SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

[email protected]

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

[email protected]

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

[email protected]

Focus on ability to perform functional tasks when designing interventions aimed at improving health-related quality of life for patients with symptomatic peripheral arterial disease (PAD), advise the authors of a study published in the Journal of Vascular Surgery.

Pavel Losevsky/iStockphoto

Clinical markers of disease severity and comorbidities are often the primary targets of interventions in PAD patients, but health-related quality of life (HRQoL) based on their functional capabilities matters more to patients, according to Andrew W. Gardner, PhD, of Penn State University, Hershey, and his colleagues.

“Interventions designed to improve HRQoL should focus on improving the quality of executing functional tasks, such as walking more steadily without stumbling; completing ADLs [activities of daily living] that are not specific to walking, such as bathing and transferring; and improving patient-based ability to walk various distances and speeds and to climb stairs,” the researchers wrote.

They studied 216 PAD patients (mean age, 65 years) with ambulatory leg pain confirmed by treadmill exercise and ankle brachial index less than or equal to 0.90 at rest or less than or equal to 0.73 after exercise. Patient HRQoL was measured using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). All patients performed a maximal treadmill test, a 6-minute walk test, and gait speed from a 4-meter walk test was measured. Their ambulatory activity was monitored for 7 days using a step monitor. In addition, patients self-assessed their ability to perform four lower-level ADLs, consisting of walking across a small room, bathing, transferring from a bed to a chair, and using the toilet. They also evaluated their ability to perform two higher-level ADLs consisting of walking up and down stairs to the second floor without help and walking a half-mile without help.

Approximately 10%-17% of the patients reported either having some difficulty with or being unable to perform basic ADLs, whereas the majority reported either having some difficulty with or being unable to perform higher-level ADLs consisting of walking up and down stairs (74%) and walking a half-mile without help (85%).

The primary novel finding, according to Dr. Gardner and his colleagues, was that patient-based measurements of physical function were the strongest predictors of both physical and mental subscales of HRQoL.

The significant predictors were Walking Impairment Questionnaire speed score (P less than .001), history of stumbling while walking (P less than .001), stair climbing score (P = .001), bathing (P = .001), 6-minute walking distance (P =.004), and daily walking cadence (P = .043). The significant predictors of the role limitations caused by emotional problems subscale of the SF-36 included a history of stumbling while walking (P less than .001), transferring from a bed to a chair (P less than .001), and the walking distance score (P = .022).

Noticeably, a history of stumbling while walking was considered particularly important to the patients. In contrast, objective measurements of physical function (6-minute walking distance and daily walking cadence) were predictive only of the physical function subscale. Comorbid conditions and objective measures of PAD severity, such as ankle brachial index, claudication onset time, and peak walking time, were not at all predictive of HRQoL, the researchers stated.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Gardner AW et al. J Vasc Surg. 2018;68:1126-34.

Focus on ability to perform functional tasks when designing interventions aimed at improving health-related quality of life for patients with symptomatic peripheral arterial disease (PAD), advise the authors of a study published in the Journal of Vascular Surgery.

Pavel Losevsky/iStockphoto

Clinical markers of disease severity and comorbidities are often the primary targets of interventions in PAD patients, but health-related quality of life (HRQoL) based on their functional capabilities matters more to patients, according to Andrew W. Gardner, PhD, of Penn State University, Hershey, and his colleagues.

“Interventions designed to improve HRQoL should focus on improving the quality of executing functional tasks, such as walking more steadily without stumbling; completing ADLs [activities of daily living] that are not specific to walking, such as bathing and transferring; and improving patient-based ability to walk various distances and speeds and to climb stairs,” the researchers wrote.

They studied 216 PAD patients (mean age, 65 years) with ambulatory leg pain confirmed by treadmill exercise and ankle brachial index less than or equal to 0.90 at rest or less than or equal to 0.73 after exercise. Patient HRQoL was measured using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). All patients performed a maximal treadmill test, a 6-minute walk test, and gait speed from a 4-meter walk test was measured. Their ambulatory activity was monitored for 7 days using a step monitor. In addition, patients self-assessed their ability to perform four lower-level ADLs, consisting of walking across a small room, bathing, transferring from a bed to a chair, and using the toilet. They also evaluated their ability to perform two higher-level ADLs consisting of walking up and down stairs to the second floor without help and walking a half-mile without help.

Approximately 10%-17% of the patients reported either having some difficulty with or being unable to perform basic ADLs, whereas the majority reported either having some difficulty with or being unable to perform higher-level ADLs consisting of walking up and down stairs (74%) and walking a half-mile without help (85%).

The primary novel finding, according to Dr. Gardner and his colleagues, was that patient-based measurements of physical function were the strongest predictors of both physical and mental subscales of HRQoL.

The significant predictors were Walking Impairment Questionnaire speed score (P less than .001), history of stumbling while walking (P less than .001), stair climbing score (P = .001), bathing (P = .001), 6-minute walking distance (P =.004), and daily walking cadence (P = .043). The significant predictors of the role limitations caused by emotional problems subscale of the SF-36 included a history of stumbling while walking (P less than .001), transferring from a bed to a chair (P less than .001), and the walking distance score (P = .022).

Noticeably, a history of stumbling while walking was considered particularly important to the patients. In contrast, objective measurements of physical function (6-minute walking distance and daily walking cadence) were predictive only of the physical function subscale. Comorbid conditions and objective measures of PAD severity, such as ankle brachial index, claudication onset time, and peak walking time, were not at all predictive of HRQoL, the researchers stated.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Gardner AW et al. J Vasc Surg. 2018;68:1126-34.

Focus on ability to perform functional tasks when designing interventions aimed at improving health-related quality of life for patients with symptomatic peripheral arterial disease (PAD), advise the authors of a study published in the Journal of Vascular Surgery.

Pavel Losevsky/iStockphoto

Clinical markers of disease severity and comorbidities are often the primary targets of interventions in PAD patients, but health-related quality of life (HRQoL) based on their functional capabilities matters more to patients, according to Andrew W. Gardner, PhD, of Penn State University, Hershey, and his colleagues.

“Interventions designed to improve HRQoL should focus on improving the quality of executing functional tasks, such as walking more steadily without stumbling; completing ADLs [activities of daily living] that are not specific to walking, such as bathing and transferring; and improving patient-based ability to walk various distances and speeds and to climb stairs,” the researchers wrote.

