Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Utilization of mesh in laparoscopic paraesophageal hernia repair (PEHR) remained steady from 2011 to 2014, despite a lack of evidence supporting its use, according to Francisco Schlottmann, MD, and his associates.

In an analysis of 9,590 laparoscopic PEHR performed from 2011 to 2014, 60.6% procedures were done without mesh and 39.4% were done with mesh. Over the 3-year study period, mesh utilization fell only 1.2% overall, with laparoscopic PEHR with mesh accounting for 39.4% of procedures in 2011 and 38.2% in 2014.

Patients who received mesh were slightly older and significantly more likely to be an inpatient admission. Postoperative urinary tract infection was less common in patients with mesh, occurring in 1% of patients, compared with 1.5% of patients without mesh. No significant difference in demographics was seen, and 30-day risk of comorbidity and mortality was the same. Mean length of stay was 2.7 days for PEHR with mesh and 2.5 days for PEHR without mesh.

“The use of mesh is associated with high expenses, and biomedical technology continues to offer newer and more expensive mesh products on the market. Given the progressive aging of the U.S. population, PEHR are expected to increase in the future. The indiscriminate and not supported by evidence use of mesh may determine unnecessary costs for the health care system,” the investigators noted.

Find the full study in the Journal of Gastrointestinal Surgery (2017 May 26. doi: 10.1007/s11605-017-3452-8).

[email protected]

Utilization of mesh in laparoscopic paraesophageal hernia repair (PEHR) remained steady from 2011 to 2014, despite a lack of evidence supporting its use, according to Francisco Schlottmann, MD, and his associates.

In an analysis of 9,590 laparoscopic PEHR performed from 2011 to 2014, 60.6% procedures were done without mesh and 39.4% were done with mesh. Over the 3-year study period, mesh utilization fell only 1.2% overall, with laparoscopic PEHR with mesh accounting for 39.4% of procedures in 2011 and 38.2% in 2014.

Patients who received mesh were slightly older and significantly more likely to be an inpatient admission. Postoperative urinary tract infection was less common in patients with mesh, occurring in 1% of patients, compared with 1.5% of patients without mesh. No significant difference in demographics was seen, and 30-day risk of comorbidity and mortality was the same. Mean length of stay was 2.7 days for PEHR with mesh and 2.5 days for PEHR without mesh.

“The use of mesh is associated with high expenses, and biomedical technology continues to offer newer and more expensive mesh products on the market. Given the progressive aging of the U.S. population, PEHR are expected to increase in the future. The indiscriminate and not supported by evidence use of mesh may determine unnecessary costs for the health care system,” the investigators noted.

Find the full study in the Journal of Gastrointestinal Surgery (2017 May 26. doi: 10.1007/s11605-017-3452-8).

[email protected]

Utilization of mesh in laparoscopic paraesophageal hernia repair (PEHR) remained steady from 2011 to 2014, despite a lack of evidence supporting its use, according to Francisco Schlottmann, MD, and his associates.

In an analysis of 9,590 laparoscopic PEHR performed from 2011 to 2014, 60.6% procedures were done without mesh and 39.4% were done with mesh. Over the 3-year study period, mesh utilization fell only 1.2% overall, with laparoscopic PEHR with mesh accounting for 39.4% of procedures in 2011 and 38.2% in 2014.

Patients who received mesh were slightly older and significantly more likely to be an inpatient admission. Postoperative urinary tract infection was less common in patients with mesh, occurring in 1% of patients, compared with 1.5% of patients without mesh. No significant difference in demographics was seen, and 30-day risk of comorbidity and mortality was the same. Mean length of stay was 2.7 days for PEHR with mesh and 2.5 days for PEHR without mesh.

“The use of mesh is associated with high expenses, and biomedical technology continues to offer newer and more expensive mesh products on the market. Given the progressive aging of the U.S. population, PEHR are expected to increase in the future. The indiscriminate and not supported by evidence use of mesh may determine unnecessary costs for the health care system,” the investigators noted.

Find the full study in the Journal of Gastrointestinal Surgery (2017 May 26. doi: 10.1007/s11605-017-3452-8).

[email protected]

CHICAGO – Androgen deprivation therapy (ADT) combined with radiation therapy can safely be reduced from 36 to 18 months without compromising outcomes or quality of life in patients with high-risk localized prostate cancer, according to the final results of a randomized phase III trial.

At a median of 9.4 year follow-up of 630 patients who were randomized to receive pelvic and prostate radiotherapy combined with either 36 or 18 months of ADT, the 10-year overall survival rate was 62.4% and 62.0% in the treatment arms, respectively (global hazard ratio, 1.024), Abdenour Nabid, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Disease-free survival was 44.5% and 39.2% in the groups, respectively (HR, 0.835). This difference did not reach statistical significance, said Dr. Nabid of Centre Hospitalier Regional Universitaire, Sherbrooke, Quebec, Canada.

The disease-free survival curves separated over the course of the study, mainly because of a significant difference in biochemical failure between the groups, which favored the 36-month arm (24.8% vs. 31.0%; HR, 0.714), but this is not an unexpected finding with longer treatment, he explained.

“Does this biochemical control give you more control of the disease? I’m not sure,” he said, noting that bone metastases alone occurred in 23 and 24 patients in the 36 and 18 month treatment groups, respectively, and bone plus other site metastases occurred in 11 patients in each group. “At the end of the day, the P value (for disease-free survival) is not significant (.0768).”

Further, a quality of life analysis showed that patients in the 18-month treatment arm performed significantly better on 6 of 21 scales and 13 of 55 items addressing various quality of life factors. On two of these items – hot flushes and enjoyable sex – a clinically relevant difference of 10 or more points in mean scores was noted, he said.

