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Multiple factors predict surgical site infection risk after lower extremity revascularization
Patient, operative, and hospital factors were found to be significant predictors of the risk of surgical site infection in patients who underwent open lower extremity bypass procedures, according to the results of a retrospective data analysis.
The study assessed the outcomes of 3,033 patients who underwent elective or urgent open LEB procedures between January 2012 and June 2015 using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Vascular Intervention Collaborative (BMC2 VIC), a statewide cardiovascular consortium of 35 hospitals, according to Frank M. Davis, MD, and his colleagues at the University of Michigan, Ann Arbor.
Demographic information, medical history, laboratory test results before and after the procedure, procedural indication, procedural urgency, technical details of procedures, and associated complications were assessed for each patient. Women comprised 31% of patients, the average patient age was 66 years, and 83% of the population was white (J Vasc Surg. 2017 Jun;65[6]:1769-78).
Among all of the patients treated, 320 developed SSIs and 2,713 did not. The procedural indications included one or more of the following: claudication (72%), rest pain (50.5%), ulcer/gangrene (32.4%), or acute limb ischemia (15.1%). Antibiotics were appropriately administered to 97% of the patients, according to the researchers, “demonstrating high compliance across the BMC2 VIC.”
- Patient factors: As indicated by previous studies, obesity (odds ratio, 1.78), dialysis dependence (OR, 4.33), and hypertension (OR, 4.29) conferred a significant increased risk of SSI after LEB, according to Dr. Davis and his colleagues. In addition, however, they found that previous vascular surgery (OR, 1.57), previous percutaneous coronary intervention (OR, 1.47), use of antiplatelet medication (OR, 4.29), and low Peripheral Artery Questionnaire symptom severity (OR, 1.48) were significant independent predictors of SSI.
- Operative factors: Prolonged procedural length (OR, 2.95), iodine-only antiseptic skin preparation (OR, 1.73), and high peak intraoperative glucose (defined as a peak glucose greater than 180 mg/dL; OR, 1.99) were significant independent predictors of SSI. However, concomitant stent placement was found to be significantly predictive (OR, .38), “perhaps due to improvement in regional and subcutaneous vascular flow after the intervention,” the researchers suggested.
- Hospital factors: Larger overall hospital size (OR, 2.22) and major teaching center (OR, 1.66) were associated with increased risk of SSI. “Interestingly, we did not find an association with SSI and the hospital annual volume or the hospital urgent/emergent procedure rate,” the researchers added.
SSIs were not found to be significantly associated with a difference in 30-day mortality. However, they were significantly associated with an increased rate of several postoperative morbidities, including transfusion, lymph leak, major amputation, and open surgical bypass revision at or within 30 days of the index operation, according to Dr. Davis and his colleagues.
“Although some factors, such as patients comorbidities, are not modifiable, others represent areas for quality improvement in at-risk patients,” the researchers indicated. “Diligence should be devoted to decreasing operative length, controlling intraoperative glucose levels, and avoiding iodine-only skin preparation to decrease the rate of SSIs and its numerous associate morbidities in vascular surgery patients.”
In discussing the issue of antiplatelet medication being an indicator of increased risk, the authors pointed out that it was a hitherto unreported factor in the vascular literature, and of concern because, “as expected, a high percentage of patients (78.7%) were taking antiplatelet medication at the time of their LEB.”
Because the association of antiplatelet medication with SSIs was independent of the need for operative transfusion or the need for repeat intervention, the researchers speculated that “all antiplatelet agents have the theoretical potential to diminish activation-dependent platelet immune functions.” They referred to previous studies showing that clopidogrel was associated with significantly higher clinical rates of infection, particularly pneumonia.
Limitations cited for the study were the retrospective nature of the database analysis, the possibility of confounders not assessed in the data, and the fact that outcomes were limited to 30-day events, which would not take into account longer-term graft failure or mortality.
The authors reported having no conflicts of interest with regard to the study.
Patient, operative, and hospital factors were found to be significant predictors of the risk of surgical site infection in patients who underwent open lower extremity bypass procedures, according to the results of a retrospective data analysis.
The study assessed the outcomes of 3,033 patients who underwent elective or urgent open LEB procedures between January 2012 and June 2015 using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Vascular Intervention Collaborative (BMC2 VIC), a statewide cardiovascular consortium of 35 hospitals, according to Frank M. Davis, MD, and his colleagues at the University of Michigan, Ann Arbor.
Demographic information, medical history, laboratory test results before and after the procedure, procedural indication, procedural urgency, technical details of procedures, and associated complications were assessed for each patient. Women comprised 31% of patients, the average patient age was 66 years, and 83% of the population was white (J Vasc Surg. 2017 Jun;65[6]:1769-78).
Among all of the patients treated, 320 developed SSIs and 2,713 did not. The procedural indications included one or more of the following: claudication (72%), rest pain (50.5%), ulcer/gangrene (32.4%), or acute limb ischemia (15.1%). Antibiotics were appropriately administered to 97% of the patients, according to the researchers, “demonstrating high compliance across the BMC2 VIC.”
- Patient factors: As indicated by previous studies, obesity (odds ratio, 1.78), dialysis dependence (OR, 4.33), and hypertension (OR, 4.29) conferred a significant increased risk of SSI after LEB, according to Dr. Davis and his colleagues. In addition, however, they found that previous vascular surgery (OR, 1.57), previous percutaneous coronary intervention (OR, 1.47), use of antiplatelet medication (OR, 4.29), and low Peripheral Artery Questionnaire symptom severity (OR, 1.48) were significant independent predictors of SSI.
- Operative factors: Prolonged procedural length (OR, 2.95), iodine-only antiseptic skin preparation (OR, 1.73), and high peak intraoperative glucose (defined as a peak glucose greater than 180 mg/dL; OR, 1.99) were significant independent predictors of SSI. However, concomitant stent placement was found to be significantly predictive (OR, .38), “perhaps due to improvement in regional and subcutaneous vascular flow after the intervention,” the researchers suggested.
- Hospital factors: Larger overall hospital size (OR, 2.22) and major teaching center (OR, 1.66) were associated with increased risk of SSI. “Interestingly, we did not find an association with SSI and the hospital annual volume or the hospital urgent/emergent procedure rate,” the researchers added.
SSIs were not found to be significantly associated with a difference in 30-day mortality. However, they were significantly associated with an increased rate of several postoperative morbidities, including transfusion, lymph leak, major amputation, and open surgical bypass revision at or within 30 days of the index operation, according to Dr. Davis and his colleagues.
“Although some factors, such as patients comorbidities, are not modifiable, others represent areas for quality improvement in at-risk patients,” the researchers indicated. “Diligence should be devoted to decreasing operative length, controlling intraoperative glucose levels, and avoiding iodine-only skin preparation to decrease the rate of SSIs and its numerous associate morbidities in vascular surgery patients.”