They studied 216 PAD patients (mean age, 65 years) with ambulatory leg pain confirmed by treadmill exercise and ankle brachial index less than or equal to 0.90 at rest or less than or equal to 0.73 after exercise. Patient HRQoL was measured using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). All patients performed a maximal treadmill test, a 6-minute walk test, and gait speed from a 4-meter walk test was measured. Their ambulatory activity was monitored for 7 days using a step monitor. In addition, patients self-assessed their ability to perform four lower-level ADLs, consisting of walking across a small room, bathing, transferring from a bed to a chair, and using the toilet. They also evaluated their ability to perform two higher-level ADLs consisting of walking up and down stairs to the second floor without help and walking a half-mile without help.

Approximately 10%-17% of the patients reported either having some difficulty with or being unable to perform basic ADLs, whereas the majority reported either having some difficulty with or being unable to perform higher-level ADLs consisting of walking up and down stairs (74%) and walking a half-mile without help (85%).

The primary novel finding, according to Dr. Gardner and his colleagues, was that patient-based measurements of physical function were the strongest predictors of both physical and mental subscales of HRQoL.

The significant predictors were Walking Impairment Questionnaire speed score (P less than .001), history of stumbling while walking (P less than .001), stair climbing score (P = .001), bathing (P = .001), 6-minute walking distance (P =.004), and daily walking cadence (P = .043). The significant predictors of the role limitations caused by emotional problems subscale of the SF-36 included a history of stumbling while walking (P less than .001), transferring from a bed to a chair (P less than .001), and the walking distance score (P = .022).

Noticeably, a history of stumbling while walking was considered particularly important to the patients. In contrast, objective measurements of physical function (6-minute walking distance and daily walking cadence) were predictive only of the physical function subscale. Comorbid conditions and objective measures of PAD severity, such as ankle brachial index, claudication onset time, and peak walking time, were not at all predictive of HRQoL, the researchers stated.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Gardner AW et al. J Vasc Surg. 2018;68:1126-34.

MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.

Results of the STAMPEDE and LATITUDE trials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.

Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.

“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.

The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.

For example, in the CHAARTED trial, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.

To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.

The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.

Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).

For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).

Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.

The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).

ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).

An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.

“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.

Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.

“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.

The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.

SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.

MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.

Results of the STAMPEDE and LATITUDE trials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.

Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.

“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.

The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.

For example, in the CHAARTED trial, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.

To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.

The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.

Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).

For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).

Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.

The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).

ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).

An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.

“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.

Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.

“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.

The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.

SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.

MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.

Results of the STAMPEDE and LATITUDE trials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.

Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.

“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.

The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.

For example, in the CHAARTED trial, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.

To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.

The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.

Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).

For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).

Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.

The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).

ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).

An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.

“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.

Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.

“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.

The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.

SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.

All adults aged 18 years and older, including pregnant women, should be screened in primary care settings for unhealthy alcohol use and offered behavioral counseling if needed, according to recommendations from the U.S. Preventive Services Task Force.

Vonschonertagen/Thinkstock

Adults who meet the criteria for unhealthy alcohol use should be offered brief behavioral counseling interventions, the task force concluded with a B recommendation.

However, the task force also concluded that evidence is insufficient to recommend screening for alcohol use in adolescents aged 12-17 years in primary care settings (an I statement), wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and colleagues. The recommendations were published in JAMA as an update of the USPSTF 2013 recommendation on screening for unhealthy alcohol use in primary care settings.

Approximately 88,000 deaths occurred each year in the United States between 2006 and 2010, the task force noted. Those deaths include death by acute causes, such as alcohol-related injuries, and chronic causes, such as alcoholic liver disease. In addition, alcohol use during pregnancy is a major preventable cause of birth defects and developmental disabilities, the task force wrote.

After reviewing the evidence, the USPSTF concluded that brief behavioral counseling offered moderate net benefits for adults 18 years and older, including pregnant women, who met criteria for unhealthy alcohol use.

Unhealthy alcohol used was defined as exceeding the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended limits of 4 drinks per day, or 14 drinks per week, for men aged 21-64 years, and 3 drinks per day, or 7 drinks per week, for women aged 21-64 years.

In the evidence review accompanying the recommendations, Elizabeth A. O’Connor, PhD, of Kaiser Permanente in Portland, Ore., and colleagues analyzed data from 113 studies, including 314,466 individuals; 10 studies included adolescents.

In 68 studies including 36,528 individuals, brief counseling was associated with fewer drinks per week, fewer individuals exceeding recommended limits for alcohol consumption, fewer drinkers reporting a heavy drinking episode, and a greater proportion of pregnant women reporting alcohol abstinence after 6-12 months.

None of the studies assessed benefits or harms, but no evidence suggested that the interventions could be harmful.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

SOURCES: Curry S et al. JAMA. 2018;320(18):1899-1909; O’Connor E et al. JAMA. 2018;320(18):1910-28.

All adults aged 18 years and older, including pregnant women, should be screened in primary care settings for unhealthy alcohol use and offered behavioral counseling if needed, according to recommendations from the U.S. Preventive Services Task Force.

Vonschonertagen/Thinkstock

Adults who meet the criteria for unhealthy alcohol use should be offered brief behavioral counseling interventions, the task force concluded with a B recommendation.

However, the task force also concluded that evidence is insufficient to recommend screening for alcohol use in adolescents aged 12-17 years in primary care settings (an I statement), wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and colleagues. The recommendations were published in JAMA as an update of the USPSTF 2013 recommendation on screening for unhealthy alcohol use in primary care settings.

Approximately 88,000 deaths occurred each year in the United States between 2006 and 2010, the task force noted. Those deaths include death by acute causes, such as alcohol-related injuries, and chronic causes, such as alcoholic liver disease. In addition, alcohol use during pregnancy is a major preventable cause of birth defects and developmental disabilities, the task force wrote.

After reviewing the evidence, the USPSTF concluded that brief behavioral counseling offered moderate net benefits for adults 18 years and older, including pregnant women, who met criteria for unhealthy alcohol use.

Unhealthy alcohol used was defined as exceeding the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended limits of 4 drinks per day, or 14 drinks per week, for men aged 21-64 years, and 3 drinks per day, or 7 drinks per week, for women aged 21-64 years.

In the evidence review accompanying the recommendations, Elizabeth A. O’Connor, PhD, of Kaiser Permanente in Portland, Ore., and colleagues analyzed data from 113 studies, including 314,466 individuals; 10 studies included adolescents.

In 68 studies including 36,528 individuals, brief counseling was associated with fewer drinks per week, fewer individuals exceeding recommended limits for alcohol consumption, fewer drinkers reporting a heavy drinking episode, and a greater proportion of pregnant women reporting alcohol abstinence after 6-12 months.

