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Study supports expanded definition of serrated polyposis syndrome
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.
FROM GASTROENTEROLOGY
Key clinical point: Risk of colorectal cancer was similar among patients with serrated polyposis syndrome and those who did not meet formal diagnostic criteria but had more than 10 colonic polyps, of which more than 50% were serrated, and their first-degree relatives.
Major finding: Standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) in patients who met criteria for serrated polyposis syndrome and 0.74 (95% CI, 0.20-1.90) in patients with multiple serrated polyps who did not meet the criteria (P = .7).
Data source: A multicenter retrospective study of 53 patients who met criteria for serrated polyposis and 145 patients who did not meet these criteria, but had more than 10 polyps throughout the colon, of which more than 50% were serrated.
Disclosures: 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.
T-DMI doesn’t wow in HER2-overexpressing NSCLC
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.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
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.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
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.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
AT ASCO 2017
Key clinical point: Some non–small cell lung cancer (NSCLC) tumors overexpress HER2, suggesting the use of T-DM1, an anti-HER2 antibody drug conjugate.
Major finding: Four of 20 patients with HER2-overexpressing NSCLC has partial responses to T-DM1 therapy.
Data source: Open-label prospective trial of 40 patients with NSCLC positive for HER2.
Disclosures: Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
Phototherapy and Nondrug Therapies for Psoriasis Considered Beneficial by Patients
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.
Mild OSA linked to hypertension
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.
AT SLEEP 2017
Key clinical point: In a random sample of adults, the presence of mild to moderate OSA was associated with a significantly higher risk of hypertension and diabetes.
Major finding: Individuals with mild to moderate OSA had more than a fourfold increased risk of hypertension over 10 years of follow-up (OR, 4.36). Moderate OSA was significantly associated with incident diabetes risk (OR, 2.78), but mild OSA was not.
Data source: An observational study including a random sample of 1,741 adults between the ages of 20 and 84 years.
Disclosures: The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.
Steatosis linked to persistent ALT increase in hepatitis B
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.
Antiviral therapy for chronic hepatitis B virus in most treated patients suppresses rather than eradicates infection. Despite this, long-term treatment results in substantial histologic improvement – including regression of fibrosis and reduction in complications.
However, as Jacobson et al. report in a histologic follow-up of 471 HBV patients treated long-term, aminotransferase elevation persisted in 18%. Factors implicated on multivariate analysis in unresolved biochemical dysfunction included HBeAg seropositivity, age less than 40 years, and steatosis at entry, in addition to steatosis at 5-year follow-up. The only association with hepatic dysfunction that persisted was steatosis when modified normal ranges for aminotransferases proposed by Prati were applied, namely 30 U for men and 19 U for women. This suggests that metabolic rather than viral factors are implicated in persistent biochemical dysfunction in patients with chronic HBV infection. Steatosis is also a frequent finding on liver biopsy in patients with chronic HCV infection.
Importantly, HCV-specific mechanisms have been implicated in the accumulation of steatosis in infected patients, as the virus may interfere with host lipid metabolism. HCV genotype 3 has a marked propensity to cause fat accumulation in hepatocytes, which appears to regress with successful antiviral therapy. In the interferon era, hepatic steatosis had been identified as a predictor of nonresponse to therapy for HCV. In patients with chronic viral hepatitis, attention needs to be paid to cofactors in liver disease – notably the metabolic syndrome – particularly because successfully treated patients are now discharged from the care of specialists.
Paul S. Martin, MD, is chief, division of hepatology, professor of medicine, University of Miami Health System, Fla. He has been a consultant and investigator for Gilead, BMS, and Merck.
Antiviral therapy for chronic hepatitis B virus in most treated patients suppresses rather than eradicates infection. Despite this, long-term treatment results in substantial histologic improvement – including regression of fibrosis and reduction in complications.
However, as Jacobson et al. report in a histologic follow-up of 471 HBV patients treated long-term, aminotransferase elevation persisted in 18%. Factors implicated on multivariate analysis in unresolved biochemical dysfunction included HBeAg seropositivity, age less than 40 years, and steatosis at entry, in addition to steatosis at 5-year follow-up. The only association with hepatic dysfunction that persisted was steatosis when modified normal ranges for aminotransferases proposed by Prati were applied, namely 30 U for men and 19 U for women. This suggests that metabolic rather than viral factors are implicated in persistent biochemical dysfunction in patients with chronic HBV infection. Steatosis is also a frequent finding on liver biopsy in patients with chronic HCV infection.
Importantly, HCV-specific mechanisms have been implicated in the accumulation of steatosis in infected patients, as the virus may interfere with host lipid metabolism. HCV genotype 3 has a marked propensity to cause fat accumulation in hepatocytes, which appears to regress with successful antiviral therapy. In the interferon era, hepatic steatosis had been identified as a predictor of nonresponse to therapy for HCV. In patients with chronic viral hepatitis, attention needs to be paid to cofactors in liver disease – notably the metabolic syndrome – particularly because successfully treated patients are now discharged from the care of specialists.
Paul S. Martin, MD, is chief, division of hepatology, professor of medicine, University of Miami Health System, Fla. He has been a consultant and investigator for Gilead, BMS, and Merck.
Antiviral therapy for chronic hepatitis B virus in most treated patients suppresses rather than eradicates infection. Despite this, long-term treatment results in substantial histologic improvement – including regression of fibrosis and reduction in complications.
However, as Jacobson et al. report in a histologic follow-up of 471 HBV patients treated long-term, aminotransferase elevation persisted in 18%. Factors implicated on multivariate analysis in unresolved biochemical dysfunction included HBeAg seropositivity, age less than 40 years, and steatosis at entry, in addition to steatosis at 5-year follow-up. The only association with hepatic dysfunction that persisted was steatosis when modified normal ranges for aminotransferases proposed by Prati were applied, namely 30 U for men and 19 U for women. This suggests that metabolic rather than viral factors are implicated in persistent biochemical dysfunction in patients with chronic HBV infection. Steatosis is also a frequent finding on liver biopsy in patients with chronic HCV infection.
Importantly, HCV-specific mechanisms have been implicated in the accumulation of steatosis in infected patients, as the virus may interfere with host lipid metabolism. HCV genotype 3 has a marked propensity to cause fat accumulation in hepatocytes, which appears to regress with successful antiviral therapy. In the interferon era, hepatic steatosis had been identified as a predictor of nonresponse to therapy for HCV. In patients with chronic viral hepatitis, attention needs to be paid to cofactors in liver disease – notably the metabolic syndrome – particularly because successfully treated patients are now discharged from the care of specialists.
Paul S. Martin, MD, is chief, division of hepatology, professor of medicine, University of Miami Health System, Fla. He has been a consultant and investigator for Gilead, BMS, and Merck.