In discussing the issue of antiplatelet medication being an indicator of increased risk, the authors pointed out that it was a hitherto unreported factor in the vascular literature, and of concern because, “as expected, a high percentage of patients (78.7%) were taking antiplatelet medication at the time of their LEB.”
Because the association of antiplatelet medication with SSIs was independent of the need for operative transfusion or the need for repeat intervention, the researchers speculated that “all antiplatelet agents have the theoretical potential to diminish activation-dependent platelet immune functions.” They referred to previous studies showing that clopidogrel was associated with significantly higher clinical rates of infection, particularly pneumonia.
Limitations cited for the study were the retrospective nature of the database analysis, the possibility of confounders not assessed in the data, and the fact that outcomes were limited to 30-day events, which would not take into account longer-term graft failure or mortality.
The authors reported having no conflicts of interest with regard to the study.
Patient, operative, and hospital factors were found to be significant predictors of the risk of surgical site infection in patients who underwent open lower extremity bypass procedures, according to the results of a retrospective data analysis.
The study assessed the outcomes of 3,033 patients who underwent elective or urgent open LEB procedures between January 2012 and June 2015 using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Vascular Intervention Collaborative (BMC2 VIC), a statewide cardiovascular consortium of 35 hospitals, according to Frank M. Davis, MD, and his colleagues at the University of Michigan, Ann Arbor.
Demographic information, medical history, laboratory test results before and after the procedure, procedural indication, procedural urgency, technical details of procedures, and associated complications were assessed for each patient. Women comprised 31% of patients, the average patient age was 66 years, and 83% of the population was white (J Vasc Surg. 2017 Jun;65[6]:1769-78).
Among all of the patients treated, 320 developed SSIs and 2,713 did not. The procedural indications included one or more of the following: claudication (72%), rest pain (50.5%), ulcer/gangrene (32.4%), or acute limb ischemia (15.1%). Antibiotics were appropriately administered to 97% of the patients, according to the researchers, “demonstrating high compliance across the BMC2 VIC.”
- Patient factors: As indicated by previous studies, obesity (odds ratio, 1.78), dialysis dependence (OR, 4.33), and hypertension (OR, 4.29) conferred a significant increased risk of SSI after LEB, according to Dr. Davis and his colleagues. In addition, however, they found that previous vascular surgery (OR, 1.57), previous percutaneous coronary intervention (OR, 1.47), use of antiplatelet medication (OR, 4.29), and low Peripheral Artery Questionnaire symptom severity (OR, 1.48) were significant independent predictors of SSI.
- Operative factors: Prolonged procedural length (OR, 2.95), iodine-only antiseptic skin preparation (OR, 1.73), and high peak intraoperative glucose (defined as a peak glucose greater than 180 mg/dL; OR, 1.99) were significant independent predictors of SSI. However, concomitant stent placement was found to be significantly predictive (OR, .38), “perhaps due to improvement in regional and subcutaneous vascular flow after the intervention,” the researchers suggested.
- Hospital factors: Larger overall hospital size (OR, 2.22) and major teaching center (OR, 1.66) were associated with increased risk of SSI. “Interestingly, we did not find an association with SSI and the hospital annual volume or the hospital urgent/emergent procedure rate,” the researchers added.
SSIs were not found to be significantly associated with a difference in 30-day mortality. However, they were significantly associated with an increased rate of several postoperative morbidities, including transfusion, lymph leak, major amputation, and open surgical bypass revision at or within 30 days of the index operation, according to Dr. Davis and his colleagues.
“Although some factors, such as patients comorbidities, are not modifiable, others represent areas for quality improvement in at-risk patients,” the researchers indicated. “Diligence should be devoted to decreasing operative length, controlling intraoperative glucose levels, and avoiding iodine-only skin preparation to decrease the rate of SSIs and its numerous associate morbidities in vascular surgery patients.”
In discussing the issue of antiplatelet medication being an indicator of increased risk, the authors pointed out that it was a hitherto unreported factor in the vascular literature, and of concern because, “as expected, a high percentage of patients (78.7%) were taking antiplatelet medication at the time of their LEB.”
Because the association of antiplatelet medication with SSIs was independent of the need for operative transfusion or the need for repeat intervention, the researchers speculated that “all antiplatelet agents have the theoretical potential to diminish activation-dependent platelet immune functions.” They referred to previous studies showing that clopidogrel was associated with significantly higher clinical rates of infection, particularly pneumonia.
Limitations cited for the study were the retrospective nature of the database analysis, the possibility of confounders not assessed in the data, and the fact that outcomes were limited to 30-day events, which would not take into account longer-term graft failure or mortality.
The authors reported having no conflicts of interest with regard to the study.
FROM THE JOURNAL OF VASCULAR SURGERY
Key clinical point:
Major finding: SSIs occurred in 10.6% of lower extremity bypasses.
Data source: A retrospective analysis of 3,033 elective or urgent open LEB procedures performed over a 3.5-year period in a statewide cardiovascular consortium of 35 hospitals.
Disclosures: The authors reported having no conflicts of interest with regard to the study.
Better bariatric surgery outcomes with lower preoperative BMI
Delaying bariatric surgery until body mass index is highly elevated may reduce the likelihood of achieving a BMI of less than 30 within a year, according to a paper published online July 26 in JAMA Surgery.
A retrospective study using prospectively gathered clinical data of 27,320 adults who underwent bariatric surgery in Michigan showed around one in three (36%) achieved a BMI below 30 within a year after surgery (JAMA Surgery 2017, July 26. doi: 10.1001/jamasurg.2017.2348). But obese patients with a body mass index of less than 40 kg/m2 before undergoing bariatric surgery are significantly more likely to achieve a postoperative BMI of under 30.
Individuals who had a preoperative BMI of less than 40 had a 12-fold higher chance of getting their BMI below 30, compared to those whose preoperative BMI was 40 or above (95% confidence interval 1.71-14.16, P less than .001). Only 8.5% of individuals with a BMI at or above 50 achieved a postoperative BMI below 30.
The likelihood of getting below 30 within a year was eightfold higher in patients who had a sleeve gastrectomy, 21 times greater in those who underwent Roux-en-Y bypass, and 82 times higher in those who had a duodenal switch, compared with patients who had adjustable gastric banding (P less than .001).
The researchers also compared other outcomes in individuals whose BMI dropped below 30 and in those who did not achieve this degree of weight loss. The analysis showed that those with a BMI below 30 after 1 year had at least a twofold greater chance of discontinuing cholesterol-lowering medications, insulin, diabetes medications, antihypertensives, and CPAP for sleep apnea, compared with those whose BMI remained at 30 or above. They were also more than three times more likely to report being ‘very satisfied’ with the outcomes of surgery.
