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David Henry's JCSO podcast, January-February 2017
For the January-February issue of the Journal of Community and Supportive Oncology, the Editor in Chief, Dr David Henry, highlights a thought-provoking article by JCSO Editor, Dr Thomas Strouse, on end-of-life options and legal pathways to physician-assisted dying. He also features a guide by Dr Adam Bagg on the diagnosis and classification of lymphomas, and an in-depth examination of blood-based biopsies by Jane de Lartigue. Three Original Reports hone in on patient care and support and quality of care: a report on the Florida CaPCaS study documents the experiences and needs of black men at the point of prostate cancer diagnosis; another, among Spanish-speaking Latinas with breast cancer, addresses the posttreatment survivorship care needs of that population; and a third looks at strategies to improve the quality of care among head and neck cancer patients. Among the Journal’s regular offerings, the Community Translations section features the approvals of atezolizumab as a therapy for bladder cancer (the first in more than 30 years) and lenvatinib for renal cell carcinoma, and there are two Case Report, one on a patient with breast cancer who experienced severe hyponatremia with seizures associated with single-, low-dose cyclophosphamide, and another about paraneoplastic leukemoid reaction as a poor prognostic marker in a patient with urothelial bladder carcinoma.
Listen to the podcast below.
For the January-February issue of the Journal of Community and Supportive Oncology, the Editor in Chief, Dr David Henry, highlights a thought-provoking article by JCSO Editor, Dr Thomas Strouse, on end-of-life options and legal pathways to physician-assisted dying. He also features a guide by Dr Adam Bagg on the diagnosis and classification of lymphomas, and an in-depth examination of blood-based biopsies by Jane de Lartigue. Three Original Reports hone in on patient care and support and quality of care: a report on the Florida CaPCaS study documents the experiences and needs of black men at the point of prostate cancer diagnosis; another, among Spanish-speaking Latinas with breast cancer, addresses the posttreatment survivorship care needs of that population; and a third looks at strategies to improve the quality of care among head and neck cancer patients. Among the Journal’s regular offerings, the Community Translations section features the approvals of atezolizumab as a therapy for bladder cancer (the first in more than 30 years) and lenvatinib for renal cell carcinoma, and there are two Case Report, one on a patient with breast cancer who experienced severe hyponatremia with seizures associated with single-, low-dose cyclophosphamide, and another about paraneoplastic leukemoid reaction as a poor prognostic marker in a patient with urothelial bladder carcinoma.
Listen to the podcast below.
For the January-February issue of the Journal of Community and Supportive Oncology, the Editor in Chief, Dr David Henry, highlights a thought-provoking article by JCSO Editor, Dr Thomas Strouse, on end-of-life options and legal pathways to physician-assisted dying. He also features a guide by Dr Adam Bagg on the diagnosis and classification of lymphomas, and an in-depth examination of blood-based biopsies by Jane de Lartigue. Three Original Reports hone in on patient care and support and quality of care: a report on the Florida CaPCaS study documents the experiences and needs of black men at the point of prostate cancer diagnosis; another, among Spanish-speaking Latinas with breast cancer, addresses the posttreatment survivorship care needs of that population; and a third looks at strategies to improve the quality of care among head and neck cancer patients. Among the Journal’s regular offerings, the Community Translations section features the approvals of atezolizumab as a therapy for bladder cancer (the first in more than 30 years) and lenvatinib for renal cell carcinoma, and there are two Case Report, one on a patient with breast cancer who experienced severe hyponatremia with seizures associated with single-, low-dose cyclophosphamide, and another about paraneoplastic leukemoid reaction as a poor prognostic marker in a patient with urothelial bladder carcinoma.
Listen to the podcast below.
Drug could treat IDA in patients with NDD CKD
Photo courtesy of CDC
Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).
Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.
A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.
Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.
Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.
These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.
The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.
Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.
The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.
The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.
The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.
During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.
Efficacy
The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).
The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).
Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).
“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.
Safety
Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.
Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).
Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.
There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.
“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.
Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration. 
Photo courtesy of CDC
Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).
Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.
A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.
Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.
Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.
These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.
The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.
Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.
The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.
The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.
The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.
During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.
Efficacy
The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).
The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).
Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).
“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.
Safety
Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.
Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).
Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.
There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.
“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.
Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.
Photo courtesy of CDC
Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).
Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.
A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.
Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.
Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.
These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.
The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.
Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.
The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.
The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.
The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.
During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.
Efficacy
The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).
The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).
Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).
“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.
Safety
Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.
Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).
Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.
There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.
“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.
Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.
FDA issues CRL for IV formulation of antiemetic agent
chemotherapy
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.
An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.
The NDA for rolapitant IV is for the same indication.
The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.
TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.
The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.
TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.
During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.
“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.
chemotherapy
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.
An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.
The NDA for rolapitant IV is for the same indication.
The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.
TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.
The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.
TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.
During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.
“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.
chemotherapy
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.
An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.
The NDA for rolapitant IV is for the same indication.
The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.
TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.
The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.
TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.
During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.
“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.
Pulmonary rehabilitation helps wide range of COPD patients
Participation in at least 20 days of pulmonary rehabilitation by patients with chronic obstructive pulmonary disease (COPD) resulted in statistically significant improvements in quality of life, perception of health status, functional capacity, dyspnea, and depression, in a retrospective analysis.
Furthermore, improvements were seen regardless of the degree of exercise function, dyspnea, or lung function at baseline, reported lead investigator Praful Schroff.
The analysis focused on 229 COPD patients enrolled in the pulmonary rehabilitation program at UAB during 1996-2013, all of whom completed questionnaires both at enrollment and after completion of their respective exercise programs. The mean forced expiratory volume in 1 second (FEV1) percent predicted for the cohort was 46.3%.The researchers used pulmonary function data from tests performed within 2 years of enrollment. Change in quality of life and perception of health status were measured using the 36-item Short Form Health Survey (SF-36), dyspnea was assessed using the San Diego Shortness of Breath Questionnaire (SOBQ), depression was assessed using the Beck Depression Inventory (BDI)-II, and functional capacity was assessed using the 6-minute-walk-distance (6MWD) test. On average, the patients reported clinically significant improvements in most components of the SF-36, including an 11.5-unit, a 16.4-U, and a 12.4-U increase in physical function, social function, and vitality, respectively (P less than .001 for all three). The patients also experienced clinically important improvements in the 6MWD test (increase of 52.4 m; P less than .001) and dyspnea (decrease of 9.1 U in the SOBQ; P less than .001). On average, patients’ depression decreased by 3 U, using the BDI II (P less than .001).
When patients in this study were divided into groups based on various aspects of their health at baseline, the levels of improvements seen by each group in most components of the SF-36, the 6MWD, the SOBQ, and the BDI-II were almost always similar.
“We add to the literature by comparing outcomes across quartiles of baseline exercise capacity and showing that patients benefit independent of underlying functional capacity,” said Mr. Schroff and his colleagues.
A few differences in the outcomes following pulmonary rehabilitation were observed between these baseline characteristics–based groups. When patients were grouped by exercise capacity, for example, those with the lowest baseline exercise capacity (as measured by the 6MWD) experienced the largest incremental improvement in the 6MWD. Additionally, when patients were grouped by dyspnea score, those with the worst baseline dyspnea experienced the greatest reduction in dyspnea. However, those with the lowest lung function made the smallest improvement in the 6MWD. Another of these differences was observed between the patients with the lowest baseline lung function and the patients in the other lung function-based quartiles. Those with the worst lung function made the smallest improvement in the 6MWD, which was 39.0 m, on average. All of these subgroups achieved clinically significant improvements in the 6MWD and SOBQ (Ann Am Thorac Soc. 2017 Jan 1;14[1]:26-32).
Each exercise session included aerobic exercises, resistance training, and breathing techniques. Cardiovascular exercise was prescribed starting at 20-30 minutes of continuous or interval bouts and was gradually increasing until 30-45 minutes of exercise was achieved. Patients also received education sessions lasting 40-60 minutes on understanding their disease, smoking cessation counseling, appropriate use of inhalers, diet and nutrition, and stress management. Subjects with other concurrent chronic respiratory diseases were excluded from the analysis.
The researchers noted that their findings may not be generalizable to patients with disease burdens causing them to drop out of the study. “Although we have previously shown that baseline levels of dyspnea, FEV1, and exercise capacity did not influence dropout rates, this could be a source of bias,” they noted.
“Patients with COPD experienced meaningful improvements in quality of life, dyspnea, exercise capacity, and depression, regardless of baseline lung function, dyspnea, and exercise capacity. Current guidelines should be amended to recommend pulmonary rehabilitation to all patients with COPD, regardless of their baseline level of disease burden,” the analysis’ authors said.
Three of the study’s authors reported receiving grants and other fees or a single grant from various sources. The other authors, including Mr. Schroff, said they had nothing to disclose.
