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Age at RRSO affects peritoneal cancer risk in BRCA mutation carriers
Carriers of the BRCA1/2 mutation who undergo risk-reducing salpingo-oophorectomy (RRSO) still face a risk of developing metachronous peritoneal carcinomatosis, according to new findings published in Cancer.
The risk was predominantly observed in BRCA1 mutation carriers, and disease development generally occurred within 5 years following RRSO. Women who underwent RRSO at an age older than that currently recommended also had a higher risk of developing peritoneal carcinoma.
Their median age was 52 years at the time they underwent surgery, and 60 years when they were diagnosed with peritoneal carcinomatosis. As compared with the control group, the patients were older at the time they underwent RRSO (P = .025).
In eight RRSO specimens that were obtained from women who subsequently developed peritoneal carcinomatosis, five (62.5%), had serous tubal intraepithelial carcinoma (STIC) and one had epithelial atypia.
“The findings of the current study can be used to refine gynecologic counseling for BRCA1/2 mutation carriers who consider risk-reducing surgery and to stress the importance of complete RRSO at the recommended ages,” wrote lead author Marline G. Harmsen, MD, PhD, of the Radboud University Medical Center, Nijmegen, the Netherlands.
BRCA1/2 mutation carriers face a higher risk of developing ovarian carcinoma, and RRSO can reduce that risk by 80%-96%. Surgery is recommended for carriers of BRCA1 mutations aged 35-40 years and for BRCA2 mutation carriers aged 40-45 years.
In this study, Dr. Harmsen and her colleagues conducted a literature search in order to collect and analyze clinical and pathological data from women with BRCA1/2 mutation who developed peritoneal carcinomatosis following RRSO. The cases that were identified were then compared with a cohort from a single institution.
Of the 36 cases that were identified, 86.1% were BRCA1 mutation carriers and the remaining 5 patients had a BRCA2 mutation. The median age at the time of surgery differed significantly between BRCA1 (51 years; range, 30-71 years) and BRCA2 mutation carriers (57 years; range, 56-65 years) (P = .006).
The majority of women had undergone salpingo-oophorectomy (31; 86.1%), and 16 (44.4%) had also had a hysterectomy.
The authors found that several statistically significant differences between the case studies and the control group: the median age surgery (52 vs. 46 years), percentage of BRCA1 mutation carriers (86.1% vs. 53.1%, P less than .001), and percentage of serous tubal intraepithelial carcinomas in the RRSO specimens (62.5% vs. 0%; P less than .001).
SOURCE: Hamsen MG et al. Cancer. 2018 Jan 9. doi: 10.1002/cncr.31211.
In an accompanying editorial, Christine S. Walsh, MD, of Cedars-Sinai Medical Center in Los Angeles, notes that the study authors have “done a commendable job in trying to shed light on a rare condition,” which occurs in about 1%-4% of women who undergo risk-reducing salpingo-oophorectomy (RRSO).
These findings can provide more information to clinicians, as they seek to guide and counsel women after they undergo RRSO, she wrote.
Dr. Walsh pointed out that National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment of breast and ovarian cancer specify the optimal ages when RRSO should be performed, but despite efforts to encourage this, occult gynecologic carcinomas still are found in approximately 4.5%-9% of women, with serous tubal intraepithelial carcinoma lesions developing in approximately 5%-8% of them.
“Ideally, the goal should be to intervene with a prophylactic surgery before the development of cancerous or precancerous pathology,” she wrote. Dr. Walsh had no disclosures.
In an accompanying editorial, Christine S. Walsh, MD, of Cedars-Sinai Medical Center in Los Angeles, notes that the study authors have “done a commendable job in trying to shed light on a rare condition,” which occurs in about 1%-4% of women who undergo risk-reducing salpingo-oophorectomy (RRSO).
These findings can provide more information to clinicians, as they seek to guide and counsel women after they undergo RRSO, she wrote.
Dr. Walsh pointed out that National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment of breast and ovarian cancer specify the optimal ages when RRSO should be performed, but despite efforts to encourage this, occult gynecologic carcinomas still are found in approximately 4.5%-9% of women, with serous tubal intraepithelial carcinoma lesions developing in approximately 5%-8% of them.
“Ideally, the goal should be to intervene with a prophylactic surgery before the development of cancerous or precancerous pathology,” she wrote. Dr. Walsh had no disclosures.
In an accompanying editorial, Christine S. Walsh, MD, of Cedars-Sinai Medical Center in Los Angeles, notes that the study authors have “done a commendable job in trying to shed light on a rare condition,” which occurs in about 1%-4% of women who undergo risk-reducing salpingo-oophorectomy (RRSO).
These findings can provide more information to clinicians, as they seek to guide and counsel women after they undergo RRSO, she wrote.
Dr. Walsh pointed out that National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment of breast and ovarian cancer specify the optimal ages when RRSO should be performed, but despite efforts to encourage this, occult gynecologic carcinomas still are found in approximately 4.5%-9% of women, with serous tubal intraepithelial carcinoma lesions developing in approximately 5%-8% of them.
“Ideally, the goal should be to intervene with a prophylactic surgery before the development of cancerous or precancerous pathology,” she wrote. Dr. Walsh had no disclosures.
Carriers of the BRCA1/2 mutation who undergo risk-reducing salpingo-oophorectomy (RRSO) still face a risk of developing metachronous peritoneal carcinomatosis, according to new findings published in Cancer.
The risk was predominantly observed in BRCA1 mutation carriers, and disease development generally occurred within 5 years following RRSO. Women who underwent RRSO at an age older than that currently recommended also had a higher risk of developing peritoneal carcinoma.
Their median age was 52 years at the time they underwent surgery, and 60 years when they were diagnosed with peritoneal carcinomatosis. As compared with the control group, the patients were older at the time they underwent RRSO (P = .025).
In eight RRSO specimens that were obtained from women who subsequently developed peritoneal carcinomatosis, five (62.5%), had serous tubal intraepithelial carcinoma (STIC) and one had epithelial atypia.
“The findings of the current study can be used to refine gynecologic counseling for BRCA1/2 mutation carriers who consider risk-reducing surgery and to stress the importance of complete RRSO at the recommended ages,” wrote lead author Marline G. Harmsen, MD, PhD, of the Radboud University Medical Center, Nijmegen, the Netherlands.
BRCA1/2 mutation carriers face a higher risk of developing ovarian carcinoma, and RRSO can reduce that risk by 80%-96%. Surgery is recommended for carriers of BRCA1 mutations aged 35-40 years and for BRCA2 mutation carriers aged 40-45 years.
In this study, Dr. Harmsen and her colleagues conducted a literature search in order to collect and analyze clinical and pathological data from women with BRCA1/2 mutation who developed peritoneal carcinomatosis following RRSO. The cases that were identified were then compared with a cohort from a single institution.
Of the 36 cases that were identified, 86.1% were BRCA1 mutation carriers and the remaining 5 patients had a BRCA2 mutation. The median age at the time of surgery differed significantly between BRCA1 (51 years; range, 30-71 years) and BRCA2 mutation carriers (57 years; range, 56-65 years) (P = .006).