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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: In patients with chronic hepatitis B virus infection, steatosis was significantly associated with persistently elevated alanine aminotransferase (ALT) levels despite successful treatment with tenofovir disoproxil fumarate.
Major finding: At baseline and after 5 years of treatment, steatosis of grade 1 (5%) or more predicted persistent ALT elevation with odds ratios of 2.2 (P = .04) and 3.4 (P = .002), respectively.
Data source: Two phase III trials of tenofovir disoproxil fumarate in 471 patients with chronic hepatitis B virus infection.
Disclosures: Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.
Improved adenoma detection rate found protective against interval cancers, death
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).
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.
The U.S. Multi-Society Task Force on Colorectal Cancer proposed the adenoma detection rate (ADR) as a colonoscopy quality measure in 2002. The rationale for a new measure was emerging evidence of highly variable adenoma detection and cancer prevention among colonoscopists. Highly variable performance, consistently verified in subsequent studies, casts a pall of severe operator dependence over colonoscopy. In landmark studies from Kaminski et al. and Corley et al. in 2010 and 2014, respectively, it was shown that doctors with higher ADRs provide patients with much greater protection against interval colorectal cancer (CRC).
Now Kaminski and colleagues from Poland have delivered a second landmark study, demonstrating for the first time that improving ADR prevents CRCs. We now have strong evidence that ADR predicts the level of cancer prevention, that ADR improvement is achievable, and that improving ADR further prevents CRCs and CRC deaths. Thanks to this study, ADR has come full circle. Measurement of and improvement in detection is now a fully validated concept that is essential to modern colonoscopy. In 2017, ADR measurement is mandatory for all practicing colonoscopists who are serious about CRC prevention. The tools to improve ADR that are widely accepted include ADR measurement and reporting, split or same-day preparations, lesion recognition and optimal technique, high-definition imaging, double examination (particularly for the right colon), patient rotation during withdrawal, chromoendoscopy, mucosal exposure devices (caps, cuffs, balloons, etc.), and water exchange. Tools for ADR improvement that are emerging or under study are brighter forms of electronic chromoendoscopy, and videorecording.
Douglas K. Rex, MD, is professor of medicine, division of gastroenterology/hepatology, at Indiana University, Indianapolis.* He has no relevant conflicts of interest.
Correction, 6/20/17: An earlier version of this article misstated Dr. Rex's affiliation.
The U.S. Multi-Society Task Force on Colorectal Cancer proposed the adenoma detection rate (ADR) as a colonoscopy quality measure in 2002. The rationale for a new measure was emerging evidence of highly variable adenoma detection and cancer prevention among colonoscopists. Highly variable performance, consistently verified in subsequent studies, casts a pall of severe operator dependence over colonoscopy. In landmark studies from Kaminski et al. and Corley et al. in 2010 and 2014, respectively, it was shown that doctors with higher ADRs provide patients with much greater protection against interval colorectal cancer (CRC).
Now Kaminski and colleagues from Poland have delivered a second landmark study, demonstrating for the first time that improving ADR prevents CRCs. We now have strong evidence that ADR predicts the level of cancer prevention, that ADR improvement is achievable, and that improving ADR further prevents CRCs and CRC deaths. Thanks to this study, ADR has come full circle. Measurement of and improvement in detection is now a fully validated concept that is essential to modern colonoscopy. In 2017, ADR measurement is mandatory for all practicing colonoscopists who are serious about CRC prevention. The tools to improve ADR that are widely accepted include ADR measurement and reporting, split or same-day preparations, lesion recognition and optimal technique, high-definition imaging, double examination (particularly for the right colon), patient rotation during withdrawal, chromoendoscopy, mucosal exposure devices (caps, cuffs, balloons, etc.), and water exchange. Tools for ADR improvement that are emerging or under study are brighter forms of electronic chromoendoscopy, and videorecording.
Douglas K. Rex, MD, is professor of medicine, division of gastroenterology/hepatology, at Indiana University, Indianapolis.* He has no relevant conflicts of interest.
Correction, 6/20/17: An earlier version of this article misstated Dr. Rex's affiliation.
The U.S. Multi-Society Task Force on Colorectal Cancer proposed the adenoma detection rate (ADR) as a colonoscopy quality measure in 2002. The rationale for a new measure was emerging evidence of highly variable adenoma detection and cancer prevention among colonoscopists. Highly variable performance, consistently verified in subsequent studies, casts a pall of severe operator dependence over colonoscopy. In landmark studies from Kaminski et al. and Corley et al. in 2010 and 2014, respectively, it was shown that doctors with higher ADRs provide patients with much greater protection against interval colorectal cancer (CRC).
Now Kaminski and colleagues from Poland have delivered a second landmark study, demonstrating for the first time that improving ADR prevents CRCs. We now have strong evidence that ADR predicts the level of cancer prevention, that ADR improvement is achievable, and that improving ADR further prevents CRCs and CRC deaths. Thanks to this study, ADR has come full circle. Measurement of and improvement in detection is now a fully validated concept that is essential to modern colonoscopy. In 2017, ADR measurement is mandatory for all practicing colonoscopists who are serious about CRC prevention. The tools to improve ADR that are widely accepted include ADR measurement and reporting, split or same-day preparations, lesion recognition and optimal technique, high-definition imaging, double examination (particularly for the right colon), patient rotation during withdrawal, chromoendoscopy, mucosal exposure devices (caps, cuffs, balloons, etc.), and water exchange. Tools for ADR improvement that are emerging or under study are brighter forms of electronic chromoendoscopy, and videorecording.
Douglas K. Rex, MD, is professor of medicine, division of gastroenterology/hepatology, at Indiana University, Indianapolis.* He has no relevant conflicts of interest.
Correction, 6/20/17: An earlier version of this article misstated Dr. Rex's affiliation.
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).
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).
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.
FROM GASTROENTEROLOGY
Key clinical point: An improved adenoma detection rate was associated with a significantly reduced risk of interval colorectal cancer and subsequent death.
Major finding: Adjusted hazard ratios were 0.6 for developing ICRC (95% CI, 0.5-0.9; P = .006) and 0.50 for dying of ICRC (95% CI, 0.3-0.95; P = .04).
Data source: A prospective registry study of 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national screening program between 2004 and 2008.
Disclosures: 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.
Capitol Hill Dems, HHS Secretary Price trade jabs on HHS budget
In back-to-back appearances on Capitol Hill Wednesday, Health and Human Services Secretary Tom Price sparred with Democrats over the Trump administration’s budget cuts for his department and the coming troubles in the individual health insurance market.
“President Trump’s budget does not confuse government spending with government success,” Price said, defending a spending plan that calls for substantial funding reductions to Medicaid, the Centers for Disease Control and Prevention, the National Institutes of Health, and other HHS agencies.