The authors noted that the cohort’s mean BMI was 48, which was above the established threshold for bariatric surgery, namely a BMI of 40, or 35 with weight-related comorbidities.
“Our results suggest that patients with morbid obesity should be targeted for surgery when their BMI is still less than 40, as these patients are more likely to achieve a target BMI that results in substantial reduction in weight-related comorbidities,” the authors wrote.
However, they stressed that their findings should not be taken as a reason to exclude patients with a BMI above 40 from surgery, pointing out that even for patients with higher preoperative BMIs, bariatric surgery offered substantial health and quality of life benefits.
They also acknowledged that 1-year weight data was available for around 50% of patients in the registry, which may have led to selection bias.
“Policies and practice patterns that delay or incentivize patients to pursue bariatric surgery only once the BMI is highly elevated can result in inferior outcomes,” the investigators concluded.
Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.
The authors’ conclusion that bariatric surgery should be more liberally applied to patients with less severe obesity is consistent with multiple reports of improved control of type 2 diabetes, if not remission, among lower-BMI patient populations following MBS [metabolic and bariatric surgery]. However, these reports generally do not refute the importance of weight loss in achieving important clinical benefit among patients with obesity-related comorbid disease.
One strength of the present study is that it is a clinical database. However, 50% attrition of the follow-up weight loss data at 1 year is potentially problematic.
Bruce M. Wolfe, MD, FACS, and Elizaveta Walker, MPH, are in the division of bariatric surgery, department of surgery, at Oregon Health & Science University, Portland. These comments are taken from an accompanying editorial (JAMA Surgery 2017 Jul 26. doi: 10.1001/jamasurg.2017.2349). No conflicts of interest were declared.
The authors’ conclusion that bariatric surgery should be more liberally applied to patients with less severe obesity is consistent with multiple reports of improved control of type 2 diabetes, if not remission, among lower-BMI patient populations following MBS [metabolic and bariatric surgery]. However, these reports generally do not refute the importance of weight loss in achieving important clinical benefit among patients with obesity-related comorbid disease.
One strength of the present study is that it is a clinical database. However, 50% attrition of the follow-up weight loss data at 1 year is potentially problematic.
Bruce M. Wolfe, MD, FACS, and Elizaveta Walker, MPH, are in the division of bariatric surgery, department of surgery, at Oregon Health & Science University, Portland. These comments are taken from an accompanying editorial (JAMA Surgery 2017 Jul 26. doi: 10.1001/jamasurg.2017.2349). No conflicts of interest were declared.
The authors’ conclusion that bariatric surgery should be more liberally applied to patients with less severe obesity is consistent with multiple reports of improved control of type 2 diabetes, if not remission, among lower-BMI patient populations following MBS [metabolic and bariatric surgery]. However, these reports generally do not refute the importance of weight loss in achieving important clinical benefit among patients with obesity-related comorbid disease.
One strength of the present study is that it is a clinical database. However, 50% attrition of the follow-up weight loss data at 1 year is potentially problematic.
Bruce M. Wolfe, MD, FACS, and Elizaveta Walker, MPH, are in the division of bariatric surgery, department of surgery, at Oregon Health & Science University, Portland. These comments are taken from an accompanying editorial (JAMA Surgery 2017 Jul 26. doi: 10.1001/jamasurg.2017.2349). No conflicts of interest were declared.
Delaying bariatric surgery until body mass index is highly elevated may reduce the likelihood of achieving a BMI of less than 30 within a year, according to a paper published online July 26 in JAMA Surgery.
A retrospective study using prospectively gathered clinical data of 27,320 adults who underwent bariatric surgery in Michigan showed around one in three (36%) achieved a BMI below 30 within a year after surgery (JAMA Surgery 2017, July 26. doi: 10.1001/jamasurg.2017.2348). But obese patients with a body mass index of less than 40 kg/m2 before undergoing bariatric surgery are significantly more likely to achieve a postoperative BMI of under 30.
Individuals who had a preoperative BMI of less than 40 had a 12-fold higher chance of getting their BMI below 30, compared to those whose preoperative BMI was 40 or above (95% confidence interval 1.71-14.16, P less than .001). Only 8.5% of individuals with a BMI at or above 50 achieved a postoperative BMI below 30.
The likelihood of getting below 30 within a year was eightfold higher in patients who had a sleeve gastrectomy, 21 times greater in those who underwent Roux-en-Y bypass, and 82 times higher in those who had a duodenal switch, compared with patients who had adjustable gastric banding (P less than .001).
The researchers also compared other outcomes in individuals whose BMI dropped below 30 and in those who did not achieve this degree of weight loss. The analysis showed that those with a BMI below 30 after 1 year had at least a twofold greater chance of discontinuing cholesterol-lowering medications, insulin, diabetes medications, antihypertensives, and CPAP for sleep apnea, compared with those whose BMI remained at 30 or above. They were also more than three times more likely to report being ‘very satisfied’ with the outcomes of surgery.
The authors noted that the cohort’s mean BMI was 48, which was above the established threshold for bariatric surgery, namely a BMI of 40, or 35 with weight-related comorbidities.
“Our results suggest that patients with morbid obesity should be targeted for surgery when their BMI is still less than 40, as these patients are more likely to achieve a target BMI that results in substantial reduction in weight-related comorbidities,” the authors wrote.
However, they stressed that their findings should not be taken as a reason to exclude patients with a BMI above 40 from surgery, pointing out that even for patients with higher preoperative BMIs, bariatric surgery offered substantial health and quality of life benefits.
They also acknowledged that 1-year weight data was available for around 50% of patients in the registry, which may have led to selection bias.
“Policies and practice patterns that delay or incentivize patients to pursue bariatric surgery only once the BMI is highly elevated can result in inferior outcomes,” the investigators concluded.
Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.
Delaying bariatric surgery until body mass index is highly elevated may reduce the likelihood of achieving a BMI of less than 30 within a year, according to a paper published online July 26 in JAMA Surgery.
A retrospective study using prospectively gathered clinical data of 27,320 adults who underwent bariatric surgery in Michigan showed around one in three (36%) achieved a BMI below 30 within a year after surgery (JAMA Surgery 2017, July 26. doi: 10.1001/jamasurg.2017.2348). But obese patients with a body mass index of less than 40 kg/m2 before undergoing bariatric surgery are significantly more likely to achieve a postoperative BMI of under 30.
Individuals who had a preoperative BMI of less than 40 had a 12-fold higher chance of getting their BMI below 30, compared to those whose preoperative BMI was 40 or above (95% confidence interval 1.71-14.16, P less than .001). Only 8.5% of individuals with a BMI at or above 50 achieved a postoperative BMI below 30.