The majority of women had undergone salpingo-oophorectomy (31; 86.1%), and 16 (44.4%) had also had a hysterectomy.
The authors found that several statistically significant differences between the case studies and the control group: the median age surgery (52 vs. 46 years), percentage of BRCA1 mutation carriers (86.1% vs. 53.1%, P less than .001), and percentage of serous tubal intraepithelial carcinomas in the RRSO specimens (62.5% vs. 0%; P less than .001).
SOURCE: Hamsen MG et al. Cancer. 2018 Jan 9. doi: 10.1002/cncr.31211.
Carriers of the BRCA1/2 mutation who undergo risk-reducing salpingo-oophorectomy (RRSO) still face a risk of developing metachronous peritoneal carcinomatosis, according to new findings published in Cancer.
The risk was predominantly observed in BRCA1 mutation carriers, and disease development generally occurred within 5 years following RRSO. Women who underwent RRSO at an age older than that currently recommended also had a higher risk of developing peritoneal carcinoma.
Their median age was 52 years at the time they underwent surgery, and 60 years when they were diagnosed with peritoneal carcinomatosis. As compared with the control group, the patients were older at the time they underwent RRSO (P = .025).
In eight RRSO specimens that were obtained from women who subsequently developed peritoneal carcinomatosis, five (62.5%), had serous tubal intraepithelial carcinoma (STIC) and one had epithelial atypia.
“The findings of the current study can be used to refine gynecologic counseling for BRCA1/2 mutation carriers who consider risk-reducing surgery and to stress the importance of complete RRSO at the recommended ages,” wrote lead author Marline G. Harmsen, MD, PhD, of the Radboud University Medical Center, Nijmegen, the Netherlands.
BRCA1/2 mutation carriers face a higher risk of developing ovarian carcinoma, and RRSO can reduce that risk by 80%-96%. Surgery is recommended for carriers of BRCA1 mutations aged 35-40 years and for BRCA2 mutation carriers aged 40-45 years.
In this study, Dr. Harmsen and her colleagues conducted a literature search in order to collect and analyze clinical and pathological data from women with BRCA1/2 mutation who developed peritoneal carcinomatosis following RRSO. The cases that were identified were then compared with a cohort from a single institution.
Of the 36 cases that were identified, 86.1% were BRCA1 mutation carriers and the remaining 5 patients had a BRCA2 mutation. The median age at the time of surgery differed significantly between BRCA1 (51 years; range, 30-71 years) and BRCA2 mutation carriers (57 years; range, 56-65 years) (P = .006).
The majority of women had undergone salpingo-oophorectomy (31; 86.1%), and 16 (44.4%) had also had a hysterectomy.
The authors found that several statistically significant differences between the case studies and the control group: the median age surgery (52 vs. 46 years), percentage of BRCA1 mutation carriers (86.1% vs. 53.1%, P less than .001), and percentage of serous tubal intraepithelial carcinomas in the RRSO specimens (62.5% vs. 0%; P less than .001).
SOURCE: Hamsen MG et al. Cancer. 2018 Jan 9. doi: 10.1002/cncr.31211.
FROM CANCER
Key clinical point: BRCA mutation carriers who undergo risk-reducing surgery at an older age have a higher risk of developing metachronous peritoneal carcinomatosis.
Major finding: Women with BRCA 1 were at a higher risk for developing peritoneal carcinomatosis, as were those who underwent surgery at an older age.
Data source: A literature search to identify patients with BRCA 1/2 mutations who had undergone risk-reducing surgery and developed peritoneal carcinomatosis; 36 cases were identified and compared with a control group from a single institution.
Disclosures: No specific funding was disclosed. The authors had no disclosures.
Source: Hamsen MG et al. Cancer. 2018 Jan 9. doi: 10.1002/cncr.31211.
FDA approves PARP inhibitor for BRCA+ advanced breast cancer
The Food and Drug Administration has approved the PARP inhibitor olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy.
This is the first PARP inhibitor approved to treat breast cancer and the first approval for treatment of patients with metastatic breast cancer who have a BRCA gene mutation, the FDA said in a press statement.
The FDA also expanded approval of the companion diagnostic, BRACAnalysis CDx, to include the detection of BRCA mutations in blood samples from patients with breast cancer.
A capsule form of olaparib (Lynparza) was first approved in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. In August 2017, the FDA granted regular approval to olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network, the FDA said.
Approval for the treatment of breast cancer was based on a 2.8 month improvement in progression-free survival with olaparib vs standard chemotherapy in the phase 3 OlympiAD trial of 302 previously treated patients with BRCA-positive, HER2-negative breast cancer. Results of the trial were presented at ASCO 2017 and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1706450).
Common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.
Severe side effects include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis. Women should be advised of the potential risk to the fetus and to use effective contraception, the FDA said.
The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP and the approval of the BRACAnalysis CDx to Myriad Genetic Laboratories, Inc.
The Food and Drug Administration has approved the PARP inhibitor olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy.
This is the first PARP inhibitor approved to treat breast cancer and the first approval for treatment of patients with metastatic breast cancer who have a BRCA gene mutation, the FDA said in a press statement.
The FDA also expanded approval of the companion diagnostic, BRACAnalysis CDx, to include the detection of BRCA mutations in blood samples from patients with breast cancer.
A capsule form of olaparib (Lynparza) was first approved in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. In August 2017, the FDA granted regular approval to olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network, the FDA said.
Approval for the treatment of breast cancer was based on a 2.8 month improvement in progression-free survival with olaparib vs standard chemotherapy in the phase 3 OlympiAD trial of 302 previously treated patients with BRCA-positive, HER2-negative breast cancer. Results of the trial were presented at ASCO 2017 and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1706450).
Common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.
Severe side effects include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis. Women should be advised of the potential risk to the fetus and to use effective contraception, the FDA said.
The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP and the approval of the BRACAnalysis CDx to Myriad Genetic Laboratories, Inc.
The Food and Drug Administration has approved the PARP inhibitor olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy.
This is the first PARP inhibitor approved to treat breast cancer and the first approval for treatment of patients with metastatic breast cancer who have a BRCA gene mutation, the FDA said in a press statement.
The FDA also expanded approval of the companion diagnostic, BRACAnalysis CDx, to include the detection of BRCA mutations in blood samples from patients with breast cancer.
A capsule form of olaparib (Lynparza) was first approved in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. In August 2017, the FDA granted regular approval to olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network, the FDA said.
Approval for the treatment of breast cancer was based on a 2.8 month improvement in progression-free survival with olaparib vs standard chemotherapy in the phase 3 OlympiAD trial of 302 previously treated patients with BRCA-positive, HER2-negative breast cancer. Results of the trial were presented at ASCO 2017 and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1706450).
Common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.
Severe side effects include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis. Women should be advised of the potential risk to the fetus and to use effective contraception, the FDA said.
