospital, Hvidovre, Denmark.

To assess long-term outcomes, Dr. Malchau and her colleagues identified all women in the mandatory Danish ART Registry who initiated fertility treatments with homologous gametes in pubic and private clinics in Denmark between 1997 and 2010. The 19,884 subjects’ treatment cycles were cross-linked with the country’s Medical Birth Registry to identify live births after treatment and spontaneous conception. Follow-up was available for up to 2 years for all of the women, up to 3 years for 14,445 women, and up to 5 years for 5,165 women.

The total live birth rates at 2, 3, and 5 years after the first treatment using ART or intrauterine insemination (IUI) were 57%, 65% and 71%, respectively. Dr. Malchau reported.

In women who had ART as the first treatment, the corresponding ART-conception live birth rates were 46.1%, 51.1%, and 52.9%, and the birth rates with spontaneous conception and IUI after 5 years were 11.2% and 0.6%, respectively.

In those with IUI first, 34.2% delivered after IUI conceptions within 2 years, with no significant increase in birth rates after 3 and 5 years. Shifting to ART in these women resulted in birth rates for ART conceptions of 15.1%, 21.1%, and 23.7% after 2, 3, and 5 years, respectively. After 5 years, the birth rate from spontaneous conception in all women starting treatment with IUI was 16.6%, she noted.

Stratification by age showed that the birth rates at 5 years were 80% for women under age 35 years, 60.5% for those aged 35-40 years, and 26.2% for those aged 40 and older.

While the national ART registry in Denmark is compulsory, underreporting can occur. However, it is cycle based, and since most women have repeated treatments, is it unlikely that the number of women with no birth was underestimated in this study, Dr. Malchau noted.

The findings – which reflect the Danish treatment strategy of three to six cycles of IUI followed by ART, explaining why birth rates after IUI did not increase after 2 years – help answer important patient questions, she said.

“Infertility patients have two key questions: What are our chances of having a baby and when will it happen?” said Dr. Malchau. “Overall chances of a live birth are good, but successful treatment takes time. Couples will often need several treatment cycles. And even though the greatest chance of conception is following treatment, there is still a reasonable chance of spontaneous conception.”

Spontaneous conception is most common in women under age 35 starting IUI (18% vs. 8% in those over 35 starting IVF treatment).

The findings are “robust and realistic,” and since those undergoing treatment have no idea how many treatment cycles they will need or have, a “prognosis based on fixed points in time better reflects their prospect of conception and delivery than birth rates after different numbers of attempts,” Dr. Malchau said.

Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.

[email protected]

NEW ORLEANS – There is a high burden of early complications among young adults with type 1 or type 2 diabetes, results from an ongoing study demonstrated.

“We are witnessing a recent increase in type 2 diabetes in the pediatric U.S. population, paralleling a somewhat more established rise in type 1 diabetes among youth worldwide,” Dana Dabelea, MD, PhD, said at the annual scientific sessions of the American Diabetes Association. “In the face of this increasing disease burden, we are left with limited information on the consequences of having diabetes on these youth, specifically the burden of diabetes-related chronic complications. No study exists in the U.S. that is able to compare this burden in youth with type 2 versus those with type 1 diabetes. Prior studies elsewhere worldwide have used mostly medical records or administrative data, have small sample sizes, and include youth with variable disease duration.”

The aim of the current study was to assess and compare the prevalence of several complications in youth with either type 1 or type 2 diabetes of similar age and disease (short) duration, and to explore the potential risk factors for observed differences by diabetes type. Dr. Dabelea of the department of epidemiology at the University of Colorado School of Public Health in Denver, and her colleagues from the SEARCH for Diabetes in Youth Study, developed a cohort of 1,746 individuals with type 1 and 272 with type 2 diabetes, diagnosed when younger than age 20, assembled from the population-based SEARCH Registry in five U.S. sites, and registered upon diagnosis between 2002 and 2008. The most recent visit was between 2011 and 2015 when participants were at least 10 years of age.

Outcomes, measured once at the cohort visit between 2010 and 2015, included diabetic kidney disease, diabetic retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension.

Dr. Dabelea reported that 32% of youth with type 1 diabetes and 72% of those with type 2 diabetes had at least one early complication. For all complications, except cardiovascular autonomic neuropathy, the prevalence was significantly higher in those with type 2 diabetes, compared with those who had type 1 disease, with a similar pattern by race, especially for minority youth. Estimates were also usually higher within type among minority vs. non-white Hispanic youth, especially for type 2 diabetes. The findings “indicate a need for heightened clinical suspicion and detection of early complications, together with aggressive risk factor control, especially in type 2 diabetes and minority youth,” she concluded.

The Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Dabelea reported having no financial disclosures.

[email protected]

NEW ORLEANS – There is a high burden of early complications among young adults with type 1 or type 2 diabetes, results from an ongoing study demonstrated.

“We are witnessing a recent increase in type 2 diabetes in the pediatric U.S. population, paralleling a somewhat more established rise in type 1 diabetes among youth worldwide,” Dana Dabelea, MD, PhD, said at the annual scientific sessions of the American Diabetes Association. “In the face of this increasing disease burden, we are left with limited information on the consequences of having diabetes on these youth, specifically the burden of diabetes-related chronic complications. No study exists in the U.S. that is able to compare this burden in youth with type 2 versus those with type 1 diabetes. Prior studies elsewhere worldwide have used mostly medical records or administrative data, have small sample sizes, and include youth with variable disease duration.”

The aim of the current study was to assess and compare the prevalence of several complications in youth with either type 1 or type 2 diabetes of similar age and disease (short) duration, and to explore the potential risk factors for observed differences by diabetes type. Dr. Dabelea of the department of epidemiology at the University of Colorado School of Public Health in Denver, and her colleagues from the SEARCH for Diabetes in Youth Study, developed a cohort of 1,746 individuals with type 1 and 272 with type 2 diabetes, diagnosed when younger than age 20, assembled from the population-based SEARCH Registry in five U.S. sites, and registered upon diagnosis between 2002 and 2008. The most recent visit was between 2011 and 2015 when participants were at least 10 years of age.

Outcomes, measured once at the cohort visit between 2010 and 2015, included diabetic kidney disease, diabetic retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension.

Dr. Dabelea reported that 32% of youth with type 1 diabetes and 72% of those with type 2 diabetes had at least one early complication. For all complications, except cardiovascular autonomic neuropathy, the prevalence was significantly higher in those with type 2 diabetes, compared with those who had type 1 disease, with a similar pattern by race, especially for minority youth. Estimates were also usually higher within type among minority vs. non-white Hispanic youth, especially for type 2 diabetes. The findings “indicate a need for heightened clinical suspicion and detection of early complications, together with aggressive risk factor control, especially in type 2 diabetes and minority youth,” she concluded.

The Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Dabelea reported having no financial disclosures.

[email protected]

NEW ORLEANS – There is a high burden of early complications among young adults with type 1 or type 2 diabetes, results from an ongoing study demonstrated.

“We are witnessing a recent increase in type 2 diabetes in the pediatric U.S. population, paralleling a somewhat more established rise in type 1 diabetes among youth worldwide,” Dana Dabelea, MD, PhD, said at the annual scientific sessions of the American Diabetes Association. “In the face of this increasing disease burden, we are left with limited information on the consequences of having diabetes on these youth, specifically the burden of diabetes-related chronic complications. No study exists in the U.S. that is able to compare this burden in youth with type 2 versus those with type 1 diabetes. Prior studies elsewhere worldwide have used mostly medical records or administrative data, have small sample sizes, and include youth with variable disease duration.”

The aim of the current study was to assess and compare the prevalence of several complications in youth with either type 1 or type 2 diabetes of similar age and disease (short) duration, and to explore the potential risk factors for observed differences by diabetes type. Dr. Dabelea of the department of epidemiology at the University of Colorado School of Public Health in Denver, and her colleagues from the SEARCH for Diabetes in Youth Study, developed a cohort of 1,746 individuals with type 1 and 272 with type 2 diabetes, diagnosed when younger than age 20, assembled from the population-based SEARCH Registry in five U.S. sites, and registered upon diagnosis between 2002 and 2008. The most recent visit was between 2011 and 2015 when participants were at least 10 years of age.

Outcomes, measured once at the cohort visit between 2010 and 2015, included diabetic kidney disease, diabetic retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension.

Dr. Dabelea reported that 32% of youth with type 1 diabetes and 72% of those with type 2 diabetes had at least one early complication. For all complications, except cardiovascular autonomic neuropathy, the prevalence was significantly higher in those with type 2 diabetes, compared with those who had type 1 disease, with a similar pattern by race, especially for minority youth. Estimates were also usually higher within type among minority vs. non-white Hispanic youth, especially for type 2 diabetes. The findings “indicate a need for heightened clinical suspicion and detection of early complications, together with aggressive risk factor control, especially in type 2 diabetes and minority youth,” she concluded.

The Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Dabelea reported having no financial disclosures.

[email protected]