None of the studies assessed benefits or harms, but no evidence suggested that the interventions could be harmful.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

SOURCES: Curry S et al. JAMA. 2018;320(18):1899-1909; O’Connor E et al. JAMA. 2018;320(18):1910-28.

All adults aged 18 years and older, including pregnant women, should be screened in primary care settings for unhealthy alcohol use and offered behavioral counseling if needed, according to recommendations from the U.S. Preventive Services Task Force.

Vonschonertagen/Thinkstock

Adults who meet the criteria for unhealthy alcohol use should be offered brief behavioral counseling interventions, the task force concluded with a B recommendation.

However, the task force also concluded that evidence is insufficient to recommend screening for alcohol use in adolescents aged 12-17 years in primary care settings (an I statement), wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and colleagues. The recommendations were published in JAMA as an update of the USPSTF 2013 recommendation on screening for unhealthy alcohol use in primary care settings.

Approximately 88,000 deaths occurred each year in the United States between 2006 and 2010, the task force noted. Those deaths include death by acute causes, such as alcohol-related injuries, and chronic causes, such as alcoholic liver disease. In addition, alcohol use during pregnancy is a major preventable cause of birth defects and developmental disabilities, the task force wrote.

After reviewing the evidence, the USPSTF concluded that brief behavioral counseling offered moderate net benefits for adults 18 years and older, including pregnant women, who met criteria for unhealthy alcohol use.

Unhealthy alcohol used was defined as exceeding the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended limits of 4 drinks per day, or 14 drinks per week, for men aged 21-64 years, and 3 drinks per day, or 7 drinks per week, for women aged 21-64 years.

In the evidence review accompanying the recommendations, Elizabeth A. O’Connor, PhD, of Kaiser Permanente in Portland, Ore., and colleagues analyzed data from 113 studies, including 314,466 individuals; 10 studies included adolescents.

In 68 studies including 36,528 individuals, brief counseling was associated with fewer drinks per week, fewer individuals exceeding recommended limits for alcohol consumption, fewer drinkers reporting a heavy drinking episode, and a greater proportion of pregnant women reporting alcohol abstinence after 6-12 months.

None of the studies assessed benefits or harms, but no evidence suggested that the interventions could be harmful.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

SOURCES: Curry S et al. JAMA. 2018;320(18):1899-1909; O’Connor E et al. JAMA. 2018;320(18):1910-28.

Despite the adoption of naloxone access laws, new findings suggest that naloxone availability without a prescription still varies between states.

Two research letters published Nov. 13 in JAMA examined pharmacy availability of naloxone in California and Texas 24 and 32 months, respectively, after implementation of expanded access laws.

In California, just 23.5% of retail pharmacies were dispensing naloxone without a prescription 2 years later. In Texas, however, 83.7% of chain pharmacies with expanded access via standing order reported that they would dispense naloxone without prescription 32 months later.

In the first study, investigators conducted an anonymous telephone survey of a 20% representative sample of California pharmacies. Posing as potential customers, interviewers asked pharmacy staff whether naloxone was available at their pharmacy without a prescription. They also inquired about what formulations were available, price, and whether naloxone could be billed to insurance, wrote Talia Puzantian, PharmD, and James J. Gasper, PharmD.

Naloxone was available at 23.5% (95% confidence interval, 21.0%-26.0%) of the 1,147 pharmacies that provided data. Chain pharmacies were more likely to dispense naloxone (31.6%; 95% CI, 28.3%-35.1%) than were independent pharmacies (7.5%; 95% CI, 5.1%-10.6%; P less than .001). Of pharmacies dispensing naloxone, 50.6% had nasal naloxone in stock, and 59.9% correctly said that naloxone could be billed to insurance, reported Dr. Puzantian, of the Keck Graduate Institute School of Pharmacy in Claremont, Calif., and Dr. Gasper, of the department of family and community medicine at the University of California, San Francisco.

Reasons for low availability in California pharmacies might include lack of knowledge and training, stigma about substance use, and time, Dr. Puzantian and Dr. Gasper said.

“Whether naloxone will become more available with training of additional pharmacists and implementation of standardized policies by pharmacy chains needs to be studied,” the authors concluded.

The second study examined naloxone availability among Texas chain pharmacies with public implementation of standing orders, for a survey of 2,317 CVS, Walgreens, HEB, and Walmart pharmacies. Interviewers posed as potential overdose responders, and inquired about purchasing naloxone without a prescription, reported Kirk E. Evoy, PharmD, of the College of Pharmacy at the University of Texas at Austin, and his coauthors.

Of the pharmacies surveyed, 83.7% (95% CI, 82.2%-85.2%) said they would dispense naloxone without a prescription, and 76.4% (95% CI, 74.7%-78.1%) currently stocked naloxone.

In addition, 79.9% (95% CI, 78.3%-81.6%) would allow purchase of naloxone for someone else, though only 49.7% (95% CI, 47.8%-51.9%) would allow the purchase to be billed to a third-party buyer’s insurance, the authors noted.

Although this study found that most pharmacies would dispense naloxone without a prescription, the findings cannot be applied to independent pharmacies, Dr. Evoy and his colleagues noted.

“Consistent naloxone supply in all pharmacies, improved pharmacist understanding of naloxone standing orders, and ubiquitous insurance coverage for third-party purchasers may further improve access,” they wrote.

Dr. Puzantian and Dr. Gasper reported no disclosures. Dr. Evoy disclosed receiving grant funding from the Institute for Integration of Medicine and Science at the UT Health in San Antonio, the Kleberg Foundation, and Texas Health and Human Services. Other authors disclosed previous receipt of donations of branded formulations of naloxone from Kaléo Pharma and Adapt Pharma.

SOURCE: Puzantian T et al. and Evoy KE et al. JAMA 2018 Nov 13.320(18):1933-7.

Despite the adoption of naloxone access laws, new findings suggest that naloxone availability without a prescription still varies between states.

Two research letters published Nov. 13 in JAMA examined pharmacy availability of naloxone in California and Texas 24 and 32 months, respectively, after implementation of expanded access laws.

In California, just 23.5% of retail pharmacies were dispensing naloxone without a prescription 2 years later. In Texas, however, 83.7% of chain pharmacies with expanded access via standing order reported that they would dispense naloxone without prescription 32 months later.