The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP and the approval of the BRACAnalysis CDx to Myriad Genetic Laboratories, Inc.
Prescribe antibiotics wisely
Clinical question: What is the incidence of antibiotic-associated adverse drug events (ADEs) among adult inpatients?
Background: Antibiotics are used widely in the inpatient setting, although 20%-30% of inpatient antibiotic prescription are estimated to be unnecessary. Data are lacking on the rates of associated ADEs.
Study design: Retrospective cohort study.
Synopsis: Of the 5,579 patients admitted to four inpatient medicine services between September 2013 and June 2014, 1,488 (27%) received antibiotics for at least 24 hours. Patients were followed through admission and out to 90 days. A total of 324 unique antibiotic-associated ADEs occurred among 298 (20%) patients within 90 days of initial therapy. The overall rate of antibiotic-associated ADEs was 22.9/10,000 person-days. The investigators determined that 287 (19%) of antibiotic regimens were not clinically indicated, and among those, there were 56 (20%) ADEs. The most common 30-day ADEs were gastrointestinal, renal, and hematologic. The highest proportion of ADEs occurred with beta-lactams, fluoroquinolones, intravenous vancomycin, and trimethoprim-sulfamethoxazole, perhaps reflecting how commonly these agents are prescribed. Nearly all ADEs were considered clinically significant (97%). There were no deaths attributable to antibiotic-associated ADEs.
Bottom line: Antibiotic associated ADEs occur in about one in five inpatients, and about one in five antibiotic prescriptions may not be clinically indicated.
Citation: Tamma PD et al. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017 Sep 1;177(9):1308-15.
Dr. Anderson is an associate program director in the internal medicine residency training program at the University of Colorado School of Medicine and a hospitalist at the VA Eastern Colorado Health Care System in Denver.
Clinical question: What is the incidence of antibiotic-associated adverse drug events (ADEs) among adult inpatients?
Background: Antibiotics are used widely in the inpatient setting, although 20%-30% of inpatient antibiotic prescription are estimated to be unnecessary. Data are lacking on the rates of associated ADEs.
Study design: Retrospective cohort study.
Synopsis: Of the 5,579 patients admitted to four inpatient medicine services between September 2013 and June 2014, 1,488 (27%) received antibiotics for at least 24 hours. Patients were followed through admission and out to 90 days. A total of 324 unique antibiotic-associated ADEs occurred among 298 (20%) patients within 90 days of initial therapy. The overall rate of antibiotic-associated ADEs was 22.9/10,000 person-days. The investigators determined that 287 (19%) of antibiotic regimens were not clinically indicated, and among those, there were 56 (20%) ADEs. The most common 30-day ADEs were gastrointestinal, renal, and hematologic. The highest proportion of ADEs occurred with beta-lactams, fluoroquinolones, intravenous vancomycin, and trimethoprim-sulfamethoxazole, perhaps reflecting how commonly these agents are prescribed. Nearly all ADEs were considered clinically significant (97%). There were no deaths attributable to antibiotic-associated ADEs.
Bottom line: Antibiotic associated ADEs occur in about one in five inpatients, and about one in five antibiotic prescriptions may not be clinically indicated.
Citation: Tamma PD et al. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017 Sep 1;177(9):1308-15.
Dr. Anderson is an associate program director in the internal medicine residency training program at the University of Colorado School of Medicine and a hospitalist at the VA Eastern Colorado Health Care System in Denver.
Clinical question: What is the incidence of antibiotic-associated adverse drug events (ADEs) among adult inpatients?
Background: Antibiotics are used widely in the inpatient setting, although 20%-30% of inpatient antibiotic prescription are estimated to be unnecessary. Data are lacking on the rates of associated ADEs.
Study design: Retrospective cohort study.
Synopsis: Of the 5,579 patients admitted to four inpatient medicine services between September 2013 and June 2014, 1,488 (27%) received antibiotics for at least 24 hours. Patients were followed through admission and out to 90 days. A total of 324 unique antibiotic-associated ADEs occurred among 298 (20%) patients within 90 days of initial therapy. The overall rate of antibiotic-associated ADEs was 22.9/10,000 person-days. The investigators determined that 287 (19%) of antibiotic regimens were not clinically indicated, and among those, there were 56 (20%) ADEs. The most common 30-day ADEs were gastrointestinal, renal, and hematologic. The highest proportion of ADEs occurred with beta-lactams, fluoroquinolones, intravenous vancomycin, and trimethoprim-sulfamethoxazole, perhaps reflecting how commonly these agents are prescribed. Nearly all ADEs were considered clinically significant (97%). There were no deaths attributable to antibiotic-associated ADEs.
Bottom line: Antibiotic associated ADEs occur in about one in five inpatients, and about one in five antibiotic prescriptions may not be clinically indicated.
Citation: Tamma PD et al. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017 Sep 1;177(9):1308-15.
Dr. Anderson is an associate program director in the internal medicine residency training program at the University of Colorado School of Medicine and a hospitalist at the VA Eastern Colorado Health Care System in Denver.
Closing the Timing Gap Between HIV Infection and Diagnosis
In 2015, nearly 40,000 people were diagnosed with HIV infection. Half of those had been living with HIV for at least 3 years. One-quarter had been infected for ≥ 7 years.
But now HIV is being diagnosed sooner than before after infection. The estimated median time from infection to diagnosis in 2015 was 3 years compared with 3 years and 7 months in 2011, according to a CDC Vital Signs report.
Estimated median time from infection to diagnosis ranged from 5 years for heterosexual men to 2 and one-half for heterosexual women and women who inject drugs. The median time was 4 years for Asian Americans, 3 years for African Americans and Latinos, and 2 years for whites.
The percentage of people at high risk for HIV who report getting a test the previous year also has risen. Despite that progress, though, the CDC says “too few are tested.”
In 2015, nearly 40,000 people were diagnosed with HIV infection. Half of those had been living with HIV for at least 3 years. One-quarter had been infected for ≥ 7 years.
But now HIV is being diagnosed sooner than before after infection. The estimated median time from infection to diagnosis in 2015 was 3 years compared with 3 years and 7 months in 2011, according to a CDC Vital Signs report.
Estimated median time from infection to diagnosis ranged from 5 years for heterosexual men to 2 and one-half for heterosexual women and women who inject drugs. The median time was 4 years for Asian Americans, 3 years for African Americans and Latinos, and 2 years for whites.
The percentage of people at high risk for HIV who report getting a test the previous year also has risen. Despite that progress, though, the CDC says “too few are tested.”
In 2015, nearly 40,000 people were diagnosed with HIV infection. Half of those had been living with HIV for at least 3 years. One-quarter had been infected for ≥ 7 years.
But now HIV is being diagnosed sooner than before after infection. The estimated median time from infection to diagnosis in 2015 was 3 years compared with 3 years and 7 months in 2011, according to a CDC Vital Signs report.