Participation in at least 20 days of pulmonary rehabilitation by patients with chronic obstructive pulmonary disease (COPD) resulted in statistically significant improvements in quality of life, perception of health status, functional capacity, dyspnea, and depression, in a retrospective analysis.
Furthermore, improvements were seen regardless of the degree of exercise function, dyspnea, or lung function at baseline, reported lead investigator Praful Schroff.
The analysis focused on 229 COPD patients enrolled in the pulmonary rehabilitation program at UAB during 1996-2013, all of whom completed questionnaires both at enrollment and after completion of their respective exercise programs. The mean forced expiratory volume in 1 second (FEV1) percent predicted for the cohort was 46.3%.The researchers used pulmonary function data from tests performed within 2 years of enrollment. Change in quality of life and perception of health status were measured using the 36-item Short Form Health Survey (SF-36), dyspnea was assessed using the San Diego Shortness of Breath Questionnaire (SOBQ), depression was assessed using the Beck Depression Inventory (BDI)-II, and functional capacity was assessed using the 6-minute-walk-distance (6MWD) test. On average, the patients reported clinically significant improvements in most components of the SF-36, including an 11.5-unit, a 16.4-U, and a 12.4-U increase in physical function, social function, and vitality, respectively (P less than .001 for all three). The patients also experienced clinically important improvements in the 6MWD test (increase of 52.4 m; P less than .001) and dyspnea (decrease of 9.1 U in the SOBQ; P less than .001). On average, patients’ depression decreased by 3 U, using the BDI II (P less than .001).
When patients in this study were divided into groups based on various aspects of their health at baseline, the levels of improvements seen by each group in most components of the SF-36, the 6MWD, the SOBQ, and the BDI-II were almost always similar.
“We add to the literature by comparing outcomes across quartiles of baseline exercise capacity and showing that patients benefit independent of underlying functional capacity,” said Mr. Schroff and his colleagues.
A few differences in the outcomes following pulmonary rehabilitation were observed between these baseline characteristics–based groups. When patients were grouped by exercise capacity, for example, those with the lowest baseline exercise capacity (as measured by the 6MWD) experienced the largest incremental improvement in the 6MWD. Additionally, when patients were grouped by dyspnea score, those with the worst baseline dyspnea experienced the greatest reduction in dyspnea. However, those with the lowest lung function made the smallest improvement in the 6MWD. Another of these differences was observed between the patients with the lowest baseline lung function and the patients in the other lung function-based quartiles. Those with the worst lung function made the smallest improvement in the 6MWD, which was 39.0 m, on average. All of these subgroups achieved clinically significant improvements in the 6MWD and SOBQ (Ann Am Thorac Soc. 2017 Jan 1;14[1]:26-32).
Each exercise session included aerobic exercises, resistance training, and breathing techniques. Cardiovascular exercise was prescribed starting at 20-30 minutes of continuous or interval bouts and was gradually increasing until 30-45 minutes of exercise was achieved. Patients also received education sessions lasting 40-60 minutes on understanding their disease, smoking cessation counseling, appropriate use of inhalers, diet and nutrition, and stress management. Subjects with other concurrent chronic respiratory diseases were excluded from the analysis.
The researchers noted that their findings may not be generalizable to patients with disease burdens causing them to drop out of the study. “Although we have previously shown that baseline levels of dyspnea, FEV1, and exercise capacity did not influence dropout rates, this could be a source of bias,” they noted.
“Patients with COPD experienced meaningful improvements in quality of life, dyspnea, exercise capacity, and depression, regardless of baseline lung function, dyspnea, and exercise capacity. Current guidelines should be amended to recommend pulmonary rehabilitation to all patients with COPD, regardless of their baseline level of disease burden,” the analysis’ authors said.
Three of the study’s authors reported receiving grants and other fees or a single grant from various sources. The other authors, including Mr. Schroff, said they had nothing to disclose.
Participation in at least 20 days of pulmonary rehabilitation by patients with chronic obstructive pulmonary disease (COPD) resulted in statistically significant improvements in quality of life, perception of health status, functional capacity, dyspnea, and depression, in a retrospective analysis.
Furthermore, improvements were seen regardless of the degree of exercise function, dyspnea, or lung function at baseline, reported lead investigator Praful Schroff.
The analysis focused on 229 COPD patients enrolled in the pulmonary rehabilitation program at UAB during 1996-2013, all of whom completed questionnaires both at enrollment and after completion of their respective exercise programs. The mean forced expiratory volume in 1 second (FEV1) percent predicted for the cohort was 46.3%.The researchers used pulmonary function data from tests performed within 2 years of enrollment. Change in quality of life and perception of health status were measured using the 36-item Short Form Health Survey (SF-36), dyspnea was assessed using the San Diego Shortness of Breath Questionnaire (SOBQ), depression was assessed using the Beck Depression Inventory (BDI)-II, and functional capacity was assessed using the 6-minute-walk-distance (6MWD) test. On average, the patients reported clinically significant improvements in most components of the SF-36, including an 11.5-unit, a 16.4-U, and a 12.4-U increase in physical function, social function, and vitality, respectively (P less than .001 for all three). The patients also experienced clinically important improvements in the 6MWD test (increase of 52.4 m; P less than .001) and dyspnea (decrease of 9.1 U in the SOBQ; P less than .001). On average, patients’ depression decreased by 3 U, using the BDI II (P less than .001).
When patients in this study were divided into groups based on various aspects of their health at baseline, the levels of improvements seen by each group in most components of the SF-36, the 6MWD, the SOBQ, and the BDI-II were almost always similar.
“We add to the literature by comparing outcomes across quartiles of baseline exercise capacity and showing that patients benefit independent of underlying functional capacity,” said Mr. Schroff and his colleagues.
A few differences in the outcomes following pulmonary rehabilitation were observed between these baseline characteristics–based groups. When patients were grouped by exercise capacity, for example, those with the lowest baseline exercise capacity (as measured by the 6MWD) experienced the largest incremental improvement in the 6MWD. Additionally, when patients were grouped by dyspnea score, those with the worst baseline dyspnea experienced the greatest reduction in dyspnea. However, those with the lowest lung function made the smallest improvement in the 6MWD. Another of these differences was observed between the patients with the lowest baseline lung function and the patients in the other lung function-based quartiles. Those with the worst lung function made the smallest improvement in the 6MWD, which was 39.0 m, on average. All of these subgroups achieved clinically significant improvements in the 6MWD and SOBQ (Ann Am Thorac Soc. 2017 Jan 1;14[1]:26-32).
Each exercise session included aerobic exercises, resistance training, and breathing techniques. Cardiovascular exercise was prescribed starting at 20-30 minutes of continuous or interval bouts and was gradually increasing until 30-45 minutes of exercise was achieved. Patients also received education sessions lasting 40-60 minutes on understanding their disease, smoking cessation counseling, appropriate use of inhalers, diet and nutrition, and stress management. Subjects with other concurrent chronic respiratory diseases were excluded from the analysis.
The researchers noted that their findings may not be generalizable to patients with disease burdens causing them to drop out of the study. “Although we have previously shown that baseline levels of dyspnea, FEV1, and exercise capacity did not influence dropout rates, this could be a source of bias,” they noted.
“Patients with COPD experienced meaningful improvements in quality of life, dyspnea, exercise capacity, and depression, regardless of baseline lung function, dyspnea, and exercise capacity. Current guidelines should be amended to recommend pulmonary rehabilitation to all patients with COPD, regardless of their baseline level of disease burden,” the analysis’ authors said.
Three of the study’s authors reported receiving grants and other fees or a single grant from various sources. The other authors, including Mr. Schroff, said they had nothing to disclose.
Key clinical point: COPD patients with a variety of baseline health characteristics experienced clinically significant improvements in quality of life, functional capacity, and dyspnea following at least 20 days of pulmonary rehabilitation.
Major finding: The patients experienced clinically important improvements in the 6-minute-walk-distance test (an average increase of 52.4 m; P less than .001) and dyspnea (an average decrease of 9.1 U in the San Diego Shortness of Breath Questionnaire, P less than .001).
Data source: A retrospective analysis of 229 COPD patients from a prospectively maintained database.
Disclosures: Three of the study’s authors reported receiving grants and other fees or a single grant from various sources. The other authors, including Mr. Schroff, said they had nothing to disclose.
Screen opioid users for depression, study recommends
Depression combined with chronic opioid analgesic use involves more symptoms and comorbidities than depression without chronic opioid use, according to a study of Department of Veterans Affairs patients seen between 2000 and 2012.
“Screening and treatment of depression in non–cancer pain patients may limit risk of persistent mood disorder and subsequent suicidal ideation,” wrote Jeffrey F. Scherrer, PhD, and his coauthors. “Opioid prescribing for pain management should be coupled with careful screening and treatment of emerging depression.”