In the first study, investigators conducted an anonymous telephone survey of a 20% representative sample of California pharmacies. Posing as potential customers, interviewers asked pharmacy staff whether naloxone was available at their pharmacy without a prescription. They also inquired about what formulations were available, price, and whether naloxone could be billed to insurance, wrote Talia Puzantian, PharmD, and James J. Gasper, PharmD.

Naloxone was available at 23.5% (95% confidence interval, 21.0%-26.0%) of the 1,147 pharmacies that provided data. Chain pharmacies were more likely to dispense naloxone (31.6%; 95% CI, 28.3%-35.1%) than were independent pharmacies (7.5%; 95% CI, 5.1%-10.6%; P less than .001). Of pharmacies dispensing naloxone, 50.6% had nasal naloxone in stock, and 59.9% correctly said that naloxone could be billed to insurance, reported Dr. Puzantian, of the Keck Graduate Institute School of Pharmacy in Claremont, Calif., and Dr. Gasper, of the department of family and community medicine at the University of California, San Francisco.

Reasons for low availability in California pharmacies might include lack of knowledge and training, stigma about substance use, and time, Dr. Puzantian and Dr. Gasper said.

“Whether naloxone will become more available with training of additional pharmacists and implementation of standardized policies by pharmacy chains needs to be studied,” the authors concluded.

The second study examined naloxone availability among Texas chain pharmacies with public implementation of standing orders, for a survey of 2,317 CVS, Walgreens, HEB, and Walmart pharmacies. Interviewers posed as potential overdose responders, and inquired about purchasing naloxone without a prescription, reported Kirk E. Evoy, PharmD, of the College of Pharmacy at the University of Texas at Austin, and his coauthors.

Of the pharmacies surveyed, 83.7% (95% CI, 82.2%-85.2%) said they would dispense naloxone without a prescription, and 76.4% (95% CI, 74.7%-78.1%) currently stocked naloxone.

In addition, 79.9% (95% CI, 78.3%-81.6%) would allow purchase of naloxone for someone else, though only 49.7% (95% CI, 47.8%-51.9%) would allow the purchase to be billed to a third-party buyer’s insurance, the authors noted.

Although this study found that most pharmacies would dispense naloxone without a prescription, the findings cannot be applied to independent pharmacies, Dr. Evoy and his colleagues noted.

“Consistent naloxone supply in all pharmacies, improved pharmacist understanding of naloxone standing orders, and ubiquitous insurance coverage for third-party purchasers may further improve access,” they wrote.

Dr. Puzantian and Dr. Gasper reported no disclosures. Dr. Evoy disclosed receiving grant funding from the Institute for Integration of Medicine and Science at the UT Health in San Antonio, the Kleberg Foundation, and Texas Health and Human Services. Other authors disclosed previous receipt of donations of branded formulations of naloxone from Kaléo Pharma and Adapt Pharma.

SOURCE: Puzantian T et al. and Evoy KE et al. JAMA 2018 Nov 13.320(18):1933-7.

Despite the adoption of naloxone access laws, new findings suggest that naloxone availability without a prescription still varies between states.

Two research letters published Nov. 13 in JAMA examined pharmacy availability of naloxone in California and Texas 24 and 32 months, respectively, after implementation of expanded access laws.

In California, just 23.5% of retail pharmacies were dispensing naloxone without a prescription 2 years later. In Texas, however, 83.7% of chain pharmacies with expanded access via standing order reported that they would dispense naloxone without prescription 32 months later.

In the first study, investigators conducted an anonymous telephone survey of a 20% representative sample of California pharmacies. Posing as potential customers, interviewers asked pharmacy staff whether naloxone was available at their pharmacy without a prescription. They also inquired about what formulations were available, price, and whether naloxone could be billed to insurance, wrote Talia Puzantian, PharmD, and James J. Gasper, PharmD.

Naloxone was available at 23.5% (95% confidence interval, 21.0%-26.0%) of the 1,147 pharmacies that provided data. Chain pharmacies were more likely to dispense naloxone (31.6%; 95% CI, 28.3%-35.1%) than were independent pharmacies (7.5%; 95% CI, 5.1%-10.6%; P less than .001). Of pharmacies dispensing naloxone, 50.6% had nasal naloxone in stock, and 59.9% correctly said that naloxone could be billed to insurance, reported Dr. Puzantian, of the Keck Graduate Institute School of Pharmacy in Claremont, Calif., and Dr. Gasper, of the department of family and community medicine at the University of California, San Francisco.

Reasons for low availability in California pharmacies might include lack of knowledge and training, stigma about substance use, and time, Dr. Puzantian and Dr. Gasper said.

“Whether naloxone will become more available with training of additional pharmacists and implementation of standardized policies by pharmacy chains needs to be studied,” the authors concluded.

The second study examined naloxone availability among Texas chain pharmacies with public implementation of standing orders, for a survey of 2,317 CVS, Walgreens, HEB, and Walmart pharmacies. Interviewers posed as potential overdose responders, and inquired about purchasing naloxone without a prescription, reported Kirk E. Evoy, PharmD, of the College of Pharmacy at the University of Texas at Austin, and his coauthors.

Of the pharmacies surveyed, 83.7% (95% CI, 82.2%-85.2%) said they would dispense naloxone without a prescription, and 76.4% (95% CI, 74.7%-78.1%) currently stocked naloxone.

In addition, 79.9% (95% CI, 78.3%-81.6%) would allow purchase of naloxone for someone else, though only 49.7% (95% CI, 47.8%-51.9%) would allow the purchase to be billed to a third-party buyer’s insurance, the authors noted.

Although this study found that most pharmacies would dispense naloxone without a prescription, the findings cannot be applied to independent pharmacies, Dr. Evoy and his colleagues noted.

“Consistent naloxone supply in all pharmacies, improved pharmacist understanding of naloxone standing orders, and ubiquitous insurance coverage for third-party purchasers may further improve access,” they wrote.

Dr. Puzantian and Dr. Gasper reported no disclosures. Dr. Evoy disclosed receiving grant funding from the Institute for Integration of Medicine and Science at the UT Health in San Antonio, the Kleberg Foundation, and Texas Health and Human Services. Other authors disclosed previous receipt of donations of branded formulations of naloxone from Kaléo Pharma and Adapt Pharma.

SOURCE: Puzantian T et al. and Evoy KE et al. JAMA 2018 Nov 13.320(18):1933-7.

ORLANDO – “Expect the unexpected” when considering the health impacts of climate change on children, Susan Pacheo, MD, advised in her presentation at the annual meeting of the American Academy of Pediatrics.

Jeff Craven/MDedge News

“We don’t know what we’re going to see, and we need to be ready,” said Dr. Pacheo of the University of Texas, Houston.