The likelihood of getting below 30 within a year was eightfold higher in patients who had a sleeve gastrectomy, 21 times greater in those who underwent Roux-en-Y bypass, and 82 times higher in those who had a duodenal switch, compared with patients who had adjustable gastric banding (P less than .001).
The researchers also compared other outcomes in individuals whose BMI dropped below 30 and in those who did not achieve this degree of weight loss. The analysis showed that those with a BMI below 30 after 1 year had at least a twofold greater chance of discontinuing cholesterol-lowering medications, insulin, diabetes medications, antihypertensives, and CPAP for sleep apnea, compared with those whose BMI remained at 30 or above. They were also more than three times more likely to report being ‘very satisfied’ with the outcomes of surgery.
The authors noted that the cohort’s mean BMI was 48, which was above the established threshold for bariatric surgery, namely a BMI of 40, or 35 with weight-related comorbidities.
“Our results suggest that patients with morbid obesity should be targeted for surgery when their BMI is still less than 40, as these patients are more likely to achieve a target BMI that results in substantial reduction in weight-related comorbidities,” the authors wrote.
However, they stressed that their findings should not be taken as a reason to exclude patients with a BMI above 40 from surgery, pointing out that even for patients with higher preoperative BMIs, bariatric surgery offered substantial health and quality of life benefits.
They also acknowledged that 1-year weight data was available for around 50% of patients in the registry, which may have led to selection bias.
“Policies and practice patterns that delay or incentivize patients to pursue bariatric surgery only once the BMI is highly elevated can result in inferior outcomes,” the investigators concluded.
Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.
FROM JAMA SURGERY
Key clinical point: A BMI below 40 prior to undergoing bariatric surgery gives patients a significantly better chance of achieving a 1-year postoperative BMI under 30.
Major finding: Obese patients with a BMI less than 40 before undergoing bariatric surgery are more than 12 times more likely to achieve a postoperative BMI of under 30.
Data source: A retrospective study using prospectively gathered clinical data of 27, 320 adults who underwent bariatric surgery.
Disclosures: Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.
First Senate vote to repeal and replace ACA fails
Senate Republicans’ first attempt to repeal and replace the Affordable Care Act failed July 25 as nine Republican senators crossed the aisle to vote against a measure that had no chance of passing.
The process started with a dramatic appearance by Sen. John McCain (R-Ariz.), recovering from surgery to diagnose glioblastoma, who returned to Washington to cast a key vote that would allow debate to move forward. The Senate split 50-50 on that vote, with Sen. Susan Collins (R-Maine) and Sen. Lisa Murkowski (R-Alaska) crossing the aisle to vote with all the chamber’s Democrats against the motion to proceed. Vice President Mike Pence cast the tie-breaking vote in favor of beginning debate.
However, the first amendment voted on would have replaced that language with the most recent version of the Senate GOP repeal-and-replace plan, the Better Care Reconciliation Act, with two additional provisions. One was from Sen. Ted Cruz (R-Tex.) and would allow insurers to offer more limited health insurance plans along side plans that cover the ACA’s essential benefits package. A second provision from Sen. Rob Portman (R-Ohio) would have added an additional $100 billion to the state stability fund to help low-income individuals whose Medicaid coverage was repealed.
The amendment was dead on arrival, as it would have needed 60 votes to pass. Throughout the repeal-and-replace effort, the 48 Senate Democrats have been firm in voting against any action. While much of the repeal-and-replace effort to date has relied on the budget reconciliation process, which requires a simple majority for passage, this legislation did not qualify and needed a supermajority of 60 votes for passage.
The nine GOP senators voting against the amendment included Collins, Murkowski, Bob Corker (Tenn.), Tom Cotton (Ark.), Lindsey Graham (S.C.), Dena Heller (Nev.), Mike Lee (Utah), Jerry Moran (Kan.), and Rand Paul (Ky.).
Earlier in the day, just after voting in favor of action on this legislation, Sen. McCain pleaded with his colleagues to return to regular order and write a bill that has bipartisan support. He criticized congressional Democrats for forcing the ACA through without bipartisan support 7 years ago and congressional Republicans for doing the exact same thing now with their repeal-and-replace efforts.
“Why don’t we try the old way of legislating in the Senate, the way our rules and customs encourage us to act,” Sen. McCain asked. “Let the Health, Education, Labor, and Pensions Committee under Chairman Alexander and Ranking Member Murray hold hearings, try to report a bill out of committee with contributions from both sides. Then bring it to the floor for amendment and debate and see if we can pass something that will be imperfect, full of compromises, and not very pleasing to implacable partisans on either side but that might provide workable solutions to problems Americans are struggling with today.”
Senate Republicans’ first attempt to repeal and replace the Affordable Care Act failed July 25 as nine Republican senators crossed the aisle to vote against a measure that had no chance of passing.
The process started with a dramatic appearance by Sen. John McCain (R-Ariz.), recovering from surgery to diagnose glioblastoma, who returned to Washington to cast a key vote that would allow debate to move forward. The Senate split 50-50 on that vote, with Sen. Susan Collins (R-Maine) and Sen. Lisa Murkowski (R-Alaska) crossing the aisle to vote with all the chamber’s Democrats against the motion to proceed. Vice President Mike Pence cast the tie-breaking vote in favor of beginning debate.
However, the first amendment voted on would have replaced that language with the most recent version of the Senate GOP repeal-and-replace plan, the Better Care Reconciliation Act, with two additional provisions. One was from Sen. Ted Cruz (R-Tex.) and would allow insurers to offer more limited health insurance plans along side plans that cover the ACA’s essential benefits package. A second provision from Sen. Rob Portman (R-Ohio) would have added an additional $100 billion to the state stability fund to help low-income individuals whose Medicaid coverage was repealed.
The amendment was dead on arrival, as it would have needed 60 votes to pass. Throughout the repeal-and-replace effort, the 48 Senate Democrats have been firm in voting against any action. While much of the repeal-and-replace effort to date has relied on the budget reconciliation process, which requires a simple majority for passage, this legislation did not qualify and needed a supermajority of 60 votes for passage.
The nine GOP senators voting against the amendment included Collins, Murkowski, Bob Corker (Tenn.), Tom Cotton (Ark.), Lindsey Graham (S.C.), Dena Heller (Nev.), Mike Lee (Utah), Jerry Moran (Kan.), and Rand Paul (Ky.).
Earlier in the day, just after voting in favor of action on this legislation, Sen. McCain pleaded with his colleagues to return to regular order and write a bill that has bipartisan support. He criticized congressional Democrats for forcing the ACA through without bipartisan support 7 years ago and congressional Republicans for doing the exact same thing now with their repeal-and-replace efforts.