The problem with many federal programs “is not that they are too expensive or too underfunded. The real problem is that they do not work – they fail the very people they are meant to help,” Price said in testimony before the Senate Finance Committee and the House Ways and Means Committee.
He cited Medicaid, the federal-state insurance program for low-income people, as an example of an area in which rising costs require reforms. The administration’s budget would reduce federal Medicaid funds to states by $610 billion over a decade. Under its proposal, states would gain latitude over how to spend those funds, which Price said would lead to innovations and efficiencies.
Sen. Sherrod Brown (D-Ohio) questioned whether HHS is budgeting enough money under Medicaid to fight the opioid-abuse epidemic. Of the $939 million that Ohio spent on opioid treatment in 2016, 70% came from federal Medicaid dollars, he said.
“You would never propose we fight cancer with a $50 million increase to a grant program,” Brown said. “How does this possibly work if you’re going to cut the biggest revenue stream to treat people?”
Price pushed back, pointing out that more than 52,000 Americans died of overdose deaths in 2015.
“We continue to tolerate a system that allows for overdose deaths, and I simply won’t allow it,” Price said.
Trump’s budget has come under heavy attack in Congress since its release last month and is expected to undergo much rewriting. The budget would take effect for the fiscal year starting Oct. 1.
Democratic senators and representatives on the committees repeatedly challenged Price on his testimony and the administration’s health care policies, sometimes using strong words and loud voices.
“It’s mean-spirited. It’s not good for America. We can do much better,” thundered Rep. John Lewis (D-Ga.).
With insurers facing looming deadlines to decide whether to participate in the Affordable Care Act’s online marketplaces next year, lawmakers also pressed Price on whether the Trump administration will pay insurers about $7 billion in “cost-sharing subsidies” for 2018. The White House has sent mixed signals, but many insurers’ decisions about next year’s premiums and where they will offer health plans hinge on the verdict.
Sen. Debbie Stabenow (D-Mich.) repeatedly asked Price if he would commit to making subsidy payments, but Price refused to answer beyond reiterating that the budget includes payments through 2018. Price said he could not elaborate because he is the defendant in a lawsuit regarding these subsidies – a still-pending case brought by the Republican-led House of Representatives during the Obama administration.
Democrats accused Price of doing little to stabilize the individual insurance marketplace as insurers have announced withdrawal plans. But, Sen. Pat Roberts (R-Kan.) said the market was failing and it wasn’t Price’s fault.
“We are in the Obama car and it’s like being in the same car as Thelma and Louise going into the canyon,” he said. “We need to get out of the car.”
Price was also asked about a draft rule from HHS that would scale back the ACA’s mandate requiring nearly all employers to offer health insurance covering birth control. The HHS proposal would allow more types of employers to claim moral or religious exemptions to the mandate. “I think that, for women who desire birth control, it should be available,” Price said.
When Sen. Maria Cantwell (D-Wash.) pressed him to answer whether birth control should be available to women through their employers, Price reiterated that it should be available to women who want it.
“This is a very big problem,” she said. ”Women cannot be discriminated against by their employers who want to cherry-pick women’s health.”
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
In back-to-back appearances on Capitol Hill Wednesday, Health and Human Services Secretary Tom Price sparred with Democrats over the Trump administration’s budget cuts for his department and the coming troubles in the individual health insurance market.
“President Trump’s budget does not confuse government spending with government success,” Price said, defending a spending plan that calls for substantial funding reductions to Medicaid, the Centers for Disease Control and Prevention, the National Institutes of Health, and other HHS agencies.
The problem with many federal programs “is not that they are too expensive or too underfunded. The real problem is that they do not work – they fail the very people they are meant to help,” Price said in testimony before the Senate Finance Committee and the House Ways and Means Committee.
He cited Medicaid, the federal-state insurance program for low-income people, as an example of an area in which rising costs require reforms. The administration’s budget would reduce federal Medicaid funds to states by $610 billion over a decade. Under its proposal, states would gain latitude over how to spend those funds, which Price said would lead to innovations and efficiencies.
Sen. Sherrod Brown (D-Ohio) questioned whether HHS is budgeting enough money under Medicaid to fight the opioid-abuse epidemic. Of the $939 million that Ohio spent on opioid treatment in 2016, 70% came from federal Medicaid dollars, he said.
“You would never propose we fight cancer with a $50 million increase to a grant program,” Brown said. “How does this possibly work if you’re going to cut the biggest revenue stream to treat people?”
Price pushed back, pointing out that more than 52,000 Americans died of overdose deaths in 2015.
“We continue to tolerate a system that allows for overdose deaths, and I simply won’t allow it,” Price said.
Trump’s budget has come under heavy attack in Congress since its release last month and is expected to undergo much rewriting. The budget would take effect for the fiscal year starting Oct. 1.
Democratic senators and representatives on the committees repeatedly challenged Price on his testimony and the administration’s health care policies, sometimes using strong words and loud voices.
“It’s mean-spirited. It’s not good for America. We can do much better,” thundered Rep. John Lewis (D-Ga.).
With insurers facing looming deadlines to decide whether to participate in the Affordable Care Act’s online marketplaces next year, lawmakers also pressed Price on whether the Trump administration will pay insurers about $7 billion in “cost-sharing subsidies” for 2018. The White House has sent mixed signals, but many insurers’ decisions about next year’s premiums and where they will offer health plans hinge on the verdict.
Sen. Debbie Stabenow (D-Mich.) repeatedly asked Price if he would commit to making subsidy payments, but Price refused to answer beyond reiterating that the budget includes payments through 2018. Price said he could not elaborate because he is the defendant in a lawsuit regarding these subsidies – a still-pending case brought by the Republican-led House of Representatives during the Obama administration.
Democrats accused Price of doing little to stabilize the individual insurance marketplace as insurers have announced withdrawal plans. But, Sen. Pat Roberts (R-Kan.) said the market was failing and it wasn’t Price’s fault.
“We are in the Obama car and it’s like being in the same car as Thelma and Louise going into the canyon,” he said. “We need to get out of the car.”
Price was also asked about a draft rule from HHS that would scale back the ACA’s mandate requiring nearly all employers to offer health insurance covering birth control. The HHS proposal would allow more types of employers to claim moral or religious exemptions to the mandate. “I think that, for women who desire birth control, it should be available,” Price said.
When Sen. Maria Cantwell (D-Wash.) pressed him to answer whether birth control should be available to women through their employers, Price reiterated that it should be available to women who want it.
“This is a very big problem,” she said. ”Women cannot be discriminated against by their employers who want to cherry-pick women’s health.”
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
In back-to-back appearances on Capitol Hill Wednesday, Health and Human Services Secretary Tom Price sparred with Democrats over the Trump administration’s budget cuts for his department and the coming troubles in the individual health insurance market.