Climate change is categorized by an increase in droughts, fires, storms, floods, mudslides, and extreme temperatures. According to the Centers for Disease Control and Prevention, the impacts of climate change on human health are multiple, but can include an increased rate of infectious disease, respiratory conditions, injury, cardiovascular-related health issues, malnutrition, and mental health problems.

These problems can especially target children, Dr. Pacheo noted. “Kids are vulnerable. You’ve heard this, you’ve experienced this, you see this every day in your pediatric population.”

Children are more vulnerable because of the increased exposure they have to the environment. They spend more time outdoors, they are closer to the ground, and they are likely to put objects in their mouth. Children also tend to swallow more water when swimming, compared with adults. A 2014 study by de Man et al. found that children exposed to storm sewers and combined sewers swallowed 1.7 mL of water per exposure event and that the risk of infection from pathogens such as noroviruses, enteroviruses, Campylobacter jejuni, Cryptosporidium, and Giardia was 23%-33% per event, compared with 0.016 mL of water per exposure in adults and a mean infection risk of 0.58%-3.90% per event (Water Research. 2014 Jan 1. doi: 10.1016/j.watres.2013.09.022).

In addition, socioeconomic status and built environment as well as a child’s immature lung development and higher respiratory rate can lead to children being impacted by factors such as air pollution. Poverty, access to medical care, and the structure and dynamics of family also can affect children.

“We need to do something because this is a problem of social justice and we, as pediatricians, are advocates of the vulnerable,” Dr. Pacheo said.

Cade Martin, Dawn Arlotta, USCDC

Expect to see an increase in the number of vector-borne, airborne, and pollution-related disease, as well as water- and food-borne diseases, as a result of climate change, in addition to other issues such as hand, foot, and mouth disease and antibiotic resistance, she noted. As historically colder parts of the world continue to have milder winters, disease-carrying insects such as ticks and mosquitoes will expand their habitats and transmission of diseases such as Zika virus, malaria, dengue fever, and chikungunya will increase.

Leptospirosis and Naegleria fowleri, the latter which can cause primary amebic meningoencephalitis, are also becoming more common. Food-borne illnesses like vibriosis are being seen in more northern areas of the world like Alaska, and ciguatera fish poisoning is expected to be more prevalent in the southeastern United States and Gulf of Mexico, Dr. Pacheo said.

Air pollution carries a risk of respiratory diseases, pneumonia, and bronchiolitis, with a 2017 systematic review by Nhung et al. finding increased exposure to ambient air pollution markers such as sulfur dioxide, ozone, nitrogen dioxide, and carbon monoxide was associated with pneumonia in children (Environ Pollut. 2017 Jul 25. doi: 10.1016/j.envpol.2017.07.063). Coccidioidomycosis, or valley fever, is caused by inhaling a fungus in the soil and is associated with dust storms primarily in the southwestern United States. Warmer temperatures also have caused toxic algae blooms that have killed marine life and caused respiratory distress; children should not go near or play in water when algae blooms are growing, she noted.

Recent studies have linked an increase in temperature with incidence of Escherichia coli, with a 2016 study by Philipsborn et al. showing a 1° Celsius increase in mean monthly temperature was associated with an 8% increase in incidence of diarrheagenic E. coli (J Infect Dis. 2016 Feb 29. doi: 10.1093/infdis/jiw081). The incidence of hand, foot, and mouth disease also is linked to temperature and humidity, with a 2018 study by Cheng et al. showing a 1° Celsius increase in temperature and humidity was significantly associated with hand, foot, and mouth disease (Sci Total Environ. 2018 Jan 12. doi: 10.1016/j.scitotenv.2018.01.006). Rates of influenza are controlled by the changing environment as well, and increasing the number of vaccinations will help lower the number of influenza cases.

“We need to be advocates, we need to educate ourselves like we’re doing now so that we can educate our patients and to create a plan for preparedness,” Dr. Pacheo said.

She reported no relevant conflicts of interest.

ORLANDO – “Expect the unexpected” when considering the health impacts of climate change on children, Susan Pacheo, MD, advised in her presentation at the annual meeting of the American Academy of Pediatrics.

Jeff Craven/MDedge News

“We don’t know what we’re going to see, and we need to be ready,” said Dr. Pacheo of the University of Texas, Houston.

Climate change is categorized by an increase in droughts, fires, storms, floods, mudslides, and extreme temperatures. According to the Centers for Disease Control and Prevention, the impacts of climate change on human health are multiple, but can include an increased rate of infectious disease, respiratory conditions, injury, cardiovascular-related health issues, malnutrition, and mental health problems.

These problems can especially target children, Dr. Pacheo noted. “Kids are vulnerable. You’ve heard this, you’ve experienced this, you see this every day in your pediatric population.”

Children are more vulnerable because of the increased exposure they have to the environment. They spend more time outdoors, they are closer to the ground, and they are likely to put objects in their mouth. Children also tend to swallow more water when swimming, compared with adults. A 2014 study by de Man et al. found that children exposed to storm sewers and combined sewers swallowed 1.7 mL of water per exposure event and that the risk of infection from pathogens such as noroviruses, enteroviruses, Campylobacter jejuni, Cryptosporidium, and Giardia was 23%-33% per event, compared with 0.016 mL of water per exposure in adults and a mean infection risk of 0.58%-3.90% per event (Water Research. 2014 Jan 1. doi: 10.1016/j.watres.2013.09.022).

In addition, socioeconomic status and built environment as well as a child’s immature lung development and higher respiratory rate can lead to children being impacted by factors such as air pollution. Poverty, access to medical care, and the structure and dynamics of family also can affect children.

“We need to do something because this is a problem of social justice and we, as pediatricians, are advocates of the vulnerable,” Dr. Pacheo said.

Cade Martin, Dawn Arlotta, USCDC

Expect to see an increase in the number of vector-borne, airborne, and pollution-related disease, as well as water- and food-borne diseases, as a result of climate change, in addition to other issues such as hand, foot, and mouth disease and antibiotic resistance, she noted. As historically colder parts of the world continue to have milder winters, disease-carrying insects such as ticks and mosquitoes will expand their habitats and transmission of diseases such as Zika virus, malaria, dengue fever, and chikungunya will increase.

Leptospirosis and Naegleria fowleri, the latter which can cause primary amebic meningoencephalitis, are also becoming more common. Food-borne illnesses like vibriosis are being seen in more northern areas of the world like Alaska, and ciguatera fish poisoning is expected to be more prevalent in the southeastern United States and Gulf of Mexico, Dr. Pacheo said.