Estimated median time from infection to diagnosis ranged from 5 years for heterosexual men to 2 and one-half for heterosexual women and women who inject drugs. The median time was 4 years for Asian Americans, 3 years for African Americans and Latinos, and 2 years for whites.
The percentage of people at high risk for HIV who report getting a test the previous year also has risen. Despite that progress, though, the CDC says “too few are tested.”
Clinical Trial Begins for Long-Acting Anti-HIV Injectable
A clinical trial to test a new, potentially more convenient HIV prophylaxis for women is starting in Africa. It is a long-acting form of the investigational drug cabotegravir and could give sexually active women a choice of biomedical HIV prevention tools for the first time, similar to the choices available for contraception, says Sinead Delany-Moretiwe, PhD, chair of the protocol.
The trial, HPTN 084, will enroll about 3,200 women aged 18 to 45 years at 20 sites in 7 countries. The women will be randomly assigned to either cabotegravir and a placebo pill or Truvada, which is a combination of emtricitabine and tenofovir disoproxil fumarate. Truvada, currently the only drug licensed for HIV pre-exposure prophylaxis, must be taken every day to achieve and maintain protective drug concentrations. The women will start with 2 cabotegravir injections 4 weeks apart, then receive injections once every 8 weeks for an average of 2.6 years. After completing the injections, participants will be offered 48 weeks of PrEP with daily oral Truvada.
The NIAID is sponsoring the phase 3 clinical trial and cofunding it in a unique partnership with ViiV Healthcare (which is providing the study medications with Gilead Sciences) and the Bill & Melinda Gates Foundation.
Participants will receive HIV prevention counseling, condoms and lubricant, and counseling to support adherence to the daily pill. Anyone who becomes HIV infected during the trial will stop receiving the study products and be referred to local medical providers for care and treatment.
The study also will evaluate how women experience long-acting injectable cabotegravir, the researchers say. They are hoping to get a better understanding of the types of safe and effective HIV prevention that also fit best in women’s lives.
A clinical trial to test a new, potentially more convenient HIV prophylaxis for women is starting in Africa. It is a long-acting form of the investigational drug cabotegravir and could give sexually active women a choice of biomedical HIV prevention tools for the first time, similar to the choices available for contraception, says Sinead Delany-Moretiwe, PhD, chair of the protocol.
The trial, HPTN 084, will enroll about 3,200 women aged 18 to 45 years at 20 sites in 7 countries. The women will be randomly assigned to either cabotegravir and a placebo pill or Truvada, which is a combination of emtricitabine and tenofovir disoproxil fumarate. Truvada, currently the only drug licensed for HIV pre-exposure prophylaxis, must be taken every day to achieve and maintain protective drug concentrations. The women will start with 2 cabotegravir injections 4 weeks apart, then receive injections once every 8 weeks for an average of 2.6 years. After completing the injections, participants will be offered 48 weeks of PrEP with daily oral Truvada.
The NIAID is sponsoring the phase 3 clinical trial and cofunding it in a unique partnership with ViiV Healthcare (which is providing the study medications with Gilead Sciences) and the Bill & Melinda Gates Foundation.
Participants will receive HIV prevention counseling, condoms and lubricant, and counseling to support adherence to the daily pill. Anyone who becomes HIV infected during the trial will stop receiving the study products and be referred to local medical providers for care and treatment.
The study also will evaluate how women experience long-acting injectable cabotegravir, the researchers say. They are hoping to get a better understanding of the types of safe and effective HIV prevention that also fit best in women’s lives.
A clinical trial to test a new, potentially more convenient HIV prophylaxis for women is starting in Africa. It is a long-acting form of the investigational drug cabotegravir and could give sexually active women a choice of biomedical HIV prevention tools for the first time, similar to the choices available for contraception, says Sinead Delany-Moretiwe, PhD, chair of the protocol.
The trial, HPTN 084, will enroll about 3,200 women aged 18 to 45 years at 20 sites in 7 countries. The women will be randomly assigned to either cabotegravir and a placebo pill or Truvada, which is a combination of emtricitabine and tenofovir disoproxil fumarate. Truvada, currently the only drug licensed for HIV pre-exposure prophylaxis, must be taken every day to achieve and maintain protective drug concentrations. The women will start with 2 cabotegravir injections 4 weeks apart, then receive injections once every 8 weeks for an average of 2.6 years. After completing the injections, participants will be offered 48 weeks of PrEP with daily oral Truvada.
The NIAID is sponsoring the phase 3 clinical trial and cofunding it in a unique partnership with ViiV Healthcare (which is providing the study medications with Gilead Sciences) and the Bill & Melinda Gates Foundation.
Participants will receive HIV prevention counseling, condoms and lubricant, and counseling to support adherence to the daily pill. Anyone who becomes HIV infected during the trial will stop receiving the study products and be referred to local medical providers for care and treatment.
The study also will evaluate how women experience long-acting injectable cabotegravir, the researchers say. They are hoping to get a better understanding of the types of safe and effective HIV prevention that also fit best in women’s lives.
Interventions can increase cord blood donations
Simple interventions can increase cord blood donations, according to research published in Scientific Reports.
Researchers saw a significant increase in cord blood donation when expectant mothers received information about the procedure and were asked to indicate their interest in donating at both early and late stages of their pregnancies.
“We more than doubled the number of cord blood units that were collected,” said study author Nicola Lacetera, PhD, of the University of Toronto Mississauga in Ontario, Canada.
“We learned a lot, and we did a little bit of good too, so that feels nice.”
Dr Lacetera and his colleagues conducted this study in Milan, Italy, where private cord blood banking is banned.
The team set out to determine if providing expectant mothers with information about cord blood donation and prompting them to consider the procedure would increase donations to a public cord blood bank.
Interventions
The researchers enrolled 850 expectant mothers and divided them into 6 treatment cohorts.
The T0 cohort included 217 control subjects who did not receive any information on cord blood donation.
The T1 cohort included 64 subjects who received information on cord blood donation during their first trimester.
The T2 cohort included 88 subjects who were given information on cord blood donation and asked about their intentions to donate in their first trimester.
The T3 cohort included 197 subjects who received information on cord blood donation in their third trimester.
The T4 cohort included 249 subjects who were given information on cord blood donation and asked about their intentions to donate during their third trimester.
The T5 cohort included 35 subjects who were given information on cord blood donation and asked about their intentions to donate during the first trimester and the third trimester.
Results
The researchers found that T5 subjects had the highest donation rate.
In the entire study sample, the donation rate was 2.3% (5/217) in controls, 6.3% (4/64) in T1 subjects, 1.1% (1/88) in T2, 8.1% (16/197) in T3, 10.0% (25/249) in T4, and 17.1% in T5 (6/35).
These results may not be entirely accurate, however, because the researchers could only confirm patients’ donation status if mothers delivered their babies at the study hospital, Ospedale dei Bambini Vittore Buzzi (also known as Buzzi Hospital, BH).
Among women who delivered at BH, donation rates were 2.7% (5/183) in controls, 11.7% (4/34) in T1, 2.2% (1/45) in T2, 8.9% (16/179) in T3, 11.4% (25/42) in T4, and 21.4% (6/28) in T5.