“Eligible patients were cancer free, HIV free. ... Because we were interested in characterizing severity of new-onset [new depression episodes] and not predictors of NDE, we measured incident substance use and psychiatric comorbidities that occurred at the same time or after NDE. Therefore, eligible patients were free of psychiatric and substance use disorders before NDE. Patients whose opioid use began after NDE and patients without NDE in follow-up were excluded,” wrote Dr. Scherrer of Saint Louis University and his coauthors (J Affect Disord. 2017 Mar 1;210:125-9).
This process left the researchers with a sample size of 4,758 patients. Of those, 4,314 developed NDE without receiving an opioid, while the remaining 444 developed NDE after opioid use of more than 90 days.
Looking at raw figures prior to the application of inverse probability of treatment weighting (IPTW), the opioid use group was more likely than was the nonopioid use group to have comorbid posttraumatic stress disorder (17.3% vs. 11.9%), opioid (4.3% vs. 0.5%) and other drug abuse/dependence (11.3% vs. 4.8%), all pain-related conditions, obesity (48.2% vs. 37.4%), and nicotine abuse/dependence (52.5% vs. 30.5%). The further calculations were made “to assess whether differences between the groups were irrespective of pain-related variables.”
With IPTW adjustments made, the differences in pain-related comorbidities went away. Opioid-using patients had higher depression severity as measured by Patient Health Questionnaire–9 scores (P = .012). They also were more likely to have had antidepressant treatment for at least 12 weeks (P less than .0001). Nonopioid use patients were more likely to have anxiety disorders other than PTSD (P = .014).
Dr. Scherrer had no conflicts of interest. The study received funding support from the National Institute of Mental Health. The views reflected in the article are those of the authors and not necessarily those of the VA, the researchers reported.
Depression combined with chronic opioid analgesic use involves more symptoms and comorbidities than depression without chronic opioid use, according to a study of Department of Veterans Affairs patients seen between 2000 and 2012.
“Screening and treatment of depression in non–cancer pain patients may limit risk of persistent mood disorder and subsequent suicidal ideation,” wrote Jeffrey F. Scherrer, PhD, and his coauthors. “Opioid prescribing for pain management should be coupled with careful screening and treatment of emerging depression.”
“Eligible patients were cancer free, HIV free. ... Because we were interested in characterizing severity of new-onset [new depression episodes] and not predictors of NDE, we measured incident substance use and psychiatric comorbidities that occurred at the same time or after NDE. Therefore, eligible patients were free of psychiatric and substance use disorders before NDE. Patients whose opioid use began after NDE and patients without NDE in follow-up were excluded,” wrote Dr. Scherrer of Saint Louis University and his coauthors (J Affect Disord. 2017 Mar 1;210:125-9).
This process left the researchers with a sample size of 4,758 patients. Of those, 4,314 developed NDE without receiving an opioid, while the remaining 444 developed NDE after opioid use of more than 90 days.
Looking at raw figures prior to the application of inverse probability of treatment weighting (IPTW), the opioid use group was more likely than was the nonopioid use group to have comorbid posttraumatic stress disorder (17.3% vs. 11.9%), opioid (4.3% vs. 0.5%) and other drug abuse/dependence (11.3% vs. 4.8%), all pain-related conditions, obesity (48.2% vs. 37.4%), and nicotine abuse/dependence (52.5% vs. 30.5%). The further calculations were made “to assess whether differences between the groups were irrespective of pain-related variables.”
With IPTW adjustments made, the differences in pain-related comorbidities went away. Opioid-using patients had higher depression severity as measured by Patient Health Questionnaire–9 scores (P = .012). They also were more likely to have had antidepressant treatment for at least 12 weeks (P less than .0001). Nonopioid use patients were more likely to have anxiety disorders other than PTSD (P = .014).
Dr. Scherrer had no conflicts of interest. The study received funding support from the National Institute of Mental Health. The views reflected in the article are those of the authors and not necessarily those of the VA, the researchers reported.
Depression combined with chronic opioid analgesic use involves more symptoms and comorbidities than depression without chronic opioid use, according to a study of Department of Veterans Affairs patients seen between 2000 and 2012.
“Screening and treatment of depression in non–cancer pain patients may limit risk of persistent mood disorder and subsequent suicidal ideation,” wrote Jeffrey F. Scherrer, PhD, and his coauthors. “Opioid prescribing for pain management should be coupled with careful screening and treatment of emerging depression.”
“Eligible patients were cancer free, HIV free. ... Because we were interested in characterizing severity of new-onset [new depression episodes] and not predictors of NDE, we measured incident substance use and psychiatric comorbidities that occurred at the same time or after NDE. Therefore, eligible patients were free of psychiatric and substance use disorders before NDE. Patients whose opioid use began after NDE and patients without NDE in follow-up were excluded,” wrote Dr. Scherrer of Saint Louis University and his coauthors (J Affect Disord. 2017 Mar 1;210:125-9).
This process left the researchers with a sample size of 4,758 patients. Of those, 4,314 developed NDE without receiving an opioid, while the remaining 444 developed NDE after opioid use of more than 90 days.
Looking at raw figures prior to the application of inverse probability of treatment weighting (IPTW), the opioid use group was more likely than was the nonopioid use group to have comorbid posttraumatic stress disorder (17.3% vs. 11.9%), opioid (4.3% vs. 0.5%) and other drug abuse/dependence (11.3% vs. 4.8%), all pain-related conditions, obesity (48.2% vs. 37.4%), and nicotine abuse/dependence (52.5% vs. 30.5%). The further calculations were made “to assess whether differences between the groups were irrespective of pain-related variables.”
With IPTW adjustments made, the differences in pain-related comorbidities went away. Opioid-using patients had higher depression severity as measured by Patient Health Questionnaire–9 scores (P = .012). They also were more likely to have had antidepressant treatment for at least 12 weeks (P less than .0001). Nonopioid use patients were more likely to have anxiety disorders other than PTSD (P = .014).
Dr. Scherrer had no conflicts of interest. The study received funding support from the National Institute of Mental Health. The views reflected in the article are those of the authors and not necessarily those of the VA, the researchers reported.
Lower BDNF levels found in older adults with bipolar I
Older patients with bipolar I disorder appear to have lower serum levels of brain-deprived neurotrophic factor than similarly aged adults without bipolar I, a study showed.
At the beginning of the study, Aline T. Soares, MD, and her colleagues recruited 118 patients from clinics in the United States and Canada with bipolar disorder who were aged 50 and over and a similar control group of 76 healthy patients. Twenty-seven of the 118 patients had type II bipolar disorder, and 91 had type I bipolar disorder; all had been clinically euthymic for at least 4 weeks when they were evaluated, reported Dr. Soares of the department of internal medicine at the University of São Paulo (Brazil).
The results showed that patients positively identified with bipolar I disorder had lowered brain-deprived neurotrophic factor (BDNF) levels, compared with their control group counterparts. Lower levels of BDNF were not detected in those with bipolar II disorder, the investigators reported (Am J Geriatr Psychiatry. 2016 Aug;24[8]:596-601).
“Our study represents a continuation of the [bipolar disorder] and BDNF story: Prolonged bipolar illness appears to lead to decreased BDNF, even in the euthymic state,” Dr. Soares and her colleagues wrote. “This reduces the brain’s capacity for neurogenesis and neuroplasticity and theoretically increases the risk of hippocampal shrinkage, cognitive deficits, and dementia.”
Future studies are needed to look into how BDNF levels affect mood, cognitive abilities, and other areas of life related to bipolar disorder, they said.
Dr. Soares and her colleagues reported that they had no conflicts to disclose.
To read more about the study, click here.
Older patients with bipolar I disorder appear to have lower serum levels of brain-deprived neurotrophic factor than similarly aged adults without bipolar I, a study showed.
At the beginning of the study, Aline T. Soares, MD, and her colleagues recruited 118 patients from clinics in the United States and Canada with bipolar disorder who were aged 50 and over and a similar control group of 76 healthy patients. Twenty-seven of the 118 patients had type II bipolar disorder, and 91 had type I bipolar disorder; all had been clinically euthymic for at least 4 weeks when they were evaluated, reported Dr. Soares of the department of internal medicine at the University of São Paulo (Brazil).
The results showed that patients positively identified with bipolar I disorder had lowered brain-deprived neurotrophic factor (BDNF) levels, compared with their control group counterparts. Lower levels of BDNF were not detected in those with bipolar II disorder, the investigators reported (Am J Geriatr Psychiatry. 2016 Aug;24[8]:596-601).
“Our study represents a continuation of the [bipolar disorder] and BDNF story: Prolonged bipolar illness appears to lead to decreased BDNF, even in the euthymic state,” Dr. Soares and her colleagues wrote. “This reduces the brain’s capacity for neurogenesis and neuroplasticity and theoretically increases the risk of hippocampal shrinkage, cognitive deficits, and dementia.”