“Why don’t we try the old way of legislating in the Senate, the way our rules and customs encourage us to act,” Sen. McCain asked. “Let the Health, Education, Labor, and Pensions Committee under Chairman Alexander and Ranking Member Murray hold hearings, try to report a bill out of committee with contributions from both sides. Then bring it to the floor for amendment and debate and see if we can pass something that will be imperfect, full of compromises, and not very pleasing to implacable partisans on either side but that might provide workable solutions to problems Americans are struggling with today.”
Senate Republicans’ first attempt to repeal and replace the Affordable Care Act failed July 25 as nine Republican senators crossed the aisle to vote against a measure that had no chance of passing.
The process started with a dramatic appearance by Sen. John McCain (R-Ariz.), recovering from surgery to diagnose glioblastoma, who returned to Washington to cast a key vote that would allow debate to move forward. The Senate split 50-50 on that vote, with Sen. Susan Collins (R-Maine) and Sen. Lisa Murkowski (R-Alaska) crossing the aisle to vote with all the chamber’s Democrats against the motion to proceed. Vice President Mike Pence cast the tie-breaking vote in favor of beginning debate.
However, the first amendment voted on would have replaced that language with the most recent version of the Senate GOP repeal-and-replace plan, the Better Care Reconciliation Act, with two additional provisions. One was from Sen. Ted Cruz (R-Tex.) and would allow insurers to offer more limited health insurance plans along side plans that cover the ACA’s essential benefits package. A second provision from Sen. Rob Portman (R-Ohio) would have added an additional $100 billion to the state stability fund to help low-income individuals whose Medicaid coverage was repealed.
The amendment was dead on arrival, as it would have needed 60 votes to pass. Throughout the repeal-and-replace effort, the 48 Senate Democrats have been firm in voting against any action. While much of the repeal-and-replace effort to date has relied on the budget reconciliation process, which requires a simple majority for passage, this legislation did not qualify and needed a supermajority of 60 votes for passage.
The nine GOP senators voting against the amendment included Collins, Murkowski, Bob Corker (Tenn.), Tom Cotton (Ark.), Lindsey Graham (S.C.), Dena Heller (Nev.), Mike Lee (Utah), Jerry Moran (Kan.), and Rand Paul (Ky.).
Earlier in the day, just after voting in favor of action on this legislation, Sen. McCain pleaded with his colleagues to return to regular order and write a bill that has bipartisan support. He criticized congressional Democrats for forcing the ACA through without bipartisan support 7 years ago and congressional Republicans for doing the exact same thing now with their repeal-and-replace efforts.
“Why don’t we try the old way of legislating in the Senate, the way our rules and customs encourage us to act,” Sen. McCain asked. “Let the Health, Education, Labor, and Pensions Committee under Chairman Alexander and Ranking Member Murray hold hearings, try to report a bill out of committee with contributions from both sides. Then bring it to the floor for amendment and debate and see if we can pass something that will be imperfect, full of compromises, and not very pleasing to implacable partisans on either side but that might provide workable solutions to problems Americans are struggling with today.”
Light Therapy May Treat Excessive Daytime Sleepiness in Parkinson’s Disease
Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues. 
Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.
One-Hour Treatment Intervals
To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.
They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.
During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.
The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.
Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.
In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.
Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.
Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.
Chronobiologic Interventions
The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce
—Jake Remaly
Suggested Reading
Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.
Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.
Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.
Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.
One-Hour Treatment Intervals
To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.
They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.
During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.
The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.
Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.
In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.
Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.
Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.
Chronobiologic Interventions
The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce
—Jake Remaly
Suggested Reading
Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.
Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.
Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.
Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.
One-Hour Treatment Intervals
To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.
They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.
During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.
The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.
Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.
In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.
Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.
Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.
Chronobiologic Interventions
The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce
—Jake Remaly
Suggested Reading
Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.
Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.
More treatments becoming available for tardive dyskinesia
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. 
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
EXPERT ANALYSIS FROM The ASCP ANNUAL MEETING
Do you talk about marijuana with your patients?
Do you talk about marijuana with your patients?
In medical school, I had a roommate. He was a smart law school graduate, good looking, outgoing, had lots of friends, was funny, and he was a great cook.
I should tell you another thing about my friend: He was a heavy, daily user of marijuana.
I believe that most of us, at a certain point of our lives, have met someone like my friend. The combination of a high-stress lifestyle, high self-expectations, and lack of appropriate skills to tackle life’s obstacles when encountered with failure frequently leads to addiction or a behavioral problem. In most cases, that will cause a pathological relationship with an outside substance or stimuli (Internet overuse/shopping too much/overeating or drinking, and so on).
Living a life filled with severe trauma and pain, especially at a developmental stage, often leads to an addiction. We frequently see people escape to the sweet narcotic-induced sleep via opioid abuse. On the other hand, for people who did not suffer trauma and are highly functional, marijuana offers a means of emotional detachment from pain, in its different form, and existential depression. That is the main benefit my patients who live with marijuana addiction get.
My friend serves as a rather stereotypical – and some may say – subjective, simplistic example of what is becoming more and more common in our society. I’m willing to bet that a good number of clinicians who read this have a similar example in mind.
With its intoxication state perceived as benign and the limited medicinal advantages, marijuana rapidly is gaining more and more legitimacy in the eyes of the general public (Addict Behav. 2008 Mar;33:397-411), (Monitoring the Future: National Results on Drug Use: 1975-2016). The risk of addiction is perceived as negligible and often nonexistent.
Almost no one knows about the potential risk of addiction (around 9%) (Drug Alcohol Depend. 2011;115:120-30). No one knows about about tolerance and withdrawal states – or about the real risk of psychosis (N Engl J Med. 2014 Jun 5;370:2219-27) or about the possible risk of schizophrenia in vulnerable populations (Schizophr Res. 2016 Mar;171:[1-3]:62-7). No one talks about the fact that it’s often used with tobacco. (How many times have you been told during history taking that a patient doesn’t smoke tobacco, only to find that in drug history he smokes 3-5 joints with tobacco daily?)
[polldaddy:9796432]
Throughout my journey in the psychiatric world (studying and working on three different continents) another typical marijuana user is the patient living with chronic mental illness. My Israeli mentor often complained about not having a single “clean” patient with schizophrenia anymore. I now see the same phenomena in Philadelphia and was also exposed to the same reality in Europe during medical school.
As physicians, and especially as psychiatrists, I believe we are obligated to educate our patients by telling them about the risks in their behaviors. Educating patients about marijuana in today’s atmosphere can be a very important preventive measure, and awareness is an important step toward change.
The current generation of psychiatrists is dealing with an opioid epidemic. Let’s educate ourselves and our patients so this current epidemic won’t be followed by another, severe cannabis epidemic.
Dr. Shilo is a second-year PGY in the department of psychiatry at Einstein Medical Center, Philadelphia.
Do you talk about marijuana with your patients?