“President Trump’s budget does not confuse government spending with government success,” Price said, defending a spending plan that calls for substantial funding reductions to Medicaid, the Centers for Disease Control and Prevention, the National Institutes of Health, and other HHS agencies.
The problem with many federal programs “is not that they are too expensive or too underfunded. The real problem is that they do not work – they fail the very people they are meant to help,” Price said in testimony before the Senate Finance Committee and the House Ways and Means Committee.
He cited Medicaid, the federal-state insurance program for low-income people, as an example of an area in which rising costs require reforms. The administration’s budget would reduce federal Medicaid funds to states by $610 billion over a decade. Under its proposal, states would gain latitude over how to spend those funds, which Price said would lead to innovations and efficiencies.
Sen. Sherrod Brown (D-Ohio) questioned whether HHS is budgeting enough money under Medicaid to fight the opioid-abuse epidemic. Of the $939 million that Ohio spent on opioid treatment in 2016, 70% came from federal Medicaid dollars, he said.
“You would never propose we fight cancer with a $50 million increase to a grant program,” Brown said. “How does this possibly work if you’re going to cut the biggest revenue stream to treat people?”
Price pushed back, pointing out that more than 52,000 Americans died of overdose deaths in 2015.
“We continue to tolerate a system that allows for overdose deaths, and I simply won’t allow it,” Price said.
Trump’s budget has come under heavy attack in Congress since its release last month and is expected to undergo much rewriting. The budget would take effect for the fiscal year starting Oct. 1.
Democratic senators and representatives on the committees repeatedly challenged Price on his testimony and the administration’s health care policies, sometimes using strong words and loud voices.
“It’s mean-spirited. It’s not good for America. We can do much better,” thundered Rep. John Lewis (D-Ga.).
With insurers facing looming deadlines to decide whether to participate in the Affordable Care Act’s online marketplaces next year, lawmakers also pressed Price on whether the Trump administration will pay insurers about $7 billion in “cost-sharing subsidies” for 2018. The White House has sent mixed signals, but many insurers’ decisions about next year’s premiums and where they will offer health plans hinge on the verdict.
Sen. Debbie Stabenow (D-Mich.) repeatedly asked Price if he would commit to making subsidy payments, but Price refused to answer beyond reiterating that the budget includes payments through 2018. Price said he could not elaborate because he is the defendant in a lawsuit regarding these subsidies – a still-pending case brought by the Republican-led House of Representatives during the Obama administration.
Democrats accused Price of doing little to stabilize the individual insurance marketplace as insurers have announced withdrawal plans. But, Sen. Pat Roberts (R-Kan.) said the market was failing and it wasn’t Price’s fault.
“We are in the Obama car and it’s like being in the same car as Thelma and Louise going into the canyon,” he said. “We need to get out of the car.”
Price was also asked about a draft rule from HHS that would scale back the ACA’s mandate requiring nearly all employers to offer health insurance covering birth control. The HHS proposal would allow more types of employers to claim moral or religious exemptions to the mandate. “I think that, for women who desire birth control, it should be available,” Price said.
When Sen. Maria Cantwell (D-Wash.) pressed him to answer whether birth control should be available to women through their employers, Price reiterated that it should be available to women who want it.
“This is a very big problem,” she said. ”Women cannot be discriminated against by their employers who want to cherry-pick women’s health.”
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Loud, frequent snoring increases preterm delivery risk
BOSTON – Women who were prepregnancy, frequent, and loud snorers during pregnancy had a significantly higher risk of preterm or early term delivery, in a study presented at the annual meeting of the Associated Professional Sleep Societies.
“The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes,” reported Galit Levi Dunietz, PhD, MPH, of the University of Michigan in a session at the meeting.
Compared with nonsnorers, frequently loud snorers had about a 60% increased risk of preterm delivery even after adjusting for baseline body mass index, smoking, education, race, and parity. Pregnancy-onset snoring and infrequent or quiet snoring were not associated with preterm birth.
A limitation on the findings was that only a small number of women (4% of the sample) fell into the chronic, frequent, and loud snoring category. These women, however, had significantly lower mean gestational age, mean baseline BMI, and were more likely to be smokers, as compared with nonsnorers and quiet frequent or infrequent snorers.
“I think this is excellent work because it’s a big question,” said Dr. Omavi Gbodossou Bailey, MD, MPH from the University of Arizona, Pheonix, in a Q&A session at the conference. “As a primary care physician, I deliver babies and I also deal with sleep and when I ask the ob.gyns. about sleep apnea in this patient population, they’re not usually interested.”
Dr. Bailey noted in an interview that, often, women who had uncomplicated first pregnancies return with later pregnancies heavier, more sleep deprived, and snoring. “Then, they have higher risk for complications in the second or third pregnancy,” he said.
Snoring is common in pregnancy, affecting about 35% of women, and pregnancy itself is a risk factor for snoring. Previous studies have associated snoring with key pregnancy morbidities including hypertension, preeclampsia, and gestational diabetes, but, prior to this research, the few studies that had looked at snoring and preterm delivery had shown inconsistent results.
The researchers recruited 904 pregnant women in their third trimester and without hypertension or diabetes from prenatal clinics at the University of Michigan cared for between 2008 and 2011. The women were queried on the frequency of their snoring (from never to three or more times per week) along with its intensity (from nonsnoring to loud or very loud snoring). They were also categorized, based on self-report, as either chronic/prepregnancy snorers or incident/pregnancy-onset snorers.
In this low-risk cohort, 25% of the women reported incident snoring and 9% reported chronic prepregnancy snoring.
“The combination of snoring frequency and intensity may be a clinically useful marker to identify otherwise low-risk women who are likely to deliver earlier,” said Dr. Dunietz.
This study was funded by the Gilmore Fund for Sleep Research, the University of Michigan Institute for Clinical and Health Research, and the National Heart, Lung, and Blood Institute. Dr. Dunietz reported having no financial disclosures.
BOSTON – Women who were prepregnancy, frequent, and loud snorers during pregnancy had a significantly higher risk of preterm or early term delivery, in a study presented at the annual meeting of the Associated Professional Sleep Societies.
“The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes,” reported Galit Levi Dunietz, PhD, MPH, of the University of Michigan in a session at the meeting.
Compared with nonsnorers, frequently loud snorers had about a 60% increased risk of preterm delivery even after adjusting for baseline body mass index, smoking, education, race, and parity. Pregnancy-onset snoring and infrequent or quiet snoring were not associated with preterm birth.
A limitation on the findings was that only a small number of women (4% of the sample) fell into the chronic, frequent, and loud snoring category. These women, however, had significantly lower mean gestational age, mean baseline BMI, and were more likely to be smokers, as compared with nonsnorers and quiet frequent or infrequent snorers.
“I think this is excellent work because it’s a big question,” said Dr. Omavi Gbodossou Bailey, MD, MPH from the University of Arizona, Pheonix, in a Q&A session at the conference. “As a primary care physician, I deliver babies and I also deal with sleep and when I ask the ob.gyns. about sleep apnea in this patient population, they’re not usually interested.”
