Ezetimibe is found to be effective in lowering LDL for primary cardiovascular prevention in patients who were 75 or older. Also today, the FDA says that the benefits of paclitaxel-coated devices outweigh risks for peripheral arterial disease, flu activity is down for the second consecutive week, and a look at homelessness among LGBT youth in the United States.

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Ezetimibe is found to be effective in lowering LDL for primary cardiovascular prevention in patients who were 75 or older. Also today, the FDA says that the benefits of paclitaxel-coated devices outweigh risks for peripheral arterial disease, flu activity is down for the second consecutive week, and a look at homelessness among LGBT youth in the United States.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Ezetimibe is found to be effective in lowering LDL for primary cardiovascular prevention in patients who were 75 or older. Also today, the FDA says that the benefits of paclitaxel-coated devices outweigh risks for peripheral arterial disease, flu activity is down for the second consecutive week, and a look at homelessness among LGBT youth in the United States.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Patients with renal failure and relapsed or refractory multiple myeloma fared better with the selective proteasome inhibitor carfilzomib, compared with bortezomib, according to a post hoc subgroup analysis of a large clinical trial.

Neil Osterweil/MDedge News

In addition, patients who had a complete renal response had longer progression-free survival (PFS) and overall survival (OS), regardless of treatment group.

Many aspects of the disease state and treatment can contribute to renal failure in multiple myeloma, but cast nephropathy from precipitation of monoclonal light chains certainly contributes to persistent renal failure, Meletios Dimopoulos, MD, professor and chair of clinical therapeutics at the University of Athens, Greece, and his coauthors wrote in Blood.

The investigators wanted to see how individuals with varying levels of renal function fared in the ENDEAVOR trial, which compared carfilzomib (56 mg/m²) plus dexamethasone (Kd56) with bortezomib plus dexamethasone (Vd) for patients with relapsed or refractory multiple myeloma.

In an intent-to-treat population of 929 patients, 85 Kd56 and 99 Vd patients had creatinine clearance (CrCL) of at least 15 but less than 50 mL/min. Of patients with mild renal failure (CrCL of at least 50 but less than 80 mL/min), 186 were in the Kd56 and 177 in the Vd group. One hundred ninety-three patients receiving Kd56 and 189 Vd patients had CrCL of 80 mL/min or greater.

For ENDEAVOR patients with the lowest CrCL, median PFS was 14.9 months with Kd56 and 6.5 months with Vd (hazard ratio [HR], 0.49). For patients with intermediate CrCL, median PFS was 18.6 versus 9.4 months with Kd56 and Vd, respectively (HR, 0.48). For patients with the highest CrCL, PFS was not reached with Kd56; with Vd, median PFS was 12.2 months (HR, 0.60).

Patterns for OS mirrored the advantage seen with Kd56. Median OS was 42.1 versus 23.7 months for those with the worst renal function in the Kd56 arm and the Vd arm, respectively (HR, 0.66). Those with intermediate renal function saw median OS of 42.5 versus 32.8 months on Kd56 and Vd, respectively (HR, 0.83). Median OS for those with the highest CrCL was not reached on Kd56 and 42.3 months on Vd (HR, 0.75).

The investigators also tracked kidney function over the course of the study, with complete renal response defined as improvement of CrCL to at least 60 mL/min in any two consecutive study visits. By this yardstick, complete renal response was 15.3% for the Kd56 arm and 14.1% for those receiving Vd.

Looking across participants regardless of therapy, those with CrCL of at least 15 but less than 50 mL/min who also had complete renal response had longer PFS, compared with nonresponders (median 14.1 versus 9.4 months, HR, .805). OS also was longer in this group of patients (median 35.3 versus 29.7 months, HR, 0.91).

“Patients with complete renal response had superior overall outcomes compared with renal nonresponders across treatment groups ... highlighting the association between improved renal function and greater survival rates,” Dr. Dimopoulos and his colleagues wrote.

Kd56 therapy was associated with a higher number of grade 3 or higher adverse events, seen in 77.1%-87.1% of Kd56 patients and 65.9%-79.4% of Vd patients.

Renal failure, common in multiple myeloma, is associated with poor prognosis. Also, therapeutic options can be limited and dosing adjustments must often be made when patients have poor renal function, Dr. Dimopoulos and his coauthors noted.

However, previous studies showed that carfilzomib clearance, exposure, and overall pharmacokinetics were similar between multiple myeloma patients with and without renal impairment, including end-stage renal disease, the investigators wrote.

The subgroup analysis from ENDEAVOR suggested that “Kd56 may overcome the poor prognosis of baseline advanced renal impairment,” Dr. Dimopoulos and his colleagues wrote. “Furthermore, patients in the Kd56 arm had deeper responses compared with the Vd arm, regardless of baseline renal impairment.”

These data suggest that Kd56 should be considered a “standard of care” in patients with relapsed or refractory multiple myeloma, regardless of a patient’s baseline renal function.

The investigators reported multiple financial relationships with pharmaceutical companies, including Amgen, which markets carfilzomib and supported the study.

koakes@mdedge.com

SOURCE: Dimopoulos M et al. Blood. 2019;133(2):147-55.

Patients with renal failure and relapsed or refractory multiple myeloma fared better with the selective proteasome inhibitor carfilzomib, compared with bortezomib, according to a post hoc subgroup analysis of a large clinical trial.

Neil Osterweil/MDedge News

In addition, patients who had a complete renal response had longer progression-free survival (PFS) and overall survival (OS), regardless of treatment group.

Many aspects of the disease state and treatment can contribute to renal failure in multiple myeloma, but cast nephropathy from precipitation of monoclonal light chains certainly contributes to persistent renal failure, Meletios Dimopoulos, MD, professor and chair of clinical therapeutics at the University of Athens, Greece, and his coauthors wrote in Blood.

The investigators wanted to see how individuals with varying levels of renal function fared in the ENDEAVOR trial, which compared carfilzomib (56 mg/m²) plus dexamethasone (Kd56) with bortezomib plus dexamethasone (Vd) for patients with relapsed or refractory multiple myeloma.

In an intent-to-treat population of 929 patients, 85 Kd56 and 99 Vd patients had creatinine clearance (CrCL) of at least 15 but less than 50 mL/min. Of patients with mild renal failure (CrCL of at least 50 but less than 80 mL/min), 186 were in the Kd56 and 177 in the Vd group. One hundred ninety-three patients receiving Kd56 and 189 Vd patients had CrCL of 80 mL/min or greater.

For ENDEAVOR patients with the lowest CrCL, median PFS was 14.9 months with Kd56 and 6.5 months with Vd (hazard ratio [HR], 0.49). For patients with intermediate CrCL, median PFS was 18.6 versus 9.4 months with Kd56 and Vd, respectively (HR, 0.48). For patients with the highest CrCL, PFS was not reached with Kd56; with Vd, median PFS was 12.2 months (HR, 0.60).

Patterns for OS mirrored the advantage seen with Kd56. Median OS was 42.1 versus 23.7 months for those with the worst renal function in the Kd56 arm and the Vd arm, respectively (HR, 0.66). Those with intermediate renal function saw median OS of 42.5 versus 32.8 months on Kd56 and Vd, respectively (HR, 0.83). Median OS for those with the highest CrCL was not reached on Kd56 and 42.3 months on Vd (HR, 0.75).

The investigators also tracked kidney function over the course of the study, with complete renal response defined as improvement of CrCL to at least 60 mL/min in any two consecutive study visits. By this yardstick, complete renal response was 15.3% for the Kd56 arm and 14.1% for those receiving Vd.

Looking across participants regardless of therapy, those with CrCL of at least 15 but less than 50 mL/min who also had complete renal response had longer PFS, compared with nonresponders (median 14.1 versus 9.4 months, HR, .805). OS also was longer in this group of patients (median 35.3 versus 29.7 months, HR, 0.91).

“Patients with complete renal response had superior overall outcomes compared with renal nonresponders across treatment groups ... highlighting the association between improved renal function and greater survival rates,” Dr. Dimopoulos and his colleagues wrote.

Kd56 therapy was associated with a higher number of grade 3 or higher adverse events, seen in 77.1%-87.1% of Kd56 patients and 65.9%-79.4% of Vd patients.

Renal failure, common in multiple myeloma, is associated with poor prognosis. Also, therapeutic options can be limited and dosing adjustments must often be made when patients have poor renal function, Dr. Dimopoulos and his coauthors noted.

However, previous studies showed that carfilzomib clearance, exposure, and overall pharmacokinetics were similar between multiple myeloma patients with and without renal impairment, including end-stage renal disease, the investigators wrote.

The subgroup analysis from ENDEAVOR suggested that “Kd56 may overcome the poor prognosis of baseline advanced renal impairment,” Dr. Dimopoulos and his colleagues wrote. “Furthermore, patients in the Kd56 arm had deeper responses compared with the Vd arm, regardless of baseline renal impairment.”

These data suggest that Kd56 should be considered a “standard of care” in patients with relapsed or refractory multiple myeloma, regardless of a patient’s baseline renal function.

The investigators reported multiple financial relationships with pharmaceutical companies, including Amgen, which markets carfilzomib and supported the study.

koakes@mdedge.com

SOURCE: Dimopoulos M et al. Blood. 2019;133(2):147-55.