Air pollution carries a risk of respiratory diseases, pneumonia, and bronchiolitis, with a 2017 systematic review by Nhung et al. finding increased exposure to ambient air pollution markers such as sulfur dioxide, ozone, nitrogen dioxide, and carbon monoxide was associated with pneumonia in children (Environ Pollut. 2017 Jul 25. doi: 10.1016/j.envpol.2017.07.063). Coccidioidomycosis, or valley fever, is caused by inhaling a fungus in the soil and is associated with dust storms primarily in the southwestern United States. Warmer temperatures also have caused toxic algae blooms that have killed marine life and caused respiratory distress; children should not go near or play in water when algae blooms are growing, she noted.

Recent studies have linked an increase in temperature with incidence of Escherichia coli, with a 2016 study by Philipsborn et al. showing a 1° Celsius increase in mean monthly temperature was associated with an 8% increase in incidence of diarrheagenic E. coli (J Infect Dis. 2016 Feb 29. doi: 10.1093/infdis/jiw081). The incidence of hand, foot, and mouth disease also is linked to temperature and humidity, with a 2018 study by Cheng et al. showing a 1° Celsius increase in temperature and humidity was significantly associated with hand, foot, and mouth disease (Sci Total Environ. 2018 Jan 12. doi: 10.1016/j.scitotenv.2018.01.006). Rates of influenza are controlled by the changing environment as well, and increasing the number of vaccinations will help lower the number of influenza cases.

“We need to be advocates, we need to educate ourselves like we’re doing now so that we can educate our patients and to create a plan for preparedness,” Dr. Pacheo said.

She reported no relevant conflicts of interest.

ORLANDO – “Expect the unexpected” when considering the health impacts of climate change on children, Susan Pacheo, MD, advised in her presentation at the annual meeting of the American Academy of Pediatrics.

Jeff Craven/MDedge News

“We don’t know what we’re going to see, and we need to be ready,” said Dr. Pacheo of the University of Texas, Houston.

Climate change is categorized by an increase in droughts, fires, storms, floods, mudslides, and extreme temperatures. According to the Centers for Disease Control and Prevention, the impacts of climate change on human health are multiple, but can include an increased rate of infectious disease, respiratory conditions, injury, cardiovascular-related health issues, malnutrition, and mental health problems.

These problems can especially target children, Dr. Pacheo noted. “Kids are vulnerable. You’ve heard this, you’ve experienced this, you see this every day in your pediatric population.”

Children are more vulnerable because of the increased exposure they have to the environment. They spend more time outdoors, they are closer to the ground, and they are likely to put objects in their mouth. Children also tend to swallow more water when swimming, compared with adults. A 2014 study by de Man et al. found that children exposed to storm sewers and combined sewers swallowed 1.7 mL of water per exposure event and that the risk of infection from pathogens such as noroviruses, enteroviruses, Campylobacter jejuni, Cryptosporidium, and Giardia was 23%-33% per event, compared with 0.016 mL of water per exposure in adults and a mean infection risk of 0.58%-3.90% per event (Water Research. 2014 Jan 1. doi: 10.1016/j.watres.2013.09.022).

In addition, socioeconomic status and built environment as well as a child’s immature lung development and higher respiratory rate can lead to children being impacted by factors such as air pollution. Poverty, access to medical care, and the structure and dynamics of family also can affect children.

“We need to do something because this is a problem of social justice and we, as pediatricians, are advocates of the vulnerable,” Dr. Pacheo said.

Cade Martin, Dawn Arlotta, USCDC

Expect to see an increase in the number of vector-borne, airborne, and pollution-related disease, as well as water- and food-borne diseases, as a result of climate change, in addition to other issues such as hand, foot, and mouth disease and antibiotic resistance, she noted. As historically colder parts of the world continue to have milder winters, disease-carrying insects such as ticks and mosquitoes will expand their habitats and transmission of diseases such as Zika virus, malaria, dengue fever, and chikungunya will increase.

Leptospirosis and Naegleria fowleri, the latter which can cause primary amebic meningoencephalitis, are also becoming more common. Food-borne illnesses like vibriosis are being seen in more northern areas of the world like Alaska, and ciguatera fish poisoning is expected to be more prevalent in the southeastern United States and Gulf of Mexico, Dr. Pacheo said.

Air pollution carries a risk of respiratory diseases, pneumonia, and bronchiolitis, with a 2017 systematic review by Nhung et al. finding increased exposure to ambient air pollution markers such as sulfur dioxide, ozone, nitrogen dioxide, and carbon monoxide was associated with pneumonia in children (Environ Pollut. 2017 Jul 25. doi: 10.1016/j.envpol.2017.07.063). Coccidioidomycosis, or valley fever, is caused by inhaling a fungus in the soil and is associated with dust storms primarily in the southwestern United States. Warmer temperatures also have caused toxic algae blooms that have killed marine life and caused respiratory distress; children should not go near or play in water when algae blooms are growing, she noted.

Recent studies have linked an increase in temperature with incidence of Escherichia coli, with a 2016 study by Philipsborn et al. showing a 1° Celsius increase in mean monthly temperature was associated with an 8% increase in incidence of diarrheagenic E. coli (J Infect Dis. 2016 Feb 29. doi: 10.1093/infdis/jiw081). The incidence of hand, foot, and mouth disease also is linked to temperature and humidity, with a 2018 study by Cheng et al. showing a 1° Celsius increase in temperature and humidity was significantly associated with hand, foot, and mouth disease (Sci Total Environ. 2018 Jan 12. doi: 10.1016/j.scitotenv.2018.01.006). Rates of influenza are controlled by the changing environment as well, and increasing the number of vaccinations will help lower the number of influenza cases.

“We need to be advocates, we need to educate ourselves like we’re doing now so that we can educate our patients and to create a plan for preparedness,” Dr. Pacheo said.

She reported no relevant conflicts of interest.

SAN DIEGO – Fewer than a quarter of patients with signs of stage 3 chronic kidney disease (CKD) underwent follow-up testing within 1 year, even though most of these patients underwent repeat cholesterol screening during the same time.

Considering that CKD can be asymptomatic until the late stages, “this is a lost opportunity to get a proper evaluation by a nephrologist,” study coauthor and nephrologist Barbara S. Gillespie, MD, MMS, of Covance, the drug development business of LabCorp, said in an interview. Dr. Gillespie and her colleagues presented their findings at Kidney Week 2018, sponsored by the American Society of Nephrology.