Long-term ADT combined with radiotherapy is a standard treatment for patients with high-risk prostate cancer, but the optimal duration of treatment has not been defined, Dr. Nabid said.

The current trial looked at treatment duration in patients 80 years and younger (median of 71 in both groups) with T3-T4 disease, PSA levels greater than 20 mg/ml, and Gleason score greater than 7, with normal hepatic function and no regional disease or distant metastases. ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months, as well as pelvic and prostate radiotherapy.

On both univariate and multivariate analyses including age, Gleason score greater than 7, treatment duration, prostate-specific antigen greater than 20, T3-T4 disease, and biochemical failure during follow-up, only age and Gleason score were significantly associated with overall survival (HR, 1.05 for age in both analyses, and 1.40 and 1.42, respectively for Gleason score greater than 7 on univariate and multivariate analyses).

“In localized high-risk prostate cancer treated with radiotherapy and androgen deprivation therapy, androgen deprivation therapy duration can be safely reduced from 36 to 18 months,” Dr. Nabid said, adding that 18 months could represent a threshold effect in ADT duration and that side effects and treatment costs can be reduced with shorter duration of therapy.

“Eighteen months of ADT represents a new standard of care,” he concluded.

This study was funded by AstraZeneca Pharmaceuticals. Dr. Nabid has been a speaker, advisory board member, and/or received financial support from Janssen Canada, Sanofi, Astellas, and Bayer.

[email protected]

CHICAGO – Androgen deprivation therapy (ADT) combined with radiation therapy can safely be reduced from 36 to 18 months without compromising outcomes or quality of life in patients with high-risk localized prostate cancer, according to the final results of a randomized phase III trial.

At a median of 9.4 year follow-up of 630 patients who were randomized to receive pelvic and prostate radiotherapy combined with either 36 or 18 months of ADT, the 10-year overall survival rate was 62.4% and 62.0% in the treatment arms, respectively (global hazard ratio, 1.024), Abdenour Nabid, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Disease-free survival was 44.5% and 39.2% in the groups, respectively (HR, 0.835). This difference did not reach statistical significance, said Dr. Nabid of Centre Hospitalier Regional Universitaire, Sherbrooke, Quebec, Canada.

The disease-free survival curves separated over the course of the study, mainly because of a significant difference in biochemical failure between the groups, which favored the 36-month arm (24.8% vs. 31.0%; HR, 0.714), but this is not an unexpected finding with longer treatment, he explained.

“Does this biochemical control give you more control of the disease? I’m not sure,” he said, noting that bone metastases alone occurred in 23 and 24 patients in the 36 and 18 month treatment groups, respectively, and bone plus other site metastases occurred in 11 patients in each group. “At the end of the day, the P value (for disease-free survival) is not significant (.0768).”

Further, a quality of life analysis showed that patients in the 18-month treatment arm performed significantly better on 6 of 21 scales and 13 of 55 items addressing various quality of life factors. On two of these items – hot flushes and enjoyable sex – a clinically relevant difference of 10 or more points in mean scores was noted, he said.

Long-term ADT combined with radiotherapy is a standard treatment for patients with high-risk prostate cancer, but the optimal duration of treatment has not been defined, Dr. Nabid said.

The current trial looked at treatment duration in patients 80 years and younger (median of 71 in both groups) with T3-T4 disease, PSA levels greater than 20 mg/ml, and Gleason score greater than 7, with normal hepatic function and no regional disease or distant metastases. ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months, as well as pelvic and prostate radiotherapy.

On both univariate and multivariate analyses including age, Gleason score greater than 7, treatment duration, prostate-specific antigen greater than 20, T3-T4 disease, and biochemical failure during follow-up, only age and Gleason score were significantly associated with overall survival (HR, 1.05 for age in both analyses, and 1.40 and 1.42, respectively for Gleason score greater than 7 on univariate and multivariate analyses).

“In localized high-risk prostate cancer treated with radiotherapy and androgen deprivation therapy, androgen deprivation therapy duration can be safely reduced from 36 to 18 months,” Dr. Nabid said, adding that 18 months could represent a threshold effect in ADT duration and that side effects and treatment costs can be reduced with shorter duration of therapy.

“Eighteen months of ADT represents a new standard of care,” he concluded.

This study was funded by AstraZeneca Pharmaceuticals. Dr. Nabid has been a speaker, advisory board member, and/or received financial support from Janssen Canada, Sanofi, Astellas, and Bayer.

[email protected]

CHICAGO – Androgen deprivation therapy (ADT) combined with radiation therapy can safely be reduced from 36 to 18 months without compromising outcomes or quality of life in patients with high-risk localized prostate cancer, according to the final results of a randomized phase III trial.

At a median of 9.4 year follow-up of 630 patients who were randomized to receive pelvic and prostate radiotherapy combined with either 36 or 18 months of ADT, the 10-year overall survival rate was 62.4% and 62.0% in the treatment arms, respectively (global hazard ratio, 1.024), Abdenour Nabid, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Disease-free survival was 44.5% and 39.2% in the groups, respectively (HR, 0.835). This difference did not reach statistical significance, said Dr. Nabid of Centre Hospitalier Regional Universitaire, Sherbrooke, Quebec, Canada.

The disease-free survival curves separated over the course of the study, mainly because of a significant difference in biochemical failure between the groups, which favored the 36-month arm (24.8% vs. 31.0%; HR, 0.714), but this is not an unexpected finding with longer treatment, he explained.