Patients with renal failure and relapsed or refractory multiple myeloma fared better with the selective proteasome inhibitor carfilzomib, compared with bortezomib, according to a post hoc subgroup analysis of a large clinical trial.

Neil Osterweil/MDedge News

In addition, patients who had a complete renal response had longer progression-free survival (PFS) and overall survival (OS), regardless of treatment group.

Many aspects of the disease state and treatment can contribute to renal failure in multiple myeloma, but cast nephropathy from precipitation of monoclonal light chains certainly contributes to persistent renal failure, Meletios Dimopoulos, MD, professor and chair of clinical therapeutics at the University of Athens, Greece, and his coauthors wrote in Blood.

The investigators wanted to see how individuals with varying levels of renal function fared in the ENDEAVOR trial, which compared carfilzomib (56 mg/m²) plus dexamethasone (Kd56) with bortezomib plus dexamethasone (Vd) for patients with relapsed or refractory multiple myeloma.

In an intent-to-treat population of 929 patients, 85 Kd56 and 99 Vd patients had creatinine clearance (CrCL) of at least 15 but less than 50 mL/min. Of patients with mild renal failure (CrCL of at least 50 but less than 80 mL/min), 186 were in the Kd56 and 177 in the Vd group. One hundred ninety-three patients receiving Kd56 and 189 Vd patients had CrCL of 80 mL/min or greater.

For ENDEAVOR patients with the lowest CrCL, median PFS was 14.9 months with Kd56 and 6.5 months with Vd (hazard ratio [HR], 0.49). For patients with intermediate CrCL, median PFS was 18.6 versus 9.4 months with Kd56 and Vd, respectively (HR, 0.48). For patients with the highest CrCL, PFS was not reached with Kd56; with Vd, median PFS was 12.2 months (HR, 0.60).

Patterns for OS mirrored the advantage seen with Kd56. Median OS was 42.1 versus 23.7 months for those with the worst renal function in the Kd56 arm and the Vd arm, respectively (HR, 0.66). Those with intermediate renal function saw median OS of 42.5 versus 32.8 months on Kd56 and Vd, respectively (HR, 0.83). Median OS for those with the highest CrCL was not reached on Kd56 and 42.3 months on Vd (HR, 0.75).

The investigators also tracked kidney function over the course of the study, with complete renal response defined as improvement of CrCL to at least 60 mL/min in any two consecutive study visits. By this yardstick, complete renal response was 15.3% for the Kd56 arm and 14.1% for those receiving Vd.

Looking across participants regardless of therapy, those with CrCL of at least 15 but less than 50 mL/min who also had complete renal response had longer PFS, compared with nonresponders (median 14.1 versus 9.4 months, HR, .805). OS also was longer in this group of patients (median 35.3 versus 29.7 months, HR, 0.91).

“Patients with complete renal response had superior overall outcomes compared with renal nonresponders across treatment groups ... highlighting the association between improved renal function and greater survival rates,” Dr. Dimopoulos and his colleagues wrote.

Kd56 therapy was associated with a higher number of grade 3 or higher adverse events, seen in 77.1%-87.1% of Kd56 patients and 65.9%-79.4% of Vd patients.

Renal failure, common in multiple myeloma, is associated with poor prognosis. Also, therapeutic options can be limited and dosing adjustments must often be made when patients have poor renal function, Dr. Dimopoulos and his coauthors noted.

However, previous studies showed that carfilzomib clearance, exposure, and overall pharmacokinetics were similar between multiple myeloma patients with and without renal impairment, including end-stage renal disease, the investigators wrote.

The subgroup analysis from ENDEAVOR suggested that “Kd56 may overcome the poor prognosis of baseline advanced renal impairment,” Dr. Dimopoulos and his colleagues wrote. “Furthermore, patients in the Kd56 arm had deeper responses compared with the Vd arm, regardless of baseline renal impairment.”

These data suggest that Kd56 should be considered a “standard of care” in patients with relapsed or refractory multiple myeloma, regardless of a patient’s baseline renal function.

The investigators reported multiple financial relationships with pharmaceutical companies, including Amgen, which markets carfilzomib and supported the study.

koakes@mdedge.com

SOURCE: Dimopoulos M et al. Blood. 2019;133(2):147-55.

Parents were much more confident about vaccinating their children against the human papillomavirus (HPV) when they were told about the diseases that the vaccine prevents rather than about safety, new research found.

Stuart Jenner/Thinkstock

In Pediatrics, researchers reported the outcomes of an online video-messaging study that attempted to address the most common parental questions and concerns about the HPV vaccine. They surveyed a national sample of 1,196 parents of children (aged 9-17 years) who watched four brief videos of a pediatrician talking about one of seven common concerns regarding HPV vaccination. The parents then were asked how each video affected them.

Parents who were exposed to messages about the diseases that the HPV vaccine prevented had the highest confidence in the HPV vaccine (46%). These messages included “HPV is a common virus that millions of people get every year. The HPV vaccine will protect your child from some cancers and genital warts” and “HPV infection can cause cancer in both men and women. The HPV vaccine will protect your child from many of these cancers.”

Similarly, parents exposed to messages about the need for HPV vaccination for both boys and girls also had the highest levels of confidence about HPV vaccination (44%).

Confidence was lower in parents exposed to messages about safety and side effects (30%)

“As such, reiterating vaccination benefits (including cancer prevention) when addressing concerns may also improve the impact of messages,” wrote Parth D. Shah, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, and his coauthors.

Parents who received messages that expressed urgency about vaccination had lower confidence in the HPV vaccine.

“One reason may be that parents who are hesitant feel inappropriately rushed or that their concerns are not being treated with appropriate care,” the authors wrote.

However, messages that required a higher reading grade level and messages that were longer also seemed to inspire more confidence among parents. Parents who were exposed to messages about cancer prevention additionally were even more confident in HPV vaccine, Dr. Shah and his associates reported.

The study also found that 84% of parents wanted to talk to their children’s doctor about the diseases that the HPV vaccine prevented, while 68% wanted to talk about safety and side effects.

The study was funded by the Centers for Disease Control and Prevention and the National Cancer Institute. Dr. Shah was partially supported by an Agency for Healthcare Research and Quality grant. Another author declared being on paid advisory boards of research grants from Merck, Pfizer, and GlaxoSmithKline. No other conflicts of interest were declared.

SOURCE: Shah PD et al. Pediatrics. 2019 Feb. doi: 10.1542/peds.2018-1872.
 

Parents were much more confident about vaccinating their children against the human papillomavirus (HPV) when they were told about the diseases that the vaccine prevents rather than about safety, new research found.

Stuart Jenner/Thinkstock

In Pediatrics, researchers reported the outcomes of an online video-messaging study that attempted to address the most common parental questions and concerns about the HPV vaccine. They surveyed a national sample of 1,196 parents of children (aged 9-17 years) who watched four brief videos of a pediatrician talking about one of seven common concerns regarding HPV vaccination. The parents then were asked how each video affected them.

Parents who were exposed to messages about the diseases that the HPV vaccine prevented had the highest confidence in the HPV vaccine (46%). These messages included “HPV is a common virus that millions of people get every year. The HPV vaccine will protect your child from some cancers and genital warts” and “HPV infection can cause cancer in both men and women. The HPV vaccine will protect your child from many of these cancers.”

Similarly, parents exposed to messages about the need for HPV vaccination for both boys and girls also had the highest levels of confidence about HPV vaccination (44%).

Confidence was lower in parents exposed to messages about safety and side effects (30%)

“As such, reiterating vaccination benefits (including cancer prevention) when addressing concerns may also improve the impact of messages,” wrote Parth D. Shah, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, and his coauthors.

Parents who received messages that expressed urgency about vaccination had lower confidence in the HPV vaccine.

“One reason may be that parents who are hesitant feel inappropriately rushed or that their concerns are not being treated with appropriate care,” the authors wrote.

However, messages that required a higher reading grade level and messages that were longer also seemed to inspire more confidence among parents. Parents who were exposed to messages about cancer prevention additionally were even more confident in HPV vaccine, Dr. Shah and his associates reported.

The study also found that 84% of parents wanted to talk to their children’s doctor about the diseases that the HPV vaccine prevented, while 68% wanted to talk about safety and side effects.

The study was funded by the Centers for Disease Control and Prevention and the National Cancer Institute. Dr. Shah was partially supported by an Agency for Healthcare Research and Quality grant. Another author declared being on paid advisory boards of research grants from Merck, Pfizer, and GlaxoSmithKline. No other conflicts of interest were declared.

SOURCE: Shah PD et al. Pediatrics. 2019 Feb. doi: 10.1542/peds.2018-1872.
 

Parents were much more confident about vaccinating their children against the human papillomavirus (HPV) when they were told about the diseases that the vaccine prevents rather than about safety, new research found.

Stuart Jenner/Thinkstock

In Pediatrics, researchers reported the outcomes of an online video-messaging study that attempted to address the most common parental questions and concerns about the HPV vaccine. They surveyed a national sample of 1,196 parents of children (aged 9-17 years) who watched four brief videos of a pediatrician talking about one of seven common concerns regarding HPV vaccination. The parents then were asked how each video affected them.

Parents who were exposed to messages about the diseases that the HPV vaccine prevented had the highest confidence in the HPV vaccine (46%). These messages included “HPV is a common virus that millions of people get every year. The HPV vaccine will protect your child from some cancers and genital warts” and “HPV infection can cause cancer in both men and women. The HPV vaccine will protect your child from many of these cancers.”