Future studies are needed to look into how BDNF levels affect mood, cognitive abilities, and other areas of life related to bipolar disorder, they said.
Dr. Soares and her colleagues reported that they had no conflicts to disclose.
To read more about the study, click here.
Older patients with bipolar I disorder appear to have lower serum levels of brain-deprived neurotrophic factor than similarly aged adults without bipolar I, a study showed.
At the beginning of the study, Aline T. Soares, MD, and her colleagues recruited 118 patients from clinics in the United States and Canada with bipolar disorder who were aged 50 and over and a similar control group of 76 healthy patients. Twenty-seven of the 118 patients had type II bipolar disorder, and 91 had type I bipolar disorder; all had been clinically euthymic for at least 4 weeks when they were evaluated, reported Dr. Soares of the department of internal medicine at the University of São Paulo (Brazil).
The results showed that patients positively identified with bipolar I disorder had lowered brain-deprived neurotrophic factor (BDNF) levels, compared with their control group counterparts. Lower levels of BDNF were not detected in those with bipolar II disorder, the investigators reported (Am J Geriatr Psychiatry. 2016 Aug;24[8]:596-601).
“Our study represents a continuation of the [bipolar disorder] and BDNF story: Prolonged bipolar illness appears to lead to decreased BDNF, even in the euthymic state,” Dr. Soares and her colleagues wrote. “This reduces the brain’s capacity for neurogenesis and neuroplasticity and theoretically increases the risk of hippocampal shrinkage, cognitive deficits, and dementia.”
Future studies are needed to look into how BDNF levels affect mood, cognitive abilities, and other areas of life related to bipolar disorder, they said.
Dr. Soares and her colleagues reported that they had no conflicts to disclose.
To read more about the study, click here.
FROM THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
When primary anti-TNF fails in axial spondyloarthritis, consider comorbidities or second anti-TNF
Most of the minority of axial spondyloarthritis patients who do not respond to their first tumor necrosis factor inhibitor still meet classification criteria for the condition 5-10 years later, but more than half respond to a second TNFi and most also have comorbidities that could affect the spondyloarthritis evaluation, according to findings from a single-center cohort study.
The study’s finding of TNFi primary inefficacy in 27 (12%) of 222 patients with axial spondyloarthritis (axSpA) who were given their first TNFi during 2004-2009 is in line with previous results of about 5%-15% primary inefficacy for a first TNFi in axSpA. However, the French investigators, led by Sandra Kossi of Cochin Hospital in Paris, noted that the difficulty of making an axSpA diagnosis and the presence of certain comorbidities “could interfere either with the activity of SpA (falsely heightened disease activity) or with the response to TNFi (falsely heightened inefficacy).” They sought to report the characteristics of axSpA patients with primary inefficacy after their first TNFi in the 5- to 10-year period after their prescription (Rheumatology [Oxford]. 2017 Jan 9. doi: 10.1093/rheumatology/kew456).
A total of 25 of the patients with primary inefficacy underwent re-evaluation 5-10 years (mean of 6 years) later. The investigators defined primary inefficacy as “treatment interruption 3-4 months after treatment onset, with a rheumatologist assessment in the medical file citing lack of efficacy as primary reason for drug interruption.”
The patients with primary TNFi inefficacy had a mean age of 53 years at the time of follow-up, and about half were female. All the patients still had symptoms and back pain, but symptoms were moderate based on a mean Bath Ankylosing Spondylitis Disease Activity Index score of 42. Overall, nine were taking a TNFi and nine were taking nonsteroidal anti-inflammatory drugs, while others used analgesics or nonpharmacologic measures.
Primary TNFi inefficacy occurred significantly more often occurred among females (48% vs. 27%; P = .04), older aged patients at first TNFi use (45 vs. 39 years; P = .04), patients with higher mean Bath Ankylosing Spondylitis Functional Index scores (68 vs. 42; P = .03), and in those who did not have an abnormally elevated C-reactive protein level (33% vs. 63%; P = .02). Patients with primary TNFi inefficacy had lower rates of HLAB27 positivity (56% vs. 72%) or radiographic sacroiliitis (67% vs. 81%), but the differences were not statistically significant.
At follow-up, 21 (84%) patients met Assessment of Spondyloarthritis International Society classification criteria for axSpA, and 20 (80%) met the axSpA diagnosis according to the rheumatologists’ opinion, with 17 (68%) fulfilling both.
A total of 18 (72%) had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression. Five patients – all females – had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.
By the time of follow-up, 16 (64%) had switched to another TNFi, including 9 who had received two TNFi drugs and 7 who had received three or more. The second TNFi was considered efficacious in nine patients. The retention rate of the second TNFi at 1 year among those with primary inefficacy was 50%, and overall, nine patients were still prescribed a TNFi at the time of follow-up.
The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation “is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.”
The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.
Most of the minority of axial spondyloarthritis patients who do not respond to their first tumor necrosis factor inhibitor still meet classification criteria for the condition 5-10 years later, but more than half respond to a second TNFi and most also have comorbidities that could affect the spondyloarthritis evaluation, according to findings from a single-center cohort study.
The study’s finding of TNFi primary inefficacy in 27 (12%) of 222 patients with axial spondyloarthritis (axSpA) who were given their first TNFi during 2004-2009 is in line with previous results of about 5%-15% primary inefficacy for a first TNFi in axSpA. However, the French investigators, led by Sandra Kossi of Cochin Hospital in Paris, noted that the difficulty of making an axSpA diagnosis and the presence of certain comorbidities “could interfere either with the activity of SpA (falsely heightened disease activity) or with the response to TNFi (falsely heightened inefficacy).” They sought to report the characteristics of axSpA patients with primary inefficacy after their first TNFi in the 5- to 10-year period after their prescription (Rheumatology [Oxford]. 2017 Jan 9. doi: 10.1093/rheumatology/kew456).
A total of 25 of the patients with primary inefficacy underwent re-evaluation 5-10 years (mean of 6 years) later. The investigators defined primary inefficacy as “treatment interruption 3-4 months after treatment onset, with a rheumatologist assessment in the medical file citing lack of efficacy as primary reason for drug interruption.”
The patients with primary TNFi inefficacy had a mean age of 53 years at the time of follow-up, and about half were female. All the patients still had symptoms and back pain, but symptoms were moderate based on a mean Bath Ankylosing Spondylitis Disease Activity Index score of 42. Overall, nine were taking a TNFi and nine were taking nonsteroidal anti-inflammatory drugs, while others used analgesics or nonpharmacologic measures.
Primary TNFi inefficacy occurred significantly more often occurred among females (48% vs. 27%; P = .04), older aged patients at first TNFi use (45 vs. 39 years; P = .04), patients with higher mean Bath Ankylosing Spondylitis Functional Index scores (68 vs. 42; P = .03), and in those who did not have an abnormally elevated C-reactive protein level (33% vs. 63%; P = .02). Patients with primary TNFi inefficacy had lower rates of HLAB27 positivity (56% vs. 72%) or radiographic sacroiliitis (67% vs. 81%), but the differences were not statistically significant.
At follow-up, 21 (84%) patients met Assessment of Spondyloarthritis International Society classification criteria for axSpA, and 20 (80%) met the axSpA diagnosis according to the rheumatologists’ opinion, with 17 (68%) fulfilling both.
A total of 18 (72%) had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression. Five patients – all females – had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.
By the time of follow-up, 16 (64%) had switched to another TNFi, including 9 who had received two TNFi drugs and 7 who had received three or more. The second TNFi was considered efficacious in nine patients. The retention rate of the second TNFi at 1 year among those with primary inefficacy was 50%, and overall, nine patients were still prescribed a TNFi at the time of follow-up.
The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation “is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.”
The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.
Most of the minority of axial spondyloarthritis patients who do not respond to their first tumor necrosis factor inhibitor still meet classification criteria for the condition 5-10 years later, but more than half respond to a second TNFi and most also have comorbidities that could affect the spondyloarthritis evaluation, according to findings from a single-center cohort study.
The study’s finding of TNFi primary inefficacy in 27 (12%) of 222 patients with axial spondyloarthritis (axSpA) who were given their first TNFi during 2004-2009 is in line with previous results of about 5%-15% primary inefficacy for a first TNFi in axSpA. However, the French investigators, led by Sandra Kossi of Cochin Hospital in Paris, noted that the difficulty of making an axSpA diagnosis and the presence of certain comorbidities “could interfere either with the activity of SpA (falsely heightened disease activity) or with the response to TNFi (falsely heightened inefficacy).” They sought to report the characteristics of axSpA patients with primary inefficacy after their first TNFi in the 5- to 10-year period after their prescription (Rheumatology [Oxford]. 2017 Jan 9. doi: 10.1093/rheumatology/kew456).