Though these data suggest the various interventions tested can increase cord blood donations, donation rates in this study could have been even higher, according to the researchers.
There were 197 women who submitted consent forms to donate cord blood, were medically eligible to donate, and delivered their babies at BH. However, only 57 of these women successfully donated cord blood.
There were 62 women (56.9%) who could not donate because of medical complications during delivery.
Thirty-three women (30.3%) failed to donate because of organizational reasons, including overcrowding of the delivery room and the absence of obstetric nurses certified to collect and process cord blood at the time of delivery.
There were 14 women (7.1%) who did not donate for institution-related reasons. For example, the women gave birth when the Milan Cord Blood Bank was closed.
There were no details on the remaining 31 women who failed to donate. 
Simple interventions can increase cord blood donations, according to research published in Scientific Reports.
Researchers saw a significant increase in cord blood donation when expectant mothers received information about the procedure and were asked to indicate their interest in donating at both early and late stages of their pregnancies.
“We more than doubled the number of cord blood units that were collected,” said study author Nicola Lacetera, PhD, of the University of Toronto Mississauga in Ontario, Canada.
“We learned a lot, and we did a little bit of good too, so that feels nice.”
Dr Lacetera and his colleagues conducted this study in Milan, Italy, where private cord blood banking is banned.
The team set out to determine if providing expectant mothers with information about cord blood donation and prompting them to consider the procedure would increase donations to a public cord blood bank.
Interventions
The researchers enrolled 850 expectant mothers and divided them into 6 treatment cohorts.
The T0 cohort included 217 control subjects who did not receive any information on cord blood donation.
The T1 cohort included 64 subjects who received information on cord blood donation during their first trimester.
The T2 cohort included 88 subjects who were given information on cord blood donation and asked about their intentions to donate in their first trimester.
The T3 cohort included 197 subjects who received information on cord blood donation in their third trimester.
The T4 cohort included 249 subjects who were given information on cord blood donation and asked about their intentions to donate during their third trimester.
The T5 cohort included 35 subjects who were given information on cord blood donation and asked about their intentions to donate during the first trimester and the third trimester.
Results
The researchers found that T5 subjects had the highest donation rate.
In the entire study sample, the donation rate was 2.3% (5/217) in controls, 6.3% (4/64) in T1 subjects, 1.1% (1/88) in T2, 8.1% (16/197) in T3, 10.0% (25/249) in T4, and 17.1% in T5 (6/35).
These results may not be entirely accurate, however, because the researchers could only confirm patients’ donation status if mothers delivered their babies at the study hospital, Ospedale dei Bambini Vittore Buzzi (also known as Buzzi Hospital, BH).
Among women who delivered at BH, donation rates were 2.7% (5/183) in controls, 11.7% (4/34) in T1, 2.2% (1/45) in T2, 8.9% (16/179) in T3, 11.4% (25/42) in T4, and 21.4% (6/28) in T5.
Though these data suggest the various interventions tested can increase cord blood donations, donation rates in this study could have been even higher, according to the researchers.
There were 197 women who submitted consent forms to donate cord blood, were medically eligible to donate, and delivered their babies at BH. However, only 57 of these women successfully donated cord blood.
There were 62 women (56.9%) who could not donate because of medical complications during delivery.
Thirty-three women (30.3%) failed to donate because of organizational reasons, including overcrowding of the delivery room and the absence of obstetric nurses certified to collect and process cord blood at the time of delivery.
There were 14 women (7.1%) who did not donate for institution-related reasons. For example, the women gave birth when the Milan Cord Blood Bank was closed.
There were no details on the remaining 31 women who failed to donate.
Simple interventions can increase cord blood donations, according to research published in Scientific Reports.
Researchers saw a significant increase in cord blood donation when expectant mothers received information about the procedure and were asked to indicate their interest in donating at both early and late stages of their pregnancies.
“We more than doubled the number of cord blood units that were collected,” said study author Nicola Lacetera, PhD, of the University of Toronto Mississauga in Ontario, Canada.
“We learned a lot, and we did a little bit of good too, so that feels nice.”
Dr Lacetera and his colleagues conducted this study in Milan, Italy, where private cord blood banking is banned.
The team set out to determine if providing expectant mothers with information about cord blood donation and prompting them to consider the procedure would increase donations to a public cord blood bank.
Interventions
The researchers enrolled 850 expectant mothers and divided them into 6 treatment cohorts.
The T0 cohort included 217 control subjects who did not receive any information on cord blood donation.
The T1 cohort included 64 subjects who received information on cord blood donation during their first trimester.
The T2 cohort included 88 subjects who were given information on cord blood donation and asked about their intentions to donate in their first trimester.
The T3 cohort included 197 subjects who received information on cord blood donation in their third trimester.
The T4 cohort included 249 subjects who were given information on cord blood donation and asked about their intentions to donate during their third trimester.
The T5 cohort included 35 subjects who were given information on cord blood donation and asked about their intentions to donate during the first trimester and the third trimester.
Results
The researchers found that T5 subjects had the highest donation rate.
In the entire study sample, the donation rate was 2.3% (5/217) in controls, 6.3% (4/64) in T1 subjects, 1.1% (1/88) in T2, 8.1% (16/197) in T3, 10.0% (25/249) in T4, and 17.1% in T5 (6/35).
These results may not be entirely accurate, however, because the researchers could only confirm patients’ donation status if mothers delivered their babies at the study hospital, Ospedale dei Bambini Vittore Buzzi (also known as Buzzi Hospital, BH).
Among women who delivered at BH, donation rates were 2.7% (5/183) in controls, 11.7% (4/34) in T1, 2.2% (1/45) in T2, 8.9% (16/179) in T3, 11.4% (25/42) in T4, and 21.4% (6/28) in T5.
Though these data suggest the various interventions tested can increase cord blood donations, donation rates in this study could have been even higher, according to the researchers.
There were 197 women who submitted consent forms to donate cord blood, were medically eligible to donate, and delivered their babies at BH. However, only 57 of these women successfully donated cord blood.
There were 62 women (56.9%) who could not donate because of medical complications during delivery.
Thirty-three women (30.3%) failed to donate because of organizational reasons, including overcrowding of the delivery room and the absence of obstetric nurses certified to collect and process cord blood at the time of delivery.
There were 14 women (7.1%) who did not donate for institution-related reasons. For example, the women gave birth when the Milan Cord Blood Bank was closed.
There were no details on the remaining 31 women who failed to donate.
EMA recommends orphan designation for pracinostat
The European Medicines Agency (EMA) has recommended that pracinostat receive orphan drug designation.
Pracinostat is an oral histone deacetylase inhibitor currently under investigation in a phase 3 study in combination with azacitidine for the treatment of acute myeloid leukemia (AML) in adult patients unfit to receive induction chemotherapy.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure. The designation also provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
Phase 2 study
The EMA’s recommendation that pracinostat receive orphan drug designation is based on results of a phase 2 study, which were presented at the 2016 ASH Annual Meeting.