Similarly, parents exposed to messages about the need for HPV vaccination for both boys and girls also had the highest levels of confidence about HPV vaccination (44%).

Confidence was lower in parents exposed to messages about safety and side effects (30%)

“As such, reiterating vaccination benefits (including cancer prevention) when addressing concerns may also improve the impact of messages,” wrote Parth D. Shah, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, and his coauthors.

Parents who received messages that expressed urgency about vaccination had lower confidence in the HPV vaccine.

“One reason may be that parents who are hesitant feel inappropriately rushed or that their concerns are not being treated with appropriate care,” the authors wrote.

However, messages that required a higher reading grade level and messages that were longer also seemed to inspire more confidence among parents. Parents who were exposed to messages about cancer prevention additionally were even more confident in HPV vaccine, Dr. Shah and his associates reported.

The study also found that 84% of parents wanted to talk to their children’s doctor about the diseases that the HPV vaccine prevented, while 68% wanted to talk about safety and side effects.

The study was funded by the Centers for Disease Control and Prevention and the National Cancer Institute. Dr. Shah was partially supported by an Agency for Healthcare Research and Quality grant. Another author declared being on paid advisory boards of research grants from Merck, Pfizer, and GlaxoSmithKline. No other conflicts of interest were declared.

SOURCE: Shah PD et al. Pediatrics. 2019 Feb. doi: 10.1542/peds.2018-1872.
 

Renal transplant is associated with a substantial survival benefit in patients with end-stage renal disease due to lupus nephritis, according to researchers who conducted a nationwide cohort study encompassing nearly all such patients treated in the United States over a 20-year period.

Transplant conferred a 70% reduction in overall death risk in these lupus nephritis end-stage renal disease (ESRD) patients, largely due to reduced deaths caused by infection and cardiovascular disease, according to the researchers, led by April Jorge, MD, and Zachary Wallace, MD, of Massachusetts General Hospital, Harvard Medical School, Boston.

Those findings suggest that patients with lupus nephritis ESRD should routinely be considered for renal transplant in a timely manner, the investigators wrote in Annals of Internal Medicine.

“Improved access to renal transplantation for this population may considerably improve outcomes,” they said.

The study was based on an analysis of 9,659 patients who had lupus nephritis ESRD between 1995 and 2014 and were waitlisted for renal transplant. The data came from the United States Renal Data System, which includes most ESRD patients treated in the country. Of those 9,659 patients, 5,738 (59%) underwent kidney transplant.

Mortality rates were 22.5 per 1,000 person-years for lupus nephritis ESRD patients who underwent transplant, and 56.3 per 1,000 person-years for those patients who did not receive transplant, the investigators found.

Renal transplant reduced risk of death by 70% in results of multivariate analysis (hazard ratio, 0.30; 95% CI, 0.27-0.33).

That lower risk of all-cause mortality was consistent across racial groups and for other characteristics, such as sex, age at ESRD onset, and Medicare enrollment status.

Risk of cardiovascular death was 74% lower with renal transplant (adjusted hazard ratio, 0.26; 95% CI, 0.23-0.30), and risk of death from infection was also markedly lower among those who underwent transplant (adjusted hazard ratio, 0.41; 95% CI, 0.32-0.52), investigators found in a cause-specific mortality analysis.

While transplant has been associated with improved survival in patients with ESRD from all causes, there are “unique concerns” regarding the potential for infections or other post-transplant complications from transplant in lupus nephritis patients with ESRD, Dr. Jorge and colleagues wrote.

“To that end, our study provides evidence for a substantial survival benefit of renal transplant among patients with lupus nephritis ESRD,” they noted.

Dr. Jorge reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study. One co-author provided additional disclosures related to Teva Pharmaceuticals and Gilead Sciences outside of the study conduct.

SOURCE: Jorge A, et al. Ann Intern Med 2019 Jan 21. doi: 10.7326/M18-1570.

Renal transplant is associated with a substantial survival benefit in patients with end-stage renal disease due to lupus nephritis, according to researchers who conducted a nationwide cohort study encompassing nearly all such patients treated in the United States over a 20-year period.

Transplant conferred a 70% reduction in overall death risk in these lupus nephritis end-stage renal disease (ESRD) patients, largely due to reduced deaths caused by infection and cardiovascular disease, according to the researchers, led by April Jorge, MD, and Zachary Wallace, MD, of Massachusetts General Hospital, Harvard Medical School, Boston.

Those findings suggest that patients with lupus nephritis ESRD should routinely be considered for renal transplant in a timely manner, the investigators wrote in Annals of Internal Medicine.

“Improved access to renal transplantation for this population may considerably improve outcomes,” they said.

The study was based on an analysis of 9,659 patients who had lupus nephritis ESRD between 1995 and 2014 and were waitlisted for renal transplant. The data came from the United States Renal Data System, which includes most ESRD patients treated in the country. Of those 9,659 patients, 5,738 (59%) underwent kidney transplant.

Mortality rates were 22.5 per 1,000 person-years for lupus nephritis ESRD patients who underwent transplant, and 56.3 per 1,000 person-years for those patients who did not receive transplant, the investigators found.

Renal transplant reduced risk of death by 70% in results of multivariate analysis (hazard ratio, 0.30; 95% CI, 0.27-0.33).

That lower risk of all-cause mortality was consistent across racial groups and for other characteristics, such as sex, age at ESRD onset, and Medicare enrollment status.

Risk of cardiovascular death was 74% lower with renal transplant (adjusted hazard ratio, 0.26; 95% CI, 0.23-0.30), and risk of death from infection was also markedly lower among those who underwent transplant (adjusted hazard ratio, 0.41; 95% CI, 0.32-0.52), investigators found in a cause-specific mortality analysis.

While transplant has been associated with improved survival in patients with ESRD from all causes, there are “unique concerns” regarding the potential for infections or other post-transplant complications from transplant in lupus nephritis patients with ESRD, Dr. Jorge and colleagues wrote.

“To that end, our study provides evidence for a substantial survival benefit of renal transplant among patients with lupus nephritis ESRD,” they noted.

Dr. Jorge reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study. One co-author provided additional disclosures related to Teva Pharmaceuticals and Gilead Sciences outside of the study conduct.

SOURCE: Jorge A, et al. Ann Intern Med 2019 Jan 21. doi: 10.7326/M18-1570.

Renal transplant is associated with a substantial survival benefit in patients with end-stage renal disease due to lupus nephritis, according to researchers who conducted a nationwide cohort study encompassing nearly all such patients treated in the United States over a 20-year period.

Transplant conferred a 70% reduction in overall death risk in these lupus nephritis end-stage renal disease (ESRD) patients, largely due to reduced deaths caused by infection and cardiovascular disease, according to the researchers, led by April Jorge, MD, and Zachary Wallace, MD, of Massachusetts General Hospital, Harvard Medical School, Boston.

Those findings suggest that patients with lupus nephritis ESRD should routinely be considered for renal transplant in a timely manner, the investigators wrote in Annals of Internal Medicine.

“Improved access to renal transplantation for this population may considerably improve outcomes,” they said.

The study was based on an analysis of 9,659 patients who had lupus nephritis ESRD between 1995 and 2014 and were waitlisted for renal transplant. The data came from the United States Renal Data System, which includes most ESRD patients treated in the country. Of those 9,659 patients, 5,738 (59%) underwent kidney transplant.

Mortality rates were 22.5 per 1,000 person-years for lupus nephritis ESRD patients who underwent transplant, and 56.3 per 1,000 person-years for those patients who did not receive transplant, the investigators found.

Renal transplant reduced risk of death by 70% in results of multivariate analysis (hazard ratio, 0.30; 95% CI, 0.27-0.33).

That lower risk of all-cause mortality was consistent across racial groups and for other characteristics, such as sex, age at ESRD onset, and Medicare enrollment status.

Risk of cardiovascular death was 74% lower with renal transplant (adjusted hazard ratio, 0.26; 95% CI, 0.23-0.30), and risk of death from infection was also markedly lower among those who underwent transplant (adjusted hazard ratio, 0.41; 95% CI, 0.32-0.52), investigators found in a cause-specific mortality analysis.

While transplant has been associated with improved survival in patients with ESRD from all causes, there are “unique concerns” regarding the potential for infections or other post-transplant complications from transplant in lupus nephritis patients with ESRD, Dr. Jorge and colleagues wrote.

“To that end, our study provides evidence for a substantial survival benefit of renal transplant among patients with lupus nephritis ESRD,” they noted.

Dr. Jorge reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study. One co-author provided additional disclosures related to Teva Pharmaceuticals and Gilead Sciences outside of the study conduct.

SOURCE: Jorge A, et al. Ann Intern Med 2019 Jan 21. doi: 10.7326/M18-1570.

A majority of U.S. healthcare professionals report that their patients have been negatively affected by the partial shutdown of the federal government. Also today, a mental disorder diagnosis increases the risk for all mental disorders, frailty may affect the expression of dementia, and nearly one-quarter of antibiotic fills are deemed unnecessary.
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A majority of U.S. healthcare professionals report that their patients have been negatively affected by the partial shutdown of the federal government. Also today, a mental disorder diagnosis increases the risk for all mental disorders, frailty may affect the expression of dementia, and nearly one-quarter of antibiotic fills are deemed unnecessary.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A majority of U.S. healthcare professionals report that their patients have been negatively affected by the partial shutdown of the federal government. Also today, a mental disorder diagnosis increases the risk for all mental disorders, frailty may affect the expression of dementia, and nearly one-quarter of antibiotic fills are deemed unnecessary.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Clinical question: Does a negative computed tomography pulmonary angiography rule out venous thromboembolism (VTE)?