A total of 25 of the patients with primary inefficacy underwent re-evaluation 5-10 years (mean of 6 years) later. The investigators defined primary inefficacy as “treatment interruption 3-4 months after treatment onset, with a rheumatologist assessment in the medical file citing lack of efficacy as primary reason for drug interruption.”
The patients with primary TNFi inefficacy had a mean age of 53 years at the time of follow-up, and about half were female. All the patients still had symptoms and back pain, but symptoms were moderate based on a mean Bath Ankylosing Spondylitis Disease Activity Index score of 42. Overall, nine were taking a TNFi and nine were taking nonsteroidal anti-inflammatory drugs, while others used analgesics or nonpharmacologic measures.
Primary TNFi inefficacy occurred significantly more often occurred among females (48% vs. 27%; P = .04), older aged patients at first TNFi use (45 vs. 39 years; P = .04), patients with higher mean Bath Ankylosing Spondylitis Functional Index scores (68 vs. 42; P = .03), and in those who did not have an abnormally elevated C-reactive protein level (33% vs. 63%; P = .02). Patients with primary TNFi inefficacy had lower rates of HLAB27 positivity (56% vs. 72%) or radiographic sacroiliitis (67% vs. 81%), but the differences were not statistically significant.
At follow-up, 21 (84%) patients met Assessment of Spondyloarthritis International Society classification criteria for axSpA, and 20 (80%) met the axSpA diagnosis according to the rheumatologists’ opinion, with 17 (68%) fulfilling both.
A total of 18 (72%) had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression. Five patients – all females – had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.
By the time of follow-up, 16 (64%) had switched to another TNFi, including 9 who had received two TNFi drugs and 7 who had received three or more. The second TNFi was considered efficacious in nine patients. The retention rate of the second TNFi at 1 year among those with primary inefficacy was 50%, and overall, nine patients were still prescribed a TNFi at the time of follow-up.
The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation “is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.”
The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.
Key clinical point:
Major finding: A total of 18 (72%) of 25 patients with primary TNFi inefficacy had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression.
Data source: A retrospective and prospective cohort study of 222 patients who received a first TNFi after being diagnosed with axial spondyloarthritis during 2004-2009.
Disclosures: The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.
New data signal paradigm shift in FMD and arterial disease
CHICAGO – New data have shown that fibromuscular dysplasia is associated with high rates of dissection and/or aneurysm, and emerging recommendations call for routine imaging early on in the diagnosis of FMD to monitor for these vascular events, a researcher who developed those recommendations reported at a symposium on vascular surgery sponsored by Northwestern University.
“Given the very high rate of aneurysms in this population, it is now recommended that all patients with FMD should undergo at least one-time head-to pelvis imaging with CT angiography or MR angiography to screen for the presence of an aneurysm or to identify other areas of FMD involvement,” said Daniella Kadian-Dodov, MD, of Icahn School of Medicine at Mount Sinai in New York (J Am Coll Cardiol. 2016;68:176-85).
First described in 1938, FMD is a non-atherosclerotic, noninflammatory disease that had been thought to be a rare cause of renovascular hypertension with a classic “string-of-beads” appearance upon imaging, Dr. Kadian-Dodov noted. However, recent data from the Fibromuscular Dysplasia Society of America–sponsored U.S. registry has changed that thinking. “We now know it occurs more frequently in the carotid and renal arteries, although it has been observed in almost every artery,” she said. “The pathogenesis is still unknown but up to 10% of cases are familial.”
And manifestations of disease now extend beyond the “string-of-beads” appearance to include aneurysm, dissection, and arterial tortuosity, she said (Circulation. 2012;125:3182-90; Circulation. 2014;129:1048-78; J Am Coll Cardiol. 2016;68:176-85). The classification system for FMD has also undergone a recent change, according to Dr. Kadian-Dodov. “Traditionally, a histopathologic scheme was used to classify FMD,” she said. “Nowadays, fewer and fewer patients are undergoing surgical procedures, so the classification has changed to an angiographic system,” the most common of which is the American Heart Association system adopted in 2014 that distinguishes between multifocal, characterized by the classic “string-of-beads” appearance, and focal FMD with a single area of stenosis.
But the diagnosis of either variant of FMD is not exclusive. “Patients may have multiple areas of disease involvement and the same patient may have both focal and multifocal FMD findings,” Dr. Kadian-Dodov said.
The U.S. registry has helped clarify the thinking on FMD, Dr. Kadian-Dodov said. More than 1,400 patients are in the registry, 90% of whom are women with multifocal disease. The average age of onset of symptoms is 47 years, but 52 is the average age for diagnosis. “So these patients are experiencing several years delay to FMD diagnosis,” she said.
Manifestations depend on the vascular bed involved. “In the case of cervical artery FMD, headaches and pulsatile tinnitus are commonly reported, whereas with renal artery involvement hypertension is the most common symptom,” she said. A recent analysis showed 41.7% of the FMD population have either aneurysm and dissection or both (J Am Coll Cardiol. 2016;68:176-185).
But no specific guidelines for treatment of FMD yet exist, Dr. Kadian-Dodov said. “General guidelines should be applied for the management of dissection and aneurysm in patients with FMD,” she said. For patients with arterial dissection, that means conservative therapy comprising either anticoagulation or antiplatelet agents for 3-6 months followed by daily low-dose aspirin therapy. “Revascularization is rarely required for these patients,” she said. “Endovascular or surgical modalities should be reserved for those with continued ischemia despite conservative management or more complicated pseudoaneurysm formations.”
Daily aspirin therapy is likewise the recommendation for patients with cervical artery multifocal or focal FMD involvement without dissection or aneurysms. “We follow up with imaging every 6 months for 2 years,” Dr. Kadian-Dodov said. “If they’re stable, we switch over to annual surveillance; and if the patient has an aneurysm or dissection, that might alter the imaging and surveillance program.”
During angioplasty, determining the severity of stenosis upon visual inspection is difficult, especially in multifocal FMD. She advised measuring the gradient across the area of FMD involvement with a pressure wire to determine if angioplasty has adequately treated the lesion. “You should see obliteration of the gradient with successful treatment; you don’t have to target your therapy to a perfect angiographic result,” she said.
In patients with FMD and hypertension, she recommended renal artery angioplasty for hypertension of less than 5 years duration or in resistant or labile hypertension. “In this setting, stents are only reserved for complicated or refractory cases; angioplasty alone is sufficient,” Dr. Kadian-Dodov said. Cure rates decline with age, and hypertension in focal disease has a higher cure rate than does multifocal disease, she said (Hypertension. 2010;56:525-32).
Dr. Kadian-Dodov had no relevant financial relationships to disclose.
CHICAGO – New data have shown that fibromuscular dysplasia is associated with high rates of dissection and/or aneurysm, and emerging recommendations call for routine imaging early on in the diagnosis of FMD to monitor for these vascular events, a researcher who developed those recommendations reported at a symposium on vascular surgery sponsored by Northwestern University.
“Given the very high rate of aneurysms in this population, it is now recommended that all patients with FMD should undergo at least one-time head-to pelvis imaging with CT angiography or MR angiography to screen for the presence of an aneurysm or to identify other areas of FMD involvement,” said Daniella Kadian-Dodov, MD, of Icahn School of Medicine at Mount Sinai in New York (J Am Coll Cardiol. 2016;68:176-85).
First described in 1938, FMD is a non-atherosclerotic, noninflammatory disease that had been thought to be a rare cause of renovascular hypertension with a classic “string-of-beads” appearance upon imaging, Dr. Kadian-Dodov noted. However, recent data from the Fibromuscular Dysplasia Society of America–sponsored U.S. registry has changed that thinking. “We now know it occurs more frequently in the carotid and renal arteries, although it has been observed in almost every artery,” she said. “The pathogenesis is still unknown but up to 10% of cases are familial.”
And manifestations of disease now extend beyond the “string-of-beads” appearance to include aneurysm, dissection, and arterial tortuosity, she said (Circulation. 2012;125:3182-90; Circulation. 2014;129:1048-78; J Am Coll Cardiol. 2016;68:176-85). The classification system for FMD has also undergone a recent change, according to Dr. Kadian-Dodov. “Traditionally, a histopathologic scheme was used to classify FMD,” she said. “Nowadays, fewer and fewer patients are undergoing surgical procedures, so the classification has changed to an angiographic system,” the most common of which is the American Heart Association system adopted in 2014 that distinguishes between multifocal, characterized by the classic “string-of-beads” appearance, and focal FMD with a single area of stenosis.
But the diagnosis of either variant of FMD is not exclusive. “Patients may have multiple areas of disease involvement and the same patient may have both focal and multifocal FMD findings,” Dr. Kadian-Dodov said.