In medical school, I had a roommate. He was a smart law school graduate, good looking, outgoing, had lots of friends, was funny, and he was a great cook.
I should tell you another thing about my friend: He was a heavy, daily user of marijuana.
I believe that most of us, at a certain point of our lives, have met someone like my friend. The combination of a high-stress lifestyle, high self-expectations, and lack of appropriate skills to tackle life’s obstacles when encountered with failure frequently leads to addiction or a behavioral problem. In most cases, that will cause a pathological relationship with an outside substance or stimuli (Internet overuse/shopping too much/overeating or drinking, and so on).
Living a life filled with severe trauma and pain, especially at a developmental stage, often leads to an addiction. We frequently see people escape to the sweet narcotic-induced sleep via opioid abuse. On the other hand, for people who did not suffer trauma and are highly functional, marijuana offers a means of emotional detachment from pain, in its different form, and existential depression. That is the main benefit my patients who live with marijuana addiction get.
My friend serves as a rather stereotypical – and some may say – subjective, simplistic example of what is becoming more and more common in our society. I’m willing to bet that a good number of clinicians who read this have a similar example in mind.
With its intoxication state perceived as benign and the limited medicinal advantages, marijuana rapidly is gaining more and more legitimacy in the eyes of the general public (Addict Behav. 2008 Mar;33:397-411), (Monitoring the Future: National Results on Drug Use: 1975-2016). The risk of addiction is perceived as negligible and often nonexistent.
Almost no one knows about the potential risk of addiction (around 9%) (Drug Alcohol Depend. 2011;115:120-30). No one knows about about tolerance and withdrawal states – or about the real risk of psychosis (N Engl J Med. 2014 Jun 5;370:2219-27) or about the possible risk of schizophrenia in vulnerable populations (Schizophr Res. 2016 Mar;171:[1-3]:62-7). No one talks about the fact that it’s often used with tobacco. (How many times have you been told during history taking that a patient doesn’t smoke tobacco, only to find that in drug history he smokes 3-5 joints with tobacco daily?)
[polldaddy:9796432]
Throughout my journey in the psychiatric world (studying and working on three different continents) another typical marijuana user is the patient living with chronic mental illness. My Israeli mentor often complained about not having a single “clean” patient with schizophrenia anymore. I now see the same phenomena in Philadelphia and was also exposed to the same reality in Europe during medical school.
As physicians, and especially as psychiatrists, I believe we are obligated to educate our patients by telling them about the risks in their behaviors. Educating patients about marijuana in today’s atmosphere can be a very important preventive measure, and awareness is an important step toward change.
The current generation of psychiatrists is dealing with an opioid epidemic. Let’s educate ourselves and our patients so this current epidemic won’t be followed by another, severe cannabis epidemic.
Dr. Shilo is a second-year PGY in the department of psychiatry at Einstein Medical Center, Philadelphia.
Do you talk about marijuana with your patients?
In medical school, I had a roommate. He was a smart law school graduate, good looking, outgoing, had lots of friends, was funny, and he was a great cook.
I should tell you another thing about my friend: He was a heavy, daily user of marijuana.
I believe that most of us, at a certain point of our lives, have met someone like my friend. The combination of a high-stress lifestyle, high self-expectations, and lack of appropriate skills to tackle life’s obstacles when encountered with failure frequently leads to addiction or a behavioral problem. In most cases, that will cause a pathological relationship with an outside substance or stimuli (Internet overuse/shopping too much/overeating or drinking, and so on).
Living a life filled with severe trauma and pain, especially at a developmental stage, often leads to an addiction. We frequently see people escape to the sweet narcotic-induced sleep via opioid abuse. On the other hand, for people who did not suffer trauma and are highly functional, marijuana offers a means of emotional detachment from pain, in its different form, and existential depression. That is the main benefit my patients who live with marijuana addiction get.
My friend serves as a rather stereotypical – and some may say – subjective, simplistic example of what is becoming more and more common in our society. I’m willing to bet that a good number of clinicians who read this have a similar example in mind.
With its intoxication state perceived as benign and the limited medicinal advantages, marijuana rapidly is gaining more and more legitimacy in the eyes of the general public (Addict Behav. 2008 Mar;33:397-411), (Monitoring the Future: National Results on Drug Use: 1975-2016). The risk of addiction is perceived as negligible and often nonexistent.
Almost no one knows about the potential risk of addiction (around 9%) (Drug Alcohol Depend. 2011;115:120-30). No one knows about about tolerance and withdrawal states – or about the real risk of psychosis (N Engl J Med. 2014 Jun 5;370:2219-27) or about the possible risk of schizophrenia in vulnerable populations (Schizophr Res. 2016 Mar;171:[1-3]:62-7). No one talks about the fact that it’s often used with tobacco. (How many times have you been told during history taking that a patient doesn’t smoke tobacco, only to find that in drug history he smokes 3-5 joints with tobacco daily?)
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Throughout my journey in the psychiatric world (studying and working on three different continents) another typical marijuana user is the patient living with chronic mental illness. My Israeli mentor often complained about not having a single “clean” patient with schizophrenia anymore. I now see the same phenomena in Philadelphia and was also exposed to the same reality in Europe during medical school.
As physicians, and especially as psychiatrists, I believe we are obligated to educate our patients by telling them about the risks in their behaviors. Educating patients about marijuana in today’s atmosphere can be a very important preventive measure, and awareness is an important step toward change.
The current generation of psychiatrists is dealing with an opioid epidemic. Let’s educate ourselves and our patients so this current epidemic won’t be followed by another, severe cannabis epidemic.
Dr. Shilo is a second-year PGY in the department of psychiatry at Einstein Medical Center, Philadelphia.
Student Hospitalist Scholars: The importance of communication
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform healthcare and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their 1st, 2nd, and 3rd years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
Quality improvement in clinical practice has recently become very important to me. What use is clinical knowledge if it cannot be appropriately used to benefit patients in a clinical setting?
Throughout my 1st year at medical school, my interest in communication continued to grow. In one of my classes, Essentials of Clinical Reasoning, we were taught to continually consider how to effectively translate our thought processes and potential diagnoses to our patients. To begin crafting effective HPIs, we created complete, whole histories from visit to visit.
At this time, I discovered the subfield of research concerning strategies surrounding handoffs as transition of care changes, with patients often suffering due to breakdowns in communication.
With my interest in handoffs, and with direction from the Society of Hospital Medicine, I reached out to Dr. Vineet Arora, a leading academic hospitalist at the University of Chicago with a highly impressive history of research concerning quality of care toward hospitalized adults. Under the supervision of Dr. Arora and Dr. Juan Rojas, a pulmonary critical care fellow, I will help investigate whether receiving floor physicians and intensive care unit physicians possess similar shared mental models in regards to the most pertinent point of care – when patients are transferred out of the ICU.