Background: Computed tomography pulmonary angiography (CTPA) is the most common diagnostic modality used to diagnose pulmonary embolism (PE) and has a high negative predictive value in patients with a low 3-month risk of VTE. In patients with higher pretest probability of PE, it is unknown whether CTPA is sufficient to rule out VTE.

Study design: Meta-analysis.

Setting: Published prospective outcome studies of patients with suspected PE using CTPA as a diagnostic strategy.

Synopsis: The authors reviewed 3,143 publications from MEDLINE, EMBASE, and the Cochrane Library and identified 22 prospective outcome studies to include in their meta-analysis. A VTE was diagnosed in 3,923 out of 11,872 participants (33%) using CTPA. Of the 7,863 patients with a negative CTPA, 148 patients had an acute VTE confirmed by venous ultrasound, ventilation/perfusion scan, or angiography, and 74 patients experienced VTE during a 3-month follow-up period, yielding an overall proportion of 2.4% of patients (95% confidence interval, 1.3%-3.8%).

Subgroup analysis showed that cumulative occurrence of VTE was related to pretest prevalence. In the subgroup of patients with a VTE prevalence greater than 40%, VTE was observed in 8.1% of patients with a negative CTPA (95% CI, 3.4%-14.5%).

Bottom line: CTPA may be insufficient to rule out VTE in patients with a high pretest probability of PE.

Citation: Belzile D et al. Outcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta-analysisof the management outcome studies. J Thromb Haemost. 2018 Jun;16(6):1107-20.

Dr. Jenkins is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Clinical question: Does a negative computed tomography pulmonary angiography rule out venous thromboembolism (VTE)?

Background: Computed tomography pulmonary angiography (CTPA) is the most common diagnostic modality used to diagnose pulmonary embolism (PE) and has a high negative predictive value in patients with a low 3-month risk of VTE. In patients with higher pretest probability of PE, it is unknown whether CTPA is sufficient to rule out VTE.

Study design: Meta-analysis.

Setting: Published prospective outcome studies of patients with suspected PE using CTPA as a diagnostic strategy.

Synopsis: The authors reviewed 3,143 publications from MEDLINE, EMBASE, and the Cochrane Library and identified 22 prospective outcome studies to include in their meta-analysis. A VTE was diagnosed in 3,923 out of 11,872 participants (33%) using CTPA. Of the 7,863 patients with a negative CTPA, 148 patients had an acute VTE confirmed by venous ultrasound, ventilation/perfusion scan, or angiography, and 74 patients experienced VTE during a 3-month follow-up period, yielding an overall proportion of 2.4% of patients (95% confidence interval, 1.3%-3.8%).

Subgroup analysis showed that cumulative occurrence of VTE was related to pretest prevalence. In the subgroup of patients with a VTE prevalence greater than 40%, VTE was observed in 8.1% of patients with a negative CTPA (95% CI, 3.4%-14.5%).

Bottom line: CTPA may be insufficient to rule out VTE in patients with a high pretest probability of PE.

Citation: Belzile D et al. Outcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta-analysisof the management outcome studies. J Thromb Haemost. 2018 Jun;16(6):1107-20.

Dr. Jenkins is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Clinical question: Does a negative computed tomography pulmonary angiography rule out venous thromboembolism (VTE)?

Background: Computed tomography pulmonary angiography (CTPA) is the most common diagnostic modality used to diagnose pulmonary embolism (PE) and has a high negative predictive value in patients with a low 3-month risk of VTE. In patients with higher pretest probability of PE, it is unknown whether CTPA is sufficient to rule out VTE.

Study design: Meta-analysis.

Setting: Published prospective outcome studies of patients with suspected PE using CTPA as a diagnostic strategy.

Synopsis: The authors reviewed 3,143 publications from MEDLINE, EMBASE, and the Cochrane Library and identified 22 prospective outcome studies to include in their meta-analysis. A VTE was diagnosed in 3,923 out of 11,872 participants (33%) using CTPA. Of the 7,863 patients with a negative CTPA, 148 patients had an acute VTE confirmed by venous ultrasound, ventilation/perfusion scan, or angiography, and 74 patients experienced VTE during a 3-month follow-up period, yielding an overall proportion of 2.4% of patients (95% confidence interval, 1.3%-3.8%).

Subgroup analysis showed that cumulative occurrence of VTE was related to pretest prevalence. In the subgroup of patients with a VTE prevalence greater than 40%, VTE was observed in 8.1% of patients with a negative CTPA (95% CI, 3.4%-14.5%).

Bottom line: CTPA may be insufficient to rule out VTE in patients with a high pretest probability of PE.

Citation: Belzile D et al. Outcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta-analysisof the management outcome studies. J Thromb Haemost. 2018 Jun;16(6):1107-20.

Dr. Jenkins is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

ORLANDO – Platelet-rich plasma offers much for patients and dermatologists: It’s low-risk, has a low cost of entry, and usefully augments other medications and procedures for androgenetic alopecia and facial rejuvenation.

But there’s work to be done in standardizing its use and really understanding where, when, and for whom platelet-rich plasma (PRP) will be best used, said Dierdre Hooper, MD, a dermatologist in private practice in New Orleans.

As far back as the 1970s, PRP was used as a transfusion product, with use expanding during the following decade. “It’s really the ‘everywhere’ product,’” said Dr. Hooper, speaking at the Aesthetic, Surgical, and Clinical Dermatology Conference (ODAC).

Over the course of the past four decades, PRP has been explored for musculoskeletal healing, in gynecology, urology, cardiac surgery, ophthalmology, and for plastic surgery. “Initial skepticism has given way as some evidence is building,” said Dr. Hooper.

PRP, considered a biologic product, is produced by centrifuging a donor venipuncture. Among the pros of using PRP in a clinical practice, said Dr. Hooper, is the fact that numerous clinical studies do show benefit. The risk is low, as is the cost, and downtime is brief. All of these contribute to attractiveness to patients, who also like the idea of an all-natural product with an autologous source.

But consensus is lacking about some key aspects of utilization, including the best mode of preparation and optimal treatment schedule. Outcomes can be unpredictable, making it tough to say how cost-effective the regimen will be for a particular patient. “The ‘cons’ just come down to no consensus,” said Dr. Hooper.

Some of the basic science makes a compelling case for PRP: Activated platelets have secretory granules. These modify the pericellular milieu through release of a variety of growth factors by secretory granules. “We all were taught back in the day that platelets adhere to promote clotting, but they do a lot more than that – when the platelet is activated, it releases growth factors,” said Dr. Hooper. “Big picture? Think: This is how we heal.”

After blood collection, the sample is centrifuged. The goal of centrifuging is to achieve a platelet concentration of 1 to 1.5 million platelets per mL, or four to six times the platelet concentration seen in whole blood. In practice, there are variations in the mode of preparation, and in an individual’s platelet level at the time of venipuncture, said Dr. Hooper, so it’s hard to know what the platelet “dose” is from PRP.

After centrifuging, the sample will be stratified into a bottom portion, consisting primarily of red blood cells, a middle portion that’s the PRP, and a top portion that is platelet-poor plasma. Dr. Hooper draws up and saves the platelet- poor plasma as well, since it probably also contains some growth factors. She’ll save that for application or injection after a PRP treatment for some patients.

koakes@mdedge.com

SOURCE: Hooper, D. ODAC 2018.

ORLANDO – Platelet-rich plasma offers much for patients and dermatologists: It’s low-risk, has a low cost of entry, and usefully augments other medications and procedures for androgenetic alopecia and facial rejuvenation.

But there’s work to be done in standardizing its use and really understanding where, when, and for whom platelet-rich plasma (PRP) will be best used, said Dierdre Hooper, MD, a dermatologist in private practice in New Orleans.

As far back as the 1970s, PRP was used as a transfusion product, with use expanding during the following decade. “It’s really the ‘everywhere’ product,’” said Dr. Hooper, speaking at the Aesthetic, Surgical, and Clinical Dermatology Conference (ODAC).

Over the course of the past four decades, PRP has been explored for musculoskeletal healing, in gynecology, urology, cardiac surgery, ophthalmology, and for plastic surgery. “Initial skepticism has given way as some evidence is building,” said Dr. Hooper.

PRP, considered a biologic product, is produced by centrifuging a donor venipuncture. Among the pros of using PRP in a clinical practice, said Dr. Hooper, is the fact that numerous clinical studies do show benefit. The risk is low, as is the cost, and downtime is brief. All of these contribute to attractiveness to patients, who also like the idea of an all-natural product with an autologous source.

But consensus is lacking about some key aspects of utilization, including the best mode of preparation and optimal treatment schedule. Outcomes can be unpredictable, making it tough to say how cost-effective the regimen will be for a particular patient. “The ‘cons’ just come down to no consensus,” said Dr. Hooper.