The U.S. registry has helped clarify the thinking on FMD, Dr. Kadian-Dodov said. More than 1,400 patients are in the registry, 90% of whom are women with multifocal disease. The average age of onset of symptoms is 47 years, but 52 is the average age for diagnosis. “So these patients are experiencing several years delay to FMD diagnosis,” she said.
Manifestations depend on the vascular bed involved. “In the case of cervical artery FMD, headaches and pulsatile tinnitus are commonly reported, whereas with renal artery involvement hypertension is the most common symptom,” she said. A recent analysis showed 41.7% of the FMD population have either aneurysm and dissection or both (J Am Coll Cardiol. 2016;68:176-185).
But no specific guidelines for treatment of FMD yet exist, Dr. Kadian-Dodov said. “General guidelines should be applied for the management of dissection and aneurysm in patients with FMD,” she said. For patients with arterial dissection, that means conservative therapy comprising either anticoagulation or antiplatelet agents for 3-6 months followed by daily low-dose aspirin therapy. “Revascularization is rarely required for these patients,” she said. “Endovascular or surgical modalities should be reserved for those with continued ischemia despite conservative management or more complicated pseudoaneurysm formations.”
Daily aspirin therapy is likewise the recommendation for patients with cervical artery multifocal or focal FMD involvement without dissection or aneurysms. “We follow up with imaging every 6 months for 2 years,” Dr. Kadian-Dodov said. “If they’re stable, we switch over to annual surveillance; and if the patient has an aneurysm or dissection, that might alter the imaging and surveillance program.”
During angioplasty, determining the severity of stenosis upon visual inspection is difficult, especially in multifocal FMD. She advised measuring the gradient across the area of FMD involvement with a pressure wire to determine if angioplasty has adequately treated the lesion. “You should see obliteration of the gradient with successful treatment; you don’t have to target your therapy to a perfect angiographic result,” she said.
In patients with FMD and hypertension, she recommended renal artery angioplasty for hypertension of less than 5 years duration or in resistant or labile hypertension. “In this setting, stents are only reserved for complicated or refractory cases; angioplasty alone is sufficient,” Dr. Kadian-Dodov said. Cure rates decline with age, and hypertension in focal disease has a higher cure rate than does multifocal disease, she said (Hypertension. 2010;56:525-32).
Dr. Kadian-Dodov had no relevant financial relationships to disclose.
CHICAGO – New data have shown that fibromuscular dysplasia is associated with high rates of dissection and/or aneurysm, and emerging recommendations call for routine imaging early on in the diagnosis of FMD to monitor for these vascular events, a researcher who developed those recommendations reported at a symposium on vascular surgery sponsored by Northwestern University.
“Given the very high rate of aneurysms in this population, it is now recommended that all patients with FMD should undergo at least one-time head-to pelvis imaging with CT angiography or MR angiography to screen for the presence of an aneurysm or to identify other areas of FMD involvement,” said Daniella Kadian-Dodov, MD, of Icahn School of Medicine at Mount Sinai in New York (J Am Coll Cardiol. 2016;68:176-85).
First described in 1938, FMD is a non-atherosclerotic, noninflammatory disease that had been thought to be a rare cause of renovascular hypertension with a classic “string-of-beads” appearance upon imaging, Dr. Kadian-Dodov noted. However, recent data from the Fibromuscular Dysplasia Society of America–sponsored U.S. registry has changed that thinking. “We now know it occurs more frequently in the carotid and renal arteries, although it has been observed in almost every artery,” she said. “The pathogenesis is still unknown but up to 10% of cases are familial.”
And manifestations of disease now extend beyond the “string-of-beads” appearance to include aneurysm, dissection, and arterial tortuosity, she said (Circulation. 2012;125:3182-90; Circulation. 2014;129:1048-78; J Am Coll Cardiol. 2016;68:176-85). The classification system for FMD has also undergone a recent change, according to Dr. Kadian-Dodov. “Traditionally, a histopathologic scheme was used to classify FMD,” she said. “Nowadays, fewer and fewer patients are undergoing surgical procedures, so the classification has changed to an angiographic system,” the most common of which is the American Heart Association system adopted in 2014 that distinguishes between multifocal, characterized by the classic “string-of-beads” appearance, and focal FMD with a single area of stenosis.
But the diagnosis of either variant of FMD is not exclusive. “Patients may have multiple areas of disease involvement and the same patient may have both focal and multifocal FMD findings,” Dr. Kadian-Dodov said.
The U.S. registry has helped clarify the thinking on FMD, Dr. Kadian-Dodov said. More than 1,400 patients are in the registry, 90% of whom are women with multifocal disease. The average age of onset of symptoms is 47 years, but 52 is the average age for diagnosis. “So these patients are experiencing several years delay to FMD diagnosis,” she said.
Manifestations depend on the vascular bed involved. “In the case of cervical artery FMD, headaches and pulsatile tinnitus are commonly reported, whereas with renal artery involvement hypertension is the most common symptom,” she said. A recent analysis showed 41.7% of the FMD population have either aneurysm and dissection or both (J Am Coll Cardiol. 2016;68:176-185).
But no specific guidelines for treatment of FMD yet exist, Dr. Kadian-Dodov said. “General guidelines should be applied for the management of dissection and aneurysm in patients with FMD,” she said. For patients with arterial dissection, that means conservative therapy comprising either anticoagulation or antiplatelet agents for 3-6 months followed by daily low-dose aspirin therapy. “Revascularization is rarely required for these patients,” she said. “Endovascular or surgical modalities should be reserved for those with continued ischemia despite conservative management or more complicated pseudoaneurysm formations.”
Daily aspirin therapy is likewise the recommendation for patients with cervical artery multifocal or focal FMD involvement without dissection or aneurysms. “We follow up with imaging every 6 months for 2 years,” Dr. Kadian-Dodov said. “If they’re stable, we switch over to annual surveillance; and if the patient has an aneurysm or dissection, that might alter the imaging and surveillance program.”
During angioplasty, determining the severity of stenosis upon visual inspection is difficult, especially in multifocal FMD. She advised measuring the gradient across the area of FMD involvement with a pressure wire to determine if angioplasty has adequately treated the lesion. “You should see obliteration of the gradient with successful treatment; you don’t have to target your therapy to a perfect angiographic result,” she said.
In patients with FMD and hypertension, she recommended renal artery angioplasty for hypertension of less than 5 years duration or in resistant or labile hypertension. “In this setting, stents are only reserved for complicated or refractory cases; angioplasty alone is sufficient,” Dr. Kadian-Dodov said. Cure rates decline with age, and hypertension in focal disease has a higher cure rate than does multifocal disease, she said (Hypertension. 2010;56:525-32).
Dr. Kadian-Dodov had no relevant financial relationships to disclose.
Key clinical point: Fibromuscular dysplasia was thought to be a rare cause of renovascular hypertension, but new data has challenged this thinking.
Major finding: FMD accounts for 15%-20% of patients with spontaneous carotid or vertebral artery dissection and 45%-86% of patients with spontaneous coronary artery dissection.
Data source: U.S. Registry for FMD maintained by the Fibromuscular Dystrophy Society of America.
Disclosures: Dr. Kadian-Dodov reported having no financial disclosures.
Oral, liquid supplement improves clinical outcomes in lactose-intolerant adults
Adults with self-reported lactose intolerance were shown to have significant improvement in their clinical outcomes, including abdominal pain, after consuming an oral, liquid supplement intended to increase lactose-fermenting gut bacteria, M. Andrea Azcarate-Peril, PhD, assistant professor of medicine at the University of North Carolina, Chapel Hill, and her colleagues have shown in a small phase IIa study (Proc Nat Acad Sci. doi: 10.1073/pnas.1606722113).
In a placebo-controlled, double-blind trial, randomly assigned in a 2:1 ratio and conducted at two U.S. sites, highly purified (more than 95%) short-chain galactooligosaccharide (GOS) was given to 42 adults with a self-reported history of lactose intolerance, confirmed by a hydrogen breath test administered after a 25-g lactose challenge. The 20 controls were given a corn syrup mixture formulated according to the same sweetness and consistency as the test drug. Each study arm was started on its regimen at 1.5 g daily, with incremental increases in dose every 5 days until reaching 15 g. Beginning with their first dose at day 1, through day 35, all participants avoided consumption of dairy foods. Stool samples were collected from both groups at days 0 and 36. After day 36, all participants were asked to resume eating dairy foods. At day 66, stool samples were once again collected. Changes in the microbiome at all endpoints were measured by testing the stools via polymerase chain reaction.
Of the 30 study arm participants for whom complete stool samples were available, 27 were found to have had a bifidobacterial response at day 36, including a significant increase in the lactose-fermenting Bifidobacterium, Faecalibacterium, and Lactobacillus species. The remaining three participants in the study arm were considered nonresponders.