“Does this biochemical control give you more control of the disease? I’m not sure,” he said, noting that bone metastases alone occurred in 23 and 24 patients in the 36 and 18 month treatment groups, respectively, and bone plus other site metastases occurred in 11 patients in each group. “At the end of the day, the P value (for disease-free survival) is not significant (.0768).”

Further, a quality of life analysis showed that patients in the 18-month treatment arm performed significantly better on 6 of 21 scales and 13 of 55 items addressing various quality of life factors. On two of these items – hot flushes and enjoyable sex – a clinically relevant difference of 10 or more points in mean scores was noted, he said.

Long-term ADT combined with radiotherapy is a standard treatment for patients with high-risk prostate cancer, but the optimal duration of treatment has not been defined, Dr. Nabid said.

The current trial looked at treatment duration in patients 80 years and younger (median of 71 in both groups) with T3-T4 disease, PSA levels greater than 20 mg/ml, and Gleason score greater than 7, with normal hepatic function and no regional disease or distant metastases. ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months, as well as pelvic and prostate radiotherapy.

On both univariate and multivariate analyses including age, Gleason score greater than 7, treatment duration, prostate-specific antigen greater than 20, T3-T4 disease, and biochemical failure during follow-up, only age and Gleason score were significantly associated with overall survival (HR, 1.05 for age in both analyses, and 1.40 and 1.42, respectively for Gleason score greater than 7 on univariate and multivariate analyses).

“In localized high-risk prostate cancer treated with radiotherapy and androgen deprivation therapy, androgen deprivation therapy duration can be safely reduced from 36 to 18 months,” Dr. Nabid said, adding that 18 months could represent a threshold effect in ADT duration and that side effects and treatment costs can be reduced with shorter duration of therapy.

“Eighteen months of ADT represents a new standard of care,” he concluded.

This study was funded by AstraZeneca Pharmaceuticals. Dr. Nabid has been a speaker, advisory board member, and/or received financial support from Janssen Canada, Sanofi, Astellas, and Bayer.

[email protected]

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

Patients with more than 10 colonic polyps, of which at least half were serrated, and their first-degree relatives had a risk of colorectal cancer similar to that of patients who met formal diagnostic criteria for serrated polyposis syndrome (SPS), according to a retrospective multicenter study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.003).

Such patients “should be treated with the same follow-up procedures as those proposed for patients with SPS, and possibly the definition of SPS should be broadened to include this phenotype,” wrote Cecilia M. Egoavil, MD, Miriam Juárez, and their associates.

SPS increases the risk of colorectal cancer (CRC) and is considered a heritable disease, which mandates “strict surveillance” of first-degree relatives, the researchers noted. The World Health Organization defines SPS as having at least five histologically diagnosed serrated lesions proximal to the sigmoid colon, of which two are at least 10 mm in diameter, or serrated polyps proximal to the sigmoid colon and a first-degree relative with SPS, or more than 20 serrated polyps throughout the colon. This “arbitrary” definition is “somewhat restrictive, and possibly leads to underdiagnosis of this disease,” the researchers wrote. Patients with multiple serrated polyps who do not meet WHO SPS criteria might have a “phenotypically attenuated form of serrated polyposis.”

For the study, the researchers compared 53 patients meeting WHO SPS criteria with 145 patients who did not meet these criteria but had more than 10 polyps throughout the colon, of which at least 50% were serrated. For both groups, number of polyps was obtained by adding polyp counts from subsequent colonoscopies. The data source was EPIPOLIP, a multicenter study of patients recruited from 24 hospitals in Spain in 2008 and 2009. At baseline, all patients had more than 10 adenomatous or serrated colonic polyps but did not have familial adenomatous polyposis, Lynch syndrome, hamartomatous polyposis, inflammatory bowel disease, or only hyperplastic rectosigmoid polyps.

The prevalence of CRC was statistically similar between groups (P = .4). There were 12 (22.6%) cases among SPS patients (mean age at diagnosis, 50 years), and 41 (28.3%) cases (mean age, 59 years) among patients with multiple serrated polyps who did not meet SPS criteria. During a mean follow-up of 4.2 years, one (1.9%) SPS patient developed incident CRC, as did four (2.8%) patients with multiple serrated polyps without SPS. Thus, standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) and 0.74 (95% CI, 0.20-1.90), respectively (P = .7). Standardized incidence ratios for CRC also did not significantly differ between first-degree relatives of patients with SPS (3.28, 95% CI, 2.16-4.77) and those with multiple serrated polyps (2.79, 95% CI, 2.10-3.63; P = .5).

A Kaplan-Meier analysis confirmed that there were no differences in the incidence of CRC between groups during follow-up. The findings “confirm that a special surveillance strategy is needed for patients with multiple serrated polyps and their relatives, probably similar to the strategy currently recommended for SPS patients,” the researchers concluded. They arbitrarily defined the group with multiple serrated polyps, so they were not able to link CRC to a cutoff number or percentage of serrated polyps, they noted.

Funders included Instituto de Salud Carlos III, Fundación de Investigación Biomédica de la Comunidad Valenciana-Instituto de Investigación Sanitaria y Biomédica de Alicante, Asociación Española Contra el Cáncer, and Conselleria d’Educació de la Generalitat Valenciana. The investigators had no conflicts of interest.

Patients with more than 10 colonic polyps, of which at least half were serrated, and their first-degree relatives had a risk of colorectal cancer similar to that of patients who met formal diagnostic criteria for serrated polyposis syndrome (SPS), according to a retrospective multicenter study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.003).

Such patients “should be treated with the same follow-up procedures as those proposed for patients with SPS, and possibly the definition of SPS should be broadened to include this phenotype,” wrote Cecilia M. Egoavil, MD, Miriam Juárez, and their associates.