Some of the basic science makes a compelling case for PRP: Activated platelets have secretory granules. These modify the pericellular milieu through release of a variety of growth factors by secretory granules. “We all were taught back in the day that platelets adhere to promote clotting, but they do a lot more than that – when the platelet is activated, it releases growth factors,” said Dr. Hooper. “Big picture? Think: This is how we heal.”

After blood collection, the sample is centrifuged. The goal of centrifuging is to achieve a platelet concentration of 1 to 1.5 million platelets per mL, or four to six times the platelet concentration seen in whole blood. In practice, there are variations in the mode of preparation, and in an individual’s platelet level at the time of venipuncture, said Dr. Hooper, so it’s hard to know what the platelet “dose” is from PRP.

After centrifuging, the sample will be stratified into a bottom portion, consisting primarily of red blood cells, a middle portion that’s the PRP, and a top portion that is platelet-poor plasma. Dr. Hooper draws up and saves the platelet- poor plasma as well, since it probably also contains some growth factors. She’ll save that for application or injection after a PRP treatment for some patients.

koakes@mdedge.com

SOURCE: Hooper, D. ODAC 2018.

ORLANDO – Platelet-rich plasma offers much for patients and dermatologists: It’s low-risk, has a low cost of entry, and usefully augments other medications and procedures for androgenetic alopecia and facial rejuvenation.

But there’s work to be done in standardizing its use and really understanding where, when, and for whom platelet-rich plasma (PRP) will be best used, said Dierdre Hooper, MD, a dermatologist in private practice in New Orleans.

As far back as the 1970s, PRP was used as a transfusion product, with use expanding during the following decade. “It’s really the ‘everywhere’ product,’” said Dr. Hooper, speaking at the Aesthetic, Surgical, and Clinical Dermatology Conference (ODAC).

Over the course of the past four decades, PRP has been explored for musculoskeletal healing, in gynecology, urology, cardiac surgery, ophthalmology, and for plastic surgery. “Initial skepticism has given way as some evidence is building,” said Dr. Hooper.

PRP, considered a biologic product, is produced by centrifuging a donor venipuncture. Among the pros of using PRP in a clinical practice, said Dr. Hooper, is the fact that numerous clinical studies do show benefit. The risk is low, as is the cost, and downtime is brief. All of these contribute to attractiveness to patients, who also like the idea of an all-natural product with an autologous source.

But consensus is lacking about some key aspects of utilization, including the best mode of preparation and optimal treatment schedule. Outcomes can be unpredictable, making it tough to say how cost-effective the regimen will be for a particular patient. “The ‘cons’ just come down to no consensus,” said Dr. Hooper.

Some of the basic science makes a compelling case for PRP: Activated platelets have secretory granules. These modify the pericellular milieu through release of a variety of growth factors by secretory granules. “We all were taught back in the day that platelets adhere to promote clotting, but they do a lot more than that – when the platelet is activated, it releases growth factors,” said Dr. Hooper. “Big picture? Think: This is how we heal.”

After blood collection, the sample is centrifuged. The goal of centrifuging is to achieve a platelet concentration of 1 to 1.5 million platelets per mL, or four to six times the platelet concentration seen in whole blood. In practice, there are variations in the mode of preparation, and in an individual’s platelet level at the time of venipuncture, said Dr. Hooper, so it’s hard to know what the platelet “dose” is from PRP.

After centrifuging, the sample will be stratified into a bottom portion, consisting primarily of red blood cells, a middle portion that’s the PRP, and a top portion that is platelet-poor plasma. Dr. Hooper draws up and saves the platelet- poor plasma as well, since it probably also contains some growth factors. She’ll save that for application or injection after a PRP treatment for some patients.

koakes@mdedge.com

SOURCE: Hooper, D. ODAC 2018.

CHICAGO – The first prospective randomized trial support for the efficacy of LDL-lowering therapy for primary cardiovascular prevention in patients age 75 and older has been provided by the Japanese EWTOPIA 75 trial.

Bruce Jancin/MDedge News

Ezetimibe (Zetia) at 10 mg/day reduced the risk of the primary endpoint, a composite of atherosclerotic cardiovascular events, by 34% compared with a dietary counseling control group over the course of 5 years of followup. Yasuyoshi Ouchi, MD, PhD, reported the findings of the 3,796-patient study at the American Heart Association scientific sessions.

There was also a 40% relative risk reduction for cardiac events in the ezetimibe group. The 22% reduction in cerebrovascular events, however, didn’t achieve statistical significance, and there was no between-group difference in all-cause mortality, said Dr. Ouchi, principal investigator in EWTOPIA 75 and professor emeritus of geriatric medicine at the University of Tokyo.

The landmark randomized clinical trials of lipid-lowering for primary cardiovascular prevention included too few elderly participants to permit assessment of its merits and possible harms in that population. This has left a major evidence gap at a time when in many parts of the world, including the United States, Europe, and Japan, the population over age 75 is growing explosively.

“Along with this population change, the number of patients age 75 and older with hypercholesterolemia has dramatically increased,” Dr. Ouchi continued.

Eligibility for EWTOPIA was restricted to patients who were at least 75 years old, had an LDL of at least 140 mg/dL, no history of CAD, and had at least one high-risk factor, such as diabetes or hypertension. Their mean age at enrollment was 80.7 years. Seventy-four percent of them were women, reflecting the significantly longer life expectancy of Japanese women compared to men.

The study design was open-label with no placebo arm. Dr. Ouchi argued that this was appropriate, given that the components of the primary composite endpoint were “entirely objective”: fatal and nonfatal MI, fatal and nonfatal stroke, sudden cardiac death, and coronary revascularization.

The mean LDL in the ezetimibe group dropped from 162 mg/dL at baseline to 120 mg/dL at 5 years, versus 131 mg/dL in the control group.

Bruce Jancin/MDedge News

Discussant Jennifer G. Robinson, MD, said that for a decade she has tried without success to get backing for a primary prevention statin trial in elderly U.S. patients, so congratulations to the Japanese investigators are in order.

She expressed doubts as to the generalizability of the EWTOPIA results to non-Japanese populations, however.

“Frankly, I was very surprised to see the large effect size. EWTOPIA had far more effect than we expected based on other trials of LDL-lowering agents to date,” said Dr. Robinson, professor of epidemiology and medicine and director of the Prevention Intervention Center at the University of Iowa, Iowa City.

“It’s a little better performance than we expected from that magnitude of LDL lowering, which was quite modest,” she added.

Among the possible explanations she cited for the greater magnitude of reduction in major vascular events seen in EWTOPIA as compared, for example, to the IMPROVE-IT trial, which also utilized ezetimibe, are genetic differences in the Japanese population. It’s known that the Japanese have different genetic polymorphisms of Niemann-Pick C1 Like 1 (NPC1L1), which is what ezetimibe binds to in order to inhibit small intestinal enterocyte uptake and absorption of cholesterol. Or it might just be that older adults, regardless of their ethnicity, have a more robust response to LDL lowering than the younger ones who’ve been the focus of previous trials.

“I think the LDL lowering from ezetimibe was very effective in Japanese older adults without cardiovascular disease, and I think that’s a very appropriate therapy for primary prevention moving forward in that population,” Dr. Robinson said.

As for herself, she’s awaiting confirmation in other populations. She’s particularly eager to see the outcome of the ongoing double-blind, randomized STAREE trial of atorvastatin (Lipitor) at 40 mg/day or placebo for primary prevention in 18,000 Australians age 70 and up. Results are expected in 2022.

Dr. Ouchi reported having no financial conflicts regarding the EWTOPIA study, funded by the Japanese government.
 

bjancin@mdedge.com

SOURCE: Ouchi Y. AHA Late Breaker 02.

CHICAGO – The first prospective randomized trial support for the efficacy of LDL-lowering therapy for primary cardiovascular prevention in patients age 75 and older has been provided by the Japanese EWTOPIA 75 trial.

Bruce Jancin/MDedge News

Ezetimibe (Zetia) at 10 mg/day reduced the risk of the primary endpoint, a composite of atherosclerotic cardiovascular events, by 34% compared with a dietary counseling control group over the course of 5 years of followup. Yasuyoshi Ouchi, MD, PhD, reported the findings of the 3,796-patient study at the American Heart Association scientific sessions.

There was also a 40% relative risk reduction for cardiac events in the ezetimibe group. The 22% reduction in cerebrovascular events, however, didn’t achieve statistical significance, and there was no between-group difference in all-cause mortality, said Dr. Ouchi, principal investigator in EWTOPIA 75 and professor emeritus of geriatric medicine at the University of Tokyo.

The landmark randomized clinical trials of lipid-lowering for primary cardiovascular prevention included too few elderly participants to permit assessment of its merits and possible harms in that population. This has left a major evidence gap at a time when in many parts of the world, including the United States, Europe, and Japan, the population over age 75 is growing explosively.

“Along with this population change, the number of patients age 75 and older with hypercholesterolemia has dramatically increased,” Dr. Ouchi continued.

Eligibility for EWTOPIA was restricted to patients who were at least 75 years old, had an LDL of at least 140 mg/dL, no history of CAD, and had at least one high-risk factor, such as diabetes or hypertension. Their mean age at enrollment was 80.7 years. Seventy-four percent of them were women, reflecting the significantly longer life expectancy of Japanese women compared to men.