We seek to identify if there are any associations present between readmission from the general floor, the providers’ rated likelihood of the patient returning to the ICU, and whether floor and ICU physicians are on the same page concerning condition management while on the floor.
I believe the experience I gain at the University of Chicago Medical Center will be invaluable to my future as a physician. I am very excited to get to know the various clinicians at UChicago, to gain clinical experience by observing the management of the general ward, and to identify how effective physicians communicate.
Above all, I hope to use any knowledge I gain this summer to become an efficient, knowledgeable, and compassionate physician capable of providing the highest quality of care to my future patients.
Anton Garazha is a medical student at Chicago Medical School at Rosalind Franklin University in North Chicago, Ill. He received his B.S. in Biology from Loyola University in Chicago in 2015 and his Master of Biomedical Science from Rosalind Franklin University in 2016. Anton is very interested in community outreach and quality improvement, and in his spare time tutors students in science-based subjects.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform healthcare and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their 1st, 2nd, and 3rd years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
Quality improvement in clinical practice has recently become very important to me. What use is clinical knowledge if it cannot be appropriately used to benefit patients in a clinical setting?
Throughout my 1st year at medical school, my interest in communication continued to grow. In one of my classes, Essentials of Clinical Reasoning, we were taught to continually consider how to effectively translate our thought processes and potential diagnoses to our patients. To begin crafting effective HPIs, we created complete, whole histories from visit to visit.
At this time, I discovered the subfield of research concerning strategies surrounding handoffs as transition of care changes, with patients often suffering due to breakdowns in communication.
With my interest in handoffs, and with direction from the Society of Hospital Medicine, I reached out to Dr. Vineet Arora, a leading academic hospitalist at the University of Chicago with a highly impressive history of research concerning quality of care toward hospitalized adults. Under the supervision of Dr. Arora and Dr. Juan Rojas, a pulmonary critical care fellow, I will help investigate whether receiving floor physicians and intensive care unit physicians possess similar shared mental models in regards to the most pertinent point of care – when patients are transferred out of the ICU.
We seek to identify if there are any associations present between readmission from the general floor, the providers’ rated likelihood of the patient returning to the ICU, and whether floor and ICU physicians are on the same page concerning condition management while on the floor.
I believe the experience I gain at the University of Chicago Medical Center will be invaluable to my future as a physician. I am very excited to get to know the various clinicians at UChicago, to gain clinical experience by observing the management of the general ward, and to identify how effective physicians communicate.
Above all, I hope to use any knowledge I gain this summer to become an efficient, knowledgeable, and compassionate physician capable of providing the highest quality of care to my future patients.
Anton Garazha is a medical student at Chicago Medical School at Rosalind Franklin University in North Chicago, Ill. He received his B.S. in Biology from Loyola University in Chicago in 2015 and his Master of Biomedical Science from Rosalind Franklin University in 2016. Anton is very interested in community outreach and quality improvement, and in his spare time tutors students in science-based subjects.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform healthcare and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their 1st, 2nd, and 3rd years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
Quality improvement in clinical practice has recently become very important to me. What use is clinical knowledge if it cannot be appropriately used to benefit patients in a clinical setting?
Throughout my 1st year at medical school, my interest in communication continued to grow. In one of my classes, Essentials of Clinical Reasoning, we were taught to continually consider how to effectively translate our thought processes and potential diagnoses to our patients. To begin crafting effective HPIs, we created complete, whole histories from visit to visit.
At this time, I discovered the subfield of research concerning strategies surrounding handoffs as transition of care changes, with patients often suffering due to breakdowns in communication.
With my interest in handoffs, and with direction from the Society of Hospital Medicine, I reached out to Dr. Vineet Arora, a leading academic hospitalist at the University of Chicago with a highly impressive history of research concerning quality of care toward hospitalized adults. Under the supervision of Dr. Arora and Dr. Juan Rojas, a pulmonary critical care fellow, I will help investigate whether receiving floor physicians and intensive care unit physicians possess similar shared mental models in regards to the most pertinent point of care – when patients are transferred out of the ICU.
We seek to identify if there are any associations present between readmission from the general floor, the providers’ rated likelihood of the patient returning to the ICU, and whether floor and ICU physicians are on the same page concerning condition management while on the floor.
I believe the experience I gain at the University of Chicago Medical Center will be invaluable to my future as a physician. I am very excited to get to know the various clinicians at UChicago, to gain clinical experience by observing the management of the general ward, and to identify how effective physicians communicate.
Above all, I hope to use any knowledge I gain this summer to become an efficient, knowledgeable, and compassionate physician capable of providing the highest quality of care to my future patients.
Anton Garazha is a medical student at Chicago Medical School at Rosalind Franklin University in North Chicago, Ill. He received his B.S. in Biology from Loyola University in Chicago in 2015 and his Master of Biomedical Science from Rosalind Franklin University in 2016. Anton is very interested in community outreach and quality improvement, and in his spare time tutors students in science-based subjects.
Secondary Cancers After Prostate Cancer: What’s the Risk?
Men with prostate cancer (PCa) have a higher risk of secondary primary cancers (SPM) in the thyroid compared with that of men without PCa, say researchers from the National Defense Medical Center in Taipei and China Medical University in Taichung, both in Taiwan. Their study of 30,964 men also found a trend toward higher risk of SPM in the urinary bladder and rectum/anus.
Related: First Cancer Treatment Based on Biomarkers Is Approved
However, the study, which covered years 2000-2010, also showed a trend toward lower risk of developing overall SPM among PCa survivors, compared with men who did not have PCa. The risks of lung and liver cancer, for instance, were significantly lower. The risk of thyroid cancer was higher in patients diagnosed when aged < 64 years, but the overall number of cases was small, particularly in that group.
When the researchers analyzed the data according to treatment, they found that patients with PCa who had radiation therapy had a higher risk of overall SPM, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer, compared with those who did not have radiation therapy. The risk of hematologic malignancies and urinary bladder cancer were significantly lower in patients with PCa treated with androgen deprivation therapy than in those who were not.
Related: Treatment and Management of Patients With Prostate Cancer
Patients who had undergone prostatectomy had a significantly lower risk of overall SPM, hematologic malignancies, liver cancer, and urinary bladder cancer; however, they had a significantly higher risk of thyroid cancer.
The researchers say, given the increases in incidence and life expectancy of patients with PCa, there is growing interest in predicting the risk of SPM. Knowing the risk factors, they note, highlights the need for continued cancer surveillance among PCa survivors.
Source:
Fan CY, Huang WY, Lin CS, et al. PLoS One. 2017:12(4):e0175217.
doi: 10.1371/journal.pone.0175217.