SPS increases the risk of colorectal cancer (CRC) and is considered a heritable disease, which mandates “strict surveillance” of first-degree relatives, the researchers noted. The World Health Organization defines SPS as having at least five histologically diagnosed serrated lesions proximal to the sigmoid colon, of which two are at least 10 mm in diameter, or serrated polyps proximal to the sigmoid colon and a first-degree relative with SPS, or more than 20 serrated polyps throughout the colon. This “arbitrary” definition is “somewhat restrictive, and possibly leads to underdiagnosis of this disease,” the researchers wrote. Patients with multiple serrated polyps who do not meet WHO SPS criteria might have a “phenotypically attenuated form of serrated polyposis.”

For the study, the researchers compared 53 patients meeting WHO SPS criteria with 145 patients who did not meet these criteria but had more than 10 polyps throughout the colon, of which at least 50% were serrated. For both groups, number of polyps was obtained by adding polyp counts from subsequent colonoscopies. The data source was EPIPOLIP, a multicenter study of patients recruited from 24 hospitals in Spain in 2008 and 2009. At baseline, all patients had more than 10 adenomatous or serrated colonic polyps but did not have familial adenomatous polyposis, Lynch syndrome, hamartomatous polyposis, inflammatory bowel disease, or only hyperplastic rectosigmoid polyps.

The prevalence of CRC was statistically similar between groups (P = .4). There were 12 (22.6%) cases among SPS patients (mean age at diagnosis, 50 years), and 41 (28.3%) cases (mean age, 59 years) among patients with multiple serrated polyps who did not meet SPS criteria. During a mean follow-up of 4.2 years, one (1.9%) SPS patient developed incident CRC, as did four (2.8%) patients with multiple serrated polyps without SPS. Thus, standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) and 0.74 (95% CI, 0.20-1.90), respectively (P = .7). Standardized incidence ratios for CRC also did not significantly differ between first-degree relatives of patients with SPS (3.28, 95% CI, 2.16-4.77) and those with multiple serrated polyps (2.79, 95% CI, 2.10-3.63; P = .5).

A Kaplan-Meier analysis confirmed that there were no differences in the incidence of CRC between groups during follow-up. The findings “confirm that a special surveillance strategy is needed for patients with multiple serrated polyps and their relatives, probably similar to the strategy currently recommended for SPS patients,” the researchers concluded. They arbitrarily defined the group with multiple serrated polyps, so they were not able to link CRC to a cutoff number or percentage of serrated polyps, they noted.

Funders included Instituto de Salud Carlos III, Fundación de Investigación Biomédica de la Comunidad Valenciana-Instituto de Investigación Sanitaria y Biomédica de Alicante, Asociación Española Contra el Cáncer, and Conselleria d’Educació de la Generalitat Valenciana. The investigators had no conflicts of interest.

Patients with more than 10 colonic polyps, of which at least half were serrated, and their first-degree relatives had a risk of colorectal cancer similar to that of patients who met formal diagnostic criteria for serrated polyposis syndrome (SPS), according to a retrospective multicenter study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.003).

Such patients “should be treated with the same follow-up procedures as those proposed for patients with SPS, and possibly the definition of SPS should be broadened to include this phenotype,” wrote Cecilia M. Egoavil, MD, Miriam Juárez, and their associates.

SPS increases the risk of colorectal cancer (CRC) and is considered a heritable disease, which mandates “strict surveillance” of first-degree relatives, the researchers noted. The World Health Organization defines SPS as having at least five histologically diagnosed serrated lesions proximal to the sigmoid colon, of which two are at least 10 mm in diameter, or serrated polyps proximal to the sigmoid colon and a first-degree relative with SPS, or more than 20 serrated polyps throughout the colon. This “arbitrary” definition is “somewhat restrictive, and possibly leads to underdiagnosis of this disease,” the researchers wrote. Patients with multiple serrated polyps who do not meet WHO SPS criteria might have a “phenotypically attenuated form of serrated polyposis.”

For the study, the researchers compared 53 patients meeting WHO SPS criteria with 145 patients who did not meet these criteria but had more than 10 polyps throughout the colon, of which at least 50% were serrated. For both groups, number of polyps was obtained by adding polyp counts from subsequent colonoscopies. The data source was EPIPOLIP, a multicenter study of patients recruited from 24 hospitals in Spain in 2008 and 2009. At baseline, all patients had more than 10 adenomatous or serrated colonic polyps but did not have familial adenomatous polyposis, Lynch syndrome, hamartomatous polyposis, inflammatory bowel disease, or only hyperplastic rectosigmoid polyps.

The prevalence of CRC was statistically similar between groups (P = .4). There were 12 (22.6%) cases among SPS patients (mean age at diagnosis, 50 years), and 41 (28.3%) cases (mean age, 59 years) among patients with multiple serrated polyps who did not meet SPS criteria. During a mean follow-up of 4.2 years, one (1.9%) SPS patient developed incident CRC, as did four (2.8%) patients with multiple serrated polyps without SPS. Thus, standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) and 0.74 (95% CI, 0.20-1.90), respectively (P = .7). Standardized incidence ratios for CRC also did not significantly differ between first-degree relatives of patients with SPS (3.28, 95% CI, 2.16-4.77) and those with multiple serrated polyps (2.79, 95% CI, 2.10-3.63; P = .5).