The study design was open-label with no placebo arm. Dr. Ouchi argued that this was appropriate, given that the components of the primary composite endpoint were “entirely objective”: fatal and nonfatal MI, fatal and nonfatal stroke, sudden cardiac death, and coronary revascularization.

The mean LDL in the ezetimibe group dropped from 162 mg/dL at baseline to 120 mg/dL at 5 years, versus 131 mg/dL in the control group.

Bruce Jancin/MDedge News

Discussant Jennifer G. Robinson, MD, said that for a decade she has tried without success to get backing for a primary prevention statin trial in elderly U.S. patients, so congratulations to the Japanese investigators are in order.

She expressed doubts as to the generalizability of the EWTOPIA results to non-Japanese populations, however.

“Frankly, I was very surprised to see the large effect size. EWTOPIA had far more effect than we expected based on other trials of LDL-lowering agents to date,” said Dr. Robinson, professor of epidemiology and medicine and director of the Prevention Intervention Center at the University of Iowa, Iowa City.

“It’s a little better performance than we expected from that magnitude of LDL lowering, which was quite modest,” she added.

Among the possible explanations she cited for the greater magnitude of reduction in major vascular events seen in EWTOPIA as compared, for example, to the IMPROVE-IT trial, which also utilized ezetimibe, are genetic differences in the Japanese population. It’s known that the Japanese have different genetic polymorphisms of Niemann-Pick C1 Like 1 (NPC1L1), which is what ezetimibe binds to in order to inhibit small intestinal enterocyte uptake and absorption of cholesterol. Or it might just be that older adults, regardless of their ethnicity, have a more robust response to LDL lowering than the younger ones who’ve been the focus of previous trials.

“I think the LDL lowering from ezetimibe was very effective in Japanese older adults without cardiovascular disease, and I think that’s a very appropriate therapy for primary prevention moving forward in that population,” Dr. Robinson said.

As for herself, she’s awaiting confirmation in other populations. She’s particularly eager to see the outcome of the ongoing double-blind, randomized STAREE trial of atorvastatin (Lipitor) at 40 mg/day or placebo for primary prevention in 18,000 Australians age 70 and up. Results are expected in 2022.

Dr. Ouchi reported having no financial conflicts regarding the EWTOPIA study, funded by the Japanese government.
 

bjancin@mdedge.com

SOURCE: Ouchi Y. AHA Late Breaker 02.

CHICAGO – The first prospective randomized trial support for the efficacy of LDL-lowering therapy for primary cardiovascular prevention in patients age 75 and older has been provided by the Japanese EWTOPIA 75 trial.

Bruce Jancin/MDedge News

Ezetimibe (Zetia) at 10 mg/day reduced the risk of the primary endpoint, a composite of atherosclerotic cardiovascular events, by 34% compared with a dietary counseling control group over the course of 5 years of followup. Yasuyoshi Ouchi, MD, PhD, reported the findings of the 3,796-patient study at the American Heart Association scientific sessions.

There was also a 40% relative risk reduction for cardiac events in the ezetimibe group. The 22% reduction in cerebrovascular events, however, didn’t achieve statistical significance, and there was no between-group difference in all-cause mortality, said Dr. Ouchi, principal investigator in EWTOPIA 75 and professor emeritus of geriatric medicine at the University of Tokyo.

The landmark randomized clinical trials of lipid-lowering for primary cardiovascular prevention included too few elderly participants to permit assessment of its merits and possible harms in that population. This has left a major evidence gap at a time when in many parts of the world, including the United States, Europe, and Japan, the population over age 75 is growing explosively.

“Along with this population change, the number of patients age 75 and older with hypercholesterolemia has dramatically increased,” Dr. Ouchi continued.

Eligibility for EWTOPIA was restricted to patients who were at least 75 years old, had an LDL of at least 140 mg/dL, no history of CAD, and had at least one high-risk factor, such as diabetes or hypertension. Their mean age at enrollment was 80.7 years. Seventy-four percent of them were women, reflecting the significantly longer life expectancy of Japanese women compared to men.

The study design was open-label with no placebo arm. Dr. Ouchi argued that this was appropriate, given that the components of the primary composite endpoint were “entirely objective”: fatal and nonfatal MI, fatal and nonfatal stroke, sudden cardiac death, and coronary revascularization.

The mean LDL in the ezetimibe group dropped from 162 mg/dL at baseline to 120 mg/dL at 5 years, versus 131 mg/dL in the control group.

Bruce Jancin/MDedge News

Discussant Jennifer G. Robinson, MD, said that for a decade she has tried without success to get backing for a primary prevention statin trial in elderly U.S. patients, so congratulations to the Japanese investigators are in order.

She expressed doubts as to the generalizability of the EWTOPIA results to non-Japanese populations, however.

“Frankly, I was very surprised to see the large effect size. EWTOPIA had far more effect than we expected based on other trials of LDL-lowering agents to date,” said Dr. Robinson, professor of epidemiology and medicine and director of the Prevention Intervention Center at the University of Iowa, Iowa City.

“It’s a little better performance than we expected from that magnitude of LDL lowering, which was quite modest,” she added.

Among the possible explanations she cited for the greater magnitude of reduction in major vascular events seen in EWTOPIA as compared, for example, to the IMPROVE-IT trial, which also utilized ezetimibe, are genetic differences in the Japanese population. It’s known that the Japanese have different genetic polymorphisms of Niemann-Pick C1 Like 1 (NPC1L1), which is what ezetimibe binds to in order to inhibit small intestinal enterocyte uptake and absorption of cholesterol. Or it might just be that older adults, regardless of their ethnicity, have a more robust response to LDL lowering than the younger ones who’ve been the focus of previous trials.

“I think the LDL lowering from ezetimibe was very effective in Japanese older adults without cardiovascular disease, and I think that’s a very appropriate therapy for primary prevention moving forward in that population,” Dr. Robinson said.

As for herself, she’s awaiting confirmation in other populations. She’s particularly eager to see the outcome of the ongoing double-blind, randomized STAREE trial of atorvastatin (Lipitor) at 40 mg/day or placebo for primary prevention in 18,000 Australians age 70 and up. Results are expected in 2022.

Dr. Ouchi reported having no financial conflicts regarding the EWTOPIA study, funded by the Japanese government.
 

bjancin@mdedge.com

SOURCE: Ouchi Y. AHA Late Breaker 02.

LA JOLLA, CALIF. — Results of a phase 1 trial suggest a four-drug combination can produce durable responses in patients with relapsed or refractory T- and B-cell lymphomas.

Seven of 15 patients responded to treatment with romidepsin, gemcitabine, oxaliplatin, and dexamethasone, including six patients who achieved a complete response (CR).

The median duration of response was 8.5 months, and three patients had responses lasting more than 24 months.

Patients with angioimmunoblastic T-cell lymphoma (AITL) in particular responded well to the combination.

Neha Mehta-Shah, MD, of Washington University in St. Louis, and her colleagues presented these results in a poster at the annual T-cell Lymphoma Forum.

“[I]t was thought that the addition of histone deacetylase inhibitors to traditional platinum-based chemotherapies, which tend to cause DNA damage, would increase the response of platinum-based therapies,” Dr. Shah said.

With that in mind, she and her colleagues added romidepsin to gemcitabine, oxaliplatin, and dexamethasone and evaluated this combination in patients with relapsed/refractory lymphomas.

The trial (NCT02181218) enrolled 15 patients — 6 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), 6 with diffuse large B-cell lymphoma (DLBCL), and 3 with AITL.

The patients’ median age was 66 (range, 55-83), and they had received a median of 2 (range, 1-4) prior therapies.

The researchers tested three dose levels of romidepsin — 8 mg/m², 10 mg/m², and 12 mg/m² — given on day 2 of a 21-day cycle. The study originally included romidepsin on day 8 as well. However, the researchers discontinued the day 8 dose after patients developed grade 4 thrombocytopenia.

Patients also received gemcitabine at 1,000 mg/m² (day 1), oxaliplatin at 100 mg/m² (day 1), and dexamethasone at 20 mg (days 1-4). All patients received pegfilgrastim at 6 mg (day 3) as well.

The patients could receive up to eight cycles of treatment if they had stable disease or better and did not experience significant toxicity.

Safety

There was one dose-limiting toxicity (DLT) — pneumonia — at the 8 mg/m² dose of romidepsin (given on days 2 and 8). There was one DLT — bleeding — at the 10 mg/m² dose (day 2 only).

Two patients experienced DLTs — neutropenic fever and grade 4 thrombocytopenia — at the 12 mg/m² dose (day 2 only).

Based on these events, 10 mg/m² was considered the maximum-tolerated dose of romidepsin.

The most common adverse events (AEs) in this trial were thrombocytopenia (n = 13), electrolyte abnormalities (n = 12), liver function abnormalities (n = 10), anemia (n = 9), neutropenia (n = 8), fatigue (n = 7), nausea (n = 7), and creatinine increase (n = 5).

Grade 3/4 AEs included thrombocytopenia (n = 13), neutropenia (n = 5), anemia (n = 3), hyperglycemia (n = 2), hyperuricemia (n = 2), febrile neutropenia (n = 1), tumor lysis syndrome (n = 1), vomiting (n = 1), peripheral sensory neuropathy (n = 1), pneumonia (n = 1), sepsis (n = 1), bleeding (n = 1), and elevated troponin (n = 1).