In an interview, Andrew Ritter, whose company, Ritter Pharmaceuticals, sponsored the trial, reported that of the 36 study arm participants who had reported abdominal pain pretreatment, 18 said they no longer had the pain at either endpoint, day 36 or day 66 (P = .019); three of 19 in the placebo group reported they no longer had abdominal pain at either endpoint. The study group was also six times more likely to report lactose tolerance at day 66 compared with their pretreatment levels (P = .0389); 28% of the placebo arm reported lactose tolerance at the endpoints. These results were previously published in Nutrition Journal in 2013. [doi: 10.1186/1475-2891-12-160]
“We’re super excited about these results,” said Mr. Ritter. “This is really one of the first clinical studies in a lactose-intolerant population that shows changes in the microbiome.” As to how long before the treatment will be ready for the Food and Drug Administration approval process, Mr. Ritter said, “We’re probably just a couple of years away.”
Two coauthors are advisers to Ritter Pharmaceuticals, which provided the highly purified GOS used in the study. The North Carolina Agriculture Foundation also provided funding for the study.
[email protected]
On Twitter @whitneymcknight
Adults with self-reported lactose intolerance were shown to have significant improvement in their clinical outcomes, including abdominal pain, after consuming an oral, liquid supplement intended to increase lactose-fermenting gut bacteria, M. Andrea Azcarate-Peril, PhD, assistant professor of medicine at the University of North Carolina, Chapel Hill, and her colleagues have shown in a small phase IIa study (Proc Nat Acad Sci. doi: 10.1073/pnas.1606722113).
In a placebo-controlled, double-blind trial, randomly assigned in a 2:1 ratio and conducted at two U.S. sites, highly purified (more than 95%) short-chain galactooligosaccharide (GOS) was given to 42 adults with a self-reported history of lactose intolerance, confirmed by a hydrogen breath test administered after a 25-g lactose challenge. The 20 controls were given a corn syrup mixture formulated according to the same sweetness and consistency as the test drug. Each study arm was started on its regimen at 1.5 g daily, with incremental increases in dose every 5 days until reaching 15 g. Beginning with their first dose at day 1, through day 35, all participants avoided consumption of dairy foods. Stool samples were collected from both groups at days 0 and 36. After day 36, all participants were asked to resume eating dairy foods. At day 66, stool samples were once again collected. Changes in the microbiome at all endpoints were measured by testing the stools via polymerase chain reaction.
Of the 30 study arm participants for whom complete stool samples were available, 27 were found to have had a bifidobacterial response at day 36, including a significant increase in the lactose-fermenting Bifidobacterium, Faecalibacterium, and Lactobacillus species. The remaining three participants in the study arm were considered nonresponders.
In an interview, Andrew Ritter, whose company, Ritter Pharmaceuticals, sponsored the trial, reported that of the 36 study arm participants who had reported abdominal pain pretreatment, 18 said they no longer had the pain at either endpoint, day 36 or day 66 (P = .019); three of 19 in the placebo group reported they no longer had abdominal pain at either endpoint. The study group was also six times more likely to report lactose tolerance at day 66 compared with their pretreatment levels (P = .0389); 28% of the placebo arm reported lactose tolerance at the endpoints. These results were previously published in Nutrition Journal in 2013. [doi: 10.1186/1475-2891-12-160]
“We’re super excited about these results,” said Mr. Ritter. “This is really one of the first clinical studies in a lactose-intolerant population that shows changes in the microbiome.” As to how long before the treatment will be ready for the Food and Drug Administration approval process, Mr. Ritter said, “We’re probably just a couple of years away.”
Two coauthors are advisers to Ritter Pharmaceuticals, which provided the highly purified GOS used in the study. The North Carolina Agriculture Foundation also provided funding for the study.
[email protected]
On Twitter @whitneymcknight
Adults with self-reported lactose intolerance were shown to have significant improvement in their clinical outcomes, including abdominal pain, after consuming an oral, liquid supplement intended to increase lactose-fermenting gut bacteria, M. Andrea Azcarate-Peril, PhD, assistant professor of medicine at the University of North Carolina, Chapel Hill, and her colleagues have shown in a small phase IIa study (Proc Nat Acad Sci. doi: 10.1073/pnas.1606722113).
In a placebo-controlled, double-blind trial, randomly assigned in a 2:1 ratio and conducted at two U.S. sites, highly purified (more than 95%) short-chain galactooligosaccharide (GOS) was given to 42 adults with a self-reported history of lactose intolerance, confirmed by a hydrogen breath test administered after a 25-g lactose challenge. The 20 controls were given a corn syrup mixture formulated according to the same sweetness and consistency as the test drug. Each study arm was started on its regimen at 1.5 g daily, with incremental increases in dose every 5 days until reaching 15 g. Beginning with their first dose at day 1, through day 35, all participants avoided consumption of dairy foods. Stool samples were collected from both groups at days 0 and 36. After day 36, all participants were asked to resume eating dairy foods. At day 66, stool samples were once again collected. Changes in the microbiome at all endpoints were measured by testing the stools via polymerase chain reaction.
Of the 30 study arm participants for whom complete stool samples were available, 27 were found to have had a bifidobacterial response at day 36, including a significant increase in the lactose-fermenting Bifidobacterium, Faecalibacterium, and Lactobacillus species. The remaining three participants in the study arm were considered nonresponders.
In an interview, Andrew Ritter, whose company, Ritter Pharmaceuticals, sponsored the trial, reported that of the 36 study arm participants who had reported abdominal pain pretreatment, 18 said they no longer had the pain at either endpoint, day 36 or day 66 (P = .019); three of 19 in the placebo group reported they no longer had abdominal pain at either endpoint. The study group was also six times more likely to report lactose tolerance at day 66 compared with their pretreatment levels (P = .0389); 28% of the placebo arm reported lactose tolerance at the endpoints. These results were previously published in Nutrition Journal in 2013. [doi: 10.1186/1475-2891-12-160]
“We’re super excited about these results,” said Mr. Ritter. “This is really one of the first clinical studies in a lactose-intolerant population that shows changes in the microbiome.” As to how long before the treatment will be ready for the Food and Drug Administration approval process, Mr. Ritter said, “We’re probably just a couple of years away.”
Two coauthors are advisers to Ritter Pharmaceuticals, which provided the highly purified GOS used in the study. The North Carolina Agriculture Foundation also provided funding for the study.
[email protected]
On Twitter @whitneymcknight
FROM THE PROCEEDINGS OF THE NATIONAL ACADEMIES OF SCIENCE
Key clinical point:
Major finding: A clinically significant response was seen in patients with lactose intolerance who were given an oral, liquid supplement intended to increase lactose-fermenting bacteria.
Data source: Phase IIa trial of 62 adults with lactose intolerance incrementally dosed with an oral, highly purified (more than 95%) short-chain galactooligosaccharide while dietary dairy was restricted.
Disclosures: Ritter Pharmaceuticals, owned by study coauthor Andrew J. Ritter, funded the study and provided the highly purified GOS used in the study. The North Carolina Agriculture Foundation also provided funding. Two coauthors are advisers to Ritter Pharmaceuticals.
AGA Clinical Practice Update: Endoscope reprocessing guidelines are an improvement
While the 2016 Multi-Society Task Force Endoscope Reprocessing Guidelines are an improvement over the 2011 guidelines, some of its minor changes are unlikely to guarantee against prevention of future outbreaks, according to Susan Hutfless, PhD, and Anthony N. Kalloo, MD.*
“The prevention of future outbreaks is left to the manufacturers to modify their protocols and the endoscopy units to adopt the protocols rapidly,” the authors, both from Johns Hopkins University, Baltimore, wrote in a commentary about the 2016 guidelines, which contain 41 recommendations and were endorsed by the AGA. “If followed, the guidelines will make it possible to better track the source of future outbreaks if the tracking and monitoring suggested is performed.” They added that the current cleaning paradigm for duodenoscopes “is ineffective and these guidelines reflect changes to contain, rather than prevent, future outbreaks.”
Some of the specific changes to the 2016 guidelines include recommendation no. 5, which has been revised to recommend “strict adherence” to manufacturer guidance. “The expectation is that all personnel will remain up to date with the manufacturer guidelines and that there will be documentation of the training,” Dr. Hutfless and Dr. Kalloo wrote. The 2016 guidelines specifically state that a “single standard work process within one institution may be insufficient, given differences among manufacturers’ instructions and varied instrument designs.” However, Dr. Hutfless and Dr. Kalloo point out that “an individual or group of individuals may need to be identified to keep up with the FDA, CDC, manufacturer and professional societies in order to modify and implement the changes to the cleaning and training protocols and update the training of all individuals in the unit. It is unclear from the guidelines what the minimum time should be between change in recommendations and updated training.”