A Kaplan-Meier analysis confirmed that there were no differences in the incidence of CRC between groups during follow-up. The findings “confirm that a special surveillance strategy is needed for patients with multiple serrated polyps and their relatives, probably similar to the strategy currently recommended for SPS patients,” the researchers concluded. They arbitrarily defined the group with multiple serrated polyps, so they were not able to link CRC to a cutoff number or percentage of serrated polyps, they noted.

Funders included Instituto de Salud Carlos III, Fundación de Investigación Biomédica de la Comunidad Valenciana-Instituto de Investigación Sanitaria y Biomédica de Alicante, Asociación Española Contra el Cáncer, and Conselleria d’Educació de la Generalitat Valenciana. The investigators had no conflicts of interest.

CHICAGO –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.

In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.

[email protected]

CHICAGO –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.

In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.

[email protected]

CHICAGO –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.

In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.

[email protected]

Oral or injected medications for psoriasis can be burdensome for patients, making them inclined to use alternative therapies such as phototherapy and other nondrug therapies, according to a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.

More than half of participants indicated that they have used phototherapy. Both positive and negative experiences were reported. One participant reported that a home UVB 3-panel light box "dramatically changed [his/her] life." Other participants indicated phototherapy was less successful for them. Participants also indicated fears about skin cancer.

RELATED ARTICLE: Does UVB phototherapy cause skin cancer?

However, several participants reported that phototherapy was more effective when used in combination with other medical therapies. Similarly, most participants indicated using 1 or more nondrug therapies to manage their psoriatic symptoms. Approximately one-third used over-the-counter products, such as coal tar, salicylic acid, and Epsom salt. Slightly more than one-fourth indicated the importance of complementary or alternative therapy, including exercise and meditation, to manage their psoriasis symptoms. Diet modifications, such as eliminating alcohol, sugar, processed foods, drugs, gluten, and tobacco, also were reported as successful.

RELATED ARTICLE: Yoga for dermatologic conditions

RELATED VIDEO: Answering patient questions about diet

Psoriasis patients emphasized that an effective multimodal approach including drug, phototherapy, and nondrug therapies usually is done through trial and error based on each patient's individual needs. Dermatologists would benefit from knowing that nearly all participants in this public meeting indicated they value the benefits of nondrug therapies, and combination therapies using drug and nondrug therapies should be discussed with patients.

The psoriasis public meeting in March 2016 was the FDA's 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.

Oral or injected medications for psoriasis can be burdensome for patients, making them inclined to use alternative therapies such as phototherapy and other nondrug therapies, according to a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.

More than half of participants indicated that they have used phototherapy. Both positive and negative experiences were reported. One participant reported that a home UVB 3-panel light box "dramatically changed [his/her] life." Other participants indicated phototherapy was less successful for them. Participants also indicated fears about skin cancer.

RELATED ARTICLE: Does UVB phototherapy cause skin cancer?

However, several participants reported that phototherapy was more effective when used in combination with other medical therapies. Similarly, most participants indicated using 1 or more nondrug therapies to manage their psoriatic symptoms. Approximately one-third used over-the-counter products, such as coal tar, salicylic acid, and Epsom salt. Slightly more than one-fourth indicated the importance of complementary or alternative therapy, including exercise and meditation, to manage their psoriasis symptoms. Diet modifications, such as eliminating alcohol, sugar, processed foods, drugs, gluten, and tobacco, also were reported as successful.

RELATED ARTICLE: Yoga for dermatologic conditions

RELATED VIDEO: Answering patient questions about diet

Psoriasis patients emphasized that an effective multimodal approach including drug, phototherapy, and nondrug therapies usually is done through trial and error based on each patient's individual needs. Dermatologists would benefit from knowing that nearly all participants in this public meeting indicated they value the benefits of nondrug therapies, and combination therapies using drug and nondrug therapies should be discussed with patients.

The psoriasis public meeting in March 2016 was the FDA's 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.

Oral or injected medications for psoriasis can be burdensome for patients, making them inclined to use alternative therapies such as phototherapy and other nondrug therapies, according to a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.

More than half of participants indicated that they have used phototherapy. Both positive and negative experiences were reported. One participant reported that a home UVB 3-panel light box "dramatically changed [his/her] life." Other participants indicated phototherapy was less successful for them. Participants also indicated fears about skin cancer.

RELATED ARTICLE: Does UVB phototherapy cause skin cancer?

However, several participants reported that phototherapy was more effective when used in combination with other medical therapies. Similarly, most participants indicated using 1 or more nondrug therapies to manage their psoriatic symptoms. Approximately one-third used over-the-counter products, such as coal tar, salicylic acid, and Epsom salt. Slightly more than one-fourth indicated the importance of complementary or alternative therapy, including exercise and meditation, to manage their psoriasis symptoms. Diet modifications, such as eliminating alcohol, sugar, processed foods, drugs, gluten, and tobacco, also were reported as successful.

RELATED ARTICLE: Yoga for dermatologic conditions

RELATED VIDEO: Answering patient questions about diet

Psoriasis patients emphasized that an effective multimodal approach including drug, phototherapy, and nondrug therapies usually is done through trial and error based on each patient's individual needs. Dermatologists would benefit from knowing that nearly all participants in this public meeting indicated they value the benefits of nondrug therapies, and combination therapies using drug and nondrug therapies should be discussed with patients.

The psoriasis public meeting in March 2016 was the FDA's 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.

BOSTON – Sleep apnea doesn’t have to be severe or even symptomatic to increase the risk of hypertension and diabetes, according to a pair of new studies.

“We found that even mild sleep apnea was strongly associated with increased risk of developing hypertension by four times, compared to individuals without sleep apnea,” said principal investigator and top sleep researcher Alexandros N. Vgontzas, MD, of Pennsylvania State University College of Medicine in a SLEEP press release. “Similarly, moderate sleep apnea was associated with increased risk of developing diabetes by almost three times, compared to individuals without sleep apnea.”