Serious AEs requiring hospitalization included pneumonia (n = 1), nausea and vomiting (n = 1), tumor lysis syndrome (n = 1), and complications of disease progression (n = 4).

Efficacy

The overall response rate was 47% (7/15). CRs occurred in all three patients with AITL and two patients with DLBCL. One patient with PTCL-NOS had a CR, and one had a partial response.

The median duration of response was 8.5 months (range, 1.2-36.6 months). Four patients remain in CR — two with AITL, one with PTCL-NOS, and one with DLBCL.

Dr. Shah noted that the CRs in the AITL patients “have been quite prolonged.” One patient had a CR lasting 27 months, and another had a CR lasting 29 months.

Dr. Shah said these results are particularly exciting because patients discontinued study treatment after eight cycles or two cycles after they achieved a CR.

“[S]ome of these patients remained in remission for 2 years without any therapy thereafter, which is quite impressive in a population where the median survival — for patients with relapsed/refractory AITL — is thought to be 6-10 months,” Dr. Shah said.

She noted that this study is ongoing with an expansion cohort of patients with T-cell lymphomas.

This research was supported by Celgene. Dr. Shah reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. — Results of a phase 1 trial suggest a four-drug combination can produce durable responses in patients with relapsed or refractory T- and B-cell lymphomas.

Seven of 15 patients responded to treatment with romidepsin, gemcitabine, oxaliplatin, and dexamethasone, including six patients who achieved a complete response (CR).

The median duration of response was 8.5 months, and three patients had responses lasting more than 24 months.

Patients with angioimmunoblastic T-cell lymphoma (AITL) in particular responded well to the combination.

Neha Mehta-Shah, MD, of Washington University in St. Louis, and her colleagues presented these results in a poster at the annual T-cell Lymphoma Forum.

“[I]t was thought that the addition of histone deacetylase inhibitors to traditional platinum-based chemotherapies, which tend to cause DNA damage, would increase the response of platinum-based therapies,” Dr. Shah said.

With that in mind, she and her colleagues added romidepsin to gemcitabine, oxaliplatin, and dexamethasone and evaluated this combination in patients with relapsed/refractory lymphomas.

The trial (NCT02181218) enrolled 15 patients — 6 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), 6 with diffuse large B-cell lymphoma (DLBCL), and 3 with AITL.

The patients’ median age was 66 (range, 55-83), and they had received a median of 2 (range, 1-4) prior therapies.

The researchers tested three dose levels of romidepsin — 8 mg/m², 10 mg/m², and 12 mg/m² — given on day 2 of a 21-day cycle. The study originally included romidepsin on day 8 as well. However, the researchers discontinued the day 8 dose after patients developed grade 4 thrombocytopenia.

Patients also received gemcitabine at 1,000 mg/m² (day 1), oxaliplatin at 100 mg/m² (day 1), and dexamethasone at 20 mg (days 1-4). All patients received pegfilgrastim at 6 mg (day 3) as well.

The patients could receive up to eight cycles of treatment if they had stable disease or better and did not experience significant toxicity.

Safety

There was one dose-limiting toxicity (DLT) — pneumonia — at the 8 mg/m² dose of romidepsin (given on days 2 and 8). There was one DLT — bleeding — at the 10 mg/m² dose (day 2 only).

Two patients experienced DLTs — neutropenic fever and grade 4 thrombocytopenia — at the 12 mg/m² dose (day 2 only).

Based on these events, 10 mg/m² was considered the maximum-tolerated dose of romidepsin.

The most common adverse events (AEs) in this trial were thrombocytopenia (n = 13), electrolyte abnormalities (n = 12), liver function abnormalities (n = 10), anemia (n = 9), neutropenia (n = 8), fatigue (n = 7), nausea (n = 7), and creatinine increase (n = 5).

Grade 3/4 AEs included thrombocytopenia (n = 13), neutropenia (n = 5), anemia (n = 3), hyperglycemia (n = 2), hyperuricemia (n = 2), febrile neutropenia (n = 1), tumor lysis syndrome (n = 1), vomiting (n = 1), peripheral sensory neuropathy (n = 1), pneumonia (n = 1), sepsis (n = 1), bleeding (n = 1), and elevated troponin (n = 1).

Serious AEs requiring hospitalization included pneumonia (n = 1), nausea and vomiting (n = 1), tumor lysis syndrome (n = 1), and complications of disease progression (n = 4).

Efficacy

The overall response rate was 47% (7/15). CRs occurred in all three patients with AITL and two patients with DLBCL. One patient with PTCL-NOS had a CR, and one had a partial response.

The median duration of response was 8.5 months (range, 1.2-36.6 months). Four patients remain in CR — two with AITL, one with PTCL-NOS, and one with DLBCL.

Dr. Shah noted that the CRs in the AITL patients “have been quite prolonged.” One patient had a CR lasting 27 months, and another had a CR lasting 29 months.

Dr. Shah said these results are particularly exciting because patients discontinued study treatment after eight cycles or two cycles after they achieved a CR.

“[S]ome of these patients remained in remission for 2 years without any therapy thereafter, which is quite impressive in a population where the median survival — for patients with relapsed/refractory AITL — is thought to be 6-10 months,” Dr. Shah said.

She noted that this study is ongoing with an expansion cohort of patients with T-cell lymphomas.

This research was supported by Celgene. Dr. Shah reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. — Results of a phase 1 trial suggest a four-drug combination can produce durable responses in patients with relapsed or refractory T- and B-cell lymphomas.

Seven of 15 patients responded to treatment with romidepsin, gemcitabine, oxaliplatin, and dexamethasone, including six patients who achieved a complete response (CR).

The median duration of response was 8.5 months, and three patients had responses lasting more than 24 months.

Patients with angioimmunoblastic T-cell lymphoma (AITL) in particular responded well to the combination.

Neha Mehta-Shah, MD, of Washington University in St. Louis, and her colleagues presented these results in a poster at the annual T-cell Lymphoma Forum.

“[I]t was thought that the addition of histone deacetylase inhibitors to traditional platinum-based chemotherapies, which tend to cause DNA damage, would increase the response of platinum-based therapies,” Dr. Shah said.

With that in mind, she and her colleagues added romidepsin to gemcitabine, oxaliplatin, and dexamethasone and evaluated this combination in patients with relapsed/refractory lymphomas.

The trial (NCT02181218) enrolled 15 patients — 6 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), 6 with diffuse large B-cell lymphoma (DLBCL), and 3 with AITL.

The patients’ median age was 66 (range, 55-83), and they had received a median of 2 (range, 1-4) prior therapies.

The researchers tested three dose levels of romidepsin — 8 mg/m², 10 mg/m², and 12 mg/m² — given on day 2 of a 21-day cycle. The study originally included romidepsin on day 8 as well. However, the researchers discontinued the day 8 dose after patients developed grade 4 thrombocytopenia.

Patients also received gemcitabine at 1,000 mg/m² (day 1), oxaliplatin at 100 mg/m² (day 1), and dexamethasone at 20 mg (days 1-4). All patients received pegfilgrastim at 6 mg (day 3) as well.

The patients could receive up to eight cycles of treatment if they had stable disease or better and did not experience significant toxicity.

Safety

There was one dose-limiting toxicity (DLT) — pneumonia — at the 8 mg/m² dose of romidepsin (given on days 2 and 8). There was one DLT — bleeding — at the 10 mg/m² dose (day 2 only).

Two patients experienced DLTs — neutropenic fever and grade 4 thrombocytopenia — at the 12 mg/m² dose (day 2 only).

Based on these events, 10 mg/m² was considered the maximum-tolerated dose of romidepsin.

The most common adverse events (AEs) in this trial were thrombocytopenia (n = 13), electrolyte abnormalities (n = 12), liver function abnormalities (n = 10), anemia (n = 9), neutropenia (n = 8), fatigue (n = 7), nausea (n = 7), and creatinine increase (n = 5).

Grade 3/4 AEs included thrombocytopenia (n = 13), neutropenia (n = 5), anemia (n = 3), hyperglycemia (n = 2), hyperuricemia (n = 2), febrile neutropenia (n = 1), tumor lysis syndrome (n = 1), vomiting (n = 1), peripheral sensory neuropathy (n = 1), pneumonia (n = 1), sepsis (n = 1), bleeding (n = 1), and elevated troponin (n = 1).

Serious AEs requiring hospitalization included pneumonia (n = 1), nausea and vomiting (n = 1), tumor lysis syndrome (n = 1), and complications of disease progression (n = 4).

Efficacy

The overall response rate was 47% (7/15). CRs occurred in all three patients with AITL and two patients with DLBCL. One patient with PTCL-NOS had a CR, and one had a partial response.

The median duration of response was 8.5 months (range, 1.2-36.6 months). Four patients remain in CR — two with AITL, one with PTCL-NOS, and one with DLBCL.

Dr. Shah noted that the CRs in the AITL patients “have been quite prolonged.” One patient had a CR lasting 27 months, and another had a CR lasting 29 months.

Dr. Shah said these results are particularly exciting because patients discontinued study treatment after eight cycles or two cycles after they achieved a CR.

“[S]ome of these patients remained in remission for 2 years without any therapy thereafter, which is quite impressive in a population where the median survival — for patients with relapsed/refractory AITL — is thought to be 6-10 months,” Dr. Shah said.