The study included 50 patients who had a median age of 75 (range, 66-84). Sixty-six percent of patients had de novo AML, and 34% had secondary AML.
The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine at 75 mg/m2 subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.
As of October 15, 2016, 90% of patients had discontinued treatment, 42% due to progressive disease, 28% due to adverse events (AEs), 14% due to patient decision, and 6% due to investigator decision.
Fifty-two percent of patients (n=26) achieved the primary endpoint of complete response (CR) plus CR with incomplete count recovery (CRi) plus morphologic leukemia-free state (MLFS).
Forty-two percent of patients had a CR, 4% had a CRi, and 6% achieved MLFS. The median duration of CR/CRi/MLFS was 13.2 months. The median duration of CR/CRi was 17.2 months.
The median overall survival was 19.1 months. The 1-year survival rate was 62%, and the 2-year survival rate was 41%.
The most common treatment-emergent AEs were nausea (78%), constipation (70%), fatigue (62%), decreased appetite (56%), diarrhea (50%), vomiting (40%), cough (36%), dyspnea (34%), hypokalemia (34%), peripheral edema (34%), pyrexia (34%), dizziness (32%), back pain (28%), insomnia (28%), febrile neutropenia (48%), thrombocytopenia (46%), anemia (38%), and neutropenia (38%).
Treatment-emergent AEs led to discontinuation in 14 patients. Three of these patients developed sepsis that proved fatal.
The other AEs leading to discontinuation included grade 3 acute axonal neuropathy, grade 3 parainfluenza, grade 3 prolonged QTc/atrial fibrillation, grade 1 acute kidney injury, grade 3 diverticulitis, grade 3 supraglottic ulcer, grade 2 upper respiratory infection, grade 3 fatigue (n=2), and grades 1 and 3 intermittent fatigue (n=2).
The European Medicines Agency (EMA) has recommended that pracinostat receive orphan drug designation.
Pracinostat is an oral histone deacetylase inhibitor currently under investigation in a phase 3 study in combination with azacitidine for the treatment of acute myeloid leukemia (AML) in adult patients unfit to receive induction chemotherapy.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure. The designation also provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
Phase 2 study
The EMA’s recommendation that pracinostat receive orphan drug designation is based on results of a phase 2 study, which were presented at the 2016 ASH Annual Meeting.
The study included 50 patients who had a median age of 75 (range, 66-84). Sixty-six percent of patients had de novo AML, and 34% had secondary AML.
The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine at 75 mg/m2 subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.
As of October 15, 2016, 90% of patients had discontinued treatment, 42% due to progressive disease, 28% due to adverse events (AEs), 14% due to patient decision, and 6% due to investigator decision.
Fifty-two percent of patients (n=26) achieved the primary endpoint of complete response (CR) plus CR with incomplete count recovery (CRi) plus morphologic leukemia-free state (MLFS).
Forty-two percent of patients had a CR, 4% had a CRi, and 6% achieved MLFS. The median duration of CR/CRi/MLFS was 13.2 months. The median duration of CR/CRi was 17.2 months.
The median overall survival was 19.1 months. The 1-year survival rate was 62%, and the 2-year survival rate was 41%.
The most common treatment-emergent AEs were nausea (78%), constipation (70%), fatigue (62%), decreased appetite (56%), diarrhea (50%), vomiting (40%), cough (36%), dyspnea (34%), hypokalemia (34%), peripheral edema (34%), pyrexia (34%), dizziness (32%), back pain (28%), insomnia (28%), febrile neutropenia (48%), thrombocytopenia (46%), anemia (38%), and neutropenia (38%).
Treatment-emergent AEs led to discontinuation in 14 patients. Three of these patients developed sepsis that proved fatal.
The other AEs leading to discontinuation included grade 3 acute axonal neuropathy, grade 3 parainfluenza, grade 3 prolonged QTc/atrial fibrillation, grade 1 acute kidney injury, grade 3 diverticulitis, grade 3 supraglottic ulcer, grade 2 upper respiratory infection, grade 3 fatigue (n=2), and grades 1 and 3 intermittent fatigue (n=2).
The European Medicines Agency (EMA) has recommended that pracinostat receive orphan drug designation.
Pracinostat is an oral histone deacetylase inhibitor currently under investigation in a phase 3 study in combination with azacitidine for the treatment of acute myeloid leukemia (AML) in adult patients unfit to receive induction chemotherapy.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure. The designation also provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
Phase 2 study
The EMA’s recommendation that pracinostat receive orphan drug designation is based on results of a phase 2 study, which were presented at the 2016 ASH Annual Meeting.
The study included 50 patients who had a median age of 75 (range, 66-84). Sixty-six percent of patients had de novo AML, and 34% had secondary AML.
The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine at 75 mg/m2 subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.
As of October 15, 2016, 90% of patients had discontinued treatment, 42% due to progressive disease, 28% due to adverse events (AEs), 14% due to patient decision, and 6% due to investigator decision.
Fifty-two percent of patients (n=26) achieved the primary endpoint of complete response (CR) plus CR with incomplete count recovery (CRi) plus morphologic leukemia-free state (MLFS).
Forty-two percent of patients had a CR, 4% had a CRi, and 6% achieved MLFS. The median duration of CR/CRi/MLFS was 13.2 months. The median duration of CR/CRi was 17.2 months.
The median overall survival was 19.1 months. The 1-year survival rate was 62%, and the 2-year survival rate was 41%.
The most common treatment-emergent AEs were nausea (78%), constipation (70%), fatigue (62%), decreased appetite (56%), diarrhea (50%), vomiting (40%), cough (36%), dyspnea (34%), hypokalemia (34%), peripheral edema (34%), pyrexia (34%), dizziness (32%), back pain (28%), insomnia (28%), febrile neutropenia (48%), thrombocytopenia (46%), anemia (38%), and neutropenia (38%).
Treatment-emergent AEs led to discontinuation in 14 patients. Three of these patients developed sepsis that proved fatal.
The other AEs leading to discontinuation included grade 3 acute axonal neuropathy, grade 3 parainfluenza, grade 3 prolonged QTc/atrial fibrillation, grade 1 acute kidney injury, grade 3 diverticulitis, grade 3 supraglottic ulcer, grade 2 upper respiratory infection, grade 3 fatigue (n=2), and grades 1 and 3 intermittent fatigue (n=2).
Dental Health: What It Means in Kidney Disease
Q) I teach nephrology at a local PA program, and they want us to integrate dental care into each module. What’s the connection between the two?
Dental health is frequently overlooked in the medical realm, as many clinicians feel that dental issues are out of our purview. Hematuria worries us, but bleeding gums and other signs of periodontal disease are often ignored. Surprisingly, many patients don’t seem to mind when their gums bleed every time they brush; they believe that this is normal, when really, it’s not.