Dr. Bailey noted in an interview that, often, women who had uncomplicated first pregnancies return with later pregnancies heavier, more sleep deprived, and snoring. “Then, they have higher risk for complications in the second or third pregnancy,” he said.
Snoring is common in pregnancy, affecting about 35% of women, and pregnancy itself is a risk factor for snoring. Previous studies have associated snoring with key pregnancy morbidities including hypertension, preeclampsia, and gestational diabetes, but, prior to this research, the few studies that had looked at snoring and preterm delivery had shown inconsistent results.
The researchers recruited 904 pregnant women in their third trimester and without hypertension or diabetes from prenatal clinics at the University of Michigan cared for between 2008 and 2011. The women were queried on the frequency of their snoring (from never to three or more times per week) along with its intensity (from nonsnoring to loud or very loud snoring). They were also categorized, based on self-report, as either chronic/prepregnancy snorers or incident/pregnancy-onset snorers.
In this low-risk cohort, 25% of the women reported incident snoring and 9% reported chronic prepregnancy snoring.
“The combination of snoring frequency and intensity may be a clinically useful marker to identify otherwise low-risk women who are likely to deliver earlier,” said Dr. Dunietz.
This study was funded by the Gilmore Fund for Sleep Research, the University of Michigan Institute for Clinical and Health Research, and the National Heart, Lung, and Blood Institute. Dr. Dunietz reported having no financial disclosures.
BOSTON – Women who were prepregnancy, frequent, and loud snorers during pregnancy had a significantly higher risk of preterm or early term delivery, in a study presented at the annual meeting of the Associated Professional Sleep Societies.
“The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes,” reported Galit Levi Dunietz, PhD, MPH, of the University of Michigan in a session at the meeting.
Compared with nonsnorers, frequently loud snorers had about a 60% increased risk of preterm delivery even after adjusting for baseline body mass index, smoking, education, race, and parity. Pregnancy-onset snoring and infrequent or quiet snoring were not associated with preterm birth.
A limitation on the findings was that only a small number of women (4% of the sample) fell into the chronic, frequent, and loud snoring category. These women, however, had significantly lower mean gestational age, mean baseline BMI, and were more likely to be smokers, as compared with nonsnorers and quiet frequent or infrequent snorers.
“I think this is excellent work because it’s a big question,” said Dr. Omavi Gbodossou Bailey, MD, MPH from the University of Arizona, Pheonix, in a Q&A session at the conference. “As a primary care physician, I deliver babies and I also deal with sleep and when I ask the ob.gyns. about sleep apnea in this patient population, they’re not usually interested.”
Dr. Bailey noted in an interview that, often, women who had uncomplicated first pregnancies return with later pregnancies heavier, more sleep deprived, and snoring. “Then, they have higher risk for complications in the second or third pregnancy,” he said.
Snoring is common in pregnancy, affecting about 35% of women, and pregnancy itself is a risk factor for snoring. Previous studies have associated snoring with key pregnancy morbidities including hypertension, preeclampsia, and gestational diabetes, but, prior to this research, the few studies that had looked at snoring and preterm delivery had shown inconsistent results.
The researchers recruited 904 pregnant women in their third trimester and without hypertension or diabetes from prenatal clinics at the University of Michigan cared for between 2008 and 2011. The women were queried on the frequency of their snoring (from never to three or more times per week) along with its intensity (from nonsnoring to loud or very loud snoring). They were also categorized, based on self-report, as either chronic/prepregnancy snorers or incident/pregnancy-onset snorers.
In this low-risk cohort, 25% of the women reported incident snoring and 9% reported chronic prepregnancy snoring.
“The combination of snoring frequency and intensity may be a clinically useful marker to identify otherwise low-risk women who are likely to deliver earlier,” said Dr. Dunietz.
This study was funded by the Gilmore Fund for Sleep Research, the University of Michigan Institute for Clinical and Health Research, and the National Heart, Lung, and Blood Institute. Dr. Dunietz reported having no financial disclosures.
AT SLEEP 2017
Key clinical point: Compared with those who were nonloud, nonfrequent, or pregnancy-onset snorers, chronic, loud, and frequent snorers were at significantly greater risk for preterm delivery.
Major finding: Of women determined to be chronic, prepregnancy, frequent, and loud snorers, 25% had preterm delivery.
Data source: An observational study including 904 pregnant women in the third trimester.
Disclosures: This study was funded by the Gilmore Fund for Sleep Research, the University of Michigan Institute for Clinical and Health Research, and the National Heart, Lung, and Blood Institute. Dr. Dunietz reported having no financial disclosures.
REMOVAL: Metformin may reduce cardiac risk in type 1 diabetes but doesn’t improve glucose control
SAN DIEGO – Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.
“The CVD benefit is suggestive, but it’s by no means conclusive,” Naveed Sattar, MD, PhD, of the University of Glasgow said in a presentation at the scientific meetings of the American Diabetic Association. As for glycemic control, “you should not prescribe metformin if you want a clinical change in hemoglobin A1c,” he said.
The findings don’t examine CVD outcomes, and researchers bemoaned their inability to launch such a project because of limitations in funding. Still, the study, funded by the Juvenile Diabetes Research Foundation, is the largest to examine metformin in type 1 diabetes.
The Food and Drug Administration has not approved metformin for type 1 diabetes. However, the American Diabetes Association’s 2017 Standard of Care guidelines note that “adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes” (Diabetes Care. 2017 Jan;40[Suppl 1]).
“Metformin has known efficacy for reducing HbA1c, and, at the time we did this, it was one of few diabetes drugs with indications of an effect on cardiovascular disease risk,” study coauthor Helen M. Colhoun, MD, of the University of Edinburgh said during the discussion following the presentation.
The REMOVAL (cardiovascular and metabolic effects of metformin in patients with type 1 diabetes) trial took place from 2011 to 2014. Involved researchers at 23 hospital diabetes clinics around the world randomly assigned 428 patients to metformin (n = 219) and placebo (n = 209) arms.
The patients were all 40 years or older, with a mean age of 55 years. All patients had been diagnosed with type 1 diabetes at least five years prior to the study and met at least 3 of 10 criteria for high risk of cardiovascular disease. Men accounted for 59% of the patients, about 98% were white, and about 79% were obese or overweight. Patients had high levels of use of statins (73%), blood pressure medications (73%), and antiplatelet drugs (39%).
Participants took oral metformin 1,000 mg twice daily or placebo. The results were reported at the ADA meeting and simultaneously online on June 11, 2017 in Lancet Diabetes Endocrinology (2017 Jun 11. doi: 10.1016/S2213-8587[17]30194-8).