Dr. Vgontzas presented his team’s results on the link between mild to moderate OSA and hypertension at the annual meeting of the American Academy of Sleep Medicine. In a separate session, his colleague at Penn State, Yun Li, MD, presented the diabetes-related findings of the same study.

After multivariate adjustment, including controlling for change in body mass index over time, both mild and moderate OSA were significantly associated with increased odds for developing hypertension, compared with controls without OSA (odds ratios, 4.36 and 3.46, respectively.).

The researchers found their test for an age interaction was also significant, indicating that younger adults with nonsevere OSA were at increased risk of hypertension, while those over 60 years of age were not.

[polldaddy:9792720]

“In young and middle-aged adults, our findings suggest that early detection and treatment of mild to moderate sleep apnea is warranted in order to prevent future cardiometabolic disease,” said Dr. Li in a press release. “Given the stronger association of sleep apnea with metabolic abnormalities in this age group, emphasis should be placed on yearly monitoring of indices of metabolic symptoms and lifestyle interventions, such as weight control, healthy diet, regular exercise, and stress management.”

For diabetes, moderate OSA was significantly associated with an almost threefold increased odds for developing diabetes after adjusting for a range of baseline and follow-up variables (OR, 2.78), but mild OSA was not associated with incident diabetes (OR, 0.47).

Both studies utilized data from the Penn State Adult Cohort, a random general population sample of 1,741 adults who underwent an overnight polysomnography sleep study and had a detailed medical history interview at baseline. Mild and moderate OSA were defined as an apnea hypopnea index from 5 to 14.9 and from 15 to 29.9, respectively. The presence of hypertension or diabetes at baseline and follow-up was defined by a self-report of receiving treatment for or having a physician diagnosis of either condition.

The age range of the studied population was wide (20-84 years), with a mean age of about 47 years. The incidence of diabetes was 10.2% at follow-up, while hypertension was found in 34.2% of patients. Dr. Vgontzas said the percentage of patients with hypertension was roughly what he had expected for this population.

“Our conclusion is that, the younger a person is, the stronger is the need for detection and treatment of sleep apnea,” said Dr. Vgontzas, though he acknowledged that putting these millions of people on continuous positive airway pressure therapy is not an easy proposition.

The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.

BOSTON – Sleep apnea doesn’t have to be severe or even symptomatic to increase the risk of hypertension and diabetes, according to a pair of new studies.

“We found that even mild sleep apnea was strongly associated with increased risk of developing hypertension by four times, compared to individuals without sleep apnea,” said principal investigator and top sleep researcher Alexandros N. Vgontzas, MD, of Pennsylvania State University College of Medicine in a SLEEP press release. “Similarly, moderate sleep apnea was associated with increased risk of developing diabetes by almost three times, compared to individuals without sleep apnea.”

Dr. Vgontzas presented his team’s results on the link between mild to moderate OSA and hypertension at the annual meeting of the American Academy of Sleep Medicine. In a separate session, his colleague at Penn State, Yun Li, MD, presented the diabetes-related findings of the same study.

After multivariate adjustment, including controlling for change in body mass index over time, both mild and moderate OSA were significantly associated with increased odds for developing hypertension, compared with controls without OSA (odds ratios, 4.36 and 3.46, respectively.).

The researchers found their test for an age interaction was also significant, indicating that younger adults with nonsevere OSA were at increased risk of hypertension, while those over 60 years of age were not.

[polldaddy:9792720]

“In young and middle-aged adults, our findings suggest that early detection and treatment of mild to moderate sleep apnea is warranted in order to prevent future cardiometabolic disease,” said Dr. Li in a press release. “Given the stronger association of sleep apnea with metabolic abnormalities in this age group, emphasis should be placed on yearly monitoring of indices of metabolic symptoms and lifestyle interventions, such as weight control, healthy diet, regular exercise, and stress management.”

For diabetes, moderate OSA was significantly associated with an almost threefold increased odds for developing diabetes after adjusting for a range of baseline and follow-up variables (OR, 2.78), but mild OSA was not associated with incident diabetes (OR, 0.47).

Both studies utilized data from the Penn State Adult Cohort, a random general population sample of 1,741 adults who underwent an overnight polysomnography sleep study and had a detailed medical history interview at baseline. Mild and moderate OSA were defined as an apnea hypopnea index from 5 to 14.9 and from 15 to 29.9, respectively. The presence of hypertension or diabetes at baseline and follow-up was defined by a self-report of receiving treatment for or having a physician diagnosis of either condition.

The age range of the studied population was wide (20-84 years), with a mean age of about 47 years. The incidence of diabetes was 10.2% at follow-up, while hypertension was found in 34.2% of patients. Dr. Vgontzas said the percentage of patients with hypertension was roughly what he had expected for this population.

“Our conclusion is that, the younger a person is, the stronger is the need for detection and treatment of sleep apnea,” said Dr. Vgontzas, though he acknowledged that putting these millions of people on continuous positive airway pressure therapy is not an easy proposition.

The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.

BOSTON – Sleep apnea doesn’t have to be severe or even symptomatic to increase the risk of hypertension and diabetes, according to a pair of new studies.

“We found that even mild sleep apnea was strongly associated with increased risk of developing hypertension by four times, compared to individuals without sleep apnea,” said principal investigator and top sleep researcher Alexandros N. Vgontzas, MD, of Pennsylvania State University College of Medicine in a SLEEP press release. “Similarly, moderate sleep apnea was associated with increased risk of developing diabetes by almost three times, compared to individuals without sleep apnea.”