More than 90% of patients with stages 1-3 CKD didn’t know they had the condition, based on 2013-2016 data gathered by the United States Renal Data System . Just 57% of those with stage 4 CKD were aware of their disease.

For the retrospective study, the researchers identified 4.9 million patients (58% were women; mean age was 71) who had estimated glomerular filtration rate (eGFR) results below 60 mL/min per 1.73 m² from 2011 to 2018, based on serum creatinine tests performed at least twice and at least 3 months apart by LabCorp. The researchers tracked the patients for a median 26 months.

Based on the initial results, 92% of the patients had stage 3 CKD, 6% had stage 4, and 2% had stage 5. However, at 1 year, the percentages of overall patients who underwent urine albumin/creatinine ratio, serum phosphorus, and plasma parathyroid hormone were 24%, 12%, and 17%, respectively, lead author Jennifer Ennis, MD, of LabCorp, said in an interview.

Kidney Disease Improving Global Outcomes guidelines from 2012 recommend “assessments of GFR and albuminuria at least annually ... and more often for individuals at higher risk of progression, and/or where measurement will impact therapeutic decisions” (Ann Intern Med. 2013 Jun 4;158[11]:825-30).

Yet 76% of these patients also underwent annual LDL cholesterol screening. “This suggests that the patients were receiving evaluation and treatment for other common conditions, but that CKD may not have been specifically addressed,” Dr. Ennis said.

SOURCE: Ennis JL et al. Kidney Week 2018, Abstract PUB111.

SAN DIEGO – Fewer than a quarter of patients with signs of stage 3 chronic kidney disease (CKD) underwent follow-up testing within 1 year, even though most of these patients underwent repeat cholesterol screening during the same time.

Considering that CKD can be asymptomatic until the late stages, “this is a lost opportunity to get a proper evaluation by a nephrologist,” study coauthor and nephrologist Barbara S. Gillespie, MD, MMS, of Covance, the drug development business of LabCorp, said in an interview. Dr. Gillespie and her colleagues presented their findings at Kidney Week 2018, sponsored by the American Society of Nephrology.

More than 90% of patients with stages 1-3 CKD didn’t know they had the condition, based on 2013-2016 data gathered by the United States Renal Data System . Just 57% of those with stage 4 CKD were aware of their disease.

For the retrospective study, the researchers identified 4.9 million patients (58% were women; mean age was 71) who had estimated glomerular filtration rate (eGFR) results below 60 mL/min per 1.73 m² from 2011 to 2018, based on serum creatinine tests performed at least twice and at least 3 months apart by LabCorp. The researchers tracked the patients for a median 26 months.

Based on the initial results, 92% of the patients had stage 3 CKD, 6% had stage 4, and 2% had stage 5. However, at 1 year, the percentages of overall patients who underwent urine albumin/creatinine ratio, serum phosphorus, and plasma parathyroid hormone were 24%, 12%, and 17%, respectively, lead author Jennifer Ennis, MD, of LabCorp, said in an interview.

Kidney Disease Improving Global Outcomes guidelines from 2012 recommend “assessments of GFR and albuminuria at least annually ... and more often for individuals at higher risk of progression, and/or where measurement will impact therapeutic decisions” (Ann Intern Med. 2013 Jun 4;158[11]:825-30).

Yet 76% of these patients also underwent annual LDL cholesterol screening. “This suggests that the patients were receiving evaluation and treatment for other common conditions, but that CKD may not have been specifically addressed,” Dr. Ennis said.

SOURCE: Ennis JL et al. Kidney Week 2018, Abstract PUB111.

SAN DIEGO – Fewer than a quarter of patients with signs of stage 3 chronic kidney disease (CKD) underwent follow-up testing within 1 year, even though most of these patients underwent repeat cholesterol screening during the same time.

Considering that CKD can be asymptomatic until the late stages, “this is a lost opportunity to get a proper evaluation by a nephrologist,” study coauthor and nephrologist Barbara S. Gillespie, MD, MMS, of Covance, the drug development business of LabCorp, said in an interview. Dr. Gillespie and her colleagues presented their findings at Kidney Week 2018, sponsored by the American Society of Nephrology.

More than 90% of patients with stages 1-3 CKD didn’t know they had the condition, based on 2013-2016 data gathered by the United States Renal Data System . Just 57% of those with stage 4 CKD were aware of their disease.

For the retrospective study, the researchers identified 4.9 million patients (58% were women; mean age was 71) who had estimated glomerular filtration rate (eGFR) results below 60 mL/min per 1.73 m² from 2011 to 2018, based on serum creatinine tests performed at least twice and at least 3 months apart by LabCorp. The researchers tracked the patients for a median 26 months.

Based on the initial results, 92% of the patients had stage 3 CKD, 6% had stage 4, and 2% had stage 5. However, at 1 year, the percentages of overall patients who underwent urine albumin/creatinine ratio, serum phosphorus, and plasma parathyroid hormone were 24%, 12%, and 17%, respectively, lead author Jennifer Ennis, MD, of LabCorp, said in an interview.

Kidney Disease Improving Global Outcomes guidelines from 2012 recommend “assessments of GFR and albuminuria at least annually ... and more often for individuals at higher risk of progression, and/or where measurement will impact therapeutic decisions” (Ann Intern Med. 2013 Jun 4;158[11]:825-30).

Yet 76% of these patients also underwent annual LDL cholesterol screening. “This suggests that the patients were receiving evaluation and treatment for other common conditions, but that CKD may not have been specifically addressed,” Dr. Ennis said.

SOURCE: Ennis JL et al. Kidney Week 2018, Abstract PUB111.

The INPACT SFA trial demonstrated the long-term safety of the IN.PACT Admiral drug-coated balloon (DCB) through 5 years, with no device-, procedure-, or paclitaxel-related deaths seen, coupled with continued low thrombosis rates throughout 5 years, according to John R. Laird, MD, of the Adventist Heart & Vascular Institute, St. Helena, Calif.

Dr. Laird presented the final, 5-year results of the combined INPACT SFA I and II trials at the 2018 Vascular Interventional Vascular Advances meeting.

The combined studies compared 220 patients treated with DCB and 111 treated with standard percutaneous transluminal angioplasty (PTA) who were followed out to 5 years. The patient population was 65% men, had a mean age of about 68 years, and none of the baseline characteristics followed were statistically significant between the treatment groups. The mean total lesion length treated was 8.9 cm for the DCB group and 8.8 cm for the PTA group, also a nonsignificant difference.