In regard to CVD indicators, the researchers did not find significant reduction in the progression of average common carotid artery intima-media thickness (cIMT) (–0.005 mm per year; 95% confidence interval, –0.012-0.002; P = .1664) in metformin, vs. placebo.
There was, however, a significant reduction in maximal cIMT (–0.013 mm per year; 95% CI, –0.024 to –0.003; P = .0093). The study describes this as a surrogate measure for atherosclerosis progression, although it’s a tertiary rather than primary outcome.
Researchers saw a slight decline in HbA1c in the metformin group (–0.13%; 95% CI, –0.22 to –0.037; P = .0060), but researchers say this occurred early and was not sustained.
In the metformin group, compared with placebo, researchers also found reductions in body weight (–1.17 kg; 95% CI,–1.66 to –0.69; p less than .0001) and LDL cholesterol (–0.13 mmol/L; 95% CI, –0.24 to –0.03; P = .0117) on average.
Researchers didn’t find a significant average reduction in insulin use in the metformin group, compared with placebo (–0.005 units per kg; 95% CI, –0.022-0.012, P = .545), although they did notice “a small but sustained reduction in patients allocated to metformin (estimated in post-hoc analyses as –0.023 units per kg; 95% CI, –0.045 to –0.0005; P = .045).”
Rates of gastrointestinal problems were higher in the metformin group, and 27% of these patients discontinued treatment, compared with 12% of placebo patients (P = .0002). Five of the metformin patients died (as did two of the placebo patients), but researchers didn’t link the deaths to medication.
The findings were clearly disappointing. “We’re certainly not claiming that this is a positive trial,” said study coauthor Dr. Colhoun.
A member of the audience at the AAD meeting asked another coauthor, Irene Hramiak, MD, of the University of Western Ontario, London, whether she would prescribe metformin to a patient with type 1 diabetes and a high risk of CVD. “Probably not,” she said, but she added that it may have value in adolescents with weight issues. In those cases, she said, there may be a benefit to improving weight control and lowering insulin doses.
In light of the study findings, the authors recommend revising guidelines that suggest the use of metformin in type 1 diabetes: “We identified a transient improvement in glycemia that reverted to baseline with insulin dose reduction and identified no suggestion of greater benefit in overweight or obese patients.”
The study adds, “Rather than a role in glycemic control, our findings suggest that long-term use of metformin in type 1 diabetes might reduce the long-term risk of cardiovascular disease via small but sustained reductions in bodyweight and LDL cholesterol.”
The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.
This article was updated June 19, 2017.
SAN DIEGO – Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.
“The CVD benefit is suggestive, but it’s by no means conclusive,” Naveed Sattar, MD, PhD, of the University of Glasgow said in a presentation at the scientific meetings of the American Diabetic Association. As for glycemic control, “you should not prescribe metformin if you want a clinical change in hemoglobin A1c,” he said.
The findings don’t examine CVD outcomes, and researchers bemoaned their inability to launch such a project because of limitations in funding. Still, the study, funded by the Juvenile Diabetes Research Foundation, is the largest to examine metformin in type 1 diabetes.
The Food and Drug Administration has not approved metformin for type 1 diabetes. However, the American Diabetes Association’s 2017 Standard of Care guidelines note that “adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes” (Diabetes Care. 2017 Jan;40[Suppl 1]).
“Metformin has known efficacy for reducing HbA1c, and, at the time we did this, it was one of few diabetes drugs with indications of an effect on cardiovascular disease risk,” study coauthor Helen M. Colhoun, MD, of the University of Edinburgh said during the discussion following the presentation.
The REMOVAL (cardiovascular and metabolic effects of metformin in patients with type 1 diabetes) trial took place from 2011 to 2014. Involved researchers at 23 hospital diabetes clinics around the world randomly assigned 428 patients to metformin (n = 219) and placebo (n = 209) arms.
The patients were all 40 years or older, with a mean age of 55 years. All patients had been diagnosed with type 1 diabetes at least five years prior to the study and met at least 3 of 10 criteria for high risk of cardiovascular disease. Men accounted for 59% of the patients, about 98% were white, and about 79% were obese or overweight. Patients had high levels of use of statins (73%), blood pressure medications (73%), and antiplatelet drugs (39%).
Participants took oral metformin 1,000 mg twice daily or placebo. The results were reported at the ADA meeting and simultaneously online on June 11, 2017 in Lancet Diabetes Endocrinology (2017 Jun 11. doi: 10.1016/S2213-8587[17]30194-8).
In regard to CVD indicators, the researchers did not find significant reduction in the progression of average common carotid artery intima-media thickness (cIMT) (–0.005 mm per year; 95% confidence interval, –0.012-0.002; P = .1664) in metformin, vs. placebo.
There was, however, a significant reduction in maximal cIMT (–0.013 mm per year; 95% CI, –0.024 to –0.003; P = .0093). The study describes this as a surrogate measure for atherosclerosis progression, although it’s a tertiary rather than primary outcome.
Researchers saw a slight decline in HbA1c in the metformin group (–0.13%; 95% CI, –0.22 to –0.037; P = .0060), but researchers say this occurred early and was not sustained.
In the metformin group, compared with placebo, researchers also found reductions in body weight (–1.17 kg; 95% CI,–1.66 to –0.69; p less than .0001) and LDL cholesterol (–0.13 mmol/L; 95% CI, –0.24 to –0.03; P = .0117) on average.
Researchers didn’t find a significant average reduction in insulin use in the metformin group, compared with placebo (–0.005 units per kg; 95% CI, –0.022-0.012, P = .545), although they did notice “a small but sustained reduction in patients allocated to metformin (estimated in post-hoc analyses as –0.023 units per kg; 95% CI, –0.045 to –0.0005; P = .045).”
Rates of gastrointestinal problems were higher in the metformin group, and 27% of these patients discontinued treatment, compared with 12% of placebo patients (P = .0002). Five of the metformin patients died (as did two of the placebo patients), but researchers didn’t link the deaths to medication.
The findings were clearly disappointing. “We’re certainly not claiming that this is a positive trial,” said study coauthor Dr. Colhoun.
A member of the audience at the AAD meeting asked another coauthor, Irene Hramiak, MD, of the University of Western Ontario, London, whether she would prescribe metformin to a patient with type 1 diabetes and a high risk of CVD. “Probably not,” she said, but she added that it may have value in adolescents with weight issues. In those cases, she said, there may be a benefit to improving weight control and lowering insulin doses.
In light of the study findings, the authors recommend revising guidelines that suggest the use of metformin in type 1 diabetes: “We identified a transient improvement in glycemia that reverted to baseline with insulin dose reduction and identified no suggestion of greater benefit in overweight or obese patients.”
The study adds, “Rather than a role in glycemic control, our findings suggest that long-term use of metformin in type 1 diabetes might reduce the long-term risk of cardiovascular disease via small but sustained reductions in bodyweight and LDL cholesterol.”