Growing evidence supports associations between dental health and multiple medical issues—chronic kidney disease (CKD) among them. Periodontal disease is one of several inflammatory diseases caused by an interaction between gram-negative periodontal bacterial species and the immune system. It manifests with sore, red, bleeding gums and can lead to tooth loss if left untreated.
Chronic inflammation in the gums is a good indicator of inflammation elsewhere in the body. In and of itself, periodontitis can set off an inflammatory cascade in the body. Poor dentition can also lead to poor nutrition, which then causes a feedback loop, leading to even more inflammation.
Patients with periodontal disease have higher levels of C-reactive protein and a higher erythrocyte sedimentation rate than those without the disease.1 And a recent study by Zhang et al showed that periodontal disease increased risk for all-cause mortality in patients with CKD.2
The high cost of CKD from both a financial and personal view makes any intervention worth exploring, as the risk factors are difficult to modify and the CKD population is growing worldwide. We, as medical providers, should reiterate what our dental colleagues have been saying for years: Encourage patients with CKD to practice good dental hygiene by brushing twice a day and flossing daily, in an attempt to improve their overall outcomes.
LCDR Julie Taylor, PA-C
United States Public Health Service, Boston
1. Zhang J, Jiang H, Sun M, Chen J. Association between periodontal disease and mortality in people with CKD: a meta-analysis of cohort studies. BMC Nephrol. 2017;18(1):269.
2. Chen YT, Shin CJ, Ou SM, et al; Taiwan Geriatric Kidney Disease (TGKD) Research Group. Periodontal disease and risks of kidney function decline and mortality in older people: a community-based cohort study. Am J Kidney Dis. 2015; 66(2):223-230.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation's Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month's responses were authored by Nicole DeFeo McCormick, DNP, MBA, NP-C, CCTC, who is an Assistant Professor in the School of Medicine at the University of Colorado, and LCDR Julie Cure, PA-C, who is with the United States Public Health Service in Boston.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation's Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month's responses were authored by Nicole DeFeo McCormick, DNP, MBA, NP-C, CCTC, who is an Assistant Professor in the School of Medicine at the University of Colorado, and LCDR Julie Cure, PA-C, who is with the United States Public Health Service in Boston.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation's Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month's responses were authored by Nicole DeFeo McCormick, DNP, MBA, NP-C, CCTC, who is an Assistant Professor in the School of Medicine at the University of Colorado, and LCDR Julie Cure, PA-C, who is with the United States Public Health Service in Boston.
Q) I teach nephrology at a local PA program, and they want us to integrate dental care into each module. What’s the connection between the two?
Dental health is frequently overlooked in the medical realm, as many clinicians feel that dental issues are out of our purview. Hematuria worries us, but bleeding gums and other signs of periodontal disease are often ignored. Surprisingly, many patients don’t seem to mind when their gums bleed every time they brush; they believe that this is normal, when really, it’s not.
Growing evidence supports associations between dental health and multiple medical issues—chronic kidney disease (CKD) among them. Periodontal disease is one of several inflammatory diseases caused by an interaction between gram-negative periodontal bacterial species and the immune system. It manifests with sore, red, bleeding gums and can lead to tooth loss if left untreated.
Chronic inflammation in the gums is a good indicator of inflammation elsewhere in the body. In and of itself, periodontitis can set off an inflammatory cascade in the body. Poor dentition can also lead to poor nutrition, which then causes a feedback loop, leading to even more inflammation.
Patients with periodontal disease have higher levels of C-reactive protein and a higher erythrocyte sedimentation rate than those without the disease.1 And a recent study by Zhang et al showed that periodontal disease increased risk for all-cause mortality in patients with CKD.2
The high cost of CKD from both a financial and personal view makes any intervention worth exploring, as the risk factors are difficult to modify and the CKD population is growing worldwide. We, as medical providers, should reiterate what our dental colleagues have been saying for years: Encourage patients with CKD to practice good dental hygiene by brushing twice a day and flossing daily, in an attempt to improve their overall outcomes.
LCDR Julie Taylor, PA-C
United States Public Health Service, Boston
Q) I teach nephrology at a local PA program, and they want us to integrate dental care into each module. What’s the connection between the two?
Dental health is frequently overlooked in the medical realm, as many clinicians feel that dental issues are out of our purview. Hematuria worries us, but bleeding gums and other signs of periodontal disease are often ignored. Surprisingly, many patients don’t seem to mind when their gums bleed every time they brush; they believe that this is normal, when really, it’s not.
Growing evidence supports associations between dental health and multiple medical issues—chronic kidney disease (CKD) among them. Periodontal disease is one of several inflammatory diseases caused by an interaction between gram-negative periodontal bacterial species and the immune system. It manifests with sore, red, bleeding gums and can lead to tooth loss if left untreated.
Chronic inflammation in the gums is a good indicator of inflammation elsewhere in the body. In and of itself, periodontitis can set off an inflammatory cascade in the body. Poor dentition can also lead to poor nutrition, which then causes a feedback loop, leading to even more inflammation.
Patients with periodontal disease have higher levels of C-reactive protein and a higher erythrocyte sedimentation rate than those without the disease.1 And a recent study by Zhang et al showed that periodontal disease increased risk for all-cause mortality in patients with CKD.2
The high cost of CKD from both a financial and personal view makes any intervention worth exploring, as the risk factors are difficult to modify and the CKD population is growing worldwide. We, as medical providers, should reiterate what our dental colleagues have been saying for years: Encourage patients with CKD to practice good dental hygiene by brushing twice a day and flossing daily, in an attempt to improve their overall outcomes.
LCDR Julie Taylor, PA-C
United States Public Health Service, Boston
1. Zhang J, Jiang H, Sun M, Chen J. Association between periodontal disease and mortality in people with CKD: a meta-analysis of cohort studies. BMC Nephrol. 2017;18(1):269.
2. Chen YT, Shin CJ, Ou SM, et al; Taiwan Geriatric Kidney Disease (TGKD) Research Group. Periodontal disease and risks of kidney function decline and mortality in older people: a community-based cohort study. Am J Kidney Dis. 2015; 66(2):223-230.
1. Zhang J, Jiang H, Sun M, Chen J. Association between periodontal disease and mortality in people with CKD: a meta-analysis of cohort studies. BMC Nephrol. 2017;18(1):269.
2. Chen YT, Shin CJ, Ou SM, et al; Taiwan Geriatric Kidney Disease (TGKD) Research Group. Periodontal disease and risks of kidney function decline and mortality in older people: a community-based cohort study. Am J Kidney Dis. 2015; 66(2):223-230.
FDA: No more codeine or hydrocodone cold medicines for children
New safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone limit their use to adults 18 years or older.
The Food and Drug Administration took this action after “conducting an extensive review and convening a panel of outside experts,” which determined that the risks of these medicines outweigh their benefits in children younger than 18 years. The agency also is requiring companies to add a boxed warning to drug labels for prescription cough and cold medicines containing codeine or hydrocodone about the “risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing,” according to an FDA safety announcement.