Recommendation no. 24 is new and includes a suggestion consistent with the 2015 FDA endoscope reprocessing communications. “Beyond the reprocessing steps discussed in these recommendations, no validated methods for additional duodenoscope reprocessing currently exist,” the guidelines state. “However, units should review and consider the feasibility and appropriateness for their practice of employing one or more of the additional modalities suggested by the FDA for duodenoscopes: intermittent or per procedure culture surveillance of reprocessing outcomes, sterilization with ethylene oxide gas, repeat application of standard high level disinfection, or use of a liquid chemical germicide.” For their part, Dr. Hutfless and Dr. Kalloo pointed out the limitations of these additional modalities. For example, they wrote, “the per procedure culture surveillance modality suggested by the FDA is not cost-effective unless the unit’s transmission probability of carbapenem-resistant Enterobacteriaceae is 24% or greater. Sterilization with ethylene oxide is problematic because a unit that used this approach still encountered an endoscope with carbapenem-resistant Enterobacteriaceae detected by culture. This unit also incurred extra costs to purchase additional scopes due to the longer reprocessing time for sterilization and had a greater number of endoscopes with damage, although the damage was not directly attributable to sterilization” (Gastrointest Endosc. 2016 Aug;84:259-62).
In 2016, the FDA approved the first disposable colonoscope, a product that is expected to be available in the United States in early 2017. Dr. Hutfless and Dr. Kalloo ended their commentary by suggesting that a disposable endoscope with an elevator mechanism, though not currently available, could be a solution to several of the unresolved issues that were present in the 2003, 2011, and 2016 guidelines. “These unresolved issues include interval of storage after reprocessing, microbiologic surveillance, and endoscope durability and longevity,” they wrote. “If the outbreaks persist after the use of disposable endoscopes it is possible that it is some other product or procedure within the endoscopic procedure that is the source of the infectious transmission.”
*This story was update on Jan. 26, 2017.
While the 2016 Multi-Society Task Force Endoscope Reprocessing Guidelines are an improvement over the 2011 guidelines, some of its minor changes are unlikely to guarantee against prevention of future outbreaks, according to Susan Hutfless, PhD, and Anthony N. Kalloo, MD.*
“The prevention of future outbreaks is left to the manufacturers to modify their protocols and the endoscopy units to adopt the protocols rapidly,” the authors, both from Johns Hopkins University, Baltimore, wrote in a commentary about the 2016 guidelines, which contain 41 recommendations and were endorsed by the AGA. “If followed, the guidelines will make it possible to better track the source of future outbreaks if the tracking and monitoring suggested is performed.” They added that the current cleaning paradigm for duodenoscopes “is ineffective and these guidelines reflect changes to contain, rather than prevent, future outbreaks.”
Some of the specific changes to the 2016 guidelines include recommendation no. 5, which has been revised to recommend “strict adherence” to manufacturer guidance. “The expectation is that all personnel will remain up to date with the manufacturer guidelines and that there will be documentation of the training,” Dr. Hutfless and Dr. Kalloo wrote. The 2016 guidelines specifically state that a “single standard work process within one institution may be insufficient, given differences among manufacturers’ instructions and varied instrument designs.” However, Dr. Hutfless and Dr. Kalloo point out that “an individual or group of individuals may need to be identified to keep up with the FDA, CDC, manufacturer and professional societies in order to modify and implement the changes to the cleaning and training protocols and update the training of all individuals in the unit. It is unclear from the guidelines what the minimum time should be between change in recommendations and updated training.”
Recommendation no. 24 is new and includes a suggestion consistent with the 2015 FDA endoscope reprocessing communications. “Beyond the reprocessing steps discussed in these recommendations, no validated methods for additional duodenoscope reprocessing currently exist,” the guidelines state. “However, units should review and consider the feasibility and appropriateness for their practice of employing one or more of the additional modalities suggested by the FDA for duodenoscopes: intermittent or per procedure culture surveillance of reprocessing outcomes, sterilization with ethylene oxide gas, repeat application of standard high level disinfection, or use of a liquid chemical germicide.” For their part, Dr. Hutfless and Dr. Kalloo pointed out the limitations of these additional modalities. For example, they wrote, “the per procedure culture surveillance modality suggested by the FDA is not cost-effective unless the unit’s transmission probability of carbapenem-resistant Enterobacteriaceae is 24% or greater. Sterilization with ethylene oxide is problematic because a unit that used this approach still encountered an endoscope with carbapenem-resistant Enterobacteriaceae detected by culture. This unit also incurred extra costs to purchase additional scopes due to the longer reprocessing time for sterilization and had a greater number of endoscopes with damage, although the damage was not directly attributable to sterilization” (Gastrointest Endosc. 2016 Aug;84:259-62).
In 2016, the FDA approved the first disposable colonoscope, a product that is expected to be available in the United States in early 2017. Dr. Hutfless and Dr. Kalloo ended their commentary by suggesting that a disposable endoscope with an elevator mechanism, though not currently available, could be a solution to several of the unresolved issues that were present in the 2003, 2011, and 2016 guidelines. “These unresolved issues include interval of storage after reprocessing, microbiologic surveillance, and endoscope durability and longevity,” they wrote. “If the outbreaks persist after the use of disposable endoscopes it is possible that it is some other product or procedure within the endoscopic procedure that is the source of the infectious transmission.”
*This story was update on Jan. 26, 2017.
While the 2016 Multi-Society Task Force Endoscope Reprocessing Guidelines are an improvement over the 2011 guidelines, some of its minor changes are unlikely to guarantee against prevention of future outbreaks, according to Susan Hutfless, PhD, and Anthony N. Kalloo, MD.*
“The prevention of future outbreaks is left to the manufacturers to modify their protocols and the endoscopy units to adopt the protocols rapidly,” the authors, both from Johns Hopkins University, Baltimore, wrote in a commentary about the 2016 guidelines, which contain 41 recommendations and were endorsed by the AGA. “If followed, the guidelines will make it possible to better track the source of future outbreaks if the tracking and monitoring suggested is performed.” They added that the current cleaning paradigm for duodenoscopes “is ineffective and these guidelines reflect changes to contain, rather than prevent, future outbreaks.”
Some of the specific changes to the 2016 guidelines include recommendation no. 5, which has been revised to recommend “strict adherence” to manufacturer guidance. “The expectation is that all personnel will remain up to date with the manufacturer guidelines and that there will be documentation of the training,” Dr. Hutfless and Dr. Kalloo wrote. The 2016 guidelines specifically state that a “single standard work process within one institution may be insufficient, given differences among manufacturers’ instructions and varied instrument designs.” However, Dr. Hutfless and Dr. Kalloo point out that “an individual or group of individuals may need to be identified to keep up with the FDA, CDC, manufacturer and professional societies in order to modify and implement the changes to the cleaning and training protocols and update the training of all individuals in the unit. It is unclear from the guidelines what the minimum time should be between change in recommendations and updated training.”
Recommendation no. 24 is new and includes a suggestion consistent with the 2015 FDA endoscope reprocessing communications. “Beyond the reprocessing steps discussed in these recommendations, no validated methods for additional duodenoscope reprocessing currently exist,” the guidelines state. “However, units should review and consider the feasibility and appropriateness for their practice of employing one or more of the additional modalities suggested by the FDA for duodenoscopes: intermittent or per procedure culture surveillance of reprocessing outcomes, sterilization with ethylene oxide gas, repeat application of standard high level disinfection, or use of a liquid chemical germicide.” For their part, Dr. Hutfless and Dr. Kalloo pointed out the limitations of these additional modalities. For example, they wrote, “the per procedure culture surveillance modality suggested by the FDA is not cost-effective unless the unit’s transmission probability of carbapenem-resistant Enterobacteriaceae is 24% or greater. Sterilization with ethylene oxide is problematic because a unit that used this approach still encountered an endoscope with carbapenem-resistant Enterobacteriaceae detected by culture. This unit also incurred extra costs to purchase additional scopes due to the longer reprocessing time for sterilization and had a greater number of endoscopes with damage, although the damage was not directly attributable to sterilization” (Gastrointest Endosc. 2016 Aug;84:259-62).
In 2016, the FDA approved the first disposable colonoscope, a product that is expected to be available in the United States in early 2017. Dr. Hutfless and Dr. Kalloo ended their commentary by suggesting that a disposable endoscope with an elevator mechanism, though not currently available, could be a solution to several of the unresolved issues that were present in the 2003, 2011, and 2016 guidelines. “These unresolved issues include interval of storage after reprocessing, microbiologic surveillance, and endoscope durability and longevity,” they wrote. “If the outbreaks persist after the use of disposable endoscopes it is possible that it is some other product or procedure within the endoscopic procedure that is the source of the infectious transmission.”
*This story was update on Jan. 26, 2017.
FROM GASTROENTEROLOGY