The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.
This article was updated June 19, 2017.
SAN DIEGO – Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.
“The CVD benefit is suggestive, but it’s by no means conclusive,” Naveed Sattar, MD, PhD, of the University of Glasgow said in a presentation at the scientific meetings of the American Diabetic Association. As for glycemic control, “you should not prescribe metformin if you want a clinical change in hemoglobin A1c,” he said.
The findings don’t examine CVD outcomes, and researchers bemoaned their inability to launch such a project because of limitations in funding. Still, the study, funded by the Juvenile Diabetes Research Foundation, is the largest to examine metformin in type 1 diabetes.
The Food and Drug Administration has not approved metformin for type 1 diabetes. However, the American Diabetes Association’s 2017 Standard of Care guidelines note that “adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes” (Diabetes Care. 2017 Jan;40[Suppl 1]).
“Metformin has known efficacy for reducing HbA1c, and, at the time we did this, it was one of few diabetes drugs with indications of an effect on cardiovascular disease risk,” study coauthor Helen M. Colhoun, MD, of the University of Edinburgh said during the discussion following the presentation.
The REMOVAL (cardiovascular and metabolic effects of metformin in patients with type 1 diabetes) trial took place from 2011 to 2014. Involved researchers at 23 hospital diabetes clinics around the world randomly assigned 428 patients to metformin (n = 219) and placebo (n = 209) arms.
The patients were all 40 years or older, with a mean age of 55 years. All patients had been diagnosed with type 1 diabetes at least five years prior to the study and met at least 3 of 10 criteria for high risk of cardiovascular disease. Men accounted for 59% of the patients, about 98% were white, and about 79% were obese or overweight. Patients had high levels of use of statins (73%), blood pressure medications (73%), and antiplatelet drugs (39%).
Participants took oral metformin 1,000 mg twice daily or placebo. The results were reported at the ADA meeting and simultaneously online on June 11, 2017 in Lancet Diabetes Endocrinology (2017 Jun 11. doi: 10.1016/S2213-8587[17]30194-8).
In regard to CVD indicators, the researchers did not find significant reduction in the progression of average common carotid artery intima-media thickness (cIMT) (–0.005 mm per year; 95% confidence interval, –0.012-0.002; P = .1664) in metformin, vs. placebo.
There was, however, a significant reduction in maximal cIMT (–0.013 mm per year; 95% CI, –0.024 to –0.003; P = .0093). The study describes this as a surrogate measure for atherosclerosis progression, although it’s a tertiary rather than primary outcome.
Researchers saw a slight decline in HbA1c in the metformin group (–0.13%; 95% CI, –0.22 to –0.037; P = .0060), but researchers say this occurred early and was not sustained.
In the metformin group, compared with placebo, researchers also found reductions in body weight (–1.17 kg; 95% CI,–1.66 to –0.69; p less than .0001) and LDL cholesterol (–0.13 mmol/L; 95% CI, –0.24 to –0.03; P = .0117) on average.
Researchers didn’t find a significant average reduction in insulin use in the metformin group, compared with placebo (–0.005 units per kg; 95% CI, –0.022-0.012, P = .545), although they did notice “a small but sustained reduction in patients allocated to metformin (estimated in post-hoc analyses as –0.023 units per kg; 95% CI, –0.045 to –0.0005; P = .045).”
Rates of gastrointestinal problems were higher in the metformin group, and 27% of these patients discontinued treatment, compared with 12% of placebo patients (P = .0002). Five of the metformin patients died (as did two of the placebo patients), but researchers didn’t link the deaths to medication.
The findings were clearly disappointing. “We’re certainly not claiming that this is a positive trial,” said study coauthor Dr. Colhoun.
A member of the audience at the AAD meeting asked another coauthor, Irene Hramiak, MD, of the University of Western Ontario, London, whether she would prescribe metformin to a patient with type 1 diabetes and a high risk of CVD. “Probably not,” she said, but she added that it may have value in adolescents with weight issues. In those cases, she said, there may be a benefit to improving weight control and lowering insulin doses.
In light of the study findings, the authors recommend revising guidelines that suggest the use of metformin in type 1 diabetes: “We identified a transient improvement in glycemia that reverted to baseline with insulin dose reduction and identified no suggestion of greater benefit in overweight or obese patients.”
The study adds, “Rather than a role in glycemic control, our findings suggest that long-term use of metformin in type 1 diabetes might reduce the long-term risk of cardiovascular disease via small but sustained reductions in bodyweight and LDL cholesterol.”
The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.
This article was updated June 19, 2017.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: Metformin may reduce cardiac risk in adult type 1 patients, but it doesn’t improve glycemic control. Discontinuation is common.
Major finding: Maximal carotid artery intima-media thickness (cIMT), a surrogate measure for atherosclerosis progression, fell by a mean –0.013 mm per year (95% CI, –0.024 to –0.003; P = .0093), although a similar measure, mean cIMT, dropped by just –0.005 mm per year (95% CI, –0.012-0.002; P = .1664). HbA1c in the metformin group fell by –0.13% (95% CI, –0.22 to –0.037; P = .0060). Of metformin patients, 27% discontinued treatment, compared with 12% of placebo patients (P = .0002).
Data source: A 3-year double-blind, randomized, placebo-controlled trial in patients, aged 40+ years with type 1 diabetes and at least 3 of 10 cardiac risk factors, assigned to oral metformin 1,000 mg twice daily (n = 219) or placebo (209).
Disclosures: The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.
Exhaustive leveling needed for diagnosis of colon adenomas
CHICAGO – A substantial number of adenomas may be missed by pathologists, but changes in the standard methodology can significantly decrease that amount, according to findings presented at Digestive Disease Week®.
A nondiagnostic result is common in histologic specimens obtained from the colon and occurs in about 9% of biopsies. However, a protocol known as “exhaustive leveling of histologically nondiagnostic specimens” can significantly increase the detection of adenomas.
“In our study, we were answering the question, Are pathologists missing adenomas?” said Lauren Suzanne Cole, MD, of the University of Arizona, Phoenix.
During a standard pathology analysis, 50% of the polyp isn’t analyzed at all, and the remaining half is cut into three different levels that are approximately 2 microns each. “Ultimately, less than 1% is actually reviewed by the pathologist,” she said.
GI physicians may perceive that the pathology review is definitive, Dr. Cole explained. “They believe that the section is viewed in its entirety, when, in reality, 50% of the tissue block is cut and less than 1% is viewed to come up with a diagnosis.”
The term nondiagnostic biopsy generally indicates that a specific diagnosis cannot be made. In their literature review, Dr. Cole and her team looked at eight published studies and found that a nondiagnostic biopsy was a very common result, ranging from 9% to 16%. In addition, the literature also showed that there was a significant conversion rate in nondiagnostic biopsies, from 4% to 20%, when additional leveling was performed.