Common side effects of opioids include drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath, and headache, according to the press release.
Reassure parents that cough because of a cold or upper respiratory infection is self-limited and generally does not need to be treated, the FDA advised. If children do need cough treatment, there are over-the-counter products such as dextromethorphan, as well as prescription benzonatate products, the FDA said. Encourage parents to check labels of nonprescription cough and cold products.
In a few states, some codeine cough medicines are available OTC. The FDA is considering regulatory action for these products, according to the safety announcement.
New safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone limit their use to adults 18 years or older.
The Food and Drug Administration took this action after “conducting an extensive review and convening a panel of outside experts,” which determined that the risks of these medicines outweigh their benefits in children younger than 18 years. The agency also is requiring companies to add a boxed warning to drug labels for prescription cough and cold medicines containing codeine or hydrocodone about the “risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing,” according to an FDA safety announcement.
Common side effects of opioids include drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath, and headache, according to the press release.
Reassure parents that cough because of a cold or upper respiratory infection is self-limited and generally does not need to be treated, the FDA advised. If children do need cough treatment, there are over-the-counter products such as dextromethorphan, as well as prescription benzonatate products, the FDA said. Encourage parents to check labels of nonprescription cough and cold products.
In a few states, some codeine cough medicines are available OTC. The FDA is considering regulatory action for these products, according to the safety announcement.
New safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone limit their use to adults 18 years or older.
The Food and Drug Administration took this action after “conducting an extensive review and convening a panel of outside experts,” which determined that the risks of these medicines outweigh their benefits in children younger than 18 years. The agency also is requiring companies to add a boxed warning to drug labels for prescription cough and cold medicines containing codeine or hydrocodone about the “risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing,” according to an FDA safety announcement.
Common side effects of opioids include drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath, and headache, according to the press release.
Reassure parents that cough because of a cold or upper respiratory infection is self-limited and generally does not need to be treated, the FDA advised. If children do need cough treatment, there are over-the-counter products such as dextromethorphan, as well as prescription benzonatate products, the FDA said. Encourage parents to check labels of nonprescription cough and cold products.
In a few states, some codeine cough medicines are available OTC. The FDA is considering regulatory action for these products, according to the safety announcement.
AUDIO: Immunotherapy’s role in NHL
ATLANTA – The use of immune checkpoint blockade is increasingly becoming standard therapy in Hodgkin lymphoma, but this approach has so far garnered mixed results in non-Hodgkin lymphoma, Stephen Ansell, MD, PhD, said at the annual meeting of the American Society of Hematology.
In an interview, Dr. Ansell, professor of medicine and chair of the lymphoma group at the Mayo Clinic, Rochester, Minn., said responses have been variable with promising results from immune checkpoint inhibitors in primary mediastinal large B-cell lymphoma, some NK/T-cell lymphomas, and primary CNS lymphoma. However, responses have been modest in low-grade lymphoma.
Dr. Ansell, who chaired a session at ASH 2017 on immunotherapy’s expanding role in non-Hodgkin lymphoma, said one of the major challenges of using immune checkpoint blockade in non-Hodgkin lymphoma is the complicated biology. For example, there are a lot of regulatory T cells that actually inhibit the immune response, and many of the T cells that are present within the tumor have an exhausted phenotype and are poorly functioning. Additionally, some of the cytokines that would seem to be stimulating the immune system can, over time, slowly produce T-cell exhaustion.
“Sort of like too much of a good thing ends up being a bad thing,” he said.
These are the issues that are fueling research today, Dr. Ansell said. Going forward he said he expects to see more combination approaches to therapy, such as using an agonistic positive signal plus the blocking of an inhibitory signal with chemotherapy.
Dr. Ansell reported that Mayo Clinic receives clinical trial support from Merck, Bristol-Myers Squibb, Seattle Genetics, Trillium, and Affimed.
ATLANTA – The use of immune checkpoint blockade is increasingly becoming standard therapy in Hodgkin lymphoma, but this approach has so far garnered mixed results in non-Hodgkin lymphoma, Stephen Ansell, MD, PhD, said at the annual meeting of the American Society of Hematology.
In an interview, Dr. Ansell, professor of medicine and chair of the lymphoma group at the Mayo Clinic, Rochester, Minn., said responses have been variable with promising results from immune checkpoint inhibitors in primary mediastinal large B-cell lymphoma, some NK/T-cell lymphomas, and primary CNS lymphoma. However, responses have been modest in low-grade lymphoma.
Dr. Ansell, who chaired a session at ASH 2017 on immunotherapy’s expanding role in non-Hodgkin lymphoma, said one of the major challenges of using immune checkpoint blockade in non-Hodgkin lymphoma is the complicated biology. For example, there are a lot of regulatory T cells that actually inhibit the immune response, and many of the T cells that are present within the tumor have an exhausted phenotype and are poorly functioning. Additionally, some of the cytokines that would seem to be stimulating the immune system can, over time, slowly produce T-cell exhaustion.
“Sort of like too much of a good thing ends up being a bad thing,” he said.
These are the issues that are fueling research today, Dr. Ansell said. Going forward he said he expects to see more combination approaches to therapy, such as using an agonistic positive signal plus the blocking of an inhibitory signal with chemotherapy.
Dr. Ansell reported that Mayo Clinic receives clinical trial support from Merck, Bristol-Myers Squibb, Seattle Genetics, Trillium, and Affimed.
ATLANTA – The use of immune checkpoint blockade is increasingly becoming standard therapy in Hodgkin lymphoma, but this approach has so far garnered mixed results in non-Hodgkin lymphoma, Stephen Ansell, MD, PhD, said at the annual meeting of the American Society of Hematology.
In an interview, Dr. Ansell, professor of medicine and chair of the lymphoma group at the Mayo Clinic, Rochester, Minn., said responses have been variable with promising results from immune checkpoint inhibitors in primary mediastinal large B-cell lymphoma, some NK/T-cell lymphomas, and primary CNS lymphoma. However, responses have been modest in low-grade lymphoma.
Dr. Ansell, who chaired a session at ASH 2017 on immunotherapy’s expanding role in non-Hodgkin lymphoma, said one of the major challenges of using immune checkpoint blockade in non-Hodgkin lymphoma is the complicated biology. For example, there are a lot of regulatory T cells that actually inhibit the immune response, and many of the T cells that are present within the tumor have an exhausted phenotype and are poorly functioning. Additionally, some of the cytokines that would seem to be stimulating the immune system can, over time, slowly produce T-cell exhaustion.
“Sort of like too much of a good thing ends up being a bad thing,” he said.
These are the issues that are fueling research today, Dr. Ansell said. Going forward he said he expects to see more combination approaches to therapy, such as using an agonistic positive signal plus the blocking of an inhibitory signal with chemotherapy.
Dr. Ansell reported that Mayo Clinic receives clinical trial support from Merck, Bristol-Myers Squibb, Seattle Genetics, Trillium, and Affimed.
EXPERT ANALYSIS FROM ASH 2017