She noted that this study is ongoing with an expansion cohort of patients with T-cell lymphomas.

This research was supported by Celgene. Dr. Shah reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

Patients use fewer opioids and have shorter hospital stays when they had transversus abdominis plane (TAP) blocks instead of epidurals for pain control after ventral hernia repair, according to a review of 246 cases at the Greenville Health System, in South Carolina.

“Regional anesthesia using TAP block[s] provides an effective alternative to epidural analgesia or opioid use alone for perioperative pain control ... In light of these findings, use of TAP block should be strongly considered as an adjunct to abdominal surgery,” wrote investigators led by general surgeon Jeremy Warren, MD, of the University of South Carolina School of Medicine, Greenville, in the Journal of the American College of Surgeons.

Prompted by favorable reports in the literature, the team switched from epidural analgesia to TAP blocks in early 2017. To see how it’s worked out, they reviewed all patients who had ventral hernia repairs at the Greenville Health System from Feb. 2015 to March 2018. They were all mesh cases, without parastomal hernias or enterostomy reversal.

Seventy-four patients had TAP blocks, which were placed in the OR after anesthesia induction and consisted of 200 mg ropivacaine, 100 mcg epinephrine, and 100 mcg clonidine in 60 ml saline, with 30 ml injected on each side under ultrasound guidance.

Their outcomes were compared with 172 patients who received epidurals, which were placed preoperatively and consisted of 0.125% bupivacaine initiated shortly before patients came out of anesthesia, at a rate of 8-12 ml/hr.

Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1, and 36.1 versus 52.5 MME on postop day 2 (P = .018).

There were no differences in the rates of surgical site infections or other wound complications. The mean duration of epidural infusion was 49.5 hours.

The shorter length of stay with TAP block was probably related to side effects of epidurals, which can include leg paresthesias, hypotension, and urinary retention, all of which get in the way of early ambulation. “Additionally, the decision of when to discontinue epidural analgesia in our series was left to the judgment of the pain management and surgical team based on reporting of patient pain, rather than duration determined by a protocol,” which may have also played a role, the study team said.

Overall, the results mirror outcomes from previous TAP block studies, but there were caveats. Epidural patients had wider hernias (median 10.8 cm versus 8.8 cm); required more myofascial releases; and had longer operative times, “indicating a higher degree of complexity that may influence the need for longer hospitalization and greater opioid use,” the investigators said.

Also, a greater number of TAP block patients received non-opioid pain killers, including ketorolac and acetaminophen.

The study was conducted within the health system’s enhanced recovery after surgery protocol, which includes a preoperative cocktail of pregabalin 75 mg, celecoxib 400 mg, and acetaminophen 1,000 mg, given within 1-2 hours of surgery. Post-operative management includes intravenous ketamine infusions at sub-anesthetic doses, NSAIDs, and acetaminophen, among other measures. The approach has pretty much eliminated patient-controlled analgesia.

There were slightly more men than women in the review. Study participants, on average, were in their late 50s. There were no significant differences in comorbidities.

No funding was reported, and the investigators didn’t have any relevant disclosures.
 

aotto@mdedge.com

SOURCE: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017

Patients use fewer opioids and have shorter hospital stays when they had transversus abdominis plane (TAP) blocks instead of epidurals for pain control after ventral hernia repair, according to a review of 246 cases at the Greenville Health System, in South Carolina.

“Regional anesthesia using TAP block[s] provides an effective alternative to epidural analgesia or opioid use alone for perioperative pain control ... In light of these findings, use of TAP block should be strongly considered as an adjunct to abdominal surgery,” wrote investigators led by general surgeon Jeremy Warren, MD, of the University of South Carolina School of Medicine, Greenville, in the Journal of the American College of Surgeons.

Prompted by favorable reports in the literature, the team switched from epidural analgesia to TAP blocks in early 2017. To see how it’s worked out, they reviewed all patients who had ventral hernia repairs at the Greenville Health System from Feb. 2015 to March 2018. They were all mesh cases, without parastomal hernias or enterostomy reversal.

Seventy-four patients had TAP blocks, which were placed in the OR after anesthesia induction and consisted of 200 mg ropivacaine, 100 mcg epinephrine, and 100 mcg clonidine in 60 ml saline, with 30 ml injected on each side under ultrasound guidance.

Their outcomes were compared with 172 patients who received epidurals, which were placed preoperatively and consisted of 0.125% bupivacaine initiated shortly before patients came out of anesthesia, at a rate of 8-12 ml/hr.

Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1, and 36.1 versus 52.5 MME on postop day 2 (P = .018).

There were no differences in the rates of surgical site infections or other wound complications. The mean duration of epidural infusion was 49.5 hours.

The shorter length of stay with TAP block was probably related to side effects of epidurals, which can include leg paresthesias, hypotension, and urinary retention, all of which get in the way of early ambulation. “Additionally, the decision of when to discontinue epidural analgesia in our series was left to the judgment of the pain management and surgical team based on reporting of patient pain, rather than duration determined by a protocol,” which may have also played a role, the study team said.

Overall, the results mirror outcomes from previous TAP block studies, but there were caveats. Epidural patients had wider hernias (median 10.8 cm versus 8.8 cm); required more myofascial releases; and had longer operative times, “indicating a higher degree of complexity that may influence the need for longer hospitalization and greater opioid use,” the investigators said.

Also, a greater number of TAP block patients received non-opioid pain killers, including ketorolac and acetaminophen.

The study was conducted within the health system’s enhanced recovery after surgery protocol, which includes a preoperative cocktail of pregabalin 75 mg, celecoxib 400 mg, and acetaminophen 1,000 mg, given within 1-2 hours of surgery. Post-operative management includes intravenous ketamine infusions at sub-anesthetic doses, NSAIDs, and acetaminophen, among other measures. The approach has pretty much eliminated patient-controlled analgesia.

There were slightly more men than women in the review. Study participants, on average, were in their late 50s. There were no significant differences in comorbidities.

No funding was reported, and the investigators didn’t have any relevant disclosures.
 

aotto@mdedge.com

SOURCE: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017

Patients use fewer opioids and have shorter hospital stays when they had transversus abdominis plane (TAP) blocks instead of epidurals for pain control after ventral hernia repair, according to a review of 246 cases at the Greenville Health System, in South Carolina.

“Regional anesthesia using TAP block[s] provides an effective alternative to epidural analgesia or opioid use alone for perioperative pain control ... In light of these findings, use of TAP block should be strongly considered as an adjunct to abdominal surgery,” wrote investigators led by general surgeon Jeremy Warren, MD, of the University of South Carolina School of Medicine, Greenville, in the Journal of the American College of Surgeons.

Prompted by favorable reports in the literature, the team switched from epidural analgesia to TAP blocks in early 2017. To see how it’s worked out, they reviewed all patients who had ventral hernia repairs at the Greenville Health System from Feb. 2015 to March 2018. They were all mesh cases, without parastomal hernias or enterostomy reversal.

Seventy-four patients had TAP blocks, which were placed in the OR after anesthesia induction and consisted of 200 mg ropivacaine, 100 mcg epinephrine, and 100 mcg clonidine in 60 ml saline, with 30 ml injected on each side under ultrasound guidance.

Their outcomes were compared with 172 patients who received epidurals, which were placed preoperatively and consisted of 0.125% bupivacaine initiated shortly before patients came out of anesthesia, at a rate of 8-12 ml/hr.

Hospital lengths of stay were significantly shorter in the TAP group, a median of 2.4 versus 4.5 days (P less than .001), and TAP patients received fewer opioids, a mean of 40 versus 54.1 morphine milligram equivalents (MME) on postop day 1, and 36.1 versus 52.5 MME on postop day 2 (P = .018).

There were no differences in the rates of surgical site infections or other wound complications. The mean duration of epidural infusion was 49.5 hours.

The shorter length of stay with TAP block was probably related to side effects of epidurals, which can include leg paresthesias, hypotension, and urinary retention, all of which get in the way of early ambulation. “Additionally, the decision of when to discontinue epidural analgesia in our series was left to the judgment of the pain management and surgical team based on reporting of patient pain, rather than duration determined by a protocol,” which may have also played a role, the study team said.

Overall, the results mirror outcomes from previous TAP block studies, but there were caveats. Epidural patients had wider hernias (median 10.8 cm versus 8.8 cm); required more myofascial releases; and had longer operative times, “indicating a higher degree of complexity that may influence the need for longer hospitalization and greater opioid use,” the investigators said.

Also, a greater number of TAP block patients received non-opioid pain killers, including ketorolac and acetaminophen.

The study was conducted within the health system’s enhanced recovery after surgery protocol, which includes a preoperative cocktail of pregabalin 75 mg, celecoxib 400 mg, and acetaminophen 1,000 mg, given within 1-2 hours of surgery. Post-operative management includes intravenous ketamine infusions at sub-anesthetic doses, NSAIDs, and acetaminophen, among other measures. The approach has pretty much eliminated patient-controlled analgesia.

There were slightly more men than women in the review. Study participants, on average, were in their late 50s. There were no significant differences in comorbidities.

No funding was reported, and the investigators didn’t have any relevant disclosures.
 

aotto@mdedge.com

SOURCE: Warren JA et al., J Am Coll Surg. 2019 Jan 7. pii: S1072-7515(19)30014-6. doi: 10.1016/j.jamcollsurg.2018.12.017