In the current study, they investigated whether the detection of adenomas is improved when pathologists examine representative levels taken from the entire tissue block of specimens that have been diagnosed as nondiagnostic.
They conducted a retrospective review of pathology results that had been performed by a large GI practice (from November 2012 to November 2016) after implementing a so-called “polyp protocol,” which included an analysis of tissue sections from the entire tissue block (exhaustive leveling) of polyps initially deemed histologically nondiagnostic.
A total of 120,115 polyps had been removed during the study period, and, of this group, 10,768 (9%) were initially found to be nondiagnostic and were selected for exhaustive leveling. After exhaustive leveling, more than one-third (37%; n = 3,964) of the diagnoses converted to adenoma.
When the detection rate for adenomas for exhaustive leveling was compared with that for standard leveling, there was a statistically significant 3.3% increase (P less than .0001) from baseline.
“Our conclusion is that adenomas are missed,” said Dr. Cole. “This is partially because pathologists are not typically evaluating an entire specimen.”
These results support the need for implementing standardized protocols for exhaustive leveling as a means of increasing the adenoma detection rate, she noted. “Our research emphasizes the need for further studies assessing pathology specimen processing and analysis.”
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Cole declared no relevant disclosures.
CHICAGO – A substantial number of adenomas may be missed by pathologists, but changes in the standard methodology can significantly decrease that amount, according to findings presented at Digestive Disease Week®.
A nondiagnostic result is common in histologic specimens obtained from the colon and occurs in about 9% of biopsies. However, a protocol known as “exhaustive leveling of histologically nondiagnostic specimens” can significantly increase the detection of adenomas.
“In our study, we were answering the question, Are pathologists missing adenomas?” said Lauren Suzanne Cole, MD, of the University of Arizona, Phoenix.
During a standard pathology analysis, 50% of the polyp isn’t analyzed at all, and the remaining half is cut into three different levels that are approximately 2 microns each. “Ultimately, less than 1% is actually reviewed by the pathologist,” she said.
GI physicians may perceive that the pathology review is definitive, Dr. Cole explained. “They believe that the section is viewed in its entirety, when, in reality, 50% of the tissue block is cut and less than 1% is viewed to come up with a diagnosis.”
The term nondiagnostic biopsy generally indicates that a specific diagnosis cannot be made. In their literature review, Dr. Cole and her team looked at eight published studies and found that a nondiagnostic biopsy was a very common result, ranging from 9% to 16%. In addition, the literature also showed that there was a significant conversion rate in nondiagnostic biopsies, from 4% to 20%, when additional leveling was performed.
In the current study, they investigated whether the detection of adenomas is improved when pathologists examine representative levels taken from the entire tissue block of specimens that have been diagnosed as nondiagnostic.
They conducted a retrospective review of pathology results that had been performed by a large GI practice (from November 2012 to November 2016) after implementing a so-called “polyp protocol,” which included an analysis of tissue sections from the entire tissue block (exhaustive leveling) of polyps initially deemed histologically nondiagnostic.
A total of 120,115 polyps had been removed during the study period, and, of this group, 10,768 (9%) were initially found to be nondiagnostic and were selected for exhaustive leveling. After exhaustive leveling, more than one-third (37%; n = 3,964) of the diagnoses converted to adenoma.
When the detection rate for adenomas for exhaustive leveling was compared with that for standard leveling, there was a statistically significant 3.3% increase (P less than .0001) from baseline.
“Our conclusion is that adenomas are missed,” said Dr. Cole. “This is partially because pathologists are not typically evaluating an entire specimen.”
These results support the need for implementing standardized protocols for exhaustive leveling as a means of increasing the adenoma detection rate, she noted. “Our research emphasizes the need for further studies assessing pathology specimen processing and analysis.”
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Cole declared no relevant disclosures.
CHICAGO – A substantial number of adenomas may be missed by pathologists, but changes in the standard methodology can significantly decrease that amount, according to findings presented at Digestive Disease Week®.
A nondiagnostic result is common in histologic specimens obtained from the colon and occurs in about 9% of biopsies. However, a protocol known as “exhaustive leveling of histologically nondiagnostic specimens” can significantly increase the detection of adenomas.
“In our study, we were answering the question, Are pathologists missing adenomas?” said Lauren Suzanne Cole, MD, of the University of Arizona, Phoenix.
During a standard pathology analysis, 50% of the polyp isn’t analyzed at all, and the remaining half is cut into three different levels that are approximately 2 microns each. “Ultimately, less than 1% is actually reviewed by the pathologist,” she said.
GI physicians may perceive that the pathology review is definitive, Dr. Cole explained. “They believe that the section is viewed in its entirety, when, in reality, 50% of the tissue block is cut and less than 1% is viewed to come up with a diagnosis.”
The term nondiagnostic biopsy generally indicates that a specific diagnosis cannot be made. In their literature review, Dr. Cole and her team looked at eight published studies and found that a nondiagnostic biopsy was a very common result, ranging from 9% to 16%. In addition, the literature also showed that there was a significant conversion rate in nondiagnostic biopsies, from 4% to 20%, when additional leveling was performed.
In the current study, they investigated whether the detection of adenomas is improved when pathologists examine representative levels taken from the entire tissue block of specimens that have been diagnosed as nondiagnostic.
They conducted a retrospective review of pathology results that had been performed by a large GI practice (from November 2012 to November 2016) after implementing a so-called “polyp protocol,” which included an analysis of tissue sections from the entire tissue block (exhaustive leveling) of polyps initially deemed histologically nondiagnostic.
A total of 120,115 polyps had been removed during the study period, and, of this group, 10,768 (9%) were initially found to be nondiagnostic and were selected for exhaustive leveling. After exhaustive leveling, more than one-third (37%; n = 3,964) of the diagnoses converted to adenoma.
When the detection rate for adenomas for exhaustive leveling was compared with that for standard leveling, there was a statistically significant 3.3% increase (P less than .0001) from baseline.
“Our conclusion is that adenomas are missed,” said Dr. Cole. “This is partially because pathologists are not typically evaluating an entire specimen.”
These results support the need for implementing standardized protocols for exhaustive leveling as a means of increasing the adenoma detection rate, she noted. “Our research emphasizes the need for further studies assessing pathology specimen processing and analysis.”
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Cole declared no relevant disclosures.
AT DDW
Key clinical point: Current methods of pathology miss between 9% and 16% of adenomas because a specific diagnosis cannot be made.
Major finding: Using exhaustive leveling allowed for a conversion of more than one-third (37%; n = 3,964) of nondiagnostic results to adenoma.
Data source: A retrospective review of the pathology findings of a large GI practice after implementation of exhaustive leveling.
Disclosures: Dr. Cole declared no relevant disclosures.