Dr. Vgontzas presented his team’s results on the link between mild to moderate OSA and hypertension at the annual meeting of the American Academy of Sleep Medicine. In a separate session, his colleague at Penn State, Yun Li, MD, presented the diabetes-related findings of the same study.

After multivariate adjustment, including controlling for change in body mass index over time, both mild and moderate OSA were significantly associated with increased odds for developing hypertension, compared with controls without OSA (odds ratios, 4.36 and 3.46, respectively.).

The researchers found their test for an age interaction was also significant, indicating that younger adults with nonsevere OSA were at increased risk of hypertension, while those over 60 years of age were not.

[polldaddy:9792720]

“In young and middle-aged adults, our findings suggest that early detection and treatment of mild to moderate sleep apnea is warranted in order to prevent future cardiometabolic disease,” said Dr. Li in a press release. “Given the stronger association of sleep apnea with metabolic abnormalities in this age group, emphasis should be placed on yearly monitoring of indices of metabolic symptoms and lifestyle interventions, such as weight control, healthy diet, regular exercise, and stress management.”

For diabetes, moderate OSA was significantly associated with an almost threefold increased odds for developing diabetes after adjusting for a range of baseline and follow-up variables (OR, 2.78), but mild OSA was not associated with incident diabetes (OR, 0.47).

Both studies utilized data from the Penn State Adult Cohort, a random general population sample of 1,741 adults who underwent an overnight polysomnography sleep study and had a detailed medical history interview at baseline. Mild and moderate OSA were defined as an apnea hypopnea index from 5 to 14.9 and from 15 to 29.9, respectively. The presence of hypertension or diabetes at baseline and follow-up was defined by a self-report of receiving treatment for or having a physician diagnosis of either condition.

The age range of the studied population was wide (20-84 years), with a mean age of about 47 years. The incidence of diabetes was 10.2% at follow-up, while hypertension was found in 34.2% of patients. Dr. Vgontzas said the percentage of patients with hypertension was roughly what he had expected for this population.

“Our conclusion is that, the younger a person is, the stronger is the need for detection and treatment of sleep apnea,” said Dr. Vgontzas, though he acknowledged that putting these millions of people on continuous positive airway pressure therapy is not an easy proposition.

The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.

About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).

“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”

Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.

After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.

Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.

Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.

Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.

About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).

“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”

Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.

After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.

Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.

Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.

Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.

About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).

“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”

Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.

After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.

Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.

Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.

Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.

An improved annual adenoma detection rate was associated with a significantly decreased risk of interval colorectal cancer (ICRC) and subsequent death in a national prospective cohort study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.006).

Eraxion/Thinkstock

Source: American Gastroenterological Association

This is the first study to show a significant inverse relationship between an improved annual adenoma detection rate (ADR) and ICRC or subsequent death, Michal F. Kaminski MD, PhD, of the Institute of Oncology, Warsaw, wrote with his associates.

The rates of these outcomes were lowest when endoscopists achieved and maintained ADRs above 24.6%, which supports the currently recommended performance target of 25% for a mixed male-female population, they reported (Am J Gastroenterol. 2015;110:72-90).

This study included 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national cancer prevention program in Poland between 2004 and 2008. Endoscopists received annual feedback based on quality benchmarks to spur improvements in colonoscopy performance, and all participated for at least 2 years. For each endoscopist, investigators categorized annual ADRs based on quintiles for the entire data set. “Improved ADR” was defined as keeping annual ADR within the highest quintile (above 24.6%) or as increasing annual ADR by at least one quintile, compared with baseline.

Based on this definition, 219 endoscopists (75%) improved their ADR during a median of 5.8 years of follow-up (interquartile range, 5-7.2 years). In all, 168 interval CRCs were diagnosed, of which 44 cases led to death. After age, sex, and family history of colorectal cancer were controlled for, patients whose endoscopists improved their ADRs were significantly less likely to develop (adjusted hazard ratio, 0.6; 95% confidence interval, 0.5-0.9; P = .006) or to die of interval CRC (95% CI, 0.3-0.95; P = .04) than were patients whose endoscopists did not improve their ADRs.

Maintaining ADR in the highest quintile (above 24.6%) throughout follow-up led to an even lower risk of interval CRC (HR, 0.3; 95% CI, 0.1-0.6; P = .003) and death (HR, 0.2; 95% CI, 0.1-0.6; P = .003), the researchers reported. In absolute numbers, that translated to a decrease from 25.3 interval CRCs per 100,000 person-years of follow-up to 7.1 cases when endoscopists eventually reached the highest ADR quintile or to 4.5 cases when they were in the highest quintile throughout follow-up. Rates of colonic perforation remained stable even though most endoscopists upped their ADRs.

Together, these findings “prove the causal relationship between endoscopists’ ADRs and the likelihood of being diagnosed with, or dying from, interval CRC,” the investigators concluded. The national cancer registry in Poland is thought to miss about 10% of cases, but the rate of missing cases was not thought to change over time, they noted. However, they also lacked data on colonoscope withdrawal times, and had no control group to definitively show that feedback based on benchmarking was responsible for improved ADRs.

Funders included the Foundation of Polish Science, the Innovative Economy Operational Programme, the Polish Foundation of Gastroenterology, the Polish Ministry of Health, and the Polish Ministry of Science and Higher Education. The investigators reported having no relevant conflicts of interest.

An improved annual adenoma detection rate was associated with a significantly decreased risk of interval colorectal cancer (ICRC) and subsequent death in a national prospective cohort study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.006).