The primary efficacy endpoint for the study was primary patency within 12 months, defined as freedom from clinically driven target lesion revascularization (CD-TLR) and duplex ultrasound–derived restenosis. The primary safety endpoint was freedom from device-and procedure-related death through 30 days, and freedom from target limb major amputation and CD-TLR within 12 months.

Although there were no significant differences seen between DCB and placebo for CD-TLR or any TLR, there was a significant difference seen in the time to CD-TLR over 1,800 days: 808 days for DCB versus 475 days for placebo (P less than .001).

There were no significant differences seen between the DCB and placebo for any of the safety endpoint components over 5 years.

INPACT SFA was the “first independently adjudicated, blinded, randomized trial to demonstrate superior effectiveness of a drug-coated balloon through 5 years,” and the “results support DCB as a first-line strategy for the treatment of femoropopliteal disease,” Dr. Laird concluded.

The trial was sponsored by Medtronic Endovascular. Dr. Laird reported that he is a consultant/advisory board member for Abbott Vascular, Bard, Boston Scientific, and Medtronic.

[email protected]

The INPACT SFA trial demonstrated the long-term safety of the IN.PACT Admiral drug-coated balloon (DCB) through 5 years, with no device-, procedure-, or paclitaxel-related deaths seen, coupled with continued low thrombosis rates throughout 5 years, according to John R. Laird, MD, of the Adventist Heart & Vascular Institute, St. Helena, Calif.

Dr. Laird presented the final, 5-year results of the combined INPACT SFA I and II trials at the 2018 Vascular Interventional Vascular Advances meeting.

The combined studies compared 220 patients treated with DCB and 111 treated with standard percutaneous transluminal angioplasty (PTA) who were followed out to 5 years. The patient population was 65% men, had a mean age of about 68 years, and none of the baseline characteristics followed were statistically significant between the treatment groups. The mean total lesion length treated was 8.9 cm for the DCB group and 8.8 cm for the PTA group, also a nonsignificant difference.

The primary efficacy endpoint for the study was primary patency within 12 months, defined as freedom from clinically driven target lesion revascularization (CD-TLR) and duplex ultrasound–derived restenosis. The primary safety endpoint was freedom from device-and procedure-related death through 30 days, and freedom from target limb major amputation and CD-TLR within 12 months.

Although there were no significant differences seen between DCB and placebo for CD-TLR or any TLR, there was a significant difference seen in the time to CD-TLR over 1,800 days: 808 days for DCB versus 475 days for placebo (P less than .001).

There were no significant differences seen between the DCB and placebo for any of the safety endpoint components over 5 years.

INPACT SFA was the “first independently adjudicated, blinded, randomized trial to demonstrate superior effectiveness of a drug-coated balloon through 5 years,” and the “results support DCB as a first-line strategy for the treatment of femoropopliteal disease,” Dr. Laird concluded.

The trial was sponsored by Medtronic Endovascular. Dr. Laird reported that he is a consultant/advisory board member for Abbott Vascular, Bard, Boston Scientific, and Medtronic.

[email protected]

The INPACT SFA trial demonstrated the long-term safety of the IN.PACT Admiral drug-coated balloon (DCB) through 5 years, with no device-, procedure-, or paclitaxel-related deaths seen, coupled with continued low thrombosis rates throughout 5 years, according to John R. Laird, MD, of the Adventist Heart & Vascular Institute, St. Helena, Calif.

Dr. Laird presented the final, 5-year results of the combined INPACT SFA I and II trials at the 2018 Vascular Interventional Vascular Advances meeting.

The combined studies compared 220 patients treated with DCB and 111 treated with standard percutaneous transluminal angioplasty (PTA) who were followed out to 5 years. The patient population was 65% men, had a mean age of about 68 years, and none of the baseline characteristics followed were statistically significant between the treatment groups. The mean total lesion length treated was 8.9 cm for the DCB group and 8.8 cm for the PTA group, also a nonsignificant difference.

The primary efficacy endpoint for the study was primary patency within 12 months, defined as freedom from clinically driven target lesion revascularization (CD-TLR) and duplex ultrasound–derived restenosis. The primary safety endpoint was freedom from device-and procedure-related death through 30 days, and freedom from target limb major amputation and CD-TLR within 12 months.

Although there were no significant differences seen between DCB and placebo for CD-TLR or any TLR, there was a significant difference seen in the time to CD-TLR over 1,800 days: 808 days for DCB versus 475 days for placebo (P less than .001).

There were no significant differences seen between the DCB and placebo for any of the safety endpoint components over 5 years.

INPACT SFA was the “first independently adjudicated, blinded, randomized trial to demonstrate superior effectiveness of a drug-coated balloon through 5 years,” and the “results support DCB as a first-line strategy for the treatment of femoropopliteal disease,” Dr. Laird concluded.

The trial was sponsored by Medtronic Endovascular. Dr. Laird reported that he is a consultant/advisory board member for Abbott Vascular, Bard, Boston Scientific, and Medtronic.

[email protected]

Clinical question: Can an opiate-prescribing standard that favors oral and subcutaneous over intravenous administration reduce exposure to intravenous opiates for hospitalized adults?

Background: IV opiates, while effective for analgesia, may have a higher addictive potential because of the rapid and intermittent rises of peak concentrations. Subcutaneous and/or oral administration is a proven method of opioid delivery with similar bioavailability and efficacy of intravenous administration with more favorable pharmacokinetics.

Study design: Intervention-based quality improvement project.

Dr. Chowdury is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Can an opiate-prescribing standard that favors oral and subcutaneous over intravenous administration reduce exposure to intravenous opiates for hospitalized adults?

Background: IV opiates, while effective for analgesia, may have a higher addictive potential because of the rapid and intermittent rises of peak concentrations. Subcutaneous and/or oral administration is a proven method of opioid delivery with similar bioavailability and efficacy of intravenous administration with more favorable pharmacokinetics.

Study design: Intervention-based quality improvement project.

Dr. Chowdury is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Can an opiate-prescribing standard that favors oral and subcutaneous over intravenous administration reduce exposure to intravenous opiates for hospitalized adults?

Background: IV opiates, while effective for analgesia, may have a higher addictive potential because of the rapid and intermittent rises of peak concentrations. Subcutaneous and/or oral administration is a proven method of opioid delivery with similar bioavailability and efficacy of intravenous administration with more favorable pharmacokinetics.

Study design: Intervention-based quality improvement project.

Dr. Chowdury is an assistant professor in the division of hospital medicine, University of Colorado, Denver.