Men with prostate cancer (PCa) have a higher risk of secondary primary cancers (SPM) in the thyroid compared with that of men without PCa, say researchers from the National Defense Medical Center in Taipei and China Medical University in Taichung, both in Taiwan. Their study of 30,964 men also found a trend toward higher risk of SPM in the urinary bladder and rectum/anus.
Related: First Cancer Treatment Based on Biomarkers Is Approved
However, the study, which covered years 2000-2010, also showed a trend toward lower risk of developing overall SPM among PCa survivors, compared with men who did not have PCa. The risks of lung and liver cancer, for instance, were significantly lower. The risk of thyroid cancer was higher in patients diagnosed when aged < 64 years, but the overall number of cases was small, particularly in that group.
When the researchers analyzed the data according to treatment, they found that patients with PCa who had radiation therapy had a higher risk of overall SPM, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer, compared with those who did not have radiation therapy. The risk of hematologic malignancies and urinary bladder cancer were significantly lower in patients with PCa treated with androgen deprivation therapy than in those who were not.
Related: Treatment and Management of Patients With Prostate Cancer
Patients who had undergone prostatectomy had a significantly lower risk of overall SPM, hematologic malignancies, liver cancer, and urinary bladder cancer; however, they had a significantly higher risk of thyroid cancer.
The researchers say, given the increases in incidence and life expectancy of patients with PCa, there is growing interest in predicting the risk of SPM. Knowing the risk factors, they note, highlights the need for continued cancer surveillance among PCa survivors.
Source:
Fan CY, Huang WY, Lin CS, et al. PLoS One. 2017:12(4):e0175217.
doi: 10.1371/journal.pone.0175217.
Men with prostate cancer (PCa) have a higher risk of secondary primary cancers (SPM) in the thyroid compared with that of men without PCa, say researchers from the National Defense Medical Center in Taipei and China Medical University in Taichung, both in Taiwan. Their study of 30,964 men also found a trend toward higher risk of SPM in the urinary bladder and rectum/anus.
Related: First Cancer Treatment Based on Biomarkers Is Approved
However, the study, which covered years 2000-2010, also showed a trend toward lower risk of developing overall SPM among PCa survivors, compared with men who did not have PCa. The risks of lung and liver cancer, for instance, were significantly lower. The risk of thyroid cancer was higher in patients diagnosed when aged < 64 years, but the overall number of cases was small, particularly in that group.
When the researchers analyzed the data according to treatment, they found that patients with PCa who had radiation therapy had a higher risk of overall SPM, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer, compared with those who did not have radiation therapy. The risk of hematologic malignancies and urinary bladder cancer were significantly lower in patients with PCa treated with androgen deprivation therapy than in those who were not.
Related: Treatment and Management of Patients With Prostate Cancer
Patients who had undergone prostatectomy had a significantly lower risk of overall SPM, hematologic malignancies, liver cancer, and urinary bladder cancer; however, they had a significantly higher risk of thyroid cancer.
The researchers say, given the increases in incidence and life expectancy of patients with PCa, there is growing interest in predicting the risk of SPM. Knowing the risk factors, they note, highlights the need for continued cancer surveillance among PCa survivors.
Source:
Fan CY, Huang WY, Lin CS, et al. PLoS One. 2017:12(4):e0175217.
doi: 10.1371/journal.pone.0175217.
Link Between Intestinal Fungi and Alcoholic Liver Disease Grows Stronger
Alcoholic liver disease (ALD) has been associated with bacterial overgrowth in the intestines, as well as a shift in the types of bacteria found there. But until now, according to the National Institute on Alcohol Abuse and Alcoholism, little was actually known about the role of intestinal fungi in ALD. A University of California-San Diego and J. Craig Venter Institute in Rockville, Maryland study offers more evidence to support the connection.
In the study, the researchers found that fungi flourished in the intestines of mice with chronic alcohol exposure, and that fungal overgrowth exacerbated alcohol-induced liver disease. Treatment with amphotericin B reduced levels of liver injury and fat accumulation.
In small preliminary studies with humans, the researchers also linked intestinal fungi to ALD. People with alcohol use disorder and various stages of liver disease tended to have an overgrowth of a specific fungal species, as well as less fungal diversity, compared with healthy control subjects. Moreover, the more prevalent the fungal overgrowth in people with ALD, the higher the risk of death.
The researchers say that if further study confirms that fungi are involved in the worsening of ALD, it may be possible to slow disease progression by adjusting the balance of fungal species in the intestine.
Alcoholic liver disease (ALD) has been associated with bacterial overgrowth in the intestines, as well as a shift in the types of bacteria found there. But until now, according to the National Institute on Alcohol Abuse and Alcoholism, little was actually known about the role of intestinal fungi in ALD. A University of California-San Diego and J. Craig Venter Institute in Rockville, Maryland study offers more evidence to support the connection.
In the study, the researchers found that fungi flourished in the intestines of mice with chronic alcohol exposure, and that fungal overgrowth exacerbated alcohol-induced liver disease. Treatment with amphotericin B reduced levels of liver injury and fat accumulation.
In small preliminary studies with humans, the researchers also linked intestinal fungi to ALD. People with alcohol use disorder and various stages of liver disease tended to have an overgrowth of a specific fungal species, as well as less fungal diversity, compared with healthy control subjects. Moreover, the more prevalent the fungal overgrowth in people with ALD, the higher the risk of death.
The researchers say that if further study confirms that fungi are involved in the worsening of ALD, it may be possible to slow disease progression by adjusting the balance of fungal species in the intestine.
Alcoholic liver disease (ALD) has been associated with bacterial overgrowth in the intestines, as well as a shift in the types of bacteria found there. But until now, according to the National Institute on Alcohol Abuse and Alcoholism, little was actually known about the role of intestinal fungi in ALD. A University of California-San Diego and J. Craig Venter Institute in Rockville, Maryland study offers more evidence to support the connection.
In the study, the researchers found that fungi flourished in the intestines of mice with chronic alcohol exposure, and that fungal overgrowth exacerbated alcohol-induced liver disease. Treatment with amphotericin B reduced levels of liver injury and fat accumulation.
In small preliminary studies with humans, the researchers also linked intestinal fungi to ALD. People with alcohol use disorder and various stages of liver disease tended to have an overgrowth of a specific fungal species, as well as less fungal diversity, compared with healthy control subjects. Moreover, the more prevalent the fungal overgrowth in people with ALD, the higher the risk of death.
The researchers say that if further study confirms that fungi are involved in the worsening of ALD, it may be possible to slow disease progression by adjusting the balance of fungal species in the intestine.
Health Canada approves new use for brentuximab vedotin
Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).
This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.
Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.
Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.
AETHERA trial
Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.
The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138). 
Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).
This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.
Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.
Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.
AETHERA trial
Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.
The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).
Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).
This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.
Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.
Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.
AETHERA trial
Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.
The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).