Eraxion/Thinkstock

Source: American Gastroenterological Association

This is the first study to show a significant inverse relationship between an improved annual adenoma detection rate (ADR) and ICRC or subsequent death, Michal F. Kaminski MD, PhD, of the Institute of Oncology, Warsaw, wrote with his associates.

The rates of these outcomes were lowest when endoscopists achieved and maintained ADRs above 24.6%, which supports the currently recommended performance target of 25% for a mixed male-female population, they reported (Am J Gastroenterol. 2015;110:72-90).

This study included 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national cancer prevention program in Poland between 2004 and 2008. Endoscopists received annual feedback based on quality benchmarks to spur improvements in colonoscopy performance, and all participated for at least 2 years. For each endoscopist, investigators categorized annual ADRs based on quintiles for the entire data set. “Improved ADR” was defined as keeping annual ADR within the highest quintile (above 24.6%) or as increasing annual ADR by at least one quintile, compared with baseline.

Based on this definition, 219 endoscopists (75%) improved their ADR during a median of 5.8 years of follow-up (interquartile range, 5-7.2 years). In all, 168 interval CRCs were diagnosed, of which 44 cases led to death. After age, sex, and family history of colorectal cancer were controlled for, patients whose endoscopists improved their ADRs were significantly less likely to develop (adjusted hazard ratio, 0.6; 95% confidence interval, 0.5-0.9; P = .006) or to die of interval CRC (95% CI, 0.3-0.95; P = .04) than were patients whose endoscopists did not improve their ADRs.

Maintaining ADR in the highest quintile (above 24.6%) throughout follow-up led to an even lower risk of interval CRC (HR, 0.3; 95% CI, 0.1-0.6; P = .003) and death (HR, 0.2; 95% CI, 0.1-0.6; P = .003), the researchers reported. In absolute numbers, that translated to a decrease from 25.3 interval CRCs per 100,000 person-years of follow-up to 7.1 cases when endoscopists eventually reached the highest ADR quintile or to 4.5 cases when they were in the highest quintile throughout follow-up. Rates of colonic perforation remained stable even though most endoscopists upped their ADRs.

Together, these findings “prove the causal relationship between endoscopists’ ADRs and the likelihood of being diagnosed with, or dying from, interval CRC,” the investigators concluded. The national cancer registry in Poland is thought to miss about 10% of cases, but the rate of missing cases was not thought to change over time, they noted. However, they also lacked data on colonoscope withdrawal times, and had no control group to definitively show that feedback based on benchmarking was responsible for improved ADRs.

Funders included the Foundation of Polish Science, the Innovative Economy Operational Programme, the Polish Foundation of Gastroenterology, the Polish Ministry of Health, and the Polish Ministry of Science and Higher Education. The investigators reported having no relevant conflicts of interest.

An improved annual adenoma detection rate was associated with a significantly decreased risk of interval colorectal cancer (ICRC) and subsequent death in a national prospective cohort study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.006).

Eraxion/Thinkstock

Source: American Gastroenterological Association

This is the first study to show a significant inverse relationship between an improved annual adenoma detection rate (ADR) and ICRC or subsequent death, Michal F. Kaminski MD, PhD, of the Institute of Oncology, Warsaw, wrote with his associates.

The rates of these outcomes were lowest when endoscopists achieved and maintained ADRs above 24.6%, which supports the currently recommended performance target of 25% for a mixed male-female population, they reported (Am J Gastroenterol. 2015;110:72-90).

This study included 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national cancer prevention program in Poland between 2004 and 2008. Endoscopists received annual feedback based on quality benchmarks to spur improvements in colonoscopy performance, and all participated for at least 2 years. For each endoscopist, investigators categorized annual ADRs based on quintiles for the entire data set. “Improved ADR” was defined as keeping annual ADR within the highest quintile (above 24.6%) or as increasing annual ADR by at least one quintile, compared with baseline.

Based on this definition, 219 endoscopists (75%) improved their ADR during a median of 5.8 years of follow-up (interquartile range, 5-7.2 years). In all, 168 interval CRCs were diagnosed, of which 44 cases led to death. After age, sex, and family history of colorectal cancer were controlled for, patients whose endoscopists improved their ADRs were significantly less likely to develop (adjusted hazard ratio, 0.6; 95% confidence interval, 0.5-0.9; P = .006) or to die of interval CRC (95% CI, 0.3-0.95; P = .04) than were patients whose endoscopists did not improve their ADRs.

Maintaining ADR in the highest quintile (above 24.6%) throughout follow-up led to an even lower risk of interval CRC (HR, 0.3; 95% CI, 0.1-0.6; P = .003) and death (HR, 0.2; 95% CI, 0.1-0.6; P = .003), the researchers reported. In absolute numbers, that translated to a decrease from 25.3 interval CRCs per 100,000 person-years of follow-up to 7.1 cases when endoscopists eventually reached the highest ADR quintile or to 4.5 cases when they were in the highest quintile throughout follow-up. Rates of colonic perforation remained stable even though most endoscopists upped their ADRs.

Together, these findings “prove the causal relationship between endoscopists’ ADRs and the likelihood of being diagnosed with, or dying from, interval CRC,” the investigators concluded. The national cancer registry in Poland is thought to miss about 10% of cases, but the rate of missing cases was not thought to change over time, they noted. However, they also lacked data on colonoscope withdrawal times, and had no control group to definitively show that feedback based on benchmarking was responsible for improved ADRs.

Funders included the Foundation of Polish Science, the Innovative Economy Operational Programme, the Polish Foundation of Gastroenterology, the Polish Ministry of Health, and the Polish Ministry of Science and Higher Education. The investigators reported having no relevant conflicts of interest.